1. Pharmaceutical Water Systems
Mason P. Waterbury
Nektar Therapeutics
28 June 05

2. Pharmaceutical Water Systems
Let’s talk about:
What is High Purity Water?
How do we make High Purity Water?
How do we store and distribute High Purity Water?
Specific challenges / solutions

3. Pharmaceutical Water Systems
What is High Purity Water?
Purified Water (PW)
Sterile Purified Water (SPW)
Water for Injection (WFI)
Sterile Water for Injection (SWFI)
Water for Irrigation
Future Monographs (e.g., Water for Hemodialysis)

4. Pharmaceutical Water Systems
What is High Purity Water?
Purified Water (PW)
Sterile Purified Water (SPW)
Water for Injection (WFI)
Sterile Water for Injection (SWFI)
Water for Irrigation
Future Monographs

5. Pharmaceutical Water Systems
Purified Water
USP: “. . .obtained by a suitable process”
Conductivity ≤ º C
Total Organic Carbon (TOC) ≤ 500 ppb
Microbial ≤ 100 cfu/ml
No endotoxin requirement
EP: “. . .prepared by distillation, by ion exchange, by reverse osmosis or by any other suitable method”
JP: “. . .purified by distillation, ion-exchange treatment, ultrafiltration or combination of these methods”

6. Pharmaceutical Water Systems
Purified Water – Example System

7. Pharmaceutical Water Systems
Water for Injection (WFI)
USP: “. . .distillation or a purification process that is equivalent of superior to distillation”
Conductivity ≤ º C
Total Organic Carbon (TOC) ≤ 500 ppb
Microbial ≤ 10 cfu / 100 ml
Endotoxin requirement < 0.25 EU/ml
EP: “. . .distillation”
JP: “. . .distillation. . .or by the Reverse Osmosis Ultrafiltration of Purified Water”

8. Pharmaceutical Water Systems
Water for Injection (WFI) Distillation Techniques
Multi-Effect Still (MES)
Uses Plant Steam to convert feedwater to pure steam
Separators allow impurities to drop out of the pure steam
Pure steam from first effect used to convert feedwater to pure steam in subsequent effects

9. Pharmaceutical Water Systems
Water for Injection (WFI) Distillation Techniques
Vapor Compression (VC)
Uses plant steam to convert initial feedwater to vapor (pure steam)
Pure steam is compressed, elevating temperature
Compressed vapor is used to evaporate new feedwater, giving up latent heat and condensing as WFI
Higher electrical demand, but lower steam demand

10. Pharmaceutical Water Systems
High Purity Water Storage and Distribution
Materials of Construction (Chemical and Heat Compatibility)
Stainless Steel (316 or 316L)
Teflon, EPDM, Silicone, Viton (gaskets, diaphragms)
Fully Drainable (minimum slope 1/8” per foot, hygienic design of components)
Minimize Dead Legs (<= 2 pipe diameters)
Smooth Surfaces (Mechanical Polish vs. Electropolish)
Clean joints (sanitary Tri®Clamp, automatic orbital welding)
Passivate interior surfaces to form barrier between water and free iron

11. Pharmaceutical Water Systems
Storage and Distribution – Sanitization
Heat (Continuous or Periodic, >81 deg. C for >1 hour)
Most popular – nothing added to system
If system continuously hot, all but eliminates concerns about sanitization
Can be a utility hog
Ozone
Gaining popularity
Ozone destruction and monitoring very important
Environmental concerns
Chemical
Must ensure that cleaning chemicals are completely removed from system
Rinsing post-sanitization time and cost intensive

12. Pharmaceutical Water Systems
Storage and Distribution – Hot vs. Cold ?
Hot storage:
WFI produced through distillation is often generated hot, so why not store it hot?
Advantageous if there will be hot WFI distribution
Cold storage:
Periodic heat-up & cool-down of storage tank time- and energy-intensive
Could expedite heat-up by dumping tank contents, but this is wasteful
Best solution will vary depending on specific user requirements

13. Pharmaceutical Water Systems
Hot Storage, Hot and Ambient Distribution

14. Pharmaceutical Water Systems
Hot Storage, Hot and Ambient Distribution
Cost-effective when there are many ambient use points
Heat Sanitization of ambient loop by displacement of AWFI or by heating ambient loop
Two loops mean increased installation labor
Only one heat exchanger means all ambient users get water at same temperature, no local temperature selection

15. Pharmaceutical Water Systems
Hot Storage, Hot Distribution with Use Point Coolers

16. Pharmaceutical Water Systems
Hot Storage, Hot Distribution with Use Point Coolers
Cost-effective when there are few ambient use points
Main distribution loop is continuously hot, therefore self-sanitizing
Can have locally adjustable use point temperatures
Ambient point-of-use piping must be sanitized by flushing or pulsing HWFI through heat exchanger to drain
Additional heat exchangers means increased capital (and maintenance) cost
Some feel POU cooler piping is a dead leg, prone to microbial growth

17. Pharmaceutical Water Systems
Hot Storage, Hot Distribution with Use Point Cooler Sub-loops

18. Pharmaceutical Water Systems
Hot Storage, Hot Distribution with Use Point Cooler Sub-loops
Cost-effective when there are few ambient use points
Main distribution loop is continuously hot, therefore self-sanitizing
Heat exchanger piping kept hot when not in use
Can have locally adjustable use point temperatures
Dead leg question replaced by “turbulent flow” question – this becomes a balancing problem
Additional heat exchangers means increased capital (and maintenance) cost