Quality Assurance

Data Integrity and Why Is It So Important?

Data Integrity can be defined as it is critical part to the plan, execution & practice of system that processes, stores & or retrieves data and maintenance & assurance of data accuracy and consistency throughout its life cycle.

Another best alternative term is Data quality which is sometimes defined as the proxy term of data integrity. It is the wide term & it can be used in different meaning depending on the framework. For data integrity, data validation is prerequisite. Data corruption is the just opposite term of Data integrity.

Also Read

What is the difference between Data and Information?

Confirm that data is recorded exactly as projected and most of the cases Data Integrity technique is the same for all type of probable data source.
The main target regarding is to prevent any type of alteration of the exact data recorded during collection of data and it can’t change at any cost. At the time of retrieval of data, it must be same as collected before.

Data Integrity denote the accuracy & consistency of data over its lifecycle. Sensitive data may loss upon uses of Negotiated data. Under this consideration, continuing it is a main focus of many enterprise security solutions. During replicated or transferred of data, it shall be intact and unaltered. To ensure the integrity of data, Error checking methods and validation procedures are typically best way to serve the same.

Don’t confuse with Data Integrity and Data security, it is process to prevent unauthorized entry to the projected data or protecting data from unauthorized expert.
Any unintended changes to data as the consequence of a storage, retrieval or processing operation, including malicious intent, unexpected hardware failure, and human error, is failure of data integrity.

Failure of Data Integrity means any unplanned changes to data as the consequence of storage, unexpected hardware failure, retrieval or human error or processing operation malicious intent etc. If you unable to protect your data from unauthorized change then it can define as data security failure.

Data Integrity denote that it is a state as well as process, so a confusion may arise. Data Integrity is a state as it denotes a data set is both valid and accurate. Validation methods & Error checking are considered as Data Integrity processes.

Study of Data Integrity

Data Integrity is significant for several reasons & need to maintain the same. Data Integrity confirms searchability, recoverability, connectivity, & traceability. To increases stability & performance as well as improving reusability & maintainability; need to protect validity & accuracy of data. Data plays a major role to drive enterprise decision-making and data undergo several stages of changes to form raw to format to become more practical and identifying relation between them. In modern enterprises Data Integrity consider the top most priority.

In a database system, Data Integrity may be Compromised in various type of ways. In the following ways, Data Integrity may be compromised-
[][]Compromised hardware, like device or disk crash
[][]Compromise of Physical devices
[][]Cyber threats, Bugs, Viruses/Malware, Hacking, & other unfamiliar process
[][]Human error, whether unintentional or malicious

Transfer errors, unintended alterations or data compromise during transfer from one device to another device.
Most of the cases, some type of data security may protect this data compromises. Data duplication is the critical para meter for data security as well as data backup process.

Data Integrity & Databases

Data Integrity encompasses strategies for data specifying, retention, or guaranteeing the length of time data. Any lessening of enforcement could cause errors in the data; all of the rules shall be consistently & regularly implemented to all data entering the system.

At time of data input, checking system shall be implement which will lessen up the number of data error for the system. Data Integrity rules shall be strictly implemented to the system which will save troubleshooting time, erroneous data subsequently errors to algorithms.

A standard Data Integrity rules must have the strict definition regarding data relation; as which type data shall link with which type of data. A selling record of a item of certain product may be linked with the specific product but is shall not be related to unrelated data such as company asset, policy, loan, promotion etc. Based on predefined rules, it may be included check & correction system for the invalid a data.

Data derivation rules shall be applicable, mentioning data derivation procedure that how a data value shall be derived based on contributors, conditions and algorithm of the system. Re-derived procedure for data value shall be mention on which condition shall be considered for this process.

Types of Data Integrity

Organizations can maintain Data Integrity through integrity constraints, which define the rules and procedures around actions like deletion, insertion, and update of information. The definition of Data Integrity can be enforced in both hierarchical and relational databases, such as enterprise resource planning (ERP), customer relationship management (CRM), and supply chain management (CRM) systems.

Organizations can achieve it through the following:

Physical Integrity

Physical integrity deals with challenges which are associated with correctly storing and fetching the data itself.

Physical integrity indicates the right storing & fetching the data itself & its associated series of challenges. Various types of Challenges are involved with it such as Physical flaws, design flaws, power outages, electromechanical faults, corrosion, material fatigue, natural disasters, environmental hazards such as ionizing radiation, high temperatures, pressures & g-forces [the force of gravity].

Various methods are available to maintain the physical integrity such as UPS [uninterruptible power supply], redundant hardware, various type of RAID arrays, error-correcting memory, radiation hardened chips, clustered file system, watchdog timer & cryptographic hash function for critical system.

Error-correcting codes is extensively use as error detecting algorithms in Physical integrity of data management systems. Simpler checks & algorithms as the Damm algorithm or Luhn algorithm is use to detect Data Integrity errors. This system is use to uphold Data Integrity at manual transcription from one computer system to another computer system through a human intermediary such as credit card numbers. Hash functions are more beneficial to detect Computer-induced transcription errors.

These techniques are used together to ensure various degrees of Data Integrity in production systems such as a fault-tolerant RAID array may be use to configured a computer system but in silent data corruption block-level checksums might not provide.

In a nutshell, Physical integrity means protecting the accuracy, correctness, and wholeness of data when it is stored and retrieved. This is typically compromised by issues like power outages, storage erosion, hackers targeting database functions, and natural disasters, which prevent accurate data storage and retrieval.

Logical Integrity

It is concerned with correctness or rationality of a piece of data provide a particular context. It denotes the topic such as Entity integrity & referential integrity in a relational database system. Design flaws, software bugs, and human errors are the major challenges. Foreign key constraints, check constraints, program assertions, and other run-time sanity checks are the common methods to ensure logical integrity.

Design flaws & Human errors, both are the common problems for physical and logical integrity which must be properly deal with the contemporaneous requests to record and retrieve data. Physical error for a specific data system is more critical than logical error. If a data system suspected to logical error, it can be reused by overwriting with the new one but if it faces physical error then the data sector is totally used of its own condition.

Logical integrity ensures that data remains unchanged while being used in different ways through relational databases. This approach also aims to protect data from hacking or human error issues but does so differently than physical integrity.

Logical integrity comes in four different formats:

Entity Integrity

Entity integrity is a feature of relation systems that store data within tables, which can be used and linked in various ways. It relies on primary keys and unique values being created to identify a piece of data. This ensures data cannot be listed multiple times, and fields in a table cannot be null.

Referential Integrity

Referential integrity is a series of processes that ensure data remains stored and used in a uniform manner. Database structures are embedded with rules that define how foreign keys are used, which ensures only appropriate data deletion, changes, and amendments can be made. This can prevent data duplication and guarantee data accuracy.

Domain Integrity

Domain integrity is a series of processes that guarantee the accuracy of pieces of data within a domain. A domain is classified by a set of values that a table’s columns are allowed to contain, along with constraints and measures that limit the amount, format, and type of data that can be entered.

User-defined Integrity

User-defined integrity means that rules and constraints around data are created by users to align with their specific requirements. This is usually used when other integrity processes will not safeguard an organization’s data, allowing for the creation of rules that incorporate an organization’s Data Integrity measures.

Types of Integrity Constraints

A set of integrity constraints or rules are followed to implement Data Integrity in a database system. Relational data model suggests the three types of integrity constraints such as domain integrity, entity integrity, & referential integrity.

First of all, Entity integrity denote the concept of a primary key. As per this system, Entity integrity states that every table shall contain a primary key and existing column or columns of the table shall be identified by the primary key & it shall be inimitable and not null.

Concept of a foreign key denote Referential integrity. As per referential integrity rule, any foreign-key value can only be in one of two states. In general condition, foreign-key value refers to a primary key value of some table in the database system. Sporadically, a foreign-key value can be null and this will rest on on the rules of data owner. Under these circumstances, it can be stated here that this relationship is unknown or there is no relationship between the objects represented in the database system.

All columns in a relational database must be stated upon a defined domain is the main concern of the Domain integrity. In the relational data model, the primary unit of data is the data item. This type of data items is known as atomic or non-decomposable. A set of values of the same type is defined as domain. Actual values appearing in the columns of a table are drawn from the Domains which are considered as pools of values.

As the User-defined integrity are set by the specific user with a set of rules which is not related to domain, entity, and referential integrity classes. The database which supports these features, it is the sole responsibility of the database to confirm Data Integrity and reliability model for the data storage & retrieval system. The database which does not support these features then it is the accountability of the applications to confirm Data Integrity though the database supports the consistency model for data storage & recovery process.

A well-controlled single and well managed data-integrity system increases.

[][]Maintainability
=>All Data Integrity administration commences from a single centralized system.

[][]Performance
=>As a single operation unit, all Data Integrity operations perform as consistency model.
[][]Re-usability
=>A single centralized Data Integrity system provides the all applications benefit.
[][]Stability
=>As avoid the multiple system, so Data Integrity operation performs sound as well as better retrieval on a one centralized system.

Examples
Data-integrity mechanism is often considered as the parent-and-child connection of interrelated records. When one or more related child records exist for a parent record then all of referential integrity methods are handled by database itself & inevitably ensures accuracy & integrity of data, so no child record can exist without parent record and subsequently no parent drops their child records. In this system if the parent record owns any child records, then no parent record can be deleted and all of the process handled by the database system.

File systems

File system including Ext, JFS, UFS, XFS, and NTFS or hardware RAID solutions can’t provide satisfactory protection against Data Integrity problems. Some special file system such as BTRFS and ZFS use for silent data corruption can provide extra protection for data integrity. Upon provide this protection and being chance raise to corrupt the data then such file system can construct the data is widely known as end-to-end data protection.

Data Integrity as applied to various industries
[][]FDA has created the draft guidance for Data Integrity system as per 21 CFR Parts 210–212.[12] for pharmaceutical manufacturers. Same guideline has been developed by UK [2015], Switzerland [2016], and Australia [2017].
[][]Data Integrity also addressed by ISO as per ISO 13485, ISO 14155, and ISO 5840.
[][]FINRA [Financial Industry Regulatory Authority], implement the Data Integrity system on 2018 under technology change management policies and procedures” and Treasury securities reviews as Data Integrity problem found in 2017 on automated trading and money movement surveillance systems.

Why Data Integrity Matter?

Now a days Data are becoming more available, a smart business strategy which are using to make decision are obtaining the several times benefits.
According to recent research, a data driven organization is more than 23 times better performer in customer acquisition, nine times more performer to retain their customer and more than 19 times profitable to their competitor.

As the power of data is increasing day by day, so Data Integrity shall be valued properly and its importance can’t be denied at current situation. Presence of any type of error in data can spoil the total organization goal. A data driven organization must protect their database system at any cost to provide better security solution.

Threats involve in Data Integrity

[][]Human error:
It may arise in such case of transferring of data manually from one share drive to another, copying data from one spreadsheet to another and subsequently deleting of row or column of a spreadsheet. Storing data on excel sheet may cause formatting problem during manually data transferring process. Updating of excel sheet from old version to new one may cause formatting problem of subsequent data.

[][]Inappropriate format:
Stored data on Microsoft excel based on cell referencing may not accurate in different format. Failure to determine the same may case Data Integrity problem.

[][]Collection error:
During collecting any type of data, proper precaution shall be taken. Collecting of data on wrong method may cause storing of incomplete data and actual data may not represent the total situation.

[][]Internal security breaches:
If the database system hacked by third part or internal or external competitor may cause serious Data Integrity failure.

Why is Data Integrity Important?

Generally, a specific individual or group of people are involved in database system of a organization. Problem arises when multiple people are responsible to operate the database system. Anyone of the team member may not aware about Data Integrity of the organization, then all of the individual shall educate regarding protection of the database system and tech them the importance of data quality, accuracy, completeness etc. & they must learn how to combat when potential data security threat arises.

If all of the team member are aware about the Data Integrity and know its importance then it is very much effect to maintain the database system.

A better Data Integrity system can save company effort, time as well as valuable overhead cost. Wrong decision may take place based on inappropriate data. Data driven organization always take critical decision based on available data, if Data Integrity of that organization are compromised by any situation, then inappropriate result may arise and the organization suffer in long run.

Data always help to make important decision additionally it protect your company image. If you are collecting your customer information then protect the collect data which you have collect from your individual customer, failure to protect the customer data in proper database system may leak your customer information to another one cause image problem of the company and also mispresent your customer to other party.

Any type of customer information may be tracked and may be asked or run a campaign over them to collect specific target data. All type of collected information may not be sensitive as SSN [Social Security number]. To protect your valuable customer, you have to take a proper step regarding Data Integrity of your existing system.

a company staff always demand to data access to the database to trace any type of data on time manner upon request. He needs to uninterrupted access to the data system. For this reason, Data Integrity is so important for the organization. Data Integrity confirm the traceability & searchability of the data from its mother source.

Effective data accuracy and data protection shall be confirmed to increase Data performance and its stability. It is very much crucial to confirm the completeness & integrity of data. Compromised data always carry the wrong value for the organization & is of no use for most companies.

Same scenario arises for big data management. It is very much important to secure the big data management system as well as to maintain the total database system. All type data is totally worthless Without integrity & accuracy. Your data can be compromised If you fail to do the same. Under this circumstances, awkward & expensive data audit trails shall be mandatory to find out error & recover the total database system.

Most companies have set specific goals for their data & it is now more important than ever. But if integrity is not assured then data is not of much use. If data loss, corrupted or compromised then data can considerably damage any type of business. To maintain it, data security shall be confirmed using proper tools.

Compromised Data is the big challenge to maintain data integrity. There are several ways to compromised the valuable data. Todays almost all of the data are digital and store then in the same than traditional method and its transferred vary rapidly in different places of the globe. So, security shall be considering first & also the collection data is main concert maintain its integrity.

Data can be unaltered if data transferring occur maintaining valid system. Every time Data is moving from one place to another and it is not static, every user of the specific system is using the data and transferring the same in different way.

Management of Data Integrity

A group of steps are available where you can maintain & achieve better Data Integrity for your organization.

Collection of Accurate, Complete, and High-Quality Data

Quality of data depends on the collecting process of the projected data; a collection process is crucial and collection depends on the proper collection method. Failure to select proper data collection technic may cause collection of erroneous data. Sourcing is prerequisite to collect data. Ensure the high-quality data source may provide one step forwards to competitor.

Meticulously Check for Errors

To make common error during collection of data is the main problem of manual collection of error but it can be rectified successfully to involve the second one to the same project. Various type of error can be overcome if proper checking process can be initiate by appropriate body. For most critical data double check or triple check can be initiate. Growing continuous attention during data collection may reduce the data error. Sometime a review of the related data may decrease the data error. A color shading on projected excel sheet in the alternative row may help to track the mentioned data.

Cybersecurity Threats

Most of the time you can’t realize that a hacker or third party is trying to access your database. Person or individual who are trying to control your data send a short link with attractive or recent hot topics or similar to company email address link. Thousand of ways a hacker can try to damage or control your database system, so a strong security system shall be established to protect Data Integrity of the system.

Data Science Course

Failure to know the technical framework of database system, you can’t protect your data properly. If you are capable to handle the system then you need not to collect data science but if you want to update your existing your practice and eagerly want to update your team capability then you can involve your team in any data science course which are already available online which help your organization as well as development of self-confidence.

Devotion to Data Integrity

To keep subjects’ information safe & giving organization’s stakeholders the highest quality, accurate, complete, most data on which to base decisions need daily commitment for your Data integrity. A proper security system and group of trained individuals can support the organization in this situation to continue the company progress.

Data Integrity vs. Data Quality

Data quality is a crucial piece of the Data Integrity puzzle. It enables organizations to meet their data standards and ensure information aligns with their requirements with a variety of processes that measure data age, accuracy, completeness, relevance, and reliability. Data quality goes a step further by implementing processes and rules that govern data entry, storage, and transformation.

Data Integrity vs. Data Security vs. Data Quality

Data security involves protecting data from unauthorized access and preventing data from being corrupted or stolen. Data Integrity is typically a benefit of data security but only refers to data accuracy and validity rather than data protection.

Data Integrity & data security are more relevant to each other. Each of them plays a vital role for each other for their individual achievement. Data Integrity only refers to validation and accuracy of data but didn’t involve to protect data. On the other hand, data security confirms the protection against corruption or unauthorized access.

Data security plays a crucial role to maintain data integrity, on the other hand, Data Integrity is the end result of data security. To maintain data integrity, data security is the vital point and this situation may arise when accidental compromise occurs for data integrity.

Data Integrity is the essential component for the modern business procedure while making decision based on accuracy and efficiency of database. The main focus of the data security leads to Data Integrity and various type of procedure are applied to achieve the same.

Data quality can be defined that the data stored in database is compliant with the organization’s standards & requirements. It maintains integrity in a database. A set of rules to a specific or whole dataset and stores it in the target database shall be implement to do the same. Data Integrity shall be considered as data accuracy as well as correctness of data.

How to Protect Your data?

Validate Input

To ensure data accuracy data entry must be validated & verified input is significant when data is provided by familiar or unfamiliar sources, such as end-users, applications, & malicious users.

Remove Duplicate Data

Sensitive data stored in secure databases cannot be duplicated & it important to ensure that publicly available spreadsheets, emails, documents, & folders. To prevent unauthorized access to business-critical data or personally identifiable information duplicate shall be remove as soon as possible with the help of authorized personnel.

Back Up Data

To confirm data security & integrity data backups are crucial. To prevent the valuable data from permanent lost data backup shall be perform on regular manner at the end of everyday work. Organizations that suffer ransomware attacks, Data backups are especially important for them to protect their potential resources.

Access Controls

To maintaining data integrity, appropriate access controls shall be introduced in the organization. Data privileged option shall be implemented for specific user to control the database access procedure. This process will help the user understand their limitation to use the database system as well as to maintain the whole system.

Audit Trail

An audit trail is the standard practice to trace the unfavorable event. Data breach may occur at anytime in a renowned organization. If audit trail facility are available for the organization then it is very much to find out when and how data breached where. If proper information is available then it is easy to trac the source of attack. So audit shall be introduce at your organization for your database management system.

Assurance of Data Quality

It is the part of the Data Integrity process. Regular shall be conduct so that data can meet the certain standard. The processes of data accessibility, data cleaning, , data standardization is the main concern of the Data quality assurance. Data cleaning deal with inputting missing data, removing invalid entries, update same on timely manner.

Data accessibility deal with availability of the data to the stakeholders in secure and appropriate manner. For encoding and entering data, business shall be maintained and unauthorized data entry or transfer shall be prohibited. All type of company rule shall be implemented increase of transfer access of data to potential sector.

Data Corruption vs Data Integrity

Data corruption shall be considered as the serious Data Integrity failure. Based on the current practice, data corruption may be occurred through multiple channels. Most of them a very common problem is human error occur during collection or transferring of data. Malware and physical damage are another potential cause of data corruption.

Most human error often cause in wrong entry of collected data, unauthorized entry of database system, involving newcomer to sensitive practice with our prior training, programming etc.

It can be traced with appropriate data validation checks & restricting access to database system. Extensive & systematic use of backups can support restore databases in case of improper data entries.

Malware is another common cause of data corruption and this is basically occurred from external source which main purpose is to stole the data from potential data server. Cyberattacks are almost always unpredicted and instantly can’t recognized the source on the most of the cases. So here come the data encryption, always try to encrypt the critical and sensitive data and if possible tight security system shall be introduced though cost may be high to do the same.

To ensure organizational network security, regular penetration testing shall be done, this will help you to secure the organizational network system. A physical damage is may cause the data lose which mainly cause by accident and disasters. To protect data, data may be store in different physical location will protect from accident and natural disasters.

Data Integrity and Why Is It So Important? Read More »

Comparative Dissolution Study procedure

Comparative Dissolution, General Overview

[][]Comparative Dissolution, Oral dosage form like Table & Capsule are more popular than IV/IM(Intravenous/Intramuscular) Injection formulation. From the very beginning, people are most familiar with oral solid dosage form (Tablet, Capsule, Powder etc.) and becoming more popular till today as no special technique or device is not require to administer these products and associated pain is not involved here.

[][]In the period of time its are considered as the most effective and efficient method to treat the patient. This orally taken drugs are dissolved in GI (Gastro Intestinal) fluid and then bioavailable at the systemic circulation as it absorbed here. To measure the bioavailability of a certain drugs (in vivo Analysis, vivo is Latin for “within the living, test perform in living organism) is not accurately possible due to its complex nature.

[][]For this reason, in vitro (vitro is Latin for “within the glass, test perform outside the living organism) methods are followed to measure the dissolution rate of a certain drugs. This method is officially recognized by certain regulatory authority and it(in vitro study) considered most convenient way to develop new formulation of oral solid dosage form.

Comparative Dissolution Consideration

[][]Dissolution method is the best option for the lower strength drug where different strength is proportionally formulated to acquire the biowaiver of certain formulated drug. For a certain product which higher strength bioequivalence study has been carried out and found proportional to the concentration then biowaiver is conceivable to the lower strength.

Dissolution test are considering the most quality control tool for the commercial batch to batch product to monitor its consistency over a certain period of time. It also provides significant information during post approval changes of the certain product as changes made in formulation, manufacturing process and different scale up procedure.

[][]The most physiological factor is considered as the dissolution and solubility of the API and its permeability through the membrane of the GI[Gastro Intestinal] tract. As this measurement is so prone to error due to its complex nature then in vitro study consider the most convenient and reliable procedure to achieve the required target. During development of a certain solid dosage form, dissolution is considered as the best option to determine its quality parameter which have the great impact on the bioavailability of the formulated product.

Comparative Dissolution, Waiver of in vivo bioavailability

[][]BCS system applied in this case so that waiver for in vivo analysis can be assured. BCS [Biopharmaceutical Classification System] is a system which measure the permeability and solubility of drugs in a certain prescribed condition.

[][]The actual aim of BCS is to aid the post approval changes and arranging approval activities based on in vitro data studies.

This system has been optimized based on the oral solid dosage unit as most of the market products are available at oral dosage form [More than 50% total market share, US$23.4 Bn in 2021, US$24.7 Bn in 2022 as estimated, growth rate 5.9%).

[][]Waivers[ means giving permission to skip in vivo bioequivalence study] is actually reserved for those products that meet the specific requirements of solubility & permeability & most of the cases rapid dissolve in body fluid.

[][]Using the BCS, appropriate formulation study shall be developed such as Type II drugs designed as Permeable but insoluble, this class is not the actual right candidate for development of a new moiety.

[][]So, solubility shall be developed to acquire the right dissolution profile. Based on the solubility and permeability BCS has classified the four categories of the product as depicted below

Dosage form challenge

[][]Comparison has been drawn from old drug to new drug formulation, where older drugs compare to the current products are more prone to solubilities. Class II compound has been remarkably increased as 30% to 60% where class I compound has down to 40% to 20% where low solubility has the main cause to encounter the issue.

 A oral solid dosage form is the preferred option but all time this can’t possible the suspension or solution is continued to prove its existence  

[][]Generally a highly soluble active substance and rapidly dissolve dosage form provide better bioavailability and in this case biowaiver can be waived for bioequivalence studies base on its dissolution profile.

[][]If a active substance found low solubility but high permeability then the rate limiting steps of absorption may be consider as dissolution. Most of the cases dissolution profile control the more than one of excipients or special design matrix compounds. So Test condition may be consider as various time frame (10, 15, 20,30, 45 & 6 minutes).

[][]Drugs that are poor soluble in water then various time frame are considered and accepted timeframe is set for dissolution profile. Here USP Type 4 apparatus to be used to develop such type dissolution profile. Most of the time, monograph for combination product is not available at BP or USP the individual monograph shall be used to set the dissolution profile.

Selection of Dissolution Media

Selection of the dissolution media is the vital point to achieve the goal. pH of the media as the key role as all of the dosage form goes to GI[Gastro Intestinal] tract so pH shall be simulate with the GI Tract environment. pH shall be 1.2 to 6.8 which is the physiologic pH range of the body.

ZonepH
[A]Pre-prandial
Stomach
1.8(1~3)
Duodenum6.0(4~7)
Upper Jejunum 6.5(5.5~7)
Lower Jejunum 6.8(6~7.2)
Upper Ileum7.2(6.5~7.5)
Lower Ileum7.5(7~8)
Proximal Colon(5.5 ~6.5)
[B]Post-prandial
Stomach
4.0(3~6)
Duodenum5.0(4~7)
Upper Jejunum 5.5(5.5~7)
Lower Jejunum 6.5(6~7.2)
Upper Ileum7.2(6.5~7.5)
Lower Ileum7.5(7~8)
Proximal Colon(5.5 ~6.5)

Dissolution Statistics

Different cases obtaining after multipoint dissolution which is calculative as follows:
[][]If Test Product and Reference Product both shows dissolution rate more than 85% within first 15 minutes then no calculation is required, they are considered as similar. If it didn’t achieved then seek for next step.
[][]Seek for f2 value[ f2, similarity factor] if f2>50% then it consider similar then in vivo study is not required.
[][]Difference Factor [f1] is the percentage (%) difference between the two curve at the each time period and also measure the relative error between two curve.

How it works

To determine the difference and similarity factor(f2) following pont shall be noted:
[][]Use the Two different products for study, from each product collect 12 unit [12 unit from Test Product & 12 Unit from Reference Product].

[][]Three time point shall be considered[Exclude Point Zero], only one measurement after 85% shall be measured.
[][]Produced curve shall be similar, f2 values shall be close to 100. Most of the time f2 value more than 50 denote similarity of the two curves as well as equivalence of the two products.

 If Three/Four Time points come to the test then following points shall be considered. 

[][]The measurement for the Test Product and the Reference product shall be same. Dissolution Time point shall be same for the both product (10,15,20,30,45,60 minutes etc.). Products which tend to faster dissolution (85% dissolve within 30 minutes) then time frame shall be consider as 10, 15, 20, 30 minutes.
[][]Only One measurement shall be consider after completion of 85% dissolution of both sample and reference products.

System Requirements to Perform Comparative Dissolution

Dissolution Activities shall be continued on USP Type I Dissolution apparatus at 100 RPM or USP Type II Apparatus at 50 RPM using 900 ml of different dissolution media mentioned below.
[][]Media Use in Comparative Dissolution
[][]Acid Media: 0.1N HCL or Simulated Gastric Fluid USP without Enzyme
[][]Acetate Buffer pH 4.5
[][]Phosphate Buffer pH 6.8 or Simulated Intestinal Fluid without Enzyme
[][]If both the Test Product and Reference product shows more than 85% dissolution within first 15 minutes then no calculation required. If not meets the above requirements then calculate f2 Value.
[][]If found f2>50, then the profile considered as similar and in vivo study is not required. Minimum 12 unit of each shall be consider for comparative dissolution.

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Functions of Quality Assurance

Functions of Quality Assurance, Purpose:

Functions of Quality Assurance, The purpose of this SOP ( Standard Operating Procedure) is to outline the functions, principle duties and responsibilities of personnel working in Quality Assurance Department.

Functions of Quality Assurance, Scope:

To provide the guidelines for the proper implementation of the Quality Assurance System at XX Pharmaceuticals Limited ( Both General and Cephalosporin Block).

Definitions / Abbreviation:

[][]Quality Control Department : The Department carrying out day to day activities for the control of procedure, tests & analysis of products/ raw materials/ packaging materials/ stability samples and other relevant analysis of samples at laboratory to assist the manufacturing functions.
[][]Quality Assurance Department: The department carrying out day to day activities for the control of procedure, analysis of documents, regulatory functions, to assist the plant functions for the manufacturing, distributions and other relevant functions.
[][]CAPA : Corrective Action and Preventive Action.

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To follow the guidelines of Quality Assurance
[][]To report their findings to their seniors

Asst. Manager, Quality Assurance

[][]To ensure implementation of the SOP.

AGM, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]Quality Assurance Department shall function for assuring the quality of all the manufactured batches and every stage of manufacturing / processing of drug Products.
[][]This shall be achieved by performing the functions of monitoring as per the laid down QA systems for the following areas:
[][]Monitor of incoming starting and packaging materials.
[][]Manufacturing process and process checks.
[][]Process monitoring and process control.
[][]Production Record Review.
[][]Final release or rejection of every batch of Drug Products for distribution and sale.
[][]Monitor stability testing and evaluation of shelf-life of products.
[][]Complaints handling and product recalls.
[][]Handling of Change Control Systems.
[][]Out of specification investigation.
[][]Investigation of Deviations.
[][]Returned products ( salvage and disposal ).
[][]Internal Quality Audits.
[][]Co-ordinate monthly Quality Review Meeting and implement the effective CAPAs regarding quality improvement.
[][]Control of non-confirming products.
[][]Co-ordinate all validation and qualification activities.
[][]Reprocessing of non-confirming products.
[][]To achieve the objectives of Quality Assurance functions of XX Pharmaceuticals Limited is classified as follows :
[][]To plan and manage all the activities of Quality Assurance Department to assure the quality of all products manufactured by the Company.
[][]To co-ordinate with manufacturing department in controlling their process and products at every stage of manufacturing to meet the established specifications though testing, auditing and reporting.
[][]To co-ordinate for the development of new product formulation, development of specifications, analytical procedure in co-ordination with Quality Control Department and Product Development Department.

[][]To review the adequacy and relevance of specifications & analytical procedures in co-ordination with Quality Control Department and Product Development Department.
[][]To co-ordinate technical audits of the Quality Control Laboratory to determine the analytical quality systems are yielding the highest quality information and to ensure that the analytical instrumentation is functioning properly and calibration and servicing is as per schedule.
[][]To be responsible for the release functions of the QA Department which shall include :
[][]Maintenance of Quality Control records of manufacturing procedures for each manufactured batch.
[][]Records of release, quarantine or rejection of components and finished products, containers, closures and labels based on Quality Control test results.

[][]Routine “Good Manufacturing Practices Auditing” of manufacturing process, control and related areas.
[][]To suggest and organize training program for the development of technical and administration skills of all the employees to meet with cGMP regulations on continuous basis, coordinating with GM, Plant and Quality Head.
[][]To assist Change Control Committee/Technical Committee for overall reviews of non-conformances, failure investigations, analyzing the Quality trends, investigations of market complaints, batch failure investigations, deviations, verifications of change control procedures, updating the specifications, test procedures, manufacturing processes etc.
[][]To liaison with regulatory authorities for new products manufacturing license and renewals of the same and other regulatory requirement.

Annexure:

N/A

Functions of Quality Assurance Read More »

Contract Manufacturing by Third Party

Contract Manufacturing, Purpose:

Contract Manufacturing, To establish a procedure that XX products are manufactured by the contractor using facilities and operations and to ensure that all batches of product manufactured at third party contract manufacturer that conforms to cGMP requirements undergo a formal evaluation of suitability for use prior to release to the market.

Contract Manufacturing, Scope:

The SOP is applicable for all products of XX Pharmaceuticals Limited manufactured & packed by a third party contract manufacturer.

Definitions / Abbreviation:

[][]QA – Quality Assurance
[][]QC – Quality Control
[][]QA – Quality Assurance
[][]BMR – Batch Manufacturing Record
[][]BPR – Batch Packaging Record
[][]ERP – Enterprise resource planning.
[][]cGMP – Current Good Manufacturing Practice
[][]COA – Certificate of Analysis

Responsibilities:

[][]The roles and responsibility is as follows:

Third party contractor

[][]To perform all the manufacturing related activities, analysis of the manufactured & packed product as per the contract/ toll manufacturing agreement

Executive, Production

[][]To check and review the production related activities.

Executive, Warehouse

[][]To supply and update the required raw and packaging materials as per forecast

Executive, QA

[][]To verify the overall manufacturing activities, collection of sample and related documents

General Manager, Plant

[][]Proper follow-up of overall activities

Manager, Quality Assurance

[][]Approval of all the toll manufacturing activities.

Procedure:

Selection of Third Party/ Contract Manufacturer

[][]Carry out GMP audit to assess the prospective contractor’s technical capability, capacity, cost effectiveness & the capability to maintain the required standards of cGMP & product quality.
[][]Document the business objectives and the justification for selecting a third party contractor.
[][]Review the manufacturing strategy which will be applied to the third party contractors.
[][]After developing a third party contract manufacturer, provide the product and their volume to the third party contractor for its technical assessment of manufacturing capability.
[][]Multiple strategies to be followed in selecting third party contractor.
[][]Consider the sources of materials which must meet the approved specification.
[][]Sign a contract manufacturing agreement with the selected contractor for manufacturing / packaging of products which will be followed accordingly.

[][]XX personnel will generate all the relevant documents as per contract manufacturer’s requirements for batch production.
[][]Production Executive will supply a production forecast of the required quantities of each product two months in advance so as to consider in third party’s

[][]production plan. XX shall have the right to revise the forecast in accordance with the market situation informing contractors one and half month in advance.
[][]Warehouse personnel of contract manufacturer will generate a month wise stock statement for raw and packaging materials to XX.
[][]Production Executive will generate the batch no. as per production forecast to Quality Assurance Executive along with requisition copy for BMR & BPR.

[][] QA Executive will issue the photocopy of BMR & BPR to Production Executive for manufacturing by third party. Master copy of all documents will be preserved at QA end.

[][]For testing procedure of raw and packaging materials will be followed as per contract manufacturing agreement. If any material (Raw/ Packaging) which will be tested by third party, will be forwarded by QC Executive from QUARANTINED stage along with forwarding letter to the contractor.
[][]After receiving the test report from third party, QC personnel will disposition the materials as PASSED/ REJECTED following the SOP.
[][]Production Executive along with warehouse Executive will supply all the materials to third party following the production forecast as per requirement within first week of running month. During supply of materials warehouse executive to be ensured the status label as per requirement by third party.
[][]Contract manufacturer will follow their production schedule and manufacturing operation will be started at the presence of Production and QA personnel of XX.

[][]XX personnel will verify all the written instruction in the BMR & BPR following the third party’s SOP as per cGMP requirement.
[][]All the in-process checks (IPC) will be conducted by contract manufacturer along with XX personnel.
[][]In case of any process validation activities will be conducted by XX personnel using the facility of third party.
[][]For testing of bulk intermediate and finished product, responsibility will be performed by XX and contract manufacturer as per contract manufacturing agreement.
[][]Sample for in-process check, chemical test and microbial test will be withdrawn as per agreement policy following the SOP of XX or contract manufacturer. [][]Finished product samples will be withdrawn as per same requirement.
[][]Retention sample will be kept at contract manufacturer’s end. If the retention sample is required for XX, then the sample will be forwarded to XX end by contract manufacturer following their own policy.
[][]Stability sample will be withdrawn from packaging line as per stability protocol and to be forwarded by contract manufacturer to XX end.

[][]If the stability test will be performed by contract manufacturer, samples will be kept in the manufacturer’s end as per protocol. In that cases test report will be forwarded to XX end accordingly. After receiving all the stability data, QA Executive will prepare the stability report.
[][]Third party contract manufacturer’s site will provide XX personnel with full batch documentation, copies of any unplanned event or deviation (including OOS), a copy of any investigation reports and COA reporting analytical test results against specification.
[][]QA and production personnel will review all the batch documents along with supportive records as per checklist for batch documentation after prior release from contract manufacturer.
[][]Original batch document or photocopy of the original will be provided by the contract manufacturer to XX end.

[][]Production personnel will issue the used quantity of raw and packaging materials in the ERP software with the help of IT personnel according to batch production record to update the material status.
[][]After reviewing the batch document, Production and QA representative will send the notification to the third party contract manufacturer about the batch disposition decision.
[][]Upon receiving the batch disposition decision from XX Pharmaceuticals Limited, the third party contract manufacturer will take step accordingly.
[][]XX shall take delivery of the finished products in XX’s own liabilities within fifteen days of intimation by contract manufacturer that the product is ready for dispatch.

[][]After completion of cost related process by both XX and contract manufacturer, central warehouse will receive the finished product and kept in the central warehouse of XX as per storage condition.

Annexure:

None

Contract Manufacturing by Third Party Read More »

Finished Product Handling, Storage & Distribution

Finished Product Handling, Purpose:

Finished Product Handling, The of these guidelines is to assist in ensuring the quality and identity of pharmaceutical products during all aspects of the distribution process such as storage, distribution, transportation, packaging, labeling, documentation and record-keeping practices.

Finished Product Handling, Scope:

This procedure is applicable for all finished products received and stored after receiving from Packaging department by Central Warehouse and different depots of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]QA – Quality Assurance
[][]DIC – Depot In Charge
[][]ERP – Enterprise Resource Planning
[][]CWH – Central Ware House
[][]FIFO – First In First Out
[][]XX – Current version no. of the SOP

Responsibilities:

[][]The roles and responsibility is as follows:

Head of Distribution

[][]Head of Distribution shall responsible for overall the distribution activities.

Depot In Charge (DIC), Central Warehouse & Different Depots

[][]To verify, receive, storage and distribution the finished goods ensuring all the quality.

Head of Sales

[][]To monitor the distribution procedure as per market requirement.

Head of Marketing

[][]Prepare the market requirement for distribution and follow-up of overall activities.

General Manager, Plant

[][]Follow-up of overall activities.

Executive, Vat

[][]Follow the distribution activities as per Government legislation

Executive, QA

[][]Responsible for effective implementation and monitoring of procedure.
[][]Annual depot audit to verify the effectiveness of this procedure.

Manager, HR & Admin

[][]Shall responsible for monitor the effective distribution procedure

Manager, Quality Assurance

[][]To approve of all the distribution activities.

Procedure :

Precautions:

[][]The entire finished product should be handle carefully during distribution, storage, ensuring the quality and identity of the product.
[][]The entire finished product should be stored in product wise respective area maintaining product’s storage condition.
[][]During distribution FIFO should be controlled to avoid mix-up & errors.

Storage :

[][]Finished product will be received by central warehouse personnel from packaging department after getting the finished product release note from QA.
[][]Released finished product will be stored in the central warehouse at the product wise respective area as per storage condition.
[][]Warehouse personnel will monitor and record the temperature in “temperature monitoring record sheet ( Annexure – I)” for twice in a day.
[][]Storage areas should be designed or adapted to ensure appropriate and good storage conditions.
[][]In particular, they should be clean and dry and maintained within acceptable temperature limits. Products should be stored in the pallet which is suitably spaced to permit cleaning and inspection.
[][]Physical or other equivalent segregation should be provided for the storage of released, rejected, expired, recalled or returned products and suspected counterfeits.
[][]Broken or damaged items should be withdrawn from usable stock and stored separately up to final disposition.
[][]Storage areas should be provided with adequate lighting to enable all operations to be carried out accurately and safely.
[][]Periodic stock reconciliation should be performed by comparing the actual and recorded stocks. Stock discrepancies should be investigated by a multidisciplinary committee headed by HR & Admin.

Distribution

[][]All parties involved in the distribution of pharmaceutical products have a responsibility to ensure that the quality of pharmaceutical products and the integrity of the distribution chain are maintained throughout the distribution process from the site of the manufacturer to the entity responsible for dispensing or providing the product to the target consumer as per Government legislation.
[][]Head of Distribution send the depot wise market allocation to central ware house as per marketing/sales requirement.
[][]Central warehouse personal will prepare the released finished product as per market allocation for different depots along with necessary tertiary packaging.
[][]In-charge, CWH will prepare invoice/challan copy as well as ERP entry as per different depot requirement approved by head of Plant or his designee.
Executive, Vat will prepare the vat challan according to depot allocation ( through Musak-11) as per Government rule.
[][]After performing all the related activities, finished products will be transferred to different depot by company own transport or transport agent along with vat challan and invoice copy.
[][]DIC or designee will receive and check the finished pack according to invoice and to be stored following the procedure described on previous steps.

Market Dispatch :

[][]DIC will allocate the finished product as per market requirement for sale. The dispatch and transportation of products should be undertaken only after the receipt of a valid delivery order, which should be documented
[][]Dispatch record will be prepared by DIC and should include at least the following information:
[][]Date of dispatch;
=>Complete business name and address (no acronyms), type of entity responsible for the transportation, telephone number and names of contact persons;
=>Complete business name, address ( no acronyms), and status of the addressee (e.g. retail pharmacy, hospital or clinic);
=>A description of the products including, e.g. name, dosage form and strength ( if applicable);
=>Quantity of the products, e.g. number of containers and quantity per container ( if applicable);
=>Applicable transport and storage conditions;
=>A unique number to allow identification of the delivery order; and
=>Assigned batch number and expiry date ( where not possible at dispatch, this information should at least be kept at receipt to facilitate traceability).

Returned :

[][]If any products undergo as expired or packet damaged which is not fit for use then record the product and stored in a separate area of the depot/warehouse with proper labeling following annexure– II under custody of depot in-charge.
[][]DIC will make an invoice of those products and sent to central warehouse after entry in the ERP to adjust the stock. Returned products will be sent to CWH at every three months interval.
[][]Head of distribution will collect this invoice/challan from different depots and sent to central warehouse after getting prior approval from Head of Sales & Head of Marketing.

[][]After receiving the returned products from different depots, in-charge, CWH will report to QA department along with the approved invoice/challan copy. In-charge, CWH will segregate the returned products according to their nature in a separate area with proper labeling as per annexure-II.
[][]QA executive will take actions following the SOP ‘Disposition of Returned Finished Products.
[][]In case of market compliant or product recall, DIC will inform to Sales or Marketing Department following the respective SOPs Head of distribution will collect the market compliant sample (s) or recalled product(s), batch(s) within seven days of initiation.
[][]Head of QA will take actions for the market compliant and product recall procedure following SOP.
[][]Stock verification of different depots will make through a physical audit by the representatives of Audit & Accounts department once in a year.
[][]A quality audit will be conducted for all the depots headed by QA representative once in a year.

Annexure:

Annexure I – Temperature monitoring record sheet
Annexure II – Returned product label

Finished Product Handling, Storage & Distribution Read More »

Returned Finished Products Disposition

Returned Finished Products Disposition, Purpose :

Returned Finished Products Disposition, The objective is to specify a system to handle the returned finished products for their appropriate and adequate review and disposition in line with the Quality Management System.

Returned Finished Products Disposition, Scope :

This procedure is applicable for disposition of returned finished products and expired ones at XX Pharmaceuticals Limited. (Both General & Cephalosporin Block).

Definitions / Abbreviation:

[][]QA : Quality Assurance
[][]DIC : Depot In Charge
[][]XX : Current Version of SOP

Responsibilities:

[][]The roles and responsibility is as follows:

Head of Distribution

[][]Head of distribution shall collect the finished products from different depots and forward to the central warehouse for final disposition as per procedure.

Depot In Charge (DIC), Central Warehouse

[][]To verify, receive and separately quarantine the returned goods.

Executive, QA

[][]Responsible for effective implementation and monitoring of procedure.

Senior Executive, Cost & Budget (Factory)

[][]To verify all the returned products and make report for stock adjustment memo.

Head of Plant Operation

[][]Follow-up of overall activities.

Head of Quality Assurance

[][]Approval of all the disposition activities.

Procedure:

[][]The returned finished products shall either be destroyed or repacked and made fit for use depending upon the reason for which they have been returned. In either case, the associated risks must be well understood and addressed.
[][]Hence the procedure for disposition of returned finished products is defined depending upon the reason for which products are returned.
[][]Head of Distribution will collect the finished product as per requirement from different depots and send to Central warehouse following the Invoice/ Challan.
[][]On receipt of the products, warehouse (Central) In Charge or designee shall verify the products as per Invoice / Challan. Then warehouse in-charge will label the products to identify the primary cause of return and segregate the returned products in the respective area.
[][]Quarantine the products in area as per classification and inform QA and Head of Plant Operation through Returned Finished Product Note, (Annexure – I).
[][]Reference number for Returned finished products shall be alphanumeric system containing 7 characters. Numbering breakdown is as follows : RG/YY/001
For example : RG/XX/001
=>The first two alphabets shall stand for Returned Goods
=>Next two numeric characters shall stand for year code XX shall denote year 20XX.
=>Next character is followed by three numerical shall stand for serial number, which shall start every year
from 001.

[][]All the expired products returned from the market shall be directed and received at the distribution Department and these shall be destroyed in presence of QA Executive following the SOP of Procedure for Disposal of Materials & Products.
[][]QA Executive shall prepare Authorization and Disposal From for Materials & Products and take authorization for disposal activities.
[][]Head of Quality Assurance or designee shall arrange to verify the reason for return/ recall of the returned products against the intimation.
[][]If the returned products (except expired products) which are fit for further use they shall be repacked through repackaging request form following the Reprocessing/reworking and Repackaging Procedure.
[][]Quality Assurance personal shall examine the products returned because of dirty labeling, packed damaged products can be repacked. To ensure the product quality, QA executive shall draw the sufficient sample for complete analysis (If necessary) and only if found satisfactory and certified accordingly, then the batch shall be allowed for repacking.
[][]For the repackaging activities minimum five unit packs are required for the returned product of same batch no. Less than five unit pack of a same batch shall be disposed following the disposal SOP.
[][]The returned products except expired products which can be repacked to be sent from central warehouse to the manufacturing site and shall be classified and stored separately depending upon the primary cause of return.
[][]Record for issue of packaging material, overprinting and packing shall be maintained on Additional Batch Packaging Record (Primary/Secondary) along with the Repackaging Request Form authorization by Head of Quality Assurance.
[][]If the returned products in the opinion of the Quality Assurance personnel are not considered fit for repackaging, the same shall be destroyed after approval from Head of Quality Assurance.
[][]This repacked part shall be released after compiling of the all related documents and shall be attached to the earlier batch record (BMR/BPR)
Products recalled voluntarily or recalled, as per the directives from Drug Control Authorities the recalled products shall be handled depending upon the reason for product recall; they may be require to be destroyed or repacked.

Annexure:

Annexure I – Returned Finished Product Note

Returned Finished Products Disposition Read More »

Cleaning Validation Procedure

Cleaning Validation, Purpose:

Cleaning Validation, To lay down a procedure for carrying out cleaning validation to establish validated cleaning procedure for manufacturing and primary packaging equipment and effectively maintain cleaning process in validated state. Cleaning must be demonstrated to be effective in order to provide assurance that unacceptable levels of contamination are not carried over into subsequent products. It defines the cleaning validation and verification requirements to ensure that all cleaning procedures which may impact product quality are formally validated or verified. Cleaning must be demonstrated to be effective in order to provide assurance that unacceptable levels of contamination are not carried over into subsequent products. It defines the cleaning validation and verification requirements to ensure that all cleaning procedures which may impact product quality are formally validated or verified.

