Rocky Mountain RAPS

Process Validation
Presentation
6/7/06

By Clay Anselmo
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

Design (Product) Validation: Establishing by objective evidence

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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 Compile and Analyze Data
and specifications Corrective Action and Re-
Define process execution as Necessary
inputs/outputs and Create / Approve Final
specifications Report
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

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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
performed
Purpose
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 Review
Protocol 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 consistency
Poor 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

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