VALIDATION MASTER PLAN (VMP) DEVELOPMENT1).pdf · • Stage 3 documents –Continued Process Verification ... 4. Design space 5. ... Study OOS and OOT (Out of Trend)

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VALIDATION MASTER PLAN (VMP)

DEVELOPMENT

Paul L. Pluta, PhD

Journal of Validation Technology

Journal of GXP Compliance

University of Illinois at Chicago (UIC) College of Pharmacy

Chicago, IL, USA

OBJECTIVES AND OUTLINE

• Validation documentation hierarchy

• Types of Validation Master Plans

• Successful practices

• Problems and solutions

PARTICIPATION INVITED

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VALIDATION DOCUMENTS

Validation Policy

• Policy and corporate templates

VALIDATION MASTER PLAN (VMP)

• COMPILATION OF INDIVIDUAL FUNCTION VMP

VALIDATION PROJECT MASTER PLAN

Validation Lifecycle Documents

• Stage 1 documents – Process Design

• Stage 2 documents – Process Qualification

– VALIDATION PLAN

– Validation Protocol(s)

– Engineering Studies

– Others

– Validation Results / Report

• Stage 3 documents – Continued Process Verification

– PQ requirements

– Routine monitoring

• Associated validation and qualification

• Other associated documents3

IMPORTANCE OF VALIDATION DOCUMENTS

• Validation documents always requested in regulatory

audits – especiallyVMP!

• Validation documentation is retained forever

• Documents reviewed long after people are gone

– Documents must “stand alone”

• FDA auditors often focus on documentation – VMP and

specific validation documents often requested ahead of

audit

• Early documents (Initiation, Plan, Protocol) reviewed

when project is in-progress or not completed

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IMPORTANCE OF VALIDATION DOCUMENTS –

NEW PROCESS VALIDATION GUIDANCE

FDA Process Validation Guidance has greatly expanded

the scope of validation

• Lifecycle approach – documents from development through

commercialization. Traditional validation documents (protocol and

results) relatively less important

• New expectations for traditional validation documents

Validation organizations should lead sites in transition to

lifecycle approach

• Multiple groups at site must now contribute to process validation

lifecycle approach

Lifecycle approach being applied to all validation and

qualification (equipment, facilities, cleaning, etc.)

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TERMINOLOGY: PROCESS VALIDATION

Process Validation – Process Qualification -- PPQ

Qualification Qualification

Equipment #1 HVAC

Utilities

Equipment #2 Facilities

Computers

Equipment #3

Analytical methods validation

Cleaning process validation

Packaging process validation

Process is validated

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UO #1

UO #2

UO #3

FDA PROCESS VALIDATION GUIDANCE (2011)

Definition: Collection and evaluation of data, from the

process design stage throughout commercial production,

which establishes scientific evidence that a process is

capable of consistently delivering quality products.

Process validation involves a series of activities over the

lifecycle of the product and process.

Three stages of activities:

• Stage 1 – Process Design – Development and scale-up activities

• Stage 2 – Process Qualification – Reproducible manufacturing

• Stage 3 – Continued Process Verification – Routine manufacturing

STAGE 1 AND STAGE 3 EMPHASIS – NEW PARADIGM

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FDA PROCESS VALIDATION GUIDANCE

DOCUMENTATION FOCUS

“Before …commercial distribution to consumers, a manufacturer should

have gained a high degree of assurance in the performance of the manufacturing process…consistently produce …”

Manufacturers should:

• Understand the sources of variation

• Detect the presence and degree of variation

• Understand the impact of variation on the process and product

attributes

• Control the variation in a manner commensurate with risk to process

and product.”

“…to justify commercial distribution of the product.”

“… use ongoing programs to collect and analyze product and process

data … state if control of the process.”

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FDA PROCESS VALIDATION GUIDANCE

DOCUMENTATION FOCUS

Good project management and good archiving to capture

scientific knowledge.

Enhance accessibility of information later in lifecycle.

