Master Validation Plan SOP and Approv al Templatepharmacentral.in/.../Master-Validation-Plan_SOP-and-Approval-Template.pdf · Master Validation Plan SOP 1.0 Purpose This standard

Master Validation Plan SOP and Approval Template

Master alidation PlanApproval Form

Table of Contents –– Master Validation Plan Approval Form

Master Validation Plan Approval Form...................................................................................................................A11.0 Purpose............................................................................................................................................................A22.0 Scope...............................................................................................................................................................A23.0 Definitions and Acronyms................................................................................................................................A24.0 Plant Operating Description.............................................................................................................................A3

4.1 Plant Layout.........................................................................................................................................A34.2 Process Flow.......................................................................................................................................A4

5.0 Project Phases / Facilities, Utilities & Equipment to be Qualified....................................................................A45.1 Facilities and Utilities............................................................................................................................A45.2 Process Equipment..............................................................................................................................A45.3 Packaging Equipment..........................................................................................................................A4

6.0 Qualification Requirements and Approach......................................................................................................A56.1 Facilities / Utilities Qualification Requirements.......................................................................................A56.2 Process Equipment Validation Requirements.......................................................................................A56.3 Packaging Equipment Qualification Requirements................................................................................A5

7.0 Product Validation Requirements....................................................................................................................A67.1 Process Validation Requirements & Rationale.......................................................................................A67.2 Packaging Validation Requirements & Rationale...................................................................................A7

8.0 Cleaning and Sanitizing Validation..................................................................................................................A88.1 Cleaning Validation Requirements........................................................................................................A88.2 Sanitization Validation Requirements....................................................................................................A9

9.0 Software Validation Requirements.................................................................................................................A109.1 Facilities / Utilities Qualification Requirements.....................................................................................A10

10.0 Project MVP Production Lot Release Requirements...................................................................................A1011.0 Schedule......................................................................................................................................................A1112.0 References...................................................................................................................................................A1113.0 Roles and Responsibilities...........................................................................................................................A1214.0 Revision History...........................................................................................................................................A12

Master Validation Approval Form

Electronic Archival Number:

Approved By:

Printed Name:

Signature: Date:

*Engineering –

Printed Name:

Signature: Date:

*Research & Development –

Printed Name:

Signature: Date:

*Project Manager –

Printed Name:

Signature: Date:

Quality Assurance / Compliance –

Printed Name:

Signature: Date:

*optional

Printed Name:

Signature: Date:

Manufacturing –

A1

1.0 Purpose

2.0 Scope

3.0 Definitions and Acronyms

Acronym Definition

A2

4.0 Plant Operating Description

4.1 Plant Layout

A3

4.2 Process Flow

5.0 Project Phases / Facilities, Utilities & Equipment to be Qualified

5.1 Facilities and Utilities

5.2 Process Equipment

5.3 Packaging Equipment

A4

6.0 Qualification Requirements and Approach

6.1 Facilities / Utilities Qualification Requirements

Table 1: Qualification Requirements – Facility/Utilities

6.2 Process Equipment Validation Requirements

Table 2: Qualification Requirements – Process Equipment

6.3 Packaging Equipment Qualification Requirements

Building / System Name Required Qualification

Building / System Name Required Qualification

A5

7.0 Product Validation Requirements

7.1 Process Validation Requirements & Rationale

Table 3: Process Validation Requirements

Product Formulation Number and Description

Product Family Formula Number –– Product Description Validation Requirement

The validation protocols will also define the batch size, number of batches, sampling requirements, which may require additional sample points and/or additional tests be performed.

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7.2 Packaging Validation Requirements & Rationale

Table 4: Process Validation Requirements

Packaging Number and Description

Product Family Packaging / SKU Product Description Validation Requirement

The validation protocols will also define the batch size, number of batches, sampling requirements, which may require additional sample points and/or additional tests be performed.

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8.0 Cleaning and Sanitizing Validation

8.1 Cleaning Validation Requirements

Product Family Description

A8

Table 6: Cleaning Validation Requirements

Product Family Worst Case Product(s) Procedure Cleaning SOP/SW

Numbers Validation

Requirements

8.2 Sanitization Validation Requirements

Table 7: Sanitizing Validation Requirements

Equipment Sanitizing Document Sanitizing SOP Validation Requirements

A9

9.0 Software Validation Requirements

9.1 Facilities / Utilities Qualification Requirements

Table 8: Qualification Requirements – Facility/Utilities

System Name System Purpose Required Validation

10.0 Project MVP Production Lot Release Requirements

A10

Table 9: Production Lot Release Requirements

Product Formulation Number and Description Lot Release Requirements

Formula Number /

Number of Batches Product Description / Family Validation Closure

11.0 Schedule

12.0 References

A11

13.0 Roles and Responsibilities

Table 10: Roles and Responsibilities

Department Responsibilities

14.0 Revision History

Reason For Change Date Revision #

A12

Master alidationSOP Form

Master Validation Plan SOP

1.0 Purpose............................................................................................................................................B12.0 Scope...............................................................................................................................................B13.0 Definitions and Acronyms................................................................................................................B14.0 Procedure.........................................................................................................................................B4

