This document discusses the need for high-quality water in pharmaceutical manufacturing. It notes that water is used directly and indirectly in products and cleaning. It then outlines the goals of understanding water quality systems, sources, and validation/qualification requirements. Various water treatment techniques are explained including filtration, softening, reverse osomosis and more. Validation involves proving the engineering design, operating procedures and maintenance plans. The presentation covers installation qualification, operational qualification, and performance qualification testing over multiple phases to verify long-term control of water systems.

1. Discussed & Presented By : Muhammad Luqman Ikram
Manager Validation
27-07-2018
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2.  High-quality water is essential for the manufacturing of
pharmaceuticals.
 Water is directly or indirectly used in the pharmaceutical
manufacturing, such as a major component in injectable products
and in cleaning.
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3. To understand:
 The need for water quality manual.
 Reason for usage of pharmaceutical water supply systems.
 The technical requirements for water supply systems.
 Different types of water sources.
 Validation requirements.
 Qualification & Inspection requirement.
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4.  Tap water is always variable due to seasonal or regional variation in quality.
 One must remove impurities and control microbes to avoid contamination of products.
 Quality of water should be specific for product quality.
Water contains,
Organic and inorganic impurities
Microbial contamination
Endotoxin
Particulate contamination
Low quality of water can lead to
 Product degradation
 Product contamination
 Loss of product and profit.
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5.  Colonize Free-swimming aquatic
bacteria on surfaces.
 Complex communities evolve which shed
microcolonies and bacteria.
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 Pipe work laid to fall (slope) - allows drainage
 Maintain system at high temperature (above 70 degrees Celsius)
 Use UV radiation
 Flow rate, life-cycle of the lamp
 Suitable construction material

6. Different grades of water
 Potable water.
 Purified water.
 Highly Purified Water
 Water for injection (Bulk).
Techniques for water Purification
 Chlorination/De-chlorination.
 Filtration (Sand/Activated Carbon etc.)
 Softening
 Precise Filters
 Revers Osmosis
 UV treatment/Ozonisation
 Distillation
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7. 7
pH 5-7 5-7 5-7
TOC < 500 ppb < 500 ppb < 500 ppb
Purified Water Highly Purified Water Water For Injection
Process
Ion exchange,
Reverse osmosis/Distillation
Double-Pass Reverse Osmosis,
Electronic Deionized
Multi-effect Distillation
Conductivity ≤ 4.3 μS/cm @ 20ºC ≤ 1.3 μS/cm @ 20ºC ≤ 1.1 μS/cm @ 20ºC
Bacteria 100 cfu/ml 10 cfu/100 ml 10 cfu/100 ml
Endotoxins - 0.25 EU/ml 0.25 EU/ml

8.  Piping
 Valves non return
 Pumps
 Filters
 RO Plant
 Sensors
 Storage Tank
 Pressure gauges
 Heat exchangers
 Electronized Deionizer
 Distillation
 Clean Steam generator
 Online monitoring system (conductivity/TOC)
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10.  To prove the performance, one must document that the processes or systems
consistently produce the specified quantity and quality of water when operated
and maintained according to specific written operating and maintenance
procedures.
 Validation involves proving
1. Engineering design
2. Operating procedures and acceptable ranges for control parameters
3. Maintenance procedures to accomplish it.
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System Build /
Implementation
Planning
VMP
SpecificationURS
FS
Verification PQ (Phase-1, 2, 3)
IQ
OQ
DS/DQ
FAT SAT
Reporting
Trend analysis,
Summary &
Recommendation
Final Report

12.  Functional Specification.(Storage, purification etc.)
 Technical/Performance specification for equipment. (requirements of water
volume and flow, define pumps and pipe sizes)
 Detailed layout of the system.
 Quality attribute of input water
 Required plant output capacity
 Designing of holding tanks pumps, heat exchangers and piping.
 Design must be in compliance with GMPs and other regulatory requirements.
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13.  Instrumentation checked against current engineering drawings and specs
 Verification of materials of construction material (SS 316L etc.)
 Installation of equipment, system with piping as per design.
 Calibration of measuring instruments
 Verification for absence of leakage & Dead Legs.
 Inspection for pipe slopes.
 Inspection document of UV lamp light intensity vs life.
 Passivation Record
 Storage Tanks & spry ball efficacy.
 Review of documentation of welds quality.
 Documentation include details of completed installation.
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14.  The purpose of OQ is to establish, through documented testing, that all critical
components are capable of operating within established limits and tolerances.
 The purpose of OQ is also to verify and document that the water supply
system provides acceptable operational control under “at-rest” conditions.
 To determine point-of-use, return and supply flow rates (velocities) on the
distribution loop.
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15.  The purpose of PQ is to verify and document that water supply system provides acceptable control under
‘ Full Operational ‘ conditions.
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There are different sampling points
• Feed Water
• After Sand Filtration
• After Activated Carbon Filtration
• After Softener Plant
• After RO
• After EDI
• After UV equipment
• Storage Tank
• After Distillation Plant
• WFI Storage Tank
• Point of use &
• Return from Distribution loop

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Phase - III
Verifying long term
control
Over One year Production
Phase Phase Type Monitoring Period Usage
Phase - I Investigation 4-6 weeks -
Phase - II Verification 4-6 weeks Production

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Again Thanks