ispe nordic cop clean utilities september 6-7 2016 · considerations for wfi and pure steam...

ISPE NORDIC COP CLEAN UTILITIESSEPTEMBER 6-7 2016

Juha MattilaSenior Product ManagerSTERIS FINN-AQUA, [email protected]

mailto:[email protected]

DESIGN ANDREQUIREMENTSCONSIDERATIONS FORWFI AND PURE STEAMSYSTEMS

Connecting Pharmaceutical Knowledge ispe.org

TOPICS

• There exists no single solution that fits everyapplication

• Consider the entire application needs anddemand the required optimal performance

• WFI quality is more than what is measured onlyvia conductivity

• How to define F0-value in WFI process

• Different types of pure steam applications andneeds

• Different process features that help maintain orimprove your critical utility quality and productioneconomy

• Always compare apples to apples

•Create a realistic LCC calculation over min. 15years of equipment life

• ASME BPE discussion

• Take-aways


DESIGN CONSIDERATIONS - WFI• Get to the basics first - determine the real average andmaximum capacity need of WFI (WFI direct need, washing,possibility to simultaneous utility demands)

•WFI in hot loop (the most common) = +80…85 C?

• WFI in cold loop (ambient temperature) = +30 C (instant use)

• Unit size vs. WFI storage tank size (peaks) – bigger tank sizefor night time filling or kick-in peak capacity additional WFIdistillation unit and tank size defined for daily average volume?

• Do you need absolute equipment redundancy for anydowntime (dual units in 24/7 operation?)

• Future capacity upgrade – consider now or leave room foradditional equipment later?

• Do you need to run WFI against back pressure? Dependingon unit type - either a distillate pump or capability to run WFI:

-Against N2 blanket in WFI storage

-Physical height difference (tank height, next floor up, etc.)

WFI distillation unit


DESIGN CONSIDERATIONS - WFI• Available floor space and unit(s) layout – the equipment needs to be serviceable at leastfrom 2 sides – reduce required footprint by installing back to the wall – 600 mm typicalservice clearance

• Available room height – minimize need to have maintenance parts on top of the unit orneed to lift up components

• Clarify the route for equipment transport on-site and in-place!!

• Ensure modular construction of major components – maintenance assembly work!

SERVICEACCESS

SERVICEACCESS


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 => APPLICATIONENGINEERING (CLOSED LOOPS, HEAT EXCHANGER SIZES)

UTILITY BACK PRESSURE (WFI DELIVERY TO STORAGE, PLANT STEAMCONDENSATE BACK PRESSURE FOR CAPACITY)


Typical utilities – WFI and PSG2 Typical Utility Connections

UTILITY CONNECTION PRESSURE TEMP.Feed Water Clamp 2 – 6 barg

(30 – 88 psig)10-20 °C

(50-68 °F)Plant Steam Flange 3 – 8 barg

(44 – 116 psig)143-175 °C,(289-347 °F)97 – 100%saturated

Condensate Return Clamp <30% of Plant Steam Pressure -Cooling Water In Clamp 3 – 7 barg

(44 – 102 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 DistillateOutput

Clamp Gravity Discharge 99 °C(210 °F)

Instrument Air G-Thread 6 – 8 bar g(88 – 116 psig)

-

Column Gas Outlet / De-aeration

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, 380-480 or575-600V or 3ph/50Hz/380-415 V0.75-11.0 kW


Feed water quality

MEASUREMENT UNITConductivity < 5.0 µS/cm at 25 °CResistivity > 0.2 Mohm-cm at 77 °FPH 5 to 7Silica < 1 ppmAmmonia < 0.1 mg/lChloride < 100 ppbCO2 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


What is blowdown?

• Concentrate from distillation process,contains impurities to be removed• The most efficient way to removeimpurities from distillation process is duringand right after the evaporation process byseparation• Only removing portion of feed waterwithout real separation process, justremoves a portion of water. Notconcentrated impurities.• Typical blowdown rates:10-15% fordistillation and 4-12 % for pure steamgeneration (calculated from WFI amount)• Too low separation level is not desirableeither


WFI QUALITYDistillate Quality

The distilled water produced meets and exceeds the requirements of the United StatesPharmacopeia, European Pharmacopoeia and Japanese Pharmacopeia for WFI.

Measurement USP Requirements EP Requirements Typical values ofFinn-AquaÒ Multiple-Effect

Water StillNon-temperaturecompensatedconductivity

<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 °C0.2 - 0.5 mS/cm at 25 °C

Resistivity >0.77 MOhm-cmat 25 °C (77 °F)>0.32 MOhm-cmat 100 °C (212 °F)

>0.91 MOhm-cmat 20 °C (68 °F)

5 - 2 MOhm-cmat 25 °C (77 °F)

1.0 MOhm-cmat 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 Endotoxinusing the Limulus Amebocyte Lysate (LAL) test method. Feed water is spikedwith a minimum of 10 EU/ml and in the final distillate the level is less than 0.25EU/ml (as defined by USP / EP as acceptance level). An independentlaboratory should perform the LAL test in accordance to internationalstandards.PARTICLES ARE SMALL. SEPARATION CAPTURES AND REMOVES THEM.


