Design and Construction of USP Purified Water Systems

1. Design and Construction of USP Purified Water Systems William V. Collentro

2. Feed Water Analysis

3. USP Purified Water System – Feed Water Analysis • Official Monograph • United States EPA NPDWR • Equivalent European Regulations • Equivalent Japanese Regulations • World Health Organization Reference

4. USP Purified Water System – Feed Water Analysis • United States EPA – National Primary Drinking Water Regulations (NPDWR) • Regulated Items • Total Viable Bacteria • “Private” Water Supplies

5. USP Purified Water System – Feed Water Analysis • Regulated Items - Microorganisms • Cryptosporidium • Giardia lamblia • Legionella • Total Coliform • Turbidity • Viruses

6. USP Purified Water System – Feed Water Analysis • Regulated Items – Disinfection Byproducts • Bromate • Chlorite • Haloacetic Acids (HAA5) • Total Trihalomethanes (TTHMs)

7. USP Purified Water System – Feed Water Analysis • Regulated Items – Disinfectants • Chlorine • Chloramines • Chlorine Dioxide

8. USP Purified Water System – Feed Water Analysis • Regulated Items – Inorganic Chemicals • Antimony • Arsenic • Asbestos • Barium • Beryllium • Cadmium • Total Chromium • Copper

9. USP Purified Water System – Feed Water Analysis • Regulated Items – Inorganic Chemicals • Cyanide • Fluoride • Lead • Mercury • Nitrate • Nitrite • Selenium • Thallium

10. USP Purified Water System – Feed Water Analysis • Regulated Items – Organic Chemicals (53 Total) • Sewage/Wastewater Treatment • Herbicides • Landfill Leachates • Chemical/Industrial Facility Waste • Fumigants • Petroleum /Refinery Waste • Insecticides

11. USP Purified Water System – Feed Water Analysis • Regulated Item – Radionuclides • Alpha Particles • Beta Particles and Photon Emitters • Radium 226 • Uranium

12. USP Purified Water System – Feed Water Analysis • Total Viable Bacteria • No limit in NPDWR • Total Coliform (Confirmed as Fecal Coliform or E. coli, used as indicator) • “Action Limit” of 500 cfu/ml in non enforceable General Information Section of USP • TVB may only indicate a fraction of viable organisms present

13. USP Purified Water System – Feed Water Analysis • Regulated Items - Testing • Municipality? • Pharmaceutical Facility? • Compliance? • Obligation? • Consequences?

14. Periodic Monitoring

15. USP Purified Water System – Periodic Monitoring • General Monitoring – Storage and Distribution System • Point-of-Use TVB • Online Conductivity • Online TOC

16. USP Purified Water System – Periodic Monitoring • General Monitoring – Water Purification System • Final TVB • Inline RO Feed Water and Product Water Conductivity plus % Rejection of Ions • Inline Post RO Polishing Conductivity

17. USP Purified Water System – Periodic Monitoring • Frequent Monitoring – Water Purification System • Silt Density Index (Test Kit) • Total Hardness (Test Kit) • Chlorine (Test Kit)

18. USP Purified Water System – Periodic Monitoring • Less Frequent Monitoring – Water Purification System • Inline ORP for Reducing Agent Injection Monitoring • Inline Total Hardness Monitor • Inline Chlorine Monitor

19. USP Purified Water System – Pretreatment Periodic Monitoring

20. USP Purified Water System – RO/Polishing Periodic Monitoring

21. USP Purified Water System – Periodic Monitoring • Summary • Monitoring of Pretreatment and Ion Removal steps identifies a problem before it effects point-of-use values. • Frequency of the monitoring program established for each application • Regulatory concerns

22. Sanitization Provisions

23. USP Purified Water System –Sanitization Provisions • Frequency • Determined by microbial monitoring • Must include storage, distribution, ion removal, and pretreatment • Employs chemical and thermal methods • Ineffectiveness of Steam • Biofilm requires chemical sanitizing agent

24. USP Purified Water System –Sanitization Provisions • Fundamentals • TVB destruction a function of concentration and time for chemical sanitization • TVB destruction a function of temperature and time for hot water with 65°C lowest temperature • Dead Leg for thermal sanitization • Dead leg for chemical sanitization

25. USP Purified Water System –Sanitization Provisions • Fundamentals • Removal of Biofilm • Activated Carbon Issues • RO Waste Recirculation Issues • Pretreatment and Ion removal Recirculation Issues • Hot water sanitizable ion removal systems • Pretreatment must be included

26. USP Purified Water System –Sanitization Provisions • Execution - Pretreatment • Hot Water Sanitizable Activated Carbon • Chemical Sanitization with 1% solution of Hydrogen Peroxide and Peracidic Acid (except activated carbon unit) • Replace activated carbon media every 6-12 months • Dynamic-Stagnant-Dynamic Procedure