4.1 Purpose...............................................................................................................................B44.2 Scope..................................................................................................................................B44.3 Definitions & Acronyms.......................................................................................................B44.4 Plant Operating Description................................................................................................B54.5 Plant Layout........................................................................................................................B54.6 Process Flow.......................................................................................................................B5

5.0 Master Validation Plan Elements.....................................................................................................B65.1 Facilities, Warehousing & Storage......................................................................................B65.2 Utilities.................................................................................................................................B65.3 Production Equipment.........................................................................................................B75.4 Product/Process Validation.................................................................................................B75.5 Cleaning Validation.............................................................................................................B85.6 Sanitizing Validation............................................................................................................B85.7 Software Validation.............................................................................................................B9

6.0 Additional MVP Elements.................................................................................................................B96.1 Signature List......................................................................................................................B96.2 Schedule & Resourcing (Optional) .....................................................................................B96.3 Project MVP Production Lot Release Requirements ........................................................B106.4 References .......................................................................................................................B106.5 Roles & Responsibilities ...................................................................................................B106.6 Revision History................................................................................................................B10

Table of Contents –– Master Validation Plan SOP Form


1.0 Purpose This standard work describes the rationale and methods used to draft and maintain

Master Validation Plans (MVPs) at . This Standard Work outlines the

process, content and rationale for facility and project MVP documents.

2.0 Scope This standard work provides guidance for Master Validation Plans utilized to document the

validation approach, requirements and justification for the qualification and validation of a facility

or project, including but not limited to:

• MVP Purpose and Scope

• Building and Facility Layout

• Process Description and Flow

• Qualification/Validation of:

o Facility & Utilities

o Production Equipment

o Manufacturing Processes

o Cleaning & Sanitizing

o Software Systems

• Supporting GMP quality systems to maintain a validated state


Acronym Definition

Master Validation Plan Documented plan for qualification of a facility/project,

which identifies layout of the operation, associated

equipment, utilities and systems to be validated. Provides

extent of qualification/validation activities via protocols,

SOPs, acceptance criteria & responsibilities.

Validation Documented evidence that processes, procedures, and

equipment consistently lead to predetermined

expectations, specifications and quality attributes.

Collection and evaluation of data from process design stage

through commercial production, which establishes

scientific evidence that a process is capable of consistently

delivering quality products.

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Validation Protocol A written plan stating how validation efforts will be

conducted. Includes test parameters, equipment/product

characteristics, and acceptance criteria to provide

documented evidence that a system, process or

equipment meets specifications or intended use.

Acceptance Criteria Specified indicators or measures employed in assessing the

ability of a component, structure, or system to perform its

intended function.

Equipment Qualification Documented evidence demonstrating that equipment is

designed/selected adequately, installed properly and

operates/performs for its intended purpose. Adequate

controls are confirmed, and the equipment is shown to be

in a state of control

Facility Qualification Documented evidence demonstrating that a production

facility is designed, selected and constructed adequately to

support manufacturing and not adulterate the product.

Utility Qualification Documented evidence demonstrating that a production

utility is designed/selected adequately and

operates/performs for its intended purpose to support

manufacturing and not adulterate the product.

Installation Qualification

(IQ)

Documented verification that all aspects of a system,

facility, utility or equipment that can affect product quality

are installed according to specifications and design criteria.

Operation Qualification

(OQ)

Documented verification that all aspects and functions of a

system, facility, utility or equipment that can affect

product quality operate properly within all anticipated

operating ranges as required by the process, capability,

procedures and design specification.

Performance

Qualification (PQ)

Documented verification that all aspects of a system,

facility, utility or equipment that can affect product quality

produce the required output over an extended period

under typical operating conditions and interferences.

Process Validation (PV) Documented evidence intended to examine the chemical

characteristics of the formula during the entire production

process, to ensure it meets specified strength, potency,


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purity and/or quality attributes. All operations that may

impact product characteristics must be examined.

Cleaning Validation (CV) Documented evidence which provides a high degree of

assurance that an approved cleaning procedure will

remove from equipment product and cleansers below

acceptable limits, such that it is suitable for processing a

product.

