Facility

Ten golden rules of GMP

1.0 GMP Golden Rule-1

Get the facility design right from the start

All the manufactures who are engage to produce Foods, Drugs, Medicine, cosmetics and other healthcare related products want to follow the all basic rule of the GMP/cGMP. This is to be stated here that the compliance of the GMP is very much easy to follow if the facility design perform right way from the start.

To run a smoot operation, this is very important to follow the principles of GMP as well as  First Golden Rule of GMP ”Get The Facility Design Right From The Start”.

“If facility didn’t design right way from the first then you may fall in great problem and may be reconsider the whole facility design”

Facility Design

There will be a healthy harmonization between the sequence of facility design where the main target of the facility design is to reduce the mix-up, cross contamination as well as smooth production process. You can’t allow blister packing room near raw dispensing area. The area must be design as such a way that change of non-compliance can be reduce.

A well planned facility design may reduce the overhead of production and least change of product failure. This also prevent back flow and increase productivity to the respective firm. The aim of the best facility design is to –

• Lest traffic movement at the production area.
• Align the material in specific room/area.
• Reduce contamination/mix-up of the products.
• Minimize the wrong interpretation.

The target of the good production design is to continue the linear production area so that man and material flow will be unidirectional no backflow the same. The Zigzag and irregular design of the facility tends to misinterpretation of the production design and design failure exhibit predominantly. To apply/introduce/change the existing facility design must be review the SME [Subject Matter Expert].

Environment

This is very important to control the water, lighting, ventilation, temperature, humidity, air etc. so that the respective variable can’t effect the product quality, safety, and efficacy. So the facility must be design must be precisely and risk of non-compliance can be reduce.

A suitable facility must be confirm-

• Temperature, Humidity, Pressure, light is appropriate to the standard practice.
• The surface of the wall must be free from all types of crack/dam/swelling/dust/rust etc.
• Wall must be design in such a way so that it can be clean easily.
• All type of drainage must contain 1% slope so that the backflow can be prevent easily.

Equipment

The equipment to be locate, design, install, operate, in such a way so that the intend use can be confirmed to its standard. A standard equipment should be-

• Well designed, properly installed, easily operable and easily cleanable.
• Easily usable
• Properly labeled
• Not reactive with the product
• Rust free
• Calibrated at specific interval

Ten golden rules of GMP

2.0 GMP Golden Rule-2

Validate processes

After design the full facility and equipment of a farm, this the mandatory rule that you must ensure the machine and the facility are operate to its standard but how do you prove this state? Now the term Validation come here first.

Documented evidence is mandatory to prove that the process and equipment doing its own function they supposed to do. To achieve a quality product the consistent function of the machine is essential and this activities can be achieved by effective validation of the process and equipment.

Validation

The validation is the documented evidence which provide the high degree of confidence that specific process will consistently produce a specific product meeting its previously approved specification and related quality parameter.

The validation is the GMP requirements which prove that a specific process, equipment and facility operates right way from the first time to every time without any significant change. The new facility, equipment, process need to validate prior its regular use. Any significant/substantial change in the existing validated system need to validate the system/process/equipment etc.

Validation usually involves:

An equipment/machine generally undergo the several process to complete its validation status. IQ[Installation Qualification] confirms that a specific machine/equipment has been installed correctly to its predefined specifications mentioned its approved IQ protocol.

OQ [Operational Qualification] confirms that the equipment has been successfully installed and operate to its specification mention its approved OQ protocol.

PQ [Performance Qualification], confirms that a specific machine/equipment can produce a product to its predefined specification mention on its approved protocol.

The above all protocol mention the specific process steps, one the work completed successfully a report must be generate to prove the specific activity.

Change control

After completion of the validation programme of the system/equipment/machine/process the maintaining the validation status is important. Once the change is made in any part of the validated facility subject to change control process. A formal change control process must follow to control the whole system. A substantial/ significant change subject to revalidation the system and record must be keep the same.

If a process/part of process/part of the equipment subject to change which may affect the quality of the product need to record keeping through change control process so that the respective firm may overcome regulatory bindings.