27. USP Purified Water System –Sanitization Provisions • Execution – Ion Removal • Continuous operation (make-up and recirculation) • Hot Water Sanitization Provisions (entire system) • RO membrane rotation every 6 months • Chemical Sanitization with 1% solution of Hydrogen Peroxide and Peracidic Acid annually • Dynamic-Stagnant-Dynamic Procedure

28. USP Purified Water System –Sanitization Provisions • Execution – Storage & Distribution • Ozonation • Periodic Hot Water • Membrane Filtration discouraged • Chemical Sanitization with 1% solution of Hydrogen Peroxide and Peracidic Acid annually • Dynamic-Stagnant-Dynamic Procedure

29. Validation Criteria

30. Validation Criteria • Commissioning Documentation • Reference in IQ and OQ • “Credit” for inspection and testing • Factory Acceptance Test (FAT) Documentation • Turnover Packages (TOP) • Coordination • Interface

31. Validation Criteria • IQ Format • Unit operation based with all support documentation for components and accessories verified. Support documents in document or as an appendix/attachment. Provides understanding of component by individuals preparing, reviewing, and executing IQ • Component based program for items such as valves, gauges, pumps, etc. Poor tool for individuals to understand the system.

32. Validation Criteria • IQ Information • Limits on material? The more information available, the better. If a accessory breaks, it must be replaced. The model number, serial number, and/or manufacturer may change or no longer exists. “Cut sheets” of accessories provide an excellent vehicle for identifying a “like-for-like” replacement which significantly reduces the “Change Control” effort.

33. Validation Criteria • IQ Information • All support information should reference the original manufacturer’s part number. Project specifications should clearly state that the name of the manufacturer as well as the part number be provided. The vast majority of this information is “coded” to the water purification equipment manufacturer’s model number, useless for replacement on a “like-for-like” basis.

34. Validation Criteria • OQ Information • Prepared and executed in an integrated basis. Individual Unit Operation will impact the operation of other components. • Execution must provide exact operating condition. As an example, if media is not installed in a pretreatment component during execution of a FAT, execution (partial) may be required after installation and start-up.

35. Validation Criteria • OQ Information – Considerations • Fixed alarm and operating set points versus adjustable set points • Processor access levels • Alarm set points and time delays • Control set points and time delays • View screen navigation • “ALERM” banner display • “OPERATOR OVERRIDE” banner display

36. Validation Criteria • PQ Criteria • Post start-up and commissioning • 30 day sample period • Sampling plan to duplicate water use • “Working days” • Attempt to duplicate water demand • Attempt to duplicate actual conditions at individual points-of-use

37. Validation Criteria • PQ Criteria • Every point-of-use every day if practical • TOC “grab” samples from each points-of-use • Conductivity “grab” samples from points-of-use • Suggest transition for about 30-60 days after successful execution • Continues for one year period • Monitoring never stops

38. Validation Criteria • PQ Microbial Monitoring • Duplicate sampling schedule over length of intense monitoring program and less frequently thereafter • Different agar (PCA versus R2A) • Different incubation temperatures (22°C and 30-35°C) • Extended incubation time period (3, 5, 8, and 10 days)

39. Validation Criteria • PQ Microbial Monitoring • EP Monograph Reference • Verify enumeration parameters • Bacteria identification • MIS • Riboprinter • Gram Stain • Objectionable organisms • Summary Report

40. Operating Procedures

41. Standard Operating Procedures • General Considerations • Prepared, reviewed, and accepted before OQ execution • Verbatim compliance • Keep as concise as possible • Do not include maintenance procedures • “Control” of copies important • Formal training

42. Standard Operating Procedures • General Considerations • Video tape training sessions • Training Manuals • System P&IDs mounted in water system area • Documentation of individual attending training sessions • Periodic retraining • Personnel incident/excursion retraining

43. Preventative Maintenance Program

44. Preventative Maintenance Program • Objective - Proactive not reactive - Shutdown Considerations – frequency - Cost of lost production time - Cost of quarantine of product - Cost of lost product - “Micro delay”

45. Preventative Maintenance Program • Pretreatment Component Example – Activated Carbon Unit

46. Preventative Maintenance Program • Ion Removal Component Example – Reverse Osmosis Unit

47. Preventative Maintenance Program • Ion Removal Component Example – Reverse Osmosis Unit

48. Preventative Maintenance Program • Storage & Distribution Loop Example – USP Purified Water Storage Tank (No Ozone)

49. Preventative Maintenance Program • Ion Removal Component Example – Reverse Osmosis Unit

50. Thank you! Questions?