Guidelines for Preparation of Validation Master Plan (VMP)

Validation is among those activities that ensure the quality of pharmaceuticals during their manufacture. Validation guarantees that all equipment, systems, processes and facilities will be able to meet all pre-defined criteria.

When managing validation activities across an entire facility, there must be a defined and organized means to manage (oversee) these activities. At this point, a Validation Master Plan (VMP) is indispensable.

A VMP is a document that provides a high-level overview of validation activities that will take place within a pharmaceutical company. It defines the validation approach, responsibilities, schedule and strategy for the company. The authorities’ expectations that there will be a VMP as part of Good Manufacturing Practices creates the need to have a well-developed compliance document.

What is a Validation Master Plan (VMP)?

A Validation Master Plan (VMP) provides an overall description of the validation strategy and policy for a pharmaceutical facility.

The VMP provides the following information for validation activities and processes that are related to the following:

• Scope of validation
• Types of Systems and Equipment to be validated
• Methodology for validation activities
• Assigned responsibilities, timelines, and approvals

The VMP serves as the central reference document for all validation related activities within an organization.

Importance of a Validation Master Plan

When a VMP is in place, it provides a systematic, consistent and compliant approach to validation for the organization. A VMP will assist an organization to:

• Develop a structured validation program
• Clearly define the responsibilities of those who will perform validation activities
• Comply with all applicable regulatory requirements or expectations
• Maintain control of validation related activities
• Be prepared for audit and inspection by regulatory agencies

If a VMP is not established, validation activities may become difficult to manage, or vary in consistency.

Objectives of a VMP

The overall objective of the VMP is to provide a framework for validation. The following are the key objectives of the VMP:

• Define the validation policy
• Identify the systems that will require validation
• Define the methodology for validations
• Define the documentation that will be needed to support validations
• Identify who is responsible for performing validation activities and what their schedule is for validation activities

A well-developed VMP will coordinate validation activities across the entire facility.

Scope of the VMP

This area of the VMP document will define the boundary of the validation program and what will be validated. Common items include:

• Manufacturing processes
• HVAC
• Water systems
• Cleaning validation
• Computerized systems
• Analytical methods
• Utilities

The document should specify if it is for a single facility or multiple locations.

Regulatory Expectations for VMP

Regulators expect pharmaceutical companies to have an overall validation system that is thoroughly documented. Through a VMP, regulators will be able to see that an organization:
1. Is aware of validation requirements.
2. Uses a systematic approach.
3. Has control and oversight over validation life cycle activities.
The document should agree with good manufacturing practices (GMPs) and good risk management practices.

Key Sections of a Validation Master Plan

The Validation Master Plan (VMP) must consist of a logical and well-organized format. The key sections of the VMP are:

1. Introduction

This section contains general information regarding the proposed facility as well as the purpose of the validation master plan. It may contain:
Company Overview: An overview of the company, i.e. the company background
Manufacturing Activities: The description of manufacturing activities completed at the facility
Purpose of Document: The purpose of this document or validation master plan

2. Validation Policy

The Validation Policy is the way that the organization approaches validation in general. It describes:
Commitment to Compliance: The way that the organization is committed to compliance to current regulations
Validation Life Cycle Approach: The approach that the organization is taking to validating the life of the product
Risk Based Methodology: The way that the organization is assessing risk in order to validate the product
The sections in this document will reflect the management’s commitment to quality.

3. Organization and Responsibilities

Having clear responsibilities between the various individuals and functions of the organization is essential for successful validation. The VMP will include definitions of roles and responsibilities for:

• Quality Assurance
• Engineering
• Production
• Validation Team
• Microbiology and Quality Control

Having clear defined responsibilities between the various functions will assure accountability and clear communication and enable smooth coordination of activities.

4. Facility and System Description

This section will contain a description of the facility and the systems associated with the validation.
Examples:

• Manufacturing Area
• Utilities
• Equipment
• Clean Room

This section provides context to the performance of the validation.

5. Validation Approach

The VMP should describe how the activities will be completed. The most commonly used qualification stages are:

• Design Qualification (DQ)
• Installation Qualification (IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)

The approach must also be based upon an industry standard.

6. Validation Documentation

The VMP must identify validation documents utilized. Some examples of these documents are:

• Validation Protocols
• Validation Reports
• Standard Operating Procedures (SOPs)
• Risk Assessments
• Change Control Records

The VMP should also describe the method of controlling documents.

