Pharmaceutical water

Pharmaceutical WaterPharmaceutical Water
SystemsSystems
Mason P. WaterburyMason P. Waterbury
Nektar TherapeuticsNektar Therapeutics
28 June 0528 June 05

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

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

• What is High Purity Water?What is High Purity Water?
– Purified Water (PW)Purified Water (PW)
– Sterile Purified Water (SPW)Sterile Purified Water (SPW)
– Water for Injection (WFI)Water for Injection (WFI)
– Sterile Water for Injection (SWFI)Sterile Water for Injection (SWFI)
– Water for IrrigationWater for Irrigation
– Future MonographsFuture Monographs

• Purified WaterPurified Water
– USP: “. . .obtained by a suitable process”USP: “. . .obtained by a suitable process”
• ConductivityConductivity ≤ 1.3 µS/cm @ 25º C≤ 1.3 µS/cm @ 25º C
• Total Organic Carbon (TOC) ≤ 500 ppbTotal Organic Carbon (TOC) ≤ 500 ppb
• Microbial ≤ 100 cfu/mlMicrobial ≤ 100 cfu/ml
• No endotoxin requirementNo endotoxin requirement
– EP: “. . .prepared by distillation, by ion exchange, byEP: “. . .prepared by distillation, by ion exchange, by
reverse osmosis or by any other suitable method”reverse osmosis or by any other suitable method”
– JP: “. . .purified by distillation, ion-exchange treatment,JP: “. . .purified by distillation, ion-exchange treatment,
ultrafiltration or combination of these methods”ultrafiltration or combination of these methods”

• Purified Water – Example SystemPurified Water – Example System

• Water for Injection (WFI)Water for Injection (WFI)
– USP: “. . .distillation or a purification process that isUSP: “. . .distillation or a purification process that is
equivalent of superior to distillation”equivalent of superior to distillation”
• ConductivityConductivity ≤ 1.3 µS/cm @ 25º C≤ 1.3 µS/cm @ 25º C
• Total Organic Carbon (TOC) ≤ 500 ppbTotal Organic Carbon (TOC) ≤ 500 ppb
• Microbial ≤ 10 cfu / 100 mlMicrobial ≤ 10 cfu / 100 ml
• Endotoxin requirement < 0.25 EU/mlEndotoxin requirement < 0.25 EU/ml
– EP: “. . .distillation”EP: “. . .distillation”
– JP: “. . .distillation. . .or by the Reverse OsmosisJP: “. . .distillation. . .or by the Reverse Osmosis
Ultrafiltration of Purified Water”Ultrafiltration of Purified Water”

• Water for Injection (WFI) DistillationWater for Injection (WFI) Distillation
TechniquesTechniques
– Multi-Effect Still (MES)Multi-Effect Still (MES)
• Uses Plant Steam to convert feedwater to pure steamUses Plant Steam to convert feedwater to pure steam
• Separators allow impurities to drop out of the pure steamSeparators allow impurities to drop out of the pure steam
• Pure steam from first effect used to convert feedwater toPure steam from first effect used to convert feedwater to
pure steam in subsequent effectspure steam in subsequent effects

• Water for Injection (WFI) Distillation TechniquesWater for Injection (WFI) Distillation Techniques
– Vapor Compression (VC)Vapor Compression (VC)
• Uses plant steam to convert initial feedwater to vapor (pure steam)Uses plant steam to convert initial feedwater to vapor (pure steam)
• Pure steam is compressed, elevating temperaturePure steam is compressed, elevating temperature
• Compressed vapor is used to evaporate new feedwater, giving upCompressed vapor is used to evaporate new feedwater, giving up
latent heat and condensing as WFIlatent heat and condensing as WFI
• Higher electrical demand, but lower steam demandHigher electrical demand, but lower steam demand

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

• Storage and Distribution – SanitizationStorage and Distribution – Sanitization
– Heat (Continuous or Periodic, >81 deg. C for >1 hour)Heat (Continuous or Periodic, >81 deg. C for >1 hour)
• Most popular – nothing added to systemMost popular – nothing added to system
• If system continuously hot, all but eliminates concerns aboutIf system continuously hot, all but eliminates concerns about
sanitizationsanitization
• Can be a utility hogCan be a utility hog
– OzoneOzone
• Gaining popularityGaining popularity
• Ozone destruction and monitoring very importantOzone destruction and monitoring very important
• Environmental concernsEnvironmental concerns
– ChemicalChemical
• Must ensure that cleaning chemicals are completely removed fromMust ensure that cleaning chemicals are completely removed from
systemsystem
• Rinsing post-sanitization time and cost intensiveRinsing post-sanitization time and cost intensive

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

Hot Storage, Hot and Ambient DistributionHot Storage, Hot and Ambient Distribution

Hot Storage, Hot and Ambient DistributionHot Storage, Hot and Ambient Distribution
– Cost-effective when there are many ambientCost-effective when there are many ambient
use pointsuse points
– Heat Sanitization of ambient loop byHeat Sanitization of ambient loop by
displacement of AWFI or by heating ambientdisplacement of AWFI or by heating ambient
looploop
– Two loops mean increased installation laborTwo loops mean increased installation labor
– Only one heat exchanger means all ambientOnly one heat exchanger means all ambient
users get water at same temperature, no localusers get water at same temperature, no local
temperature selectiontemperature selection

Hot Storage, Hot Distribution with Use Point CoolersHot Storage, Hot Distribution with Use Point Coolers

Hot Storage, Hot Distribution with Use PointHot Storage, Hot Distribution with Use Point
CoolersCoolers
– Cost-effective when there are few ambient use pointsCost-effective when there are few ambient use points
– Main distribution loop is continuously hot, thereforeMain distribution loop is continuously hot, therefore
self-sanitizingself-sanitizing
– Can have locally adjustable use point temperaturesCan have locally adjustable use point temperatures
– Ambient point-of-use piping must be sanitized byAmbient point-of-use piping must be sanitized by
flushing or pulsing HWFI through heat exchanger toflushing or pulsing HWFI through heat exchanger to
draindrain
– Additional heat exchangers means increased capitalAdditional heat exchangers means increased capital
(and maintenance) cost(and maintenance) cost
– Some feel POU cooler piping is a dead leg, prone toSome feel POU cooler piping is a dead leg, prone to
microbial growthmicrobial growth

Hot Storage, HotHot Storage, Hot DistributionDistribution with Use Pointwith Use Point
Cooler Sub-loopsCooler Sub-loops

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

Pharmaceutical water

Recommandé

Recommandé

Contenu connexe

Tendances

Tendances (20)

Similaire à Pharmaceutical water

Similaire à Pharmaceutical water (20)

Dernier

Dernier (20)

Pharmaceutical water