The Validation Master Plan: Checklist & Regulation Summary

Thank you for the question! I hear this a lot actually... Over 15 years of validating pharmaceutical, biotechnical and medical device manufacturing and storage facilities, I have always worked under a high-level Validation Master Plan. Although a review of the Code of Federal Regulations does not yield a single mention of a “Validation Master Plan” in the actual regulations, it is mentioned in many peripheral documents (mentioned and linked below). Moreover, if you scan Warning Letters and Notice of Observations (483s) on the FDA's electronic reading room, you will find several mentions of a Validation Master Plan, which reveals that this document is an expectation of the FDA’s enforcement arm, often requested (usually expected) during an inspection.

Here’s an example from a Warning Letter dated March 15, 2013 - from the FDA's Office of Global Regulatory Operations and Policy Electronic Reading Room:

‘"Process Validation" SOP4.2.1 was revised to Rev. V to include requirements for a Master Validation Plan. A Master Validation Plan for process validation of [blanked out] machines has been completed and an Installation Qualification (IQ) protocol for [blank] machines has been released.'

Pharmaceutical, biotechnology, and medical device companies are faced with several similar challenges, so we come up with similar solutions. This is the basis of industry “Best Practices,” and in my mind, the basis of GMP. What is “Good Manufacturing Practice” if not just “Best Practices” that are specific to industries that create drugs, biologicals, and devices for human use? It follows that our solutions to similar challenges create collective industry standards against which we are all measured. A “Validation Master Plan” is now part of this.

In my experience, these plans describe, briefly and at a high level, the processes, and equipment that require validation, along with who is responsible for seeing it done. As far as expectations go, most inspectors want a summary document showing that you have some practices in place to ensure that you have identified the processes/equipment that you plan to validate, including in what order and by what priority, and who is responsible for execution. Most people would call this a VMP. They will expect a solution or answer to this question. If you find a better way to address it, I’m sure they won’t care if you call it something else. But in industry jargon, that’s a Validation Master Plan.

are if you call it something else.  But in industry jargon, that’s a Validation Master Plan.

The Pharmaceutical Inspection Co-operation Scheme has published a document called: “Recommendations on the Validation Master Plan, Installation, and Operational Qualification, Non-Sterile Process Validation/Cleaning Validation.” Although the recommendations are neither mandatory nor enforceable, they can be considered “appropriate.” This document, in combination with the PIC/s’s “Good Practices for Computerised Systems in Regulated ‘GxP’ Environments” briefly outlines a Validation Master plan as comprising the following:

• A list of all validation activities: prospective, concurrent,  and retrospective
• A list or copies of any parallel Validation Plans 
• References to existing documents such as Policy Documents, SOP's and Validation Protocols/Reports 
• A list of facility management who have agreed upon the master plan 
• A statement of the firm’s validation policy 
• General description of the scope of the operations of the firm which describes the facilities, processes, and products 
• The time and location of validation activities (ideally prioritized)
• A list of personnel responsible for the VMP, SOPs and protocols
• A list relevant validation reports and documents
• A list of personnel (roles) who provide approval
• Description of any tracking systems used for reference and review
• Validation training program plans - either the plans as appendices or references to the plans as separate documents

For your reference, here is a list of some other important validation documents for Pharmaceutical Manufacturing:

• ICH Quality Guidelines (QbD:  ICH Q8, Q9, and Q10)
• FDA GUIDANCE; PROCESS VALIDATION: GENERAL PRINCIPLES AND PRACTICES (2011 JAN, REVISION I)
• EMA Draft Guideline on Process Validation (March 29, 2012)
• Final Version of Annex 15 to the EU Guide to Qualification and Validation 

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