Rocky Mountain RAPS

Process ValidationPresentation

6/7/06

By Clay Anselmo

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Learning Objectives

Understand the purpose of process validation. Understand the key components of a good process

validation (IQ, OQ, PQ). Understand how these elements and their definitions

have changed over the years. Be able to categorize processes and determine the

extent of validation required. Understand documentation requirements for

validation and the process for storage and retrieval of these documents.

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Concepts and Definitions

Let’s be perfectly clear!

◦ Process Validation (QSR): Establishing by objective evidence (documented) that a process consistently produces a result or product meeting its pre-determined specifications.

◦ Design (Product) Validation: Establishing by objective evidence (documented) that device specifications conform with user needs and intended use(s).

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Concepts and Definitions

Verification: Confirmation by examination and provision of objective evidence that specified requirements have been fulfilled.

Prospective Validation: A validation that establishes documented evidence that a product or process conforms to its specifications prior to final release of the product or process.

Retrospective Validation: A validation that establishes evidence that a product or process performs to its specifications based on a review and analysis of historical performance data.

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Concepts and Definitions

Installation Qualification (IQ):◦Installation and Installation Conditions

(electrical, air, water, etc.)◦Calibration and Preventive Maintenance◦Safety Features◦Complete Documentation including

equipment and software◦Environmental Conditions◦Training◦Does NOT typically require statistically based

sampling or data analysis

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Concepts and Definitions

Operational Qualification (OQ):◦Show equipment functionality over the range

of specifications◦Show equipment stability and capability in

worst case conditions (considering all process inputs) Equipment settings Raw material Supply variations (air, water, etc.)

◦Establishment of action and alert limits as appropriate

◦Confirmation of failure modes◦Uses valid statistical methods for analysis of

data and variation

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Concepts and Definitions

Performance Qualification (PQ): ◦Demonstrate longer-term stability and

capability of the process under nominal conditions

◦Evaluates acceptability of product against specification

◦Utilizes valid sampling and statistical techniques Multiple Lots Multiple Operators

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Concepts and Definitions

WHEN IS IT NECESSARY TO PERFORM VALIDATION?◦21 CFR 820.75 – Where the results of a

process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance…

◦ ISO 13485:2003 – The organization shall validate any processes for production and service provision where the resulting output cannot be verified by subsequent monitoring and measurement. This includes any processes where deficiencies become apparent only after the product is in use or the service has been delivered.

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GHTF Flow Chart

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Concepts and Definitions

What/When Processes Should be Validated?◦ End product tests that verify device conformance to

specifications and requirements◦ When destructive testing is required to show product

conformance to specification◦ When even state-of-the-art testing methods cannot

demonstrate conformance to specification◦ Process capability is unknown or it is suspected that the

process is barely capable of meeting device specifications

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Validation Overview

Define product requirements and specifications

Define process inputs/outputs and specifications

Plan the validation process

Develop Protocols◦ Test Method Verification /

Validation Measuring equipment suitability

(i.e. – gage R&R)◦ IQ – Installation Qualification◦ OQ – Operational Qualification◦ PQ – Performance Qualification

Execute Protocols

Compile and Analyze Data

Corrective Action and Re-execution as Necessary

Create / Approve Final Report

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Validation Planning Elements

Why Create a Validation Plan◦ Allows quick overview of validation activities◦ Reduced approval cycle iteration

Pre-Requisites◦ Clear Requirements/Specifications◦ Basic Test Methods (verified or validated)

Test Definition/Description◦ Plan should include a clear description of each set

of tests to be performedPurpose

◦ Plan should contain the purpose of each set of tests

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Validation Planning Elements

Requirements◦Plan should briefly describe the requirements

for each set of tests and be traceable to product or process specifications

Acceptance Criteria◦Plan should contain the general acceptance

criteria for each set of tests or cross reference the location.

Analytical Techniques◦Define the method for analyzing data using

commonly accepted statistical techniques.

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Protocol Development

All Validations should be executed per a formal, pre-approved protocol◦ Pre-approval is not a regulatory requirement, just a good

practice that prevents delays and re-executions.Protocol format is OPTIONAL but must include

the following key sections:◦ Purpose / Background◦ Configuration of product or process◦ Material and Equipment (including Calibration data)◦ Sampling, Data Analysis Methods◦ Test Procedure◦ Clear Acceptance Criteria

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Protocol Development

Key Protocol Sections (cont.)◦ Data Sheets◦ Conclusions◦ Deviations◦ Revision History

Key Points◦ Provide background and justification for approach◦ Ensure test method is appropriate (verified or validated)

Protocol ReviewProtocol Pre-Execution Approval

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Validation Completion

Execution◦Follow the protocol!◦Note any deviations◦Use good documentation practices◦Sign the data sheets◦Collect equipment calibration information◦Make sure training is documented

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Validation Completion

Final Report◦May be an addition to protocol or a separate

document◦Summarize the results specifically related to

each test or challenge◦Document and justify your deviations

Deviations are not for changes to acceptance criteria

◦Document your data analysis◦Reach formal conclusions regarding the

overall outcome of the validation◦Needs approval

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Special Considerations

Deviations◦Document all deviations from pre-approved

procedure in the Deviations section of the protocol.

◦Changes to acceptance criteria should be documented in the protocol and re-approved prior to re-executing the testing.

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Special Considerations

Test Method Verification◦Suitability of Test Instrumentation

Gage Accuracy and Sensitivity Operator Variation Characterization of Alpha and Beta Errors

◦Training and Confirmation of Effectiveness◦Yes, it applies to visual inspection,

dimensional verification, and automated test methods

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Software Validation

Equipment With Embedded Software◦Software must be validated◦Can be done stand-alone (if possible), or as a

part of verifying equipment function (IQ or OQ)

◦Requires an understanding of the software logic and the functions to be utilized

◦Should include nominal/margin testing and error handling

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Special Considerations

IQ / OQ / PQ◦Question: Does it really matter what goes

where?◦Answer: Sometimes, if one validation activity

depends on others. (i.e. – training)◦Question: I often hear the terms PQ, PPQ,

Product Performance Qualification, Process Performance Qualification. What’s the difference??

◦Answer: These are often defined differently across organizations. However, typically PQ is the overarching term that refers to both process and product performance qualifications.

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Common Mistakes

Poor Organization◦ Lack of program structure◦ Lack of templates and rules for ensuring program

consistencyPoor Planning

◦ No documentation to tie stand-alone validations together (i.e. – Master Validation Plan)

◦ No method to ensure re-validations occur when required (i.e. – sterilization)

Poor Documentation◦ Little background information◦ Story not told◦ No links to CO/ECO process to ensure changes do not

invalidate prior validation activities