Ten golden rules of GMP

3.0 GMP Golden Rule-3

“Write good procedures and follow them”

It can’t be imagine a good company without proper written procedure. An unwanted situation may arise to repeat the specific job from memory. Most of the manufacturer of the firm rely on the experienced operator rather than new one.

This is very logical than an experienced person is always expected to perform the right job but it is not possible to memorize the right job every time may be forget to perform the any specific critical steps resulting failure of the product.

This is the best practice to write down the whole process at actual which perform on the machine/specific stage.

A firm must be document specific not operator specific.

In a foods, drugs, cosmetics industry this is very important that the specific procedure must be clear, concise and logical and must be in place so that anyone can trace and realize it when required and this is the important part of the GMP.

You may consider the SME [Subject Matter Expert]/Third Party Audit Team/Experienced Existing Professional to develop your documentation. When an independent team/party/organization audit your firm they will develop your documented activities and find out your loop hole of the specific process/ procedure/stage and then you will get the huge opportunity to develop it.

List of documents require for standard Firm:

A typical Firm [Foods, Drugs, Medical Device, cosmetic industry] contains the following document but not limited to-

Standard Operating Procedure: Describe the details written procedure/instructions/process to complete the specific task where relevant.

Product/Materials Specification: This the core of the product/Materials which have to confirm/meets to evaluate its quality attribute.

Records Keeping: This state provides history/executed option of the certain products/materials that the products/Materials are following its predefined approved criteria and repeated the criteria each time when produced.

How to write good procedures:

First of all, before writing a good procedure you have to read the all relevant document then start write the main procedure. Use small breakdown of the large paragraph and use Flow Diagram, Chart, Table, Keyword, etc. for precise and easy understanding.

Generally, people don’t have the much time to read the whole procedure from the start to end; want to eye through the whole procedure on the keyword.

A critical/Big process/ procedure can be divided several small things as-

• Bold Text
• Bullet Points
• Charts
• Follow Diagram
• Heading
• Highlighted Text
• Image
• Instructions
• Table

This type of activities reduce the man hour as well as easy understanding the documented evidence. Write down the language in very easy process, where required mother language rather than English use the same for better result. Don’t include extra paragraph for a little information. Write down the whole process in imperative sentence. An ambiguous word mislead the information; so use easy word that is more familiar to everyone.

Use as many simple sentence as possible so that anyone can read it easily. You can follow ALCOA[Attributable, Legible, Contemporaneous, Original and Accurate] and ALCOA+[ Attributable, Legible, Contemporaneous, Original and Accurate with Complete, Consistent, Enduring and Available] method to create a better legible document.

After creating an initial document, printout the same and handover this copy to the relevant personnel and collect the feedback from the personnel and request them to notify which part of the document is confusing and hard to understand the main content of the document.

Mark this section and review the document and apply the correction to the document then you will able to create desirable document for the relevant personnel. This is the method to make a simple standard document but not limited to, you can apply various methods to generate a better documents. 

A crated documents need to review it’s periodically to keep it up to date. Most of the company review their document at a Two/Three year’s period. You can review the document yearly or anytime when the relevant topics change based on the available/reliable approved information. Without strong reference/approved information, changing a document create hassle to the existing system.

Follow the written procedures

This is the best practice to have the better written procedure at the place in controlled manner and everyone is following it. A document may be descriptive to the specific process/procedure where alternative/shortcut process/procedure may save the time or you can do it efficiently. Don’t do that.

Do the thing what is written on the document, if require any change, notify the respective authority/your supervisor/Head of Site Quality Person about the issue. Change the document through change control process and until change the document you have to follow the document due to your proposal may not accept if critical change require to apply the proposed change.

You can’t apply your proposed change without approval, due to-

• Your process/proposal may not be cost effective in the long run.
• Each validated steps/procedure/process has its importance which change may affect the product quality/efficacy/safety.

