The document outlines the principles of process validation and qualification in drug manufacturing, emphasizing GMP (Good Manufacturing Practice) and the steps necessary to ensure product quality. It details various types of validation, such as process, method, and cleaning validation, and includes guidelines for installation and operational qualification of equipment. Additionally, it references key regulatory frameworks and described the responsibilities of personnel in maintaining compliance with these standards.

1. 1
PRINCIPLES OF PROCESS VALIDATION
& QUALIFICATION

2. 2
ACCURATE &
RETRIEVABLE
Analytical Data
Trained
Personnel
Validated
Methods
Structurally
Validated
Software
Calibrated
/Qualified
Equipment
cGMP/GALP
Laboratory
System
Suitability
Analysis
Laboratory
SOPs

3. 3
Safety Review
by NRA
Preclinical R&D
(GMP/GLP)
Clinical Trial
(GCP)
NDA or
Licensure
Post-market
surveillance
Phase 1 Phase 2 Phase 3
STAGES INVOLVED in REGULATING DRUGS

4. 4
The minimal necessary level
of operation and administration
of facilities, methods and controls
To manufacture drug products
of consistently high quality
(to assure that the products meets the requirements of the act
as to safety and effectiveness which the product purports)
GMP(Good Manufacturing Practice)

5. 5
 Designation of a Responsible Person
 And Independent Quality Assurance Unit
 Maintenance of Suitable Facilities
 Definition of Scientifically Sound
(Validated) Analytical Methods)
 The issuance of a Final Report
 Fully Retrievable and Available Raw Data
 Use of Calibrated Equipment
 Accuracy and precision
 Use of well Maintained Equipment
 Conducted by Standard Operating Procedures (SOP’s)
 Conducted by Qualified Personnel
cGMP Laboratory 21 CFR Ch. 1, Part 211

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FOUR BASIC ELEMENTS of GMP: “4Ms”FOUR BASIC ELEMENTS of GMP: “4Ms”
 Men: adequate training
 Materials: raw materials, products, reagents,
labels, containers
 Machinery: facilities, systems, equipment
 Methods: manufacturing, control, validation,
documentation

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VALIDATIONVALIDATION
Establishing documented evidence which provides
a high degree of assurance that a specific process
will consistently produce a product meeting its
pre-determined specifications and quality attributes

8. 8
REFERENCESREFERENCES
 US FDA
 Guideline for general principles of process validation
May, 1987
 Guideline on sterile drug products produced by
aseptic processing, June, 1987
 WHO
 A WHO Guide to GMP, Requirements, Part 2:
Validation, January, 1997
 European Commission
 Final Version of Annex 15 to the EU Guide to GMP
Title: Qualificaiton and Validation, September, 2001

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CLASSIFICATION of VALIDATIONCLASSIFICATION of VALIDATION
 Prospective validation
 Retrospective validation
 Concurrent validation
 Re-validation

10. 10
CLASSIFICATION of VALIDATIONCLASSIFICATION of VALIDATION
 Process validation
 Method validation
 Cleaning validation
 Computer validation
 Support system validation

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ELEMENTS of VALIDATIONELEMENTS of VALIDATION
 Equipment validation: Installation Qualification(IQ)
Operational Qualification(OQ)
 Process validation: Performance Qualification(PQ)

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STEPS INVOLVED in VALIDATIONSTEPS INVOLVED in VALIDATION
 Validation master plan
 Validation protocol
 Execution of validation
 Validation report
 Preparation of SOPs

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MAJOR VALIDATION ITEMSMAJOR VALIDATION ITEMS
 Steam-sterilization
 Depyrogenation
 Freeze-drying
 Clean in place
 Sterilization in place
 Purification
 Filling
 Inactivation
 Decontamination
 Sterile Filtration(Liquid)
 Water for Injection system
 Air Handling system
 Clean Steam system

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 FDA Guideline Definition…
“PROCESS VALIDATION” is establishing documented evidence
which provides a high degree of assurance that a specific
process consistently produce a product meeting it’s
predetermined specifications and quality attributes”
From….
Guidelines on General Principles of Process Validation
May, 1987. US FDA
PROCESS VALIDATIONPROCESS VALIDATION

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PROCESS VALIDATION

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Validation versus Qualification
 VALIDATION:
Refers to the total life cycle of a product from development
through use and maintenance.
Customers(Owners) are responsible for Validating Their
Processes(personnel, equipment, methods, SOPs) to ensure
compliance to CGMP/GLP regulations.
 QUALIFICATION: (Inspection, functional testing and documentation review)
Is a part of the validation process which verifies module and
system functional performance prior to being placed on-line
and thereafter according to a standard operating procedure.
VALIDATION vs. QUALIFICATIONVALIDATION vs. QUALIFICATION

