Transcript Document 7110590

Supplementary Training Modules on
Good Manufacturing Practice
Water for
Pharmaceutical Use
Part 2:
Water purification and
engineering
WHO Technical Report Series
No 929, 2005. Annex 3
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Water for Pharmaceutical Use
Objectives
To examine the basic technology and requirements for:
 Water treatment systems
 Storage and distribution requirements
 Sampling and testing
 Sanitization
6.
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Slide 2 of 19
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Water for Pharmaceutical Use
General
 Part 1 – reviewed types of water and water purification
systems
 Water can be used directly, or stored in a storage vessel for
subsequent distribution to points of use
 Design appropriately to prevent recontamination after
treatment
 Combination of on-line and off-line monitoring to ensure
compliance with water specification
6.1
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Slide 3 of 19
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Water for Pharmaceutical Use
WPU system contact materials
 Contact materials include:
–
–
–
–
–
–
Pipes
Valves and fittings
Seals
Diaphragms and instruments
Tanks
Pumps, etc.
 Proper selection to ensure these are suitable
6.2
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Slide 4 of 19
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Water for Pharmaceutical Use
WPU system contact materials (2)
 Factors to consider (including components)
– Compatibility and leaching effect
– Corrosion resistance
– Smooth internal finishing, ease of jointing
– Hygienic / sanitary design
– Documentation
– Materials of construction (MOC) - (including original/certified
copies of material certificates
6.2
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WPU system contact materials (3)
 Compatibility
– With temperature and chemicals used in the system
 Leaching effect
– Non-leaching at temperature range
 Corrosion resistance
– PW, HPW, WFI highly corrosive
– Stainless steel Grade 316L to be used
– System passivated after installation and modification
according to SOP
6.2
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WPU system contact materials (4)
 Smooth internal finish
– Biofilms and microbial contamination
– Crevices and roughness result in problem areas associated
with contamination and corrosion
– Internal finish to have arithmetical average surface
roughness not greater than 0.8 micrometer arithmetical
mean roughness (Ra)
– Mechanical and electropolishing needed when stainless
steel is used
6.2
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Slide 7 of 19
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WPU system contact materials (5)
 Joints
– System materials easily jointed, e.g. by welding
– Process controlled including requirements such as:
• Qualification of operator
• documentation of welder set up
• work session test pieces
• weld logs
• visual inspection of defined proportions of welds
6.2
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WPU system contact materials (6)
 Suitable materials include:
– Stainless steel Grade 315 L (low carbon)
– Polypropylene (PP)
– Polyvinylidenedifluoride (PVDF)
– Perfluoroalkoxy (PFA)
 Unplasticized polyvinylchloride (uPVC) used for nonhygienic designed water treatment equipment such as ion
exchangers and softeners
6.2
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System sanitization and bioburden control
 Systems in place to control proliferation of microbes
 Techniques for sanitizing or sterilization
 Consideration already during design stage – then validated
 Special precautions if water not kept in the range of 70 to 80
degrees Celsius
6.3
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Storage and distribution - Storage vessels
 Design and size important
– Serves as buffer between generation and use
– Avoid inefficiencies and equipment stress during frequent onoff cycles
– Short-term reserve in case of failure
 Contamination control consideration
– Headspace (kept wet with spray ball / distributor device)
– Nozzles (no dead zone design)
6.4
– Vent filters (type, testing, use of heat)
– Pressure relief valves and burst discs (sanitary design)
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Storage and distribution – Pipes and heat
exchangers
 Continuous circulating loop needed
 Filtration not recommended in loop and take-off point
 Heat exchangers:
– Double tube plate or double plate and frame type
– Designed to ensure no stasis of water
 Where water is cooled before use, done in minimum time, and
validated process
6.5, 6.5.1
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Storage and distribution – Circulation pumps
 Sanitary design with appropriate seals
 Standby pumps
– Can be used
– Configured or managed in a way to avoid trapped dead
zones
6.5.2
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Typical water storage and distribution schematic
Hydrophobic air filter
& burst disc
Feed Water
from
DI or RO
Cartridge
filter 1 µm
Spray ball
Optional
in-line filter
0,2 µm
Water must
be kept
circulating
UV light
Outlets
Heat Exchanger
Ozone Generator
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Hygienic pump
Air break
to drain
Water for Pharmaceutical Use
Biocontamination control techniques
 Continuous turbulent flow circulation
– Specified velocity proven (qualification), and monitored
 Avoid dead legs
 Hygienic pattern diaphragm valves
 Shortest possible length of pipe work
 Pipe work of ambient temperature systems, isolated from hot
pipes
6.5.3
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Biocontamination control techniques (2)
There should be no dead legs
D
Flow direction arrows
on pipes are important
Dead leg section
If D=25mm & distance X is
greater than 50mm, we have
a dead leg that is too long
X
>1.5D
Sanitary Valve
Water scours dead leg
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Biocontamination control techniques (3)
1. Ball valves are unacceptable
2. Bacteria can grow when
the valve is closed
3. The water is contaminated as it
passes through the valve
Stagnant water
inside valve
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Biocontamination control techniques (4)
 Pressure gauges separated from system membranes
 Pipe work laid to fall (slope) – allows drainage
 Maintain system at high temperature (above 70 degrees Celsius)
 Use UV radiation
– Flow rate, life-cycle of the lamp
 Suitable construction material
6.5.3
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Biocontamination control techniques (5)
 Periodic sanitization with hot water
 Periodic sanitization with super-heated hot water or clean steam
– Reliable
– Monitoring temperature during cycle
 Routine chemical sanitization using, e.g. ozone
– Removal of agent before use of water important
6.5.3
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Slide 19 of 19
January 2006