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PRINCIPLES OF PROCESS VALIDATION & QUALIFICATION
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ACCURATE &RETRIEVABLE Analytical Data
TrainedPersonnel
ValidatedMethods
StructurallyValidatedSoftware
Calibrated/QualifiedEquipment
cGMP/GALPLaboratory
SystemSuitabilityAnalysis
LaboratorySOPs
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Safety Review by NRA
Preclinical R&D(GMP/GLP)
Clinical Trial(GCP)
NDA orLicensure
Post-marketsurveillance
Phase 1 Phase 2 Phase 3
STAGES INVOLVED in REGULATING DRUGS
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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)
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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”
Men: adequate training
Materials: raw materials, products, reagents,
labels, containers
Machinery: facilities, systems, equipment
Methods: manufacturing, control, validation,
documentation
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VALIDATION
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
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REFERENCES
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 VALIDATION
Prospective validation
Retrospective validation
Concurrent validation
Re-validation
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CLASSIFICATION of VALIDATION
Process validation
Method validation
Cleaning validation
Computer validation
Support system validation
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ELEMENTS of VALIDATION
Equipment validation: Installation Qualification(IQ)
Operational Qualification(OQ)
Process validation: Performance Qualification(PQ)
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STEPS INVOLVED in VALIDATION
Validation master plan
Validation protocol
Execution of validation
Validation report
Preparation of SOPs
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MAJOR 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 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. QUALIFICATION
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QUALIFICATION vs. CALIBRATION
QUALIFICATION CALIBRATION
Qualification Workbooks(IQ, OQ, PQ) & Project Diskettes
Accuracy, Linearity andPrecision Tests
Appropriate for companies without approved qualification procedures
Meets or exceeds US FDA qualification requirements.
Calibration Protocols
Accuracy Tests Only
Appropriate for companiesthat 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
StructurallyValidatedProducts
DQ
Functional Validation
Installation Operational Performance
Qualification Qualification Qualification
Maintenance
OQPQIQ OQ PQ
System Suitability During Use
VALIDATION 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