Ten golden rules of GMP

GMP Golden Rule-4

 “Identify who does what”

Every employee must have the clear, precise, specific responsibilities to the respective department. He must know what he supposed to do or what not his responsibility. The specific responsibility will reduce the man hour and better working environment. Every department of the firm must have job description of their employee. A typical job description will contain the specific point such as-

• Job Title
• Duties and Responsibility
• Experience
• Total Service length
• Service length of the existing firm
• Core Responsibility
• Additional Responsibility
• Administrative Activities
• Special Responsibility

The responsibility must be stand alone. No overlapping isn’t acceptable. Doing similar job by multiple employee cause serious misunderstanding and job undone. Better to display the everyone responsibility on the firm notice board at specific department will show that who does what. The cross functional department will easily contact with the responsible personnel if job description available on intranet/sharing folder/common FTP sharing within the firm.

The responsibility may be overlap in the following cases but not limited to-

• Calibration Activities
• Cleaning Activities
• Validation Activities
• IPC in multiple section
• Production activities
• Analytical Activities

Before assigning a specific task for a specific employee, he must be train first and a mock test will be perform before final certification of the employee. An employee must confirm that he is capable for the specific job.

Especially critical activities like Validation of the specific product/process/facility, a series of work to be done precisely without any significant non-compliance, then a person must be assign who is capable to perform the series of task with great responsibility.

Ten golden rules of GMP

GMP Golden Rule-5

“Keep good records”

A good records determine that your system is under control and you are compliance with the GMP which also demonstrate your visibility in terms of quality matters. A good records exhibit that you have followed the all steps and activities describe in the batch production history from dispensing to finished products. This is the part and parcel of the GMP to keep the good records of your production activities.

How to keep Good record?

Make a culture to keep the good record in daily activities. Never try to memorize the activities. Keep your record up to date on the right time at right place.

• Don’t perform any type of activities which you are not responsible for or you don’t have proper training to do the same. If you think that the work has been completed without proper documentation then you are in wrong concept. If you are unable to record the activity then it didn’t happen!!
• Try to develop less signature option at your document, unnecessary signature creature signature fatigue to the employee.
• Record all types of activities carried out during production.
• Never try to memorize the activities, record it on time.
• Record all type of activities if deviation occur, then inform the Site quality department and take the decision for the same.
• Record all type of record in legible ink. Signing any type of record reveal that you are accepting the described activates.
• Notify all type of mistakes drawing a single line and write the actual, give the date with sign and mention the reason for the correction.

Documents Record Keeping

Generally you should keep the record of all documented activities. Some important records are-

• Analyst Personal Analytical Logbook
• Batch Production Records
• Cleaning/Equipment Logbook
• Cleaning/Equipment Logbook
• Environmental Monitoring Records
• Material/Product storage condition records
• Training Records of Employee

Keep the validation/calibration records life time of the company. Keep batch/production record for expiry date of the product with additional one year. After expiration, keep record for destruction of the document and you can take critical data from the expired documents on validated spreadsheet for further reference. You can keep your document as per your own define period.

Ten golden rules of GMP

GMP Golden Rule-6

“Train and develop staff”

If a firm is properly equipped with the right tools then consider the skilled employee to operate the machine. Document the activities through proper training before starting any type of commercial activates in a validated facility.

Every personnel of the firm must be trained before assigning any type of job. Confirm that the respective personnel have the desired skilled and capability to perform the right job at right time in right place. If you able to do the same then you can develop the GMP culture at your firm.

Training

First of all you have to train the all personnel related to production activities, Laboratory Activities, Quality Assurance activities or whose activities directly affect the quality of the product. Some basic training need to include their training curricula. A training need assessment to be arrange before engaging someone at specific duty.

Some training is common for all employee such as basic GMP training, personal safety and hygiene, Fire Fighting, emergency evacuation plan etc. to be include to the personal training profile.

If any situation occurs, where you have to allow someone to enter the specific area like production then you have to give him some instructions what to do or what not to do, additionally assign a experienced person with him for close monitoring purpose.

Train the employee as relevant as per job description, unnecessary training cause haphazard situation. Identify the group of employee for common training curricula will save your valuable time. Arrange the training as when required.

After completion of the training program certify the employee for specific task and record the same. Initially you may follow up the new employee with the close supervision of a senior experienced skilled person. If everything goes well then give him signing authority to the respective document.

Verified job capability

An employee must prove his job competence during everyday activities producing quality products/documents. After proper training of the respective employee, he must be prove himself that he is very much capable to do the same from the first time to every time in right way.