Sanitizing Validation Documented evidence which provides a high degree of

assurance that an approved sanitization procedure will

reduce microbes and provide equipment contact surface

bioburden reduction below acceptable limits, such that it

is suitable for processing a product.

Critical Equipment Equipment that has direct product contact/impact or

ensures proper labeling and traceability of the product.

Equipment which can affect the strength, identity, purity,

potency, quality and/or quality of the product.

Software Validation Confirmation by examination and provision of objective

evidence that software specifications conform to user

needs and intended uses, and that the particular

requirements implemented through the software can be

consistently fulfilled.

Critical Process

Parameter (CPP)

A process parameter that must be controlled within

predefined limits to ensure the product meets its pre-

defined quality attributes

Critical Quality Attribute

(CQA)

A CQA is a physical, chemical, biological, or microbiological

property or characteristic that should be within an

appropriate limit, range, or distribution to ensure the

desired product quality.


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4.0 Procedure

4.1 Purpose

4.2 Scope



B4

4.4 Plant Operating Description

4.5 Plant Layout

4.6 Process Flow


B5

5.0 Master Validation Plan Elements

5.1 Facilities, Warehousing & Storage

5.2 Utilities


B6

5.3 Production Equipment

5.4 Product/Process Validation


B7

5.5 Cleaning Validation

5.6 Sanitizing Validation


B8

5.7 Software Validation

6.0 Additional MVP Elements

6.1 Signature List

6.2 Schedule & Resourcing (Optional)


B9

6.3 Project MVP Production Lot Release Requirements

6.4 References

6.5 Roles & Responsibilities

6.6 Revision History


B10

alidation Master Plan

Abstract

This discussion addresses basic considerations associated with the topic of the Validation Master Plan (VMP). While VMP is a well-known term, its use, structure, and content is not consistent across organizations and in the industry. Organizations may utilize VMP very differently in their respective sites. Further, alternate VMP terminology may be used in organizations.

This discussion identifies four different VMP types commonly used in pharma and related industries. These include site documents, function documents, major project documents, and single project documents. Different terminology, content, and applications in VMPs lead to confusion. Sites should consider developing a procedure that defines VMP and all other terms used at their site with consideration for industry and regulatory standards. Such a procedure will unify terminology used by personnel in the respective areas of the site and help to clarify communications.

The site Validation Approval Committee (VAC) has a vital responsibility to the manufacturing site and is critical to the success of the site validation program. Whatever structure and content, the site VAC should consider the VMP as their document. The VAC should consider themselves to be a surrogate FDA (or other regulatory agency) auditor when they are reviewing VMP. Clarifying and unifying VMP terminology used at a site should be a joint responsibility of the VMP and the site validation function. The terminology, content, and applications of VMP should be consistent with industry and regulatory norms and expectations.

Validation Master Plan (VMP)Part 1: Differences in Terminology, Content & Applications

By: Paula L. Pluta

Bonus Article: Re-purposed from Journal of Validation Technology, Vol. 24, Issue 1

A division of UBM Americas Published on IVT Network (http://www.ivtnetwork.com)C1

1. VMP – Site document. This document comprisesall fundamental information about the site. It includesspecific individual sections about functions at the site.

2. VMP – Function document. This document com-prises all fundamental information about a specificfunction at the site. A VMP function document isone of the sections in the above-described VMP sitedocument

The above two categories may be considered validation overview documents describing the general validation program at a site.

3. VMP -- Major project document. This documentcomprises all information about a specific majorvalidation project at the site such as a new facility ad-dition with multiple validation activities and protocols.

4. VMP -- Single project document. This documentcomprises all information about a specific individualvalidation project at the site. This document is oneof the sections in the above-described VMP majorproject document

Documents #3 and #4 are specific validation project documents containing project details.

The above four categories are the most widely used terms associated with VMP. There are numerous lesser-used terms also used with-in organizations to describe equivalent informa-tion. A recent industry meeting with representa-tion from pharma, medical devices, nutritionals, blood processing, and other validation-com-pliant regulated industries from USA, Canada, Puerto Rico, and other global sites reported a variety of VMP and associated terminology.

In addition to VMP, other terms included validation plan, qualification master plan, qual-ification plan, project plan, validation project master plan, qualification project master plan, validation approach, qualification approach, validation strategy, qualification strategy, proj-ect strategy, project approach, and many other terms. Some organizations do not have a specif-ic VMP, but simply list validation documents in a spreadsheet.