Cleaning Validation, Scope:

This procedure is applicable for equipment’s used in product manufacturing and primary packaging of XX Pharmaceuticals Limited (Both General & Cephalosporin Block).

Definitions / Abbreviation:

[][]QA : Quality Assurance
[][]QC : Quality Control
[][]CIP : Clean-in-place
[][]OOS : Out of Specification
[][]MACO : Maximum Allowable Carryover

Responsibilities:

[][]The roles and responsibility is as follows:

Concerned Department

[][]To cooperate the validation team to make the cleaning validation job successful.

Quality Assurance

[][]Responsible for the developing and co-ordinate the entire cleaning validation activities as a team leader.

Quality Control

[][]Ensure that analytical method has been prepared and validated before conducting cleaning validation and coordinate all analytical & Microbiological test.
To coordinate all the sampling activities.

Head of Plant Operation

[][]Proper follow-up of overall activities.

Head of Quality Assurance

[][]Approval of all the validation activities.

Procedure:

[][]Prior to conducting a cleaning validation study on an Active Ingredient (of previous product) following activities need to be summarized. A Validation team shall be formed comprising of members from Production, Engineering, Quality Control, Validation / Quality Assurance.

Defining the key elements

[][]Define solubility, toxicity of active ingredient in cleaning validation protocol. If any of the active ingredients are deemed to be more potent or less soluble in water than the ingredients for which cleaning validation has already been completed, or deemed to be particularly difficult to clean from equipment, a new validation study will be carried out.
[][]Define the product-equipment matrix.
[][]Prepare the equipment matrix. Determine the total contact surface area of the equipment/ instruments which are to be used in the manufacturing of that product with the help of Engineering and Production Department.
[][]Determine the scope and establish acceptance criteria.
[][]Develop and validate sampling procedure and analytical method.
[][]Designing the cleaning validation protocol. All protocols shall be as per the Format given I Annexure- I.
[][]Execute the cleaning validation study and protocol.
[][]Summarize the data and compilation of the final report.
[][]Devising and monitoring program to establish that the cleaning process is continued to be in validated state.
[][]Establishing conditions for which re-validation would be required.

Describing the key elements

[][]The product – equipment matrix
[][]Prepare a Product–equipment matrix (Annexure-II) & Equipment matrix (Annexure-III) for the products, equipments used in the cleaning validation study.
[][]The matrixes will provide information about the manufacturing and packing line used for multiple products and possible product contact surface area.
[][]The matrix will indicate the worst case at a glance and justify the acceptance criteria for a cleaning validation.

Determining the scope

[][]The scope includes evaluation of residual contamination of active ingredient.
[][]Cleaning validation to be done based on matrix for including any new product in to the matrix for supplying product to local market. However, all products deemed to be supplied to highly regulated markets, the cleaning validation to be done for every product.
[][]Acceptance criteria for Residual active ingredients: The approach for setting limits can be (1) product specific cleaning validation for all products; (2) grouping into product families and choosing a worst case product; (3) grouping into groups of risk (e.g. cleaning difficulty, solubility, toxicity potency of API, facility volume of product); (4) setting limits on not allowing more than a certain fraction of carryover; (5) different safety factors for different dosage forms.
[][]For determining cleaning validation process, widely used criteria, i.e. 1/1000, will be consider for MACO calculation and to evaluate the cleaning effectiveness.
Establish the limit for Maximum Allowable Carryover (MACO) according to the following equation.

MACO = TDD Previous X MBS/ SF X TDD Next

Where,
=>MACO = Maximum Allowable Carryover: acceptable transferred amount from the investigated product ( “previous” )
=>TDD Previous = Standard therapeutic dose of the investigated product ( in the same dosage form as TDD next)
=>TDD Next = Standard therapeutic dose of the daily dose for the next product.
=>MBS = Minimum Batch Size for the next product(s) (where MACO can end up)
=>SF = Safety Factor ( normally 1000 is used in calculation based on TDD )
#(Ref. APIC : Active Pharmaceutical Ingredients Committee)

[][]However, the other criteria i.e. 10 ppm Criteria, API toxicity data will also be taken into consideration for evaluation of cleaning effectiveness. The cleaned equipment’s will also be checked visually to ensure the cleaning effectiveness.
[][]1/1000 Criteria: NMT 0.1% of the normal therapeutic dose of any product to appear in the maximum daily dose of the following product.
[][]10 ppm Criteria : NMT 10 ppm of any product to appear in another product;
[][]Based on toxicity : LD50 Value of API will be considered;
[][]Visual Inspection: No quantity of residue to be visible on the equipment after cleaning procedures is performed.
[][]API Solubility: The solubility of drug in washing solvent plays a great role in cleaning. The lesser the solubility greater will be the difficulty to remove the residue from surface.
[][]Thus least soluble molecule (based on the pharmacopoeia or other reliable reference) will be taken for the analysis since if least soluble molecule gives satisfactory result in cleaning validation and routine monitoring then we can rest assure for the other higher soluble drug.
[][]API Toxicity: An evaluation according to the toxicities should be carried out based on the material safety data sheet (MSDS).
[][]Other risk factors such as potency and facility volume of a particular product should also be taken into consideration during designing cleaning validation program.
[][]Develop and validate analytical method for cleaning validation sample analysis.

Swab sampling

[][]Generally method involves swabbing of 5 cm2 but larger area could be considered as per regulatory dossier or with proper justification and difficult to clean areas will be considered as per below Diagrammatic representation.
[][]Define the most difficult to clean areas in the piece of equipment (show delineate pictorially as far as possible).
[][]A polyester tipped swab (Texwipe, Alpha swab with long handle) shall be used. One side of swab shall be given horizontal 10 strokes and then reverse side of the swab shall be given vertical 10 strokes.
[][]The swab stick shall be dipped into the screw cap test tubes/ vials containing solvent (Approximately 10 ml). One test tube / vial will be taken for each swab sample.
[][]The test tube / vial will be labeled specifying the particular piece of equipment swabbed & the location (where appropriate).
[][]The soaked swab (in solvent) to be firmly squeezed along the side of the test tubes / vials and then sampling side to be swabbed. After taking samples from the equipment/utensils the swab to be returned to the respective screw cap test tube/vial.

[][]Each vial will be closed with swab inside & sent to QC for analysis of the swab sample.
[][]Study and establish the stability of sample solution storage condition & storage time, based on a protocol.
[][]Perform the recovery analysis on the swab with spiked SS surface/ similar to the equipment material of construction. Recovery of drug shall be not less than 85% after taking into account interference of swabbing material.
[][]Perform the recovery study of the API from the swab stick for record only.
[][]Mention the swab sampling point details in the cleaning validation protocol.

Rinse sampling

[][]For rinse sample collection graduated plastic mug/container, plastic squeezer, stainless steel container to be used, will be cleaned first with 70% IPA followed by sufficient purified water (Wipe with lint free cloth soaked in 70% IPA if required after visual inspection).
[][] After collection of each rinse the required quantity will be transferred to the conical flask for QC submission. To discard the leftover residue in the SS container/ plastic mug these utensils will be cleaned with sufficient purified water before next use.
[][]Same procedure will be followed for MDI unit except for cleaning purpose only absolute ethanol will be used instead of 70% IPA and purified water.
[][]Rinse sample can be evaluated at intervals during the cleaning and at the completion of the cleaning process. Collection of rinse samples should consider location, timing and volume.
[][]Rinse sample allow sampling of a large surface area and of inaccessible systems or ones that cannot be routinely disassembled. However consideration should be given to the fact that the residue or contaminant may be insoluble or may be physically occluded in the equipment.
[][]Study and establish the stability of sample storage conditions and storage time, based on a protocol.
[][]For those equipment or parts (e.g. turret, die and punch of compression machine, hopper) rinse sampling method is not feasible, only swab sampling method will be applied.
[][]At first swab sample will be collected as per plan and will be sent to QC. Then the swab taken area will be cleaned with purified water and finally with lint free cloth.
[][]At first the equipment will be cleaned as per the equipment cleaning SOP and the dismantled parts will be stored in the clean equipment store room after drying.
[][]After collecting rinse samples the cleaned equipment’s will be allowed for self drying before next use. Finally the rinse sample in a closed conical flask with proper labeling will be sent to QC for analysis.

[][]Perform the recovery analysis on the rinse with spiked SS surface/ similar to the equipment material of construction. Recovery of drug shall be not less than 85%.
[][]Microbiological considerations: weather or not CIP systems are used for cleaning of processing equipment, consider the microbiological aspects of equipment cleaning.
[][]The equipment/utensils are considered clean if the total microbial count is less then 25 CFU per 25 cm2/ per swab or 100 cfu/ml taken from equipment/utensils surface and there are no objectionable organisms present ( e.g. E.coli, Salmonella, Pseudomonas aeruginosa, Staphylococcus aureus).

[][]If any growth is observed, appropriate tests to identify the organisms are to be conducted. If the acceptance limit is exceeded, or an objectionable microorganism is identified, then then an OOS investigation must be initiated by the Microbiological Laboratory to identify the source of microbial contamination. Investigation should be done by the manufacturing department.

[][]Contaminated equipment must be re-cleaned and re-swabbed/re-rinsed and it be must meet acceptance limits prior to release for further manufacturing.
For all the types of equipment initial cleaning validation shall be performed on at least three consecutive batches or three runs.

Bracket Approach

[][]The design uses the extremes to cover in between range. That is the largest pieces of identical equipment could cover all of the in between sizes.
[][]The lowest and highest strength of the products.

Worst Case Approach

[][]The most difficult to clean equipment could cover all the easier to clean equipment also.

[][]Initially cover all the types of equipment for three runs.
[][]Type A cleaning done after 6 days (144 hours) from the first day of use of the equipment or area of solid dosage forms.
[][]The dirty holding period of manufacturing equipment should not be more than 5 days.
[][]In case of batch size change, either increase or reduction in the batch size, the matrix shall be re-evaluated.
[][]If a drug product is manufactured in different strengths, cleaning procedures shall be validated for the highest strength of that particular drug product. If the manufacturing line contains multiple products or a single product contains multiple active ingredients, the active ingredient which is least soluble/more in concentration and/or more toxic, hard to clean shall be taken into consideration for cleaning validation/verification.
[][]If there are multiples of particular equipment with same configuration, material of construction and cleaning procedure then cleaning validation of one piece of that particular equipment will be adequate.
[][]If there are different sizes of the same equipment with same cleaning procedure, cleaning validation for the largest size of that particular equipment is adequate.
[][]The worst case selection criteria will be a) Hard to clean product (Color and Flavor) b) Least soluble API c) Maximum toxicity of API d) Minimum therapeutic daily dose e) Facility volume of a particular product.

Execution of cleaning validation protocol/study

[][]Adequate training to the operators (Production, QC and Engineering) shall be given and documented to execute the protocol efficiency.
[][]Ensure that during validation study the results and activities represent regular daily operations.
[][]Ensure that the same piece of equipment is available for the execution of the cleaning by the operators.
[][]Ensure that operator’s variability is addressed during the process design to maximize the representation of results.

=>Cleaning Validation Protocol number shall be given as follow;
CVR/XXX/YY
Where
=>CVP stands for Cleaning Validation Protocol/stands for separator
=>XXX stands for the sequential number which starts from 001 for calendar year.
=>YY stands for the last two digit of the year.

Summarize the data and generate the report

[][]The final result of particular sampling site shall be ‘difficult to clean’ reported and incorporated in the calculations.
[][]Test results shall be complied by Validation/QA.
[][]Any change in procedure shall be approved by QA.
[][]Evaluation of product matrix shall be done periodically or during introduction of any new product into the existing facility.
[][]Objective & Scope: Describe the objective and scope of the cleaning validation / verification in cleaning validation /verification protocol.
[][]Cleaning Validation/Verification Protocol: provides the tabulated test results and the acceptance criteria for each piece of equipment and equipment train.
[][]Cleaning Validation/Verification process shall be concluded with a summarized report incorporated as a final report, which is written and approved.
[][]Tabulation of test results: provides the tabulated test results and mention the acceptance criteria for each piece of equipment and equipment train.
[][]Discussion and Conclusion: discuss the cleaning validation program under study and summarize the outcome of the cleaning validation program.
[][]Cleaning Validation Report number will be same as protocol no. given as follows.
=>CVR/XXX/YY
=>Where, CVR stands for Cleaning Validation Report.
=>Revalidation of cleaning procedure is required in case of following change
=>Equipment or equipment configuration changes.
=>Changes in cleaning procedure and change of formulation where active quality is increased (e.g. overage).
=>Change in acceptance criteria due to change in batch size or introduction of new product (the matrix shall be Re-evaluated by preparing a separate cleaning validation protocol).
=>Process change in manufacturing process (e.g. wet granulation to direct compression and vice versa).
=>The significance of change shall be evaluated collectively by Production, Engineering and QA.
=>Whenever any change control is made to a validated cleaning procedure, due to change in equipment, process, repair or any other valid reason, then the need evaluation shall be done jointly by the Head of Production, Head of Engineering and finally approved by Manager QA.
=> If the decision is made to revalidate, the same be implemented.

Annexure:

Annexure I-Cleaning Validation Protocol
Annexure II-Product Equipment Matrix
Annexure III-Equipment Matrix

Cleaning Validation Procedure Read More »

Product Quality Review

Product Quality Review, Purpose :

Product Quality Review, The objective of carrying out Product Quality Review (APR) is to establish that the product is manufactured as per approved procedures and the trends of results of critical quality attributes are well within acceptable limits.

PQR will also address the review of raw & primary packaging materials used, process validation & revalidation, analytical method validation, cleaning validation & revalidation, stability testing reports, yields, change controls, out of specification results, deviations, failure investigations, CAPAs, rework & reprocessing, market complaints report, trend analysis data, vendor addition/deletion, supplier performance review, retention sample review, batch documentation, drug authority (legal) notices, equipment/utility required, environmental monitoring, etc. done during the review period.

Scope :

[][]This procedure applies to all product manufactured XX Pharmaceuticals Limited (both General & Sterile Block) and is carried out for products manufactured for during calendar year e.g., January to December.

Definition/Abbreviation:

[][]SOP : Standard Operating Procedure
[][]CAPA : Corrective and Preventive Action
[][]PQR : Product Quality Review

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, QA

[][]Responsible to carry out the periodic review of particular product and prepare a report.

Asst. Manager, QA

[][]Responsible to ensure that a formal review of Drug Product / API is undertaken and reported periodically and demonstrate control of the process and effectiveness of any corrective actions required.

Head of Concern Department

[][]To ensure implementation of suggested CAPA.

Head of Quality Assurance

[][]Approval the SOP

Procedure:

Selection of batches

[][]Select the all batches of a product manufactured in the review period.
[][]The batches which are reworked / reprocessed are used must be included in product quality review.
[][]Frequency
[][]Product quality reviews of Drug Products shall be conducted and documented annually.

Schedules for Review

[][]A suitable schedule has to be drawn up by assigning products to person so that review of all products is completed for the stipulated period. The compilation data should preferably to be completed within one month after receiving all data of last batch of evaluation period.
[][]Review of Batch Manufacturing and Packing Records
[][]Review the batch production records for the following particulars:
[][]Review the batch production and packing records of all the batches selected for PQR and record the details like batch numbers, batch production record number and final yields etc.
[][]Review any batch rejections and reprocessing or reworking done during the review period. In such cases highlight the reason, and record the corrective action taken.
[][]Review the process deviation reports are duly adequately investigated, completed and approved.
[][]Record yields of all isolated stages of the product and the yield ranges for all the batches reviewed. Highlight reasons for out of specification yields if any as well as extremes, which are well within limits.
[][]Compile the yield data and prepare the trend charts. Analyze the trend charts, identify and investigate any discernible trends, which are within acceptable upper and lower specifications. Attach the trend charts as in graphical presentation a part of PQR report.
[][]Review in-process control data for key process steps carried out during the manufacture and highlight critical deficiencies.

Review of Environmental Condition

[][]Record the observation for Assurance with environmental condition of manufacturing areas. Critical deviation, if any must be examined in detail to assure how the deviations were taken care of and record observations.

Review of Analytical Reports

[][]For all the batches under product quality review verify all the analytical reports for the following:
[][]Validity of analytical specifications and methods for the products, raw materials and primary packaging materials employed.
[][]Any out of specification analysis and re-testing carried out with explanations for the same.
[][]Review the analytical results for critical parameters like assay, dissolution, loss on drying/water content, related substances etc.
[][]Review any specification changes and also any new analytical instruments added for the testing of the product and raw/primary packaging materials involved in manufacturing the batches for PQR.
[][]Review the calibration /qualification status of instruments used in the analysis of the batches under review.
[][]Review the retention samples randomly for deterioration.
[][]Compile all the critical analytical data (e.g. assay, dissolution) in a graphical presentation as a part of PQR.

Review of Stability Study Program and Data

[][]Stability review data generated for the product during the review period must be verified and critical observations, if any, highlighted with corrective action recommended. On need basis, the review should be extended to previous years as well.

[][]Any recommendations for changes in shelf life must be examined. Record any changes to stability testing protocol and methods during the review period. Any stability failure during the period must be reviewed in detail.

Review of Market Complaints, Returns and Recalls

[][]Market complaints received during the 12 months period of review should be verified for appropriate closure. The corrective & preventive actions taken subsequent to the complaint investigations should be reviewed in detail. Any recall during the period also must be reviewed in detail.

Review of Regulatory Actions

[][]Any regulatory queries with respect to the product under review must be examined in detail. The corrective actions taken and company response to the queries must be examined.

Review of Validation Status

[][]Any validation or revalidation exercises carried out for the process or equipment related to the product under review must be reviewed and findings to be highlighted. Corrective & preventive actions (CAPA) taken, if any, must also be reviewed. Analytical method validation and cleaning validation/revalidation performed during review period must be recorded.

Review of Change Control Documents

[][]Review all the changes made to the system related to the product under review and report the impact on the regulatory and or customer requirements.
[][]Review of Non-conformity and CAPAs
[][]Review the non-conformities and corrective & preventive actions (CAPA), if any, during the internal quality audits.

Review of Critical Equipment & Utility performance

[][]Performance of the critical equipment & utilities used for manufacturing, packaging & testing of the product during the period to be reviewed.

Review of Raw & Primary Packaging Materials

[][]All the batches/ lots of raw materials (active & excipients) and primary packaging materials used for manufacturing & packing of product during the review period to be reviewed.

Review of Vendor Addition/Deletion and Supplier Performance Report

[][]Vendor addition/deletion and supplier performance reports of raw materials (active & excipients) and primary packaging materials to be reviewed.

Review of Retain Sample

[][]Retain samples (retention samples) of all the batches of the finished products to be reviewed every year by visual examination for any evidence of deterioration and observation shall be documented in respective retention sample register. A summary report to be prepared based on the visual inspection. The same report will go to the PQR.

Review of previous APR Report

[][]Observations/recommendations of the previous Product Quality Review report to be reviewed.

Review of Environmental Monitoring:

[][]Annual review of environmental monitoring summary report to be reviewed and a copy of the summary to be affixed as an annexure with the PQR. Any result exceeds the action limit and the actions against the exceed results to be recorded in the review report.

Report:

[][]An overall summary of the annual product review report shall be prepared by the person conducting the review.

[][]Any other observations or improvements or recommendations for improvements if any shall be given in the report.
[][]The report should include trend charts for all relevant data supporting the review.
[][]The report should include a summary and recommendations for actions to be initiated for any deficiencies.
[][]Document Numbering:
[][]Annual Product Review report shall be numbered as follows:
=>PQR/XX/YYY
=>Where ‘PQR’ represents for Product Quality Review.
=>‘XX’ represents the last two digits of the year (e.g. XX for 20XX).
=>“YYY’ represents for serial number of the PQR report.

Annexure: Product Quality Review

N/A

Product Quality Review Read More »

Environment, Health & Safety Procedure

Environment, Health & Safety, Purpose :

Environment, Health & Safety, To establish a system for the environment, health and safety procedure. This covers the various steps that are required to be followed for EHS policy.

Environment, Health & Safety, Scope :

This procedure is applies for all the employees, visitors, suppliers, contractual third party employee and all the persons enter into the premises of XX Pharmaceuticals Limited (Both General and Cephalosporin Block).

Definitions / Abbreviation:

[][]QA : Quality Assurance
[][]QC : Quality Control
[][]PD : Product Development
[][]EHS : Environment, Health and Safety

Responsibilities:

[][]The roles and responsibility is as follows:

All Concerned Personnel

[][]To be responsible to follow the SOP

Emergency Response

[][]Team Member
[][]Key personnel to perform their duties as per procedure

Head of Plant Operation

[][]Responsible to ensure the overall procedure

Head of Quality Assurance

[][]Responsible to Assurance the overall procedure

Procedure:

[][]All the concerned personnel to be followed the updated systems for safety, health and environmental Hazards & risks associated with activities and products.
[][]All the personnel should be followed the improve conditions in order to prevent accidents, health hazards & pollutions.
[][]Everyone should be aware of minimization of waste generation, promote recycling and green Chemistry.
[][]Every personnel should be well known about energy consumption.
[][]Reduce harmful solids, liquids and gas generation.
[][]Safety awareness to be created to our suppliers and customers.
[][]The best extent possible to work with suppliers who themselves have sound safety, health and environmental policies.
[][]To set environmental, health and safety objectives and targets by all departments to improve EHS Performance.

Periodic Health Check-up

[][]After the employment of a new employee, health check-up is conducted by plant physician.
[][]Every employee, particularly production, QA, QC, PD and Warehouse department personnel will have to undergo health examination include health status and personal health history.
[][]Health examination covers general status, respiratory tract status, eyes status, skin cleanliness, cephalosporin sensitivity test.
[][]Personal health report covers the details history of his/her health status.
[][]Health report will be preserved by Executive, HR & Admin.
[][]General frequency of health check-up: At least twice a year.

Personal Hygiene

[][]Any person shows at any time to have an apparent illness or open leisions that may adversely affect the quality of products is not be allowed to handle starting materials, packaging materials, in-process materials or drug products until the condition is no longer judged to be a risk.
[][]All employees will report to their immediate supervisor about any conditions (relating to plant, equipment or personnel) that they consider may adverse effect the products. Health, safety and environment department manage record/documentation of each employee’s health status and maintain the record/documentation updating.
[][]Direct contact is avoided between the operator’s hand and starting materials, primary packaging materials and immediate or bulk product. All personnel are trained in the practices of personnel hygiene.

Emergency Responses

First Aid:

[][]All injuries, regardless of how small, must be reported and treated as soon as possible after an injury.
[][]First Aid facilities are located throughout the working areas.
[][]Supervisor will show his/her employee for the facility locations. If anyone becomes injured or ill any here due to an industrial or non-industrial problem and need immediate medical aid, he/she has to report the Emergency Responses Team and go to the nearest first aid facility the medical department or the security desk.
[][]If the immediate aid is not needed, notify his/her supervisor before proceeding to the nearest first aid facility.
[][]Whenever outside medical assistance is needed, designed first aid responder as per annexure-1 or plant head will call for this assistance.

Fire Emergency Procedure

[][]Every employee will be familiarize themselves during their induction training period with the location of the evacuation routes(Primary &Secondary),first aid station or kit, each fire alarm, each fire extinguisher, the nearest public telephone and the location of the stairway (as indicated on the emergency evacuation Diagrams).
[][]If any person discover fire anywhere in the building, immediately active the nearest fire alarm pull box and call the HR & Admin. State his/her name, location and type of fire.
[][]Only consider attempting to extinguish a fire if it is a very minor and every person should have been trained in the proper operation and use of portable fire extinguishers.
[][]Use procedure of fire extinguisher.
[][]Pull the pin of the extinguisher.
[][]Stand about six to eight feet from the fire where aim is the hose at the base of the fire.
[][]Squeeze the trigger.
[][]Mount, Locate and identify extinguishers so that they are readily accessible to employees.
[][]Only approved extinguisher shall be used. Maintain extinguisher in a fully charged and operable
[][]Condition and keep in their designated places at all times except during use.
[][]Soldered or riveted shell inverting type extinguisher shall be permanently removed from service.
[][]Extinguisher shall be visually inspected monthly, maintained annually and hydrostatically tested
[][]Periodically by Engineering personnel.

Fire protection and control

[][]All employees shall know the location and be properly trained in the operation of all firefighting equipment.
[][]Portable fire extinguishers shall be suitable to the conditions and hazards involved. They also will be provided and maintained in good operating condition.
[][]Each extinguisher will be serviced at least once a year and tagged and dated and dated to show this.
[][]An approved safety container shall be used for handling flammable liquids up to five gallons.
[][]The employee should immediately leave the area using the designated evacuation route through emergency exit path.
[][]When evacuating no one should use elevators, keep to the right, walk-not to run and remain calm but take immediate action.
[][]A preplanned procedure has been established to assist non-ambulatory individuals and have to obey the directions of building Emergency Response Officials.
[][]Small fires can spread rapidly and overwhelmed an area. To contain the fire close all doors behind exit the building. Before opening any door of a room or office that leads to the main hallway feel the door first to see if it is hot.
[][]Open the windows for fresh air and hang a sheet or other similar article, out the window to let the HR department to know him are still inside.
[][]If all exists from a floor are blocked or if any reason personnel must remain in a room/office during a fire or other emergency and advice of his location and situation. Wait for the fire department to assist him.
[][]After exiting the building get far away from the building, all staff members are to assemble in the emergency assembly point located east or west corner of the plant premises for accountability.
[][]Everyone should remain outside the building until the management staff informs him/her that it is safe to return to the building.
Plant head will count the total present employee as per total employee list provided by HR Executive to become sure that there is no one remains contact in the fire.

Emergency disaster procedure

[][]Everyone will be familiarizing with the location of the evacuation routes(Primary and secondary) the nearest public telephone and the location of the stairway (as indicated on the Emergency Evacuation Diagrams).
[][]Depending on the disaster the watch period should be used to prepare for an easy transition into the nearest designated emergency assembly point.
[][]Plant head will count the total present employee as per total employee list provided by HR Executive to become sure that there is no one remains contact in risk area for easy rescue.

Annexure:

Annexure-I: Emergency Response Team (General Block & Cephalosporin Block)

Environment, Health & Safety Procedure Read More »

Disposal of Materials & Products Procedure

Disposal of Materials, Purpose:

Disposal of Materials, To establish a system for the authorization and disposal of rejected/expired materials and products. This covers the various steps that are required to be followed for destruction of rejected/expired materials and products in a safe and legal way with proper authorization.

Disposal of Materials, Scope:

This SOP applies to quality related non-complies or undesirable materials in XX Pharmaceuticals Ltd. (Both General & Cephalosporin Block) from any one of the following interface steps.

Rejected Raw & Packaging Materials

[][]Expired Retention Samples
[][]Manufacturing waste and in process waste (Both raw & packaging materials)
[][]Rejected Intermediate/Bulk Products/Batch Tails/Finished Products
[][]Trial sample for product development
[][]Laboratory waste (Reagent, analysis sample etc.)

Definitions / Abbreviation:

[][]QA – Quality Assurance
[][]QC – Quality Control
[][]PD – Product Development
[][]BMR – Batch Manufacturing Record
[][]Waste – Materials if they no longer are fit for their originally intended purpose.
[][]Non-Waste – Materials that can be recovered and reused in a process.
[][]Hazardous Waste – Waste is considered to be hazardous if it exhibits any of a number of properties related to flammability, explosivity, water/air reactivity, corrosivity, oxidizing potential, acute or chronic toxicity, ecotoxicity or infection.
[][]Non- Hazardous Waste – Waste is considered to be non-hazardous if it DOES NOT exhibit any of the properties related to flammability, explosivity, water/air reactivity, corrosivity, oxidizing potential, acute or chronic toxicity, ecotoxicity or infection.

Responsibilities:

[][]The roles and responsibility is as follows:

Concerned Department

[][]To collect, disposition and proper storage & disposal of rejected materials/products according to this SOP.

Quality Assurance

[][]To review and get prior approval for initial disposition.

HR Executive

[][]To check and monitor regular disposition activities

Senior Executive, Cost & Budget (Factory)

[][]To verifying that all the disposed items and make report for stock adjustment memo.

Head of Plant Operation

[][]Proper follow-up of overall activities

Head of Quality Assurance

[][]Approval of all the disposal activities

Procedure:

Precautions / Special instructions

[][]Wear masks, gloves & safety goggles (eye protective glasses) and other necessary precautions during destruction works and disposal of wastage and expired materials/products.
[][]Avoid scattering after completion of work.
[][]Always keep the plastic bucket/dustbin covered with lids after work.
[][]Wash the container after completion of work.
[][]Do not dispose the waste tablets and capsules directly into drain.
[][]Do not store the in-process waste for disposal for next day.

Disposal procedure for manufacturing & In-process waste from production area

[][]Departmental executives/ operators will ensure that the waste materials are segregated at sources of generation as hazardous & non-hazardous.
[][]Departmental executives/ operators will ensure the waste materials are in their respective designated containers and their physical segregation from passed, approved, quarantined or any finished good materials. They will also separate solid & non-solid waste materials.
[][]In case of new product, Product Development will assess and identify the nature of materials as hazardous & non-hazardous at development stage. Product [][]Development will notify the relevant owners about the disposal procedure of wastes.
[][]The waste packaging materials (polythene bags/cartons/labels/drums/fiber board boxes etc.) will be removed daily from the sections and transferred to salvage yard according to nature of disposal process by service people.

[][]The manufacturing related solid waste materials (waste raw materials, products, IPC materials etc.) will be removed daily from the sections.
Each working area contains separate waste bin with proper labeling for different types of waste as per annexure-V.

[][]Put all the tablets checked during in process check (IPC) for hardness, thickness, friability and weight variation in waste bin placed in respective compression room, IPC room. The same procedure will be applicable for capsule, powder for suspension, rejected tablets, and capsule from blister area and bottles which are used for leak test.
[][]Collect the dust from Dispensing, Granulation, Compression, Encapsulation and Powder filling area in the waste bin placed in the respective area except hazardous waste.
[][]Take all the waste in the washing area. Production & QCOM Executive will be present during disposal and follow up the whole activities.
[][]Take approximately 10 – 15 liters of potable water into a bucket. Dissolve any types of waste mentioned above in this water in quantity sufficient.
[][]After dissolving, transfer the dissolved wastes into washing area and dispose them into drain with plenty of water to ensure proper cleanliness of the drain.
[][]Clean the bucket using Sodium bi carbonate & Sodium Lauryl Sulphate (detergent) powder solution.
[][]Dispose the dust or tablets or capsules collected in a vacuum cleaner in the same way as described above.
[][]The manufacturing waste should have to be disposed immediately the same day of waste produced.
[][]Disposal procedure for laboratory waste (Reagent, analysis sample etc.)
[][]For laboratory waste follow the SOP “Waste management in Quality Control Laboratory” Where XX denote current version.
[][]Disposal procedure for waste generated in the Product Development Laboratory
[][]For the waste generated in the PD laboratory follow the SOP “General waste disposal procedure for product development lab.”  Where XX denote current version.
[][]Disposal procedure for intermediate/bulk products/batch tails/finished products/hazardous waste from manufacturing area
[][]When a finished product/ intermediate products/ bulk product/ batch tails, hazardous waste is to be rejected, the concerned department Head shall raise “Disposal Form for Materials & Products” as per annexure-I for write-off in the part-A.
[][]The form is first to be signed by Concerned Department Head followed by concerned personnel of Factory Accounts & Budget, HR & Admin personnel, General Manager plant and approved by Head of Quality Assurance.
[][]After approval of the Disposal Form for Materials & Products, concerned department will attached the “To Be Disposed” label as per Annexure-III with the rejected materials and to be kept in a dedicated area of the respective production department before the schedule for disposal activities.

[][]The disposal activities to be carried out in the concerned department in the respective washing area.

[][]All the disposal activities will be conducted in a dedicated washing area with direct supervision of QA Executive

Tablets, Capsules & PFS : Non-Betalactam

[][]Wear appropriate Personal Protective Equipment/Clothes.
[][]Sort out the blister strips of tablets & capsules.
[][]Tear the blister strips and take out the tablets from the pouches.
[][]For PFS: Open the Alu. Cap & tear the label.
[][]Pour the powder of the bottles into a plastic bucket.
[][]Keep aside the deformed Alu. Cap, LDP stopper & spoon and send to salvage yard.
[][]Keep the Dry powder, tablets and capsules in a bucket; mix/dissolve the tablets/capsules with water and stirring.
[][]Neutralize the liquid (pH 6 – 9) by using acid/alkali. Dilute 10 – 20% of the liquid by fresh water and drain out with plenty of water or burg.

[][]Tear the printed packaging materials and transfer all the torn packing materials to the salvage yard.

Tablet, Capsules and PFS (Cephalosporin)

[][]Wear appropriate Personal Protective Equipment/Clothes.
[][]Make sufficient quantity of 0.4% (v/v) sodium hypo-chlorite solution.
[][]Sort out the products.
[][]Take out the strips from the cartons.
[][]Tear the blister strips and take out the capsules/tablets & keep in a bucket.
[][]Keep the torn blister strips into a polythene bag.
[][]For PFS: Open the Alu. Cap, LDP stopper & tear the label.
[][]Pour the powder of the bottles into a plastic bucket.
[][]Keep aside the deformed Alu. Cap & spoon and send to salvage yard.
=>Dissolve/mix the dry powder, tablets and capsules in a covered plastic bucket with previously made 0.4% (v/v) sodium hypochlorite solution and stir with a rod. Leave it overnight for at least 12 hrs.
=>Neutralize the liquid (pH 6 – 9) by using acid/alkali. Dilute 10 – 20% of the liquid by fresh water and drain out slowly the materials on the following working day.
=>Clean the drain with adequate water flushing.
=>Tear all packaging materials and transfer the torn packaging material for salvage yard.
[][]After disposal of the product/ materials, Part B of the Disposal Form for Materials & Products shall be signed by concerned person with designation who disposed the products and then jointly checked by Executive, QA and Executive, HR & Admin. and finally approved by Head of QA.
[][]All master copy of disposal records shall be maintained and kept by QA department and another copy will be sent to Concerned Department, HR & Admin Department and Cost & Budget (Factory) department.

Expired Retention Samples

[][]For expired retention sample the same procedure to be followed the procedure stated in 7.4 by raising the Authorization and Disposal Form for materials & products.

Waste Packaging Materials

[][]Collect all the in-processed waste produced from packaging area from the waste bin placed in the respective area.
[][]Tear the wastage label, carton, leaflet and put into a polythene bag by attaching “To Be Disposed” label as per Annexure-III.
[][]All wastage of cap, spoon, and dropper are to be deformed and then put into a polythene bag by attaching “To Be Disposed” label. All wastage of foils, films to be cut and put into polythene bag.
[][]All the wastage packaging materials are to be checked by Production and QA Executive daily. Then the daily waste materials sent to the dedicated salvage yard through warehouse with waste material transfer note (Annexure-IV) with proper notification to HR executive.
[][]After receiving of this waste transfer note by HR executive, this copy will be returned to respective department and to be preserved.
[][]All these packaging waste materials are kept in the salvage yard. These wastages are disposed by the third party as per company policy.
This procedure also applicable for the online rejected materials.
[][]In case of large number of online rejected materials the disposal procedure to be followed by prior approval from Head of QA following the Authorization and Disposal Form for Materials & Products.

Stock Adjustment Procedure

[][]After approval of Authorization and Disposal Form for Materials & Products for Rejected Intermediate / Bulk Products / Batch Tails / Finished Products and online rejected materials, stock adjust memo to be filled up by Cost & Budget (Factory) personnel as per Annexure-II.
[][]After approval from relevant personnel the main copy to be kept in the Cost & Budget department and another copy will be attached with the relevant Authorization and Disposal Form for Materials & Products.

[][]Finally the adjustment to be done on the ERP.

Annexure:

Annexure I- Authorization and Disposal Form for Materials & Products
Annexure II- Stock Adjustment Memo
Annexure III- Label for “To be disposed”
Annexure IV- Waste Material Transfer Note
Annexure V- Waste Collection & Disposal Procedure

Disposal of Materials & Products Procedure Read More »

Quality Review Meeting

Quality Review Meeting, Purpose :

Quality Review Meeting, To define the Quality Review Meeting requirements to ensure that the review and escalation of quality and. Assurance risks, improvement opportunities and strategy settings are handled effectively.

Quality Review Meeting, Scope :

This SOP is applicable for holding Quality review meeting of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]CAPA : Corrective Action and Preventive Action
[][]IPC : In-Process Check
[][]QMS : Quality Management System
[][]OOS : Out of Specification
[][]PPR : Periodic Product Review

Responsibilities:

[][]The roles and responsibility is as follows:

Manager, Quality Assurance

[][]Facilitate the Quality Review Meeting.
[][]Prepare the yearly calendar for the meeting.
[][]Recommend the participant list.
[][]Prepare the meeting agenda.
[][]Communicate with the participants for the meeting.
[][]Prepare and issue the minutes.

Manager, Quality Control

[][]Update Environmental monitoring/ Laboratory system/ KPI/ Rejection.

Head of Engineering

[][]Update maintenance status of plant/machinery.

Head of Plant Operation

[][]Chair the Quality Review Meeting.

Head of Quality Assurance

[][]Approve the yearly calendar for the meeting.
[][]Approve the meeting agenda.
[][]Approve the participant list.

Procedure:

Overview of Quality Review Meeting:

[][]Quality Review Meeting is an essential part of the governance and improvement framework for Quality and Regulatory Assurance within XX Pharmaceuticals Limited.

Operation of the Site Quality Review Meeting:

Attendance

[][]It is essential to have adequate senior representation of quality, operational, and supporting roles at the QRM. The ownership of this Quality Review Meeting lies with Head of Quality Assurance. The meeting will be chaired by Head of Plant Operation or his designee.
[][]The Team members of Quality Review Meeting will be all technical person of the Plant. It is essential that the members shall be present in all the meetings. To conduct a meeting at least 70% participation of the members is mandatory. However, either one of i e Head of Plant or Head of Quality Assurance must be present in the meeting.

Frequency

[][]The QRM will be held on monthly basis. A yearly calendar will be followed, which will be issued at the beginning of the year. The responsibility lies with Head of Quality Assurance.

Meeting Process and Communication

[][]It is the responsibility of Head of Quality Assurance to notify the members of QRM a week before the meeting with agenda (Annexure I).
[][]The members will give their feedback on their part of actions at least three days before the
[][]meeting to the Head of Quality Assurance. This will facilitate the process of updating the previous meeting.

[][]The minutes will contain the following attributes:

For actions and decisions

=>Owner (a single name in preference to group actions)
=>Content
=>Context for full understanding/reason including related agenda item.
=>Current status of action
=>Target completion date

Record Maintenance

[][]Manager, Quality Assurance will maintain all records of the Quality Review Meeting as per SOP for Document Archiving, Retention, and Retrieval & Destruction. Following records will be maintained:
=>Minutes
=>Actions taken
=>Decisions taken
=>Communications

Brief Description of Agenda items

Review of CAPA status

=>Review actions for most significant CAPAs
=>CAPA update on Level of internal audits
[][]Changes to regulatory requirements
=>Quality Review Meeting will Review of any new regulatory requirement that is to be addressed.
[][]Quality Management System
=>Confirm that the review of current practices/standards gaps versus the QMS is rigorous.
=>Review actual QMS performance versus target.
=>Review significant changes within the QMS.

Risk Management – Governance and Improvement

[][]Risk Register: The Quality Risk Register must be reviewed to ensure
=>Risks are being identified.
=>Risks are being assessed.
=>Action plans are being progressed.

[][]Periodic Review of QRM Plan
=>Schedule adherence of QRM Plan
=>Endorse new Quality Plan and any change in Quality plan

[][]Quality KPI Review
=>Batches Not Right First Time (Process & Testing error)
=>Batches Not Right First Time (Documentation error)
[][]Change Controls
=>Review the overall status of Change Control Tracker and ensure there is no overdue.
=>Endorse the final closing of Change Control
=>Review all critical and major change controls.
=>Check that the closure is timely and the actions taken are effective

[][]Deviations, Out of Specifications, Rejects and Reworks
=>Quality Review Meeting will
=>Review deviations, OOS, rejects and reworks
=>Assure itself that reporting is full and complete and that closure is timely (Investigation will not open more than 30 days).
=>Review overall trends and set strategic improvement actions.
[][]Complaints – Vendor and Customer
=>QRM will Ensure that all vendor and customer complaints are reviewed.
=>Ensure that any ‘unofficial’ complaints or comments are reviewed
=>Review the root cause and proposed CAPA
=>Review overall trends and set strategic improvement actions.
=>Review Recalls and Product Incident Review. .
=>Understand and endorse resultant CAPAs.
[][]Periodic Product Review
=>Quality Review Meeting will review.
=>Schedule adherence for the year, and monitor timely completion.
=>Key findings (executive summary) of PPR.
=>Improvement recommendations (CAPA) in PPRs are actioned and tracked.
=>Adverse quality trends are reviewed and actioned.
=>Positive quality trends are reviewed to ensure sustainability (or transfer of a good practice).
=>Correlate change controls with product quality trends.

[][]Validation
=>Schedule adherence of VMP
=>Issue triggered from validation
[][]Stability Studies
=>Review stability test status.
=>Review any adverse stability data and assess impact on product quality and shelf life
=>Take corrective action to mitigate the risk.
[][]Environmental/Utility Issues
=>Review any adverse trend of environmental monitoring results and results of water testing and to assess impact on product quality.
=>Take corrective action to mitigate the risk.

[][]Training
=>Progress against plan (Schedule adherence)
=>Man-hours utilized Retention & Archiving of Documents
[][]Retention & Archiving of Documents
=>Progress against plan
[][]Preventive Maintenance
=>Schedule adherence
[][]IPC Trending
=>Review the monthly IPC observations for any GMP non Compliance
=>Review the IPC observation trend to minimize the IPC failure/ error.
[][]Review of last minutes
=>Comments on previous minutes from the participants.
=>Track progress of actions in the previous minutes of the meeting.
[][]Any other matters to discuss
=>Any other matters not discussed earlier but have an impact on product quality.
[][]After Action Review
=>At the end of the meeting members will review the meeting process, confirm whether it has met the purpose and identify the needs for its improvement for the next meeting.

Annexure:

Annexure-I: Agenda of Quality Review Meeting

Quality Review Meeting Read More »

Personnel Movement, Documents & Materials Transfer Between Cephalosporin & General Block

Personnel Movement, Purpose:

Personnel Movement, To define the procedure to be applied for the movement of people & transfer of documents & materials between Cephalosporin & General block.

Personnel Movement, Scope:

This document lays down the guidelines for the movement of people & transfer of documents & materials between the Cephalosporin & General block of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]QC – Quality Control
[][]QA- Quality Assurance
[][]QA – Quality Assurance
[][]SOP – Standard Operating Procedure

Responsibilities:

[][]The roles and responsibility is as follows:

All Concerned Personnel

[][]To be responsible to follow the SOP

General Manager, Plant

[][]Proper follow-up of overall activities

Manager, Quality Assurance

[][]Responsible to ensure the Assurance to the procedure.

Procedure:

[][]Where the need arises to move or to transfer documents & materials between the Cephalosporin and General block, care should be taken to prevent contamination, to eliminate the potential sources of contamination. Following provisions have to be maintained in such cases:

Movement of people

[][]Entry of the people working in the Cephalosporin Block is restricted to the General Block during or after their working time. They can enter General Block only before entering the Cephalosporin Block as per requirement.
[][]People working in the General Block can enter into the Cephalosporin Block at any time as per requirement. But it should be maintained that they will not enter again into the General Block at that day.
[][]To transfer any documents / samples / tools / equipment from the General Block to the Cephalosporin Block, the assigned personnel will handover that to the person who work at the lobby area of Cephalosporin Block.
[][]The people working in the lobby area will then handover those to the persons inside the change room.

Transfer of Documents

[][]All the master documents related with Cephalosporin block will be preserved in the document archive room of Cephalosporin Block.
Issuing of BMR, BPR, Logbooks, Forms etc. which control is in the General Block will be done after receiving the requisition from the concerned department to Quality Assurance.
[][]But all the requisition will be performed electronically through mail.
[][]Some common SOPs are shared both by Cephalosporin & General Block. In such cases, all the master copies will be preserved in AGM, QA room of the General Block and controlled copies will be distributed in the Cephalosporin Block.
[][]All signatories will be taken within the Cephalosporin Block.
[][]No documents are allowed to be transferred from the Cephalosporin Block to the General Block. If any document is necessary to be sent to the General Block from Cephalosporin Block (e.g. atomic absorption spectrophotometer reading) it will be sent as an information copy through fax or scan or as a form of soft copy through LAN / Internet.
[][]Before the transfer of materials, the required amount of material is collected & to be placed on a pallet. The material is then transferred manually from General warehouse to the receiving bay of the Cephalosporin warehouse. From the receiving bay, the material is transferred to another pallet (dedicated for Cephalosporin block).
[][]For washed & dried glass bottle or crushed sucrose the same procedure stated in above will be followed.
[][]The pallets/ HDPE drums which were used for transferring materials from the General warehouse can be used only after proper cleaning. These pallets must not be used in the production floor; they will be used only in the warehouse.
[][]For analytical purpose, a set of reference / working standard which is required for analysis must be available in the Cephalosporin QC/ Microbiology laboratory.
[][]Product Development Activities: Any kind of process or product development work related with Cephalosporin product must be conducted within the Cephalosporin block.
[][]Engineering Activities: Any kind of maintenance, calibration activities will be done by the dedicated personnel and equipment’s. In case of single calibration instruments, after finishing the tasks at Cephalosporin Block, all the equipment’s will be transferred to Calibration lab. after proper cleaning and de-contamination.

Annexure:

Annexure I- Inter Departmental Materials Transfer Record
Annexure II- Status Label for Inter Departmental Transferred Materials

Personnel Movement, Documents & Materials Transfer Between Cephalosporin & General Block Read More »

Document Control Procedure

Document Control, Purpose:

Document Control, To describe the procedure for activities involved in the preparation, control, retrieval and archiving of quality related documents.

