Validation and Qualification

Documentation

Sangeeta Sardesai
Sanofi-Aventis
 Introduction

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 Documented demonstration of
Validation =
expected Quality + Consistency

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 Definitions (EU)

Action of proving, in accordance with the principles

of GMP, that any procedure, process, equipment,
material, activity or system actually leads to the
expected results.

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 Definitions (USFDA)

Establishing documented evidence which provides a

high degree of assurance that a specific process
will consistently produce a product meeting its
predetermined specifications and quality attributes.

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 Definitions - WHO
The collection and evaluation of data, beginning
at the process development stage and continuing
through the production phase, which ensures that
the manufacturing processes - including
equipment, buildings, personnel and materials - are
capable of achieving the intended results on a
consistent and continuous basis.

Validation is the establishment of documented

evidence that a system does what it is supposed
to do.
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 Definitions - ICH

A documented process that provides a high

degree of assurance that a facility, laboratory,
computer, process or system will consistently and
reproducibly produce product, or perform to a
predetermined specification.

Validation covers all activities from design through

to final approval for use.

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 Qualification or Validation?
A system must be qualified to operate in a
validated process
 Qualify a system and/or equipment
 Validate a Process
 Qualification versus validation,
e.g.
you qualify an autoclave, you validate a sterilization
process

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 Qualification / Validation
Qualification and validation work
require:
• Collaboration of data A Validation
Master Plan
• Budget helps both the
manufacturer
• Meticulous and careful planning and the
auditor

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 Validation
documentation

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 Validation Documentation
• Site validation master • Commencement of Site
plans (SVMP)
• Project specific validation • Start of specific validation
master plans (VMP) project
• Validation protocols • Start of individual
validation activity
• Validation reports • Completion of individual
activity
• Validation summary • Completion of entire
reports (VSR) validation activity
• Validation review reports • Periodic review, Major
(VRR) Changes / deviations.
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 Validation Documentation
Hierarchy

Site Validation
Master Plan

Project Specific Validation

Master Plans/Rationales

Discipline Specific Protocols

(DQ, IQ, OQ, PQ)
Testing

Validation Raw Data

Reports Paper/Electronic

Validation
Summary Report

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 Validation Documentation

• Must form part of a GMP controlled system.

• Must be prepared and authorised prior to
initiation of activity.
• Must include the following:
 Unique Reference Number
 Version number
 Revision history
 Issue Date
 Signatures section

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 Site Validation Master Plan
(SVMP)
• Effective Management Tool
• Provides overview of validation activities and progress
• Is a living Document
 Should be revised at pre-determined intervals periodically
 When there are changes to validation program
• For large / complex sites, specific SVMP may be written
• Must be authorised by Site Director and Quality Head
• Planning schedule should exist
• List all identified validation activities
• Revisions should be tracked
• Significant changes require clear explanation and
justification
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 Validation Master Plan (VMP)
• Must have an accurate description of the validation
intent
• Justification is the most important part
• Rationale for designing of the exercise
• Must be based on good scientific and technical
reasoning
• Enables overview of the entire validation project
• Lists items to be validated with the planning schedule
as its heart
• Is like a map
• Must ensure that level of validation is appropriate

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 Validation Master Plan (VMP)

• VMP should describe:

 why?  by whom?
 what ?  how?
 where?  when?

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 Validation Master Plan (VMP)

• Justification / Rationale for validation (WHY)

• Protocols and other documentation (WHAT)
• Location / Area / Equipment (WHERE)
• Departments Involved (WHOM)
• Method / List of relevant SOPs (HOW)
• Planning and scheduling (WHEN)

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 VMP – Introduction / Objective
Introduction -
• Brief write-up of the project
• Overall objective of validation exercise
• General description of facility or process
• Reference to applicable compliance documents to
which the facility or process has been designed (may be
internal or external)

Objective
• A concise statement of the tasks to be performed to
allow a complete understanding of the validation
exercise.

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 VMP – Approach
Approach
• A definition of how the validation will be conducted
• Describes information and documents required
 Applicable Standards
• Cross references to documents
• Personnel Attributes
 Expertise and training
• Support from External Parties
 Consultants
 Supplier

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 VMP – Scope
Scope
• Should indicate clear boundary of the exercise
• List of units, systems, and processes to be validated and
the level of testing (DQ, IQ, OQ, PQ)
• May be updated through the project life to include
protocol references

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 VMP - Responsibilities
VMP should state who is responsible for:
• Document preparation and control
• Validation work
• Approval/authorisation of validation protocols
and reports in all stages of validation process
• Tracking system
• Training needs in support of validation

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 VMP – Justification / Rationale
• An accurate discussion as to why process steps or
devices will or will not be subject to testing during the
validation exercise (CRITICAL or NON-CRITICAL)
• Validation list (What to validate)
 premises, systems and equipment
 processes
 products
• Specific process considerations / characteristics briefly
outlined
• Will cover all steps as described in Scope / Objectives
• Sometimes a separate document to VMP but closely
referenced (If required)
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 VMP – Acceptance Criteria

• Acceptance Criteria for each unit to be tested will be

defined in broad terms
 Internal / External / National standards
 Regulatory / Pharmacopoeial Requirements
• Specific Acceptance Criteria will be recorded in the
individual test protocols