Integrated team approach: Process engineering, industrial

pharmacy, analytical chemistry, microbiology, statistics,

manufacturing, and quality assurance.

Scientific studies throughout the product lifecycle planned,

documented, and approved.

Greater control over higher-risk attributes.

Reevaluate risks throughout product/process lifecycle.

Homogeneity with batch and consistency between batches

are goals of process validation.

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TYPES OF VALIDATION MASTER PLANS

1. Validation Master Plan – site document

2. Validation Master Plan – function document

• Process Validation Master Plan

• Cleaning Validation Master Plan

• Other

3. Validation Project Master Plan – major project

management document

4. Validation Plan – Individual validation

document (Validation Initiation / Plan)

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RECOMMENDATION: SITE DICTIONARY

• Validation

• Qualification

• FAT

• SAT

• IQ

• OQ

• PQ

• PV

• PPQ

• VMP

• Validation Project Plan

• Validation Plan

• Others

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1. VALIDATION MASTER PLAN –

SITE DOCUMENT

• Overview, approach, content, risk analysis

• Chapters

• Major commitments timelines

• Accomplishments

• Document management – Revisions

CRITICAL DOCUMENT

DESCRIPTION OF VALIDATION QUALITY SYSTEM

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VALIDATION MASTER PLAN –SITE DOCUMENT

OVERVIEW, CONTENT, APPROACH, RISK ANALYSIS

Overview: Description of VMP content

Approach: Lifecycle approach to all types of validation /

qualification

• Stage 1. Design and development

• Stage 2. Demonstration

• Stage 3. Monitoring and maintenance

Content: Chapter list and chapter content

Risk analysis: Basis for all activities

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LIFECYCLE APPROACH RAMIFICATIONS

• Integration of validation with technical support

– Product R&D

– Product technical support

– Equipment/facilities/utilities engineering

– Process engineering

– Analytical R&D

– Analytical QA/QC

– Computer systems

– Others

• Integration of validation with QA

– Annual Product Reviews

– Stability

– Others

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VALIDATION MASTER PLAN – SITE DOCUMENT

CHAPTERS

1. Introduction

2. Facilities

3. Utilities

4. Equipment

5. Process

6. Analytical

7. Cleaning

8. Computer systems

9. Others

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CHAPTER CONTENT

• Chapter description, approach, content, risk analysis

• Policies

• Procedures

• Commitments (projects, CAPA, others)

• Appendix

– Reference list

– List of all products and reference #

– List of all cleaning and reference #

– List of all equipment and reference #

– List of all HVAC and reference #

– List of all utilities and reference #

– Other

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CHAPTER APPENDIX EXAMPLE

• Product #

• Product name

• Primary reference validation #

• Supplement validation #

• Dates approved

CRITICAL REFERENCE SECTION -- AUDIT USE

SAME FOR EQUIPMENT, CLEANING, UTILITIES, OTHERS

MAINTENANCE PROBLEMS

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MAJOR COMMITMENTS TIMELINES

MAJOR PROJECT LIST

• Validation project #

• Project title

• Major dates

• Responsibility

Benefits / Negatives

• Management tool

• Audit tool -- benefits

• Communication +/-

• Motivational tool

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ACCOMPLISHMENTS

• List of completed process validations

• List of completed qualifications

• Improvement projects

• Validation Quality System changes

Benefits / Negatives

• Accomplishments list – management tool

• Audit tool -- benefits

• Credibility / communication +/-

• Motivational tool

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ACCOMPLISHMENTS

DATE # TITLE

1-25-14 xxxx Process Validation Product X

1-25-14 xxxxx Cleaning Validation Product X

_____ _____ _______________________

_____ _____ ________________________

_____ _____ ________________________

_____ _____ ________________________

_____ _____ ________________________

_____ _____ ________________________

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DOCUMENT MANAGEMENT -- REVISIONS

