ispe_sfc pharma water sys

7/27/2019 ISPE_SFC pharma water sys

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Pharmaceutical WaterSystems

Mason P. Waterbury

Nektar Therapeutics

28 June 05
http://www.ispe.org/


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Pharmaceutical Water Systems

Lets 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


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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)


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Purified Water (PW)

Sterile Purified Water (SPW)


Sterile Water for Injection (SWFI)

Water for Irrigation

Future Monographs


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Purified Water

USP: . . .obtained by a suitable process Conductivity 1.3 S/cm @ 25 C Total Organic Carbon (TOC) 500 ppb Microbial 100 cfu/ml No endotoxin requirement

EP: . . .prepared by distillation, by ion exchange, byreverse osmosis or by any other suitable method

JP: . . .purified by distillation, ion-exchange treatment,ultrafiltration or combination of these methods


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Purified Water Example System


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USP: . . .distillation or a purification process that isequivalent of superior to distillation Conductivity 1.3 S/cm @ 25 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 OsmosisUltrafiltration of Purified Water


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Water for Injection (WFI) DistillationTechniques

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 topure steam in subsequent effects


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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 uplatent heat and condensing as WFI

Higher electrical demand, but lower steam demand


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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, hygienicdesign of components)

Minimize Dead Legs (


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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


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Storage and Distribution Hot vs. Cold ?

Hot storage:

WFI produced through distillation is often generated hot, sowhy not store it hot?

Advantageous if there will be hot WFI distribution

Cold storage:

Periodic heat-up & cool-down of storage tank time- andenergy-intensive

Could expedite heat-up by dumping tank contents, but this is

wasteful Best solution will vary depending on specific

user requirements


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Hot Storage, Hot and Ambient Distribution


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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 ambientloop

Two loops mean increased installation labor

Only one heat exchanger means all ambientusers get water at same temperature, no localtemperature selection


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Hot Storage, Hot Distribution with Use Point Coolers


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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 temperaturesAmbient point-of-use piping must be sanitized byflushing or pulsing HWFI through heat exchanger todrain

Additional heat exchangers means increased capital

(and maintenance) cost Some feel POU cooler piping is a dead leg, prone tomicrobial growth


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Hot Storage, Hot Distribution with Use PointCooler Sub-loops


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Hot Storage, Hot Distribution with Use Point CoolerSub-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 problemAdditional heat exchangers means increased capital

(and maintenance) cost

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