If he fail to do the specific job then arrange retraining for the same topic then involve the same. If any employee fail to do the same job in several times after retraining then change his job description to the next available job responsibilities.

You can assess the employee through annual appraisal plan, taking record for good/poor activities and discuss the employee with his week point and try to develop it. You can discuss a series of topic with the respective employee-

• Attractive compensation package
• Bonus/Festival Bonus/Daily Allowance/Overtime Package
• Current position Analysis
• Departmental plan
• Document the poor records
• Foreign Training/Foreign Tour/Local Tour
• Gift hamper/Family day/Tour/Annual Picnic
• Insurance Plan/Group Insurance Facility
• Responsibility Analysis/Remind his responsibility
• Roles and responsibilities

Record Keeping

You must keep the record of all training record of the specific employee including retraining record, evaluation of the specific training at his training record file in a traceable place. A training coordinator to be available to monitor the training activity of the firm.

A person from every department will be responsible to communicate with the training coordinator regarding departmental training activities. Training coordinator will arrange the all type of training of the respective firm.

Ten golden rules of GMP

GMP Golden Rule-7

“Practice good hygiene”

Product contamination will be at higher level if proper hygiene and sanitation program is not maintained. Cleanliness is the key factor in the pharmaceutical industry due to some products like Injections/Infusions are directly administer to the blood stream, if products are contaminated/compromise with pyrogen then any one can face moderate to serious health hazard.

A Standard Operating Procedure [SOP] to be develop regarding hygiene and sanitation. The procedure to be maintained from the first time to every time before starting any type of production activities. A better hygiene practice can develop better GMP culture at your firm. Every employee must confirm to the sanitation and hygiene procedure.

Good to practices in everyday manufacturing-

• Maintain personal hygiene everyday by wash your hand, wearing protective gloves, head cover, beard musk, protective musk, hand sanitizer [70%IPA] especially when you are in production area as when required.
• Notify your senior/supervisor/authority/Department in-charge/Manager if you are ill/having open wound and probably you are not allowed to manufacturing are till you feel well.
• Less/Minimum personnel to be allowed at direct manufacturing/filling area and less product contact to be your first priority.
• All type of Eating/Drinking must be prohibited at any type of production/packaging area.
• Cleaning and sanitation instructions to be hang on different area of factory premises to increase awareness regarding this issue to the existing employee.
• Visitor/Outsider/Auditor Entry to be prohibited to the direct production/manufacturing area.
• Notify any type of non-compliance to your Superior/In-charge.
• Before starting any batch, remove all type of waste, dust, excess materials except relevant materials.

If possible arrange a personal hygiene and sanitation training program in each month. A schedule may be prepared for different department if it not possible to cover all employee in single time frame. Schedule to be organize in such way that every employee get training at least once in month. If this procedure can develop then you can hope that your firm is conforms to its GMP compliance.

Ten golden rules of GMP

GMP Golden Rule-8

“Maintain facilities and equipment”

Maintenance schedule must be established to facilitate the activities of the daily work. A regular maintenance activities reduce the sudden machine failure during production. Maintenance activities also reduce the product contamination.

A maintenance schedule to be followed effectively and supporting machine parts, oil, coolants, Lubricants, grease, Mobil etc. must be available to continue the activities. Maintenance schedule must be available in place and authorized personnel to be assigned to perform the specific job.

Maintenance Logbook:

A maintenance record must be keep in a specific form and store the same at the custody of maintenance department and must be traceable as when required. Maintenance trend to be done in monthly/yearly basis to identify the machine breakdown frequency and corrective action.

You may use maintenance Logbook for better documentation activities. A maintenance logbook generally contains-

• Activities performed
• Clean date
• Calibration date
• Equipment use date
• Last maintenance date

Ten golden rules of GMP

GMP Golden Rule-9

“Design quality into the whole product lifecycle”

Personnel engage in Foods, Drugs, Cosmetics, Medical Device Manufacturing company to aware about the safety parameters of the end user[Patient]. Final stage of the products are tested by the Quality Control Personnel to identify/confirms its predetermine specifications only so quality to be ensure all the stage of manufacturing prior marketing in whole product lifecycle.

