ISPE NORDIC COP CLEAN UTILITIES SEPTEMBER Juha Mattila Senior Product Manager STERIS FINN-AQUA, FINLAND

Transcription

1 ISPE NORDIC COP CLEAN UTILITIES SEPTEMBER Juha Mattila Senior Product Manager STERIS FINN-AQUA, FINLAND

2 DESIGN AND REQUIREMENTS CONSIDERATIONS FOR WFI AND PURE STEAM SYSTEMS

3 TOPICS There exists no single solution that fits every application Consider the entire application needs and demand the required optimal performance WFI quality is more than what is measured only via conductivity How to define F 0 -value in WFI process Different types of pure steam applications and needs Different process features that help maintain or improve your critical utility quality and production economy Always compare apples to apples Create a realistic LCC calculation over min. 15 years of equipment life ASME BPE discussion Take-aways

4 DESIGN CONSIDERATIONS - WFI Get to the basics first - determine the real average and maximum capacity need of WFI (WFI direct need, washing, possibility to simultaneous utility demands) WFI in hot loop (the most common) = C? WFI in cold loop (ambient temperature) = +30 C (instant use) Unit size vs. WFI storage tank size (peaks) bigger tank size for night time filling or kick-in peak capacity additional WFI distillation unit and tank size defined for daily average volume? Do you need absolute equipment redundancy for any downtime (dual units in 24/7 operation?) Future capacity upgrade consider now or leave room for additional equipment later? WFI distillation unit Do you need to run WFI against back pressure? Depending on unit type - either a distillate pump or capability to run WFI: -Against N 2 blanket in WFI storage -Physical height difference (tank height, next floor up, etc.)

5 DESIGN CONSIDERATIONS - WFI Available floor space and unit(s) layout the equipment needs to be serviceable at least from 2 sides reduce required footprint by installing back to the wall 600 mm typical service clearance Available room height minimize need to have maintenance parts on top of the unit or need to lift up components Clarify the route for equipment transport on-site and in-place!! Ensure modular construction of major components maintenance assembly work! SERVICE ACCESS SERVICE ACCESS

6 DESIGN CONSIDERATIONS - WFI Availability of all required utilities quantity, quality, supply pressure, temperatures / allowed differentials, back pressure UTILITY QUALITY => SURFACES CLEANING INTERVAL (Feed water, cooling water) SUPPLY PRESSURE => MAXIMUM CAPACITY COOLING WATER TEMPERATURE => COOLING CAPACITY ALLOWED TEMPERATURE AND/OR PRESSURE DIFFERENTIALS => APPLICATION ENGINEERING (CLOSED LOOPS, HEAT EXCHANGER SIZES) UTILITY BACK PRESSURE (WFI DELIVERY TO STORAGE, PLANT STEAM CONDENSATE BACK PRESSURE FOR CAPACITY)

7 Typical utilities WFI and PSG 2 Typical Utility Connections UTILITY CONNECTION PRESSURE TEMP. Feed Water Clamp 2 6 barg (30 88 psig) C (50-68 F) Plant Steam Flange 3 8 barg ( psig) C, ( F) % saturated Condensate Return Clamp <30% of Plant Steam Pressure - Cooling Water In Clamp 3 7 barg ( psig) Dp min 2 barg (30 psig) 5-20 C (41-68 F) Cooling Water Out Clamp - 97 C (206 F) Distillate Output Clamp Gravity Discharge 99 C (210 F) Rejected Distillate Output Clamp Gravity Discharge 99 C (210 F) Instrument Air G-Thread 6 8 bar g - ( psig) Column Gas Outlet / Deaeration Clamp 0.1 barg (2 psig) - Blow down Output Clamp Gravity Discharge 99 C (210 F) Pressure Relief Device NPT or G-Thread / Flange 8.6 bar g (125 psig) - Electricity 3ph Terminal 3ph/60Hz/208, 240, or V or 3ph/50Hz/ V kw

8 Feed water quality MEASUREMENT UNIT Conductivity < 5.0 µs/cm at 25 C Resistivity > 0.2 Mohm-cm at 77 F PH 5 to 7 Silica < 1 ppm Ammonia < 0.1 mg/l Chloride < 100 ppb CO 2 content < 2 mg/l Softened water? It is cheaper as utility, but: Adds to feed water consumption Adds to hot discharge (blow down) Can lead to increased equipment cleaning needs = downtime Softening does not remove all impurities (silica, amines, chloramines) = quality

