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Validation of Water System For Pharmaceutical Use
Validation of Water System For Pharmaceutical Use
PHARMACEUTICAL USE
o Introduction
1
INTRODUCTION
o Information on Water for Pharmaceutical Use (WPU)
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BACKGROUND TO WATER REQUIREMENTS AND USE
o Water is the most widely used substance / raw material
o Used in production, processing, formulation, cleaning, quality
control
o Unique chemical properties
Able to dissolve, absorb, adsorb, suspend compounds and contaminants
o Different grades of water quality available
o Control quality of water
Production
Storage and distribution
3
WATER SYSTEM REQUIREMENTS
o Design, installation, commissioning, qualification / validation, operation,
performance and maintenance to ensure reliable, consistent production
of water of required quality
o Operate within design capacity
o Prevent unacceptable microbial, chemical and physical contamination
during production, storage and distribution
o Quality Assurance involved in approval of use after installation and
maintenance work
o Monitoring of water sources regularly
Chemical and microbiological
Endotoxin level where relevant
o Monitoring of system performance, storage and distribution systems
o Records of results, and action taken
o Validated sanitization procedure followed on a routine basis
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WATER QUALITY SPECIFICATIONS
o Drinking water / potable water
o Purified water (PW)
o Highly Purified Water (HPW)
o Water for Injection (WFI)
o Storage tanks
Closed, with protected vents
Allows visual inspection, draining and sanitization
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PRODUCTION OF PURIFIED WATER (PW)
o Use appropriate, qualified methods for production
o Factors to consider:
10
COMMISSIONING, QUALIFICATION AND OPERATION
CONSIDERATIONS
Monitoring
Maintenance
System reviews
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START UP AND COMMISSIONING
o Should be planned, well defined, well documented
o Includes setting to work
o Includes system set-up
o Includes recording of system performance parameters
Qualification
o WPU,PW, HPW and WFI systems are "direct impact and quality critical systems“
DQ: Design review influenced by source water and required water quality
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Three phase approach recommended over extended period – proves
reliability and robustness
Phase 1
o A test period of 2-4 weeks – monitoring the system intensively
o Deploying all the refined SOPs after the satisfactory completion of phase 1
o Demonstrate
Consistent operation within established ranges
Consistent production and delivery of water of the required quantity and
quality when the system is operated in accordance with the SOPs
Phase 3
o Demonstrate
extended reliable performance
Ensure that seasonal variations are evaluated
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PURPOSE OF VALIDATION
o High quality of water – essential for manufacturing of pharmaceuticals
o DQ of water systems
o Sanitization
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QUALIFICATION OF EQUIPMENT AND COMPONENT
FOR WATER SYSTEM
o Equipment and components used for the water system must maintain integrity
and be anticorrosive and assured for technical integrity
o Piping – Stainless steel
Cleaning for removing contaminants
o Material – Compatible with material use for sanitizing and cleaning purpose
o Valves
o Pumps – Cleanable pumps, centrifugal pumps, rotary lobe pumps, peristaltic
pumps and diaphragm pumps
o Pressure gauges
o Heat exchangers
o Distillation equipment
o Filters
o Deionizers
o Ultraviolet light
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SANITIZATION
Thermal Approach
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Chemical method
o Oxidizing agents
Hydrogen peroxide
Ozone
Per-acetic acid
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VALIDATION OF SANITIZATION STEPS
o Sanitization steps require validation to demonstrate the capability of
reducing and holding microbial contamination at acceptable levels
21
SYSTEM MONITORING
o After phase 3 – system review needed
o Based on review including results, establish a routine monitoring plan
o Monitoring to include a combination of on-line monitoring and off-
line sample testing
Online monitoring includes
Flow
Pressure
Temperature
Conductivity
Total organic carbon
Offline sample testing includes
Physical attributes
Chemical attributes
Microbial attributes
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MAINTENANCE OF WATER SYSTEMS
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SYSTEM REVIEWS
o WPU (PW, HPW and WFI) systems to be reviewed at appropriate
regular intervals
o Review team includes engineering, QA, operations and maintenance
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INSPECTION OF WATER SYSTEMS
o WPU (PW, HPW and WFI) systems are likely to be the subject of
regulatory inspection from time to time
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