Document Control, Scope:

This procedure covers all the documents issued by Quality Assurance and it also includes documents related to regulatory, calibration, qualification and validation activities at XX Pharmaceuticals Limited (Both General & Sterile Block)

Definitions / Abbreviation:

[][]QA – Quality Assurance
[][]SOP – Standard Operating Procedure
[][]XX – Current Version of SOP

Responsibilities:

[][]The roles and responsibility is as follows:

Procedure:

[][]This procedure shall be applicable for all the new documents, which are prepared from the effective date of this document. The existing document shall be modified as per this procedure whenever due for periodic review or whenever they need to be revised on need basis.
[][]The layout of the Quality Related documents
[][]The layout of SOPs, calibration, validations, guidelines, QA policies, and qualification should be as per the respective templates.
[][]Formats: The format can be designed according to the data that is to be entered. The document number along with revision number, concerned document reference number shall be placed at the top of each page of the format.
[][]Validation protocols and Reports: The format and contents are described in the procedure for validation protocols and Reports.

[][]Quality related documents are essential documents, which establish the quality systems, and are required as per Good Manufacturing Practices (GMP).
Batch Manufacturing Record (BMR) & Batch Packaging Record (BPR): The format and contents are described in the procedure for Preparation, approval, distribution, control & revision of Batch processing records according to SOP.
[][]Specifications, Method of analysis & analytical work sheet: The format and contents are described in the procedure SOP.

Preparation, review and approval/ authorization of documents:

[][]All documents (new or existing) are to be drafted by appropriately qualified personnel of the concerned department and submit to the head of the department for checking. Before submission for checking, the responsible personnel shall initiate a draft copy.
[][]The department Head shall circulate the draft document to concern section Heads for checking. All the comments / inputs shall be written directly on the draft, signed and dated by the respective persons.
[][]After the draft document has been commented on by all the concerned Heads, a final checking /review is carried out by the QA department.
[][]If there are changes, a further document is prepared and circulated until the final draft is agreed.
[][]Concerned department then shall prepare the final copy and assign sequential number (in case of new documents). In case of existing documents, only the version number will be changed.

[][]The final document shall then be signed by the responsible staff. All the draft copies are to be destroyed subsequently.
[][]Concerned department Head shall send the approved master copy to QA for distribution or Issuance of controlled copies.
[][]QA shall issue the controlled copy of documents to concerned departments.

Standard Operating Procedures

[][]Follow the previous step
[][]Sufficient time is given between issue date and effective date to enable training of concerned people.
[][]Batch Manufacturing Records (BMRs) and Batch Packaging Records (BPRs)
[][]After finalization of Manufacturing Record and Batch Packaging Record shall be prepared by Product Development department.
[][]BMR & BPR shall be drafted by Product Development by using relevant template.
[][]Product Development shall send duly signed master copy of BMR & BPR to QA for distribution or Issuance of controlled copies.
[][]QA shall issue the controlled copy of documents to concerned departments.

Specifications, Method of Analysis

[][]Specification: A list of tests, references to analytical procedures and appropriate acceptance criteria that can be numerical limits, ranges or other criteria to which a material must conform to be considered acceptable for intended use.
[][]Test Procedure: Analytical procedures that are to be followed against any test described in method of analysis.
[][]Each material must have unique specifications and test procedures. The test procedure shall give the details of methods to be carried out against each test parameter defined in the specifications.
[][]QC shall prepare final copy of documents and assign sequential number to all specifications, method and analytical work sheet. These Documents shall be prepared, checked and approved by persons as defined in the responsibility.
[][]QC shall send the duly approved master copy to QA for distribution or issuance of controlled copies.
[][]QA shall issue the controlled copy of documents to concerned departments as per previous step.

Qualification and Validation Documents

[][]Concerned Department shall prepare the Qualification documents by using relevant templates.
[][]After finalization of BMR and BPR concerned QA personnel shall be prepared validation documents by using relevant template.
[][]Other qualification and validation documents shall be prepared, checked and approved by persons as defined in the responsibility.
[][]QA shall issue the controlled copy of documents to concerned departments as per previous step.

Distribution or Issuance of Controlled and Uncontrolled documents

[][]All the GMP documents related to the manufacturing plant will be issued by Quality Assurance. The Controlled copies of documents shall be made by Quality Assurance by photocopying the master copy and sealed as

CONTROLLED
Initial………Date..…

=>in blue ink with initial & date of QA Personnel.

[][]If an additional copy of document is required by any department for operational use then Quality Assurance dept. shall issue an additional copy only after written approval from Head of Quality. Such requests shall be obtained through the Request Form as per Annexure – I.
[][]The controlled copies of new documents shall be distributed to the concerned departments and sufficient time should be given before the effective date of the document to enable training of the concerned people.
[][]All formats shall be controlled by QA. The required number of working format shall be copied from control copy by respective department head or his nominee and reconciliation of copied format shall be done by respective department head or his nominee.

Revision of existing documents

[][]Documents such as SOPs, BMR, BPR etc which requires revision due to change control shall be revised by concerned department.
[][]Revised documents shall be given sequential revision No. and controlled by Quality Assurance.
[][]Documents undergoing change due to regulatory requirements / audit Assurance shall also be revised through proper change control by the concerned department.
[][]QA shall distribute the controlled copies of revised documents to concerned departments as per previous step.

Document Archive

[][]All the master documents will be archived at QA end at the document archiving room of both two blocks. At the archiving room, master documents will be kept after recording the archiving no. in the document archive register as per annexure-V.
[][]In the archive room, master document will be kept in a departmental manner as per allocated area for the individual department.
=>Document archive no. will be given as the following format-
=>GDA/XXXX/YYYY
=>Where, GDA represents as General Document Archive. For Sterile block it will be CDA that’s represents as Sterile Document Archive.

=>XXX represents as the Departmental Code as per following List-

[][]Quality Assurance/QA
[][]Quality Control/QC
[][]Engineering/ENG
[][]Production/PRD
[][]Product Development/PD
[][]Microbiology/MICRO

=>YYYY- represents as sequential number which starts from 001.

[][]Document archive room will be lock & key controlled system. Only authorized personnel of QA department will enter in this room for documents preservation. Any other will take authorization from Head of QA to enter this room for document checking or reviewing.
[][]Retrieval or Recall of Obsolete Controlled copies and Superseding of Obsolete Master documents
[][]When the document has been revised following a change request, the older version must be superseded.
[][]Obsolete versions of documents are retrieved and reconciled and entries are made in the specific obsolete register.
[][]All retrieved controlled copies of documents shall be destroyed immediately & recorded.
[][]The Master Copies of the superseded documents along with document change /approval request form shall be archived in the QA department stamped as in Red Ink maintaining the a register.

OBSOLETE
Initial………Date..…

=>in RED ink with initial & date of QA Personnel.

Document Retention

[][]The Retention period of quality related documents is mentioned in Annexure – II.
[][]All quality related documents should be stored securely and safely with controlled access, protected from damage and mutilation. The storage areas and access restriction to the retention of these documents are in the documents archiving room.
[][]The documents related to legal proceeding should be securely kept till the legal proceeding are over.
[][]All documents relevant to quality of the in-house manufactured products must be included in the documents archiving register having a archiving no.

[][]Quality Assurance shall maintain all the Master documents
[][]Responsible Quality Assurance executive shall maintain a log register for taking & re-archiving of documents from Documentation Archiving Room of QAD.
[][]A log register shall be maintained by responsible Quality Assurance executive to archive the Batch Production Records.

Destruction

[][]QA department shall destroy the documents after the retention period is over and maintain a record of the same.
[][]The destruction may be performed by shredding, cutting, tearing, to make the documents non-usable.
[][]A file note will be prepared. A list of documents with sufficient information like document number, effective date, review date etc. (or manufacturing date, expiry date, batch number or lot number of the materials or products etc.) will be attached as an annexure in the file note. Destruction approval will be given by GM, Plant and Manager, Quality Assurance.

Annexure:

Annexure-I: Request for Issuance of Additional Copy of Documents
Annexure-III: Retention Period of Quality Related Documents.
Annexure-III: Document Control Register
Annexure-IV: Log Register for Obsolete Documents
Annexure-V : Document Archive Register

Document Control Procedure Read More »

Hold Time Study

Hold Time Study, Purpose:

Hold Time Study, To establish a procedure for determination of in-process holding time limits.

Hold Time Study, Scope:

This procedure is applicable for all products to be manufactured at both General block and Sterile block of XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]RH – Relative Humidity
[][]NMT – Not more than
[][]QA – Quality Assurance
[][]SOP – Standard Operating Procedure

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure proper handling & storage of hold time sample following this SOP.

Executive, Quality Control

[][]To be responsible to provide analytical support

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]Hold time study for dispensed materials (Active materials), blended granules, bulk tablet, coated tablets, bulk capsules, blister strips, filled bottles to be done.

[][]The sampling & testing frequency will be 7 days and 15 days. In addition for blister and filled bottles-60 days study to be performed. Based on the holding time study the holding period will be fixed.
[][]During holding time study all products were considered withstand the controlled environmental condition (The environmental condition is; %RH: NMT 55.0% and Temperature NMT 25deg.C).
[][]If the holding period of dispensed active materials, blended granules, bulk tablets/capsules, filled bottle and blister strips is more than the time period specified in this SOP then further assessment/retesting to be conducted before further proceeding.
[][]However in case of recoverable residue consumption of capsule products the h. study will be conducted up to four months and based on the analytical data the holding period will be fixed.
[][]The numbering of hold time study report for individual products shall be assigned as per
=>HSR/PXXXXX/YY
=>Where, HSR means Hold time Study Report
=>PXXXXX means the product code
=>YY means the version number of the study report.
[][]Sampling, analytical testing shall be conducted according to annexure- I.
[][]Hold time test of dispensed active materials for a product of different strengths will be done once.
[][]Data shall be compiled and used for establishing in-process holding time limits for different stages of product manufacturer.
[][]The  H. study for equipment should be performed and both clean and unclean state of equipment also be considered. Based on the documented data the equipment holding time period will be established.
[][]After collecting all data the H. time study report will be generated for each product following the annexure-II.

Annexure:

Annexure-I: Sampling stage and testing frequency for hold time study
Annexure-III: Hold time study Report format

Hold Time Study Read More »

Retention Sample Handling

Retention Sample, Purpose:

Retention Sample, To establish general guidelines for sampling, handling and storage of Retention sample of finished products for regulatory testing and for resolution of customer complaints.

Retention Sample, Scope:

This procedure is applicable for both General block and Sterile block at XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]BPR: Batch Packaging Record
[][]QA: Quality Assurance
[][]QA: Quality Assurance

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure proper handling & storage of retention sample following this SOP.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]At the start of packaging operation, retention sample of every batch for different dosage form shall be taken by the Quality Assurance personnel engaged in In-process checking as follows-

[][]Tablet: Not less than 60 Tablets (Equivalent to unit packs)
[][]Capsule: Not less than 60 Capsules (Equivalent to unit packs)
[][]Powder for Suspension: Pack size is 35ml or less- 6 unit packs & Pack size is above 35 ml- 4 unit packs
[][]Kidney Dialysis Fluid: 1 Pack (10 L)
[][]Liquid Sterile: Not less than 60 ml (Equivalent to unit ampoule or pack)
[][]Sterile Powder for Injection: Not less than 10 unit packs

[][]Retention samples of finished product shall be collected from each part (i.e., each type of pack -commercial, trial aid, export, institutional, etc.) of a batch. During collection of retention sample followings shall be considered –
[][]Full retention sample shall be collected from first time packaging whether it is commercial or export.
=>One or two unit packs shall be collected from next each part.
=>Representative samples shall be collected from any pack of export or trial aid pack.
[][]Quantity of the retention sample shall be recorded and signed with date on Batch Packaging Record by the concerned Quality Assurance executive.

[][]Quantity of the retention sample shall be recorded and signed with date on Batch Packaging Record by the concerned Quality Assurance executive.
[][]The samples shall be sent to retention sample store after keeping record into the “Annexure-I: Retention Sample Archiving Log Book” of specific Quality Assurance station.
[][]Before archiving the retention sample in the specific rack, entry shall be given for Product name, quantity, Batch No., Mfg. Date and Exp. Date. At the same time, Serial No. shall be given on the outer side of the carton/pack of retention sample for easy identification.
[][]Serial number of retention sample shall be given as follows-

GR/XX/YYY
Where,
=>“GR” stands for General Retention (For Sterile Block it will be CR)
=>“XX” stands for the last two digit of the year. It will be changed for next year.
=>For example- AA for year 20AA, BB for 20BB and so on.
=>“YYY” is the sequential number. In every new year it will be started from 001 and so on.

[][]Retention sample of each batch shall be kept up to the product shelf life plus one year (minimum).
[][]The Retention samples shall be stored under ambient temperature of the retention sample store (Temperature should be NMT 30ºC). For sterile powder for Injection products this room temperature will be controlled as not more than 25º C.
[][]Temperature of Retention sample store shall be recorded in “Annexure-II: Temperature Record Sheet” regularly (at least two times in a day i.e. at 9:00 AM and 4:00 PM) using calibrated thermo hygrometer. At the same time maximum and minimum temperature shall be recorded at 8:30 AM in each day.
[][]Requisition for Retention sample shall be raised through Annexure-III: Requisition Form for Retention Sample. Samples/Documents shall be provided to requester dept. after getting approval of Head of Quality Assurance. No of supplied retention samples to be recorded in the retention sample register.
[][]After the stipulated storage time (Shelf life plus one year), all the retention samples will be discarded through the SOP of “Procedure for disposal of material and products”, SOP.

Annexure:

Annexure-I: Retention Sample Archiving Log Book
Annexure-II: Temperature Record Sheet
Annexure-III: Requisition Form for Retention Sample

Retention Sample Handling Read More »

Batch Issuance Procedure

Batch Issuance, Purpose :

Batch Issuance, The purpose of this SOP (Standard Operating Procedure) is to provide a documented procedure for issuance of BMR and BPR.

Scope :

Batch Issuance, This procedure is applicable for issuance of BMR and BPR at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]BMR: Batch Manufacturing Record
[][]BPR: Batch Packaging Record
[][]QCOM: Quality Assurance

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Assurance

[][]To ensure implementation of the SOP.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]Issuance Procedure of Batch Manufacturing and Packaging Record (BMR/BPR).
[][]Fill up the respective BMR/BPR details in requisition form (Annexure-II) with signature of user and send to C for the issuance of respective BMR/BPR.
[][]On receipt of BMR/BPR requisition form from production department, QA shall enter the issuance entry in BMR/BPR issue register and then, photocopy the required copy of respective product BMR/BPR from the master copy of BMR/BPR.
[][]QA personnel shall enter the information related to Batch like Batch Number, Manufacturing Date, Expiry Date to photocopy of BMR/BPR.
[][]Send the photocopy of BMR/BPR to production department.

Annexure:

Annexure-I: Batch Issuance Register
Annexure-II: Batch Requisition Form

Batch Issuance Procedure Read More »

Risk Assessment Procedure

Risk Assessment , Purpose :

Risk Assessment , The objective of carrying out the Risk Assessment is to ensure the potential threats to the product quality/ supply are properly assessed and appropriate control measures are in place.

Risk Assessment , Scope :

This procedure applies for the risk assessment of facilities, utility services, equipment & machinery, warehousing, manufacturing, packaging, testing and transfer of quality products from at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Risk assessment: Risk assessment consists of the identification of product quality risk and evaluation of risks. Quality risk assessments begin with a well-defined problem description or risk question. When the risk in question is well defined, an appropriate risk management tool and the types of information needed to address the risk question will be more readily identifiable.

Responsibilities:

[][]The roles and responsibility is as follows

All concerned department heads

[][]To perform the risk assessment associated in his area in a cross-functional team, including one QA personnel as a mandatory member.

Manager, Quality Assurance

[][]To ensure that proper risk assessment is done if there any potential risk(s) involved in the product quality/ supply.

Head of Quality Assurance

[][]Approval of the SOP.
[][]Implementation of risk assessment procedure

Procedure:

=>Risk assessment: Risk assessment consists of the identification of product quality risk and evaluation of risks. Quality risk assessments begin with a well-defined problem description or risk question. When the risk in question is well defined, an appropriate risk management tool and the types of information needed to address the risk question will be more readily identifiable. As an aid to clearly defining the risk(s) for risk assessment purposes, three fundamental questions are often helpful:
[][]What might go wrong?
=>Output for Question 1: Problem/ Failure descriptions- Cause – Failure mode – Effects
[][]What is the likelihood (probability) it will go wrong?
[][]What are the consequences (severity)?
=>Output for Question 2 & 3: Risk Class, Job/Action Priority, Failure rates, Risk priority number (RPN).

[][]Risk identification: Risk identification is a systematic use of information to identify product quality risk or problem description. Information can include historical data, theoretical analysis, informed opinions, and the concerns of stakeholders.

[][]Risk analysis: Risk analysis is the estimation of the risk associated with the product quality. It is the qualitative or quantitative process of linking the likelihood of occurrence and severity of harms. In some risk management tools, the ability to detect the harm (detectability) also factors in the estimation of risk.

[][]Risk evaluation: Risk evaluation compares the identified and analyzed risk against given risk criteria. Risk evaluations consider the strength of evidence for all three of the fundamental questions.

[][]The output of a risk assessment is either a quantitative estimate of risk or a qualitative description of a range of risk. When risk is expressed quantitatively, a numerical probability is used.

[][]Alternatively, risk can be expressed using qualitative descriptors, such as “high”, “medium”, or “low” (Risk class one, Risk class two or Risk class three) , which should be defined in as much detail as possible.

[][]Sometimes a “risk score” is used to further define descriptors in risk ranking. In quantitative risk assessments, a risk estimate provides the likelihood of a specific consequence, given a set of risk-generating circumstances.

[][]Thus, quantitative risk estimation is useful for one particular consequence at a time.

[][]To access and manage risk the following recognized tools will be applied:
=>Risk ranking and filtering will be applied for qualitative (High, Medium or low) risk analysis.
=>Failure Mode Effect Analysis (FMEA) will be used for quantitative estimate of risk. (Score of RPN).
=>Fish Bone Diagram/ Cause & Effect Diagram Analysis

Procedure for Risk ranking and filtering:

[][]Identify the key stages for the part of the supply chain for which the company has responsibility from material supply through to use of product by patients & customers.
[][]Identify potential threats that could impact the product quality or security at each key stage.
[][]Estimate the consequences both in terms of threats and opportunities may be high, medium or low.

[][]Evaluate the exiting control measures for their effectiveness at controlling the threats.
[][]Determine the risk to product quality associated with each threat.
[][]Establish a plan for the introduction of improved controls (additional control measures) where existing threats are not adequately addressed.
[][]Implement the additional control measures and monitor their effectiveness.
[][]To identify the threats the following points should be considered:
=>Patient : Hazard/ risk to the patient safety, patient compliance.
=>Personnel : Attributes, training, education, competence, communication
=>Equipment : Type, design, condition, capacity, location, installation, operation, maintenance & calibration.
=>Facility : Layout, utilities, maintenance, dedication & hygiene.
=>Methods & Procedures : Checking, content, alterations, distribution, utilization, condition, change control, storage, trends, handling planned & abnormal events.
=>Materials : Identity, status, control, quantity, handling, specification, security arrangements, counterfeiting controls & material condition.
=>Environment : Physical effects of climatic & storage conditions (temperature, time, humidity, rain, air pressure, light, vibration etc.), pest infestation, contamination, and damage due to fire or natural disaster like flood, tornado, earthquake etc.

[][]When threats have been identified and commented upon, the table in Annexure – I should be completed.
[][]A judgment should be made on the severity of the consequences & the probability/ likelihood of the adverse events occurring taking into consideration any current control measures that are in place. Each of this can be “low”, “medium”, or “high”.
[][]Considering the severity and probability/likelihood of the events risk will be expressed Risk class one, Risk class two or Risk class three (or, High risk”, “medium risk”, or “low risk).
[][]Risk filtering will be done considering the Risk class (i.e. Risk class one, Risk class two or Risk class three) and detection of the events. Jobs/ actions will be prioritized as High priority, Medium priority or Low priority.
[][]All the jobs/actions for the changed situation shall be identified with in-depth analysis making sure all the impacted areas and the actions with the documentation requirements are assessed and completion date against all the identified actions are set.
[][]Below are two matrixes for clear understanding.

Procedure for Failure Mode Effect Analysis (FMEA):

[][]Risk in an FMEA evaluation has three components: Severity, Probability and detection/ detectability. The first step in any risk assessment is to define the component of FMEA
[][]Definition of the components of the FMEA are:
[][]Severity: if a failure were to occur, what effect would that failure have on the product quality and on the patient (if any)?
[][]Probability of occurrence: how likely is it for a particular failure to occur?
[][]Detectability (ability to detect): what mechanisms are in place (if any) to detect a failure if it were occur?
[][]Each of the above components requires clear descriptions and a corresponding scale to rank or score the projected impact (i.e. a scale for Severity; a scale for Probability; and a scale for ability to Detect). In addition, a composite score would then need to be calculated (e.g. severity multiplied by Probability multiplied by ability to detect)
[][]Non sequential number (e.g. 1,3,5,7, 9) will be used for probability and detection as the use of non-consecutive numbers allow more distinction between rating (table 2 & table 3) and to put more emphasis on the severity criteria a non-linear scoring scale will be utilized (e.g. 1, 4, 9,16, 25) . Please see table 1 for details.

[][]Table 1: Severity criteria for FMEA

Severity
ValueDescriptionCriteria
1IrrelevantNo impact to product quality and process robustness
4SlightNo impact to product quality
9ImportantNoticeable impact to product quality, but can be recovered by reprocessing
16CriticalDefinite impact to product quality that may require rework
25DisastrousBatch failure, not recoverable by rework

Note: Criteria in the above table will be changed based on the subject under assessment

[][]Table 2: Probability criteria for FMEA

Probability
ValueDescriptionCriteria
1An unlikely probability of occurrenceFailure has never been seen in any relevant lab experiments, or scale-up batches yet but it is theoretically possible.
3A remote probability of occurrenceFailure only seen once or twice in relevant lab experiments, never in scale-up batches.
5An occasional probability of occurrenceFailure potential has been noted in several relevant lab experiments, or at scale-up. If procedures are followed the failure potential is minimal.
7A moderate probability of occurrenceFailure potential has been noted in several relevant lab experiments, or at scale-up, in-process control maybe required to avoid failure.
9A high probability of occurrenceFailure potential has been noted in several relevant lab experiment, or at scale-up, an active non-standard feedback control loop may be required.

Note: Criteria in the above table will be changed based on the subject under assessment

[][]Table 3: Detectability criteria for FMEA

Detection
ValueDescriptionCriteria
1High degree of detectabilityA: Validated automatic detection system that is a direct measure of failure.
B: Two or more manual operated validated detection systems, direct or indirect. (e.g. Control range and IPC)
3Good detectabilityA: Single manually operated validated detection system that is a direct measure of failure. (e.g. IPC of failure, validated PAT)
5Likely to detectA: Single manually operated validated detection system that is not a direct measure of failure.
(e.g. PAT measurements or IPC's not directly linked to failure)
7Fair detectabilityA: Non validated (manual or automated) detection.
(e.g. visual level check, visual inspection of vessels).
9Low or no detectabilityNo ability to detect the failure

Note: Criteria in the above table will be changed based on the subject under assessment

Risk Scoring Matrix

[][]The composite risk score for each unit operation step is the product of its three individual component ratings: severity, probability, and detection. This composite risk is called a risk priority number (RPN).
RPN = S x P x D (S= Severity; P= Probability & D= Detection)
[][]The RPN number is not absolute and should be considered in context with other factors that influence the product risk outside the scope of this evaluation. The RPN provides a relative priority for taking action – the bigger the RPN, the more important to address the corresponding failure being assessed.

[][]The table in Annexure – III will be used for FMEA. For each formulation component or manufacturing processing step under evaluation, the function of the component or processing step, potential failure mode and effect of the failure mode should be recorded.

[][]A severity score is then assigned. The root cause of the failure is described and a score is assigned to the probability of occurrence of the failure. Controls that are currently in place to detect the failure are listed and a detection score is then assigned.

[][]The RPN number is calculated. The action(s) that need to be taken to reduce or mitigate the risk are listed and individuals or departments responsible for implementing the actions are identified with target dates for completion.

[][]All the actions for the changed situation shall be identified with in-depth analysis making sure all the impacted areas and the actions with the documentation requirements are assessed and completion date against all the identified actions are set.

Fish Bone Diagram/ Cause & Effect Diagram Analysis

[][]The root cause analysis tool used for major or critical deviation, OOS, market complaint to identify quality defect prevention and potential factors causing an overall effect. Each cause or reason for imperfection is a source of variation. Causes are usually grouped into major categories to identify these sources of variation.

Defining “Effect”

[][]The first step in using the fishbone diagram as a problem solving tool is to clearly define your effect, or outcome that you don’t like. This could be a quality issues, not meeting metrics or troubleshooting the introduction of a new process or product line. This becomes the “head” of the diagram. Use butchers paper or a whiteboard to sketch out the fishbones template.

[][]Defining an effect takes a little practice. Make sure it is brief and succinct. Use facts and numbers where possible. Spend a few minutes reflecting on your effect with the team; does everyone agree that the statement defines the problem as fully as possible?
Brainstorming the “Causes”
[][]With your team, we want to add the bones to this diagram, brainstorming all of the possible influencing factors. Each idea needs to be put into a category or branch.
[][]The following probable categories to be assessed the probable causes through brainstorming is also known as 6M as per annexure-IV
=>Man
=>Machine
=>Method
=>Measurement
=>Material
=>Mother Nature

[][]Man/People/Personnel: Everyone involved with the process across the value stream, including support functions Processes / Methods: This defines how the process is performed and the all requirements needed for doing it, including quality procedures, work orders / travelers / work instructions, drawings.
[][]Machines / Equipment: All machines and equipment, needed to accomplish the job, including tools.
[][]Materials: Raw & Packaging materials, purchased parts and sub-assemblies that feed into the end product.
[][]Measurements: defines how have we determined that the outcome is wrong.

[][]Mother Nature: The standard one which turns to wrong or deviation of the standard outcome
[][]As the team suggests possible causes, determine which heading that idea belongs under, jotting it down clearly. Also add another branch, covering “why” that cause would influence the effect we are investigating. Continue until the team runs out of ideas.

[][]If is there any branches of the diagram that are missing, develop into that area further, asking questions; “Is it possible that the environment has affected our problem” too hot, too cold, too wet?
Document Numbering
[][]The unique document numbering for Risk Assessment shall consist of 9 (nine) alpha-neumerical characters, broken down as follows –
=>e.g. RA/XXX/YY
Where,
=>RA is the Risk Assessment
=>/ is separator
[][]XXX is the sequential number starting from 001, 002 & so on for a calendar year which will be further start from 001 for the next year.
=>YY is the last two digits of the year
=>For example; RA/001/YY
=>Here RA means Risk Assessment
=>001 is the sequential number
=>YY represents for the year 20YY
[][]QA shall issue the Risk Assessment document number and maintain the log register (Annexure – II).

Annexure:

Annexure-I: Risk Assessment Table and Action Plan
Annexure-II: Log Register for Risk Assessment
Annexure-III: Risk Assessment Table and Action Plan
Annexure-IV: Fish Bone Diagram Chart

Risk Assessment Procedure Read More »

Rework and Repackaging Procedure

Rework, Purpose :

Rework, To establish general guidelines for reprocessing, reworking of a full batch or part of a batch of product of an unacceptable quality from defined stage of production so that its quality may be rendered acceptable by one or more additional operation and to set forth method for repackaging of product with proper approval & proper documentation

Rework, Scope :

This procedure is applicable for concern department at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Reprocessing: Reprocessing means the reworking of all or part of a batch of product of an unacceptable quality from a refined stage of production so that its quality may be rendered acceptable by one or more additional operation.
[][]Reworking: Reworking is taking an out of spec. of product and running it through a non–standard process to bring it back in to spec.
[][]Repackaging: Repackaging requires that the final bulk product/ final product be repacked into a specific size or configuration for a special customer order.
[][]SAF: Sample Advice Form
[][]QA: Quality Assurance

Responsibilities:

[][]The roles and responsibility is as follows:

Production

[][]To ensure that Reprocessing/Reworking and Repackaging is done following this SOP.

Concern Department Head

[][]Responsible to perform the job accordingly

Quality Assurance

[][]To monitor and implementation of the procedure

General Manager, Plant

[][]To ensure that the implementation of the procedure as per SOP.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Procedure:

[][]Acceptable Reasons for Reprocessing
[][]Granules or Powder: Granules or Powder shall be reprocessed / reworked to correct uniformity of mixing, uniformity of fill wt. and potency to achieve required quality of granules.
[][]Plain and core tablets: Plain and core tablets shall be reprocessed to correct poor appearance, thickness, weight, hardness to improve content uniformity, disintegration or dissolution rate.
[][]Coated tablets: Coated tablets may be reprocessed to correct poor appearance, disintegration or dissolution.
[][]Capsules: Capsules may be reprocessed to correct weight variation, potency, dissolution rate etc.

Reprocessing/Reworking procedure:

Initiation & Approval of Reprocess/Rework Request form:
[][]If any reprocessing or reworking seems necessary, concerned Department shall raise Reprocess/Rework Request Form (Annexure-I) upon agreement of Product Development Department and Quality Assurance Department.

[][]Each Reprocess/Rework Request Form shall contain a full explanation of the reason for reprocessing and the proposed reprocessing steps.
[][]An investigation shall be carried out by QA with the help of PD and concerned department (if required) to identify the reason and process for reprocessing.
[][]After that the concerned Department Head, Head of PD and General Manager, Plant shall give their comments.
[][]The Reprocessing work shall start only after getting approval of the proposed reprocessing steps from Head of Quality Assurance.
[][]After completion of reprocess, concerned department shall advice Quality Control for analysis through SAF.
[][]When the test result is received from QC, QA shall then give decision about release of the product.
[][]The appropriately filled Reprocess/Rework Request Form (Annexure-I) along with other necessary documents shall become the part of the batch document.
[][]Assignment of Batch No., Manufacturing Date, Expiration Date and Reference No. for Reprocessing/Reworking batch.
[][]In case of reprocessing a part of a batch or full batch, the Batch No. of part shall be the original Batch No.
[][]In case of reprocessing of a product from different batches tails, the batch no. shall be the first batch of among those batches which are to be reprocessed and “R” shall be suffixed for identification of reprocessed batch.

[][]Manufacturing Date of different batches tails that composed/reformed a batch should be within two months.
[][]Reference No. for Reprocessing/Reworking shall be as
RW-001/07/XX
where-
=>RW represents Reprocess/Rework
=>001 represents monthly sequential number
07 represents Month of July. It will be changed in next month
=>XX represents year of 20XX. It will be changed in next year.

Repackaging Procedure (Primary & Secondary):

[][]When any repackaging of product seems necessary, concerned department shall raise proposal through Repackaging Request Form (Annexure-II)
[][]When any finished product (local/export) returned from central store and are required to convert into physician/local/export pack, it shall be processed through Repackaging Request Form (Annexure-II)
[][]An investigation shall be carried out by QA with the help of PD and concerned department (if required) to identify the reason for repackaging and product quality of the part of the batch which shall be repackaged. Necessary analytical work shall be done for repackaging part of the batch by QC (if required).
[][]Concerned Department shall forward sample through SAF (Sample Advice Form ) to QC for analytical work of repackaging part of the batch.
[][]After completion of analytical work, QC shall forward the analytical test result to concerned department.
[][]Concerned Department Head shall forward Repackaging Request Form to PD and subsequently to General Manager, Plant for their comments.
[][]After that, the Concerned Department forwards the Repackaging Request Form along with test result (SAF) to Head of QA for approval.
[][]Reference No. for Repackaging shall be as
RP-001/07/YY where-
=>RP represents Repackaging
=>001 represents monthly sequential number
=>07 represents Month of July. It will be changed in next month
=> YY represents year of 20YY. It will be changed in next year.
=>Finally Repackaging Request Form and related QC test results shall be the part of the batch document.

Annexure:

Annexure-I: Reprocess/Rework Request Form
Annexure-II: Repackaging Request Form

Rework and Repackaging Procedure Read More »

Artwork Management Procedure

Artwork Management , Purpose:

Artwork Management , To lay down the general guideline about preparation, approval and preservation of artwork, printed specimen and approved color and design standard of printed packaging materials that are required to develop packaging materials for products.

Artwork Management , Scope:

This SOP is applicable for art work development of new as well as existing products of both General and Sterile Block in XX pharmaceuticals limited.

Definition/Abbreviation:

[][]PD : Product Development
[][]PMD : Product Management Department
[][]QC : Quality Control
[][]QA : Quality Assurance
[][]SCM : Supply Chain Management
[][]XX : Current Version

Responsibilities:

[][]The roles and responsibility are as follows:

Marketing Department

[][]Preparation and checking of text for the packing materials.
[][]Raise a change control in case of any change in the existing art work.
[][]Prepare the final art work for regulatory submission.
[][]Design of all art work as per dimension and text.

Product Development Department

[][]Checking the draft art work for dimension and texts.
[][]Checking dummy carton and machine proof sample and shade card.

Quality Control

[][]Generation of packing specification according to approved artwork and shade card.

Quality Assurance

[][]Checking the text of draft, dummy and machine proof sample.
[][]Preparation and timely review of the SOP.

Head of Marketing

[][]Check and review of all Art works.

Head of Plant Operation

[][]Review of all art work.

Head of Quality Assurance

[][]Approval of all art works as per XX specification.
[][]Approval of the SOP.

Procedure:

[][]After receiving product proposal report from PMD, PD will generate Artwork Technical specification according to Annexure–I and send to PMD. PD will also preserve a copy in the product master file.
[][]PMD will generate the artwork as per Artwork Technical specification (Annexure-I) and send two copies artwork to Quality Assurance. PMD will also generate material code in ERP.
[][]Each artwork will contain the respective material code and version no. with signature of PMD personnel.
[][]Quality Assurance will check the artwork and will take comment from PD regarding label claim, pack size, primary packaging information, and width of foil etc. for any new product and new width of foil or new dimension of carton for existing products. For any correction Quality Assurance will forward the artwork copy to PMD department for further action.

[][]After all reviewing, Quality Assurance & PD will sign the artwork and then forward to Head of Plant Operation for checking.
In the meantime, size and shape (dimension) of the Packaging materials will be confirmed by machine trial or by operation with dummy samples. After receiving dummy samples from PMD, PD and Production will work jointly to finalize the size and shape.
[][]PD will provide samples of required size strips/blisters to PMD for preparation of dummy carton when requested.

[][]Head of Plant Operation will review the artwork and send to Head of Quality Assurance for final approval.
[][]Quality Assurance will send one copy of approved artwork to PMD and preserve another copy at QA.

[][]For new product, PMD will raise commercial requisition after getting three month stability declaration from PD. After commercial requisition Supply Chain will find out the source for preparation of shade card.

Selection of Color:

[][]PMD will suggest the color of Printed components by considering the following:
[][]Preferably color shall be dissimilar in different strengths of same product.
[][]Color shall be stable and not fade on storage or during any operation of the material.
[][]Suggested color shall be forwarded to PD and Quality Assurance for comment.
[][]In case of any major anomaly in color selection, final decision shall be taken jointly by PMD and PD.

Approved Color and Design Standard of Printed Packaging material:

[][]PMD will then send 5 standards of packaging materials to Quality Assurance. Quality Assurance will check the text of printed components against approved artwork and give comments. These standards are for:
=>PMD Copy
=>Quality Control Copy
=>Quality Assurance Copy
=>Supply Chain Copy
=>Supplier Copy
[][]Quality Assurance will send one copy of approved shade card along with artwork to QC for preparation of specification.
[][]After approval of specification, QA will send controlled copy of specification along with shade card to QC, PMD, Supply Chain and the Supplier.
[][]For supplier approval / alternate source development, Supply Chain will send source approval document to QC through PMD. Source approval documents are:
=>Duly filled Vendor Questionnaire
=>Vendor Approval Form
=>Certificate of Analysis/ Conformation
=>Supplied list of material

Change Control:

[][]Any change in the printed components like foil/ carton/ leaflet/ label shall be processed following SOP.
[][]Any change in pack size or brand name of the product shall require approval of local Drugs Authority/Regulatory Authority.
[][]When any change in packaging components, PMD and Supply Chain should ensure that following documents will be collected from the supplier through Obsolete Form of Artwork/ Supplier (Annexure-II). Documents are:
=>Previous version of Artwork
=>Previous version of Shade card
=>Previous version of Plate positive
=>When any supplier will be rejected from approved vendor list, Supply Chain will be proceed through Obsolete Form of Artwork/ Supplier (Annexure-II).

Annexure:

Annexure – I: Artwork Technical Specification
Annexure – II: Obsolete Form of Artwork/ Supplier

Artwork Management Procedure Read More »

Line Clearance Procedure

Line Clearance Procedure, Purpose :

Line Clearance Procedure, To ensure that the area and equipment to be used for the dispensing, manufacturing and packing of products are free from remnants of previous product/batch.

Line Clearance Procedure, Scope :

This procedure is applicable for clearance of dispensing, manufacturing, packing area & equipments at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]N/A

Responsibilities:

[][]The roles and responsibility is as follows:

Quality Assurance Personnel

[][]Responsible to perform the activities as per SOP.

Concerned department

[][]To maintain procedure as described in SOP

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Procedure:

Dispensing:

[][]Before start of dispensing of raw material/coating material Production Executive shall check the following and keep record in BMR.
[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Equipment cleanliness
[][]Removal of material of previous batch/product from dispensing area
[][]Balance calibration records, daily accuracy check/ function check of balance
[][]Entry in Log book
[][]Status label of material/ component
[][]Cleanliness of container of material to be dispensed.
[][]Quality Assurance Executive shall monitor and then provide counter check/ signature to ensure that line clearance checking has been performed properly by dispensing people and all above stated parameters are satisfactory.

Manufacturing:

[][]For Granulation/ Compression/ Blending of Powder or Pellets/Coating
[][]Before start of any manufacturing operation concerned Production Executive shall check the following parameters and keep the records in BMR.
[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Equipment/ machinery cleanliness
[][]Removal of material of previous batch/product from granulation/ compression/ blending/ coating area.
[][]Balance calibration records, daily accuracy check/ function check of balance
[][]Room Temperature and % Relative Humidity of the granulation/ compression/ blending/ coating area (if applicable)
[][]Entry in Log book
[][]Room display/ Product display

For Powder for Suspension/ Encapsulation:

[][]Before start of any manufacturing operation concerned Production Executive shall check the following parameters and keep the records in BMR.
[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Equipment/ machinery cleanliness
[][]Removal of material of previous batch/product from area
[][]Balance calibration records, daily accuracy check/ function check of balance
[][]Room Temperature and % Relative Humidity of the manufacturing area (if applicable)
[][]Entry in Log book
[][]Room display/ Product display

Packaging:

[][]Before start of any packaging operation concerned Production Executive shall check the following parameters and keep the records in BPR.
[][]Printing Line Clearance
[][]Name of the previous product (to be recorded)
[][]Batch No. of previous product (to be recorded)
[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Entry in Log book
[][]Room display/ Product display

Packaging Area Equipment Clearance:

[][]Area cleanliness, absence of irrelevant/ foreign material
[][]Equipment/ machinery cleanliness
[][]Removal of material of previous batch/product in packaging line
[][]Room Temperature and % Relative Humidity of the packaging area (if applicable)
[][]Entry in Log book
[][]Room display/ Product display

Annexure:

N/A

Line Clearance Procedure Read More »

Batch Release Procedure

Batch Release, Purpose:

Batch Release, This procedure defines the correct procedures for the release and distribution of finished products to ensure Assurance with the requirements of GMP and includes details of the responsibility of the Authorized Persons.

Batch Release, Scope:

This SOP is applied to storage, release and distribution of finished products and it’s supporting activities at XX Pharmaceuticals Limited (Both General & Sterile).

Definitions / Abbreviation:

[][]QA : Quality Assurance
[][]SOP : Standard Operating Procedure
[][]FIFO : First In First Out
[][]COA : Certificate of Analysis

Responsibilities:

[][]The roles and responsibility is as follows:

Production Executive

[][]Check the quantity of the product before transfer into the ware house.
[][]Transfer the finished goods to warehouse.
[][]Issue Transfer Note accordingly

Warehouse Executive

[][]Receive finished goods from the production floor after proper checking.
[][]Keep the finished product into the ware house accordingly.
[][]Transfer the finished goods to central warehouse after getting release note from QA.

Quality Assurance Executive

[][]Check the quantity of the product before transfer into the ware house.
[][]Compilation of Batch Production Record.
[][]Follow the overall batch release procedure.
[][]Quality Control Executive/ Microbiologist
[][]To provide analytical support for various samples drawn for batch release.
[][]Prepare Certificate of Analysis (COA).

Head Of Quality Assurance

[][]Give approval to release the finished goods into the market.
[][]To ensure Assurance of the SOP.
[][]Approval the SOP.

Annexure:

Annexure-I: Checklist for Batch Documentation
Annexure-II: Finished Product Release Note
Annexure-III: Final Inspection Sheet

Procedure:

[][]After completion of packaging operation, finished packed shipper cartons will be stored at the Quarantine area of packaging hall. Production Executive will raise the Finished Goods Transfer Note  to Quality Assurance Department for final inspection mentioning product name, batch number, quantity, master carton number.

[][]The finished product will be transferred to warehouse after physical checking by Quality Assurance Executive according to final inspection sheet (Annexure- III).
[][]Warehouse Executive will check the product name, batch number, quantity, pack size, and label of finished product(s) against the transfer note during receiving.
[][]If all information (Product name, batch number, quantity, pack size, label) of finished product transfer note is matched with transferred quantity, then Warehouse Executive will receive & store the product in QUARANTINE AREA (for finished product) of warehouse maintaining storage condition as per attached product label on the shipping carton.
[][]After completion of full batch packaging, Production Executive will submit the Batch Packaging Record to Quality Assurance Department mentioning the transferred quantity in the BPR for release of the product.
[][]Quality Assurance personnel will review all the documents / parameters according to checklist . If all parameters are found complies, then he/she will compile the full batch production record (BMR, BPR) along with all related documents.
[][]After compilation of the batch documents, QA Executive will entry in the ERP of release note verification and Head of QA will approve the release in the software.
[][]Quality Assurance will attach the Approved Label  in every pallet containing released product. (One labels per pallet).
[][]During reviewing the documents according to the check list, following matters need to be considered.
[][]Batch Manufacturing Record (BMR)
[][]Evaluate all the in-process result are within limit, cleaned/partially cleaned label are available, dispensing weights are accurate & dispensing slip along with print out is available, all manufacturing part has been done as per instruction, all the responsible persons have signed in respective operation stages in BMR.
[][]If any deviation/change control was raised, reference number is recorded in the respective place of BMR.
[][]Review the reconciliation steps are correctly calculated and loss result is justified.
[][]Review the line clearance in each steps of manufacturing and Packaging stages are signed by responsible person.
[][]Review the related Deviation/Change Control is closed and the reference number of this documents are recorded in the respective area of the BMR.
[][]Review the completed BMR is approved by Quality Assurance and Production after completion of operation.
[][]Review the associated documents such as all relevant labels, IPC record, particle count record (If any) is correct and signed. Review all the results are within limit or not. If any results are found out of limit, then related Out of Specification (OOS) is attached with the document.
[][]Review the completed BMR is approved by Head of Production or his/her designate and Head of Quality Assurance or his/her designate after completion of operation.

Certificate of Analysis (COA)

[][]Review the Certificate of Analysis (Chemical and Microbial) is signed and approve by responsible person. Review all the results are within the specification. Review all the print out of QC analysis result attached with COA.

Batch Packaging Record /BPR (Primary and Secondary)

[][]Review all the packaging materials are correctly dispensed and authentication information for packaging start up is correct.
[][]Review the in process checks are routinely performed.
[][]Review the reconciliation steps are correctly calculated and Yield & loss result is justified.
[][]Review the line clearance in each step (i.e. primary packing, secondary packing), inspection and labeling are signed by responsible person.
[][]Review the related Deviation/Change Control is closed check the presence of the Deviation/Change Control reference number into the respective place of BPR.
[][]Review the completed BPR is approved by Head of Production or his/her designate and Head of Quality Assurance or his/her designate after completion of operation.

Review the quantity of the packs and presence of all signatures accordingly.

[][]Head of QA/Designee shall verify the Batch Production Record as per checklist (Annexure-I) for correct entries, reconciliation of quantity, yield, change control, deviation, out of specification (OSS), (if any), in-process checking records analytical test results etc. After reviewing if all the parameters found satisfactory then the Manager, /designee shall release the product for dispatch.
[][]For dispatch of finished product, Quality Assurance personnel will issue the Finished Product Release Note (Annexure-II) for getting approval from Head of Quality Assurance. Finish Product Release Note is a self carbonated pre-printed copy as per the original approved copy of Annexure-II
[][]Which contains three different colors Then one carbonated (Yellow colored) copy of the finished product release note will send to central warehouse for distribution. The original blue colored copy will be attached with the batch document.
[][]In case of release of any optimization or validation batch before completion of process validation report, & risk analysis report must be conducted before release. All the documents are approved accordingly by Head of Quality Assurance or his/her designate.
[][]Full batch will be released at a time after completion of the total packaging operation of the batch.
[][]After QA release, Warehouse Executive will store the released product orderly in separated passed area maintaining storage condition. FIFO must be maintained by warehouse executive during dispatch of the released product for distribution.
[][]Quality Assurance Executive will compile all the batch records and kept in the respective Batch Production Record archive area after keeping record in the document archiving log book.
[][]Batch history which must be kept for one year after expiry of the batch.
[][]Fraction batch quantity can only be released with same batch number (while the batch is fractioned as Commercial, Trial Aid or Export) after approval of Head of Quality Assurance.

Batch Release Procedure Read More »

Room Numbering System

Room Numbering , Purpose:

Room Numbering , To provide guidelines for numbering system to all rooms of General Block and Sterile Block in XX Pharmaceuticals Limited.

Room Numbering , Scope:

This procedure is applicable for assigning sequential identification number to all rooms located on each floor of the production, PD/QC/Microbiology area and other area related to Plant operations such as warehouse, plant room, utility area etc are also included in room numbering system.