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 VMP – Risk Assessment
• Identify and describe briefly risks associated with the
project / process being validated
• Classify risks based on impact
• Indicate brief remedial measures

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 Validation Master Plan Contents
VMP should contain at least:
• Validation policy
• Validation Organization
• Summary of facilities, systems, equipment, processes to be
validated
• Documentation format for protocols and reports
• Planning and scheduling
• Change control
• Training requirements
• Annexures / Formats

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 Validation Protocols
• Key Documents defining the actual work and action
• Must be prepared and approved for each validation
activity
• Must be in place (approved and issued) prior to the
activity
• Must specify the actual length and duration of the
validation
• Objective / Subjective and measurable criteria must be
specified
• Definition of non-conformance
• Criteria for revalidation
• Criteria for change control
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 Validation Protocols
Identify and detail –
• Process
• Quality of utilities
• Equipment / Instrument involved
• Operators / operator training and qualification
• Special controls or conditions
• Process parameters to be monitored
• Methods for controlling and monitoring
• Samples and sampling methods
• Relevant specifications and tests
• Maintenance and repairs
• Statistical methods
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 Validation Protocols

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 DQ Protocols
• End Use and function – All needs to be addressed
• Operating environment and any constraints
• List all requirements - business, technical, engineering,
product quality and regulatory
• Design review, testing and traceability.
• Unambiguous, clear, concise
• All needs to be addressed
• System schematics / mark up

DQ = URS + FS + DS

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 IQ Protocol
• System Description
• As-built schematic (P&ID Schematic diagrams)
• Equipment list
• Checks to be performed
• Utilities Requirements
• Documentation listing – Reference to
procedures
• Drawings
• Spare parts list

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 OQ Protocol
• System description
• Sequence of operation
• List of Components to be qualified / calibrated
• SOPs – Operation / Calibration / Maintenance
• Calibration Requirements
• Operational parameter requirements
• Acceptance Criteria

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 PQ Protocols
• Define test scope
• List of critical steps
• List controls - process and quality
• Identify the variables
• Give details of tests
 Sample sizes
 Frequency
 Equipment to be used
• Define acceptance criteria
• Use diagrams for sample points
• Add as appendices to VMP

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 Validation Reports
• Each qualification stage to be reported
• Results to be entered against acceptance criteria
• Past data or trend may be used (if available)
• Intra-batch and Inter batch variability may be checked
• Clear conclusions should be drawn
• Discuss failures or deviations

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 DQ Reports
• Inspection Reports
 Matches as given in DQ
• SAT / FAT Reports
• Vendor Manuals
• FS confirmation
• Engineering review (fit for purpose)
• Any deviations or changes from DQ

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 IQ / OQ Report
• Could be combined report
• Details of test results
• List of components that are qualified
• Engineering changes
• Any outstanding actions with action plan
• Details of document / data archive
• Conclusions of exercise

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 PQ Report
• Record any deviations or failures
• List any remedial actions with timescales
• Summarise results
• Reference locations for access to raw data and test
results
• Discuss results and draw conclusions
• Change in Batch records, SOPs, procedures,
specifications
• Define requirement for Validation Review

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 After the work then report your findings...

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 Report your Findings
• Are all results as expected?
• Is more trial testing work required?
• Does your data really achieve objectives?
• What are the conclusions of the exercise?
• Any Deviations, Investigations, OOS

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 Validation Summary Reports (VSR)
• To be prepared at the end of the entire qualification /
validation activity
• Should include discussion and rationale
• Should include deviations, investigations, OOS, change
control
• Should include impacted areas
• Should include conclusion

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 Validation
Maintenance

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 You’ve done it…...

But what if things change?

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• Change Control Program
• Periodic Validation Review
• Trained Personnel

Trained Personnel

Change
Management Validation Review

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 Change Control
• Ensure amendments or changes are evaluated
• Ensure the extent of validation
• Ensure approval is received before using the system,
facility, equipment, utility or process
• Ensure documentation updates
• Ensure post-approval implementation are under control

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 Validation Review Reports (VRR)
• Routine review of the validated status
• “IS OUR SYSTEM STILL BALANCED” – Ask in VRR
• To ensure that on-going validation maintenance is
being performed

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 Annexures
• Glossary
• Process flow diagrams / sheets
• Validation method references
• Facility lay-out plans
• Process / People / Material flow diagrams
• HVAC pressure differentials diagram
• Test Protocols
• Gantt Chart for schedules

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 Schedule
• List the pre-requisites to start the validation
• Lists anticipated constraints to the successful completion
of the programme
• List may include requirements for services, manpower,
supplies, documentation, test equipment, lab & other
support services like external agencies
• Allows for resource and project planning

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 Support Programmes
• Triggers a check of all the required systems to achieve
and maintain a Validated state
• May include
 Training
 Calibration / Qualification
 Preventive maintenance
 Deviation reporting
 Change control
 Validation review
 Annual Product Review

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 Key Messages

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 Summary
• Don’t get bogged down with terminology
• Don’t worry about whether something should be
in the validation document
• Validation requires formal documentation
• Content over format
• Be consistent
• Will the documents be meaningful after 10
years
• Requires a structured approach
• It is an ever-evolving process
• There is help & guidance available so don’t “re-
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invent the wheel”

 If in any doubt then please ask...

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