Water for Injection (WFI) and Pure Steam Production in a Lean Manufacturing Environment Larry Zanko Project Manager STERIS Corporation
Agenda Brief overview of multiple-effect water stills (MWS) Lean advancements in MWS technology How and when to integrate pure steam production Takeaways
Water for Injection (WFI) - Definition Measurement USP 28 Requirements EP 4 Requirements Typical values of WFI Nontemperature compensated conductivity <3.1 μs/cm at 100 C <1.3 μs/cm at 25 C <1.1μS/cm at 20 C 1 μs/cm at 100 C 0.2-0.5 μs/cm at 25 C TOC <500 ppb <500 ppb <500 ppb Endotoxin content <0.25 EU/ml <0.25 EU/ml <0.01 EU/ml USP Purified Water
Multiple-Effect Water Stills Distillation is the preferred WFI production method Evaporation is the best way to remove impurities that tend to remain in the liquid phase Easy to monitor process Evaporation and subsequent condensation are inefficient, energy intensive processes Goal is to minimize energy consumption
Impurity Separation Falling Film evaporator and two-stage separation technology DB Column Separator
Typical WFI Outlet Quality Chemical and Biological Analysis Plant steam press (bar) 3 8 Acceptance Criteria Endotoxin (EU/ml) <0,01 <0,01 <0.25 Endotoxin Reduction (log) >4,9 >4,9 >3,0 TOC (ppb) 110 70 500 CFU 0 0 0 Conductivity (µs/cm @20 o C) 0.5 0.5 <1.1 ph 6.3 6.3 5 to 7 Nitrates (ppm) <0,2 <0,2 <0.2 Heavy metals (bar) <0,1 <0,1 <0.1 NOTE: Feed water in above tests spiked with 800 EU/ml!! (Typical drinking water quality 1-5 EU/ml)
More Effects = Less Energy Multiple Effect Water Still Principle of Energy Consumption
The Lean Water Still Recent development efforts have centered on flexible products to most closely match the required applications, utilities, and layouts The result is new equipment features that were not available just a few years ago Benefits include lower overall operating and process validation costs
Distillation Against Backpressure Eliminate distillation pump Reduce cost, installation time, and maintenance Remove a potential contamination source Condenser can be sealed (no vent filters) to allow for pressurization Location of the MWS not as critical and allows for N2 gas jacket in WFI Tank
Non-Condensable Gas Separation DB Column Top/Gas Separator Tubes expanded in both flanges! Spray Nozzle! Weap Hole! Gas Outlet!
Proportional Capacity Control Proportional Capacity Control Distillate is rejected to drain during start-up Should be avoided as much as possible Less valve actuations extend equipment life Not stuck with limited choices still can be sized perfectly for the application Heating Steam Pressure Level (bar) 8 7 6 Distillate Capacity (maximum) Start Unit Distillate Capacity (minimum) 5 4 3 Stop Unit 0 10 20 30 40 50 60 70 80 90 100 Distillate Tank Level % (0%=4 ma, 100%=20 ma)
Enhanced Blowdown Removal Remove blowdown from each stage so that it is not concentrated at the last stage Improves equipment life Allows part of the blowdown to be recirculated back to the feedwater break tank (Nonevaporated feedwater recirculation) 50-67% less blowdown!
Self Sterilization Efficient sterilization in case of emergency situation Flow directed from condenser to feedwater piping Minimum temperature of 80 C
Automatic Balancing In the past flow rate adjustments required highly qualified service personnel and took a fairly long period of time Auto-tune system measures critical process parameters and adjusts the process without operator intervention Process can be configured to start after normal production hours
Lean Construction More efficient evaporator Wider to increase surface area - Smaller footprint Reduced height New column design (separator on bottom) is more efficient for heat transfer Unit can easily be separated into pieces for rigging Smaller component size Dismantling and reassembling heavy parts introduces a safety risk and is time consuming Dividing the unit into several columns reduces size of largest component Allows for easier access and removal
Lean Construction Reduced weight Eliminates need to reinforce supporting floors No moving parts (quiet operation) Important for health and safety Minimized components to simplify operation Ergonomic layout Utility inputs all on single side Most components located around first column to simplify service access Column halves can replaced independently
Required Feed Water Quality Myth - Feed water must be validated USP Evaporation + separation is a purification process! Traditionally, DI water required mainly due to chemical impurities + hot system + SS New concepts (falling film and continuous recirculation) have eased feed water quality requirement
Feed Water Quality - Typical MEASUREMENT UNIT Conductivity <5.0 µs/cm at 25 C PH 5 to 7 Silica <1 ppm Chloride <100 ppb Note: All chlorine-bearing compounds should be measured as chloride. The total chloride content should not exceed 100 ppb. All chlorine bearing compounds should be removed from the feed water prior to the unit.
