ISPE NORDIC COP CLEAN UTILITIES

SEPTEMBER 6-7 2016

Juha Mattila
Senior Product Manager
STERIS FINN-AQUA, FINLAND
Juha.mattila@steris.com
DESIGN AND
REQUIREMENTS
CONSIDERATIONS FOR
WFI AND PURE STEAM
SYSTEMS
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 F0-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

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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) = +80…85 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?)
WFI distillation unit
• Future capacity upgrade – consider now or leave room for
additional equipment later?

• Do you need to run WFI against back pressure? Depending

on 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.)

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 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

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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)

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Typical utilities – WFI and PSG
2 Typical Utility Connections

UTILITY CONNECTION PRESSURE TEMP.

Feed Water Clamp 2 – 6 barg 10-2 0 °C
(30 – 88 psig) (50-68 °F)
Plant Steam Flange 3 – 8 barg 143-175 °C,
(44 – 116 psig) (289-347 °F)
97 – 100%
saturated
Condensate Return Clamp <30% of Plant Steam Pressure -
Cooling Water In Clamp 3 – 7 barg 5-20 °C
(44 – 102 psig) (41-68 °F)
Dp min 2 barg (30 psig)
Cooling Water Out Clamp - 97 °C
(206 °F)
Distillate Output Clamp Gravity Discharge 99 °C
(210 °F)
Rejected Distillate Clamp Gravity Discharge 99 °C
Output (210 °F)
Instrument Air G-Thread 6 – 8 bar g -
(88 – 116 psig)
Column Gas Outlet / De- Clamp 0.1 barg (2 psig) -
aeration
Blow down Output Clamp Gravity Discharge 99 °C
(210 °F)
Pressure Relief Device NPT or G-Thread 8.6 bar g -
/ Flange (125 psig)
Electricity 3ph Terminal 3ph/60Hz/208, 240, 380-480 or
575-600V or 3ph/50Hz/380-415 V
0.75-11.0 kW

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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
CO2 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

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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

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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-AquaÒ Multiple-Effect
Water Still
Non-temperature <3.1 mS/cm at 100 °C <1.1mS/cm at 20 °C 1.0 mS/cm at 100 °C
compensated <1.3 mS/cm at 25 °C 0 .2 - 0.5 mS/cm at 25 °C
con ductivity

Resistivity >0.77 MOhm-cm >0.91 MOhm-cm 5 - 2 MOh m-cm

at 25 °C (77 °F) at 20 °C (68 °F) at 25 °C (77 °F)
>0.32 MOhm-cm 1.0 MOh m-cm
at 100 °C (212 °F) 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.

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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

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Proportional Capacity Control vs.
START/STOP operation

Heating Steam Pressure Level (bar)

Distillate Capacity (maximum)
8
Start Unit
7
Distillate Capacity (minimum)
6

5 Stop Unit
4

0 10 20 30 40 50 60 70 80 90 100
Distillate Tank Level % (0%=4 mA, 100%=20 mA)

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

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HOW MANY COLUMNS?

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ENSURING WFI QUALITY
What is F0?

Dimensionless value to show equivalence to exposure time in minutes at

sterilization temperature of +121.1 C [250 F]. Typical required F0 for
sterilization is 15 (=equals to 15 minutes at +121.1 C).

Increasing or decreasing temperature from +121.1 C has exponential

effect – in both ways.

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F0 accumulation in ME WFI process

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

Accumulation begins
at +102 C

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ENSURING WFI QUALITY
§ Sufficient exposure time to high enough processing
temperature (F0)
§ 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 F0 = 15
100 1932,37 min
110 193,24 min
120 19,32 min
130 1,93 min
140 11,59 s
150 1,16 s
160 0,12 s Pyrogen removal by
170 0,01 s centrifugal separation

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 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

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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

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 Central PSG
ENSURING PURE Point-of-use
STEAM QUALITY

• 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)

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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

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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

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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

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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

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 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!

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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!

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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 F0-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!!

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 THANK YOU!
QUESTIONS?

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