Water for Pharmaceutical Use Part 3: Inspection of water systems

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Water for Pharmaceutical UsePart 3 Inspection
of water systems

• Supplementary Training Modules on Good
  Manufacturing Practice

2

• Objectives
• To understand
• The specific requirements for inspecting
  water systems, including
• the need for a Water Quality Manual
• validation of water treatment systems
• Water system inspection techniques

3

• 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

4

• 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
5

• WHO water treatment guidance (2)
• For reliable production, water treatment plants
  should be
• Designed
• Constructed
• Maintained
• Operated within design limits
• Controlled to prevent microbial growth

Annex 1, 17.33
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• Prepare a checklist or an aide-memoire
• and review
• Water Quality Manual
• Water system drawing
• Validation
• Sampling procedures, locations and plan
• Records of testing
• Sanitation and maintenance
• Schedules of maintenance

7

• Review water quality manual (1)
• A water quality manual is advisable
• A brief description of water systems is required
• Include drawings of the purification, storage
  distribution system (PID)

8

• 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
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• Review water quality manual (3)
• The manual should contain
• Specification for each system element
• Standard procedures for use
• System changes
• Routine and non-routine maintenance
• Investigations and corrective action
• Validation studies

10

• Review water quality manual (4)
• The manual should contain
• Chemical and microbiological specifications
• Sampling instructions
• Test procedures
• Responsible persons
• Training requirements

11

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

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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

13

• 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

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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
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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

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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

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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
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• Conducting the inspection (5)
• Check maintenance records
• Check maintenance of pump seals and O rings

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Conducting the inspection (6)

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

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Conducting the inspection (7)

• Carefully check by-pass valves and lines
• These sometimes leak or are inadvertently
  left open
• A blanking piece is better during operation
  phase

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• Conducting the inspection (8)
• Further points to check
• Activated carbon bed sanitization
• Temperature-compensated conductivity meters
• Influence of plastic pipe adhesive on TOC
• Non-condensable gases in pure steam

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

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• Conducting the inspection (10)
• Further points to check (Contd.)
• UV light monitoring performance and
• lamp life and intensity
• 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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• Group Session
• You are given a schematic drawing of a water
  system to discuss
• List any problems and their solutions. 

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Group Session