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


Proportional Capacity Control vs.START/STOP operation

0 10 20 30 40 50 60 70 80 90 100

3

4

5

6

7

8

Distillate Tank Level % (0%=4 mA, 100%=20 mA)

Start Unit

Stop Unit

Heating Steam Pressure Level (bar)Distillate Capacity (maximum)

Distillate Capacity (minimum)


How much can be saved with proportional capacity control?CASE evaluation:WFI distillation with 5 columns, 26,000 liters/day, existing installationOperational: 48 weeks / year, 7 days/week, 24 hours/dayTypical operation: 5 starts & stops per dayUnit runs with 5.5 bar plant steamStandard 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 tanklevel = 30 min instead of 75 min = saves 45 minutes of running time per day that isnormally spent on starts/stops-PCC adjusts start-up with 4 bar output capacity instead of 5,5 bar => reduces utilityconsumptions

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: 12 669 €/year [$16 400/year] savings potential, with optimal use of equipment


HOW MANY COLUMNS?


ENSURING WFI QUALITY

What is F0?

Dimensionless value to show equivalence to exposure time in minutes atsterilization temperature of +121.1 C [250 F]. Typical required F0 forsterilization is 15 (=equals to 15 minutes at +121.1 C).

Increasing or decreasing temperature from +121.1 C has exponentialeffect – in both ways.


F0 accumulation in ME WFI process

Highest temperature (typical +160...170 C)!

Accumulation beginsat +102 C


ENSURING WFI QUALITY

§ Sufficient exposure time to high enough processingtemperature (F0)§ Pyrogen removal by centrifugal separation (and proven byendotoxin test)§ Size can be only nanometers – not captured by filters

DISTILLATE CONDUCTIVITY IS NOT THE ONLY PROOF OFQUALITY!

Exposure Exposure time requiredtemperature [°C] to reach F0 = 15100 1932,37 min110 193,24 min120 19,32 min130 1,93 min140 11,59 s150 1,16 s160 0,12 s170 0,01 s

Pyrogen removal bycentrifugal separation


Pure Steam Applications

Pure Steam is required in the use in pharmaceuticalmanufacturing processes where the steam or resultingcondensate comes in direct or indirect contact with thepharmaceutical product


PURE STEAM: CLEAN STEAM vs. PURE STEAM

ASME BPE:”Clean Steam:” steam free from boiler additivesthat may be purified filtered or separated. Usuallyused for incidental heating in pharmaceuticalapplications

”Pure Steam:” steam that is producedby a steam generator which, when condensed,meets requirements for Water For Injection (WFI)

Pure Steam is free of pyrogen and impurities


ENSURING PURESTEAM QUALITY

• What is your application:

-Central pure steam system?

-Point-of-use system?

-Integrated system (e.g. tosterilizer)?

-24/7 operation or start/stopusage when needed?

-Additional capacity for peaks?

-Cost of pure steam distributionline vs. integrated system(sterilizer upgrades)?

Central PSGPoint-of-use

Integrated (sterilizer)


ENSURING PURE STEAM QUALITY

• Continuous pure steam generation vs.start/stop – energy savings, minimizescleaning needs

• Continuous gas separation forensuring steam quality (NCG <3,5%)

• EN 285 testing for steam quality (NCG,dryness, superheat)

• Control over sudden steam demandpeaks (simultaneous autoclave start-upswith maximum pure steam demand) –fast response time to ensure pure steamquality

• Continuous quality monitoring of puresteam (centralized systems)

• Endotoxin test for pyrogen removal


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 steamdistribution system should be well insulated and have a welldesigned and installed condensate removal system (steamtraps 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, causingthe increased steam velocity to carry them to the points of use


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


Well executed FAT at supplier’s factory testing area saves insite 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

Validation - Equipment Qualification – FAT


ASME BPE CONSIDERATIONS

• ”The ASME Bioprocessing Equipment Standard was developed toaid in the design and construction of new fluid processingequipment used in industries that require a defined level of purityand bioburden control. The standard typically applies to componentsin contact with the product and systems that are critical part ofproduct manufacture – e.g. Water for injection (WFI)”• Demand a statement from the vendor – there is always therequirement, application and offering that need to meet!


ASME BPE - DISCUSSIONS

• 2D-rule – always feasible or not? Vs. pipe size vs. holding volumesvs. 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 acomponent or system has been pickled and passivated or is in apickled and passivated condition• Again – requirements need to meet the offering!


THE TAKEAWAYS:

• There exists no solution that fits every application• Consider the entire application needs and demand the requiredoptimal performance•WFI quality is more than what is measured only via conductivity(pyrogen free, sufficient exposure to heat)• How to define process F0-value• Demand the features that help maintain or improve your criticalutility quality and production economy• Create a realistic LCC calculation over min. 15 years of equipmentlife• ASME BPE considerations• Always compare apples to apples!!


THANK YOU!QUESTIONS?

ispe nordic cop clean utilities september 6-7 2016 · considerations for wfi and pure steam...

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