Definition / Abbreviation:

[][]None

Responsibilities:

[][]The roles and responsibility are as follows:

Executive / Sr. Executive, Engineering

[][]He / she shall be responsible for assigning the sequential identification number to all rooms.

Quality Assurance personnel

[][]He/she shall be responsible for effective implementation and monitoring of procedure.

Quality Assurance Head or Designee

[][]To ensure implementation of SOP.

Procedure:

[][]Numbering for Room
[][]Each room shall be assigned a unique identification number.
[][]Engineering department shall assign floor wise alpha numeric sequential identification Number to all rooms in a logical order on lay out and record the numbering details in Annexure –I.
[][]Do not repeat the same number to another room.
[][]The room numbering shall be a floor wise sequential number having 6 characters as shown below.
=>e.g. GPRXXX
where
=>(G) is the code for General Block
=>(PR) is the working area code for production
=>(XXX) is the first sequential number of room start from 001 to 999
=>Next room shall be numbered GPR002 ……….& so on.

[][]The Building code for each building is given below.

Building name/ Code

=>General Block/G
=>Sterile Block/C
[][]The Working area code for each area is given below.

Area/ Code

=>Production/PR
=>Packaging/PK
=>Warehouse/ WH
=>Product Development/ PD
=>Quality Control/QC
=>Microbiology/MB
=>Mezzanine /ME
=>Roof Top/RT
=>Engineering/EN

Annexure:

Annexure – I: List of rooms

Room Numbering System Read More »

In Process Check (IPC) Procedure

In Process Check, Purpose :

In Process Check, To set up a general guideline for in-process checking that will be followed during the course of manufacturing. This SOP also includes handling of IPC parameters failure during production.

In Process Check, Scope :

This procedure is applicable to all Production activities such as Manufacturing, Packing and warehouse department at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure
[][]QA: Quality Assurance

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Manager, Quality Assurance

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure: In Process Check

General Instruction:

[][]Check the general environment in the department
[][]Ensure proper gowning by the personnel in concerned work area.
[][]Check for the daily calibration of balance.
[][]Check the calibration status label of machines.
[][]Ensure that the line clearance is obtained before starting the next step.
[][]Ensure the destruction of all In-process, rejects, excess overprinted packing material after packing.
[][]Ensure that the every stage of process, appropriate status label is affixed on equipment /machines and containers.
[][]Non Assurance shall be reported immediately to concerned department Head.
[][]Ensure the completion of documentation at the end of each processing stage.

Warehouse Raw Material: In Process Check

=>Ensure line clearance before commencement of dispensing activity.
=>Ensure all the material having properly labeled.
=>Ensure that only “Quarantine” material is stored in quarantine area.
=>Ensure the transfer of Approved material in “Approved Area”.
=>Ensure that storage conditions of raw material are met.

Ensure the following points on Approved Quality Control labels.

=>Analytical Report Number.
=>Re-test date.
=>Ensure that the loose containers are properly closed after dispensing.
=>Ensure that the material is issued on FIFO basis.
=>Ensure that the environmental conditions are maintained in the respective areas.
=>Ensure that the details on dispensed material, material issues slip/dispensing slip are matching with Material Issuance form.

Warehouse Packaging Material:

[][]Ensure proper segregation of materials.
[][]Ensure proper disposal of the rejected items.
[][]Ensure that the material is issued on First In First Out (FIFO) basis.

Warehouse Finished (Drug) Product:

[][]Ensure that the products are dispatched only after QA release.
[][]Ensure the proper storage of goods.
[][]Ensure that “Quarantine” drug product are stored in quarantine area of Warehouse drug product

Parameter for In-process checking during Dispensing:

[][]Area cleanliness, absence of irrelevant/ foreign material.
[][]Equipment cleanliness.
[][]Cleaning record.
[][]Removal of material of previous batch/product from dispensing area.
[][]Balance calibration records, daily accuracy check/ function check of balance.
[][]Status label checking of raw materials prior to weigh.
[][]Weight checking of materials.
[][]Room temperature and Relative Humidity of Dispensing area.

Parameter for In-process checking during Manufacturing:

[][]Generally following parameters shall be checked during manufacturing of tablet/ capsule/ dry powder
[][]Area cleanliness, absence of irrelevant/ foreign material.
[][]Equipment/ machinery cleanliness.
[][]Cleaning record.
[][]Removal of material of previous batch/product from granulation/ compression/ blending/ encapsulation/filling area.
[][]Balance calibration records, daily accuracy check/ function check of balance.
[][]Room temperature and Relative Humidity of the granulation/ compression area (if applicable).
[][]Room display/ product display.

For Tablets:

[][]In Granulation Stage:
[][]Moisture
[][]Temperature (if applicable)
[][]Relative Humidity (if applicable)

In Compression Stage: In Process Check

[][]Appearance (Shape, Surface texture, Physical flaws, Consistency, Identification marking etc.)
[][]Average weight
[][]Uniformity of weight
[][]Relative Standard Deviation
[][]Hardness
[][]Thickness
[][]Diameter
[][]Friability
[][]Room temperature
[][]Relative Humidity (if applicable)
[][]Disintegration time
[][]Machine speed
[][]Organoleptic test (if applicable)

In Coating Stage:

[][]Appearance (Physical flaws)
[][]Average weight
[][]Disintegration time
[][]Weight gain/ coating loss

For Capsules:

[][]In Encapsulation Stage:

[][]Appearance (Color, Size, Identification marking)
[][]Average fill weight
[][]Uniformity of weight
[][]Disintegration time
[][]Relative Humidity of encapsulation room/ area
[][]Temperature of encapsulation room/ area
[][]Locking of capsule

For Powder for Suspension or Syrup:

[][]In Blending Stage:
[][]Relative Humidity of blending/ manufacturing area.
[][]Temperature of blending/ manufacturing area.

In Filling Stage:

[][]Appearance
[][]Relative Humidity of filling room/ area
[][]Temperature of filling room/ area

[][]For Kidney Dialysis Fluid
=>In Manufacturing Stage:
=>Relative Humidity of manufacturing area
=>Temperature of manufacturing area.
[][]In Filling Stage:
=>Uniformity of filling weight
=>pH of solution
=>Conductivity of solution

Checking procedure for IPC during manufacturing:

[][]Room Temperature and Relative Humidity:
[][]Room Temperature and Relative Humidity shall be checked by using Digital Hygrometer and the result shall be recorded in the Batch Manufacturing Record (BMR) in mentioned stage. Room Temperature and Relative Humidity shall be checked as per frequency specified in BMR/BPR.

Moisture:

[][]Moisture shall be checked by using Mettler Toledo balance following corresponding SOP and the result shall be recorded in the Batch Manufacturing Record (BMR) in mentioned stage.

Appearance:

[][]Parameters (as applicable for dosage form type) as mentioned below shall be checked during start-up and in every fifteen (15) minutes interval. About 500 coated tablets from each part shall be checked after completion of coating. Physical flaws of coated tablets shall be recorded in Coated Tablet Visual Inspection Record Sheet.
[][]Color/ Clarity
[][]Shape of tablet
[][]Identification marking
[][]Physical flows in case of capsule

Physical Flaws/ Acceptable Quality Level

[][]Uncoated Tablet
=>Critical Defects (Cracking, Capping/Lamination)/ 0.025%
=>Major Defects (Erosion, Picking/ Sticking)/ 0.25%
=>Minor Defects (Roughness, Illegible logo, Peeling)/ 1.5%
[][]Coated Tablet
=>Critical Defects (Cracking) / 0.025%
=>Major Defects (Blocking, Color Variation, Erosion, Picking/ Sticking) / 0.25%
=>Minor Defects (Twinning, Roughness, Peeling, Core Erosion, Loss of Logo Definition, Logo Bridging ) / 1.5%

The acceptable quality level of physical flaws of coated/ uncoated tablet are as follows:

[][]Weight:

Tablet:

[][]Weight of 05 composite samples, each of which consists of 10/20 tablets shall be checked during start-up and in every fifteen (15) minutes and the result shall comply with the specification as mentioned below:
=>If theoretical tablet weight is ≤80 mg then composite weight shall be in between ±4.0% of theoretical tablet weight.
=>If theoretical tablet weight is >80 mg or <250 mg then composite weight shall be in between ±3.0% of theoretical tablet weight.
=>If the theoretical tablet weight is >250 mg then composite weight shall be in between ±2.5% of theoretical tablet weight.

Capsule:

[][]Composite Fill weight of 10/20 capsules shall be checked during start-up and in every fifteen (15) minutes and the result shall comply with the specification as mentioned below:
=>If fill weight is ≤300 mg then composite fill weight shall be in between ±5.0% of fill weight.
=>If fill weight is >300 mg then composite fill weight shall be in between ±3.0% of fill weight.

Dry powder:

[][]Empty bottle/ plastic container shall be weighted and then tare button of Mettler Toledo balance shall be recorded.
=>After filling with dry powder the filled bottle/ plastic container shall be weighted again to determine the fill weight.
=>Fill weight shall be checked from each filling nozzle. In case of single filling nozzle at least five fill weight shall be checked.
=>The fill weight shall be within the range as specified in BMR. Fill weight shall be checked during start-up and in every thirty (30) minutes interval.

Uniformity of weight: In Process Check

Uniformity weight for tablet and capsule shall be checked during start-up and in every two (2) hours interval.

Tablet:

[][]A number of tablets shall be weighted individually as per the number of punch (if no. of punch is less than 20, then uniformity of weight shall be checked with minimum 20 tablets) of the compression machine. The printed record of statistical data shall be taken and the result of average tablet weight, range of individual weight and % RSD shall be recorded in BMR. The result shall comply with the specification as mentioned below:
[][]Observed average weight shall be within the range calculated with ±2.5 of theoretical tablet weight.
[][]Relative Standard Deviation (RSD) shall be NMT 6.0%.
=>Observed individual tablet weight shall comply with the specification as mentioned below:
=>If tablet weight is ≤80 mg then NMT two tablets shall be outside ±10.0% and none shall be outside ±20.0% range of theoretical tablet weight.
=>If tablet weight is >80 mg or <250 mg then NMT two tablets shall be outside ±7.5% and none shall be outside ±15.0% range of theoretical tablet weight.
=>If tablet weight is ≥250 mg then NMT two tablets shall be outside ±5.0% and none shall be outside ±10.0% range of theoretical tablet weight.

Capsule:

[][]The uniformity of capsule’s fill weight shall be checked by weighing 20 capsules individually. Then the printed record of statistical data shall be taken and the result of average capsule weight shall be recorded in BMR. The result shall comply with the specification as mentioned below:
[][]Observed average capsule fill weight shall be within the range calculated with ±3.0 of theoretical capsule fill weight.
[][]Specification of Relative Standard Deviation (RSD) shall be NMT 6.0%.
Observed individual capsule fill weight shall comply with the specification as described below:
=>If capsule fill weight is ≥300 mg then NMT two shall be outside ±7.5% and none shall be outside ±15.0% range of theoretical capsule fill weight.
=>If capsule fill weight is <300 mg then NMT two shall be outside ±10.0% and none shall be outside ±20.0% range of theoretical capsule fill weight.

Hardness, Thickness and Diameter:

Tablet:

=>Hardness, thickness and diameter of randomly taken 10 tablets shall be checked by ERWEKA TBH 125 machine and a print of found data with statistical evaluation shall be taken and the result shall be recorded in BMR. Hardness, thickness and diameter shall comply with the limit as specified in BMR. Hardness and =>thickness shall be checked during start-up in every one hour interval and diameter shall be checked during start-up.

Disintegration Time: In Process Check

[][]Randomly selected 6 tablets/ capsule shall be placed in 6 different glass tubes of Electrolab ED2 disintegration tester with/without disc (as applicable). The time by which each tablet/ capsule is disintegrated into smaller particles or granules expressed in minutes shall be recorded in BMR. DT of tablet/capsule shall be checked during start-up and every five hours if the batch runs for more than five hours. General guideline for DT of different forms of tablet/ capsule is as follows:
=>Uncoated/ core tablet : NMT. 15 minutes
=>Film coated tablet : NMT. 30 minutes
=>Effervescent tablet : NMT. 5 minutes
=>Hard capsule : NMT. 30 minutes
=>Soft capsule : NMT. 30 minutes
=>Gastro-resistant capsule : 1-2 or 3 hours in acid medium and NMT. 1 hour in buffer medium.

Friability:

[][]Randomly 20 tablets/ 6.5 gm of tablets (for average weight ≤650 mg) or 10 tablets (for average weight >650 mg) shall be selected for friability test. Initially weight of tablets (W1) shall be taken and then be placed in the Friabilator.
[][]The Friabilator shall be run for four minutes at 25 rpm and then tablets of this machine shall be reweighted (W2).Friability of tablets shall be calculated with following formula:

% Friability =W1–W2/ W1×100

[][]A Maximum weight loss NMT 1.0% is considered acceptable for most of the products. Friability of effervescent tablets and chewable tablets may have different specifications.
[][]In case of hygroscopic tablets, an appropriate humidity-controlled environment is required for friability.
[][]Friability shall be checked during start-up and in every two (2) hours interval and be recorded in BMR.

Reconstituted volume for dry powder:

[][]Glassware required for doing the test is 50 ml or 100 ml graduated cylinder.
[][]Water (quantity) shall be taken as specified for the product with a graduated cylinder.
[][]Water shall be poured to the filled bottle and syrup/ suspension shall be made as specified in Leaflet/ Inner carton of the product.
[][]Any observed anomaly (e.g. color, odor, consistency etc.) and the volume with the same cylinder shall be checked.

Parameter for In-Process Checking during packaging:

[][]In case of export besides the following some additional parameters (where applicable) shall be checked like registration no. on foil/label/carton, Text of foil (English/ Bengali), Security overprint on blister/strip etc.

Area:

[][]Room cleanliness
[][]Machine cleanliness
[][]Temperature (0C) [if applicable] [][]% Relative Humidity (if applicable)

Bulk Product:

[][]Product name and strength
[][]Appearance of bulk
[][]Strip/ Blister packing:
[][]General appearance of bulk
[][]Cutting/ perforation
[][]Pocket formation, empty or ruptured pocket
[][]Broken tablets in pocket
[][]Print and color of foils
[][]Color and cleanliness of film (if applicable)
[][]Printing/embossing of Batch No., Mfg. Date and Expiry Date on blister/strip (as applicable)
[][]Improper or inadequate knurling
[][]Sealing (Leak Test)
[][]Camera challenge test (If available on blister machine)

Glass Bottle/ Plastic Container Filling & Packing (Tablets & Capsule):

[][]Appearance of bulk
[][]Quantity per bottle/ container
[][]Cap sealing/ Leak test (as applicable)
[][]Relative Humidity (RH) and Temperature in filling area
[][]Product name with strength on label
[][]Coding Batch no./ Mfg Date/ Exp. Date/ MRP on label (as applicable)
[][]Print and color of label
[][]Security overprint (if applicable)

Inner Cartoning:

[][]Product name and strength
[][]Coding Batch no./ Mfg. Date/ Exp. Date/ MRP (overprinting)
[][]Presence of Leaflet/ Dropper/ Spoon/ Cup/ Cylinder (if applicable)
[][]Adaptability
[][]No. of strip/ blister per pack
[][]Placing of Holographic sticker (if applicable)

Shipping Carton:

[][]Product name and strength
[][]Coding Batch no./ Mfg. Date/ Exp. Date (as applicable)
[][]No. of inner cartons
[][]Serial no.
[][]Size no. and adaptability
[][]Date of cartoning
[][]Signature of the person closing the shipping carton

Checking procedure for IPC during Packaging:

Room Temperature and Relative Humidity:

Room temperature and relative humidity shall be checked as stated above

Leak Test:

[][]At least one sample of conventional strip/ blister/ bottle/ plastic container from each delivery/ cutting channel of the machine shall be picked up from packaging line except sealing machine of one delivery/ cutting channel where two samples shall be collected and checked for integrity following corresponding SOP.
Frequency of Leak test shall be as per following table:

Sample/ Frequency

=>Blister/ Start-up and every hour
=>Empty sealed glass bottles/Start-up and in every hour

[][]If color solution enters into any of the pocket of the strip(s)/blister, into bottle(s)/ plastic container(s) it indicates the leakage.
[][]Calculate the percentage of leakage and record in Leak Test Record Sheet.

Tablet/ Capsule Counting Procedure:

[][]Tablet/ capsule counting procedure shall be performed during start-up and in every 30 minutes.

Annexure: In Process Check

Annexure-I: Coated Tablet Visual Inspection Record Sheet
Annexure-I: Leak Test Record Sheet

In Process Check (IPC) Procedure Read More »

Recall Procedure

Recall, Purpose :

Recall, To ensure recall of products that are known or suspected to be defective or hazardous in accordance with a pre-determined plan promptly and effectively from the market

Recall, Scope :

This procedure is applicable for all products manufactured and distributed from XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Recall: A process for withdrawing or removing a pharmaceutical product from the pharmaceutical distribution chain because of defects in the product, complaints of serious adverse reactions to the product and/ or concerns that the product is or may be counterfeit. The recall might be initiated by the manufacturer, wholesale dealer, license holder, or Department of Health.
[][]Market Withdrawal: Market Withdrawal means a firm’s removal or correction of a distributed product which involves a minor violation that would not be subjected to legal action by the Drugs Administration or which involves no violation, e.g., normal stock rotation practices, routine equipment adjustments and repairs etc.
[][]PMD: Product Management Department
[][]QA: Quality Assurance

Responsibilities:

The roles and responsibility is as follows:

Head of PMD

[][]Responsible for determining the intensity of recall to be taken by consultation with Head of QA and taking necessary action.
[][]When product is distributed in domestic/ overseas market, Head of PMD or his authorized nominee shall inform Head of QA for the action to be taken for recall.
[][]Coordinate the recall after obtaining approval from Managing Director.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Classification of Recall:

[][]Recalls are classified according to the following system
Class I recalls: Occur when products are potentially life-threatening or could cause a serious risk to health.

Examples of Class I Defects

[][]Wrong Product (label and contents are different products)
[][]Correct product but wrong strength, with serious medical consequences
[][]Microbial contamination of sterile injection or ophthalmic product
[][]Chemical contamination with serious medical consequences
[][]Mix up of some products (‘rogues’) with more than one container involved.
[][]Wrong active ingredient in a multi-component product with serious medical consequences

Class II recalls: Occur when product defects could cause illness or mistreatment, but are not Class I.

Examples of Class II Defects

[][]Mislabeling e.g. wrong or missing text or figures
[][]Missing or incorrect information- leaflets or inserts
[][]Microbial contamination of non-injectable, non-ophthalmic sterile product with medical consequences
[][]Chemical/ physical contamination (significant impurities, cross contamination, particulates)
[][]Mix up of products in containers (“rogues”)
[][]Non-Assurance with specification (e.g. assay, stability, fill/ weight or dissolution)
[][]Insecure closure with serious medical consequences (e.g. cytotoxics, child resistant containers, potent products)
Class III recalls: occur when product defects may not pose a significant hazard to health, but withdraw may be initiated for other reasons.

Examples of Class III Defects

[][]Faulty packaging e.g. wrong or missing batch number or expiry date
[][]Faulty closure
[][]Contamination- microbial spoilage, dirt or detritus, particulate matter
[][]Recall system shall be followed in case of Instructions from Regulatory authorities or Voluntary recall by XX authority.

Reason:

=>Reports of adverse reaction.
=>Non-conforming result of on-going stability study.
=>Formulation problem/ Mix-up/ contamination.
=>Labeling errors.
=>Any other reasons.
[][]Head of Quality Assurance shall advise to carry out proper investigation for confirmation of reported defects either jointly or independently by QC, PD, Production & Quality Assurance. PMD personnel can also participate in investigation.
[][]After confirmation and justification of reported defects, Head of Quality Assurance shall discuss with Head of Production and Head of PMD.
[][]Once it is agreed to recall the product(s), Head of Quality Assurance shall seek permission for it from Managing Director (Annexure-III). A Recall Reference no. shall be given on this form as follows:

PR/XX/001
=>Where, ‘PR’ represents Product Recall.
=>‘XX’ represents the last two digits of the year 20XX
=>‘001’ represents for serial number

Recall Panel:

=>Managing Director (MD)
=>Head of Quality Assurance
=>Head of Production
=>Head of PMD
=>Head of Sales
=>Head of Distribution
=>Head of Quality Assurance shall furnish the batch details for recall notification in Annexure-IV. This shall be then forwarded to Head of PMD and Head of sales.

Recall notification shall include:

=>Products name including brand name, its strength and pack size and other details like,
=>Product License (D.A number) if applicable.
=>Batch or Lot number, Batch size, Mfg. date, Exp. date.
=>Nature of defect and reason.
=>Action to be taken (urgent within time frame/ immediate quarantining of stock /return stock) with labeling instruments & specific precautions.
=>Date of  withdrawal.

[][]The Head of PMD through Distribution shall send a product recall circular, immediately upon receiving the product recall decision, to all concerned persons requesting them to return all stock of the batch under question to the depots and informing them that a credit note for the stocks returned shall be issued to them at the earliest.
[][]All product recall requests shall be given top priority unless otherwise indicated by recall coordinator.
[][]The Head of PMD along with Distribution shall immediately arrange to freeze all stocks of the batch lying with distributors, agents and customers. He shall also instruct the entire sales force to freeze further sales of batch at every distribution, sales point (stockiest, chemists, doctors, hospitals etc). This shall also include goods under transit.

[][]In case of recall as per directives of competent or Regulatory Authorities, the information shall be forwarded to them (To include Regulatory Authorities of other Countries to which the batch has been distributed). The decision of disposal of recalled batch shall be as per their directives and the destruction or disposal shall be done under notification and the Drugs Inspector’s supervision.
[][]Quality Assurance Department will record the receipt, origin & quantity of any recalled product received & holds the recalled product in a secure place to avoid mix up with other materials.
[][]The progress  should be reviewed at regular, frequent intervals to monitor its effectiveness and ultimately to decide that the recall is completed.
[][]Completion will normally be reached when:
=>All the acknowledgement forms issued are returned.
=>The material listed in the acknowledgement forms has been returned.
=>There have been no further returns or further adverse reports concerning the product for a period of 2 weeks.
[][]After thorough investigation, Head of Quality Assurance will issue instructions for safe disposal of the recalled stock in due course and a disposal record will be maintained. An investigation into the root cause analysis of any product defect which led to a recall must be carried out and CAPAs to be prepared to prevent if happing again.
[][]Details of recalls shall be added to the batch dossier for all the batches concerned.
[][]Detailed records of all product returned as part of a recall must be kept.
[][]In case of recall when initiated by company (Voluntarily) this shall be informed to the Regulatory Authority.
[][]In case of voluntary recall, product when received back from market to our depots shall be identified and stored separately in a secured area while awaiting a decision on its disposal. The product shall be written off and destroyed as per the standard procedure.

Documentation:

[][]The decisions, activities and actions including progress of recall shall be documented and duly authorized.
[][]On completion of recall procedure, summary report shall be prepared which shall include the following (Annexure V).
[][]Reason for recall of a product (with Batch No. and other details about the product).
[][]Effectiveness of recall.
[][]Corrective action to prevent reason for recall.
[][]Appropriate training to concern as applicable.

[][]This summary report shall be prepared by Head of Quality Assurance and be circulated to all concerned departments (PD, Production, Accounts, Sales, PMD) and Managing Director.
[][]Distribution records should be readily made available to the person(s) responsible for recall and contain sufficient information of wholesalers, retailers, stockiest and customers/agents for prompt and effective it. (Examples: Addresses, Telephone numbers, inside or outside office working hours, batch number and its quantity with them for both domestic and exported products).

Recall Simulation:

[][]The recall procedure shall be regularly reviewed to ensure that it is up-to-date and shall be simulated ‘in house’ to ensure its effectiveness and familiarity to all key personnel.

[][]The required time limit for simulation exercise (from initiation of  simulation to completion) will be not more than 15 days.

Annexure:

Annexure-I: Product Recall Flowchart
Annexure-II: Product Recall Log Book
Annexure-III: Product Recall Form
Annexure-IV: Recall Notification Form
Annexure-V: Summary Report of Recall

Recall Procedure Read More »

Floor Inspection by QA Inspector

Floor Inspection, Purpose :

Floor Inspection, The purpose of this SOP is to describe the roles, responsibilities and activities of production and QC floor inspection and IPCs check by QA personnel and to ensure Assurance with cGMP requirements.

Floor Inspection, Scope :

This procedure is applicable for cGMP observations of production and QC floor at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]IPC : In Process Check
[][]QA : Quality Assurance
[][]QC : Quality Control
[][]OOS : Out Of Specification
[][]DT : Disintegration Time

Responsibilities:

[][]The roles and responsibility is as follows:

Quality Assurance Personnel

[][]Responsible for inspection of Production and QC floor to find out any cGMP observations.

Manager, Quality Assurance

[][]To ensure implementation of the procedure

Head of Quality Assurance

[][]Approval of SOP

Procedure:

[][]To assure Assurance with specification throughout a production process, Production Department will conduct the IPC checks following the In-process checks procedure.
[][]IPC inspectors of QA will verify the IPC data independently.
[][]The IPC specification will be mentioned in the relevant product specification and BMR & BPR.
[][]All OOS results will be investigated as per OOS results procedure.
[][]IPC inspector will verify the IPC data based on the frequency described in Annexure–I.
[][]During manufacturing of a batch, production personnel will check the IPC parameters.
[][]If a IPC data goes outside specification, production IPC checking personnel and QA IPC inspector will inform to production Executive for corrective measures.
[][]If QA IPC inspector observes that there is frequent failure of the IPC results then QA IPC inspector will notify the issue to Departmental Manager and Manager, Quality Assurance.

All IPCs will be performed by trained and certified QCOM and Production personnel. Inspection of

=>Adherence to Line clearance
=>Environmental conditions
=>Log books
=>General house keeping
=>Labelling status
=>Sampling
=>Reconciliation
=>Calibration status
=>Deviation
=>Pest controls
=>Cleaning & Contamination
=>Change Control
=>Document management
=>Adherence to maintenance schedule

Inspect GMP compliance in

=>Storage of Raw/Packaging materials/Finished packs
=>Manufacturing/packaging/cleaning operations
=>Dispensing of materials
=>Compliance with SOPs
=>Daily balance monitoring records
QA inspectors will visit the production floor daily. The inspection applies to all operations, specially The following:
=>If any unusual observation comes to the notice of area QA inspector, he will immediately communicate to the Departmental Executive. This report will be recorded in Daily IPC report format (Annexure-II).
=>This inspection report will be forwarded to Manager, Quality Assurance for further action.
=>QA inspectors will collect retention samples of finished packs from the running Secondary packaging line belts & record sampling date and quantity sampled in BPR with sign & date as per Sampling SOP.

In-Process Controls Check:

[][]QA Inspectors will independently conduct all In-process checks in addition to that done by production personnel as Procedure for In-Process Checks.
[][]QA inspectors will conduct the following IPC checks as per frequency described in Annexure–I and as a minimum at least once from every batch of product. This should be done at the start of every batch:

[][]Product: Tablets/Capsule

=>Manufacturing Stage: Encapsulation/ Compression/Coating
=>IPC Checks: Appearance, Average weight, Uniformity of weight, Hardness, Thickness, DT, RH & Temperature
=>Manufacturing Stage: Blister Packing
=>IPC Checks: Leak test, Overprinting, Cutting, RH, Temperature, Product name, Strength, Product code, Mfg & Expiry date, Price and Status label etc.

[][]Product: Powder for Suspension

=>Manufacturing Stage: Manufacturing, Filling & Packing
=>IPC Checks: Appearance, Uniformity of weight, Leak Test, RH, Temperature, Product code, Mfg & Expiry date, Overprinting, Price and Status label etc.

[][]Product: Sterile (Capsules/ Tablets)

=>Manufacturing Stage: Encapsulation/ Compression/Coating
=>IPC Checks: Appearance, Average weight, Uniformity of weight, Hardness, Thickness, DT, RH & Temperature.
=>Manufacturing Stage: Blister Packing
=>IPC Checks: Leak Test, Overprinting, Cutting, RH, Temperature, Product code, Mfg & Expiry date, Price and Status label etc.

[][]Product: Sterile (Powder for Suspension )

=>Manufacturing Stage: Manufacturing, Filling & Packing
=>IPC Checks: Appearance, Uniformity of weight, Leak Test, RH, Temperature, Product code, Mfg. & Expiry date, Overprinting, Price and Status Label etc.

[][]Product: Dialysis Fluid

=>Manufacturing Stage: Manufacturing, Filling & Packing
=>IPC Checks: A Appearance, pH, Weight, Induction Sealing, Cap Sealing, Leak Test, Temperature, Pressure

[][]QA inspectors will verify the IPC results as per specification.
[][]If any batch is completed before inspection of QA IPC inspector, then again QA IPC inspectors will verify the some critical parameters.
[][]In-process test failures must be brought to the attention of the Departmental Executive/ Manager & also Manager, Quality Assurance and appropriate action shall be taken and recorded.
[][]Any problem identified at production floor during printing or in-process checking during packaging, Problem observer immediately inform it, to his/her supervisor and if required Online Problem Notification Form (Annexure-III) to be raised by production through QA.
[][]Reference No. for Online Problem Notification will be as
PN-001/02/XX
Where-
=>PN represents Problem Notification
=>001 represents sequential number
=>02 represent Month of February
=>XX represents year of 20XX

[][]If any receiving quantity of packaging material requires replacement to run production smoothly, it shall be raised by production with Material Replacement Form (Annexure-IV) to warehouse through QA with justified reason for replacement.
[][]Reference No. for Material Replacement will be as
MR-001/02/XX
Where-
=>MR represents Material Replacement
=>001 represents sequential number
=>02 represent Month of February
=>XX represents year of 20XX
[][]The copy of raised Online Problem Notification Form should be sent to Manager, Supply Chain & Management with recommendation of Head of Quality Assurance if required.

QC Floor Inspection:

[][]QA IPC Inspector will also visit the Quality Control laboratory once daily for GLP in place and in use check.

Annexure:

Annexure-I: In-Process Checks
Annexure-II: Daily IPC Finding and Observation Report Sheet
Annexure-III: Online Problem Notification Form
Annexure-IV: Material Replacement Form

Floor Inspection by QA Inspector Read More »

Market Complaint Handling

Market Complaint , Purpose :

Market Complaint , To provide a system for timely response to a product complaint and to make relevant investigation and recommendation with proper documentation.

Market Complaint , Scope :

This procedure is applicable to all types of market complaints received from the market, related to quality, packing and shortage of the products manufactured at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Market Complaint: A written or verbal report originating from customer, retailers, physicians, field supervisor, regional sales coordinator, medical representative, hospitals, regulatory agency and our employees which relates to the inadequacy of the quality, i.e. non Assurance with standards or customer requirements and includes any packaging and labeling requirements, any query regarding specifications, analytical procedure, incomplete text and non conformance with customer requirements should be treated as complaint.
[][]Customer: The person or institution making the complaint.
[][]PMD: Product Management Department.

Responsibilities:

[][]The roles and responsibility is as follows:

Executive/ Manager, PMD

[][]Send the complaints with appropriate details & samples to Manager, Quality Assurance.

Quality Assurance Manager/ designee

[][]Responsible for registering, carrying out the investigation and taking necessary corrective actions, providing necessary technical response to PMD in consultation with General Manager, Plant and Manager, Quality Assurance, generation of the complaint report and closure of the complaint.

Manager, Quality Control

[][]Responsible for carrying out the analysis of samples as per requirement.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the procedure as per SOP.

Procedure:

Classification of Complaints:

[][]Market complaints to be classified as minor, major and critical.
[][]Minor: Complaints related to physical appearance of packaging of the product.
[][]Major: Complaints related to physical appearance of the products (e.g. broken tablets, fading, spots etc), packaging quantity (e.g. empty blister, empty bottles, empty content etc), label missing, batch printing missing etc.
[][]Critical: Chemical property complaints related to any chemical test failure of a product, e.g. low purity, change in the impurity level and degradation and shall also include the complaints arising due to stability failure. In the event that a batch is considered to be actually or potentially harmful to user, thereby requiring a recall, following relevant SOP.

Raising of Product Complaint:

[][]Any market complaint received or to be raised by PMD / Sales team shall be filled up in the market complaint form (Annexure-III) along with complaint details (Attach original complaint document to this Annexure if applicable). If the details of the complain are not available in the document then the details of the chemist shop or recipient from where the complaint has been received will be recorded in the market complaint form.
[][]Customer complaints which are received by PMD or complaint raised by PMD will be forwarded to Manager, Quality Assurance with appropriate details in the market complaint form (Annexure- III).
[][]Head of Quality Assurance shall send the complaints along with complaint sample, if received, to Manager, Quality Assurance.
Manager, Quality Assurance shall arrange the investigation and generate a comprehensive report on the market complaints investigation form (Annexure–I).

Investigation of complaints:

[][]Manager, Quality Assurance shall record the complaint in a market compliant logbook (Annexure–II). This detail should include a complaint number, name of the product, batch No., Mfg. date, Expiry date, nature of the complaint, name & address of complainant and date of receipt at the investigating site.
[][]Quality Assurance shall assign a distinct control number to every complaint as follows:
MC/XX/001
Where,
MC – Market Complaint.
‘XX’ represents the last two digits of the year 20XX
‘001’ represents for serial number of the market compliant on continuous basis starting from
001 for the calendar year.
[][]If complaint sample is received along with the market complaint, the investigator shall record the quantity of sample received in the market complaint investigation form (Annexure–I).
[][]If no complaint sample is received along with the complaint, the investigator shall record the relevant details disclosed in the complaint form.
[][]Quality Assurance Manager shall carry out the detailed investigation of the market complaint under the supervision of Head of Quality Assurance to find out the root cause of the complaint and to generate corrective & preventive actions. In his/her absence, Head of Quality Assurance shall nominate any other person to carryout activities in this regard.
[][]Investigator shall carefully inspect and record the physical appearance of the sample, seal etc. and compare the details of the references available in documents of the same batch number. Chemical analysis shall be done on the sample at this point of time.
[][]The investigator in consultation with Head of Quality Assurance shall arrange to carry out chemical and / or microbiological analysis of the reference sample (along with the complaint sample, if available). The investigator must also scrutinize the analytical report of the product under reference.
[][]The investigator shall then discuss the results of the analysis with General Manager, Plant for the investigation at production end.
[][]General Manager, Plant along with the respective departmental manager shall investigate the complaint in details.
[][]The investigation should include scrutiny of batch production records for any manufacturing and/or packing problems encountered during the production of the batch.
[][]Any equipment breakdowns recorded during production of the batch and any material quality problems faced during manufacturing and packing of the batch also must be studied.
[][]In case of following nature of the market complaints, AGM, Quality Assurance in consultation with Managing Director may decide to recall the product / batch as per Recall procedure.
[][]Product mix up and label mix up
[][]Failure to meet regulatory specification (i.e. Assay, impurity)
[][]Adverse drug reaction due to product defect.
[][]Contamination due to foreign matter. (e.g. Glass pieces, metal pieces, black particles, particulate matter, microbial growth etc.)

[][]The closure of complaints along with redressal should be completed within 1(one) month period after the receipt of the complaints. Any delays shall be justified.

Product Complaint Redressal:

[][]Head of Strategic Marketing and Communication after consultation with Managing Director shall appraise the customer on the corrective actions taken and on the redressal actions, wherever necessary and a copy of such shall be forwarded to Head of Quality Assurance for his/her reference.
[][]Management Reviews of Complaints:
[][]The product complaint report, the trends, effectiveness of the corrective actions etc. shall be summarized and reviewed in management review meeting.

Annexure:

Annexure-I: Market Complaint Investigation Form
Annexure-II: Market Complaint Log Book
Annexure-III: Market Complaint Form
Annexure-IV: Flow Diagram For Handling of Market Complaints

Market Complaint Handling Read More »

Leak Test Apparatus Operation, Calibration and Cleaning

Leak Test Apparatus , Purpose :

Leak Test Apparatus , The purpose of this SOP (Standard Operating Procedure) is to describe the operation, calibration and cleaning of leak test apparatus.

Leak Test Apparatus , Scope :

This procedure is applicable for leak test apparatus (Model: Electrolab, LT-101P ) used in the In Process Check of General Block at XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.

Asst. Manager, Quality Assurance

[][]To ensure that this procedure is kept up to date.
[][]To arrange training on the SOP to all concerned personnel.
[][]To ensure implementation of the SOP after training.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Precaution(s):

[][]Laboratory coat must be worn while handling the instrument.
[][]Disconnect the power supply before moving or cleaning of the instrument.
[][]Prior to use, user must ensure that equipment is calibrated.
[][]Preparation of Rhodamine B Dye Solution:
[][]Prepare a 2 liters solution of Rhodamine B dye by dissolving 0.5 gm of the dye in water. Take 800 ml water in a 1000 ml beaker and make it colored by adding about 5 ml of the dye solution.

Operating Procedure:

[][]Place the sample in the desiccators which is filled with Rodamin solution to the desired level.
[][]Connect the vacuum tubing between desiccators and the Vacuum Inlet Nozzle provided on the back panel of the instrument.
[][]Switch ON the power switch, then LCD screen displays LEAK TEST APPARATUS followed by SERIAL NUMBER of the instrument and changes over to Vacuum in mm, Hg and Time.
[][]Press the SET key to change to vacuum and input required data by using UP, DOWN and SHIFT keys.
[][]To change HOLD TIME press the SET key and input required data by using UP, DOWN and SHIFT keys.

[][]To show USER ID on screen, press SET key. To setup USER ID press UP or DOWN key.
[][]To change SAMPLE ID press the SET key and input required data by using UP, DOWN and SHIFT keys.
[][]To change No. of samples press the SET key and input required data by using UP, DOWN and SHIFT keys
[][]To change BATCH NO. press the SET key and input required data by using UP, DOWN and SHIFT keys.
[][]After all the data is entered, press the ENTER key and then press the RUN key to run the program which is set for required test. Then vacuum release takes place for three seconds and the pump starts and the vacuum built up which is displayed on the LCD screen. If no vacuum builds up then press desiccator top lid for a few seconds.
[][]When vacuum release reaches zero place automatically then press the print key to get full details of the test.
[][]Leak test parameters

Type of product/Pressure/Time

[][]Tablet, Capsule, Vial/450 mm-hg/5 minutes
[][]Powder for Suspension/450 mm-hg/2 minutes

Procedure for setup time, date and serial number:

[][]Switch ON the instrument and press up arrow key until hear a buzzer sound, then shows password.
[][]Enter password.
[][]The password is four digit 8824 and press enter key.
[][]Date format is 2013 02 16 (Year Month Day) and Time format is 12:15(Hours, Minutes).
[][]Input necessary data by using up, down and right shift key, Date and time can be changed.
[][]To show Serial No. on screen press Enter key
[][]Input necessary data by using up, down and right shift key, Serial No. can be changed.
[][]When all data is entered completing then press Enter key.
[][]Switch OFF the instrument.
[][]Switch ON the instrument after few minutes and check the above recorded data and verify.

Calibration procedure:

[][]Calibrated stopwatch and start timer of leak test apparatus and stop watch simultaneously.
[][]Note the reading at intervals of 60 seconds, 180 seconds and 300 seconds respectively.
[][]Acceptance criteria: 10 seconds for each interval.
[][]Vacuum gauge calibration done by external party.
[][]Frequency of calibration: Twelve months (for timer, vacuum gauge and vacuum holding capacity).

Cleaning procedure:

[][]After completion of the testing, switch off the instrument.
[][]Cleaning of leak test apparatus by using purified water and clean outer and inner surface with the help of lint free cloth.
[][]Place the apparatus for dryness for half an hour.
[][]Change the desiccator Rodamin solution twice in a week or as per required.

Annexure:

Annexure-I: Log Book of Leak Test Apparatus.

Leak Test Apparatus Operation, Calibration and Cleaning Read More »

Training Procedure

Training Procedure, Purpose:

Training Procedure, To lay down guidelines for training of new entrants and periodic retraining of technical staff.

Training Procedure, Scope:

[][]This procedure is applicable for all employees of General block and Sterile block at XX Pharmaceuticals Ltd. for
[][]On the job training (OJT)
[][]Class room training (CT)
[][]External training
[][]Basic GMP training

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, HR & Admin.

[][]To ensure that this procedure is followed.
[][]To maintain the records properly as per SOP.
[][]To check the records of training filled by trainee.
[][]To maintain employ training record.
[][]To prepare list of training given to the employees.
[][]To file all records of training in their individual training file.
[][]Training is given in all departments as per the induction form.

Manager, Human Resources

[][]To preserve all training record
[][]To co-ordinate in all training program

General Manager, Plant

[][]To ensure that this procedure is kept up to date.
[][]To ensure implementation of the training as per SOP.
[][]To assess the training requirement.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

[][]The manufacturer should provide training for all the personnel whose duties take them into production areas or into the control laboratories (including the technical, maintenance and cleaning personnel) and for other personnel whose activities could affect the quality of the product.

New Entrants:

New entrants to the organization shall be given induction training and brief cGMP/GLP training by Head of Quality assurance or Quality Assurance within 10 days of joining.
[][]New entrants should be given technical training (need based) by the departmental manager depending upon the nature of job for one month.
[][]New entrant should be instructed to observe the activity in the recruited department for one month after the initial induction program.
[][]A written feedback is collected from new entrants after the training to ascertain his/her competence in both technical and cGMP skills.
[][]Quality Assurance shall prepare a regular annual schedule for training/retraining of technical staff.
[][]The Qualified trainer who has conducted the training should review and assess the feedback.
[][]Based on the assessment, trainer shall identify training retraining needs.
[][]Individual Training record should be maintained for each new entrant along with their feedback.
[][]Once the induction is over the new employees hand over induction training format duly filled with all required signatures to HR & Admin. Department.

Classroom training:

[][]Prepare the training schedule and circulate to all Department Heads for information.
[][]Upon finalization of training schedule, intimate to participants.
[][]Prepare required training aids and conduct the training program.
[][]On completion of the training, evaluate the training imparted by giving a questionnaire. Trainer is required to set the questionnaire.
[][]Trainer evaluates the answer & ranks them as Excellent (>90%), Very good (>80-90%), Good (>60-80%), Poor (<50%).
[][]Poor performers are retrained and re-examined.
[][]After training, trainer provides “Individual Training Record” to the trainee for getting feedback.

[][]All trainees fill the same immediately after the program gets over & submit it to the trainer.
[][]Trainer notes the contents, signs each reports & forward the same to HR & Admin. Department who keep all training related records.
[][]Maintain the training record in training file and update the Employee training card.

On-the-job training:

[][]On need base a competent person organizes on job training to concerned persons either individually or in small group preferably of 5 to 7.
[][]Trainer first explains the theoretical aspects making use of writing boards/printed literature diagram etc.
[][]Explain or demonstrate the actual operation or system to participant.
[][]Training record is maintained in the form as explained above.

External training:

[][]Upon information from various agencies nominate the person on consultation with department head.
[][]Make the necessary arrangement like tickets, hotel arrangement etc. to attend the external training.
[][]After training, trainee will submit the report in the prescribed format as per Annexure- V, to HR & Admin. Department through Department Head. Brief [][]information about the program need to be enclosed with the report.
[][]Maintain the training record in training file and update the Employee training card of concerned employees who have undergone external training as per SOP.
[][]Trainee shares the literature & knowledge gained in the program with all this colleagues.
[][]Department Head may ask the concerned employee to make a presentation on the topic concerned for the benefit of all those concerned who were not sent for training.

Training on basic GMP practice:

[][]Department Head training the new comer on following points:

Production :

[][]Importance of good manufacturing practices and requirements.
[][]Systems related to manufacturing.
[][]System related to packaging (printed and unprinted component code etc).
[][]Documentation.

Warehouse:

[][]General warehousing procedure.
[][]Function carried out by Warehouse.
[][]Document related to warehouse.

Engineering:

[][]Facilities and services
[][]Brief working of the services
[][]Documentation

Quality Assurance:

[][]General information on SOP, GMP Documentation.
[][]Activities of Quality Assurance, Product Development, Microbiology & Quality Control.
[][]Product information.
[][]Other specific activity related to the employees department.

Training schedule:

[][]New entrant: General factory rules and cGMP –10days
[][]Regular training for staff and operators
[][]cGMP – Once in 6 months
[][]GLP – Once in 6 months
[][]Technical training – Once in 3 months
[][]A training session by an External Agency shall be conducted as and need/opportunity arises.
[][]Apart from the schedule, training/retraining sessions will be conducted as and when need arises.

Annexure:

Annexure-I: Individual Training Record.
Annexure-II: Training Log.
Annexure-II: Induction Training Format.
Annexure-IV: Employee Training Card.
Annexure-V: Training Program Report.

Training Procedure Read More »

Manufacturing & Expiration Date Assigning of Products

Manufacturing & Expiration Date, Purpose :

Manufacturing & Expiration Date, The purpose of this SOP (Standard Operating Procedure) is to provide a system for assigning of manufacturing & expiration date of products manufactured in XX Pharmaceuticals Limited.

Manufacturing & Expiration Date, Scope :

All departments of XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions/Abbreviation:

[][]BMR : Batch Manufacturing Record
[][]BPR : Batch Packaging Record
[][]LPL : XX Pharmaceuticals Limited
[][]MFG. : Manufacturing Date
[][]EXP. : Expiry Date
[][]VAT : Value Added Tax
[][]IP : Indicating Price

Responsibilities:

[][]The roles and responsibility is as follows:

Executive, Quality Assurance

[][]To ensure that this procedure is followed.

Executive, Production

[][]To follow laid down procedure.

Manager, Quality Assurance

[][]To ensure implementation of the SOP.

Head of Quality Assurance

[][]Approval of the SOP.

Annexure:

N/A

Procedure:

Assigning of Manufacturing Date
[][]Determine the manufacturing date of a batch from the month and year at which manufacturing of that batch starts (i.e. dispensing). Consider the BMR issue date as starting point of a batch. So the month and year of issuing BMR will consider as manufacturing date.
[][]First 3 (three) letters of month and last 2 (two) numerical digits of year representing the manufacturing date.
[][]Assign the manufacturing date in block letters.
Assigning of Expiry Date
[][]Determine the expiry date from the manufacturing date and claimed shelf life of the product.
[][]First 3 (three) letters of month and last 2 (two) numerical digits of year representing the expiration date.

