water for pharmaceutical uses: inspection
TRANSCRIPT
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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
Water for Pharmaceutical Use
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
Water for Pharmaceutical Use
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
Water for Pharmaceutical Use
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
Water for Pharmaceutical Use
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
Water for Pharmaceutical Use
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
Water for Pharmaceutical Use
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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