[ 1 ]CONFIDENTIAL

Understand Critical Components of a

Validation Master Plan

Jorge A. Cordero-Monroig; BSChE, MBA-GM

Validation Site Leader

B+L Greenville Solutions Plant

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Agenda:

Introduction

Definition and Responsibilities

Regulatory Requirements

VMP Requirements

Interactive Exercise

Using real life examples, participants study how to define critical components for a Validation Master Plan

Q&A

Understand Critical Components of a Validation Master Plan

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Introduction

The Validation Master Plan (VMP) summarizes the what, why, when, and how equipment and systems are validated and qualified in your facility.

Provides a list of systems / equipment that require validation during the year and present the validation program and philosophy in one document.

The VMP is the primary document showed to the FDA and any other regulatory agency to present the site validation program. Even though is not a regulatory requirement in USA, it is for EU.

The VMP provides visibility of the validation group work load and help to align business goals with validation requirements.

Justify resources and budget needs to perform the plan

Keep the validation recourse focused in the ultimate goal, VMP completion.

Understand Critical Components of a Validation Master Plan

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Definitions and Responsibilities

Validation Master Plan (VMP) is a living document that identify critical elements of the validation program at the site including details of current validation and plans for future validation.

Validation strategy (VS) is the document that provides a description of a particular project and summarize in high level the activities and documents required on the project.

Validation is the process that assures that a system, service, or product meets the intended purpose. Validations are typically a combination of several qualifications

E.g. Manufacturing line validation, product validation, Calibration management Software, etc…

Revalidation is a repeat of some or all of the process validation to as a result of a process failure, adverse trend, major process change, etc.

Understand Critical Components of a Validation Master Plan

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Definitions and Responsibilities

Qualification is the process that demonstrates that an equipment has been installed properly and works as intended meeting the expected acceptance criteria.

E.g. filler, capper, labeler, cartoner, etc…

Requalification is a repeat of some or all of the process validation to provide an assurance that the process continues to perform as intended.

Author (i.e. Quality, Validation, SQA, etc.) - Develop VMP and perform periodic updates.

Approvers ( i.e. Quality, Operations, Engineering, Site Leader, etc.) - Approve VMP by confirming information is accurate and meets site objectives, schedules and plans are in compliance with procedures and policies.

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Regulatory Requirements and Guidelines

API:

ICH Q7 12.1 “The company’s overall policy, intentions, and approach to validation including the validation of production processes, cleaning procedures, analytical methods, in-process control test procedures, computerized systems, and persons responsible for design, review, approval and documentation of each validation phase, should be documented”.

12.12 “Validation should extend to those operations determined to be critical to be quality and purity of the API”.

Pharma (Medicinal Products)

EU Annex15 Qualification and Validation 1.4 “The key elements of the site qualification and validation programme should be clearly defined and documented in a validation master plan (VMP) or equivalent document”.

Understand Critical Components of a Validation Master Plan

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Regulatory Requirements

Pharma (Medicinal Products)

PIC/S - Pharmaceutical Inspection Co-operation Scheme has a whole section, section 4, about Validation Master Plan

WHO – World Health Organization Supplementary Guidelines on Good Manufacturing Practices (GMP) Validation: This guideline focuses mainly on the overall concept of validation and is intended as a basic guide for use by GMP inspectors and manufacturers. Section 8 summarize minimum key requirements on a VMP.

Health Canada – Validation Documentation Requirements and Responsibilities for Drug Fabricators, Packagers / Labelers, Testers, Distributors and Importers: “At the site of fabricators, packagers/labelers and testers, inspectors will evaluate the validation master plan, the qualification of systems and equipment and the validation of cleaning and test methods, as applicable”. http://hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/validation/req_resp-exig_resp_tc-tm-eng.php

Understand Critical Components of a Validation Master Plan

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Regulatory Requirements

Pharma (Medicinal Products)

Health Canada – Validation Guidelines for Pharmaceutical Dosage Forms (GUI-0029): “A validation master plan is a document that summarizes the company's overall philosophy, intentions and approaches to be used for establishing performance adequacy. The validation master plan should be agreed upon by management”. http://hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/validation/gui_29-eng.php#a418

USA does not require in specific validation master plan but is expected by the FDA.

Understand Critical Components of a Validation Master Plan

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Warning Letters and 483

Thermedx LLC from 04/08/15

Understand Critical Components of a Validation Master Plan

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483 to Ben Venue Laboratories, Inc.