Other terms along with common asso-ciated terms such as Factory Acceptance Test (FAT), Site Acceptance test (SAT), Installation Qualification (IQ), Operational Qualification (OQ), Process Qualification (PQ), combination terms

IntroductionValidation Master Plan (VMP) is a universally

known term. Essentially all pharmaceutical and related industry manufacturing sites have some type of VMP in their facility. Despite widespread awareness of VMP, there is great diversity re-garding its structure, content, and application. Meetings with validation professionals at phar-maceutical meetings indicate much different understandings of the VMP -- the VMP to cer-tain individuals is not the same as the VMP to others. The more people involved, the more companies represented, the more industries represented, and the geographic diversity of attendees all contribute to increasing confusion when attempting to discuss VMP structure, content, and application. Validation managers comment about frustration with inconsistent terms used between various functional groups even within their facilities. VMP is widely known in general, but specifics are not universally con-sistent.

This discussion identifies basic categorizes of VMP as presented at pharma meetings, in published papers, and in group and personal discussions. Four different types of documents, all of which are termed VMP, are addressed. Other less frequently used terms for VMP are also described.

VMP – Terminology & StructureA lack of uniformity in VMP terminology

and structure is a definite impediment in discus-sions about VMP. Validation managers attend-ing VMP discussions at pharma meetings often leave more confused after attending a VMP session than before it started because of differ-ences in terminology and structure. A participant may describe their VMP as a comprehensive site document while other participants understand VMP to be the validation approach for a specific project. The more participants in the discussion, the greater the diversity in opinions, and the greater the confusion.

This discussion addresses four VMP approaches experienced by the author in pre-sentations and discussions at pharma meetings and in written submissions to the Journal. These include the following:

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such as IOQ and IOPQ, and similar terms make for potentially great confusion, both within the site and with external auditors.

Sites should consider developing a docu-mented and approved procedure defining terms used at their site. Such procedure will unify terminology used by personnel in the respec-tive areas of the site. When developing such a procedure, industry and regulatory norms and expectations should be considered.

This document will further serve to clarify terms when the site is audited by regulatory or other outside auditors. Preparing a lexicon will also obviate the need to make changes in nu-merous site documents such as the FDA change to Process Performance Qualification (PPQ) from process validation (PV). Confusion with inconsistencies in global regulatory documents will be minimized with an approved site lexicon.

VMP – Site DocumentThe VMP site document is one of the

most common types of VMP. This document comprises all fundamental validation information about the site. It includes individual sections about specific validation functions at the site. For example, specific sections with describe the facility design, equipment program, HVAC pro-gram, cleaning program, manufacturing process program, and so on. All these sections are con-tained in a single major document or electronic file under the responsibility of the site Validation / Quality function.

The site VMP is a critical document. Early review of the VMP by regulatory audi-tors often sets the tone for the remaining days of inspection. A thorough and well-designed VMP demonstrates a well-run facility. A current / recently-updated VMP further conveys the message that the VMP is valued and useful to the organization. A site that expends good effort in the design and maintenance of the VMP will reap benefits both internally and with external auditions. A site VMP may be divided into indi-vidual chapters such as the following:

� VMP Introduction, Scope, and Objectives� Responsibilities� Site Facility Overview and Design� General Validation / Qualification Approach

� Facility Heating, Ventilation, and Air Conditioning� Utilities� Equipment� Computer Systems� Products and Manufacturing Processes� Cleaning� Analytical Methods� Appendix

� Projects – Current and Completed� Facility Heating, Ventilation, and Air Conditioning (HVAC) Qualifications� Utilities Qualifications� Equipment Qualifications� Computer Systems Qualifications� Products and Manufacturing Process Validations� Cleaning Validations� Analytical Methods Validation

ProjectsSome companies describe validation-re-

lated projects in the VMP. Other companies prefer not to list ongoing project work. Auditors have expressed that a documented prior com-mitment to an ongoing project may eliminate it as a regulatory citation, i.e., the site is aware of the deficiency and is addressing the problem.

Appendix Reference List of Validations & QualificationsThis section lists the current complete

validation for each equipment, process, clean-ing, and so on. When an auditor asks for the val-idation supporting a specific topic, this section provides the reference and facilitates access to approved documentation.

VMP UpdateThe VMP site document must be updated

to retain its usability. The updating frequency depends on the frequency of external audits. Quarterly updates are done by many validation managers.

VMP – Function DocumentThe VMP function document comprises

all fundamental information about a specific validation function at the site. This document is one of the sections in the above-described VMP site document. For example, a manufacturing process VMP would include a list of all products manufactured at the site, product groupings, all SOPs associated with product manufacturing, references to all process validation, and other relevant information.