[][]Those products which have no manufacturing steps except encapsulation / filling, expiry date will be declared as the manufacturer’s claimed expiry date of the active material (i.e. pellets, ready granules, different materials for injectable etc.).
[][]When the active material of two different Lab. Control No. will use in one batch, then the expiry date of the product should be considered as like shorter expiry date of API claimed by the manufacturer.
[][]Assign the expiry date in block letters.
Example: a) When claimed shelf life is 1 years.
[][]For example: Cerolab 10 Tablet
[][]If manufacturing starts (or BMR issue) at January .
[][]The manufacturing date is JAN  and expiry date is DEC of the following year
b) When claimed shelf life is 1.5 (One and half) years.
[][]For example: Cerporal PFS, 50 ml
[][]If manufacturing starts (or BMR issue) at January
[][]The manufacturing date is JAN  and the expiry date is JUN of the following year

[][]Batch number, manufacturing date, expiry date and indicating price should be printed in different packaging material as following procedure:
For inner carton (if product shelf life is 1 year)
BATCH NO. : XX0001
MFG. DATE : JAN XX
EXP. DATE : DEC XX
IP (with VAT) :

Manufacturing & Expiration Date Assigning of Products Read More »

Qualification Procedure

Qualification ,Purpose :

Qualification , The purpose of this SOP (Standard Operating Procedure) is to provide guidelines for carrying out the qualification at the site.

Qualification , Scope :

This SOP is applicable for qualification of all equipment, instrument, facility and utility at the site of General Block and Sterile Block of XX Pharmaceutical Ltd.

Definitions / Abbreviation:

[][]Qualification: The action of proving and documenting that equipment or utility are properly installed, work correctly, and actually produce the expected results.
[][]User Requirement Specification (URS): Documented requirement of the equipment, utility for its intended purpose. Functional design and specification according to cGMP and regulatory requirements.
[][]Design Qualification (DQ): Documented verification that the proposed design of the equipment, utility is suitable for the intended purpose.
[][]Installation Qualification (IQ): Documented verification that the equipment, utility as installed or modified, comply with the approved design, manufacturer’s recommendations and user requirement. FAT& SAT to be added.
[][]Performance Qualification (PQ): Documented verification that the equipment, utility is performing effectively and reproducibly, based on approved method and specifications.
[][]Factory Acceptance Test (FAT): Documented verification of the equipment at vendor’s site against approved design.
[][]Site Acceptable Test (SAT): Documented verification of the equipment at user site against approved design.
[][]HVAC: Heating, Ventilation & Air Conditioning
[][]LAF: Laminar Air Flow

Responsibilities:

[][]The roles and responsibility is as follows:

User department

[][]To prepare the URS of equipments, instruments, facility, utility.
[][]To prepare DQ (if required).
[][]To prepare PQ protocols

Validation Team

[][]He I She shall be responsible to carry out this procedure as defined

Engineering Department

[][]To prepare IQ, OQ protocols whenever required.
[][]To provide technical assistance to the user department for preparation of require documents.
[][]To prepare protocols for facility and utility in co- ordination with user department

Quality Assurance

[][]To review protocols and to provide technical inputs
[][]To review  reports for its completeness and correctness all data and report.

Head of Engineering

[][]He I She shall Be Responsible for Effective Implementation of this Procedure.

Head of Plant

[][]He I She shall Be Responsible for Effective Implementation of this procedure.

Head of Quality Assurance

[][]He/ She shall be responsible for effective implementation of this procedure.
[][]To approve protocols, reports and master plan.
[][]Approval of the SOP.

External agency

To provide technical assistance for preparation of documents and execution of activities whenever required

Procedure:

Methodology

[][]Facilities, Utilities and Equipment’s used for manufacturing, processing, packaging, labeling, storing, testing and controlling of drug products shall be qualified prior to use.
[][] It shall be performed for new equipment /instruments/utility/facility, after major breakdown in equipment/utility, after modification in equipment/instrument/utility and facility.
[][]Re-qualification shall be performed at define frequency.

Introduction of a new equipment/ facility/ utility:

[][]After receiving the new Equipment Engineering shall make entry in respective format and Concern
[][]department shall update the Equipment Master List as per respective of SOP.
[][]Equipment no. shall be assigned as per the SOP for Equipment and Instrument Numbering System.
[][]For new equipment following activities shall be done to demonstrate conformance to design documents, characteristics, and capabilities specified in required documents.
[][]User requirement specification (URS)
[][]Design qualification(DQ)
[][]Factory Acceptance Tests (FAT)
[][]Site Acceptance Test (SAT)
[][]Installation Qualification(IQ)
[][]Operation qualification(OQ)
[][]Performance Qualification(PQ)

User Requirement Specification:

[][]The URS is made to verify that the owner/user requirement, which includes establishment of critical operating or operational parameters or specifications before the final design agreed, has been met.
[][]User shall prepare the URS considering all operational, safety and GMP requirements.
[][]The user requirement shall be submitted to manufacturer/supplier, based on which manufacturer/supplier will prepare design.

DQ:

[][]The DQ is made to verify that the owner/user requirement, which include establishment of critical operating or operational parameters or specifications before the final design is agreed, has been met.
[][]Based on URS, manufacturer/supplier shall prepare design it documents and submit to user for approval.
[][]On the basis of approved design it documents, manufacturer /supplier shall start manufacturing/fabricating the equipment/utility.

Factory Acceptance Test:

[][]The FAT is prepared to verify that the main items or system meets design specification and conforms to agreed performance intent.
[][]User shall prepare FAT protocol according to URS/DQ, manufacturer specification and purchase order User shall ensure that the equipment/system is manufactured as per designed specification at manufacturer’s site.
[][]User also check the basic performance of the equipment/ system delivered at plant meets the design specification.
[][]User shall take photocopy of the approved FAT protocol and execute at the manufacturer’s site with QA and Engineering representative.
[][]All the test shall be performed and reported by the supplier. All tests performed during FAT must be performed in accordance with reviewed and and approved protocol and procedure.

Site Acceptance Test:

[][]The SAT is to establish documented evidence that the receipt of the item at site confirms with the standards laid down in the protocol, FAT, purchase order and manufacturer’s specification.
[][]User shall prepare SAT protocol according to the manufacturer specification, purchase order and FAT report.
[][]User shall take photocopy of the approved SAT protocol and will check the entire test mentioned in protocol with the QA & Engineering representative at the site when item I equipment I system reaches to the factory premises and reported by the production and engineer.

Installation Qualification:

[][]Installation Qualification of Equipment/utility shall be carried out is to ensure that the equipment I utility is installed according to design documents, purchase. Specifications, FAT and SAT report and planned modification.
[][]The parts of the systems, which are disassembled prior to shipping, shall be noted and be verified again after re-assembly at the final site during IQ.
[][]Equipment/utility shall be inspected either visually or by measurement for its critical parts. Wherever applicable other instruments shall be used for this purpose.
[][]All the relevant tests mentioned in protocol shall be checked after proper installation of equipment. Calibration of instrument attached with equipment and other related shall carried out before starting OQ.
[][]After completion of IQ the equipment shall be released OQ.

Operation Qualification:

[][]The Operational Qualification is carried out to verify that an Equipment/system or subsystem performs as intended throughout all anticipated operating ranges.
[][]Operation qualification activities shall start only after completion of successful IQ.
[][]QA and User representative shall use photocopy of approved protocol, which is used earlier during IQ.
[][]User department shall verify proper operation by performing the critical operating parameters that have significant impact on the equipment ability to operate and meet specifications satisfactory.
[][]User department shall prepared final conclusion after the test functions are checked and observed within specification.
[][]After completion of OQ the equipment shall be released either for PQ or for routine use as the case may be.

Performance Qualification:

[][]The performance qualification is carried out to provide documented evidence that an integrated system or processing operation is capable of performing consistently (during multiple cycles or extended periods) to give an outcome that meets predetermined specifications.
[][]PQ activities shall start only after completion of successful OQ.
[][]PQ of equipment depends upon equipment intended use and its operation.
[][]Data shall be generated to establish that the equipment meets the requirement as expected of it.
[][]A final report shall be prepared, summarizing the results obtained, commenting on any deviation observed and final conclusion shall be given after the PQ.
[][]PQ can be performed on commercial batches for new equipment. The batches shall be released only after the qualification of the equipment is completed or can be performed on placebo /dummy / trials wherever applicable.
[][]PQ shall be performed for consecutive three batches/trials with load.
[][]After completion of execution, all raw data and reports shall be compiled and a final conclusion shall be drawn.
[][]After final approval of conclusion/report by plant head and quality head the respective equipment, instrument, facility and utility shall be allowed for routine use.

Note: Operation and PQ shall be carried only if desired utility is available and environmental conditions (wherever applicable) are achieved in the area.
Qualification for introduction of a new Instrument:

[][]For new Instrument following activities shall be done to demonstrate conformance to design documents, characteristics, and capabilities specified in requirements documents.
=>Installation Qualification (IQ)
=>Operation qualification (OQ)
=>Performance Qualification (PQ)

[][]IQ : for new Instrument shall be carried out as per procedure mention above.
[][]OQ : OQ for new Instrument shall be carried out as per procedure mention above.
[][]PQ : OQ for new Instrument shall be carried out as per procedure mention above.

Protocol Preparation for FAT, SAT, IQ, OQ and PQ:

[][]The protocol for Qualification (FAT/SAT/ IQ / OQ / PQ) shall address and include, but not necessarily be limited, to the following topics.
[][]FAT: Approval, purpose, procedure, verification criteria, Manufacturer’s Machine Identification Code / Identification No., Final report approval.
[][]SAT: Approval, purpose, procedure, Documentation, Verification criteria, Final report approval.
[][]IQ/OQ/PQ: Purpose, Scope, Responsibility, Intended Use, Location, Reference, History, Attachments, Study for qualification, Responsibilities, Signature log, Training record.
[][]IQ : Equipment/Instrument Detail, Procedure, IQ table, Conclusion.
[][]OQ : SOP training, Procedure, OQ table, Observed deviation, Conclusion.
[][]PQ: Procedure, Acceptance criteria, Observed deviation, Final Conclusion Report approval sheet.
[][]Specimen of Header and Footer for above protocol is as per given below.

At the Header Section

1st Column: Company Logo
2nd Column: Company Name, Address Details
3rd Column: Doc. Title, Document No., & Location

Specimen of Footer on all Page

CONFIDENTIAL TECHNICAL DOCUMENT

[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document numbering system.

Area Qualification:

[][]Area Qualification is carried out to provide the documentary evidences that particular area is constructed and qualified as per predefined specification.
[][]Below mentioned activities shall be performed during execution of Area Qualification, but not limited to.
[][]Construction and finishing of wall, floor, doors, view panels and ceiling.
[][]Dimension measurement wherever applicable.
[][]All the required utilities and other facilities supplied.

[][]Lighting lux of every room in all four corners and center of the room.
[][]Temperature Mapping for Classified area.
[][]Environmental condition monitoring for classified area.
[][]Water drains ability of drains.
[][]Cleaning and Sanitization Procedure.
[][]User department shall prepare the qualification protocol and organize the qualification study in co- ordination with Quality Assurance and Engineering department.
[][]Protocol/Report shall be finally reviewed by Multidisciplinary authorized personnel along with QA personnel and approved by Quality Head.

[][]Specimen of Header and Footer for above protocol is as mentioned above.
[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document numbering system.

Qualification of HVAC system:

[][]HVAC qualification shall be carried out to supply the required air quality to the various section of individual department to provide product protection from air borne contamination, to maintain the temperature and humidity, to provide differential room pressure or air flow movement to provide product protection from cross – contamination.
[][]All HVAC system like AHU’s shall be qualified as per procedure described above as per approved protocols.
[][]Engineering department shall prepare the qualification protocol and organize the qualification study in co-ordination with Quality Assurance.
[][]Engineering person shall record the observations as per designed protocol and prepare a report.
[][]Below mentioned test shall be performed during qualification of AHU, but not limited to.

DOP or PAO Test
Air velocity & Air changes Test
Non viable particle count
Filter efficiency & integrity.
Particle count Test.
Microbial Count.
Air Flow Direction & Air Flow Pattern
Recovery Study
Protocol/Report shall be finally reviewed by QA and approved by Head of QA.
Specimen of Header and Footer for above protocol is as mentioned above.

[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document
numbering system.

Qualification of LAF:

[][]Qualification of LAF shall be carried out to provide the air with high-pressure compare to surrounding area and to prevent microbial and particulate matters contamination during dispensing/sampling of Raw material, prevent dusting during dispensing/Sampling.
[][]All LAF shall be qualified as per procedures described  as per approved protocol.
[][]User department shall prepared the qualification protocol and organize the qualification study in co-ordination with QA & Engineering department.
[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document numbering system.

[][]Installation Qualification: IQ of LAF shall be carried out to check LAF size as per requirement, to check pre-filter, motor blower, Magnehelic gauge and final HEPA filter as per specification.
[][]Operational Qualification: OQ of LAF shall be carried out to run the LAF and to check the operational parameter functioning.
[][]Performance Qualification: PQ of LAF shall be carried out to check LAF air velocity, Air flow pattern, air cleanliness by non viable particle count and HEPA filter efficiency & integrity, etc.
[][]User department shall record the observations as per designed protocol and prepared a report.
[][]Protocol/Report shall be finally reviewed by QA and approved by Head of QA.

Qualification of Water System:

[][]Water system qualification shall be carried out to generate Potable water & purified water of desired quality.
[][]Engineering department shall prepared the qualification protocol and organize the qualification study in co-ordination with QA.
[][]Qualification protocol shall carried following details but not limited to, IQ: Equipment/instrument details, procedure, Acceptance criteria, Pre-
qualification, Installation check, summary & conclusion.
[][]OQ: Training, Procedure, Acceptance criteria, operating inputs, summary & conclusion.
[][]PQ: Study plan, sampling Frequency, user point, summary & report.
[][]PQ of water system shall be carried out in a two phase.
[][]In phase 1, water quality parameter trend shall be evaluated on monthly basis.
[][]In phase 2, water quality parameter trend shall be evaluated after one year to evaluate impact of seasonal changes on quality of water.
[][]Engineering department shall record the observations as per designed protocol and prepared a report.
[][]Protocol/Report shall be finally reviewed by QA and approved Head of QA.
[][]Numbering and Issuance system for Qualification protocol shall be as per SOP for Document numbering system.

Re-qualification strategy:

[][]Equipment futility shall be re-qualified either in following conditions:
[][]Major Break Down.
[][]After modification in equipment, utility, facility which may have an impact on product quality only.
[][]Design change of spares that have impact on the performance of equipment and quality of product.
[][]In case of during Location change of equipment. (In case of balances only recalibration shall be done).
[][]As per scheduled re-qualification of critical and non equipment/utility.
[][]OQ & PQ shall be performed during requalification.
[][]PQ shall be performed with one batch during requalification.

Re-qualification criteria for critical equipment:

[][]Operational and performance qualification shall be done as per approved protocol for re-qualification of critical equipment.
[][]All critical equipments shall be re-qualified after every three years ± 1 month.
[][]During re-qualification of critical equipment/utility, only 00 and PO shall be performed. PO shall be conducted with one batch only.

[][]Re-qualification criteria for non critical equipment.
[][]Re-qualification of non critical equipment shall be conducted whether there is significant change that has influence on quality of product.
[][]For re-qualification of non-critical equipment, history of maintenance and utilization of the equipment shall be reviewed and documented as per format of Re qualification of non-critical Equipments (Attachment 1).
[][]All non – critical equipments shall be re-qualified after every three years ± 6 months.

Re-qualification criteria for Instrument in following conditions:

[][]When the instrument is shifted from one laboratory (Change in premises) to another laboratory, re qualification (10, 00 and PO) is required.
[][]When the instrument is upgraded or after having a major repairing, qualification (OO/PO) is required.
[][]When the instrument is shifted within the laboratory premises (one room to another room), re qualification is not required, in house calibration is required.

Re-qualification criteria for HVAC System:

[][]Re qualification of HVAC(AHU) shall be carried out in below mention criteria, but not limited to Change in a location of the equipment/system.
[][]Major change in equipment, Change of spare/ parts that have a direct bearing on the Performance of the equipment.
[][]Schedule Re-Qualification.
[][]Frequency of Re-qualification of AHU shall be One Year.± One month. Below mentioned test shall be carried out at defined frequency.

Parameter/Frequency

=>Air Velocity /Initially and Once in year
=>Air Changes /Initially and Once in year
=>Filter Integrity Test /Initially and Once in year
=>Particle Count /Initially and Once in year
=>Microbial Count /Initially and Once in year
=>Air Flow Direction /Initially and Once in year
=>Air Flow Pattern /Initially and Once in year
=>Recovery Study /Initially and Once in year

Re-qualification criteria for LAF:

[][]Re qualification of LAF shall be carried out in below mention criteria, but not limited to.
[][]Change in a location of the equipment/system.
[][]Major change in equipment, Change of spare/ parts that have a direct bearing on the Performance of the equipment.
[][]Critical gauges shall be replaced or corrected if the gauge is found out of calibration during calibration of the gauges.
[][]Schedule Re qualification.
[][]Frequency of Re-Qualification of LAF shall One Year.± One month.

Re-qualification criteria for utilities:

[][]Re-qualification shall be carried out to ensure that change I modification in utilities remain under
[][]Control and within the parameters defined and certified.
[][]Re qualification of utilities shall be carried out in below mention criteria, but not limited to.
[][]Change in location

[][]Any modification that has a potential to impact the product quality.
[][]Scheduled re-qualification after every 3 years.

Re-Qualification of Compressed Air:

[][]Re qualification of Compressed Air shall be carried out in below mention criteria, but not limited to,
[][]In case of any modification which has impact on product quality.
[][]Scheduled re-qualification after everyone year.

Annexure:

Annexure-I: Requalification of non-critical Equipment’s

Qualification Procedure Read More »

CAPA Procedure

CAPA, Purpose:

CAPA, The purpose of this document is to define a systemic, standardized and effective approach to ensure that a system is in place to address quality and compliance issues and to continually improve operations by identifying any required remedial, corrective and preventive actions and implement them in a controlled fashion.

CAPA, Scope:

The process applies to quality related non-conformities or undesirable situations in XX Pharmaceuticals Ltd. (Both General & Sterile Block) from any one of the following interface processes where CAPA is required to prevent recurrence or potential occurrence of the :
[][]Critical or major deviation.
[][]Critical or major justified market complaints.
[][]Outcomes of change control procedure
[][]Internal audit
[][]Risk Management
[][]Product incidents and recall
[][]Batch rejects and reworks
[][]Periodic product reviews
[][]Stability Test Failure
[][]Out of specification results investigations.
[][]Output of monthly quality review meeting
[][]Any other investigation
[][]The process does not apply to the following as these are managed separately by individual SOPs:
[][]Minor deviation.
[][]Triggered from various gap analysis

Definitions / Abbreviation:

[][]QA: Quality Assurance
[][]SOP: Standard Operating Procedure
[][]CAPA: Corrective action and preventive action
[][]Remedial action: Action to eliminate the immediate compliance issue associated with a deviation or non conformance.
[][]Corrective action: Action to eliminate the cause of a detected non conformity or other undesirable situation & avoid reoccurrence.
[][]Preventive action: Action to eliminate the cause of a potential non conformity or any undesirable potential non conformity & avoid occurrence.

Responsibilities:

The roles and responsibility is as follows:

Head of Quality Assurance or his/her Designee

[][]Provide effective governance of the CAPA process
[][]Ensure local process are managed according to SOP
[][]Post approved CAPA in CAPA tracking system and update it
[][]Follow up and verify close-out
[][]To authorize the closure CAPA’s

Functional Head or his designee

[][]To approve and ensure implementation of the solution into routine use

CAPA owner

[][]Accountable for CAPA objective
[][]To assess possible impact on other functions
[][]Nominate CAPA leader
[][]To approve implementation of the solution into routine use.
[][]To implement the CAPA into routine use
[][]To collect data for long term monitoring of the CAPA

CAPA Team

[][]To support CAPA leader by means of their knowledge skill and experiences.
[][]To review and accept root cause and objective.
[][]To select best solution option(s) for evaluation.
[][]To select solution for implementation into routine use.
[][]Track and close out as per commitment and target date
[][]Provide physical evidence of CAPA closing

Manager, Quality Assurance

[][]Nominate CAPA Team.
[][]To select best solution option(s) for evaluation.
[][]To select solution for implementation into routine use.
[][]To approve implementation of the solution into routine use.
[][]To record and approve closure
[][]Define ongoing monitoring criteria of the Process Owner.
[][]To review and approve the root cause and objective.
[][]To assess the possible impacts on other functions
[][]Ensure that process is ‘in place’ and ‘in use’
[][]To approve implementation of the solution into routine use
[][]Approve changes to an agreed CAPA or date extension request

Procedure:

CAPA Objective

[][]After identification of a significant quality and compliance incident (triggered by any one of the interface process stated in scope) Departmental Head/CAPA Owner will prepare the [][]CAPA objective. Source of the CAPA objective may be anyone from the following:
[][]Formal investigation report according to SOP on Deviation & Investigation
[][]Audit findings and Audit report
[][]Significant risk in the Risk Register
[][]Investigation report triggered from OOS/Stability Failure/Market Complaints/Recall/ Change control
[][]Out comes from monthly quality review meetings

[][]CAPA objective constitutes the following information:
=>Current Situation/Problem to be solved
=>Actual or most probable root cause.
=>Criticality Classification (Critical/Major/Minor)
=>Time scale for resolving the issue depending on criticality.

[][]Departmental Head/CAPA owner is accountable for CAPA objective. Depending upon the criticality/priority settings in CAPA objective, CAPA owner will take the role of CAPA leader or assign a competent person as CAPA leader.
[][]The CAPA Leader will request for a reference number from the Quality Compliance. The number format will be as CAPA/YY/XXX, where YY represent for the last two digit of a year and XXX stands for the three digit sequential number derived from a CAPA register (Annexure-III) maintained by Quality Compliance personnel.

CAPA Team:

[][]Manager, Quality Assurance determines the Leader Depending upon the nature of CAPA objective and CAPA leader may form a team.
[][]For simple CAPAs one person may take the roles of Owner, CAPA leader and CAPA team.
[][]For complex CAPAs Operators, inspectors and others involved directly with the manufacture of affected product or processes should be considered for CAPA team membership.
[][]Based on the gravity, Functional Head/Department Manager will allocate resources to CAPA team.

Review & Source of CAPA :

[][]The CAPA team will review the source and all data gathered during preparation of investigation of incidence of CAPA to ensure that full understanding of the root cause.
[][]If team requires additional data they will identify and drive to collate it.
[][]Based on the risk analysis of the root cause, CAPA leader will define the criticality of the CAPA as critical, major or minor.

Determine the scope:

[][]The CAPA team will determine the possible impact of root cause on other functions/departments and record it as scope of CAPA.
[][]CAPA leader will record all the above information in the designated place of CAPA form (Annexure I)

Define and agree solution options:

[][]Determine Ideal Solution specifications
=>The CAPA team will prepare a list of criteria for an effective CAPA which will lead a robust and permanent solution to the problem. These will include any critical success factors, without which the solution will not work.
=>It may include resources required, particular people need to involve or get support from, or time constraints, cost and communication.

Develop a list of solutions

[][]The CAPA team will list all possible solution options either to eliminate the root cause permanently or to mitigate the problem where it is not possible to eliminate the root cause.

Assess the solutions

[][]The CAPA team will assess each solution option, or combination of options against ideal solution specification to determine the best solution option. At this stage the CAPA team considers practicalities such as cost effectiveness, ease of implementation, reduction of associated risk and ability to meet business needs.

Select the solution option (s)/Actions

[][]After assessment CAPA team will select the best solution option for implementation. For maximum CAPA only one selected option will meet all the criteria/requirement to eliminate/ mitigate the root cause. (At least mitigate the risk if it is not possible to eliminate the root causes).
[][]Where more than one solution options are available, select the solution which best meets the acceptance criteria.
[][]CAPA leader can escalate the issue to Monthly quality review meeting where it is not possible to define and select any solution for a CAPA objective.

Approval of proposed CAPA:

[][]Proposed CAPAs that require any trial or changes to process, ways of working, procedures or equipment, CAPA leader will raise Change Control which will be progressed through Change Control Procedure through SOP.
[][]For all major/critical CAPA, CAPA leader will consider the requirement of following at this stage:
[][]Requirements of revision/creation of any controlled documents (SOP, BMR or BPR) and associated training.
[][]Resume of operation until the CAPA is complete.
[][]CAPA leader will ensure the closing of Change Control within the defined timeframe.
[][]Then CAPA leader will submit the dully filled CAPA form (Annexure I) to Manager, Quality Assurance and Audit along with associated Change Control and validation report (if available).
[][]Manager, Quality Assurance will review and ensure that all necessary input and decision point is available in CAPA form.
[][]He/She will ensure that while developing the CAPA scope is clearly and comprehensively defined. If he/she finds any short coming CAPA will sent back for further review.
[][]After approval/authorization, QA personnel will post the CAPA in the CAPA tracking system and handover the original CAPA form to CAPA leader.

Closing of CAPA:

[][]CAPA leader will coordinate the implementation of CAPA within agreed timeframe and collect the short term monitoring data (if available).
[][]During implementation for any deviations, changes or delays to the plan, CAPA owner will raise a date extension request (Annexure II).
[][]QA Executive will ensure that an assessment of the delay has been properly conducted and will forward it to Manager, Quality Assurance.
[][]Manager, Quality Assurance will review the date extension request and the risk assessment conducted. If the justification and risk assessment appropriate, he/she will approve it and QA Executive will update the CAPA Tracking system accordingly.
[][]All date extension approvals will be formally endorsed in Monthly Quality Review Meeting.

[][]CAPA leader and CAPA owner both define the monitoring system for short and longer term monitoring of the effectiveness of the solution. Monitoring system may include any of the following (but not limited to):
=>Monthly Quality review meeting
=>Specification
[][]Duration and levels of monitoring (e.g. higher frequency initial, lower frequency longer term, extensive sampling for impacted batches etc.)
Note: For CAPA where Change Control is not required, CAPA leader and CAPA Owner directly define the monitoring criteria.

[][]After closing CAPA leader will submit the duly filled CAPA form along with closing evidences to Manager, Quality Assurance for verifying the effective closing of the CAPA. Manager, Quality Assurance will ensure that CAPA has been effectively closed.
[][]QA personnel will update the status of CAPA tracking system and post the necessary closing evidences.
[][]CAPA owner is responsible for implementing/sustaining the CAPA as routine activities.

Review of CAPA effectiveness:

[][]If requirement of long /short term monitoring data is defined as a part of monitoring system, CAPA owner will collate and communicate the monitoring data or trend to AGM, Quality Assurance for review.
[][]Executive, Quality Assurance will categorize, trend and sort the area/systems from where maximum CAPA has been triggered. He will conduct an unnoticed inspection at any time to verify the sustainable improvement of those particular systems.

Annexure:

Annexure I- Corrective and preventive action (CAPA) form
Annexure II- Date extension request
Annexure III- CAPA Issuance Log Book

CAPA Procedure Read More »

Instrument Numbering System at Laboratory

Instrument Numbering, Purpose:

Instrument Numbering, To provide a system for allocating identification number to Laboratory instrument in order to have better traceability and reference in all related documents.

Instrument Numbering, Scope:

This SOP is applicable to all Laboratory instruments and equipment’s installed in quality control laboratory, microbiology laboratory, product development laboratory and IPC laboratory of General block and Sterile block at XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]SOP: Standard Operating Procedure.

Responsibilities:

[][]The roles and responsibility is as follows:

Concerned Personnel

[][]He / she shall be responsible for assigning / allocating the sequential number to all equipment / instrument.

Quality Assurance Personnel

[][]He / she shall be responsible for effective implementation and monitoring of procedure.

Manager, Quality Assurance

[][]To ensure effective implementation of SOP.
[][]To approve the document.

Procedure:

[][]Numbering for Individual Laboratory Instrument:
[][]Each individual Laboratory instrument shall be assigned on unique identification number.
[][]Concerned department shall assign the sequential number to all instruments at the time of Installation Qualification and record the details in respective department register as per Annexure-II.
[][]Do not repeat the same number to another instrument.
[][]Give identification no. to all instruments as XXX/YY/000.

Where,
=>XXX corresponds to three alphabets denoting the area code of the Laboratory.
=>YY corresponds to two alphabets denoting the instrument name as per approved list available in Annexure-I.
=>000 corresponds to three numerical figures starting from 001 denoting the number of instrument in continuous manner.
=>As per Example of Balance GQC/BA/030

Where,
=>GQC = Corresponds to three alphabets denoting the Area code of Quality Control Laboratory at General Block.
=>BA = Corresponds to two alphabets denoting the instruments code.
=>030 = Number of instruments in continuous manner.

The Area Code for each Laboratory is given below:

Area Description/ Area Code

[][]Quality Control Laboratory (General Block)/ GQC
[][]Quality Control Laboratory (Sterile Block)/ CQC
[][]In-Process Laboratory (General Block)/ GIP
[][]In-Process Laboratory (Sterile Block)/ CIP
[][]Product development Laboratory (General Block)/ GPD
[][]Product development Laboratory (Sterile Block)/ CPD
[][]Microbiology (General Block)/ GMB
[][]Microbiology (Sterile Block)/ CMB

[][]Quality Assurance will prepare the Master list of Laboratory instrument with identification number and get it approved by Manager, Quality Assurance as per Annexure-III.
[][]Update the list and approve it whenever require and give serial number to list prepared.
[][]All instruments will be tagged containing instrument name and Identification number (Bold Type). Format of instruments identification tag is as follows:

INSTRUMENT / DEVICE

Name:

ID Number:

[][]In case of advent of new type of instruments, there is an option for extending Annexure-I by hand writing of Manager, Quality assurance with signature and date without reviewing the whole SOP.
[][]For this, the respective department will inform to it to the Quality Assurance Department for new code number.
[][]The new instrument (Handwritten by Manager, Quality Assurance) will be included in SOP during the next version.

Annexure:

Annexure-I: Code number for Laboratory Instrument.
Annexure-II: Laboratory Instrument Register.
Annexure-III: Master List of Laboratory Instrument

Instrument Numbering System at Laboratory Read More »

Batch Tailing of Products

Batch Tailing, Purpose:

Batch Tailing, To establish general guidelines for batch tailing of products. It is the process whereby residual defective product (e.g. Granules, broken tablets, capsules etc.) which is satisfactory on quality, is to be added to the subsequent batches as a relatively small portion of the final batch quantity (where to be added) without affecting the quality of finished product.

Batch Tailing, Scope:

This procedure is applicable for oral solid dosages form that manufactured at XX Pharmaceuticals Limited (both General and Sterile Block).

Definition / Abbreviation:

[][]N/A

Responsibilities:

[][]The roles and responsibility are as follows:

Production Personnel

[][]To ensure that the residual product to be added is physically and chemically okay and the entire process is done following SOP.

Concerned department head

[][]To ensure that above procedure is followed properly.

Quality Assurance personnel

[][]To monitor the entire process done according to SOP.

Manager, Quality Assurance

[][]Approval of the SOP.

Procedure:

Storage and Selection Criteria of Batch Tail:

[][]The product/material to be added shall be kept in a double lined poly bag in a container with lid closed by mask tape.
[][]The container and the polybag shall be labeled properly mentioning Product Name, Batch No., quantity and date of manufacturing and to be stored in cool & dry place of well-defined areas of production.
[][]Only Product from approved batches can be added.
[][]If any batch is reprocessed once, leftover material of that batch must be disposed immediately.
[][]Addition of any leftover material/product shall be completed within the same manufacturing month or subsequent month. In case of slow moving product, it shall be completed with next manufacturing batch but the difference between two batches shall not exceed more than 3 months.
[][]Products/materials must not be added from a batch which is kept for more than three months (i.e. 90 days) in bulk condition (e.g. bulk tablets, bulk powder of capsules, blended pellets etc.).
[][]Within above time limits, if there is any sign of deterioration of the product is seen visually, they must be discarded.
[][]The weight of the material/product to be added should be equal to or less than 5% of the original batch size (weight) of the product. Maximum 10% can be allowed with justification.
[][]If the quantity is huge, a reprocessed batch can be manufactured using all tailed quantity. In that case, Batch No., Mfg. & Exp. Date shall be according to the oldest batch of accumulated batches.
[][]Powder for Suspension cannot be added to any other batch(s). This is to be discarded with proper reconciliation in the batch document.

Steps for prior Approval of Batch Tailing

[][]Concerned department Executive shall raise Batch Tailing Form (Annexure-I) and fill up the relevant information in section A & B. There must be clear statement regarding the reason for Batch tailing.
[][]In section C of Batch Tailing Form, Manager of concerned department shall provide his comments ensuring the statement provided by his officer and suitability of reprocessing/reworking of the product.
[][]Before taking decision of addition of batch tailings to subsequent batch, physical verification of batch tails must be carried out by Quality Assurance Executive and shall record observation in section D of Batch Tailing Form.
[][]In section E of Form, Manager, Quality Assurance shall give comments to ensure its suitability of re-use.
[][]In section F of Batch Tailing Form, comments shall be given by General Manager, Plant.
[][]In section G of Form, Head of Quality Assurance shall provide comments regarding approval.
[][]The approved Batch Tailing Form shall be the part of batch records

Annexure:

Annexure – I: Batch Tailing From

Batch Tailing of Products Read More »

Good Documentation Practice

Good Documentation Practice, Purpose:

Good Documentation Practice, To define the common practice to be followed for data entry in all GMP / GLP records.

Good Documentation Practice, Scope:

This procedure is applicable to all GMP / GLP records filled manually at XX Pharmaceutical Limited (Both General & Sterile Block). This SOP is general guideline and will be superseded whenever any specific requirements are mentioned in other SOP or approved document.

Definitions / Abbreviation:

[][]GMP / GLP Records: GMP / GLP records are defined as all records which directly or indirectly and individually or collectively control the strength, identity, safety, purity and quality of drug product.
[][]Annotate: To add explanatory notes.
[][]SOP: Standard Operating Procedure.
[][]N/A: Not Applicable

Responsibilities:

[][]The roles and responsibility is as follows:

Concerned Personnel

[][]To carry out the documentation as mentioned in SOP.

Department Head or Designee

[][]To ensure training and implementation of SOP.

Manager, Quality Assurance

[][]To ensure implementation of SOP.

Procedure: Good Documentation Practice

[][]General Guidelines for documentation practices:
[][]Sign and date all data entries on the date of data entry, as applicable.
[][]Date to be written numerically in the DD/MM/YY form. E.g. write 13/01/16 for 13th January 2016.
[][]Time to be written numerically in the HH:MM form in the document using 12 hours cycle daily. For e.g., 8:30 AM, 4:30 PM etc.
[][]Time duration to be written as shown below:
[][]e.g. If for some process the observed time duration is 2 minutes and 30 seconds then it’s should be written as 2min 30 sec and not as 2:30min.
[][]In case of wrong entry, strike out with single line and put initial and date nearby it. Do not overwrite or block the wrong entry.
[][]Do not leave blank space, Write N/A.
[][]Do not use the ” if the entry is repeated in next line.
[][]Use of pencil is not allowed.
[][]Correction fluid / white ink / eraser should not be used.
[][]Entries to be made in legible handwriting.
[][]Unusual observations shall be recorded, signed and dated.
[][]Entries in logbook shall be done in the chronological order.

General Guidelines for using indelible ink pen:

[][]Write all GMP records only with permanent BLUE indelible ink pen.
[][]Permanent BLUE indelible ink pen should be used for signing of master documents.
[][]The QA supervisor should use the permanent GREEN indelible ink pen to sign after checking the data on shop floor.
[][]Data entries should be recorded, signed and dated immediately after the completion of each activity, as applicable.

Correction of Recording Error / Overwriting or Incorrect Entry:

[][]In case of any wrong entry, do not over write or block the entry to make it obscure or unreadable. Strike out the wrong entry with straight single line passing through incorrect entry in [][]such a way that it remains readable.
[][]Make correct entry nearby it.
[][]For major changes annotate the actual reason for the correction or change, as the case may be.
[][]The correcting person shall put the initials along with date on which correction was done.
[][]Suppose ‘Cleaned’ is recorded in place of ‘Ensured’ by mistake on 10/01/XX and observed later during BMR review on 18/01/XX, it can be corrected at later date in the following way:
[][]Correct way for Correction on 18/01/XX:
[][]Initial Cleaned Ensured
[][]Date
[][]If space is not sufficient for correction, strike out the wrong entry with single line and highlight the same with an asterisk (*) nearby it. Define the asterisk at the bottom of the page and [][]Correct the wrong entry with initial and date.
[][]Entry of Missed Step:
[][]Entry of any missed step can be done later only if it can be proved that the step had been performed but the doer/performer and/or checker failed to document the same.
[][]The person making entry of missed step shall put the initials along with the date on which entry is done nearby entry of missed step.
[][]Working with Blank or Unused page/space :
[][]Do not leave blank space in any GMP record.
[][]Strike out any blank space or page with cross line and write in between the line N/A.
[][]Put initial and date at the end of the line, e.g., for following unused space strike out as specified :

Rounding – off of values:

[][]The rounding off values is applicable only to the calculations and not to the observed readings. Limits which are fixed numbers shall not be rounded off.
[][]e.g., If limit is 2 – 8 °C, then observed value 8.2 cannot be rounded off. Any value or figure which displayed by any equipment/instrument shall not be rounded off, e.g. if pH meter displayed is 3.79 than it should be mentioned as such and should not be rounded off to 3.8.
[][]When rounding off of any value is required, follow the below procedure.
[][]If last digit is equals to or greater than 5, it is eliminated and the preceding digit is increased by one.
[][]If last digit is smaller than 5, it is eliminated and the preceding digit remains unchanged.
[][]For examples see the below Illustration:
[][]Illustration of Rounding of Numerical Values for comparison with Requirements
[][]Requirements: Product Yield Limit (99.0% to 101.0%)

Unrounded Value to Rounded Value

[][] 98.926 shall be 98.93
[][] 100.124 shall be 100.12
[][] 99.655 shall be 99.66

Assigning Due Date:

[][]For assigning Due Date in all GMP records, calculate due date as per frequency for that particular activity from the day on which that activity is performed.
[][]Status of the activity can be valid up to the due date.
[][]For example, consider the case of assigning due date for re-cleaning of pre-filter for which cleaning frequency is 15 days.
[][]Suppose cleaning of pre-filter is done on 02/01/XX, since frequency of pre-filter is 15 days, due date for re-cleaning of pre-filter can be assigned 16/01/XX and cleaning can be considered valid up to 16/01/XX.
[][]Record all information in legible handwriting in all GMP records.
[][]Printouts from the instruments relevant to the analysis shall be retained and no such document shall be discarded even if they are not of use in the calculation.

Additional Documentation Practices for Quality Control Laboratory:

[][]Entries like “Complies/Does not comply” only allowed for the binary observations but the binary observation shall be specific.
[][]E.g. Limit test shall mention the observation noticed and TLC shall mention the comparison with the spot.
[][]Calculations shall be documented and rounding off shall be done as per SOP.
[][]Concordance of another analyst shall be taken for observations of subjective tests. E.g. limit tests, TLC plates etc. Both the analyst shall initialize and sign the observation.
[][]Printouts from the instruments relevant to the analysis shall be retained and no such document shall be discarded even if they are not of use in the calculation.

Annexure: Good Documentation Practice

N/A

Good Documentation Practice Read More »

Labelling Procedure

Labelling , Purpose :

Labelling , To describe the procedure for status labeling to identifying correct status of Equipment, area, Stage of product, Raw Material & Packaging Material at a given point of time.

Labelling , Scope :

This procedure is applicable for all materials/products received and stored in General Block & Sterile Block at XX Pharmaceuticals Ltd. that has the potential to affect GMP and quality, safety or efficacy of the finished product.
This procedure is also applicable for control of status identifying labels, process label and product labels used in Production, Warehouse, Quality Control and Quality Assurance departments in General Block & Sterile Block at XX Pharmaceuticals Ltd.

Definitions / Abbreviation:

[][]Labeling: Displaying status and identity of a material or a thing.

Responsibilities:

[][]The roles and responsibility is as follows:

Concerned Department

[][]Concerned department Officers/ Executive shall be responsible to carry out the activity as per procedure.
[][]To affix the status label as per procedure.

Head, Concerned Department

[][]Concerned Department Heads shall be responsible for effective implementation of procedure and activities.

Quality Assurance

[][]To ensure implementation of labeling procedure & proper labeling as per SOP.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure the overall implementation of the SOP.

Procedure:

[][]In order to avoid mix-ups and contamination, for easy identification and traceability, of product and to ensure working as per GMP standards it is important to affix status label at each stage of process on equipment’s, products, containers, accessories and areas. Labels of various types are used in manufacturing functions.
[][]The purpose, type and use of each label are described as below.

General procedures for label handling:

[][]Every status-identifying label shall have distinctive format number and master copy for all computers generated and printed label formats shall be preserved securely under lock and key with Manager, Quality Assurance.
[][]Each and every container of active pharmaceutical ingredients (APIs), excipients, raw materials, intermediate products, primary and printed packaging components will have to be labeled denoting proper status.
[][]Every supplier batch will have status label (e.g. Passed label) with one unique batch/ lot number.
[][]For tertiary packing materials (product nonspecific i.e. shipper carton, master carton) pallet wise labeling process will be followed.
[][]All labels will be preprinted self-adhesive labels which provide blank space for printing/ writing necessary information.
[][]After printing/ generating of status label an authorized person will verify the correctness of printing.
[][]Containers/packs where self-adhesive label cannot be pasted securely (Sack/ polythene bag) transparent tapes will be used at every side for affixation. Stapler pin will never be used for affixation of label.
[][]No material/ product/equipment without status label shall be stored either in the warehouse or production floor.
[][]Warehouse personnel cannot issue material from any container to production where ‘PASSED’ label is not available.
[][]During dispensing of active raw materials, Officer/ Executive will ensure that every container contains three status label (QUARANTINED, SAMPLED, UNDER TEST and PASSED).
[][]In case of other raw materials (excipients) & packaging materials, all containers/ pack/ pallet must have ‘UNDER TEST’, ‘PASSED’ and ‘QUARANTINED’ label. ‘SAMPLED’ labels will be found between ‘QUARANTINED’ and ‘UNDER TEST’ label only on containers from which the samples were taken.

[][]Label must not be applied on the container lids.
[][]Labels will be applied on the body of the containers so that it will be easily visible. Label must not be overwritten and erased out.
[][]Labels will be handled securely in a segregated manner (under the custody of an authorized person) with controlled access.

Quarantined Label:

[][]After receipt and checking of incoming materials, warehouse Officer/ Executive will print ‘QUARANTINED’ labels with necessary information for all containers/packs for each batch of materials.
[][]Authorized warehouse personnel will provide all the entry required for ‘QUARANTINED’ label.
[][]Warehouse Officer/ Executive will verify and ensure that all the information printed on the labels of first sheet is correct and then will give command to authorized warehouse personnel for printing total ‘QUARANTINED’ labels required for the respective lot. Any label with printing error will be destroyed instantly.
[][]Warehouse Officer/ Executive will sign (issued by) and authorized person of the warehouse will affix all ‘QUARANTINED’ labels on each container of the incoming materials.
[][]This label is printed with black overprint on Orange background.

Approved Label:

[][]Quality Assurance Executive shall affix the ‘Approved Label’ on respective process container after receiving the certificate of analysis of that material / Product from QC.
[][]Quality Assurance Executive shall issue this label to approving In-process Granules/Powder, Uncoated /Coated Tablet for Work in progress.
[][]This label is printed with black overprint on Blue background.

Sampled Label:

[][]On receipt of Good Received Note (GRN) from warehouse, QC personnel will follow the SOP for Raw material sampling and release procedure or SOP for Packing material sampling and release procedure to determine the sampling plan and the number of the containers to be sampled.
[][]QC Officer/ Executive/ authorized person will issue and print required ‘SAMPLED’ labels according to sampling plan.
[][]After sampling, duly signed ‘SAMPLED’ label will be affixed on the containers or packs from which samples are withdrawn.
[][]The ‘SAMPLED’ label will be affixed beneath the ‘QUARANTIED’ label in a cascading manner (slight overlapping) without hiding any information of ‘QUARANTIED’ label.
[][]This label is printed with black overprint on Yellow background.

Hold Label:

[][]Manager, Quality Assurance may hold any raw material, packaging material or finished product when necessary.
[][]Quality Assurance personnel will print ‘HOLD’ label with necessary information.
[][]After signed by authorized person, Quality Assurance personnel will affix ‘HOLD’ label on the pallet/ container that will be hold for long time for a decision of passing or rejection.
[][]When final decision of passing or rejection is taken, Quality Assurance personnel will remove the ‘HOLD’ label and destroy them. Then, ‘PASSED’/ ‘REJECTED’/ ‘APPROVED’ labels will be affixed.
[][]This label is printed with black overprint on orange background.

Passed Label:

[][]QC Officer/ Executive will follow the SOP for Raw material sampling and release procedure or SOP for packing material sampling and release procedure and issue the ‘PASSED’ label.
[][]QC officer / Executive will take required sheets of blank ‘PASSED’ labels. The quantity of ‘PASSED’ label will be based on number of containers/packs for each batch of materials
Officer/ Executive, QC will provide all the entry required for ‘PASSED’ labels and take the print-out of one page first.
[][] Another Officer/ Executive, QC will verify and ensure that all the information printed on the first sheet of labels is correct and then will give the command for printing total ‘PASSED’ labels required for the respective lot. Any label with printing error will be destroyed instantly. Officer/ Executive, QC will sign ‘PASSED’ labels.

[][]Authorized QC person will affix the ‘PASSED’ label on each and every single container of raw materials or packaging materials with the help of warehouse personnel.
[][]‘PASSED’ label will be affixed just beneath the ‘UNDER TEST’ label in a cascading manner (slight overlapping) without hiding any information of previous label.
[][]This label is printed with black overprint on Green background.