DATE TITLE REASON FOR REVISION

1-30-13 4Q 20120Update Completed validations

New equipment

4-30-13 1Q 2013 Update Completed validations

New equipment



New commitments


2014 goals



New equipment

UPDATE FREQUENCY DEPENDS ON NEED AND WORKLOAD

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2. VALIDATION MASTER PLAN –

FUNCTION DOCUMENT

• Overview, content, approach, risk analysis

• Policies

• Procedures

• Commitments (projects, CAPA, others)

• Document management – Revisions

• Appendix

– Reference list

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VMP CHAPTER EXAMPLE – CLEANING VALIDATION

Strategy and approach

• Comprehensive lifecycle approach, Science and technical basis, Risk analysis,

Variation identification and control (consistent with site and corporate docs)

Procedures

• List of approved procedures

Supporting information with reference documentation

• Product cleaning matrix

• Equivalent equipment

• Equipment surface area calculations

• Residue calculations

• Technical reports

• Templates

Validation commitments and timelines

• Planned validations

Improvement projects and timelines

• Planned projects

Validation references

• List of all completed cleaning validations, #, date

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3. VALIDATION PROJECT MASTER PLAN

MAJOR PROJECT

Definition: Major project involving multiple functions,

multiple protocols, and extended timeline

• Construction

• Equipment

• Facilities

• Utilities

• Product / process

• Cleaning

• Project manager responsibility

ABOVE TO BE INCORPORATED INTO SITE VMP

DURING / AFTER COMPLETION

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MAJOR PROJECT

Project overview

• Major timeline commitments

Project functional components

Individual function sections

• Functional project overview

• Individual validation /qualification titles

• Timeline commitments

• Summary report recommended

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FUNCTION PLAN

Function project overview– Strategy

– Approach

– Risk analysis

– Other

List of validation / qualification titles

Validation titles reference #

Responsibility

Timeline

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MAJOR PROJECT

PROBLEMS

• Scope changes

• Amendments

• Mistakes

• Errors

• Others

AIM FOR PERFECTION

AMENDMENTS ARE A PLANNING FAILURE

DELAY OFFICIAL APPROVAL AS LONG AS POSSIBLE

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4. VALIDATION PLAN –

INDIVIDUAL VALIDATION / QUALIFICATION PROJECT

• Validation initiation document

• Validation #

• Risk analysis / change impact

• Templates and model documents

• Protocol, results, report continuum

• Problems and solutions

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VALIDATION PLAN – LIFECYCLE APPROACH

• Validation plan include all lifecycle stages

– Stage 1 – Design and development

– Stage 2 – Demonstration

– Stage 3 – Monitor and maintain

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STAGE 1, PROCESS DESIGN

(PROCESS UNDERSTANDING)

1. Building and capturing process knowledge and understanding.

2. Establishing a strategy for process control.

Define commercial-scale process

Define unit operations and process parameters

Identify and understand sources of variability

Identify critical process parameters

Studies to understand effects of scale

Establish mechanisms to control variability• Process Analytical Technology

Designed experiments

Lab scale and pilot scale experiments

PROCESS DESIGN (PROCESS UNDERSTANDING)

Objective

API and excipient pharmaceutics

Quality attributes

Risk analysis

Process parameters

Design of experiments

Design space

Normal operating range

In-process controls

Product development – key inputs to design stage

Variability by different component lots, production operators,

environmental conditions, and measurement systems

Use risk analysis tools to screen variables

Establish a strategy for process control

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QUALITY BY DESIGN (QbD)

1. Quality target product profile (QTTP)

2. Critical quality attributes (CQA), critical material

attributes (CMA)

3. Critical process parameters (CPP)

4. Design space

5. Scale-up and technology transfer

6. Identify input variables

7. Input variable control strategy

8. Continuous improvement

Other considerations: PAT, Risk analysis32

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STAGE 2, PROCESS QUALIFICATION

(VALIDATION PERFORMANCE)

1. Design of a facility and qualification of utilities and equipment

2. Process performance qualification

3. PPQ protocol

4. PPQ protocol execution and report

Confirmation at commercial scale of process design information

Qualification of equipment, utilities, facilities

Performance qualification

Conclusion that process consistently produces quality product.

