Pharmaceutical Water

Systems

Mason P. Waterbury
Nektar Therapeutics
28 June 05
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

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)

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
Pharmaceutical Water Systems
• Purified Water
– USP: “. . .obtained by a suitable process”
• Conductivity ≤ 1.3 µS/cm @ 25º 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”
Pharmaceutical Water Systems

• Purified Water – Example System

Pharmaceutical Water Systems
• Water for Injection (WFI)
– USP: “. . .distillation or a purification process that is
equivalent of superior to distillation”
• Conductivity ≤ 1.3 µS/cm @ 25º 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”
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
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
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
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
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
Pharmaceutical Water Systems

Hot Storage, Hot and Ambient Distribution

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

Hot Storage, Hot Distribution with Use Point

Cooler Sub-loops
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