Rejected Label:

[][]QC Officer/ Executive will follow the SOP for Raw material sampling and release procedure or SOP for packing material sampling and release procedure and issue the ‘REJECTED’ label.
[][]QC officer will take required sheets of blank ‘REJECTED’ labels. The quantity of ‘REJECTED’ label will be based on number of containers/packs for each batch of materials
[][]Officer/ Executive, QC will provide all the entry required for ‘REJECTED’ labels and take the print-out of one page first. Another Officer/ Executive, QC will verify and ensure that all the information printed on the first sheet of labels is correct and then will give the command for printing total ‘REJECTED’ labels required for the respective lot. Any label with printing error will be destroyed instantly.
[][]Manager, QC will sign ‘REJECTED’ labels.
[][]Authorized QC person will affix the ‘REJECTED’ label on each and every single container of raw materials or packaging materials with the help of warehouse personnel.
[][]‘REJECTED’ label will be affixed just beneath the ‘QUARANTIED’ label or ‘UNDER TEST’ label in a cascading manner (slight overlapping) without hiding any information of previous label.
[][]This label is printed with black overprint on Red background.

Under Retest Label:

[][]Ware house Officer will identify any requirement for retesting of materials and immediately paste a ‘UNDER RETEST’ label on the container just beneath the previous ‘PASSED’ label and transfer the material to quarantined area. Warehouse Officer will inform the Manager, QC to arrange sampling for retesting
[][]This label is printed with black overprint on Yellow background.

Returned label

[][]The ‘RETURNED’ Label is displayed on the container/material for identification of Product status.
[][]Concerned Department shall affix this label on excess material that is to be left after Primary Processing, e.g Drying/ Pulverization/ packaging operation.
[][]Ensure that the materials returned are clean, free of dust, properly covered and in uniform countable bundles or pack.
[][]This label is printed with black overprint on White background.

Cleaned Card Label

[][]The “CLEANED” label is displayed for the identification status of the equipment after completion of cleaning activity.
[][]Use this label after complete cleaning, as per SOP.
[][]In case of start of the operation, filled this label to be affixed in BMR/BPR.
[][]This label is printed with black overprint on green background.
[][]Following are the details to be filled up in the respective blank spaces. Label to be filled by operator / supervisor.
[][]Equipment Name: Name and/or ID no of the equipment, which is cleaned.
[][]Previous Product: Name of the product for which cleaning activity is completed in that particular equipment.
[][]Batch No.: Batch No. of the above product.
[][]Date of cleaning: Date on which equipment is cleaned.
[][]Use on or before: Date before which equipment can be used.
[][]Cleaned by: Signature or name of the person by whom equipment is cleaned.
[][]Checked by: Signature of production supervisor after verification of the filled contents in the label and after visual verification of cleanliness of the equipment.
[][]Verified by: Signature of the QCOM person, after visual verification of cleanliness of the equipment’s.
[][]To be used for product: The product which will be taken for process after the equipment cleaning.
[][]Batch No.: Batch no. of the product which will be taken for process after equipment cleaning.

Partially Cleaned Label

[][]The PARTIALLY CLEANED label is displayed for the identification status of the equipment after completion of cleaning activity.
[][]Use this label after partial cleaning, as per SOP.
[][]In case of start of the operation, filled this label to be affixed in BMR/BPR.
[][]This label is printed with black overprint on Yellow background.
[][]Followings are the details to be filled up in the respective blank spaces. label to be filled up by the operator/ supervisor.
[][]Equipment Name: Name and/or code no of the equipment, which is cleaned.
[][]Previous Product: Name of the product for which cleaning activity is completed in that particular equipment.
[][]Batch No.: Batch No. of the above product.
[][]Date of cleaning: Date on which equipment is cleaned.
[][]Use on or before: Date before which equipment can be used.
[][]Cleaned by: Signature or name of the person by whom equipment is cleaned.
[][]Checked by: Signature of production supervisor after verification of the filled contents in the label and after visual verification of cleanliness of the equipment.
[][]Verified by: Signature of the QCOM person, after visual verification of cleanliness of the equipment’s.
[][]To be used for product: The product which will be taken for process after the equipment cleaning.
[][]Batch No.: Batch no. of the product which will be taken for process after equipment cleaning.

To be Clean Label:

[][]This label is displayed for the identification status of the equipment, accessories and containers after its use.
[][]Followings are the details to be filled up in the respective blank spaces. label to be filled up by the operator/ supervisor.
[][]Previous Product: Name of the product for which processing activity is completed in that particular equipment.
[][]Batch No.: Batch No. of the above product.
[][]Signature: Signature of the production supervisor after verification of the filled contents in the label.
[][]Date: Date on which the equipment is due for cleaning.
[][]This label is printed with black overprint on Orange background.

Loose Label:

[][]‘Loose’ Label is to be affixed on loose container/shipper by Production Department.
[][]This label is printed with black overprint on White background.
[][]Executive, Production will provide all the entry required for ‘Loose’ labels and take the print-out. Any label with printing error will be destroyed instantly.

Material Dispensing Slip Label:

[][]This label is displayed for the identification status of the Dispensed Material.
[][]Use this label during of dispensing of material as per SOP.
[][]Officer/ Executive, Production will provide all the entry required for this label and take the print-out.
[][]In case of start of the operation, Executive, Production will affix this label in BMR.
[][]This label is printed with black overprint on White background.
[][]Followings are the details to be filled up in the respective blank spaces.
[][]Balance No.: Name of the Balance ID
[][]Operation: Material dispense for either Granulation or Coating.
[][]Material: Name of the Raw material
[][]Code: Code No. of the Raw material
[][]Lab Ref. No.: Lab Control No. of the Raw material
[][]Product: Name of the product that is to be manufactured.
[][]Batch No. : Batch no. of the concerned product.
[][]Batch size: Actual batch size of the concerned product.
[][]Gross Wt.: Total weight (wt) of the filled container without lid in kilogram (kg).
[][]Tare wt.: Weight of the empty container along with Polyethylene bags without lid before taking it in use in kg.
[][]Net Wt.: Subtract the tare wt. from gross wt. in kg.
[][]Container No.: Number of that particular container out of total no. of container used for the above batch.
[][]Dispensed by: Signature of dispensing Operator
[][]Checked by: Signature of Production Executive after verification of the filled contents in the label.
[][]Verified by: Signature of QCOM officer after verification of the filled contents in the label.

Process Label:

[][]This label is displayed on the container for identification of the product status.
[][]This label is to be used on the container during the manufacturing stage. For Example: Under sifting, under granulation, under solution preparation, Ready for Granulation / Drying / [][]Blending / Solution ready for coating.
[][]This label is printed with black overprint on White background.
[][]Following are the details of preprinted label to be filled up in the respective blank spaces and to be filled by operator / supervisor.
[][]Product: Name of the product collected / to be collected in the container.

[][]Batch No.: Batch no. of the concerned product.
[][]Status: Stage in which the product is ready for next step.
[][]Container No.: Number of that particular container out of total no. of container used for the above batch.
[][]Batch Size: Actual batch size of the concerned product.
[][]Mfg. Date & Exp. Date: Manufacturing and Expiry date of the concerned product.
[][]Gross wt.: Total weight (wt) of the filled container without lid in kilogram (kg).
[][]Tare wt.: Weight of the empty container along with Polyethylene bags without lid before taking it in use in kg.
[][]Net wt.: Subtract the tare wt. from gross wt. in kg.
[][]Checked by: Signature of Production officer after verification of the filled contents in the label.

Product Label:

[][]This label is displayed on the Shipper for identification of the product status.
[][]This label is to be used on the Shipper during the Secondary Packaging Operation.
[][]This label is printed with black overprint on White background.
[][]Following are the details of preprinted label to be filled up in the respective blank spaces and to be filled by operator / supervisor.
[][]Product: Name of the product collected / to be collected in the shipper.
[][]Batch No.: Batch no. of the concerned product.
[][]Mfg. Date & Exp. Date: Manufacturing and Expiry date of the concerned product.
[][]Pack Quantity: Total no. of pack in Shipper.
[][]Sr. No.: Total No. of Shipper

[][]Packed by: Name / sign of the Operator /Supervisor who are involved in shipper Making & closing.
[][]Storage Condition: Storage Condition of the concerned product.

Area / Equipment Label:

[][]This label is used to exhibit the process that is being carried out in the area/equipment, tick (√) whichever is applicable.
[][]This label is printed with black overprint on Green background.
[][]The area is labeled at the start-up of the batch.
[][]Following are the details to be filled up in the respective blank spaces. Label to be filled by operator / supervisor.
[][]Product: Name of the product taken or to be taken for processing on that particular equipment.
[][]Batch No.: Batch number of the above product.
[][]Batch size: Actual batch size in written in the BMR.
[][]Status: Particular stage of activity in process.
[][]Checked by: Signature of Production supervisor after verification of the filled contents in the label.
[][]Date: Date on which the process takes place.

Retention Sample:

[][]QC / QA officer shall affixed sample Label on the sample Poly bag or container which is to be sample for retaining.
[][]This label is printed with black overprint on White background.

[][]Officer/ Executive, QC or QCOM will provide all the entry required for ‘Retention Sample’ labels.

Cleaned Label:

[][]This label is displayed for the identification status of the accessories and containers after completion of cleaning activity.
[][]This label should not be attached with BMR/BPR.
[][]This label on containers and accessories should be defaced with a cross-line and destroyed when taken for use.
[][]In case of start of the operation, this label has to be removed from container and ‘ Process’ label to be affixed.
[][]In case of start of the operation, this label has to be removed from accessories and ‘Area/ Equipment’ label to be affixed.
[][]This label is printed with black overprint on Green background.

Under Test Label:

[][]This label is displayed on the container/ Packet for the identification status of the material/product after sampling for QC Test.
[][]QC / QCOM Executive shall affix this Label after completion of sampling activity.
[][]This label is printed with black overprint on Yellow background.

Annexure: Download all here

Annexure-I: Blank format for ‘Quarantined’ label.
Annexure-II: Blank format for ‘Approved’ label.
Annexure-III: Blank format for ‘Sampled’ label.
Annexure-IV: Blank format for ‘Hold’ label.
Annexure-V: Blank format for ‘Passed’ label.
Annexure-VI: Blank format for ‘Rejected’ label.
Annexure-VII: Blank format for ‘Under Retest’ label.
Annexure-VIII: Blank format for ‘Returned’ label.
Annexure-IX: Blank format for ‘Cleaned’ label.
Annexure-X: Blank format for ‘Partially Cleaned’ label.
Annexure-XI: Blank format for ‘To Be Cleaned’ label.
Annexure-XII: Blank format for ‘Loose’ label.
Annexure-XIII: Blank format for ‘Material Dispensing Slip’ label.
Annexure-XIV: Blank format for ‘Process’ label.
Annexure-XV: Blank format for ‘Product’ label.
Annexure-XVI: Blank format for ‘Area/ Equipment’ label.
Annexure-XVII: Blank format for ‘Sample’ label.
Annexure-XVIII: Blank format for ‘Retention Sample’ label.
Annexure-XIX: Blank format for ‘Cleaned’ label.
Annexure-XX: Blank format for ‘Under Test’ label.

Labelling Procedure Read More »

Batch Numbering and Coding System

Batch Numbering, Purpose :

Batch Numbering, The purpose of this SOP is to describe the procedure of batch numbering system of finished product and issuing code number of raw, packaging and finished product.

Batch Numbering, Scope :

This procedure is applicable for coding of all raw materials, packaging materials, finished products and batch numbering system of finished product at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Batch Number: A distinctive combination of numbers and/or letters which uniquely identifies a batch on the labels, its batch records and corresponding certificates of analysis, etc.
[][]Code Number: An arrangement of numbers providing a unique identity to the items which they are assigned.

Responsibilities:

[][]The roles and responsibility is as follows:

Executive/ Manager, Product Development

[][]To inform and request Supply Chain department that the new materials to be used for product development.

Executive/ Manager, Supply Chain

[][]Issue the unique material code number of each raw material and packaging materials and as well as finished product

Executive/ Manager, PMD

[][]To inform and request Supply Chain Department to issue material & product code for new products.

Executive/ Manager, Quality Control

[][]Implementation of the total coding system.

Executive/ Manager, Quality Assurance

[][]Implementation of the total coding and batch numbering system.

Executive/ Manager, Production

[][]Implementation of the total coding and batch numbering system

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the system as per SOP.

Procedure:

Raw Material Coding System:
[][]Maintain seven alphanumerical characters (first three characters are alphabetic and last four characters are numerical) for Raw Material Coding System.
[][]Start the coding with ‘RM’ which stands for ‘Raw Material’ and it is common for every raw material coding system
[][]For the Active Raw Material select ‘A’ as the third character of the code. When the raw material is excipient then select ‘E’ instead of ‘A’.
[][]At last specify the code number with four numerical characters to indicate the separate material. Following this procedure, raw material code for the first enlisted Active Material (API) will be RMA0001 and the second one (API) will be RMA0002.
[][]When the same material has different categories (such as compacted, granular, pharma grade etc.) then for every category, a new code number will be generated maintaining previous procedures.
[][]For example: Raw Material Code Number ‘RMA0001’ stands for
RM=Raw Material
A=Active (In case of Excipient it will be ‘E’)
0001=Individual number of raw material

Packaging Material Coding System:

[][]Maintain seven alphanumerical characters (first four characters are Alphabetic and last three characters are numerical) for Packaging Material Coding System.
[][]First characters which stands for packaging material. Second character will be changed for primary and secondary packaging material, When primary packaging material it will be ‘P’ and when secondary packaging material it will be ‘S’.
For example
=>PP= Primary Packaging Material
=>PS= Secondary Packaging Material

[][]Next two characters which stand for sub category of packaging material. It will be changed for every sub category of packaging material as Annexure-I.
[][]Last three characters which stand for sequential number. Every sub category material starts with sequential number 001. Such as
=>AB-001= Alu- Bottom foil
=>TF-001= Alu-Lid foil
=>And so on

[][]The sequential number will be changed when different types of materials come in same sub category. For example
=>AB-001= Alu –Bottom foil 206 mm
=>AB-002= Alu –Bottom foil 183 mm
=>And so on

[][]Finally the coding system of packaging material is like
=>PP-AB-001
Where
=>PP stands for primary packaging material
=>AB-001 stands for alu bottom foil 206 mm

Finished Product Coding System:

[][]Maintain seven alphanumerical characters (first digit is alphabetic and last five digits are numerical) for finished product coding system.
[][]Start the coding with ‘P’ which stands for finished product. P is common for every finished product code numbering system.

[][]The last five digits 00001 is sequential number. It will be changed in every finished product coding system. It will be also changed when same product in different strength. For example finished product code of Cexoral 200 capsule is P-00001 and Cexoral 400 capsule is P-00002.
[][]Finally the finished product coding system is P-00001
[][]Where P stands for finished product
[][]is dash
[][]00001 stands for sequential number of individual product with strength.

Batch Numbering System for Finished Product:

[][]Maintain six characters (All six digits are numerical) for batch numbering system.
[][]First two digits stand for year. It will be changed for next year.
[][]For example
=>20AA for AA
=>20BB for BB
=>20CC for CC
And so on..
[][]The last four digits are yearly batch requisition serial number of products manufactured in XX Pharmaceutical Limited, Which (last four digits) will be started from 0001, next batch requisition serial will be started from 0002 and so on.
[][]In every new year, the last four digits (batch requisition serial number) will be started from 0001.
[][]Example for presentation of the Product Batch Number on the Inner Carton, Sample Pack, Label and Shipping Carton:
XX0001
Where
XX stands for year of 20XX
0001 sands for serial number of batch manufactured in year of 20XX.

Batch Numbering System for Water for Injection:

[][]Maintain six characters (six digits are alphanumerical) for batch numbering system.
[][]First digit stands for water for injection
[][]Second and third digits stand for year. It will be changed for next year.
For example
20AA for AA
20BB for BB
20CC for CC
And so on…

[][]The last three digits are yearly batch requisition serial number of water for injection which (last three digits) will be started from 001, next batch requisition serial will be started from 002 and so on.
[][]In every new year, the last three digits (batch requisition serial number) will be started from 001.
[][]Example for presentation of the preprinted ampoule:
WXX001
Where
[][]W stands for Water for injection
[][]XX stands for year of 20XX
[][]001 sands for serial number of batch manufactured in year of 20XX.

Annexure:

Annexure-I: Packaging Material Code

Batch Numbering and Coding System Read More »

Logbook Handling

Logbook , Purpose :

Logbook , The purpose of this SOP is to describe the procedure for issuance and control of logbooks authorized to use GMP related activities.

Logbook , Scope :

This procedure is applicable for all departments at XX Pharmaceuticals Limited (Both General and Sterile Block).

Definitions / Abbreviation:

[][]Logbook: A bound book, which contains preprinted serially page no. and preprinted pages as per the respective SOP’s requirement.

Responsibilities:

[][]The roles and responsibility is as follows:

Quality Assurance Personnel

[][]To issue as per SOP.
[][]To close the completed one.

Concerned Department

[][]To write raw data in it as per defined procedure
[][]To maintain it properly
[][]To submit the completed book.

Manager, Quality Assurance

[][]Approval of the SOP.
[][]To ensure that the implementation of the system as per SOP.

Procedure:

Concerned department shall prepare it for equipment/instrument used in their department. It will be issued by Quality Assurance.

Issue of Log book:

[][]Concerned department shall raise logbook issuance request (Annexure–I) for authorization of it to Quality Assurance.
[][]Quality Assurance shall assign Reference number to new logbook as given below.
e.g. PRO/1
Where
=>PRO is the department code of Production (General)
=>/ is the separator
=>1 is the sequential number of log book
=>Next logbook number shall be 2, 3, 4………and so on.
=>The code of each department is given below.

Department /Code

[][]Production (General)/PRO
[][]Production (Sterile)/C-PRO
[][]Packaging (General)/PKG
[][]Packaging (Sterile)/C-PKG
[][]Warehouse (General)/WH
[][]Warehouse (Sterile)/C-WH
[][]Quality Assurance (General)/QCOM
[][]Quality Assurance (Sterile)/C-QCOM
[][]Quality Control (General)/QC
[][]Quality Control (Sterile)/C-QC
[][]Microbiology (General)/MICRO

Quality Assurance will prepare the front cover of log book (Annexure-III) with unique Reference number.

Review of the log books:

[][] It will be periodically reviewed by the departmental head make an initial.
[][]Concern personnel will ensure proper control and data record during day to day use of logbooks.
[][]After completion of any logbook, a new will be issued by Quality Assurance under same reference no. of the next serial no. of logbook.

Annexure:

Annexure-I: Log book Issuance Request
Annexure-II: Log book Issuance Record
Annexure-III: Log book Front Cover

Logbook Handling Read More »

Internal Audit/Self-Inspection

Internal Audit, Purpose :

Internal Audit, The purpose of this document is to define a systemic, standardized and effective approach of Self Inspection which is performed by personnel within their own functional or departmental unit. This SOP defines the requirements to ensure that self inspection processes are ‘In Place’ and ‘In Use’ which will
help to:
[][]Promote awareness of quality and GMP to avoid quality problems.
[][]Identify risk and manage it as per Risk Management process.
[][]Encourage ownership of continuous improvement actions.

Internal Audit, Scope :

This SOP applies to the all departments which are included in Audit universe (activity of which may affect quality of products of XX Pharmaceuticals Limited). Audit universe is a list of all departments/sections at the site that are to be audited by a Quality function in a calendar year.

Definitions / Abbreviation:

N/A

Responsibilities:

[][]The roles and responsibility is as follows:

Departmental Head/ Manager

[][]Nominate the self inspection team
[][]Prepare the CAPA against Audit findings and agree the CAPA with Quality Compliance.
[][]Ensure the implementation of CAPA
[][]Ensure the completion of JDI activities

Manager, Quality Assurance

[][]In conjunction with Head of Quality Assurance ensure that audit process is ‘in place’ and ‘in use’
[][]Create and maintain department profile
[][]Posting of CAPA in CAPA tracking system and verify follow up & close-out of CAPA
[][]Prepare the self inspection schedule which identifies areas to be inspected.
[][]Review the audit process and present the status in Quality Review Meeting.

Self Inspection Team

[][]Conduct audit against the standard and identify risk
[][]Assess disclosed risk
[][]Prepare audit report and issue it to Head of Quality Assurance

Head of Quality Assurance

[][]Ensure that audit process is ‘in place’ and ‘in use’
[][]Approve the self inspection schedule
[][]Approve the CAPA
[][]Approve changes to an agreed CAPA or date extension request

Procedure:

[][]Self Inspection Frequency:
[][]Frequency of self inspection in every function/department will be twice a year.
[][]It will be recorded in Quality Assurance Department.
[][]Change of frequency of a section/department must be approved by Head of Quality Assurance.

Create and Maintain the Audit Schedule:

[][]Every department/section will conduct checklist based self inspection in twice a year.
[][]Manager, Quality Assurance will prepare a schedule of self inspection and submit it to Head of Quality Assurance for approval by November of each year for implementation in the next year.
[][]The schedule (Annexure I) will contain the following minimum (but not limited to):
=>Name of the area
=>Type of the inspection
=>Systems (QMS) to be audited
=>Month of the audit
=>Name of the Self Inspection team
=>Proposed period (usually 2nd Week of the month)

[][]The approved schedule for the following year will be communicated by Manager, Quality Assurance to all concerned departments by December.
[][]Manager, Quality Assurance will maintain the audit schedule. Every scheduled inspection can be moved within the +/- 10 days time window, however, any change beyond that would require a formal approval of Head of Quality Assurance.
[][]The schedule adherence will be monitored in every Quality Review Meeting.

Preparation for the self inspection

[][]Head of Quality Assurance will assign a self inspection team. A self inspection coordinator will lead the team.
[][]Self Inspection Coordinator must be trained on audit process. The team members must have at least training on the basic cGMP and auditing process.
[][]Self Inspection team will first identify the Department/Sectional SOPs related to specified systems. In addition, the team will review the minimum following (not limited to):
=>Related SOP
=>Department Practices
=>Procedures
=>Worksheets
=>Checklist
=>Departmental CAPAs from CAPA tracking system

Conduct the self inspection

[][]Self Inspection Team will spend sufficient time of a day for the inspection.
[][]The main focus of the team will be to verify whether the site or sectional SOPs are being followed accurately. Self Inspection team will have to ensure ‘In Place’ and ‘In Use’ of the following:
=>Sectional SOP
=>Relevant SOP
=>Procedures (BMR/BPR/Analytical method etc.)
=>Worksheet (Record of Temperature, log books, analytical sheets etc.)
=>Checklist (Line Clearance, machine cleaning, house keeping)
=>Material & Product standards (Specification, storage etc.)

[][]The self inspection team should take a sample of the documents or procedures for those processes or systems running at the time of the self inspection and review it. The review procedure may be as follows:
=>Ask the operator to describe the task/process
=>Check the description against the procedure (SOP/BMR/BPR/Check sheet)
=>Follow/observe the operation/process
=>Verify the records against specified standards

Record and Report findings

[][]The Self Inspection Team must record the non Assurance from the departmental practices and documentation in the specified template (Annexure II).
Based on the associated risks finding will be classified as either
=>Critical
=>Major
=>Minor
=>Note

[][]Team will follow the Annexure III for categorizing the findings.
[][]Self Inspection Team immediately notify critical finding to Department Manager. Operation associated with the critical finding must be stopped immediately until the issue has been resolved.
[][]Self Inspection Coordinator will prepare a full report (Annexure II) detailing all the self-inspection findings within seven (7) working days of the self-inspection and submit it to Head of Quality Assurance.

Propose, Review and Agree the Corrective and Preventive Actions

[][]Head of Quality Assurance will review the self inspection report and send it to Department Manager.
[][]Department Manager will review the inspection report and immediately address the findings which can be corrected by ‘Just Do it (JDI)’. Few example of the JDI is as follow:
=>Immediate correction of line/material labeling errors
=>Operational errors that can be immediately discussed face to face
=>General good housekeeping requirements, such as, emptying of bags, disposal of waste box, and clearing and tidying of the area.
[][]The JDI action implementation date is to be documented in the report (Annexure II).
[][]Department Manager will prepare an action plan (CAPA) for the findings which require more than 30 days implementing.
[][]Department Manager will forward the report to Manager, Quality Assurance along with CAPA within 4 working days of completing Inspection.
[][]Manager, Quality Assurance will verify that proposed CAPAs would adequately manage the root causes of the identified risk and get it approved by Head of Quality Assurance.
[][]After the approval of CAPAs, Manager, Quality Assurance will formally notify the Department Manager and post all the CAPAs in CAPA tracking system within 2 days where every CAPA has a unique reference number mentioned in the inspection report.
[][]Progress CAPA action to closure
[][]Department Manager will close the CAPA as per target date and inform Manager, Quality Assurance formally with physical evidence (SOP, Validation Report or other as appropriate).
[][]After verifying the evidences Manager, Quality Assurance will close the CAPA in the CAPA tracking system.
[][]For any date extension, approval is to be taken from Head of Quality Assurance before the due date.
[][]In every Quality Review Meeting, CAPA status will be reviewed

Annexure:

Annexure-I: Self Inspection Schedule
Annexure-II: Self Inspection Report
Annexure-III: Classification of findings

Checklist for Internal Audit/Self-Inspection

1.Self Inspection Checklist for Quality Control
2.Self-Inspection Checklist for Production _ Packaging Operation
3.Self Inspection Checklist for Quality Compliance
4.Self-Inspection Checklist for Warehouse

Internal Audit/Self-Inspection Read More »

Source Approval of Raw Materials & Packaging Materials

Source Approval, Purpose :

Source Approval, The purpose of this SOP is to describe the procedure for selection, approval of new vendors / sources for raw materials, packaging materials and evaluation of existing ones.

Source Approval, Scope :

This SOP is applicable to all vendors / sources for raw materials, packaging materials which may have an impact on product quality manufactured by XX Pharmaceuticals Limited. This SOP is applicable for both General and Sterile block of XX Pharmaceutical Limited.

Definitions / Abbreviation:

[][]Vendor: A vendor, or a supplier, is an enterprise in the supply chain that contributes goods and services available to companies or consumers. A vendor can operate both as the supplier of goods (seller) and the manufacturer. Generally, a supply chain vendor manufactures inventory/stock items and sells them to the next link in the chain. Today, the terms refers to a supplier of any good or service.
[][]SOP – Standard Operating Procedure
[][]PD – Product Development
[][]QA – Quality Assurance
[][]QC – Quality Control
[][]SCD – Supply Chain Department
[][]COA – Certificate Of Analysis
[][]API – Active Pharmaceutical Ingredient
[][]MSDS – Material Safety Data Sheet
[][]TSE – Transmissible Spongiform Encephalopathy
[][]BSE – Bovine Spongiform Encephalopathy

Responsibilities: Source Approval

The roles and responsibility is as follows:

Executive, PMD

[][]To inform PD, QA and supply chain department about new product with expected production forecast.

Executive, PD

[][]To raise requisition for any new materials required for new product development with PD trial quantity and forward to supply chain department.

Manager, Supply Chain

[][]Sourcing of raw and packaging materials from vendors and to initiate Vendor approval form.
[][]To collect documents as required.
[][]To procure raw materials and packaging materials from approved sources.

Executive, QC

[][]To analyze the source samples from new or existing vendor including raw materials.
[][]To prepare and review of approved source list for raw materials, packaging materials.
[][]Vendor rating.

Executive, Quality Assurance

[][]Evaluation of vendor documents.
[][]Preparation of vendor audit schedule.

Manager, Quality Assurance

[][]Approval/not approval of vendor.

Procedure:

The following procedure is to be followed for procurement from a new source or vendor.

Required Document

[][]To evaluate raw materials vendor following document are required
[][]Duly filled Vendor Approval Questionnaire
[][]Duly filled Vendor Approval form
[][]Certificate of Analysis (COA)
[][]Method of Analysis (in case of non-compendial method)
[][]Stability data (both accelerated and long term) justifying shelf-life
[][]Material Safety Data Sheet (MSDS)
[][]Working Standard of Active Material with COA

[][]Manager, Supply Chain forwards the sample along with these documents to Quality Control Department.
[][]To evaluate primary packaging material vendor following document are required. For secondary packaging material vendor 1st four are required.
=>Duly filled Vendor Approval Questionnaire
=>Duly filled Vendor Approval form
=>Certificate of Analysis
=>Method of Analysis
=>Design and specification
=>TSE/BSE free Certificate
=>Material Safety Data Sheet (MSDS)
=>Certificate of Composition

Approval of new vendor of raw materials:

[][]After getting information about new product with expected production forecast from PMD; PD will sent purchase requisition to supply chain department for procurement of new materials required for PD trial and share necessary information of new product to QC for preparation of specification.
[][]QC generates draft specifications for new material with the concern of PD. Any in-house specification that should be included on the basis of literature survey or PD requirement. For INN material QC develops specification based on Manufacturer’s COA / specification and PD requirement.
[][]Supply Chain department identify suitable vendors for required material and ask for COA of that specific material to forward to QC. Evaluating manufacturer’s COA, QC will ask for QC test sample (mentioning quantity) from suitable vendors through SCD.

[][]Supply Chain collects QC test sample / PD sample with documents from suitable vendors and then forwards to QC along with filled Vendor Approval Form (as per Annexure- I).
[][]QC receives source sample and documents and makes entry in a register with lab control no., name of material, lot. No., code no., manufacturer, supplier / local agent / indenter, manufacturing date, expiry date, quantity received, received by and date and review documents, if any anomalies observed then inform supplier through SCD.

[][]After testing QC makes entry of analyzed by and date; checked by and date; remarks in that register and shares QC test result of source sample with supplier and SCD.
On the basis of QC test result, SCD can procure PD trial sample of API from selected vendor.
[][]In receipt of PD trial sample of API, QC will arrange test for the same and then forwards PD trial sample to PD for formulation development along with analytical result and filled Vendor Approval Form.
[][]Sr. Executive / Asst. Manager, QC will put his comment on Vendor Approval Form after QC test of PD trial sample of API and QC test sample of excipients.
[][]On the basis of PD trial and stability report of formulated product with PD trial sample, PD will put his comment on Vendor Approval Form, then forward to Quality Assurance Department.
[][]Quality Assurance reviews the analytical data, PD trial report, available relevant documents and records and then put comment on Vendor Approval Form.
[][]If all reports comply the requirements, Manager, QA will grant approval for purchase of one initial consignment and the source will be included in approved source list as Category B (New sources on trial). If requirement does not comply, Manager, QA shall not approve the sample for procurement from that vendor.
[][]Product analytical results of at least three consecutive commercial batches to be evaluated to approve the supplier as Category A (Established source).

Approval of new vendor of packaging materials:

[][]For packaging materials other than printed one, Supply Chain collects source sample /Machine trial sample (Foil/Film -5 kg; Other materials -50 pcs or as per requirement) and required documents including Vendor approval questionnaire from supplier and then forward to QC along with filled Vendor Approval Form.
[][]QC receives source sample and documents and makes entry in a packaging material vendor sample register with lab control no., name of material, lot. No., code no., manufacturer, supplier / local agent / indenter, manufacturing date (where applicable), expiry date (where applicable), quantity received, received by and date.
[][]After testing, QC forwards machine trial sample along with machine trail report form (Annexure-IV) to production for machine trial.
[][]If the machine trial report is satisfactory, PD will arrange 6 months stability study for all primary packaging materials.
[][]Manager, QA will grant approval for purchase of one initial consignment on the basis of QC test result, machine trial report and stability study and the source will be included in approved source list as Category B (New sources on trial).
[][] If requirement does not comply, Manager, QA shall not approve the sample for procurement from that vendor. SCD can procure commercial sample after vendor approval.
[][]The analytical results of at least three consecutive commercial batches to be evaluated to approve the supplier as Category A (Established source).

Vendor Rating:

[][]A cross functional team shall jointly perform the vendor rating which consist of QC, SCD & QCOM
[][]To evaluate the performance of vendor Quality rating, Delivery rating, Price rating and Vendor rating shall be calculated in the following way.

Carry out the incoming inspection, analysis and calculate the ‘Quality rating’ as follows:

QR = Q1 + X1Q2 + X2Q3/Q

Where,
Q = Quantity Received
Q1 = Quantity Accepted without any comment/ problem
Q2 = Quantity Accepted with deviation; X1 = 0.7 (factor for deviation)
Q3 = Quantity Accepted with rectification; X2 = 0.5 (factor for rectification)

[][]Send the Quality Rating to Manager, SCM.

[][]SCM shall carry out the Delivery rating and Price rating as follows

Calculation of Delivery Rating of Vendor:

DR = q1 + 0.5q2/q

Where,
q = Quantity Ordered
q1 = Quantity received as on before time
q2 = Quantity received beyond due date

Calculation of Price Rating of Vendor:

PR = Minimum quotation received/ Price paid

[][]After completion of Delivery rating and Price rating, Executive, QCOM shall calculate and classify the vendor rating and approved by Head of QA.
Calculation of Vendor rating: VR = (0.5 QR + 0.3 DR + 0.2 PR) X 100

Classification of the Vendor Rating:

VR = 100 Good
90 ≤ VR < 100 Satisfactory
50 ≤ VR < 90 Deficient
VR < 50 Rejected

[][]Delete the vendor from “Approved Vendor list” when the level reaches “Rejected”.
[][]Finalize the list and forwarded the same to Quality Assurance Department for approval. Quality Assurance shall then circulate the “Approved Vendor/ Supplier list” to relevant department.
[][]The records of “Vendor Rating” will be kept for a minimum period of 3 years and the evaluation will be done at 3 years interval.

Procedure for exclusion of vendor from approved vendor’s list:

[][]The vendor shall be disqualified and removed from the approved vendor’s list for following reasons during regular assessment.
[][]If consecutive three consignments of material fail to comply the specifications or if the approval rate is below 70%.
[][]Three out of ten consignments fail to comply the specification.
[][]The delivery schedule is not met for 40% of supplies.

Corrective and preventive action:

[][]The vendor shall be made aware of the reasons for his exclusion and shall agree improvement action plans.
[][]The vendor, who has been excluded from the approved vendor list, may be included again by taking following corrective action and preventive actions.
[][]Manager, Quality Assurance or his representatives shall conduct facility audit of the vendor in order to ensure that quality system exists in the organization.
[][]Carry out the discussion on other non-quality issues like delivery schedule and rate etc.
[][]After Satisfactory outcome of all above points the vendor shall be approved as per the new vendor evaluation procedure.

Auditing

[][]Supplier audits will be conducted by experienced auditors nominated by Manager, Quality Assurance. Auditors will have experience/training in GMP auditing.
[][]Pre-audit meeting: A meeting of Manager, Quality Assurance, auditors and any other relevant personnel such as Procurement/ Technical expert shall be conducted 2 weeks prior to the audit.
[][]This meeting shall review all information available and any previous audit recommendations (in case it is done earlier) and status, complaints raised, number of deliveries since the last audit and any issues.
[][]The audit report (Annexure-V Audit Report Template) shall be finalized within 4 weeks after the audit and sent to SCM for forwarding it to the supplier/vendor with an advice that the supplier/vendor will give their feedback within 1 month of receipt of the report and prepare an action plan to close the gaps identified during the audit.

[][]Reference No. for Audit Report shall be as
AR/RM or PM/20xx-1
Where-
=>AR represents audit report
=>RM represents raw materials
=>PM represents packaging materials
=>20xx represents auditing year
=>1 represents sequential number
[][]SCM will follow up with the Supplier/vendor on the progress of recommended actions and any response or follow up correspondence shall be filed with the audit report in the appropriate supplier file.
[][]When a supplier/vendor is audited for the first time, a follow up audit should be conducted as per agreed time line with the supplier for the confirmation of the status of the Supplier.
[][]A supplier quality audit shall be performed at every 3 years interval which based on supplier’s documentations followed by desktop audit.

Supplier Status

[][]Updated approved source list must be maintained / amended / updated by Quality Control, that will be reviewed in every 6 months accordingly. Copy of approved source list will be shared to SCD, Warehouse, Production, Quality Assurance department. The list will hold two categories of suppliers:
=>Category B – New supplier/vendor under study.
=>Category A – Supplier/vendor having 3 consecutive satisfactory supplies
[][]If a supplier’s status is downgraded due to a quality problem, an unsatisfactory audit or any other issues, immediate action must be taken. The following actions must be considered:
=>Inform Manager, Quality Assurance
=>Amend Suppliers List
=>Source an alternative supplier on urgent basis
=>Review retrospective impacts on product quality

Supplier Files

[][]All related supplier approval documentation must be collated and filed in the appropriate supplier file. This should include the following where relevant:
=>Quality assessment questionnaire
=>Audit Checklist, Audit Report and Audit Summary Report
=>Response from the supplier
=>Relevant documents, i.e, Deviation Reports or Customer Complaint forms
=>Any other correspondence

Annexure: Source Approval

Annexure-I: Vendor Approval Form
Annexure-II: Vendor approval questionnaire – Raw materials
Annexure-III: Vendor approval questionnaire – Packaging materials
Annexure-IV: Machine trial report form
Annexure-V: Vendor Audit Report Template
Annexure-VI: Vendor Rating Form

Source Approval of Raw Materials & Packaging Materials Read More »

Deviation Procedure

What is Deviation?

A deviation in many industrial contexts is a deviation from an established, accepted process, procedure, guideline, specification, or standard. Especially in the pharmaceutical industry, deviations can occur at many stages, including development, manufacturing, labeling, packaging, sampling, testing, storage, distribution, and other complex industrial processes.

It is important to note that the definition of deviation may vary slightly depending on the regulatory body overseeing a company’s operations and the specific requirements governing these processes. These different definitions reflect the complex and highly regulated nature of the pharmaceutical industry, where strict compliance with standards is critical.

The International Council for Harmonization of Pharmaceuticals for Human Use (ICH) defines a deviation as a deviation from approved guidelines or established standards, as described in the ICH Q7 Good Manufacturing Practices (GMP) Guidelines for Active Pharmaceutical Ingredients. This highlights ICH’s commitment to ensuring consistency and reliability in pharmaceutical manufacturing practices.

For example, the International Organization for Standardization (ISO) provides a comprehensive definition in the context of quality management systems under ISO 9001:2015. Deviation here refers to the positive or negative effects resulting from deviations from expected or established values. This highlights ISO’s emphasis on maintaining a strong quality management framework.

Within the U.S. Food and Drug Administration (FDA), which plays a central role in drug regulation, it defines deviations from quality management system guidelines for the pharmaceutical industry and current good manufacturing practice (CGMP) regulations. External falls do not fall within the limits or do not meet certain requirements. The FDA’s rigorous standards emphasize the importance of maintaining high levels of quality and safety throughout the drug manufacturing chain.

Basically, deviations in the pharmaceutical industry are perceived not only as deviations from established standards, but also as events that can lead to positive or negative consequences. The variety of definitions provided by different regulatory authorities highlights the importance of a concise understanding of deviations to maintain the integrity and safety of pharmaceutical processes and promote regulatory compliance.

Type of Deviation

Deviation can be classified mainly Two types
  • Planned Deviation
  • Unplanned Deviation
Based on risk then it can be classified as
  • Critical Deviation
  • Major Deviation
  • Minor Deviation
  • Incident

Deviation, Purpose :

  • Deviation, This procedure provides a standardized process for handling quality related unplanned events & GMP deviation.
  • To develop a systemic approach for handling quality related failures & GMP deviation.
  • To ensure that deviations are recorded and assessed for their impact on product quality, patient safety and regulatory compliance.
  • Action is taken to address any immediate risks, including impact on other batches and products.
  • Investigation requirements and identification of any corrective and preventive actions (CAPAs) are based upon the level of risk.

Deviation, Scope :

The process applies to all quality & GMP failures and unplanned deviations in General Block and Sterile Block of XX Pharmaceuticals Ltd. which are related (but not limited) to the following:

  • Manufacturing Processes/operations (manufacturing, packing, testing, distribution), yield and reconciliation limit.
  • Facilities including equipment, utilities failure and critical instrument calibration failure.
  • Equipment/machinery breakdown during operation.
  • Failure of PLC based system that directly affects product quality
  • Equipment and facility Operation outside validated ranges
  • Storage condition of raw and packing materials
  • Storage period of bulk product
  • Documentation error affecting product quality.
  • Product standards
  • Standard Operating Procedure
  • Work Instructions including validation protocols.
  • Incidents impacting GMP & product or material quality
  • The process does not apply to the following as these are managed separately by individual SOPs:
  • Out of Specifications (OOS/Atypical) analytical and microbiological results.
  • Environmental action and alert limit excursions, where these have arisen as a result of laboratory testing
  • Stability failures/ stability protocols
  • Customer complaints and adverse events
  • Equipment/machinery breakdown during routine maintenance
  • Out of calibration noticed at the time of calibration activity
  • Recalls
  • Outside of in-process parameter followed by immediate rectification
  • Vendor complaints (On line rejection)
  • Deviations associated with outcome of any non-routine activity or trials.
  • Where actions have been justified, documented and pre-approved by Quality Assurance e.g. via SOP, BMR, BPR, Analytical Method.

Investigation process will be mandatory in the following instances:

  • Major/critical deviation/complaints/significant incidents.
  • OOS
  • Rejection
  • Recall
  • Consecutive 3 time excursions of alert limits.
  • Any incident agreed by management

Definitions / Abbreviation:

Deviation:

Deviation is an unplanned departure from SOPs, methods, specifications, protocols, batch records or other official documentation. A deviation may also be defined as a departure from instructions, processes, process specifications or normal conditions or any departure from good manufacturing practice.

Planned Deviation:

A deviation or change to test method, laboratory or manufacturing procedures that has been planned and approved before the process conducted as a part of temporary change. Planned Deviation should be reported before the process. Planned deviations will be handled through the QA approved change control procedures.

The deviations are classified as critical, major and minor. The definition is as under

Critical Deviation

A critical GMP deviation/exception could endanger product safety and/or efficacy due to the use of an inadequate process or controls. Failure of detection would lead to a product recall/withdrawal/serious complaint.

Major Deviation

A major GMP deviation/exception does not directly influence product safety and efficacy but may require remedial action before approval of manufacture or continue to manufacture. This could lead to serious regulatory compliance implications, Major cost to business or adverse comments from inspectors.

Minor Deviation

A minor GMP deviation/exception does not directly influence product safety and efficacy but may have an impact on cosmetic quality. This also includes minor document irregularities. This could lead to Cosmetic pack complaint or Late orders.

Investigation-

It is the process of identifying the cause of deviations/unwanted incidents. Purpose of Investigations are:
=>Identify
=>Correct
=>Evaluate product impact / disposition
=>Prevent similar events from happening in the future;

Responsibilities:

The roles and responsibility is as follows:

Observer(who observed the incident)

To notify Section in Charge/Departmental Manager immediately after observing any event.

Initiator (Section in Charge/ Dept. Manager)

  • To take any possible immediate actions to contain the event.
  • To record the event in log book and batch document.
  • To fill the “Deviation and Investigation Form” immediately after “On the spot investigation”.
  • To escalate the event to Functional Head

Functional Head or his designee

  • To decide in conjunction with Quality Compliance whether the incident is deviation or not and, if confirmed, any subsequent investigation required.
  • To ensure proper recording of deviation
  • To carry out initial assessment of the incident after collection of required data and ensure recording in batch document.
  • To decide on the requirement of assembling investigation team (in consultation with Manager Quality Assurance) for further investigation to find out root
  • cause and define recommendation.
  • To invoke CAPA process if require by forming CAPA team.

Head of Quality Compliance or his designee

  • Maintain the register for deviation & investigation
  • To provide the guidance on whether the incident is a deviation or not
  • To participate the initial assessment & follow up of remedial action.
  • To assess the severity of deviation and define criticality.

Manager, Quality Assurance

  • To approve the initial assessment & remedial action.
  • To approve the deviation & investigation
  • Investigation Leader (Any competent person nominated by Functional Head)
  • To lead the investigation and find out the root cause
  • To complete investigation within stipulated time.

Procedure: (Management of deviation)

Observation and notification of Deviation:

  • If any staff observes any of the incidents (described in scope), he/she will immediately notify the incident to Section in Charge/Departmental Manager.
  • Section in Charge/Departmental Manager will immediately conduct initial impact assessment and take any remedial action. e.g.
  • Stopping operation to prevent production of further faulty product,
  • Segregating material that may be affected.
  • Immediate correction
  • Departmental Manager will record the detail incident in the associated log book and/or BMR/BPR in a timely manner. The record must be clear, concise, and traceable and include all relevant details (e.g. time, date and nature of the incident, name of the observer).
  • Departmental Manager will immediately escalate the event to Functional Head (Head of Department)
  • Departmental Manager in consultation with Functional Head will determine whether the incident constitutes a deviation based on its potential impact on material/product quality or regulatory compliance.
  • For the ease of detection they can take the guidance of scopes . If there is any doubt as to the potential impact, the event will be treated as a deviation.

Recording of Deviation

  1. If it is determined that the incident constitutes a deviation, then the Departmental Manager will record all the information in section A of Deviation Report Form (Annexure-I).
  2. The Functional Head will decide
    =>if the production/operation should be stopped or not
    =>With proper authorization & justification allow the product to proceed.
  3. Departmental Manager will record the decision in Deviation Report Form. Departmental Manager will assign a unique reference number (obtained from Quality Compliance Department) to the Deviation Form.
  4. The number will be derived from Deviation register (Annexure-II). Deviation register will be maintained in both hard copy and Microsoft Excel based spreadsheet.
  • Deviation Form number shall be alphanumeric system containing 11 characters. Numbering breakdown is as follows: DRyy/Area code/xxx.
    Area Code is as follows:
    =>General Block : GB
    =>Sterile Block : CB
    =>For example: DRyy/GB/001.
  • The first two alphabets shall stand for Deviation Report
  • Next two numeric characters shall stand for year code 16 shall denote year 20xx.
  • Next character is slash (/), followed by two capital letter stands for area code of General Block at XX Pharmaceuticals Ltd.
  • Next character is slash (/), followed by three numerical shall stand for serial number, which shall start every year from 001. For example first Deviation Report no DRyy/GB/001 and second DRyy/GB/002, third DRyy/GB/003 and so on.
  • In case of Sterile block, Deviation Report number shall be DRyy/CB/001 and so on. Two capital letter CB stands for area code of Sterile block at XX Pharmaceuticals Ltd.
  • The number will be unique; if proposal is withdrawn/ rejected the same number will never be used again.
  • If incident implicates a batch then the unique reference number is to be recorded in related batch documents.
  • The deviation must be recorded with the following information:
    =>A unique reference number
    =>The date on which the deviation was first identified
    =>Name of person recording the deviation
    =>The identity (Batch No.) of any batch or batches implicated by the deviation
    =>A description of the deviation
    =>The identity of any process, equipment or system implicated by the deviation
    =>Initial actions taken
  • Functional Head will ensure that all relevant data/information is gathered to allow an initial assessment of the deviation.

