Pharmaceutical Water
Systems
Alain Kupferman
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
Nanjing, November 2009
FACTORS CONTRIBUTING TO QUALITY PRODUCTS
Personnel
Validated processes
Procedures
Water for Pharmaceutical Use
PW
HPW
WFI
Raw Materials
Equipment
CS
Packing Materials
Environment
Premises
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
2|
Nanjing, November 2009
PREREQUISITES FOR OPERATION AND
(RE)QUALIFICATION
As usual……
Good design
Good engineering
Good execution
Good operation
Good documentation
and
Good maintenance
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
3|
Nanjing, November 2009
DEFINING THE NEEDS
• Regulatory (Pharmacopeia)
PW
HPW
WFI EU ? PICS ? FDA ?
• User requirements
• Data on raw water
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
4|
Nanjing, November 2009
DEFINING THE NEEDS:
WHICH TYPE OF WATER WHERE ?
 Regulatory (Pharmacopeia)
PW
HPW
WFI
EU ? PICS ? FDA ?
 Regulatory (EMEA)
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
5|
Nanjing, November 2009
DEFINING THE NEEDS:
WHICH TYPE OF WATER WHERE ?
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
6|
Nanjing, November 2009
GMP + GEP
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Drainability : slopes
Flow speed
In-process controls, sampling points
Valves and accessories
Size of generator(s) and storage tanks
Critical parameters handling
Etc.
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
7|
Nanjing, November 2009
USER REQUIREMENTS
• Quantitative data:
• Installation type:
how much when ?
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:
• Materials:
• Heat exchangers:
heat, chemical, ozone
stainless steel ? + treatment
type
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
8|
Nanjing, November 2009
QUALIFICATION ITEMS
Critical parameters handling
ICRA
I
=
Indicate
C
=
Control
R
=
Record
A
=
Alarm
Base for
instrumentation
qualification
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
9|
Nanjing, November 2009
QUALIFICATION 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 ???)
FDA
not having an unused portion greater in length than six diameters
of the unused pipe measured from the axis of the pipe in use
WHO
Deadlegs in the pipework installation greater
than 1,5 times the branch diameter should be avoided
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
10 |
Nanjing, November 2009
GMP + GEP CALCULATION
Size of generator(s) and storage tanks
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
11 |
Nanjing, November 2009
QUALIFICATION ITEMS IQ
 Welding documentation
(material certificates for pipes and fittings, FDA certificates for gaskets)
Isometric drawings with weld numbers
Welded seam documentation (machine protocols)
Welder approval test certificate
Pickling and passivation protocol
Endoscopic photos
Analytical certificate of inert gas
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
12 |
Nanjing, November 2009
QUALIFICATION ITEMS OQ
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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)
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
13 |
Nanjing, November 2009
QUALIFICATION 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
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
14 |
Nanjing, November 2009
PERFORMANCE QUALIFICATION
3-phased approach
Phase I
(2-4 weeks)
Water is not used for production purposes
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
15 |
Nanjing, November 2009
PERFORMANCE QUALIFICATION
3-phased approach
Same sampling scheme as phase I
Phase II
(2-4 weeks)
Water can be used for production purposes
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
16 |
Nanjing, November 2009
PERFORMANCE QUALIFICATION
3-phased approach
Phase III
(50 weeks)
Water can be used for production purposes
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
17 |
Nanjing, November 2009
SUBSEQUENT PERIODS
 Continuous system monitoring
 Maintenance (preventative)
 System reviews
trending, performance, changes
failures, investigations, OOS, etc.
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
18 |
Nanjing, November 2009
Questions, please…. ?
Manufacture of sterile medicines – Advanced workshop for SFDA GMP inspectors,
19 |
Nanjing, November 2009