Soft Feed Water Option Eliminates need for (2 x) RO or CDI/EDI capital investment Blowdown increases but total water sent to drain is less than combined RO/MWS configuration Feed water conductivity up to 300uS/cm Must remove chlorine bearing compounds Water quality can vary seasonally Increases MWS cost by ~8%
Feed Water Quality - Soft Water Measurement Unit Acceptable Range ph @25 o C 5-9 Conductivity @15ºC µs/cm Typically <300 Pretreatment system requirements Possible RO Dissolved solids mg/l <5 Sand filter required Chloride mg/l <1 ppm Active carbon filter required for ensuring proper chloride levels as it relates to chlorine. Possible RO for chloride removal. Silica Total Hardness 3 mg SiO 3 /L mg CaCO 3 / L <10 Possible RO <2 Water softener
Pure Water & Steam 5 Options 1) Pure steam valve after 1st column (SSQ) 2) Simultaneous pure steam and distillation (controlled option) 3) Pure Steam Generator (PSG) operation mode 4) Independent PSG 5) PSG with Condenser
Pure Steam - Definition Meets WFI Requirements when Condensed The FDA requires the use of clean steam in pharmaceutical manufacturing processes where the steam or resulting condensate comes in direct or indirect contact with the pharmaceutical product.
Pure Steam Applications Autoclaves / Steam Sterilizers GMP Applications Terminal Sterilization Sterilization of Pharmaceutical Packaging Sterilization of WFI System Components Steam-In-Place Systems Filter Sterilization Sterilization of Loop Piping Filling Lines Reactors Clean Room Humidification
Pure Water & Steam Option 1 Pure steam valve after 1st column PS capacity limited with an orifice (10% of MWS capacity) WFI is produced simultaneously (even if not needed) External PRV needed to control pressure Response time to set point - good Suitable for tank, filter, and loop sterilization; not recommended for sterilizers Most economical option (~$3,000)
Pure Water & Steam Option 2 Simultaneous PS and WFI operation PS pressure set point 2,5 3,5 bar (controlled) PS amount max 30 % of corresponding PSG capacity Response time to set point good WFI is produced simultaneously (even if it not needed) Suitable for tank, filter, and loop sterilization; not recommended for sterilizers Adds approximately $10,000 to cost of unit
Pure Water & Steam Option 3 Pure Steam Generator (PSG) operation mode Unit produces WFI or Pure Steam Pure steam flow max 75-80 % of corresp. PSG capacity Response time 1 minute from 0 % 70 %, and > 1min from 70 % 0 % (set point +/- 10 %) Suitable for sterilizers Cost is 30 % of corresponding PSG cost
Pure Water & Steam Option 4 Independent Pure Steam Generator (PSG) Maximum flexibility and optimum performance Unchains water and steam production Best choice for large steam demands and high performance applications Most expensive option
Pure Water & Steam Option 5 PSG with condensers to produce WFI Pure Steam 0-100 % WFI at one production rate PS production higher prioritization WFI production limit ~500 l/h (7 liters of cooling water (15 C) per liter of WFI Best applied when WFI need is low (smaller Bio / Pharma) Adds ~$50,000 to cost of PSG
Takeaways Distillation will always be an energy intensive process Modern water stills incorporate several lean features to reduce wasted energy Operational savings should be balanced against the capital investment Usage patterns, performance requirements, and demand ratios determine the most efficient way to produce pure steam
Thank You! Questions?