Assessment of risk

  • Departmental Manager along with Quality Compliance Manager and any other expert in this field (i.e. Engineering Manager/Compliance Manager/Quality Control Manager/Microbiology Manager) will assess the impact of the deviation considering the following issues (section B in Annexure-I) and will propose a remedial action within 1 day of recording the deviation:
    =>Patient/customer risk & product efficacy
    =>Quality Implication (strength, identity, purity and stability)
    =>Effect on regulatory compliance
    =>Impact on any batch (es) immediately affected.
    =>Impact on any other batch(es)/processes which may be affected, considering any other areas/sites
    =>Current location and status of any implicated batch (whether the implicated batch is on the market or within XX’s control).
    =>Any remedial action taken/required
    =>Detection point of failure (detected by chance/detected during checking/detected at the point of error)
  • The initial assessment may result in wider implications than originally identified e.g. more batches than just the batch the deviation was detected on.
  • Quality Compliance Manager will assess the risk of deviation considering the above and categorize or prioritize the event as:
    =>Critical
    =>Major
    =>Minor
  • The aim of this categorizations are to determine the:
    =>Priority for resolving the deviation
    =>The time scale for addressing the deviation
  • Communication details & person to whom incident is to be communicated (if required).
  • Non conformity which is not detected through any standard process or detected only by chance will be treated as critical/major deviation. In all cases where the deviation relates to, or may implicate product already in the market place, will also be treated as critical.
  • Critical deviation will be immediately escalated to Head of Quality Assurance. He/she will communicate the matter to Managing Director and other stakeholders accordingly.
  • If requires Head of Quality Assurance will communicate the matters to Contact Manufacturer and collect their recommendation for the correction of the product.
  • Quality Compliance Manager in consultation with other Technical /Quality Experts will provide a recommendation/ remedial action to ensure that any adverse condition arising from the deviation are controlled and pose no further risk.
  • Determine Root Cause Investigation Requirements
  • Manager, Quality Assurance in consultation with Head of department will assess whether root cause investigation is required.
  • Root cause investigation is required where there is a risk to patient/ customer safety or serious regulatory compliance issues assigned through severity assessment in section 7.3.3. . For example:
    =>The severity of deviation is Critical/Major.
    =>Remedial actions have not fully mitigated the risk
    =>The deviation is a recurrence
  • If root cause investigation is not required, AGM, Quality Assurance will give a rationale and the deviation process can be progressed toward to point close.
Perform root cause investigation
  • The investigation will be conducted as per process described in previous point
  • The key output from this investigation will be a statement of actual root cause or most probable cause of the deviation and recommendation with timescale to address root causes.
  • After completion of the investigation, a copy of the investigation will be attached with the deviation report.
Identify Corrective and Preventive Action (CAPA)
  • On the basis of the severity of investigation, the Head of department jointly with AGM, Quality Assurance & Quality Compliance Manager will decide on the requirement to invoke CAPA process and develop Corrective and Preventive action to address the root cause identified in previous section and prevents recurrence of happening in future.
  • In case of CAPA process not applicable, this process should be closed with the comments and authorization by Manager, Quality Assurance.
CAPA will not be required if AGM, Quality Assurance confirms the followings:

=>If the deviation categorized as minor.
=>Implementation of identified CAPA is no longer applicable-for instance the root cause relates to equipment that has been replaced, or is planned to be replaced as part of an existing approved action.
=>Remedial actions taken address the root cause
=>The risk related to recurrence is low

If CAPA process is applicable, Head of Department will identify competent person to be a CAPA Leader to implement the CAPA objectives. CAPA leader will follow the formal CAPA process as per SOP: Corrective and Preventive Action Handling Procedure.
The Deviation Handling process will be closed when the CAPA triggered from this process is approved.

Handling of deviation implicated batch

  • No batch will be released until the deviation is closed.
  • All actions required to assure the quality of any impacted batches must be identified, agreed by the Quality Compliance, and completed prior to batch release
  • The copy of closed deviation report and investigation report must be filed with associated batch document (if implicated with any batch) during batch release.
  • Manager, Quality Assurance has ultimate authority to take decision on progression or release after completion of all actions.
  • Time limit, Follow up and Management Review
  • If investigation is not required deviation is to be closed within 7 days of initiation.
  • For deviation associated with investigation will be closed within 15 days of deviation initiation.
  • Initiator will coordinate the implementation of recommended/remedial action within agreed timeframe.
  • Quality Compliance will ensure that deviation has been effectively closed within the agreed timeframe. After closing Quality Compliance Manager will update the deviation tracker & register and archive the hard copy of original deviation form.
  • A copy to be provided to attach with the relevant document such as validation protocol.

Handling of Investigation:

  • Investigation will be triggered to address any unexpected discrepancy from different interfaces:
    =>Critical/Major Deviation
    =>Critical/Major market compliant
    =>Any GMP Quality incident
    =>Recall, reject and Reprocess
  • Functional Head (Head of Department) and Head of Quality Assurance will jointly decide where the investigation is required.
  • If root cause investigation is required, the Functional Head(Head of Department) will check the criticality of incident (critical/major/minor) as defined in the interface to determine the scale of investigation e.g. extent of investigation team, amount of structure for problem solving, level of documentation, requirement of resources or capital budget etc.
  • The Functional Head (Head of Department) will nominate an Investigation Leader & other members of investigation team who will conduct the investigation.
  • Generally Departmental Manager of impacted area will be selected as Investigation leader.
  • For the complex investigation, team should be cross functional composing the members of Quality Unit, Engineering and any other Technical Experts.
  • The team will take a unique reference number of investigation from Quality Compliance Office. Quality Compliance Officer will log the details in the investigation register (Annexure- IV).
  • All investigation will be conducted through this form (Annexure-III: Template of an investigation report).
  • Investigation Report numbers are assigned by Quality Compliance. Investigation Report number shall be alphanumeric system containing 11 characters. Numbering breakdown is as follows: IRyy/Area code/xxx.
    Area Code is as follows:
    =>General Block : GB
    =>Sterile Block : CB
    For example: IR16/GB/001.
  • The first two alphabets shall stand for Investigation Report
  • Next two numeric characters shall stand for year code 16 shall denote year 2016.
  • Next character is slash (/), followed by two capital letter stands for area code of General Block at XX Pharmaceuticals Ltd.
  • Next character is slash (/), followed by three numerical shall stand for serial number, which shall start every year from 001. For example first Investigation Report no IR16/GB/001 and second IR16/GB/002, third IR16/GB/003 and so on.
  • In case of Sterile block, Investigation Report number shall be IR 16/CB/001 and so on. Two capital letter CB stands for area code of Sterile block at XX Pharmaceuticals Ltd.
  • The number will be unique; if proposal is withdrawn/ rejected the same number will never be used again.
  • The team will collate the facts and data in consultation with relevant personnel and document.
  • Investigation team will prepare a report of investigation within the time line. All steps & findings will be recorded in the report.
  • The key aim of the investigation is to identify the root cause or most probable cause of the deviation incident.
  • Where the identification of actual or most probable root cause is not possible, the risk associated with uncertainty is to be assessed & recoded with adequate control.
  • The maximum time for the identification of root cause is 15 working days after recording of incident.
  • Investigation report will be approved by Functional Head (Head of Department) and Manager, Quality Assurance.

 

What challenges might arise when dealing with Deviation Management?”

Managing deviations within an organizational framework poses a myriad of challenges, demanding a nuanced approach to navigate these intricacies effectively. The intricate realm of deviation management encompasses the intricate task of addressing situations where the realized performance or outcomes veer off course from the meticulously laid out plans or anticipated expectations. As organizations grapple with this multifaceted process, several challenges may emerge, each requiring careful consideration and strategic resolution.

One of the primary challenges encountered in the domain of deviation management is the inherent complexity associated with identifying the root causes of deviations. Organizations often find themselves immersed in a labyrinth of factors contributing to these deviations, ranging from internal processes and external influences to unforeseen circumstances. Unraveling these complexities demands a thorough investigation and a keen understanding of the interplay between various variables, enabling organizations to pinpoint the factors triggering deviations accurately.

Moreover, deviation management is intricately linked with the need for efficient communication channels within an organization. The timely and transparent dissemination of information pertaining to deviations is paramount, as it empowers stakeholders at all levels to make informed decisions. Inadequate communication may exacerbate the impact of deviations, leading to misunderstandings, delays, and a potential erosion of trust within the organizational fabric.

In addition, the challenge of striking a balance between corrective actions and the preservation of operational efficiency looms large. Organizations must devise strategies that not only rectify the immediate deviations but also do so in a manner that minimizes disruptions to ongoing operations. The intricacies of this balancing act require a holistic approach that considers the long-term implications of corrective measures on the overall organizational performance.

Furthermore, the globalized and interconnected nature of modern businesses introduces an additional layer of complexity to deviation management. Organizations often operate within a network of suppliers, partners, and stakeholders, each contributing to the intricate web of dependencies. Managing deviations becomes a collaborative effort, necessitating effective coordination and cooperation among various entities to address and mitigate the ripple effects across the entire ecosystem.

In conclusion, the challenges associated with deviation management underscore the need for organizations to cultivate resilience, adaptability, and a proactive approach. Addressing these challenges requires a comprehensive understanding of the underlying dynamics, coupled with strategic initiatives aimed at fostering a culture of continuous improvement and proactive deviation anticipation. Successfully navigating these challenges not only ensures smoother operations but also positions organizations to thrive in an ever-evolving business landscape.

1. Identification and Detection of Deviations:

Navigating complexity poses a formidable challenge when it comes to recognizing deviations, particularly within intricate systems or processes characterized by the interplay of numerous factors influencing performance outcomes. The intricacies inherent in such environments demand a heightened level of scrutiny and analytical precision to successfully pinpoint variations from the norm.

The critical importance of timeliness in the detection of deviations cannot be overstated. Swift and accurate identification is paramount, as any delay in the recognition of anomalies may result in protracted issues and expose the system or process to potential negative impacts. The urgency in timely detection stems from the need to address deviations swiftly, thereby preventing the escalation of problems and mitigating any adverse consequences that might ensue.

Moreover, the time-sensitive nature of detecting deviations underscores the significance of establishing efficient monitoring mechanisms and implementing proactive measures. A proactive approach involves anticipating potential deviations, implementing real-time monitoring, and deploying predictive analytics to foresee issues before they manifest fully. This forward-thinking strategy not only minimizes the risk of prolonged disruptions but also allows for the implementation of corrective actions before deviations escalate into critical problems.

In the realm of complexity, it becomes imperative to foster a comprehensive understanding of the intricate web of factors influencing performance outcomes. This entails not only identifying deviations when they occur but also gaining insights into the underlying dynamics that contribute to such variations. An in-depth comprehension of the contributing factors enables a more holistic approach to deviation detection, enhancing the capacity to discern subtle deviations that might otherwise go unnoticed.

In conclusion, the challenges presented by complexity necessitate a multifaceted approach to the identification of deviations. Timeliness emerges as a crucial factor, emphasizing the need for swift detection to prevent prolonged issues and potential negative impacts. Implementing proactive measures and gaining a profound understanding of the intricate interdependencies within complex systems further fortify the capability to navigate and manage deviations effectively.

2. Root Cause Analysis:

In order to effectively identify the underlying reasons for deviations, a profound depth of analysis is imperative. This entails delving deep into the intricacies of the situation, as superficial investigations often yield only temporary solutions, failing to tackle the root causes that perpetuate issues over time.

The significance of resource intensity becomes evident when undertaking comprehensive root cause analyses. Such endeavors demand considerable resources, not just in terms of time but also requiring a wealth of expertise. Thoroughly examining the multifaceted aspects of a problem necessitates a commitment of substantial time and the involvement of individuals with specialized knowledge in the relevant domains.

Delving into the depth of analysis implies a meticulous examination of various factors contributing to deviations. This involves scrutinizing processes, systems, and interactions at a granular level to uncover the fundamental sources of problems. It goes beyond addressing symptoms on the surface and aims at understanding the intricacies that give rise to deviations, thereby enabling the development of more robust and sustainable solutions.

Furthermore, the resource intensity associated with comprehensive root cause analyses extends beyond temporal considerations. It involves tapping into a reservoir of expertise, leveraging the insights and knowledge of individuals who possess a nuanced understanding of the subject matter. This collaborative effort ensures a holistic examination of the issue, fostering a comprehensive perspective that facilitates the identification and rectification of root causes.

The depth of analysis and resource intensity are intertwined aspects that underscore the importance of adopting a strategic and well-organized approach to problem-solving. By investing the necessary time and expertise, organizations can move beyond superficial fixes and address the core issues that may be impeding their efficiency and effectiveness. This proactive stance not only promotes long-term sustainability but also cultivates a culture of continuous improvement within the organizational framework.

3. Communication and Reporting:

Transparency stands as a cornerstone in any organizational framework, emphasizing the critical importance of fostering open communication regarding deviations. The significance lies in the fact that challenges can swiftly emerge in the absence of transparency, given that stakeholders rely on comprehensive information to make well-informed decisions.

In the realm of effective reporting, the imperative is to establish a robust system that not only highlights deviations but also ensures clarity, conciseness, and ease of understanding. Crafting such a reporting mechanism poses a noteworthy challenge, as it requires a careful balance between providing detailed insights and presenting information in a manner that is easily comprehensible to a diverse audience. This calls for the implementation of streamlined processes that not only capture the intricacies of deviations but also translate them into a format that resonates with stakeholders at various levels within the organization.

Moreover, effective reporting transcends mere documentation; it serves as a strategic tool for organizational improvement. By investing in a reporting system that goes beyond the perfunctory and delves into the root causes of deviations, organizations can uncover valuable insights. These insights, in turn, pave the way for proactive problem-solving and the implementation of preventative measures, fostering a culture of continuous improvement.

In essence, the synergy between transparency and effective reporting forms a formidable foundation for organizational resilience and adaptability. It is not just about acknowledging deviations but also about leveraging them as opportunities for growth and refinement. As organizations navigate the complexities of their environments, embracing a culture that places a premium on transparent communication and meticulous reporting becomes pivotal in steering towards sustainable success.

4.Decision-Making:

Navigating the Decision-Making Tightrope: Striking the right chord in determining the suitable course of action to rectify deviations necessitates a nuanced and intricate balancing act. It requires a careful assessment that takes into account the urgency of the situation, the potential ripple effects, and the array of resources at our disposal. This process is akin to walking a tightrope, where precision and equilibrium are crucial.

Urgency Consideration: Delving deeper into the intricacies, the urgency of the situation stands as a pivotal factor. Decisions made must be time-sensitive, recognizing the immediacy of the deviations at hand. This involves evaluating the degree of impact and the potential consequences of delayed action, emphasizing the need for a swift and strategic response.

Impact Analysis: The ripple effects stemming from addressing deviations should be meticulously analyzed. Understanding the potential impacts on various facets of the organization allows for a comprehensive decision-making process. This involves foreseeing both short-term repercussions and long-term consequences, ensuring that the chosen course of action aligns with overarching organizational goals.

Resource Evaluation: The availability and allocation of resources play a significant role in the decision-making process. A thorough examination of the resources at hand is imperative, encompassing financial, human, and technological aspects. This evaluation not only aids in determining the feasibility of various courses of action but also ensures optimal resource utilization for maximum efficiency.

Conundrum of Conflicting Priorities: A common challenge emerges when addressing deviations intersects with other organizational priorities. This creates a conundrum, compelling decision-makers to grapple with intricate dilemmas related to resource allocation. In such scenarios, decisions become a delicate juggling act, requiring a keen understanding of organizational priorities and strategic alignment.

Strategic Resource Allocation: The clash of priorities necessitates a strategic approach to resource allocation. Decisions must be guided by a keen awareness of the broader organizational landscape, considering the potential repercussions on other projects or initiatives. This strategic resource allocation involves prioritizing tasks and projects based on their criticality and alignment with overarching organizational objectives.

In essence, the decision-making process in addressing deviations involves a multifaceted examination that encompasses urgency, impact, and resource considerations. Negotiating the complexities of conflicting priorities requires a strategic mindset and a keen understanding of the broader organizational context, ultimately leading to decisions that harmonize with the organization’s overarching goals and priorities.

5. Implementation of Corrective Actions:

Navigating Resistance to Change: The introduction of corrective actions may encounter resistance among employees who have grown accustomed to established processes. This resistance can emanate from a variety of sources, including a fear of the unknown, concerns about job security, or simply a reluctance to step out of one’s comfort zone. It is imperative to recognize that fostering a culture of adaptability is pivotal in overcoming these challenges. Change management, therefore, emerges as a critical component in these scenarios, demanding thoughtful strategies to communicate the benefits of change, address concerns, and ultimately garner support from the workforce.

Cultivating Change Management Strategies: To successfully implement corrective actions, organizations must invest in robust change management strategies. This involves clear communication channels that elucidate the rationale behind the changes, the expected benefits, and the role each employee plays in the transition. Additionally, providing training and support mechanisms can empower employees to embrace the changes confidently. By cultivating a sense of ownership and involvement, organizations can minimize resistance and enhance the likelihood of successful implementation.

Monitoring and Ensuring Effectiveness: The implementation of corrective actions is just the initial phase; ongoing monitoring and follow-up are indispensable for sustained success. Organizations must establish systematic mechanisms to track the effectiveness of the implemented changes, identifying any areas that may require further adjustment. This involves setting up key performance indicators (KPIs) and regularly assessing progress against these benchmarks. Moreover, fostering a culture of continuous improvement ensures that organizations remain agile and responsive to evolving challenges.

Dynamic Attention to Change: The dynamic nature of the business environment necessitates a continuous commitment to monitoring and follow-up. Changes in market conditions, technological advancements, or internal dynamics may require organizations to adapt and refine their corrective actions. Therefore, a proactive approach to monitoring, coupled with an agile response mechanism, enables organizations to stay ahead of potential challenges and capitalize on emerging opportunities.

Employee Engagement in the Monitoring Process: Actively involving employees in the monitoring and follow-up process is a crucial aspect of ensuring sustained success. Soliciting feedback, conducting regular check-ins, and creating a feedback loop where employees can express concerns or suggest improvements fosters a sense of inclusivity. This not only enhances the effectiveness of corrective actions but also strengthens the overall organizational culture, promoting a collaborative and adaptive ethos.

In conclusion, addressing resistance to change and ensuring the effectiveness of corrective actions are multifaceted challenges that demand a comprehensive approach. By prioritizing change management strategies, implementing robust monitoring mechanisms, and actively engaging employees in the process, organizations can navigate these challenges and foster a culture of continuous improvement and adaptability.

6. Documentation and Compliance:

Documentation Integrity and Learning Enhancement: The meticulous recording of deviations, including their root causes and corresponding corrective actions, plays a pivotal role in ensuring accountability and facilitating future reference. The comprehensive and accurate documentation of these aspects is crucial for fostering a robust learning process within an organization. Incomplete or inaccurate documentation has the potential to impede the learning curve, hindering the ability to derive valuable insights from past experiences.

Navigating Regulatory Compliance Challenges: The adherence to regulatory requirements in the management and documentation of deviations presents a multifaceted challenge for organizations. Meeting these regulatory standards necessitates a thorough understanding of the intricate frameworks governing various industries. Failure to comply with these regulations can have severe repercussions, ranging from legal ramifications to financial consequences. As such, organizations must invest in robust systems and processes to ensure that their deviation management practices align with the ever-evolving regulatory landscape.

Legal and Financial Implications of Non-Compliance: The failure to meet regulatory compliance standards in handling and documenting deviations can expose an organization to significant legal and financial risks. Legal consequences may include fines, penalties, or even legal actions, while financial implications can extend to reputational damage and a loss of stakeholder trust. Proactive measures to ensure compliance not only mitigate these risks but also contribute to the overall sustainability and resilience of the organization in the face of regulatory scrutiny.

Continuous Improvement Through Documentation: Beyond mere compliance, the meticulous documentation of deviations serves as a catalyst for continuous improvement. Analyzing past deviations and their resolutions provides valuable insights into organizational weaknesses and areas for enhancement. This iterative process fosters a culture of learning and adaptability, positioning the organization to proactively address challenges and optimize its operations over time.

In summary, the interplay of documentation integrity, regulatory compliance, and the associated legal and financial considerations underscores the critical role that robust deviation management practices play in organizational success. A proactive approach to documentation not only ensures compliance with regulatory standards but also serves as a cornerstone for continuous improvement, contributing to the overall resilience and adaptability of the organization in an ever-changing business environment.

7. Continuous Improvement:

Embracing a Culture of Continuous Improvement through Learning from Deviations:

Fostering a culture of continuous improvement is a fundamental necessity for organizations striving for excellence. The process begins with acknowledging that deviations from established norms are not merely setbacks but valuable opportunities for growth and refinement. The proactive approach of transforming deviations into learning experiences is pivotal for organizational development.

Challenges in Turning Deviations into Opportunities:
Despite the inherent importance of learning from deviations, many organizations grapple with the practical implementation of this philosophy. It is not uncommon for entities to face difficulties in seamlessly integrating deviations into their operations to derive meaningful insights. Overcoming this challenge requires a concerted effort to create an environment that not only tolerates deviations but actively encourages the extraction of valuable lessons from them.

The Role of Adaptability in Organizational Evolution:
Adaptability emerges as a cornerstone for organizational success in the face of deviations. The ability to evolve based on insights gleaned from past experiences is paramount. However, this adaptability is often hindered by various factors such as resistance to change and institutional inertia. Organizations must navigate these hurdles to effectively implement changes that lead to continuous improvement and innovation.

Navigating Resistance and Inertia:
Resistance to change and inertia are common adversaries that organizations encounter in their pursuit of adaptability. Overcoming these challenges necessitates a strategic and empathetic approach to change management. Addressing concerns, fostering a sense of ownership among stakeholders, and providing adequate support are crucial components in dismantling barriers to change.

Incorporating a Holistic Approach to Continuous Improvement:
A comprehensive strategy for continuous improvement involves not only learning from deviations but also proactively addressing the impediments to change. Organizations should cultivate a mindset that views deviations as opportunities for innovation and refinement. By fostering a collaborative and open culture, entities can create a resilient framework that embraces change and propels the organization towards sustained growth.

In conclusion, the journey towards continuous improvement requires a multifaceted approach. Organizations must not only recognize the importance of learning from deviations but also actively work towards creating an adaptive environment that can effectively translate these lessons into tangible enhancements. By overcoming resistance and inertia, and by incorporating a holistic approach to continuous improvement, organizations can thrive in an ever-evolving landscape.

8. Cultural Factors:

Culture of Accountability: When an organization fosters a culture of blame, it creates an environment where individuals may feel reluctant to report deviations or actively participate in root cause analysis due to the looming fear of facing negative consequences. This detrimental culture not only hinders transparency but also impedes the identification and resolution of issues that could potentially impact organizational success.

Nurturing a Feedback-Friendly Environment: Building a workplace culture that not only tolerates but actively encourages openness to feedback is a formidable yet indispensable task. Embracing deviations as invaluable opportunities for improvement, rather than as grounds for punishment, is essential for the sustained growth and prosperity of the organization. This mindset shift can foster a collaborative atmosphere where employees feel empowered to share insights and contribute to the continuous enhancement of processes.

Proactive Deviation Management: Effectively addressing these challenges demands a proactive and systematic approach to deviation management. This approach should prioritize continuous improvement as a central goal, emphasizing the need for robust systems that facilitate the reporting of deviations without fear of reprisals. Implementing clear communication channels and mechanisms for employees to express concerns and suggestions can further fortify an environment conducive to openness.

Commitment to Learning: A commitment to learning from experiences is a cornerstone of a healthy organizational culture. Instead of viewing deviations as failures, organizations should perceive them as valuable learning opportunities. Leaders should promote a growth mindset that encourages employees to analyze deviations, understand their root causes, and collaboratively implement solutions. By embracing a culture of continuous learning, organizations can adapt, evolve, and ultimately thrive in an ever-changing business landscape.

Emphasizing Communication: Effective communication is a linchpin in overcoming the challenges associated with blame culture and fostering openness to feedback. Leaders should prioritize transparent and timely communication, ensuring that employees are aware of the importance of their contributions in identifying and rectifying deviations. This not only builds trust but also reinforces the idea that addressing issues is a collective responsibility.

In conclusion, tackling a blame culture and cultivating openness to feedback necessitates a multifaceted and dedicated approach. By prioritizing continuous improvement, fostering a feedback-friendly environment, and instilling a commitment to learning, organizations can build resilience, adaptability, and a culture that thrives on collective efforts towards excellence.

 

How can we effectively handle a Deviation?

Effectively addressing deviations requires using a systematic approach that includes identification, in-depth analysis, strategic controls, and deep learning for deviations within a process or project. This requires a comprehensive approach that aims not only to address deviations but also gain valuable insights to improve overall performance. The ability to effectively address deviations contributes significantly to organizational resilience and continuous improvement.

To successfully master the complexities of deviation management, it is essential to introduce step-by-step instructions that serve as a guide for professionals and teams. This guide provides a structured framework for identifying deviations early, investigating root causes through careful analysis, implementing effective control measures to mitigate their impact, and most importantly, leveraging each deviation as a learning opportunity. do.

The first step involves a careful identification process that systematically pinpoints any deviations that may occur. Monitoring a process or project requires a keen eye for detail and a proactive approach. Once discrepancies are identified, the focus shifts to a comprehensive analysis that not only addresses the immediate problem, but also investigates the root cause. This analysis step is essential for developing a valid strategy to prevent similar deviations in the future.

Effective control systems are implemented to manage and mitigate the effects of identified deviations. Corrective actions are used that not only address the immediate consequences but also contribute to the overall improvement of the system. Control steps are essential to maintain operational stability and minimize disturbances due to deviations.

The final aspect of the guide emphasizes the importance of learning from deviations. Each example provides a unique opportunity to gain insight into weaknesses, inefficiencies, or unexpected problems in a process or project. Companies can leverage these learning opportunities to continually improve and optimize their operations. The iterative process of identifying, analyzing, monitoring and learning creates a cycle of improvement that strengthens resilience and adaptability.

In other words, an effective deviation management strategy goes beyond simple remediation and involves a holistic approach that includes proactive detection, in-depth analysis, strategic control, and continuous learning. By introducing step-by-step guidance, companies can flexibly address deviations and turn challenges into opportunities for growth and development.

1. Identify Deviations:

Define precise standards and expectations for both processes and projects to ensure a transparent framework. We encourage a culture of continuous improvement by continually evaluating and measuring performance against these established standards. We actively foster open communication channels to quickly identify and report deviations from established standards, supporting a proactive and collaborative approach to resolving issues and maintaining optimal project or process efficiency. These practices not only ensure accountability, but also create a dynamic environment where feedback is valued, leading to improved strategy and achievement of broader organizational goals.

2. Documentation:

Gather comprehensive information about the deviation by documenting intricate details, including its specific nature, broad scope, and potential impact. Record any deviations carefully and include relevant data, such as the date and time the deviation occurred. We also identify everyone involved in the deviation and create a comprehensive report that not only highlights the deviation but also provides a full understanding of the situation and potential impact. This careful documentation is critical to a complete analysis and allows for an informed assessment of the root cause of the deviation, its contributing factors, and its overall impact on the process or system involved. By collecting detailed records, companies can lay the foundation for informed decisions, corrective actions, and preventive actions to improve overall performance and compliance.

3. Root cause Analysis:

Conduct a comprehensive investigation of the underlying factors contributing to observed changes to gain a deeper understanding of the causes. Use analysis tools such as fishbone diagrams, five-cause diagrams, or failure mode and effects analysis (FMEA) to systematically identify and decipher the underlying issues causing deviations. This in-depth investigative approach is important not only for identifying surface symptoms, but also for exploring complex layers of causes.

Involve a multidisciplinary team of relevant stakeholders throughout the analysis process to ensure a holistic and diverse perspective. Including people with diverse skills and insights can increase the completeness and accuracy of your research. These joint efforts not only promote a more complete understanding of the disorder, but also the development of effective, targeted solutions.

Also consider integrating qualitative and quantitative data sources to strengthen your analysis. By combining empirical evidence, expert opinion, and historical data, you can create a more concise and accurate explanation of the root cause. This interdisciplinary approach contributes to a more resilient and adaptable research framework that can account for the complexities associated with identifying and resolving deviance.

Uncovering the complex web of factors contributing to change requires a multifaceted approach that leverages advanced analytical tools, engages multiple stakeholders, and integrates multiple data sources. This in-depth investigation lays the foundation for informed decision-making, strategic problem-solving, and implementation of preventive measures to prevent similar deviations in the future.

4. Impact Assessment:

Assess the impact of deviations on the overall workflow or project and carefully examine their impact and impact. Address the potential risks and consequences of deviating from the established path, considering both immediate and long-term impacts. Assess the broader impact on project planning, resource allocation, and stakeholder expectations to ensure a full understanding of how variations may disrupt the overall trajectory. It also analyzes the impact on interconnected processes and identifies dependencies that may be affected. By performing a thorough assessment, you can gain insight into many aspects of the transition and develop strategies to mitigate its impact, promoting a proactive and informed approach to project management.

5. Risk Mitigation:

Develop a comprehensive risk mitigation strategy in response to identified deviations. This involves developing a detailed plan that not only addresses the immediate problem, but also investigates root causes, implements corrective actions to fundamentally address these problems, and establishes preventative measures to prevent potential recurrence.

The first step involves an in-depth analysis of the risks associated with the deviation, identification of its causes, and assessment of its potential impact on the overall objectives. Once you have a clear understanding of these risks, you need to develop a structured plan that defines the specific actions you need to take to mitigate each risk. The plan should include both short-term measures to provide immediate relief and long-term strategies to ensure sustainable risk management over time.

It is important to implement corrective actions during this process. Addressing these causes of variation requires a targeted approach. It’s not just about solving an immediate problem, it’s about implementing systemic changes to prevent similar deviations from occurring in the future. This proactive attitude creates stronger and more resilient systems.

Additionally, it is important to consider both short-term and long-term strategies for a holistic approach to risk management. Short-term strategies may involve quick corrections and immediate responses to current deviations, while long-term strategies focus on sustainable solutions that protect the system from potential future risks. This dual approach allows organizations to effectively manage risk both immediately and over the long term.

The process involves a multifaceted approach that includes a combination of risk identification, detailed planning, corrective action, and short-term and long-term strategies. By adopting this comprehensive strategy, companies can not only mitigate the risks associated with deviations, but also strengthen systems that can successfully manage uncertainty.

6. Communicate:

Inform stakeholders of any deviations from established plans and explain the potential impact of such departures. Promote a culture of transparency by regularly informing all stakeholders of ongoing actions to address and mitigate the impact of deviations. Establish clear lines of communication for open exchange of information and ensure stakeholders fully understand the situation. This proactive approach to communication not only builds trust, but also ensures that everyone involved is well informed and promotes a collaborative environment where joint efforts can be focused on solving problems and achieving common goals.

7. Change Control:

When a deviation occurs, it is essential to carefully assess the situation and, if deemed necessary, improve and modify existing procedures or processes to smoothly implement the valuable lessons learned from the deviation experience. This proactive approach allows organizations to continuously develop and improve their operations based on real-world feedback.

Incorporating lessons learned from deviations into established procedures not only solves immediate problems, but also contributes to the larger process of organizational learning and continuous improvement. This adaptive mindset creates a culture of resilience and agility, allowing companies to effectively overcome unexpected challenges.

To maintain consistent standards and maintain compliance with quality standards, any changes or updates to procedures must be implemented through a formal change management process. This structured approach ensures that changes are thoroughly evaluated, documented, and approved prior to implementation. By establishing a formal change control process, organizations create a strong framework for managing change, mitigating risk, and maintaining a consistent and stable operating environment.

In other words, proactively updating processes to incorporate lessons learned from deviations, combined with a formal change control process, not only addresses immediate issues, but also promotes a culture of continuous improvement, adaptability, and quality assurance within the organization.

8. Continuous Improvement:

Create an organizational environment that grows through continuous improvement through careful review of deviations. Regularly participates in comprehensive process and project reviews to identify and analyze areas for improvement and optimization. Create a collaborative environment where you actively seek opinions and ideas from team members and value their unique perspectives and insights as valuable contributions to shared excellence. Develop a mindset that views change as a catalyst for growth and encourages continuous learning and adaptation. By building this culture of continuous improvement, companies can develop effectively, innovate, and remain resilient in the face of dynamic challenges.

9. Training and Awareness:

Conduct in-depth training for employees involved in specific processes to proactively mitigate similar deviations in the future. Increase employee awareness and understanding of the importance of following required procedures and policies. The purpose of this training plan is not only to correct past deviations but also to establish a culture of procedural discipline and integrity within the organizational structure. By increasing awareness of established protocols, employees can perform their roles accurately, reducing the likelihood of future deviations and promoting a culture of continuous improvement. The emphasis on training isn’t just limited to corrections. It represents a strategic investment in your organization’s operational efficiency and long-term compliance. When employees gain a deeper understanding of the rationale behind established procedures, they are more likely to internalize the importance of compliance, helping to create a work environment characterized by accountability, efficiency, and commitment to best practices. Additionally, these training plans can be designed to include interactive elements, case studies and real-world scenarios to increase engagement and put the knowledge gained into practice. Through regular refresher courses, feedback mechanisms and continuous reinforcement through performance evaluations, we will promote a resilient organizational culture that integrates best practices into daily operations, prioritizes procedural integrity and minimizes the risk of future deviations.

10. Document Corrective Actions:

Carefully record and document corrective actions taken to address identified deviations within the operating framework. Maintains complete records of changes to existing processes, policies or procedures in direct response to identified discrepancies. This document is a collection of important insights into the evolving organizational landscape and demonstrates the adaptability and resilience of existing systems. By carefully recording the corrective actions taken, an organization not only ensures transparency and accountability, but also creates a valuable resource for continuous improvement and future decision-making. These documented changes provide a holistic view of the dynamics of an organization’s response to deviations, fostering a culture of learning and agility. This systematic approach allows organizations to not only solve immediate problems, but also build a solid foundation for sustainable excellence and adaptability in the face of increasing challenges.

11. Performance Monitoring:

Continuous monitoring of the performance of modified processes is essential to ensure sustainable improvement. Establish a strong feedback mechanism to quickly identify and resolve any potential problems that may arise during implementation of revised processes.

It is important to emphasize that deviation management is not a one-time task, but a continuous and dynamic process. To prevent future recurrences, it is important to maintain a relentless commitment to continuous improvement and be proactive in identifying and mitigating potential deviations. Build a culture of adaptability and improvement by regularly evaluating performance indicators and collecting feedback from a variety of sources. By adopting a proactive, continuous improvement mindset, companies can foster resilience and improve the overall efficiency and reliability of their processes.

What happen when a Deviation is not properly investigated?

When a deviation is not properly investigated, several negative consequences can arise, depending on the context. Deviations refer to variations or departures from established processes, procedures, or standards. Failing to investigate deviations thoroughly can lead to the following issues:

1. Quality and compliance issues:

If variations within the manufacturing process are not addressed, product quality integrity can be compromised. Failure to correct these deviations can lead to a number of negative consequences, including potential defects, reduced product quality, and safety hazards. Moreover, when compliance is compromised, the impact extends beyond the product. Many industries have strict regulations that require any deviations from established manufacturing standards to be carefully inspected and documented.

When a manufacturing process deviates from prescribed standards, a variety of problems can arise that can seriously impact the final product. Quality control errors can result in defective components being installed, which can lead to defective items that not only erode consumer trust but also pose potential safety hazards. The presence of defective products not only damages the manufacturer’s reputation, but can also lead to legal consequences.

Additionally, in sectors where strict guidelines apply, compliance with the regulatory framework is essential. Not only does non-compliance expose companies to legal risk, but it also puts safety and public trust at risk as production deviations go unchecked. Regulatory authorities often require thorough investigation and detailed documentation to ensure that manufacturing processes meet established standards.

Preventive and corrective actions taken in response to production deviations play a critical role in maintaining overall product quality, maintaining regulatory compliance, and protecting consumer welfare and the reputation of the industry as a whole.

2. Repetition of errors:

Without thorough investigation, the underlying factors causing churn cannot be identified. Failure to identify this root cause greatly increases the likelihood that the same mistake will occur again in the future. This perpetuates a problem cycle in which unresolved problems resurface over and over again, creating ongoing problems and preventing sustainable solutions from being achieved. Thorough investigation is essential not only to resolve immediate problems, but also to break the vicious cycle of repeated failures and build more resilient and stable systems over the long term. By investigating the root causes of deviations, companies can take preventative action, strengthen processes, and take proactive action.

3. Risk of security incidents:

Deviations from established security protocols in industries such as healthcare, pharmaceuticals, and manufacturing can pose serious risks to the well-being of employees, consumers, and the general public. If these deviations are not thoroughly reviewed, they can go beyond simple procedural errors and lead to potentially serious safety incidents or incidents that threaten the operational integrity of these critical sectors.

In the healthcare sector, where patient well-being is fundamental, compliance with safety protocols is not only a regulatory requirement, but also a fundamental aspect of ensuring quality care. Deviations from established procedures can lead to uncertainty in the treatment process and potentially put the patient’s health and safety at risk. It is therefore important to carefully investigate any deviations from safety standards to maintain the trust and well-being of both healthcare professionals and patients.

In the pharmaceutical industry, where accuracy and precision are critical, deviations from safety guidelines can affect the quality and effectiveness of the drug product. If these discrepancies are not promptly addressed and investigated, substandard medicines may be distributed, posing a threat to public health and undermining trust in the industry. Rigorously reviewing any deviations from safety protocols is critical to maintaining the integrity of the pharmaceutical supply chain and protecting the health of end users.

Even in the manufacturing industry, where product production is a complex and complicated process, deviations from safety standards can lead to operational inefficiencies, product defects, and in extreme cases, major accidents. Failure to thoroughly investigate these deviations not only exposes workers to unnecessary risk, but also endangers the end users of the manufactured products. Strict safety protocols and careful investigation of any deviations are essential to maintaining the overall reliability and reputation of a manufacturing operation.

Strict adherence to safety protocols in this inherently important sector is not a mere bureaucratic formality. This is an important part of protecting the well-being of individuals, ensuring product quality, and maintaining the integrity of the industry as a whole. Close investigation of violations plays a critical role in preventing safety incidents, promoting continuous improvement, and creating a culture of responsibility and accountability in the healthcare, pharmaceutical, and manufacturing industries.

4. Financial Consequences:

Inefficient or faulty operating processes can result in serious financial disaster for a company. A good example of this is when deviations in the manufacturing process go unnoticed. These oversights can result in a variety of negative consequences, including product defects and product recalls, legal penalties, and serious damage to the company’s reputation in the marketplace.
Digging deeper into the complexity of the problem, the financial losses caused by inefficient processes go beyond the immediate cost of correcting the errors. For example, product recalls require significant financial resources to recover, replace, and dispose of defective items. Additionally, the legal consequences of these deficiencies could result in prolonged litigation, resulting in significant fines, settlements and legal fees, which could further weaken the Company’s financial stability.

The damage is not limited to financial impacts. It also has a domino effect on the company’s reputation. Consumers who hear or learn about a defective product may lose trust in the brand, resulting in loss of customer loyalty and market share. Negative publicity from recalls and lawsuits can tarnish a company’s image and make it difficult to regain the trust of existing and potential customers.

This means that troubleshooting problems and fixing inefficient or flawed processes is not only a matter of preventing immediate financial loss, but is also critical to ensuring your company’s long-term financial health, reputation, and profitability in a competitive marketplace. This highlights the importance of strong quality management systems and proactive management strategies to reduce risk and ensure sustainable success.

5. Loss of customer trust:

When a product or service deviates from established quality standards during manufacturing or distribution, the impact goes beyond immediate concerns. In these cases, loss of customer trust becomes a critical issue with far-reaching consequences. This loss of trust can cause lasting damage to a company’s brand reputation and threaten customer loyalty, negatively impacting the company’s overall success and sustainability.

Product or service quality is the foundation for fostering a positive customer experience. When inconsistencies arise and these fundamental aspects are compromised, customers may perceive the brand as unreliable or unable to maintain promised standards. These negative perceptions can lead to a trickle-down effect where customers are not only dissatisfied with a particular transaction, but also question the company’s overall integrity and commitment.

When customer trust declines, it can have a domino effect that affects purchasing decisions and brand promotion. In an age when consumers have so many choices, loss of trust in a company’s ability to deliver consistent quality can lead consumers to look for alternatives. Reputational damage can extend beyond your immediate customer base as negative word of mouth spreads and impacts potential customers who may dissuade them from engaging with your brand.

Moreover, the long-term consequences of declining customer trust extend beyond the immediate financial impact. Building and maintaining a positive brand image is an ongoing process that requires time, resources, and a strong commitment to quality. When trust is damaged, the process of rebuilding and regaining customer trust can be difficult and requires significant investments in marketing, communications and quality improvement initiatives.

In essence, the impact of deviations from quality standards extends beyond the immediate realm of product or service nonconformity. This has far-reaching implications for the fundamental structure of a company’s relationship with its customers, influencing its perception, behavior and ultimately its sustainability in a competitive marketplace. Therefore, an ongoing commitment to maintaining quality standards becomes not only a business imperative, but also a strategic imperative that ensures the company’s continued success.

6. Ineffective problem solving:

Without a thorough and complete investigation, an organization may not fully understand the root causes of deviations from established processes or standards. This lack of understanding is a serious barrier to formulating and implementing corrective and preventive actions. A thorough investigation is essential to address the complexity of irregularities as it reveals multiple aspects that contribute to deviations.

By performing a thorough audit, organizations gain valuable insight into the complex factors that lead to deviations. This in-depth understanding is the basis for developing targeted and effective corrective actions. Without this deep understanding, organizations risk adopting superficial solutions that only address the symptoms and not the root cause.

Additionally, a thorough investigation not only uncovers the immediate causes of deviations, but also addresses institutional issues and procedural deficiencies. This holistic approach ensures that advanced corrective actions are not only reactive but also preventative in nature, protecting your organization from recurring problems in the future.

In-depth research also provides learning opportunities for organizations and promotes a culture of continuous improvement. This allows you to identify potential vulnerabilities in existing processes and systems, allowing you to take proactive steps to improve overall operational resilience. If you don’t invest time and resources in comprehensive research, you may miss out on opportunities for organizational learning and improvement.
In summary, the absence of a proper investigation jeopardizes the organization’s ability to comprehend the intricate web of factors contributing to deviations. This lack of insight undermines the development of effective corrective and preventive actions, leaving the organization susceptible to the recurrence of similar issues. A thorough investigation not only addresses immediate concerns but also serves as a catalyst for organizational learning and improvement, reinforcing the organization’s capacity to navigate future challenges with resilience and foresight.

7. Audit and inspection results:

As part of their important duties, regulatory agencies carry out thorough audits and inspections to ensure compliance with established standards and regulations in various sectors. The main purpose of these audits is to ensure compliance with the various rules and guidelines applicable to a particular sector. Failure to thoroughly investigate and address deviations from these standards can expose your organization to significant risk.

If regulators find discrepancies in an audit, there are potential consequences that could have far-reaching consequences. Non-compliance may result in fines, penalties or other regulatory actions. These sanctions serve not only as a deterrent, but also as a mechanism to strengthen and maintain the integrity of the regulatory framework.

Moreover, failure to promptly address identified issues can damage the reputation and credibility of the organization being investigated. In addition to financial penalties, more serious consequences may include: B. Closure of activity, revocation of license or legal action. Collateral damage goes beyond the immediate financial impact and impacts the overall performance and sustainability of the organizations involved.

It is important for businesses and organizations to take a proactive approach to regulatory compliance and conduct rigorous internal reviews and investigations to identify and address potential non-compliance before regulators take action. This not only reduces the risk of disciplinary action, but also establishes a culture of care and accountability within the organizational structure.

In essence, government audit and inspection processes serve as an important mechanism to maintain the integrity of the industry and ensure that companies operate within established legal and ethical boundaries. By understanding and proactively addressing deviations, companies can navigate a complex regulatory environment, protect their operations, and contribute to the overall stability and reliability of the industries in which they operate..

8. Operational Inefficiencies:

Operational inefficiencies can arise due to unresolved deviations and can lead to a cascade of problems arising from the root cause of the problem. These unresolved inconsistencies can have a serious impact on many aspects of an organization’s performance, including productivity, resource utilization, and overall business performance.

To effectively address these risks, companies must establish and maintain a strong deviation management system. These systems include comprehensive investigation processes, careful documentation practices, and implementation of corrective and preventive actions. By carefully following these protocols, companies can not only solve immediate problems, but also create a path for continuous improvement.

An in-depth investigation process helps identify the root cause of the anomaly and provides insight beyond the symptoms above. This deep understanding allows for targeted, effective corrective action that not only resolves the immediate problem, but also helps prevent similar incidents in the future.

Documentation plays a key role here as it serves as detailed documentation of deviations, investigations and actions taken. A well-maintained documentation system not only contributes to accountability, but also provides a valuable resource for future reference, allowing companies to learn from past experiences and continually improve their processes.

The basis of a proactive approach to deviation management is the implementation of corrective and preventive actions. Corrective actions address existing problems, while preventive actions aim to eliminate potential problems. This dual strategy not only addresses immediate challenges, but also strengthens the company against future obstacles and promotes a culture of continuous improvement.

By emphasizing variation management, companies not only protect their day-to-day operations, but also maintain critical aspects such as quality and compliance. This commitment to maintaining high standards contributes to the overall effectiveness of the organization and strengthens the company’s resilience and adaptability in an ever-changing environment.

This means that a proactive, comprehensive approach to variance management is essential for companies looking to improve operational efficiency, maintain quality standards, and improve overall business performance. Implementing a strong deviation management system promotes a culture of continuous improvement and empowers your organization to overcome challenges and succeed in a dynamic business environment.

