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BEWARE of Biofilm Buildup
SOURCE: http://www.fda.gov/ICECI/Inspections/InspectionGuides/ucm074905.htm 164
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Process Water System
Design Phase • Assemble cross-functional team
• Determine quality of feed water
• Determine required specifications
• Write protocols
Pre-validation • Calibration of instruments
• Validation of test methods
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Purified Water System Design Considerations
• 316LSS material of
construction• Sanitary electro-polishing and
passivation
• Sanitary clamp fittings or orbitalwelds
• Lines sloped to drain 1/8 in/ft
• Recirculation loop 3-5ft/sec
• Sanitary pumps, Submicronfilters (0.2μm) on tanks andvents
• Use-point fittings or GMPvalves
• Sanitary diaphragm-type and
stem valves only. No ball, gate,plug, butterfly, globe or discvalves.
• Drains must have air-break toprevent back-siphoning
• Minimize dead-legs to 6D
• Control biofilm buildup(recirculation, 85oC,ozonation)
• No added substances
SOURCE: Manfredi, Joe, “Myths, Rumors, Fantasies about Water
System Design”, Pharmaceutical Technology CGMP Compliance 2006,
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Cationic column Anionic column
Hygienic pump
Outlets or storage.
Ozone generator
UV light
HCl NaOH
Eluates to
neutralization
plant
Air break to sewer
Drain line
from water softener
Watermust bekeptcirculatin
g
Typical deionizer schematic
1
2345
6
1
23
4
5
6
Return to deioniczer
Cartridge
filter 5 µm
Cartridge
filter 1 µm
Water for Pharmaceutical Use
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Installation Qualification
• Assure that the system is installed per designcriteria
• Test water before and after each piece of
equipment in-line. Not just at point-of-use!
• Use that data to write your SOPs
(backflushing, regeneration, etc.)
• For example . . .
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Qualification of Mixed Bed Deionizers
• Conductivity
• PSID (scaling)
• Run lengthgallonage
• Amount of
regenerate• Rinse water
gallonage
• Silica(channeling)
• Bacterial load
• Other (eg. Airquality)
Monitor feed water and effluent
Regeneration In-UseDilute Base
Anion
Cation
Air Dilute Acid To Waste Purified Process Water
Cation
&Anion
Mixed
Bed
Mixed bed regeneration requires backwashing for separate treatment with acid andbase. They are mixed with air before start-up. 7
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Operation Qualification
• Is the system operating correctly? – Pumps at right pressure?
– Water flow correct?
• Continue to test feed water, sample ports andpoints-of-use
• Monitor system changes to validate the SOPs
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Water Validation and the
Corporate Audit • Allow extra time to audit the water system
• Trained persons are needed to maintain the
water system• Must check for specifications and acceptance
criteria for each sampling point
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Water for Process Use
• Designed, constructed andvalidated to prevent microbial
proliferation and assure quality
• SOPs for maintenance, cleaning &sanitization on frequent basis
• Monitor & test to assureconformance to chemical, physical
and microbiological specifications
• Sanitary sampling portsafter each component
• Check at point-of-use daily
• Record & document test results
• Alert & action limits
• Corrective action plan
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Performance Qualification
• Test all sample ports for 30 consecutive days
(spring, summer, fall and winter)• Validation complete after one full year
• Trend analysis may help avoid having torevalidate
• Develop change control procedures• Establish acceptance criteria for each piece of
equipment
• Establish alert and action limits
• Develop corrective action plans• Confirm the action had the desired affect
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Establish microbial quality control
using trend analysis
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The Validation Timeline