pharmaceutical water systems alain kupferman manufacture of sterile medicines – advanced workshop...
TRANSCRIPT
Pharmaceutical Water Systems
Alain Kupferman
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
FACTORS CONTRIBUTING TO QUALITY PRODUCTS
Raw Materials
Personnel
ProceduresValidated processes
Equipment
Premises
EnvironmentPacking Materials
Water for Pharmaceutical Use
PWHPWWFI
CS
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
PREREQUISITES FOR OPERATION AND (RE)QUALIFICATION
PREREQUISITES FOR OPERATION AND (RE)QUALIFICATION
As usual……
Good designGood engineeringGood executionGood operationGood documentationandGood maintenance
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
DEFINING THE NEEDS DEFINING THE NEEDS
• Regulatory (Pharmacopeia)PWHPWWFI EU ? PICS ? FDA ?
• User requirements
• Data on raw water
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
DEFINING THE NEEDS: WHICH TYPE OF WATER WHERE ?
DEFINING THE NEEDS: WHICH TYPE OF WATER WHERE ?
Regulatory (Pharmacopeia)PWHPWWFI EU ? PICS ? FDA ?
Regulatory (EMEA)
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
DEFINING THE NEEDS: WHICH TYPE OF WATER WHERE ?
DEFINING THE NEEDS: WHICH TYPE OF WATER WHERE ?
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
GMP + GEPGMP + GEP
Drainability : slopes Flow speed In-process controls, sampling points Valves and accessories Size of generator(s) and storage tanks Critical parameters handling Etc.
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
USER REQUIREMENTSUSER REQUIREMENTS
• Quantitative data: how much when ?
• Installation type: IE, RO, double RO, EDI Multi-effect, thermocompression,..
• Loop type and storage:hot, cold, mixed, multiple fixed or variable speed pump deadlegs, valve types, …
• Sanitisation: heat, chemical, ozone
• Materials: stainless steel ? + treatment
• Heat exchangers: type
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
Critical parameters handling
I C R A
I=Indicate
C=Control
R=Record
A=Alarm
Base for instrumentationqualification
QUALIFICATION ITEMSQUALIFICATION ITEMS
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
QUALIFICATION ITEMS IQQUALIFICATION ITEMS IQ
Inspection of mechanical installation and documentation (manuals, data sheets, components certificates)
System installed in accordance with P&I diagram
Check of components (agree with description in components list)
Gap between waste water and drain
Dead legs in distribution system (6D, 3D, 1,5 D ???)
FDAnot having an unused portion greater in length than six diameters
of the unused pipe measured from the axis of the pipe in use
WHODeadlegs in the pipework installation greater
than 1,5 times the branch diameter should be avoided
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
GMP + GEP CALCULATIONGMP + GEP CALCULATION
Size of generator(s) and storage tanks
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
QUALIFICATION ITEMS IQQUALIFICATION ITEMS IQ
Welding documentation (material certificates for pipes and fittings, FDA certificates for gaskets)Isometric drawings with weld numbersWelded seam documentation (machine protocols)Welder approval test certificatePickling and passivation protocolEndoscopic photosAnalytical certificate of inert gas
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
QUALIFICATION ITEMS OQQUALIFICATION ITEMS OQ
Calibration of measuring equipment (Pressure, temperature, conductivity)
Leak test Operation of softener (residual hardness, regeneration)
Operation of RO plant (flow rates, conductivity)
Operation of bisulphite dosing (if required)
Function of regulating circuits in RO plant Operation of ozone generator and ozone meter (ozone concentration)
Operation of UV unit (Ozone concentration, intensity of light)
System parameters and limit-value settings Flow rate (Reynolds value) Water quality (conductivity, microbiological situation, TOC)
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
QUALIFICATION ITEMS OQQUALIFICATION ITEMS OQ
Gradients in distribution system
Drainability of distribution system
Inspection of electrical hardware
Emergency-off switch
Analogue inputs and outputs
Program steps disinfection softener, RO
Program steps sanitisation softener, RO, EDI, loop
Alarms
Access rights, passwords
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
PERFORMANCE QUALIFICATIONPERFORMANCE QUALIFICATION
3-phased approach
Phase I
(2-4 weeks)
Water is not used for production purposes
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
PERFORMANCE QUALIFICATIONPERFORMANCE QUALIFICATION
3-phased approach
Phase II
(2-4 weeks)
Same sampling scheme as phase I
Water can be used for production purposes
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
PERFORMANCE QUALIFICATIONPERFORMANCE QUALIFICATION
3-phased approach
Phase III
(50 weeks)
Water can be used for production purposes
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
SUBSEQUENT PERIODSSUBSEQUENT PERIODS
Continuous system monitoring
Maintenance (preventative)
System reviews trending, performance, changesfailures, investigations, OOS, etc.
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Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
Questions, please? .…Questions, please? .…