Example of Deviation

Several instances of deviations have been observed in drug or device firms, highlighting potential challenges and risks in their operations. These deviations encompass a spectrum of issues, and it is crucial to address them effectively to ensure the safety, efficacy, and quality of pharmaceutical products. Here are several common examples that underscore the diverse nature of these deviations:

1. Unanticipated Delays:

Unforeseen delays in manufacturing or testing processes pose a considerable risk, potentially leading to product degradation or expiration. Identifying and mitigating the causes of these delays require a proactive approach, emphasizing effective project management, supply chain resilience, and contingency planning to maintain product quality and meet regulatory timelines.

2. Environmental Deviations:
Deviations in environmental conditions, such as fluctuations in temperature, humidity, or air quality, can exert a profound impact on product stability and sterility. It is imperative for firms to implement stringent environmental monitoring programs to detect and address deviations promptly, thereby ensuring the integrity of the manufacturing environment.

3. Equipment Failures and Malfunctions:

One prevalent deviation involves equipment failures or malfunctions, which have the potential to introduce contamination or yield inaccurate test results. These technical glitches can compromise the reliability and precision of manufacturing processes, necessitating a rigorous approach to equipment maintenance and monitoring.

4. Human Errors:

Human errors represent another significant category of deviations, encompassing miscalculations, mislabeling, or the failure to adhere to approved procedures. These mistakes can occur at various stages of the production and testing processes, underscoring the importance of continuous training, process validation, and robust quality management systems.

5. Raw Material and Supply Chain Issues:

Deviations related to raw materials or supply chain disruptions can result in variations in product composition or quality. Establishing robust supplier quality management programs, conducting thorough risk assessments, and implementing contingency measures are essential strategies for mitigating these deviations and maintaining the consistency and reliability of pharmaceutical products.

By recognizing and comprehensively addressing these diverse deviations, drug and device firms can enhance their overall quality management systems, uphold regulatory compliance, and ultimately ensure the delivery of safe and effective products to consumers. This approach fosters a culture of continuous improvement and risk mitigation, aligning with the industry’s commitment to patient safety and product excellence.

 

 

 

Annexure:

Annexure-I: Deviation Form
Annexure-II: Deviation Register
Annexure-III: Investigation Template
Annexure-IV: Investigation Register

Deviation Procedure Read More »

Change Control Procedure

Change Control, Purpose:

Change Control, The purpose of this SOP is to define the requirements that all planned changes which have potential to impact the quality of the product are controlled through a systematic, standard and effective approach. This approach of controlling change will ensure:
[][]Safeguard of quality (Safety and efficacy of the product)
[][]Ensure compliance with legal and regulatory requirements
[][]Traceability of changes made through the lifecycle of a product or facility
[][]Assessment and management of all risks (Quality, Business and EHS) associated with the implementation of changes.

Change Control, Scope:

Applies to all planned changes (including emergency/temporary/permanent changes) that have the potential to affect GMP, Product Quality, Safety, Efficacy, Stability, EHS and the Validation status of Processes, Facilities and Systems of General Block and Sterile Block at XX Pharmaceuticals Ltd.
[][]Few examples of planned changes within the scope of this SOP are:

Production

GMP Documents :
Validation protocol.

Processes :

[][]Manufacturing or Packaging processes
[][]Process (time, mixing speed, temperature, order of addition etc).
[][]Removal/replacement/addition of API or excipients (Formula amounts, overage)
[][]Batch size, production scale
[][]In process controls
[][]Cleaning methods or processes.
[][]Coating weight of tablets, weight of capsule shell, fill weights or volumes.
[][]Any trial (machine/process) work.
[][]Shelf life, expiry (including hold times at intermediate production stages).

Manufacturing Facilities & Equipment :

[][]Equipment, critical device.
[][]Manufacturing/packaging suite/ location.
[][]Introduction of new product/ machinery.
[][]Change of critical spare parts of machineries.
[][]Product & materials
[][]Shape or dimension of product.
[][]Imprints/embossing or other markings on product.
[][]Colour of the product
[][]Packaging Components
[][]Intermediate/Primary/Secondary packs
[][]Product contact components
[][]Disinfectants / Detergents
[][]Product Contact Lubricants

Quality Assurance

Control Documents :

[][]Specification (product, API, excipients, packaging) and Control Direction
[][]Stability protocol.
[][]Artworks.
[][]Qualification protocol
[][]Technical agreements with third party or any service provider.
[][]Colour shades.
[][]Approved supplier list

Methods & procedure :

[][]Sampling or Testing processes
[][]Test parameters (time, run time, temperature, solvent etc).
[][]Removal/replacement/addition of tests.

[][]Environmental monitoring system.
[][]Microbiological monitoring location, frequency and limits

Facilities & Equipment :

[][]Laboratory equipment.
[][]Critical spare parts of equipment.
[][]Introduction of new equipment.

Supplier :

[][]Supplier of API, excipients or packaging components
[][]Change in supplier, manufacturing location, material, pack size or mode of packaging.

Engineering Services

GMP Documents :

[][]Qualification protocol
[][]Drawing & facility layout
[][]Master Calibration list

Facilities & Equipment :

[][]New/additional location for assembly, manufacturing, packaging and testing.
[][]Building Management e.g. Building Management system, pest control.
[][]Calibration frequency or limits/tolerance.
[][]Utilities such as facilities cleaning, compressed air, vacuum, electricity and water.
[][]Building / structural work (e.g. new facility, or installation of utility equipment).
[][]Any change in equipment design
[][]Substitution of any engineering parts.

Services /Utilities :

[][]Water Generation and Distribution
[][]Steam Generation and Distribution
[][]HVAC, vacuum and compressed air modification

Others

[][]Any change relating to a product manufactured at third party
[][]Change relating to product/technology transfer.
[][]Any activity that have the potential to affect EHS
[][]Format change of any controlled documents such as Batch Manufacturing Record, Batch Packaging Record & Control Direction

The process does not apply to the following as these are managed separately by individual SOPs:

[][]Any unplanned incident/changes
[][]Engineering replacement with identical/equivalent parts (procured from the approved sources having the same functionality , specification and serial number)
[][]Routine servicing or preventive maintenance.
[][]Changes during Product Development/trial
[][]Routine revision of any controlled documents (e.g. SOP, BMR, Test methods etc)
[][]SOP/BMR/BPR change to comply with any requirements where the reason and history of changes are mentioned in the revision details.
[][]Like for Like Change

Definitions / Abbreviation:

[][]Change Control Procedure: A formal controlled documented process by which qualified representatives from appropriate discipline, review, propose and make changes to an approved system.
[][]Temporary change: A change (departure from any established procedure/system/process) initiated for the evaluation of proposed procedure/system/process, which has been taken with prior approval to achieve the desired output, allowed for one time change and limited to a particular batch or campaign batches. For example change in manufacturing equipment.
[][]Permanent change: A change initiated based upon scientific rational or historical cGMP data or data generated through temporary changes.

[][]Minor Change: A change unlikely to have a detectable impact on the critical attributes of a system, process, material, product or procedure. (For example: equivalent rewording of instructions or batch record format changes
[][]Major Change: A change that could have a significant impact on the critical quality attributes of a system, process, material, product or procedure. (For example: packaging design change, order of addition of components, mixing parameters in a process).
[][]Critical Change: A change that would be likely to have a significant impact on the critical attributes of a system, process, materials, product or procedure. (For example: a change in critical equipment or change in manufacturing site.)

[][]Planned Change: A change that is planned and given the associated lead time.
[][]Unplanned Change: An unplanned change is a change that occurs unexpectedly on an individual batch or process and is documented via the deviation system.
[][]Engineering replacement with identical parts: Parts that meet the following criteria are known as identical parts and replacement for these Change Control is not required:
=>Same functionality.
=>Same specification.
=>Same manufacturer.
=>Same part number.
[][]Engineering replacement with equivalent parts: Parts that meet the following criteria are known as equivalent parts and replacement for these Change Control is not required:
=>Same functionality.
=>Same specification.
=>Could be a different manufacturer.
=>Could be a different part number from the same manufacturer.

Responsibilities:

[][]The roles and responsibility is as follows:

Concern Department (change initiator)

[][]To propose the change.
[][]Assess if the change is within scope of the change control process.
[][]Provide sufficient supporting information necessary for initial assessment of the change.
[][]To intimate Quality Compliance for issuance of the change control form.
[][]To make necessary entries in the change control form.
[][]To take approval of Department Head and send the form to Quality Compliance for review.
[][]To take approval from Manager, Quality Assurance
[][]To take execution approval from Manager, Quality Assurance prior to execute the change.
[][]To generate relevant supporting data in consultation with related department for compliance of the recommendation provided in reference to change implemented.

Quality Assurance Personnel

[][]To make necessary entries in the change control register.
[][]To issue change control form after assigning change control number and making necessary entries.
[][]To review the change control form and provide the recommendations as impact analysis against the change initiated.
[][]To review actionable mentioned in the impact analysis that are required to be in place prior to implement proposed change and to provide execution approval.
[][]To send the change control for approval to Manager, Quality Assurance in case of impact on regulatory aspects and to obtain approval.
[][]To intimate third party for changes related to their products.
[][]To intimate the changes related to customer, in accordance with the provision as defined in the quality agreement.
[][]To generate and issue corrective action and preventive action (CAPA) form if required for recommendations provided to complete the activity in concern to change implemented.
[][]To review and evaluate the data / assessment report generated during study in consultation with Manager, Quality Assurance.
[][]To close the change control after ensuring implementation and to make necessary entries in change control register.
[][]To retain all change controls in Quality Assurance department.
[][]To circulate a list of change controls which are in issued status for follow up and progress review. The list shall be circulated on monthly basis

Concern Department Head

[][]To review and evaluate filled change control form and give approval.
[][]To recommend possible impact in change control form.
[][]To send the filled change control form for review to Quality Compliance.
[][]To revise the document in consultation with all respective department.
[][]To arrange and ensure generation of the supporting data/ assessment report to comply the recommendations.
[][]To take execution approval from Manager, Quality Assurance prior to execution of the changes.

Manager, Quality Assurance

[][]To provide recommendations / review the adequacy of impact analysis for recommendation provided in respect to change initiated.
[][]To decide change review level of changes proposed.
[][]To approve the change control.
[][]Ensure all relevant changes are managed according to SOP.
[][]Trending of change controls.
[][]Assess, review and approve a proposed change for implementation

Procedure:

Checking of scope for Planned Change:

[][]Before initiating the process the initiator will check if the planned change is within the scope defined in this SOP. If there is any doubt about the scope of change then the initiator will discuss with Quality Assurance Department.
[][]Before initiating the proposal the initiator will check whether any change proposal on the similar subject (Product/equipment/process/materials) still remains open that need to be implemented.

Procedure for Change Initiation :

[][]Upon identification of need of change(s), concern person shall ask Quality Assurance personnel to issue “Change Control Form” (Refer Annexure-I).
[][]Quality Assurance personnel shall make following entries in “Change Control Form” while issuance and similar entries in “Change Control Register” (Refer Annexure-II).
[][]Change Control No. :
[][]Change control No. shall be assigned as per below explained numbering system.
[][]Change control number shall be changed every year.

[][]Change control number shall be alphanumeric system containing 11 characters. Numbering breakdown is as follows: CCyy/Area code/xxx.
Area Code is as follows:
=>General Issues GI, Common issues that affects more than one area.
=>General Block : GB
=>Sterile Block : SB
=>For example: CCXX/GB/001.

[][]The first two alphabets shall stand for Change control
[][]Next two numeric characters shall stand for year code XX shall denote year 20XX.
[][]Next character is slash (/), followed by two capital letter stands for area code of General Block at XX Pharmaceuticals Ltd.
[][]Next character is slash (/), followed by three numerical shall stand for serial number, which shall start every year from 001. For example first change control no CCXX/GB/001 and second CCXX/GB/002, third CCXX/GB/003 ….. for any change.
[][]In case of Sterile block, Change control number shall be SC13/CB/001 and so on. Two capital letter CB stands for area code of Sterile block at XX Pharmaceuticals Ltd.

[][]The number will be unique; if proposal is withdrawn/ rejected the same number will never be used again.
[][]Initiator: Name of the person to whom the change control is issued shall be written.
[][]Originating Department: The name of the department to whom the change control is issued shall be written.
[][]Issued By: The Quality Assurance Personnel who is issuing the change control shall put his/her initial with signature.
[][]Date of Issuance: Date on which the change control is issued shall be written.
[][]Product / Material / Document Name / SOP Title: Name of product/ material/ document title whatever applicable shall be mentioned for which the change is initiated and rest shall be stricken out.

[][]Batch no. /Lab control no. / Document No. : In case of temporary change, batch number of the product or Lab control No. of material for which the change is initiated shall be written.
In case of permanent change, document number (Master BMR No., SOP No., Specification No. etc. with version number) for which change is initiated shall be written.
[][]Type of Product (Country): Whether product is for domestic market or export market shall be mentioned. Specify the name of country as applicable, If the change is related to export product, name of region or country for which the product is being manufactured shall be mentioned.

[][]Change Type: Put the tick mark on appropriate change type.
[][]Concern person shall further fill the change control form as explained under below. In case space provided in change control form is not sufficient to accommodate the changes, below details shall be given on separate sheet in following type of table. This attachment shall be prepared and checked by concern department and reviewed by Quality Assurance.

Sl. No.Existing SystemProposed ChangeReason/ Justification Impact analysisChange review level
Prepared by/date
(Change Initiator )
Checked by/date:
(Department Head)
Reviewed by/date:
(Manager, Quality assurance)

[][]Existing System: Write details of existing process / formula / procedure / equipment or specification that is being followed.
[][]Description of Proposed Change: Write details of proposed process / formula / procedure / equipment or specification that is to be followed.
[][]Reason/Justification/Benefits for proposed change :In case of Direct Change, write the clear reason (wherever possible) for change initiated along with justification based on supporting data like history, trend, stability data, scientific rationale, event / audit observations and experience or any other to ensure no adverse impact on product quality.
[][]Temporary changes: Confirm that a search for similar changes been performed. Put the tick mark on appropriate box and write the date of expiry for temporary change.
Evaluation for Requirement of Change: If not justifiable
[][]The filled change control shall be reviewed by Concern Department Head and Manager, Quality Assurance or Designee. If the requirement for change is not justifiable or not agreed, either to Concern Department Head or Manager, Quality Assurance or Designee, they shall include justification to close the change control.
[][]The change control form and register shall be updated for closure by Quality Assurance personnel and change control form shall be retained in Quality Assurance department.
[][]Evaluation for Requirement of Change: If justifiable.
[][]Upon evaluation, if the requirement for change is justifiable or agreed, Concern Department Head and Quality Assurance personnel, they shall further allow carrying forward change control by signing it, for approval of GM, Plant and Manager, Quality Assurance.

Recommendations for Impact Analysis :

[][]Concern Department Head and Manager, Quality Assurance or his Designee shall provide recommendations for impact analysis to support ultimate output.
[][]The respective impacted Department Head shall be informed for the recommendations provided under each impact and approval for the same shall be taken from the impacted Department Head.
[][]Change control shall be informed to customer, in accordance with the provision as defined in the quality agreement.
[][]Based on feedback obtained further course of change control implementation shall be decided.
[][]If change control is not approved by third party or not acceptable to third party as per quality agreement, then change control shall be closed with the justification that particulate batch cannot be dispatched to respective third party but it can be sent to different third party if it fulfills requirements of different third party.
[][]If that particular drug product has to be dispatched to the third party with current formula then different product Item Code shall be given.
[][]While batch release Quality Assurance shall ensure that product requirement is fulfilled as per quality agreement during dispatch to different third party.
[][]Adequacy of impact analysis through recommendation shall be approved by Manager, Quality Assurance or Designee.
[][]For new system introduction change control shall be raised upon finalization of draft SOP.

Approval :

[][]All change controls shall be approved by Manager, Quality Assurance.
[][]Upon ensuring all approval, the originating department shall initiate preparatory work as recommendation provided to execute the changes proposed.
[][]The Quality Assurance Executive or his Designee shall review / verify all required actionable mentioned in the impact analysis(possible impact) that are required to be in place before implementation of proposed changes and provide execution approval by signing the change control.
[][]Originating department shall start to execute or implement the change only after getting approval for execution from Quality Compliance. The approved change control shall be provided to change initiator for execution of changes.

CAPA (Corrective Action and Preventive Action) Issuance and Monitoring :

[][]Quality Assurance shall issue CAPA form for long term corrective action and preventive action(s) to the concern impacted Department Head to monitor the recommendation as applicable.
[][]The CAPA shall be issued based on discretion of Manger, Quality Assurance.

Execution :

[][]Details of changes shall be explained by Quality Assurance personnel to concern persons either through mail or by conducting training as recommended in impact analysis / by sending scanned copy of change control form through mail.
[][]The concern person shall execute the change in coordination with Quality Assurance & shall prepare assessment report / data.

Review of Recommendations :

[][]After execution of the change the Concern Department Head and the impacted Department Head shall submit the CAPA form along with respective supporting data / assessment report if applicable to Quality Assurance for review of recommendations.

Impact Evaluation and Conclusion :

[][]Based on review of data / assessment report / outcome / results (satisfactory / not satisfactory) Quality Assurance shall make final conclusion, whether the change was executed successfully or not and shall close the same.

Time Line for Closure of Change Control Form :

[][]After the change is implemented, then the CC form shall be closed by Quality Assurance personnel, within 30 calendar days.
[][]Quality Assurance shall track the open change controls while issuing new change control to initiating department.
[][]New change control shall not be issued if for a same system/equipment/material/product/document and same stage about 3 change controls are already open.

Updating of Change Control Register :

[][]After closing the Change Control Quality Assurance shall update the Change Control register.
[][]All the Change Controls – Permanent / Temporary shall be retained in Quality Assurance Department.
[][]Note: In case of a change initiated for one document which may impact other document(s), the respective document(s) can be revised with reference to the same change control initiated for mother change. The document dedicated change control number system shall not applicable in this case.
[][]In addition to mother changes other changes if required can be clubbed and a separate attachment can be attached to mother change control and all persons who have involved in approval of mother change control shall sign the addendum of mother change control.

Batch release of Change Control impacted batch:

[][]Change Control impacted batch will not be released until formal closing.
[][]Any validation/trial batches produced as supporting evidence for the change proposal will be quarantined until formal closing of Change Control proposals.
[][]In some circumstances, to allow batch release, Manager, Quality Assurance may approve concurrent release of the impacted batches through a risk assessment by the owner.

Annexure:

Annexure-I: Change Control Form
Annexure-II: Change Control Register

Change Control Procedure Read More »

SOP for SOP Preparation and Handling Procedure

SOP for SOP, Purpose :

SOP for SOP, The purpose of this SOP is to define the stages, responsibilities and structure for the creation, distribution, handling, controlling, revision & retrieval of all operating procedures of XX Pharmaceuticals Ltd.

SOP for SOP, Scope :

This SOP applies to all functions in order to prepare, review, control and authorize/approve any procedure.

Definitions / Abbreviation:

[][]Standard Operating Procedure (SOP): A written authorized procedure, which gives instructions for performing operations.

Responsibilities:

[][]The roles and responsibility is as follows:

Author(Who prepares the SOP)

[][]Ensure that the document is technically correct and reflects the required working practices.
[][]Initiate the preparation of SOP through the inputs from the employees directly concerned with the activity.
[][]Responsible for circulation of SOP for comment and resolution of any differences of opinion.

Technical Expert

(Any person who has basic understanding on the subject matter)
[][]Review the SOP and formally notify their agreement to SOP owner within a stipulated time.

Functional Head

[][]To confirm the content, accuracy and detailing about of SOP.
[][]Verify the SOP against XX Pharmaceuticals Ltd. master documents and current regulatory requirements and approve it.

Quality Assurance Executive

[][]To maintain the original copy of the SOP.
[][]To issue controlled copy of the SOP and maintain issuance record.
[][]To retrieve the controlled copy of the SOP when it is superseded.
[][]To destroy the SOP as per procedure.
[][]To control and monitor the review process of the SOP.

Manager, Quality Assurance

[][]Approve all SOPs that have direct/indirect impact on product quality.

Procedure:

[][]Note: It will be applicable for any SOP of general precautions or operational safety.
[][]The process for developing and managing any SOP includes picking of right format, number generation, drafting, review, approval, issuance, distribution, periodic review, revising, withdrawing, archiving and destruction.

[][]Layout Designing for SOP: Before preparation of a SOP, following preliminary requirements are to be meet:

Format of SOP

[][]Standard Format (Annexure-I) shall be used for preparing any Standard Operating Procedure.
[][]The format of this SOP should be used to maintain the same text fonts, page borders, and general document format as explained here.

ParticularsFont sizeFont Font Style
In Header: Company LogoN/AN/APosition is ‘Left side’
In Header: Company Name14ArialBold, All Letters in Capital, Position is ‘Centered’ (both in Horizontally & Vertically)
In Header: Plant Address08ArialAll words are Regular but “Plant” is in bold. Position is ‘Centered’ (both in Horizontally & Vertically)
SOP Title10ArialBold & Uppercase
Heading10ArialBold
Text10ArialRegular
In footer10ArialBold, Position is ‘Left (indent)’ in Horizontally & ‘Centered’ in Vertically

Page Set Up

Margin:

[][]Top : 0.75

[][]Bottom : 0.75

[][]Right : 0.75

[][]Left : 0.75

[][]Gutter : 0.00

[][]Header : 0.5

[][]Footer : 0.5

Note: All Measurements at Inch.

[][]Paper size: A4 size, offset paper

[][]Orientation: Portrait (However landscape orientation may be used for annexure or if required).

[][]Header: Same for all pages [Annexure-I]

[][]Footer: Same for all pages except first. In first page there is no footer. [Annexure-I].

[][]Heading of the main content should use appropriate heading number such as 1, 2, 3 etc.
[][]Subheading may be included in any of the content sections using appropriate heading numbering such as 1.1, 1.2 etc.
[][]Further subheading may be included in any of the sub content sections using appropriate heading numbering such as 1.1.1, 1.1.2 etc.
[][]Header & Footer: Each page header must contain the following information:
[][]Title: Mention title of the SOP, which is expressive of the subject of the SOP.
[][]SOP Number: All the SOP numbers must be unique, unambiguous and unanimous. Referencing should be done in such a manner that it reflects either the function or purpose of this SOP. Standard format of SOP number is as – ‘SOP /Sectional Ref/Sequential SOP No. / Version No.’
[][]Sectional Reference is the predefined department/Section code to identify the SOP controlling department.

The following ‘Sectional Ref’ numbers must be used at the time of preparation of SOPs.

[][]Production (General):  PRO
[][]Production (Sterile): S-PRO
[][]Packaging (General): PKG
[][]Packaging (Sterile): S-PKG
[][]Warehouse (General): WH
[][]Warehouse (Sterile): S-WH
[][]Quality Assurance (General): QA
[][]Quality Assurance(Sterile): S-QA
[][]Quality Control(General): QC
[][]Quality Control(Sterile): S-QC
[][]Microbiology(General): MIC
[][]Microbiology(Sterile): S-MIC
[][]Product Development(General): PD
[][]Product Development(Sterile): S-PD
[][]Engineering: ENG
[][]HR & Admin: HR
[][]Supply Chain: SC
[][]Information Technology: IT
[][]Environment, Health &safety: EHS

A three digit Sequential number shall be assigned to the SOP. This number cannot be reassigned to any other SOP even after deletion of that SOP. The sequential number will be followed by two digit Version number which indicates the number of the revision of the respective SOP.

[][]Version No: In case of new SOP, mention “01” in this column. In case of revision, mention number of version in this column.
[][]Superseded: In case of new SOP, mentions “N/A” in this column. In case of revision, SOP No. of old version shall be written in this column.
[][]Page No.: Mention page No. in this column. It shall be mentioned in “Page X of Y” format.
[][]Prepared By (Signature in Blue Ink on Every Page): Signature of a person, who has written the SOP, shall appear in this column. The signature shall be done using a blue ink to identify the copy as master copy.
[][]Checked By (Signature in Blue Ink on Every Page): Signature of Head of SOP Controlling Department /User department head or any concerned reviewer, who has checked the SOP, shall appear in this column.
[][]Agreed By: Signature of Head of other departments excluding SOP owner /User department head or any concerned reviewer, who has checked & agreed the SOP, shall appear in this column.

[][]Define Content of SOP: Every SOP must contain the following standard sections and contents. Guide line to write these contents is in below:
[][]Issue Date: This is the date when the SOP is issued for signature/approval. This should be in the day-month-year (dd-month-yyyy) format i.e. 30-August-2012.
[][]Effective Date: Mention the effective date from which the SOP shall be implemented after proper training. This should be within 7 working days of approval.
[][]Review Date: It will be 36 months from the issue date in day-month-year (dd-month-yyyy) format. However, revision may be made as and when required before schedule.
[][]Review and Approval: This section must include the printed name, signature, job title, and signing date for the following four disciplines:
[][]Prepared by
[][]Checked by
[][]Agreed by( it would be included where necessary)
[][]Approved by
[][]Distribution List: This section will have a list with job title of individual or sectional name to which the SOP will be distributed for execution.
[][]Purpose: The purpose must state why the SOP is needed

[][]Scope: Mention the application of the SOP in this section. It shall describe the extent of areas covered by the SOP. If the same SOP is used in different location, mention the location in the scope of that SOP.
[][]Definition / Abbreviation: Definitions of words, abbreviations, or actions that may not be readily understandable.
[][]Responsibility: Briefly describes the detailed responsibilities of individuals/departments for implementation of the SOP.
[][]Revision Details: In case of revision, point out the specific changes of current version with previous version. For a new SOP the Revision Details text must read: “First issue”.
[][]Annexure: The mandatory features of an annexure are:

Annexure-I: Format of SOP
Annexure-II: SOP Issue Register
Annexure-III: Request for Issuance of Additional copy of SOP
Annexure-IV: Authorization for Discontinuation of SOP

Procedure:

[][]Note: It will be applicable for any SOP of general precautions or operational safety.
[][]The process for developing and managing any SOP includes picking of right format, number generation, drafting, review, approval, issuance, distribution, periodic review, revising, withdrawing, archiving and destruction.
[][]Layout Designing for SOP: Before preparation of a SOP, following preliminary requirements are to be meet:
[][]Format of SOP
[][]Standard Format (Annexure-I) shall be used for preparing any Standard Operating Procedure.
[][]The format of this SOP should be used to maintain the same text fonts, page borders, and general document format as explained here.

ParticularsFont sizeFont Font Style
In Header: Company LogoN/AN/APosition is ‘Left side’
In Header: Company Name14ArialBold, All Letters in Capital, Position is ‘Centered’ (both in Horizontally & Vertically)
In Header: Plant Address08ArialAll words are Regular but “Plant” is in bold. Position is ‘Centered’ (both in Horizontally & Vertically)
SOP Title10ArialBold & Uppercase
Heading10ArialBold
Text10ArialRegular
In footer10ArialBold, Position is ‘Left (indent)’ in Horizontally & ‘Centered’ in Vertically

Page Set Up

Margin:
[][]Top: 0.75
[][]Bottom: 0.75
[][]Right: 0.75
[][]Left: 0.75
[][]Gutter: 0
[][]Header: 0.5
[][]Footer: 0.5
[][]Paper size: A4 size, offset paper
[][]Orientation : Portrait (However landscape orientation may be used for annexure or if required).
[][]Header : Same for all pages [Annexure-I] [][]Footer: Same for all pages except first. In first page there is no footer. [Annexure-I].
[][]Heading of the main content should use appropriate heading number such as 1, 2, 3 etc.
[][]Subheading may be included in any of the content sections using appropriate heading numbering such as 1.1, 1.2 etc.
[][]Further subheading may be included in any of the sub content sections using appropriate heading numbering such as 1.1.1, 1.1.2 etc.
[][]Header & Footer: Each page header must contain the following information:
[][]Title: Mention title of the SOP, which is expressive of the subject of the SOP.

[][]SOP Number: All the SOP numbers must be unique, unambiguous and unanimous. Referencing should be done in such a manner that it reflects either the function or purpose of this SOP. Standard format of SOP number is as – ‘SOP /Sectional Ref/Sequential SOP No. / Version No.’
[][]Sectional Reference is the predefined department/Section code to identify the SOP controlling department.

The following ‘Sectional Ref’ numbers must be used at the time of preparation of SOPs.

[][]Production (General): PRO
[][]Production (Sterile): S-PRD
[][]Packaging (General): PKG
[][]Packaging (Sterile): S-PKG
[][]Warehouse (General): WH
[][]Warehouse (Sterile)S-WH
[][]Quality Assurance (General): QA
[][]Quality Assurance(Sterile)S-QA
[][]Quality Control(General): QC
[][]Quality Control(Sterile): S-QC
[][]Microbiology(General): MIC
[][]Microbiology(Sterile): S-MIC
[][]Product Development(General): PD
[][]Product Development(Sterile):S-PD
[][]Engineering: ENG
[][]HR & Admin: HRD
[][]Supply Chain: SC
[][]Information Technology: IT
[][]Environment, Health & Safety: EHS

A three digit Sequential number shall be assigned to the SOP. This number cannot be reassigned to any other SOP even after deletion of that SOP. The sequential number will be followed by two digit Version number which indicates the number of the revision of the respective SOP.

[][]Version No: In case of new SOP, mention “01” in this column. In case of revision, mention number of version in this column.
[][]Superseded: In case of new SOP, mentions “N/A” in this column. In case of revision, SOP No. of old version shall be written in this column.
[][]Page No.: Mention page No. in this column. It shall be mentioned in “Page X of Y” format.
[][]Prepared By (Signature in Blue Ink on Every Page): Signature of a person, who has written the SOP, shall appear in this column. The signature shall be done using a blue ink to identify the copy as master copy.
[][]Checked By (Signature in Blue Ink on Every Page): Signature of Head of SOP Controlling Department /User department head or any concerned reviewer, who has checked the SOP, shall appear in this column.

[][]Agreed By: Signature of Head of other departments excluding SOP owner /User department head or any concerned reviewer, who has checked & agreed the SOP, shall appear in this column.
[][]Define Content of SOP: Every SOP must contain the following standard sections and contents. Guide line to write these contents is in below:
[][]Issue Date: This is the date when the SOP is issued for signature/approval. This should be in the day-month-year (dd-month-yyyy) format i.e. 30-August-2012.
[][]Effective Date: Mention the effective date from which the SOP shall be implemented after proper training. This should be within 7 working days of approval.
[][]Review Date: It will be 36 months from the issue date in day-month-year (dd-month-yyyy) format. However, revision may be made as and when required before schedule.
[][]Review and Approval: This section must include the printed name, signature, job title, and signing date for the following four disciplines:

[][]Prepared by
[][]Checked by
[][]Agreed by( it would be included where necessary)
[][]Approved by
[][]Distribution List: This section will have a list with job title of individual or sectional name to which the SOP will be distributed for execution.
[][]Purpose: The purpose must state why the SOP is needed.
[][]Scope: Mention the application of the SOP in this section. It shall describe the extent of areas covered by the SOP. If the same SOP is used in different location, mention the location in the scope of that SOP.
[][]Definition / Abbreviation: Definitions of words, abbreviations, or actions that may not be readily understandable.

[][]Responsibility: Briefly describes the detailed responsibilities of individuals/departments for implementation of the SOP.
[][]Revision Details: In case of revision, point out the specific changes of current version with previous version. For a new SOP the Revision Details text must read: “First issue”.
[][]Annexure: The mandatory features of an annexure are:
[][]No annexure can be updated without updating the SOP.
[][]No need to update Annexure during only updating the SOP.

[][]Procedure: This section provides the detailing about the step-wise activities to be performed within a system.
[][]Preparation of SOP:
[][]SOP author will prepare a procedure in clear unambiguous language which describes the process to be conducted against the SOP in sufficient detail that they can be performed in a reproducible, systematic and consistent manner. During preparation of SOP author must consider the following:
[][]Understand the full process first and then write the procedure/SOP.
[][]Write procedure using simple, clear, concise & easy sentences.

[][]Abbreviations must be defined in full on the first occasion of use. All the resources that can give ideas about preparing the procedure shall be explored.

[][]It is preferable to use positive sentence structure in the SOP.
[][]High level process flowcharts or diagrams must be used for clear understand of the process
[][]User Department Head confirms the content, accuracy and detailing of SOP.
[][]Review of the Documents:
[][]The author collect all comments from the review of the document and update the document as appropriate and be able to provide the Approvers with a justification for any comments from key reviewers that are not accepted.

[][]Approval of SOP:
[][]After final verification, All SOP’s must be approved by Manager, Quality Assurance.
[][]Training on SOP:
[][]After final sign off the originator or controlling department will initiate the training program on SOP.
[][]Training must be conducted before the effective date of the SOP.
[][]The originator will inform to Human Resources Department [HR] with a formal request for organizing training.

Issue of SOP:

[][]SOP controlling department will make required photocopies of the SOP from Master SOP as per distribution list.
[][]Put the “CONTROLLED” stamp in blue ink at the top of the right side of each page of the SOP.

[][]Controlling Department issues the SOP for implementation after making necessary entries in the controlled copy issuance record (Annexure-II) at the time of issuing. The record sheet will be attached with master SOP.
[][]Controlling Department will retrieve all controlled copies of the superseded version.
[][]Controlling Department person shall put the “OBSOLETE” stamp (sample is given below) in red colour on each page of the Master SOP of the superseded version. The Controlling

[][]Department shall keep the OBSOLETE MASTER SOP in the master OBSOLETE file.

[][]All other copies of superseded version will be destroyed after keeping a record.
[][]Photocopy of the “CONTROLLED COPY” is not permitted.
[][]Any photocopy that is not having blue stamp of “CONTROLLED” shall not be considered valid for use.
[][]Master SOP will be kept by Quality Assurance department.

[][]There shall be a Master List of all main SOPs and it shall be maintained by Quality Assurance Department.

Implementation:

[][]The user department after receiving “CONTROLLED” copy of the new SOP shall implement the SOP after training.

Periodic review of SOP:

[][]SOP shall be reviewed at least every 3 years. However SOP’s may be revised before the next review date if required.
[][]In case of any change in the SOPs that may affect the product quality a Change Control Proposal shall be raised by the user’s section/department.

Issuance of Additional Copy of SOP:

[][]If an additional copy of SOP is required by any department for non-operational use then QA dept. shall issue an additional copy only after written approval from Manager, quality [][]Assurance. Such requests shall be obtained through the Request Form as per Annexure -III and shall be forwarded through the department head.

Discontinuation of the SOP:

[][]The existing SOP may be discontinued with proper justification and approval of Departmental Head / Manager, Quality assurance. The SOP number of deleted SOP cannot be reassigned to any other SOP. Fill the details for discontinuation of the SOP as per Annexure-IV.
[][]QA person shall retrieve and destroy all the controlled copies of the discontinued SOP after the authorization of Manager, Quality assurance.
[][]QA person shall put the ‘OBSOLETE’ stamp in red color on the every page of the original copies of the discontinued SOP.

Annexure:

Annexure-I: Format of SOP
Annexure-II: SOP Issue Register
Annexure-III: Request for Issuance of Additional copy of SOP
Annexure-IV: Authorization for Discontinuation of SOP
Annexure-V: SOP Index

SOP for SOP Preparation and Handling Procedure Read More »

Validation Master Plan, How to write for a GMP compliance firm

Validation Master Plan[VMP] encompass all type of validation activates of a site especially for the new firm, the firm must be validated before run any routine commercial production. The validation activities which consider the major area as Facility, Utility, Machine, Process etc.. Facility, utility, and machine must be validated before run the production operation.

Validation procedure and Validation Master plan is not the same and doesn’t implies the same thing. Validation protocol describe the specific procedure to perform the specific activities where as Validation Master Plan is the series of plan/schedule which describe the plan with a tentative define timeline. Any plan/schedule may be change which to be cover by raising deviation management with proper justification and action to be triggered followed by CAPA.

Validation Master Plan is beneficial for planning purpose and subsequently identifying the related resources to complete the assigned activates on due time. It covers the all type of major documentation like procedures, processes, product, facilities, utilities and equipment.

How a Validation Master Plan works?

Validation master plan is the core guidance of the firm which implies that how the validation activates of the firm will perform within a time frame. It details the activities of the all functional department like production, quality control, Engineering will operate their activities regarding validation events.

The plan demonstrate by the Validation master plan is set upon the agreement of the all functional department and any type of failure is properly justified which satisfy the regulatory body. The proper implementation of the VMP of the respective firm denote that they have the proper control over their quality system.

Functions of the Validation Master Plan

Management learning

Top management of the company is not concern about the requirement of the qualification and validation activities of the respective firm. Here VMP plays the major role and provide the essential information to the company top management. The content of the VMP describe the total quality requirement events of the validation process. It also denote that only the properly validated facility can provide the repeated/continuous quality product through daily activities.

Project nursing and management

By preparing the Gantt chart from the content of the VMP, the management can track the activities of the new facility and set a tentative deadline for the competition of the defined activities. Everyone will be proactive when set a tentative deadline with proper justification through a site quality review meeting. Assigned personnel must be monitored for the progression of the events by daily /weekly /fortnightly/ monthly then VMP will be fully effective and action will cover on due date.

Conducting the validation program

Validation master plan describe the all events in the validation process and the qualification of the processing equipment’s and utilities. As the VMP provide the timeline for the completion of the defined activates base on the criticality. All related resource must be on site to conduct the validation activities and recheck/double/ triple check may be conduct before starting validation activities, for any shortcoming notify the same and after solving the events proceed to validation activities.

Planning purposes

As the VMP detect the list of resources which is required to perform the validation activities in a time line then the list of document may affect by this activity-

  • Equipment
  • Facilities
  • Product
  • Processes
  • Procedures
  • Utilities
Criteria of a Validation Master Plan

VMP require specific preparedness and vigorous planning of different steps in the particular process. All type of activates need to perform in due time as per approved working plan avoiding any type of major/critical deviations. Beside this a VMP is generally written off as-

Multidisciplinary methodology:

This is not the one man job, its require multidepartment involvement, various type of SME [Subject Matter Expert] from various department are involve to perform the specific job. Expert such as chemical analysts, pharmacists, microbiologists, technologists, engineers, metrologists, and SME from QA departments must involve to this activities.

Time bound:
Any type of validation

Generally validation work is submitted to rigorous time schedules. These studies are always the last stage prior to taking new processes, facilities into routine operation.

Costing matters:

To run a successful validation activities to the site, huge resources and expert personnel are involve so that no deviation occur on the site. Lot of financial involvement require to perform the designated activities. A new machine/equipment may be involve to solve the emergency issue.

List of critical point of Standard VMP

All VMPs must include the following:

Title page with Authorization where appropriate signing with date will be present. Title page must be include title of the document, document number and version no. and Signature from the appropriate body including Head of site quality. List content to be present on a VMP-

  • Table of contents
  • Abbreviations and glossary
  • Validation plan
  • Purpose and approach to validation
  • Scope of validation
  • Roles and responsibilities
  • Outsourced services
  • Deviation management in validation
  • Change control in validation
  • Risk management principles in validation
  • Training
  • Validation matrix
  • References
Table of contents

The table content is the brief of the major substance/content present in the VMP. It contains all of the critical area of VMP. Page no. to be mentioned on the table of the content page along with the major content. It will denote where will find the major content of the VMP.

Abbreviations and glossary

Abbreviations and glossary provides necessary information’s to the reader regarding the various term or short/abbreviate form use in the VPM which may not familiar to the respective reader.

Validation plan

A VMP implies that what should be validated and when, where, how and why it should be executed. Critical process mention on the VMP must breakdown into several parts and criticality must identified to perform require validation.

Purpose and approach to validation

Purpose provides an overview of the every process also describe validation approach with supporting data. It must be sum up clearly so that the respective user can understand the actual process/procedure by tracking the document. Validation approach states the persistence of the VMP denoting critical process, equipment and system as described.

This methodology confirm that all validation events to be conducted in prospective manner following approved protocols. VMP speaks about the change control and qualification of equipment and systems and confirm the stipulated events has been done based on existing policies and procedures.

Scope of validation

Scope of the VMP describe all evets relating to the processes, systems, equipment, utilities, and procedures which may affect the quality of the product at the manufacturing site.

Specific equipment, utilities, systems, and procedure be mentioned properly and validation execution to be done based on the documented risk assessment. Define clearly which area will be under validation and where not under the scope. Procedure to be describe in such a way so that anyone possess the same understanding to coverage VMP.

Roles and responsibilities

This area specially denote the dedicated responsibility for the designated department. Generally validation department/team is responsible for preparing all type of validation protocols, validation reports, List of SOP’s deviation reporting, and change control procedure and achieving, storage of validation related all documents.

Generally, Engineering, Production, QC, Microbiology and QA personnel prepare the validation documents as when required based on define timeframe subsequently. Quality Assurance department is responsible to review the all protocol, reports, SOP’s etc. then approve the same.

Outsourced services

Any type of out sources activities regarding qualification and validation must be mention the validation master plan and record/supporting documents/agreements must be keep the same. Certified vendor to be involve to the validation activities, before engage the validation/qualification activities vendor competency certificate to be check.

Deviation management in validation

Any deviation regarding validation to be address and record must be keep for further clarification, if machine involve then call the supplier to resolve the problem. All of critical deviation must be investigate and corrective action to be taken. All validation report to be approve before starting the operation.

Change control in validation

VMP must implies all change management which have the potential impact on the validated process/system must be notify and it should be handle with the existing change management procedure.

Risk management principles in validation

Quality Risk Management Procedure to be define on the Validation Master Plan as to perform the validation activities, quality risk may be the major to be notify same and record must be done and impact to be analyze properly through FMEA[Failure mode and effects analysis] method.

Training

The defined personnel who will perform the validation activates must be trained properly and to be ensure that they have the proper knowledge and skill to perform the right job at the right time.

All validations

This include the following area-

  • Analytical method
  • Cleaning
  • Computer validation
  • Equipment
  • Premises
  • Processes
  • Qualification
  • Revalidation
  • Utilities

The description of the major area must be include VMP such as Manufacturing, Material Management, Facilities, and Central Plant. Attachment with VMP must define the GMP compliance area and non-GMP compliance areas. Describe the cleaning validation strategy and manufacturing process steps, use process flow diagram to describe the specific product manufacturing activities with major equipment involvement on the diagram. Performance qualification of the major equipment to be done showing that it repeats its intended use subsequently.

Validation matrix

Performing an effective validation matrix by prioritizing the critical validation at first then the next one. In this way the VMP activities may be more fruitful. List the all critical validation then perform the task as per justified time frame.

References

List of references to be add at the end of the VMP documentation. Proper guideline reference is mandatory to prove your documented evidence.

Writing the VMP

To write the effective VMP, a team may be form due to a single/individual/specific person didn’t contain the all idea/knowledge regarding different activates. A QA person may not be expert about Engineering activates and a QC person may not be expert about production activities, so a team from different functional department may be effective way to gather comprehensive knowledge from different perspectives then write down the right VMP.

 Involving the multidepartment people from different parts confirm that all equipment, utilities, processes, and systems has been properly addressed on the VMP. T write an effective VMP, every team member must be proactive to address the every point of view seems critical to his side.

What “WHO” says about Preparation of VMP?

“A manufacturer should have a validation master plan that reflects the key elements of validation. It should be concise and clear and at least contain reference to/have a short description”.

validation master plan, validation WHO

List of Major content of VMP as per WHO GMP guideline-

  • Analytical method validation
  • Change control
  • Cleaning validation
  • Computerized system validation
  • Deviation management
  • Equipment & instrument qualification
  • Outsourced services
  • Personnel qualification
  • Premises qualification
  • Process validation
  • Validation matrix
  • Validation policy
  • References
  • Risk management principles
  • Roles and responsibilities
  • Scope of qualification & validation
  • Training
Conclusion

A well described VMP is the true asset of the firm as well as the critical document to avoid the regulatory noncompliance. An incomplete VMP always brought more 483 with subsequent warning letters from FDA. A standard VMP must be more precise, to the point and actual to the system, process, and procedure.

Every sentence of the VMP must be “may”, “may be”, “should be” etc. free, sentence must be in active form in present tense. A well decorated VMP implies the organization positive image as well as quality products avoiding non-compliance, deviation etc.

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Audit Checklist for QA Department in Pharmaceutical Company

Audit Checklist for QA Department: here is the Audit Checklist for QA Department. You can find the best checking point for QA [Quality Assurance] Department in pharmaceutical Company-

Audit Checklist for QA
  1. Annual product review/Product Quality Review reports
  2. Batch Document Archiving /Retrieval system/Disposal records
  3. CAPA [Corrective And Preventive Action]
  4. Calibration Records of balance, equipment’s, machine etc.
  5. Change Control
  6. Destruction of samples & Chemicals reports
  7. Deviation Management
  8. Drug Master file of existing & new products
  9. Failure Investigation
  10. Finished products Released records
  11. GMP/Self-Inspection audit reports
  12. Job Description
  13. Incineration by third party Records
  14. List of finished products, Raw materials & packing materials
  15. Logbook maintaining & Issuance Records
  16. Label Control Procedure
  17. Market Complaint Investigation Report
  18. Machine/Equipment Qualification status records with index
  19. Organogram (Factory)
  20. Previous Self Inspection/Internal Audit Report
  21. Process Validation Protocols & reports
  22. Quality Manual
  23. Risk Management
  24. Retention Sample Management
  25. Rework/Re-process records
  26. Reagent Management records with index
  27. Recall Procedure
  28. Retention samples records with index
  29. Records of market return Goods destruction
  30. Site Mater File (SMF)
  31. Source approval procedure and its records
  32. Standardization of volumetric solution records
  33. Stability studies report of both accelerated and long term
  34. Storage condition of RM, PM, intermediate, bulk & finished products
  35. Specimen signature list
  36. Technology transfer records
  37. Validation Master Plan (VMP)
  38. Vendor/ Supplier Audit reports
  39. Write off & Disposal records of Non-conforming/Rejected materials & products
  40. Yearly Training Calendar and its records for both on Job & GMP
  41. SOP Index
  42. SOP for
  • CAPA
  • Change Control
  • Deviation Management
  • Hold Time Study
  • IPC[In-Process Control] Instruments
  • Job Description
  • Labelling & Label Control
  • Market Complaint Handling
  • Quality Manual
  • Quality Risk Management[QRM]
  • Recall Procedure
  • Site Master File
  • Training Manual
  • Waste Disposal

This all about the Audit Checklist for QA Department but not limited to.

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