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Water System

Water System. Supaporn Phumiamorn 17-18 Jan, 2006. GMP course. Topic. Water system - Objectives and Principles - Storage, Treatment - Contaminants, Sampling Water system inspection. Objectives. - Introduction to water for pharmaceutical use - Sources and types of water for

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Water System

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  1. Water System Supaporn Phumiamorn 17-18 Jan, 2006 GMP course

  2. Topic • Water system - Objectives and Principles - Storage, Treatment - Contaminants, Sampling • Water system inspection Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  3. Objectives - Introduction to water for pharmaceutical use - Sources and types of water for pharmaceutical use - Storage of bulk, untreated raw water - Pre-treatment of water Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  4. Principles • Like any starting material, water must conform to GMP norms. • It must be “potable and comply with WHO guidelines for drinking-water quality. Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  5. Principles • Potential for microbial growth • Systems must be properly validated • Water for parenteral use could not be contaminated with pyrogens or endotoxins • Specifications and periodic testing is required Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  6. Water hardness Water hardness mg/L or ppm Classification as CaCO3 Soft 0-60 Moderate 61-120 Hard 121-180 Very hard >180 Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  7. Raw water storage • May be required prior to pre-treatment according to local circumstances • Check material of construction - Concrete, steel are acceptable but check corrosion - Plastics or plastic linings may leach Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  8. Raw water storage • Check cover - to keep out insects, birds and animals • Check contamination Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  9. Types of water used in pharmaceutical processes • Water for Injections – PFW & WFI • Softened Water • Water for Final Rinse • Pure, or Clean Steam • Purified Water • Water for Cooling Autoclaves Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  10. Pre-treatment steps • Primary filtration and multi-media filter • Coagulation of flocculation • Desalination • Softening Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  11. Water pre-treatment complex External raw water storage Pretreatment room

  12. Chlorine removal Activated-carbon (AC) filtration or bisulphite • AC removes chlorine but bacteria can then grow. • AC filtration can remove organic impurities. • Bisulphite leaves sulphate residues but is anti-microbial. Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  13. Why purify raw water? • Although reasonably pure, it is always variable • Seasonal variations may occur in water • Some regions have very poor quality water • Must remove impurities to prevent productcontamination. • Controlmicrobesto avoid contaminating products Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  14. Contaminants of water (1) • There is no pure water in nature, as it can contain up to 90 possible unacceptable contaminants • Contaminant groups: • Inorganic compounds • Organic compounds • Solids • Gases • Micro-organisms Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  15. Contaminants of water (2) Treatment depends on water’s chemistry and contaminants, influenced by: 1. Rainfall 5. Evaporation 2. Erosion 6. Sedimentation 3. Pollution 7. Decomposition 4. Dissolution Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  16. Contaminants of water (3) Problem minerals • Calcium and magnesium • Iron and manganese • Silicates • Carbon dioxide • Hydrogen sulfide • Phosphates Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  17. Contaminants of water (4) Further problem minerals • Copper • Aluminium • Heavy metals • Arsenic, lead, cadmium • Nitrates Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  18. Contaminants of water (5) Micro-organisms – Biofilm • Algae • Protozoa • Cryptosporidium • Giardia • Bacteria • Pseudomonas • Gram negative, non-fermenting bacteria • Escherichia coli and coliforms Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  19. Pretreatment – schematic drawing float operated valve To water softener & DI plant activated carbon filter excess water recycled from deioniser sand filter air filter spray ball Water is kept circulating raw water in break tank cartridge filter 5 micrometers centrifugal pump air break to drain « S” trap to sewer

  20. Plumbing Source water Pre-treatment Distillation S S S S S Holding Take  80oc chlorination S . 1.Filtration -Sand filter -Charcoal filter -Cartridge filter S S Pump * S: Sampling • 2. Primary water treatment • Water solftener • Deionizer • Reverse Osmosis

  21. by pass valve brine and salt tank "soft" water to deioniser brine "hard" water in • zeolite water softener • exchanges • Ca and Mg for Na drain Water Softener – schematic drawing

  22. Water purification RO / Deionizer Cartridge filtration

  23. Water purification Reverse Osmosis Remove particles, bacteria, pyrogen, organic, inorganic ions and silica

  24. Water purification Deionization Remove organic, inorganic ions, silica and carbon dioxide

  25. Water purification Distillation Remove particles, bacteria, pyrogen, organic, non-volatile, inorganic ions and silicafor WFI

  26. Water purification Ultrafiltration Kill bacteria and breakdown TOC

  27. Auto DI RO/Auto DI 2 stages RO Purified water

  28. -Conductivity meter - pH meter -Temperature meter(80oC) -Alarm meter

  29. Sampling • There must be a sampling procedure. • Sample integrity must be assured. • Sampler training • Sample point • Sample size • Sample container Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  30. Sampling • Sample label • Sample storage and transport • Arrival at the laboratory • Start of test Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  31. Water for Injections • International pharmacopoeia requirements for WFI are those for purified water plus it must be free from pyrogens. • Usually prepared by distillation. • Storage time should be less than 24 hours. • Microbial limits must be specified. Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  32. Pyrogens and endotoxins • Any compound injected into mammals which gives rise to fever is a “Pyrogen”. Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  33. WFI testing • Microbial test, < 1 CFU/10 ml WFI • Endotoxin test, < 0.25 Eu/ml • Total organic count,< 500 g/l Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  34. Water system inspection Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  35. Inspection plan Water quality manual - water system drawing - validation - sampling procedures, location and plan - records of testing - sanitation and maintenance - schedules of maintenance Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  36. Review water quality manual • A water quality manual is advisable. • A brief description of water systems is required. • Include drawings of the purification, storage distribution system. Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  37. The manual should contain • Chemical and microbiological specifications • Sampling instructions • Test procedures • Responsible persons • Training requirements Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  38. Review validation Validation for water systems consists of 3 phases: Phase 1: 2-3 weeks Phase 2: 4 weeks Phase 3: 1 year Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  39. 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 1, develop SOPs for the water system Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  40. Phase 2 • Verifying control (4- 5 weeks) - Demonstrate the system is in control -Sampling as in phase 1 Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  41. Phase 3 • Verifying long- term control ( 1 year) - Demonstrate the system in control over a long period of time -Weekly sampling Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  42. Conducting the inspection • Take the drawing and walk around the entire system • Check: - dead legs - pumps -filter - UV light -pipe and fittings - sample points -DI - RO -storage tank - non return valves -by –pass lines - heat exchangers

  43. Check: - stainless steel – PVC and most plastics not recommended - water quality - hygienic couplings - passivation - air breaks or “Tundish” Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  44. Check: - condition and equipment corrosion on plates of heat exchangers indicates possible contamination - maintenance records Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  45. Check: - air filter - integrity testing, sterilization - replacement frequency - burst discs Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

  46. References • WHO,1997. Joint training on GMP for biological products in Thailand, 2-11 September, 1997 • Chung Keel Lee, 2003. GMP and related topics, 13-15 October, 2003. • Chung Keel Lee, 2004. Current GMP for biological products and its practical implementation, 22-23 March, 2004. • FDA and WHO, 2004. GMP inspection workshop, 21-29 June, 2004. Supaporn Phumiamorn, GMP course, 17-18 Jan,2006

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