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

Presented by Dr. Errol Allcoc 30 June 2005, Pretoria, South Africa

Errol.Allcock@microsep.co.za083-459 6267

Supplementary Training Modules on Good Manufacturing Practice

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 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 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

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 documentedAnnex 1, 17.32

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. Designed

2. Constructed

3. Maintained

4. Operated within design limits

5. Controlled to prevent microbial growthAnnex 1, 17.33

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

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

Water for Pharmaceutical Use

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 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

s

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

Water for Pharmaceutical Use

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 10 of 25 WHO - EDM

Water for Pharmaceutical Use

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 11 of 25 WHO - EDM

Water for Pharmaceutical Use

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

Water for Pharmaceutical Use

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 13 of 25 WHO - EDM

Water for Pharmaceutical Use

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 14 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 15 of 25 WHO - EDM

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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

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

Water for Pharmaceutical Use

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 17 of 25 WHO - EDM

Water for Pharmaceutical Use

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 18 of 25 WHO - EDM

Water for Pharmaceutical Use

Staining on water storage tanks

Corrosion on plates of heat exchangers indicates possible contamination

Conducting the inspection (4)Check condition of equipment

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Conducting the inspection (5) Check maintenance records

Check maintenance of pump seals and O rings

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Check air filters

Check integrity testing, sterilization and replacement frequency

Check burst discs

Conducting the inspection (6)

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

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• Carefully check by-pass valves and lines

• These sometimes leak or are

inadvertently left open

• A blanking piece is better during operation phase

Conducting the inspection (7)

Zeolite water softenerexchanges Ca and Mg for Na

Softened waterout to deionizer

By-pass valveBy-pass lines

Module 2, Part 3: Inspection of water systems Slide 22 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 23 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 24 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 25 of 25 WHO - EDM

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I N 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

Group Session You are given a schematic drawing of a water

system to discuss

List any problems and their solutions. 

Module 2, Part 3: Inspection of water systems Slide 26 of 25 WHO - EDM

Water for Pharmaceutical Use

M O D I F I E D W A T E R T R E A T M E N T P L A N T

Group Session