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WHO: Supplementary Training Modules on Good Manufacturing Practice
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Water | Slide 1 of 19 January 2006
Water for Pharmaceutical Use
Part 2: Water purification and
engineering
Supplementary Training Modules on Good Manufacturing Practice
WHO Technical Report Series No 929, 2005. Annex 3
Water | Slide 2 of 19 January 2006
Objectives
To examine the basic technology and requirements for:
Water treatment systems
Storage and distribution requirements
Sampling and testing
Sanitization
Water for Pharmaceutical Use
6.
Water | Slide 3 of 19 January 2006
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
Water for Pharmaceutical Use
6.1
Water | Slide 4 of 19 January 2006
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
Water for Pharmaceutical Use
6.2
Water | Slide 5 of 19 January 2006
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
Water for Pharmaceutical Use
6.2
Water | Slide 6 of 19 January 2006
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
Water for Pharmaceutical Use
6.2
Water | Slide 7 of 19 January 2006
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
Water for Pharmaceutical Use
6.2
Water | Slide 8 of 19 January 2006
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
Water for Pharmaceutical Use
6.2
Water | Slide 9 of 19 January 2006
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 non-hygienic designed water treatment equipment such as ion exchangers and softeners
Water for Pharmaceutical Use
6.2
Water | Slide 10 of 19 January 2006
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
Water for Pharmaceutical Use
6.3
Water | Slide 11 of 19 January 2006
Storage and distribution - Storage vessels
Design and size important– Serves as buffer between generation and use– Avoid inefficiencies and equipment stress during frequent on-
off cycles– Short-term reserve in case of failure
Contamination control consideration– Headspace (kept wet with spray ball / distributor device)– Nozzles (no dead zone design)– Vent filters (type, testing, use of heat)– Pressure relief valves and burst discs (sanitary design)
Water for Pharmaceutical Use
6.4
Water | Slide 12 of 19 January 2006
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
Water for Pharmaceutical Use
6.5, 6.5.1
Water | Slide 13 of 19 January 2006
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
Water for Pharmaceutical Use
6.5.2
Water | Slide 14 of 19 January 2006
Typical water storage and distribution schematicTypical water storage and distribution schematic
Water must be kept
circulating
Spray ball
Cartridgefilter 1 µm
Air breakto drain
Outlets
Hygienic pump
Optionalin-line filter
0,2 µm
UV light
Feed Water from
DI or RO
Heat Exchanger
Ozone Generator
Hydrophobic air filter& burst disc
Water for Pharmaceutical Use
Water | Slide 15 of 19 January 2006
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
Water for Pharmaceutical Use
6.5.3
Water | Slide 16 of 19 January 2006
Biocontamination control techniques (2)
There should be no dead legs
Water scours dead leg
If D=25mm & distance X isgreater than 50mm, we havea dead leg that is too long
Dead leg section
>1.5D
Flow direction arrows on pipes are important
Sanitary Valve
D
X
Water for Pharmaceutical Use
Water | Slide 17 of 19 January 2006
3. The water is contaminated as it passes through the valve
2. Bacteria can grow when the valve is closed
Biocontamination control techniques (3)
1. Ball valves are unacceptable
Stagnant water
inside valve
Water for Pharmaceutical Use
Water | Slide 18 of 19 January 2006
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
Water for Pharmaceutical Use
6.5.3
Water | Slide 19 of 19 January 2006
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
Water for Pharmaceutical Use
6.5.3