9 What is blowdown? Concentrate from distillation process, contains impurities to be removed The most efficient way to remove impurities from distillation process is during and right after the evaporation process by separation Only removing portion of feed water without real separation process, just removes a portion of water. Not concentrated impurities. Typical blowdown rates:10-15% for distillation and 4-12 % for pure steam generation (calculated from WFI amount) Too low separation level is not desirable either

10 WFI QUALITY Distillate Quality The distilled water produced meets and exceeds the requirements of the United States Pharmacopeia, European Pharmacopoeia and Japanese Pharmacopeia for WFI. Measurement USP Requirements EP Requirements Typical values of Finn-Aqua Ò Multiple-Effect Water Still Non-temperature compensated conductivity <3.1 ms/cm at 100 C <1.3 ms/cm at 25 C <1.1mS/cm at 20 C 1.0 ms/cm at 100 C ms/cm at 25 C Resistivity >0.77 MOhm-cm at 25 C (77 F) >0.32 MOhm-cm at 100 C (212 F) >0.91 MOhm-cm at 20 C (68 F) 5-2 MOhm-cm at 25 C (77 F) 1.0 MOhm-cm at 100 C (212 F) Endotoxin content <0.25 EU/ml <0.25 EU/ml <0.01 EU/ml IMPORTANT Demand to demonstrate an effective reduction of Endotoxin using the Limulus Amebocyte Lysate (LAL) test method. Feed water is spiked with a minimum of 10 EU/ml and in the final distillate the level is less than 0.25 EU/ml (as defined by USP / EP as acceptance level). An independent laboratory should perform the LAL test in accordance to international standards. PARTICLES ARE SMALL. SEPARATION CAPTURES AND REMOVES THEM.

11 DESIGN CONSIDERATIONS WFI AND PSG Materials of construction Surface finish requirements Gasket materials (e.g. USP Class VI) Non-proprietary components Minimize number of moving parts (service and reliability) Minimize any cross-contamination possibilities Complete equipment factory testing helps on-site tests and validation Overall required level of documentation (GAMP 5, cgmp) Traceability, certificates, manufacturing documentation Electronic data security needs audit trail is possible for utility equipment

12 Proportional Capacity Control vs. START/STOP operation Heating Steam Pressure Level (bar) Distillate Capacity (maximum) Start Unit Distillate Capacity (minimum) Stop Unit Distillate Tank Level % (0%=4 ma, 100%=20 ma)

13 How much can be saved with proportional capacity control? CASE evaluation: WFI distillation with 5 columns, 26,000 liters/day, existing installation Operational: 48 weeks / year, 7 days/week, 24 hours/day Typical operation: 5 starts & stops per day Unit runs with 5.5 bar plant steam Standard feed water & cooling water temperatures available (+15 C) Cutting the running time: -Start-up dumping time of system: 15 minutes -2 starts & stops per day instead of 5 due to PCC operation that follows the tank level = 30 min instead of 75 min = saves 45 minutes of running time per day that is normally spent on starts/stops -PCC adjusts start-up with 4 bar output capacity instead of 5,5 bar => reduces utility consumptions Utility costs in this specific case: Cost of heating steam: 17 / 1000 kg of steam -Cost of cooling water: 0,27 / m3 -Cost of feed water given: 6 / m3 -Electricity & compressed air: Not evaluated in this case only marginal effect Annual savings potential: Total: /year [$16 400/year] savings potential, with optimal use of equipment

14 HOW MANY COLUMNS?

15 ENSURING WFI QUALITY What is F 0? Dimensionless value to show equivalence to exposure time in minutes at sterilization temperature of C [250 F]. Typical required F 0 for sterilization is 15 (=equals to 15 minutes at C). Increasing or decreasing temperature from C has exponential effect in both ways.