Conformance batches

• All support systems, documents, training, personnel, etc. in place

• Target / nominal operating parameters within design space

• Additional testing

• Decision to “release process” for routine commercial manufacturing

STAGE 2, PROCESS QUALIFICATIONConformance Lots

Procedures

Validation plans

Protocols

Sampling

Testing

Results

Plan to maintain validation

ALL EQUIPMENT, ANALYTICAL, AND SUPPORTING

SYSTEMS MUST BE QUALIFIED.

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PERFORMANCE QUALIFICATION APPROACH

Higher level of sampling, testing, and scrutiny of process performance.

Protocol should address:

• Operating parameters, processing limits, and raw material inputs

• Data to be collected and how evaluated

• Test to be performed and acceptance criteria

• Sampling plan – sampling points, number of samples, frequency

• Statistical methods used

• Statistical confidence levels

• Provisions to address deviations and non-conformances

• Facility, utility, and equipment qualification

• Personnel training

• Status of analytical method validation

• Review and approval by appropriate departments and quality unit

DETAILS FROM PV GUIDANCE

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PERFORMANCE QUALIFICATION APPROACH

“The PPQ lots should be manufacturer under normal conditions by

personnel expected to routinely perform each step of each unit

operation in the process. Normal operating conditions should cover

the utility systems (air handling and water purification), material,

personnel environment, and manufacturing procedures.”

PQ report:

• Discuss all aspects of protocol

• Summarize and analyze data as specified in protocol

• Evaluate unexpected observations and additional data

• Summarize and discuss non-conformances

• Describe corrective actions or changes

• Clear conclusions

• Approval by appropriate departments and quality unit


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STAGE 3, CONTINUED PROCESS VERIFICATION

(VALIDATION MONITORING AND MAINTENANCE)

Activities to assure process remains in validated state

Annual Product Review

Trend and assess data

Study OOS and OOT (Out of Trend) data

Timely monitoring of critical operating and performance parameters.

Monitor product characteristics, materials, facilities, equipment, and SOP changes

Establish process history based on ongoing process performance

Improve process

Improve control to detect and reduce variability

Change control; evaluate impact of change and test as necessary

CONTINUED PROCESS VERIFICATION

Monitoring

Statistical process control

Trend analysis

Change control

Continuous improvement

Revalidation

Management review

STATISTICIAN RECOMMENDED BY FDA

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ITEMS TO BE REVIEWED

• Product and process data

• Relevant process trends

• Quality of incoming materials or components

• In-process material

• Finished products

• Defect complaints

• OOS findings

• Deviations

• Yield variations

• Batch records

• Incoming raw material records

• Adverse event reports

• Production operator and quality staff feedback

Above should help identify possible product / process improvements


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SUMMARY OF GUIDANCE RECOMMENDATIONS

Stage 1: Product Design

• QTPP, Development information, Identification of CQA, CMA, and CPP

• Identification of sources of variation and control plan

• Experimental studies

• Technology transfer / scale up

Stage 2: Process Qualification

• Protocol requirements

• Statistical sampling and acceptance criteria

• Equipment qualification and analytical method validation

Stage 3: Continued Process Verification

• Post PQ plan

• APR, batch data, yields, deviations, OOS, non-conformances, etc.

• Incoming material data

• Change control

• Statistical analysis of data / control charting

• Product complaints

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PROCESS VALIDATION HISTORY

1978

CGMP includes Validation

1987

Development -- VALIDATION -- Control

2008-2011

Lifecycle approach

Continuum of understanding – validation – maintenance

UNDERSTANDING -- VALIDATION -- MAINTENANCE

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VALIDATION PHILOSOPHY

• Validation is confirmation.

• Acceptable (passing) results are expected.

