Supplementary Training Modules on Good Manufacturing Practice

1. Water for Pharmaceutical UsePart 3: Inspection of water systemsPresented byDr. Errol Allcoc 30 June 2005, Pretoria, South AfricaErrol.Allcock@microsep.co.za083-459 6267 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

6. 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. Reviewwater 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 (P&ID)

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

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

12. Reviewvalidation (1) Validation for water systems consists of three phases • Phase 1: 2 – 4 weeks • Phase 2: 4 weeks • Phase 3: 1 year

13. 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

14. 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 long period of time • Weekly sampling

15. 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

16. Conducting the inspection (2) Check: • Stainless steel - PVC and most plastics not recommended • Weld quality • Hygienic couplings • Passivation • Air breaks or “Tundish”

17. Conducting the inspection (3) • Check pipes and pumps • hygienic couplings • welded pipes • hygienic pumps • hygienic sampling points • acceptable floor • no leaks

18. Conducting the inspection (4) Check condition of equipment Staining on water storage tanks Corrosion on plates of heat exchangers indicates possible contamination

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

20. Conducting the inspection (6) • Check air filters • Check integrity testing, sterilization and replacement frequency • Check burst discs

21. Softened water out to deionizer By-pass lines By-pass valve Zeolite water softener exchanges Ca and Mg for Na 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

22. 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

23. 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

24. 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

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

26. Group Session