Understand Critical Components of a Validation Master Plan

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VMP Requirements

Document format

Introduction – Establish the purpose of the document, overall approach and intentions of validation activities. General statement for VMP rules such as flexibility and update frequency among others.

Scope – Define boundaries for the VMP such as areas covered, type of validation acceptable, and what is not covered under the VMP such as enterprise software, other facilities and non-GMP systems/equipment.

Site Description – Overall description of the facility, processes and product manufactured. Also provide a process flow description, utilities required and their capacity.

Supporting Quality Systems – Provide all quality system that affect validation such as Preventive Maintenance, Metrology, training, Manufacturing cleaning and sanitization, Software Development life cycle, Change control and Non-conformance among others. Refer to applicable SOPs, as applicable.

Understand Critical Components of a Validation Master Plan

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VMP Requirements (Cont.)

Document format (Cont.)

Key Definitions – It is important define concept, abbreviations, and acronym use through the document. This avoid misunderstanding and misconceptions (There is only one 1st impression).

Roles and Responsibilities - It is important define the team (Functional areas) and the responsibilities for each department involved, not only for the person that is reading the plan but to be successful in the VMP implementation.

Validation Approach – Define validation strategies such as risk based approach and traditional approach, and any special guidance per type of validation activity (equipment, process, cleaning, software, control system, labs, etc..). Define rules for impact and criticality assessment.

Validation Methodology and Requirements – How the individual validation methodology and requirements will be addressed. Typically refers to the validation protocol SOP.

Understand Critical Components of a Validation Master Plan

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VMP Requirements (Cont.)

Document format (Cont.)

Revalidation – Establish rules for revalidation, annual revalidation and for cause revalidations.

Decommissioning – Establish minimum requirements for retirement or disposal of qualified equipment or systems such as removal of preventive maintenance and metrology systems and SOP updates among others.

Validation Activities, Plans and Milestone – This section defines the rules of how the validation activities will be presented and summarizes the results and status of the previous year validation activities and the plan for the current year validation activities.

Resources – This section define requirements for personnel (internal or external) performing validation activities such as background, experience and training. Also, define any exclusion for previous training such as subject matter expert reviewing technical data.

References – Ensure that only applicable reference were included.

Understand Critical Components of a Validation Master Plan

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VMP Requirements

In addition to general VMP template requirements, there are some critical components that will help to keep the VMP organized and easy to follow the validation activities completion.

Critical Components:

Impact and Criticality Assessment by system and areas: Equipment, Control Systems, Software, facility, processes, product, cleaning, test method, among others.

Provide Validation Matrix by area: All the validated equipment/system in bulk, filling, packaging, labs, etc…, with type identification and description of the equipment/system.

Divide the validation activities by type: requalification, reassessments, remediation projects, capital projects, etc…

Understand Critical Components of a Validation Master Plan

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Understand Critical Components of a Validation Master Plan

VMP Requirements

Critical Components (Cont.):

Divide the validation activities by period: Previous year update and current year plan

Provide a project milestone: Type of project, validation description and high level milestone schedule. The purpose is not to be precise but understand what activities will be performed during the year and plan accordingly.

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Understand Critical Components of a Validation Master Plan

In addition to the site Validation Master Plan the following validation plan are recommended:

Aseptic Process Simulation Validation Master Plan (Media Fill Master Plan)

Cleaning Validation Master Plan

Software Validation Master Plan

These plans are not required for any agency but has been recommended by FDA and NSAI (National Standard Authority of Ireland) in previous audits in our facility.

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Summary

The VMP is a good practice that helps to present the validation program and philosophy to auditors, upper management, and help to provide clear expectations to the validation group.

Even though is not a regulatory requirement in USA, it is for Health Canada, EU and recommended by WHO and PIC/S for Pharma product and ICH Q7 require an overall policy and intention for validation.

Critical Components in a VMP are but not limited to:

Impact and Criticality Assessment

Validation Matrix

Validation Activities (Requalification/Capital Projects/etc…)

Validation updates (previous year validation update)

Validation plan (current year validation plan)

Project milestone

Understand Critical Components of a Validation Master Plan

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Interactive Exercise:

Participants will develop a Validation Master Plan outline emphasizing in overall strategy for the site and the critical components:

Manufacturing sites:

Biopharma for recombination protein not finish product

Parenteral Facility – Raw materials are mixed and product compounded, filled and package.

Manufacturing of Contact Lens including packaging

Understand Critical Components of a Validation Master Plan

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Questions and Answers?

Understand Critical Components of a Validation Master Plan