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This information is contained in a single major document or electronic file under theresponsibility of the site manufacturing process or product technical support function. A site would thus have multiple VMP function docu-ments dispersed among the respective depart-ments at the site. A function VMP should con-tain all relevant validation information associated with the function. For example, the content of cleaning validation function VMP may include the following:

� Strategy and approach� Comprehensive lifecycle approach, Science and technical basis, Risk analysis, variation identification and control� Policies� Approved procedures� Supporting information with referencedocumentation� Product cleaning matrix� Equivalent equipment� Equipment surface area calculations� Residue calculations� Technical reports references� Templates� Validation commitments and timelines� Planned validations� Improvement projects and timelines� Cleaning validation references

ification activities for the specific project. The responsibility for this document would rest with the site project manager for the specific project. This VMP as described above would be a major document likely comprising hundreds of pages.

VMP – Single Project DocumentThe VMP single project document com-

prises all information about a specific individual validation project at the site. This document is one of the sections in the above-described VMP major project document for a given validation; for example, the validation plan for extensions to the Purified Water System. Literally every validation project should have a plan – entitled validation master plan, validation plan, validation approach, validation strategy, or other terms.

This plan would describe:� Statement of the validation� What was being validated� Why needed� Approach to accomplish validation� Details of work to accomplish validation� Description of strategy and approach� Risk analysis� References supporting validation� Protocols� Approvals

The responsibility for this document would rest with the individual project leader for the specific project.

Validation Approval CommitteeManufacturing sites commonly have a

Validation Approval Committee (VAC) that re-views and approves validation protocols, vali-dation results, process and equipment changes, and related documentation including VMP. The VAC is a multidisciplinary group with represen-tation from Quality Assurance, Manufacturing Operations, Engineering, Product Technical Support, Analytical, Microbiology, Regulatory Affairs, Validation, and other groups as needed. The VAC is a critical partner with the validation function in development, review, and approval of a VMP. The role of the VAC is extremely import-ant. The site validation function depends on the judgment and decisions of the VAC.

VMP – Major Project DocumentAnother common type of VMP document

is the major product VMP document. The VMP major project document comprises all informa-tion about a specific major validation project at the site. This is significantly different than the aforementioned site or function documents in that it describes the respective validations including individual protocols and results for the major project.

For example, a new facility might include utilities qualification, HVAC qualification, water system qualification, equipment qualification, manufacturing process validation, cleaning validation of products manufactured in the new facility, and so on – all of which would be includ-ed in a single major document. This document would ultimately contain the specific validation plan, protocol, and results for utilities, HVAC, Purified Water, equipment, manufacturing pro-cesses, cleaning, and other validation / qual-

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Final Thoughts

The VAC should consider themselves to be a surrogate FDA (or other regulatory agency) auditor. Whatever structure and content, the site VAC should consider the VMP as their docu-ment. Clarifying and unifying VMP terminology used at a site should be a joint responsibility of the VMP and the validation function. VMP and other validation documents should be designed to meeting industry and regulatory standardsand expectations.

The above discussion describes two major categories of Validation Master Plans. The first and more commonly used category is as an overview document containing fundamental information about a site validation program. This may be structured as a single document containing information on all functions, or may be separated as individual function documents. The second category describes specific validation project plans including protocols and results for either major validation projects or individual validation projects. These respective different use of the same VMP terminology causes confusion when individuals attempt to discuss VMP topics.

Sites should consider clarifying VMP terminology, content, and applications, and then developing a procedure that defines terms used at their site. Such procedure will unify terminology used by personnel at the site. It will further serve to clarify terms when the site is audited by regulatory or other outside auditors. Preparing a lexicon will also obviate the need to make changes in numerous site documents such as the recent FDA change to Process Performance Qualification (PPQ) change from PV when new terminology is implemented. Confusion with inconsistencies in global regulatory documents is minimized with a site lexicon.

The VAC has a key responsibility in the site validation program. The VAC should consider themselves to be a surrogate FDA auditor when they are reviewing validation documents including VMP. They represent the last review of a document before FDA or other auditors review documentation. While the validation group leads

the validation program at the manufacturingsite, the program will not be successful without the competence, responsibility, maturity, and full commitment of the VAC. The site validation group and the VAC should jointly lead a site initiative to clarify VMP terminology, content, and application in the site, and ensure that VMP is consistent with industry and regulatory norms and expectations.

ReferencesFDA. Guidance for Industry. Process Validation. General Principles and Practices. January 2011.

Source URLhttp://www.ivtnetwork.com/article/validation-master-plan-vmp-part-1-dif-ferences-terminologycontent-and-applications

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