Validation

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”.

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.