• Validation is not

– R&D

– Final stage of development process

– Optimization

– Fine-tuning

– Debugging

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STAGE 1 DOCUMENTS -- PROCESS DESIGN

Technical areas must be aware that their documents are critical to

validation throughout the product lifecycle.

• Direct support of Stage 2 PQ – their work is basis of validation

• R&D technical reports consistent with raw data

• Rapidly retrieved (within 30 minutes)

• Accessed throughout product lifecycle

• Personal support of regulatory audits

• Stand-alone documents

• Applies to processes, cleaning, analytical, equipment, facilities,

utilities, control systems, others.

R&D / TECHNICAL AREAS NOT ACCUSTOMED TO THESE

REQUIREMENTS AND EXPECTATIONS

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STAGE 1 DOCUMENTS – POTENTIAL PROBLEMS

• Reports not available

• Reports not retrievable

• Reports incomplete

• Reports poorly written

• Reports not approved

• Personnel not available

• Original data not available

• Substandard documentation practices – original data

• No signature / date

• Data transpositions

• Data transfer problems

• Data transfer not verified

• Inconsistent data

• Multiple sources of same data inconsistent

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VALIDATION STAGE 2 DOCUMENTS

OPTIONS

• Outlines

• Templates

• Model documents

RECOMMENDATION

1. Develop outlines for authors – get agreements from

functional organizations and approval committee

2. Write or collect good documents

3. Documents available to writers

4. Replace (upgrade) as appropriate

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STAGE 2 DOCUMENTS – PROCESS QUALIFICATION

VALIDATION INITIATION AND VALIDATION PLAN

Initiation: Statement of recommended validation

• What?

• Why needed?

• Why acceptable?

• Impact of validation – risk analysis

• Approach to accomplish – Validation Plan

• Approvals

Plan: Details of work to accomplish validation

• Description of strategy and approach

• References from Stage 1 work supporting validation

• Approvals

MAY BE SINGLE DOCUMENT OR TWO SEPARATE DOCUMENTS

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VALIDATION INITIATION OUTLINE

• Objective of validation

• Why needed?

• Impact of validation

– Risk analysis

• Why acceptable?

– Compliance to internal requirements, policies, engineering standards, etc.

– Regulatory impact (Prior approval, CBE, CBE30, etc.)

– Other systems or product impacted

– Procedure changes or other document changes

– Notifications to affected groups (internal, external, labs)

• Validation plan -- Approach to accomplish validation

Above applicable to equipment and other qualification

HAVE MODEL DOCUMENTS AVAILABLE

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VALIDATION INITIATION -- PROBLEMS

• Poorly written– Inadequate information

• Prematurely written– Written to meet business goals

– Written to demonstrate future intent

• Amendments necessary -- changes usually required

Validation initiatiions should be submitted for approval only

after objective and scope of validation is determined and

work details (risk/testing/sampling) determined.

Amendments are a planning failure regardless of

justification.


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VALIDATION INITIATION TERMINOLOGY EXAMPLES

Validation initiation:

Process validation of Product A

System: New product validation

Change impact: High impact. New product validation

Reason: New product to be manufactured at site

Acceptability:• Compliant with policies

• Regulatory approval

• Other systems impacted (e.g., cleaning)

• Procedures approved

• Notifications (Labs)

Justification: See Validation Plan

Approvals

SIMPLE AND CLEAR49



Qualification of 150 cu. ft. blender

System: New equipment qualification

Change impact: High impact. New equipment and new size at site

Reason: New equipment to increase manufacturing efficiency and

throughput

Acceptability:

• Compliant with policy

• Regulatory approval

• Other systems impacted (e.g., cleaning)

• Procedures approved

• Notifications (Labs)


Approvals

SIMPLE AND CLEAR

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Change air supply and return ductwork to coincide with Line 1 floor space

changes

System: HVAC system #3

Change impact: Medium impact. Change to direct product contact support

utility

Reason: Room configuration change to increase manufacturing efficiency

Acceptability:

• Compliant with policy

• Regulatory approval not needed

• Other systems impacted

• Procedures approved, drawings modified, etc.