7. Risk Management Approach

Modern validation programs use a risk-based approach in determining how validation activities are prioritized. ICH Q9 Quality Risk Management states that Risk Assessment helps to prioritize validation activities based on the impact to product Quality and Patient Safety.
The VMP should address:

• The methodology used for risk assessment
• Criticality Assessment criteria
• Risk Assessment review methodology

8. Change Control and Revalidation

Changes may impact or change the validated condition of the system.
The VMP should include:

• Change Control Procedures
• Revalidation Triggers
• Impact Assessment requirements

To ensure the system remains in compliance throughout its lifecycle.

9. Calibration and Maintenance

Validation is directly related to both calibration and preventive maintenance.
The VMP should provide descriptions of:

• Calibration Program
• Maintenance schedules
• Responsibilities for equipment maintenance

Proper calibration and maintenance support validated performance.

10. Validation Schedule

A validation schedule (or matrix) provides an overview of planned validation activities.
This document includes:

• Equipment Qualification Timeline
• Process Validation Plans
• Revalidation Schedules

The information contained within these documents will help with planning and resource management.

Procedure for Preparation of a Validation Master Plan

The first step to prepare the VMP will be done in a systematic way.

Step 1: Gather Facility Information

The following information will be necessary for gathering during the VMP preparation:
- Manufacturing processes
- Equipment & Utilities
- Current Validation Status
- Organizational Structure
This information will be the starting point for the VMP.

Step 2: Define the Validation Scope

The scope of the validation should include the systems and processes that will need to be validated. Each of these systems/processes shall also be classified into groups according to:
- Criteria for criticality
- Product Impact
- Regulatory Impact

Step 3: Establish the Validation Strategy

Define how the qualification and validation activities will be performed and the methodology:
- Lifecycle Basis
- Risk Assessment Methodology
- Document Requirements

Step 4: Define Responsibilities

Indicate which department and personnel will be responsible for completing each of the validation activities.

Step 5: Prepare the Validation Matrix

Prepare the List of Systems with their Validation Status. This Validation matrix will indicate the:
- Qualification Stage
- Department Responsible For
- The Date of Planned Onset

Step 6: Prepare the VMP Document

Create the VMP Document as specified & required by company procedures, maintaining consistency throughout the document.

Step 7: Review and Approve

The draft VMP will be reviewed by the following departments: QA, Engineering & Production. Final approvals will be provided by a responsible individual.

Step 8: Implement and Periodically Review

Implement the VMP when approved, review it periodically and make updates due to:
- Changes to the facility
- New Equipment
- Changes in Regulations

Common Mistakes in VMP Preparation

Mistakes are frequently made by organizations when creating their VMPs (Vaccine Management Plans). The most common mistakes are:

• Content that is too generic
• No clear roles/responsibilities
• No stated validation scope
• Outdated or incorrect information
• Poor links to change controls

These types of issues will cause problems at inspection time.

Best Practices for an Effective VMP

Best practices for creating an effective VMP include:

• Use a risk-based approach when creating your VMP
• Keep It Simple (clear, concise)
• Update your VMP's regularly
• Coordinate the VMP with the actual operations of the facility
• Include representatives from all areas within an organization in developing and maintaining your VMP.

A practical and current VMP has greater value than an overly complicated VMP that is not used frequently.

Role of Quality Assurance in Validation Master Plan

The VMP is greatly supported by the role of Quality Assurance. Quality Assurance has several responsibilities regarding the VMP:

• Reviews the validation plan and strategy to update any new protocols or Systems.
• Approves the protocols and validation reports for the validation master plan and any subsequent activities/projects.
• Provides the initial analysis to ensure compliance with Good Manufacturing Practices (GMPs) and that the Validation Master Plan (VMP) is compliant with GMPs during approval of the protocols.
• Monitors change control/revalidation process for processes/products that have previously been validated.

Quality assurance ensures that the validation program remains valid.

Benefits of a Strong VMP

A well-prepared Validation Master Plan provides numerous benefits.
The main advantages are:

• Increased control of validation activities
• Improved readiness for regulatory compliance
• Easier and clearer two-way communication between departments
• Decreased risk of regulatory problems
• Improved documentation management.

The Validation Master Plan is the centerpiece of the validation program.

Pharmaceutical manufacturing requires a Validation Master Plan (VMP) which provides a framework to support all of its validation processes. This framework will ensure that every validation activity performed on the systems, equipment, utilities and processes is done so in a consistent and scientific manner.

By adhering to VMP guidelines and keeping the VMP current, pharmaceutical manufacturers can enhance compliance, enhance operational effectiveness and ensure quality of products produced by the company. A sound VMP is not just an expectation of regulatory authorities in today’s regulated world; it serves as an essential component of effective quality management.

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