Supplementary Training Modules on Water for Pharmaceutical Use Good Manufacturing Practice

Water for Pharmaceutical Use

Part 3: Inspection of water systems

Module 2, Part 3: Inspection of water systems

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Water for Pharmaceutical Use

Objectives
To understand:
1.

The specific requirements for inspecting water systems, including

2.

the need for a Water Quality Manual validation of water treatment systems Water system inspection techniques

Module 2, Part 3: Inspection of water systems

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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

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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

Module 2, Part 3: Inspection of water systems

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Water for Pharmaceutical Use

WHO water treatment guidance (2)
For reliable production, water treatment plants should be:
1. 2. 3. 4. 5.

Designed Constructed Maintained Operated within design limits

Controlled to prevent microbial growth

Annex 1, 17.33

Module 2, Part 3: Inspection of water systems

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Water for Pharmaceutical Use

Prepare a checklist or an aide-memoire

and review:
1. 2.

Water Quality Manual Water system drawing

3.
4. 5. 6. 7.

Validation
Sampling procedures, locations and plan Records of testing Sanitation and maintenance Schedules of maintenance
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Module 2, Part 3: Inspection of water systems

Water for Pharmaceutical Use

Review water quality manual (1)
1.
2. 3.

A water quality manual is advisable

A brief description of water systems is required

Include drawings of the purification, storage

distribution system (P&ID)

Module 2, Part 3: Inspection of water systems

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Water for Pharmaceutical Use

Review of water quality manual (2)

The water quality manual should show:

pipelines
velocities

non-return (or check) valves breather points couplings pipe slopes

valves sampling points drain points instrumentation flow rates

Module 2, Part 3: Inspection of water systems

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Water for Pharmaceutical Use

Review water quality manual (3)
The manual should contain:
1. 2.

Specification for each system element Standard procedures for use

3.
4. 5.

System changes
Routine and non-routine maintenance Investigations and corrective action

6.

Validation studies

Module 2, Part 3: Inspection of water systems

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Water for Pharmaceutical Use

Review water quality manual (4)
The manual should contain
1. 2.

Chemical and microbiological specifications Sampling instructions

3.
4. 5.

Test procedures
Responsible persons Training requirements

Module 2, Part 3: Inspection of water systems

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Water for Pharmaceutical Use

Review validation (1)
Validation for water systems consists of three phases

Phase 1:

2 4 weeks

Phase 2:
Phase 3:

4 weeks
1 year

Module 2, Part 3: Inspection of water systems

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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

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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 PQ Demonstrate the system in control over a long period of time Weekly sampling
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Phase 3 verifying long-term control (1 year)

Module 2, Part 3: Inspection of water systems

Water for Pharmaceutical Use

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

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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

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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

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Water for Pharmaceutical Use

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 17 of 25
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Water for Pharmaceutical Use

Conducting the inspection (5)

Check maintenance records

Check maintenance of pump seals and O rings

Module 2, Part 3: Inspection of water systems

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Water for Pharmaceutical Use

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

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

By-pass lines Carefully check by-pass valves and lines These sometimes leak or are inadvertently left open A blanking piece is better during operation phase
Zeolite water softener exchanges Ca and Mg for Na

Module 2, Part 3: Inspection of water systems

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Water for Pharmaceutical Use

Conducting the inspection (8)
Further points to check:
1. 2. 3. 4.

Activated carbon bed sanitization Temperature-compensated conductivity meters Influence of plastic pipe adhesive on TOC Non-condensable gases in pure steam

Module 2, Part 3: Inspection of water systems

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Water for Pharmaceutical Use

Conducting the inspection (9)
Further points to check: (Contd.)
1.

Polypropylene welding inspection checking pin holes

2.
3. 4.

Retrospective validation of WFI system

Rouging of WFI storage systems Spray ball efficacy

Module 2, Part 3: Inspection of water systems

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Water for Pharmaceutical Use

Conducting the inspection (10)
Further points to check (Contd.)
1.

UV light monitoring performance and lamp life and intensity

1.
2.

Validating ozone dosage

Specifications for acids, alkalis for DI and sodium chloride for water softener Normally open and normally closed valves
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3.

Module 2, Part 3: Inspection of water systems

Water for Pharmaceutical Use

Group Session

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

IN CO RRECT WA TER TREA TM EN T PLA N T

Module 2, Part 3: Inspection of water systems

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Water for Pharmaceutical Use

Group Session

M O DIFIED WA TER TREA TM EN T PLA N T

Module 2, Part 3: Inspection of water systems

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