• Notifications


Approvals

SIMPLE AND CLEAR

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VALIDATION PLAN OUTLINE

• Introduction

• Technical information

• Validation strategy and testing

• Validation documentation– List of required protocols, reports, procedures, etc.

– Administrative benefit

• References– List of reports and scientific references (including Stage 1

reports)


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VALIDATION PLAN

INTRODUCTION

• Overview describing validation / product / process /

equipment / etc. (consistent with request)

• Requirements to complete validation

– Conformance to regulations and internal policy

– Impact of change to maintain the validated state

– Impact on regulatory submission

– Impact of change on procedures, drawings, other documents

– Notifications to other areas internal and external (e.g.,

environmental agency, internal test labs) impacted by validation

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VALIDATION PLANTECHNICAL INFORMATION

• Basic product / process / equipment description

– Formula

– Process

– Specifications

– Include non-technical description information

• Technical aspects of validation / qualification

• Reference to technical reports from Design Stage

• Total validation approach

– Experimental studies

– Past data (retrospective data)

– Validation protocols

– Monitoring and maintenance (Stage 3)

– Other work

– New procedures

• Number of lots – related to impact of change and risk

WRITTEN FOR THE READER

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VALIDATION PLAN

VALIDATION STRATEGY AND TESTING

• Prospective validation only

• Types of testing -- general

– Regulatory specifications

– Internal controls

– Process tests

• Tests and rationale – general

– Address changes – based on risk analysis

• Sampling and rationale – general

– Exceed routine QA testing – based on impact and risk analysis

• Data treatment – general

– Statistical data treatment and confidence limits

• Acceptance criteria – general

• Post-validation testing

DETAILS OF ABOVE PROVIDED IN PROTOCOLS55

VALIDATION PLAN

VALIDATION DOCUMENTATION

Doc # Title Date closed

01 Validation request

02 XXX Dryer Engineering Study

03 XXX Dryer Qualification

04 XXX Process Scale-up Engineering Study

05 XXX Process Validation

06 Update Validation Master Plan – Product and

Equipment sections

07 XXX Project Summary Report

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VALIDATION PLAN

REFERENCES

• R&D Reports

• Development and analytical reports

• Published literature

Scientific and technical support to validation plan

Report copies should be stored in validation area

or readily accessible (within 30 minutes)

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PRODUCT / PROCESS DESIGN INFORMATION

• Technical reports from R&D or other technical areas

• Pharmaceutics reports

• Formulation and process development reports (CQA, CMA, CPP)

• Technology transfer / Scale-up reports

• Identification of sources of variation

• Variation control plans

• Analytical methods

• Other technical reports

REPORTS SHOULD BE REVIEWED FOR CONSISTENCY BETWEEN

GROUPS

REPORTS SHOULD BE REFERENCED IN VALIDATION PLAN

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TECHNICAL REPORTS

• Readily available

• Consistent across large technical groups

• Approved by management

• Linked to original data

– Observe / store original data

– Original documentation practices?

VALIDATION MUST REVIEW ORIGINAL DATA

• Rapidly retrievable

• Consistent with technical report

• Documentation practices

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VALIDATION PROTOCOLS

• Execution of the Validation Plan

• Testing details

• Sampling details

• Data sheets

• Data treatment

• Acceptance criteria

• Minimal text repetition from Validation Plan

PROTOCOL EASILY WRITTEN IF

VALIDATION PLAN IS THOROUGH

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VALIDATION RESULTS

• Compilation of testing required in protocol

• Deviations or adverse events

• Discussion

• Conclusion

WRITE GOOD PLAN

PROTOCOL CONSISTENT WITH PLAN

RESULTS CONSISTENT WITH PROTOCOL

WRITE DISCUSSION FIRST – MOST IMPORTANT SECTION

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VALIDATION REPORT FORMAT

APPLICATION FOR MAJOR PROJECTS

WITH MULTIPLE PROTOCOLS

• Introduction

• Key information from Validation Plan

• Supporting information

• Protocol #1 results – “Cut and paste”



• Protocol #n results – “Cut and paste”

• Write transitional narrative

• Project conclusions (for Validation Plan)

• Validation statement

– “Results indicate that ______ is validated.”