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QUALIFICATION vs. CALIBRATIONQUALIFICATION vs. CALIBRATION
QUALIFICATION CALIBRATION
Qualification Workbooks(IQ, OQ,
PQ) & Project Diskettes
Accuracy, Linearity and
Precision Tests
Appropriate for companies
without approved
qualification procedures
Meets or exceeds US FDA
qualification requirements.
Calibration Protocols
Accuracy Tests Only
Appropriate for companies
that have approved validation
procedures
Basic documentation for
maintenance and calibration

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The Validation Time Line
Vendor’s
Site
Owner’s site
Before
Purchase
Before Use After Use
Structurally
Validated
Products
DQ
Functional Validation
Installation Operational
Performance
Qualification Qualification
Qualification
Maintenance
OQ
PQIQ OQ PQ
System Suitability During Use
VALIDATION TIME LINEVALIDATION TIME LINE

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DESIGN QUALIFICATION (DQ)
“A documented review of the design, at an appropriate stage of stages
in the project, for conformance to operational and regulatory
expectations.”
Applies to the Critical Equipment/systems
DQ Check Items
- GMPs and Regulatory Requirements
- Performance Criteria (URS & FS)
- Facility Air Flow, Movement Flow & Pressure Regimes
- Reliability & Efficiency
- Commissioning Requirements
- Construct ability & Installation of Equipment
- Maintenance & Access to Critical Equipment & Instrumentation
- Safety & Environment Impact

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DQ REVIEW DOCUMENTS
 User Requirement Specification (URS)
 Functional Specification (FS)
 System impact Assessments
 Tender Specifications, P&ID’s and Drawings
 Vendor Quality procedures and documents
 Purchase Specification

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INSTALLATION QUALIFICATION (IQ)
“Documented verification that all aspects of a facility, utility or
equipment that can affect product quality adhere to approved
specifications and are correctly installed.”
 Applies to the Critical Equipment/Systems
 Protocols
 Purpose
 Description
 References
 Responsibilities
 Installation Qualification (Test Plan)
 IQ Acceptance Criteria
 Modification/ Change Control and Revalidation
 Comments/ Action Items
 IQ Attachments

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TEST PLAN (CHECK LISTS)
 Identification : Sanitary Vessel Data Sheet
 Identification : Agitator Data Sheet
 Equipment List
 Filters
 Materials in Product Contact
 Recommended Spare Parts List
 Instrument Calibration : Critical Instrument
 Instrument Calibration : Reference Instrument
 Documentation
 Drawings
 Piping IQ Check List
 Utility Requirement : Electrical
 Utility Requirement : Other Utilities
 Grounding Checkout
 Validation Test Instruments and calibrations
 Installation Qualification Summary
 Comments/Action Items

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OPERATIONAL QUALIFICATION (OQ)
“Documented verification that all aspects of a facility, utility or
equipment that can affect product quality operate to Intended
throughout all anticipated ranges.”
 Applies to the Critical Equipment/Systems
 Protocols
 Purpose
 Description
 References
 Responsibilities
 Installation Qualification (Test Plan)
 OQ Acceptance Criteria
 Modification/ Change Control and Revalidation
 Comments/ Action Items
 OQ Attachments

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TEST PLAN (CHECK LISTS)
 Validation Test Instruments and Calibrations
 Alarm checkout
 Control Panel Checkout
 Pressure Hold Test
 Water Batch Test-Agitator System checkout
 Water Batch Test-Heating / Cooling System Checkout
 Transfer System Check Out
 CIP Qualification Check Out
 SIP Sterilization Temperature Mapping
 SIP Sterilization Filter Integrity Test Results
 Filter Adsorption / Component Removal / Release of Extractable
 PLC Screen Verification
 SOP & Personnel Training
 Operational Qualification Summary
 Acceptance of New Equipment Form
 Comments/Action Items

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PERFORMANCE QUALIFICATION (PQ)
“Documented verification that all aspects of a facility, utility or equipment
Perform as intended in meeting predetermined acceptance criteria.”
 Applies to the Critical Systems (i.e.: HVAC Systems, Pharmaceutical
Grade Water Systems, Clean Compressed Gases, Clean Steam
System,
Process Package Systems)
 Protocols
 Purpose
 Description
 References
 Responsibilities
 Performance Qualification (Test Plan)
 PQ Acceptance Criteria
 Modification/ Change Control and Revalidation
 Comments/ Action Items
 PQ Attachments
-Test Data Sheet
-Test Instrument Calibration and Analytical Instrument Validation

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PERFORMANCE QUALIFICATION (PQ)
PQ Protocol should include the following:
 Acceptance criteria
 Number of samples for analytical testing
 Location of sampling points
 Duration of testing
 Processing steps for testing
 Batch records
 Number of runs

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Validation in PharmaceuticalsValidation in Pharmaceuticals