Supplementary Training Modules

Water for Pharmaceutical Use on

Good Manufacturing Practice

Water for Pharmaceutical Use

Part 3:
Inspection of water systems

Presented by Dr. Errol Allcoc

30 June 2005, Pretoria, South Africa
Errol.Allcock@microsep.co.za
083-459 6267

Module 2, Part 3: Inspection of water systems Slide 1 of 25 WHO - EDM

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Objectives
To understand:
1.Thespecific requirements for inspecting
water systems, including
 the need for a Water Quality Manual
 validation of water treatment systems
2.Water system inspection techniques

Module 2, Part 3: Inspection of water systems Slide 2 of 25 WHO - EDM

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Review
 What is the water to be used for?
 sterile products
 non-sterile products
 liquid products
 solid dose products
 washing and rinsing
 Check specifications and trends

Module 2, Part 3: Inspection of water systems Slide 3 of 25 WHO - EDM

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WHO water treatment guidance (1)

 All water-treatment systems should be subject to:
 planned maintenance
 validation
 monitoring
 Maintenance work should be documented

Annex 1, 17.32

Module 2, Part 3: Inspection of water systems Slide 4 of 25 WHO - EDM

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WHO water treatment guidance (2)

For reliable production, water treatment plants should be:
1. Designed
2. Constructed
3. Maintained
4. Operated within design limits
5. Controlled to prevent microbial growth
Annex 1, 17.33

Module 2, Part 3: Inspection of water systems Slide 5 of 25 WHO - EDM

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Prepare a checklist or an aide-memoire
and review:
1. Water Quality Manual
2. Water system drawing
3. Validation
4. Sampling procedures, locations and plan
5. Records of testing
6. Sanitation and maintenance
7. Schedules of maintenance

Module 2, Part 3: Inspection of water systems Slide 6 of 25 WHO - EDM

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Review water quality manual (1)

1. A water quality manual is advisable

2. A brief description of water systems is required

3. Include drawings of the purification, storage

distribution system (P&ID)

Module 2, Part 3: Inspection of water systems Slide 7 of 25 WHO - EDM

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Review of water quality manual (2)

 The water quality manual should show:
 pipelines  valves
 non-return (or check) valves  sampling points
 breather points  drain points
 couplings  instrumentation
 pipe slopes  flow rates
 velocities

Module 2, Part 3: Inspection of water systems Slide 8 of 25 WHO - EDM

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Review water quality manual (3)

The manual should contain:
1. Specification for each system element
2. Standard procedures for use
3. System changes
4. Routine and non-routine maintenance
5. Investigations and corrective action
6. Validation studies

Module 2, Part 3: Inspection of water systems Slide 9 of 25 WHO - EDM

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Review water quality manual (4)

The manual should contain
1. Chemical and microbiological specifications
2. Sampling instructions
3. Test procedures
4. Responsible persons
5. Training requirements

Module 2, Part 3: Inspection of water systems Slide 10 of 25 WHO - EDM

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Module 2, Part 3: Inspection of water systems Slide 11 of 25 WHO - EDM

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Review validation (1)
Validation for water systems consists of three
phases
 Phase 1: 2 – 4 weeks
 Phase 2: 4 weeks
 Phase 3: 1 year

Module 2, Part 3: Inspection of water systems Slide 12 of 25 WHO - EDM

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Review validation (2)
Phase 1 – Investigational Phase (2 – 4 weeks)
 DQ, IQ and OQ
 Develop
 operational parameters
 cleaning and sanitization procedures and frequencies
 Sample daily at each point of use
 End of Phase I, develop SOPs for the water system

Module 2, Part 3: Inspection of water systems Slide 13 of 25 WHO - EDM

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Review validation (3)
Phase 2 – verifying control (4 - 5 weeks)
 Demonstrate the system is in control
 Same sampling as in phase 1

Phase 3 – verifying long-term control (1 year)

 PQ
 Demonstrate the system in control over a long
period of time
 Weekly sampling

Module 2, Part 3: Inspection of water systems Slide 14 of 25 WHO - EDM

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Conducting the inspection (1)

 Take the drawing and walk around the entire system
 Check:
 dead legs  pumps
 filter  UV lights
 pipes and fittings  sample points
 DI  RO
 storage tanks  non return valves
 by-pass lines  heat exchangers

Module 2, Part 3: Inspection of water systems Slide 15 of 25 WHO - EDM

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Conducting the inspection (2)

Check:
 Stainless steel - PVC and most plastics not
recommended
 Weld quality
 Hygienic couplings
 Passivation
 Air breaks or “Tundish”

Module 2, Part 3: Inspection of water systems Slide 16 of 25 WHO - EDM

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Conducting the inspection (3)

 Check pipes and pumps
 hygienic couplings
 welded pipes
 hygienic pumps
 hygienic
sampling points
 acceptable floor
 no leaks

Module 2, Part 3: Inspection of water systems Slide 17 of 25 WHO - EDM

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Conducting the inspection (4)

Check condition of equipment

Staining on
water storage
tanks

Corrosion on plates of heat

exchangers indicates possible
contamination
Module 2, Part 3: Inspection of water systems Slide 18 of 25 WHO - EDM
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Conducting the inspection (5)

 Check maintenance records
 Check maintenance of pump seals and O rings

Module 2, Part 3: Inspection of water systems Slide 19 of 25 WHO - EDM

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Conducting the inspection (6)

 Check air filters
 Check integrity testing,
sterilization and
replacement frequency
 Check burst discs

Module 2, Part 3: Inspection of water systems Slide 20 of 25 WHO - EDM

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Conducting the inspection (7)
Softened water
out to deionizer By-pass lines
By-pass valve

• Carefully check by-pass

valves and lines
• These sometimes leak or are

inadvertently left open

• A blanking piece is better
Zeolite water softener during operation phase
exchanges Ca and Mg for Na

Module 2, Part 3: Inspection of water systems Slide 21 of 25 WHO - EDM

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Conducting the inspection (8)
Further points to check:

1. Activated carbon bed sanitization

2. Temperature-compensated conductivity meters

3. Influence of plastic pipe adhesive on TOC

4. Non-condensable gases in pure steam

Module 2, Part 3: Inspection of water systems Slide 22 of 25 WHO - EDM

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Conducting the inspection (9)
Further points to check: (Contd.)
1. Polypropylene welding inspection
 checking pin holes
2. Retrospective validation of WFI system
3. Rouging of WFI storage systems
4. Spray ball efficacy

Module 2, Part 3: Inspection of water systems Slide 23 of 25 WHO - EDM

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Conducting the inspection (10)
Further points to check (Contd.)
1. UV light – monitoring performance and
lamp life and intensity
1. Validating ozone dosage
2. Specifications for acids, alkalis for DI and
sodium chloride for water softener
3. “Normally open” and “normally closed” valves

Module 2, Part 3: Inspection of water systems Slide 24 of 25 WHO - EDM

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Group Session
 You are given a schematic drawing of a water system to
discuss
 List any problems and their solutions. 

IN C O R R E C T W A T E R T R E A T M E N T P L A N T
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Group Session

M O D IF IE D W A T E R T R E A T M E N T P L A N T

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