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STAGE 3 DOCUMENTS –


POST PQ DOCUMENTS

TYPES OF DOCUMENTS

• Post PQ requirements – work required based on PQ

results

• Ongoing monitoring – routine process monitoring

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DOCUMENT OUTLINES / TEMPLATES

PLANS, PROTOCOLS, RESULTS, REPORTS

Site manufacturing

• Few products / processes

• Multiple products / processes

Recommendations

• Templates for few products/processes sites

• Outlines for multi product/process sites

– Document outline of major sections

– Document outline evolves

– Model approved documents available

– Model approved documents improved and are replaced

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VALIDATION DOCUMENT APPROVAL

VALIDATION APPROVAL COMMITTEE (VAC)

VAC must review documents with perspective of an

external regulatory auditor

• Assure acceptability of technical validation and product

quality

• Assure compliance with regulations, policies, and

industry expectations

• Assure acceptability of documentation.

– Spelling and grammar

VAC IMPORTANT PARTNER WITH VALIDATION

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VALIDATION DOCUMENT APPROVAL

VALIDATION PLAN

Technical validation

• Scientific and technical principles

• Consistent approach

• Supports objective of validation

• Supports routine manufacturing in type of testing and sampling

• Support routine manufacturing in duration of sampling and testing

• Results and discussion support data

• Correct technical conclusions

• Equipment testing support entire operating range used in

manufacturing

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VALIDATION APPROVAL COMMITTEE

• Training consistent with area of expertise

• Specialized training on validation function

• Emphasize role of internal auditor

VALIDATION APPROVAL COMMITTEE

IS NOT

Training for new personnel

Expeditor for engineering documents

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SUMMARY –

COMPREHENSIVE, CONSISTENT, AND EFFECTIVE

VALIDATION DOCUMENTS

Validation documents consistent with validation guidelines and

expectations – based on risk

VMP and Lifecycle Approach

Stage 1 -- Emphasis on development work supporting Stage 2

• Technical basis for validation

Stage 2 -- Work should consider validation guidance recommendations

• Plans, protocols, results

Stage 3 – Emphasis on maintaining validated state through lifecycle

• Specific needs and routine monitoring

Associated documents

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SUMMARY – TYPES OF VMP

1. Validation Master Plan – site document

2. Validation Master Plan – function document

• Process Validation Master Plan

• Cleaning Validation Master Plan

• Other

3. Validation Project Master Plan – major project

management document

4. Validation Plan – Individual validation

document (Validation Initiation / Plan)

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SUMMARY – VALIDATION MASTER PLAN

SITE DOCUMENT

• Program description at site

• Multi-chapter document

• Updated as needed (annual, quarterly, monthly)

• Improvement projects commitments and

timelines

• Consistent with corporate policies

• State key points from Process Validation

Guidance – Stage approach

• Risk-basis

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SUMMARY – VALIDATION MASTER PLAN

FUNCTION DOCUMENT

• VMP for individual functions

• Same structure as in site document

• Organization preference or major project

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SUMMARY


• Major project management document

• Multiple functions

• Multiple protocols

• Extended time

• Project manager

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SUMMARY – VALIDATION PLAN

Individual validation document

Validation Initiation / Plan

Plan Protocol Results

Plan Format

• Introduction

• Technical information (Stage 1)

• Validation strategy and testing (Stage 2 and Stage 3)

• Validation documentation

• References


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PAUL L. PLUTA, PhD

Editor-in-Chief

Journal of Validation Technology

Journal of GXP Compliance

Advanstar Communications

Associate Professor of Biopharmaceutics

University of Illinois at Chicago (UIC) College of Pharmacy

Chicago, IL, USA

Contact: [email protected]

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