Pharmaceutical Water Systems - ISPE

aboundingdriprockΠολεοδομικά Έργα

29 Νοε 2013 (πριν από 3 χρόνια και 8 μήνες)

86 εμφανίσεις

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
µ
S/cm @ 25
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”


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
µ
S/cm @ 25
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”


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