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

Water for Pharmaceutical Use

Water for Pharmaceutical Use

Part 3:

Inspection of water systems

Supplementary Training Modules onGood Manufacturing Practice

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

Water for Pharmaceutical Use

Objectives

To understand:

1. The specific requirements for inspectingwater systems, including

the need for a Water Quality Manual

validation of water treatment systems

2. Water system inspection techniques

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

Water for Pharmaceutical Use

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

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

Water for Pharmaceutical Use

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

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

Water for Pharmaceutical Use

WHO water treatment guidance (2)

For reliable production, water treatment plants should be:

1. Designed2. Constructed

3. Maintained

4. Operated within design limits

5. Controlled to prevent microbial growth

Annex 1, 17.33

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

Water for Pharmaceutical Use

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

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

Water for Pharmaceutical Use

Reviewwater 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)

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

Water for Pharmaceutical Use

Review of water quality manual (2)

The water quality manual should show:

pipelines

non-return (or check) valves

breather points

couplings

pipe slopes

velocities

valves

sampling points

drain points

instrumentation

flow rates

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

Water for Pharmaceutical Use

Reviewwater 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

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

Water for Pharmaceutical Use

Reviewwater quality manual (4)

The manual should contain

1.

Chemical and microbiological specifications2. Sampling instructions

3. Test procedures

4. Responsible persons

5. Training requirements

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

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Reviewvalidation (1)

Validation for water systems consists of threephases

Phase 1: 2 4 weeks

Phase 2: 4 weeks

Phase 3: 1 year

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

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Reviewvalidation (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

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

Water for Pharmaceutical Use

Reviewvalidation (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 longperiod of time

Weekly sampling

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

Water for Pharmaceutical Use

Conducting the inspection (1) Take the drawing and walk around the entire system

Check:

dead legs

filter

pipes and fittings

DI

storage tanks

by-pass lines

pumps

UV lights

sample points

RO

non return valves

heat exchangers

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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 notrecommended

Weld quality

Hygienic couplings

Passivation

Air breaks or Tundish

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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

hygienicsampling points

acceptable floor

no leaks

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

Water for Pharmaceutical Use

Staining onwater storagetanks

Corrosion on plates of heatexchangers indicates possiblecontamination

Conducting the inspection (4)

Check condition of equipment

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Module 2, Part 3: Inspection of water systems Slide 18 of 25 WHO - EDM

Water for Pharmaceutical Use

Conducting the inspection (5)

Check maintenance records

Check maintenance of pump seals and O rings

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

Water for Pharmaceutical Use

Check air filters

Check integrity testing,sterilization andreplacement frequency

Check burst discs

Conducting the inspection (6)

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

Water for Pharmaceutical Use

Carefully check by-passvalves and lines

These sometimes leak or are

inadvertently left open

A blanking piece is better

during operation phase

Conducting the inspection (7)

Zeolite water softener

exchanges Ca and Mg for Na

Softened water

out to deionizerBy-pass valve

By-pass lines

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

Water for Pharmaceutical Use

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

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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

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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

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

Water for Pharmaceutical Use

IN CORRECT WA TER TREA TMENT PLANT

Group Session

You are given a schematic drawing of a water system todiscuss

List any problems and their solutions.

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