Transcript Process Water System Design Phase

Reminder:
Resistivity (ohms) is the reciprocal to
conductivity (micro-Siemens)
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BEWARE of Biofilm Buildup
SOURCE: http://www.fda.gov/ICECI/Inspections/InspectionGuides/ucm074905.htm
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Process Water System
Design Phase
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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 orbital
welds
• Lines sloped to drain 1/8 in/ft
• Recirculation loop 3-5ft/sec
• Sanitary pumps, Submicron
filters (0.2μm) on tanks and
vents
• Use-point fittings or GMP
valves
• Sanitary diaphragm-type and
stem valves only. No ball, gate,
plug, butterfly, globe or disc
valves.
• Drains must have air-break to
prevent 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,
pp 28-38
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Water for Pharmaceutical Use
Typical deionizer schematic
from water softener
HCl
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5
4
3
2
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NaOH
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5
4
3
2
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Water
Cartridge
Cartridge
Cationic column Anionic column
must be
UV light
filter 5 µm
filter 1 µm
kept
Eluates to
circulatin
neutralization
plant
g
Hygienic pump
Return to deioniczer
Outlets or storage.
Drain line
Air break to sewer
Ozone generator
Installation Qualification
• Assure that the system is installed per design
criteria
• 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
Regeneration
Dilute Base
Monitor feed water and effluent
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Anion
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Cation
Air
Dilute Acid
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To Waste
Conductivity
PSID (scaling)
Run length
gallonage
Amount of
regenerate
Rinse water
gallonage
Silica
(channeling)
Bacterial load
Other (eg. Air
quality)
In-Use
Cation
&
Anion
Mixed
Bed
Purified Process Water
Mixed bed regeneration requires backwashing for separate treatment with acid and
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base. They are mixed with air before start-up.
Operation Qualification
• Is the system operating correctly?
– Pumps at right pressure?
– Water flow correct?
• Continue to test feed water, sample ports and
points-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
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Designed, constructed and
validated to prevent microbial
proliferation and assure quality
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SOPs for maintenance, cleaning &
sanitization on frequent basis
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Monitor & test to assure
conformance to chemical, physical
and microbiological specifications
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Sanitary sampling ports
after each component
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Check at point-of-use daily
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Record & document test results
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Alert & action limits
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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 to
revalidate
• 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
The Validation Timeline