16 F 0 accumulation in ME WFI process Highest temperature (typical C)! Accumulation begins at +102 C

17 ENSURING WFI QUALITY Sufficient exposure time to high enough processing temperature (F 0 ) Pyrogen removal by centrifugal separation (and proven by endotoxin test) Size can be only nanometers not captured by filters DISTILLATE CONDUCTIVITY IS NOT THE ONLY PROOF OF QUALITY! Exposure Exposure time required temperature [ C] to reach F 0 = ,37 min ,24 min ,32 min 130 1,93 min ,59 s 150 1,16 s 160 0,12 s 170 0,01 s Pyrogen removal by centrifugal separation

18 Pure Steam Applications Pure Steam is required in the use in pharmaceutical manufacturing processes where the steam or resulting condensate comes in direct or indirect contact with the pharmaceutical product

19 PURE STEAM: CLEAN STEAM vs. PURE STEAM ASME BPE: Clean Steam: steam free from boiler additives that may be purified filtered or separated. Usually used for incidental heating in pharmaceutical applications Pure Steam: steam that is produced by a steam generator which, when condensed, meets requirements for Water For Injection (WFI) Pure Steam is free of pyrogen and impurities

20 ENSURING PURE STEAM QUALITY Central PSG Point-of-use What is your application: -Central pure steam system? -Point-of-use system? -Integrated system (e.g. to sterilizer)? -24/7 operation or start/stop usage when needed? -Additional capacity for peaks? -Cost of pure steam distribution line vs. integrated system (sterilizer upgrades)? Integrated (sterilizer)

21 ENSURING PURE STEAM QUALITY Continuous pure steam generation vs. start/stop energy savings, minimizes cleaning needs Continuous gas separation for ensuring steam quality (NCG <3,5%) EN 285 testing for steam quality (NCG, dryness, superheat) Control over sudden steam demand peaks (simultaneous autoclave start-ups with maximum pure steam demand) fast response time to ensure pure steam quality Continuous quality monitoring of pure steam (centralized systems) Endotoxin test for pyrogen removal

22 Distribution piping design General piping design equal to WFI piping design (material, surface finish, components, dead-leg length) Distribution piping sizing for sufficient steam velocities To minimize deterioration of steam quality, the steam distribution system should be well insulated and have a well designed and installed condensate removal system (steam traps and separators) Piping should always have a slope towards steam traps. Sagging steam piping can allow pockets of water to accumulate Large water pockets can impede the steam pipe flow, causing the increased steam velocity to carry them to the points of use

23 LIFE CYCLE COST CALCULATION Calculate at least 15 years of equipment life Equipment cost is typically only a fraction of total cost of ownership Use correct utility costs and consumption data Consider annual inflation / cost increase factor Calculate in annual service and maintenance costs (planned preventive maintenance) Consider amount and cost of replacement parts Annual calibrations / re-qualifications if applicable Consider any known major renovation items Evaluate effect of running cost saving features

24 Validation - Equipment Qualification FAT Well executed FAT at supplier s factory testing area saves in site validation time: Simulated Utilities Alarm tests Installation qualification (IQ) Instrument calibration Process tests operational qualification (OQ) Capacity tests Gas removal tests Familiarize with the equipment Equipment training Service training possibilities Familiarize with documentation Check all documentation Additional passivation? => SAT (Site Acceptance Testing) on location

25 ASME BPE CONSIDERATIONS The ASME Bioprocessing Equipment Standard was developed to aid in the design and construction of new fluid processing equipment used in industries that require a defined level of purity and bioburden control. The standard typically applies to components in contact with the product and systems that are critical part of product manufacture e.g. Water for injection (WFI) Demand a statement from the vendor there is always the requirement, application and offering that need to meet!

26 ASME BPE - DISCUSSIONS 2D-rule always feasible or not? Vs. pipe size vs. holding volumes vs. flow velocity? Number of welds and connections vs. pipe bending Handwelds vs. orbital welds vs. 2D-rule? Self-sterilizing conditions of hot process areas Drainability physical restraints vs. ASME Section VIII safety! There are no universally accepted tests to ensure that a component or system has been pickled and passivated or is in a pickled and passivated condition Again requirements need to meet the offering!

27 THE TAKEAWAYS: There exists no solution that fits every application Consider the entire application needs and demand the required optimal performance WFI quality is more than what is measured only via conductivity (pyrogen free, sufficient exposure to heat) How to define process F 0 -value Demand the features that help maintain or improve your critical utility quality and production economy Create a realistic LCC calculation over min. 15 years of equipment life ASME BPE considerations Always compare apples to apples!!

28 THANK YOU! QUESTIONS?