An inferior quality products tends to degrade in market in a short period of time loss its potency from marginal level fail to confirm its intended use. Patients didn’t receive the desired effect, unable to get early recovery cause unwanted health hazard. The patients start to believe that the product is not fit for him as its fail to satisfy his basic need.

The manufacturing step of the product need to effectively control so that a product can achieve its desired quality parameter through its life cycle.

Checking and Testing of Incoming Materials:

Check all the incoming materials during receiving and sort out the damaged container at specific area to prevent mix-up. Attached “Quarantine Label” to the good one and store it Quarantine area and inform Quality Control Department for Sampling and next activities after completion of Warehousing Activities.

Collect Approval from Quality Control department then use it for manufacturing activities. If the sampled products fail then segregate it and store it Reject Area for further decision[Destroy/Return]

A checklist may be develop to check the basic parameters of the incoming material will prevent the missing/discrepancy of the materials. Purchase order number, material description, quantity, accepted, conditionally accepted, or rejected materials etc. parameters may be add the Checklist for Inspection of Incoming materials.

Manufacturing Process Control

A series of procedure to be perform at the manufacturing of a specific products. Process and procedure must be clearly defined on the Batch Manufacturing Record and the personnel engage in manufacturing activities must be trained properly. A GDP[Good Documentation Practice] to be develop to practice on time record keeping.

Approved master record to be develop and available in a secure place. A batch record must be represent the master record and update document to be issued prior its intended use. All data must be input on specific area of the batch document. All actions must be record including all QMS[Quality Management System] related activities. Specially cleaning activities during/prior batch manufacturing must be record.  

Batch Packaging and Labelling Activities

Labeling is the vital part where maximum chance to mix-up of the products. Printed Label to be store securely especially in cut label/single label. Printed label to be store as per batch number/lot number to assure traceability.

Before starting a new batch, all the materials in previous batch must be remove from the packaging line. Follow the Line clearance procedure describe in Batch Manufacturing Record. Record the all activities during product change over and time interval to be define for In Process Control action.

Ten golden rules of GMP

GMP Golden Rule-10

“Perform regular audits”

Internal Audit/Self Inspections to be performed before a face any type of regulatory audit. External regulatory bodies Like UKMHRA [Medicines and Healthcare products Regulatory Agency], FDA [Food and Drug Administration], and TGA [Therapeutic Goods Association] will conduct audit. A self inspection checklist to be prepare and self inspections/Internal Audit to be perform at least once in a year, multiple times in a year may be the best practice.

Self-Audit Checklist

Written Procedures/Specification

Is approved procedure clearly defined the step by step instruction?

Do the procedure follow by the employee?

Is the procedure is up to date?

Is everyone is strictly adhere on the approved written procedure?

Skill

Is everyone is properly educated, trained, experienced in relation to their job?

Is everybody is performing their job right way?

Documentation and Recording

Is document is properly recorded on time?

Is everyone is using legible ink as required to fill the document?

Is all document/critical steps are checked/double checked?

Sanitation and Cleanliness

Is personal good hygiene is in practice?

Is gowning system is properly defined on production/Laboratory?

Is clean equipment’s/machine is stored properly?

Is regular health checkup is in practice?

Maintenance of the Workplace

Is scheduled preventive maintenance perform on time?

Is environment is controlled to minimize product contamination, mix-up, error etc.?

Is equipment logbook is properly maintained?

Quality Control

Is everyone is clear regarding quality control and quality assurance activities?

Is right batch number is declaring from QC department.

IS sampling is properly done & sampling SOP is up to date?

Is all machine calibration up to date?

Quality Assurance Are we concern about quality of our product? If satisfactory result didn’t get then take initiative to implement the same. All audit must be take positively, this the process where we can find our quality related observations and we can update the same.

This is all about the Ten golden rules of GMP which is mandatory to follow for successful operation of an ideal pharmaceuticals. The Ten golden rules of GMP define the ten different areas of a Pharmaceuticals company so this is very crucial to follow Ten golden rules of GMP to develop GMP culture of your firm.