Water system qualification in pharmaceuticals Read More - http://www.pharmaguideline.com/2011/06/purified-water-system.html

1. Design & validation
of water systems.

2. Design of the system.
• Type of water-
-Purified water
-Water for injection
• Product to be manufactured
• Temperature of system

3. Water for injection.
• Distillation.
• Reverse osmosis.
However in the bulk pharmaceuticals and
biotechnology ultrafiltration is employed to
minimize endotoxins.

4. Water for injection.
• Some opthalmic irrigating solution and
inhalation products where there are pyrogen
specification.
• Otherwise purified water.

5. Purified water.
• Opthalmic.
• Inhalation.
• Oral.
• Topical.
• Cosmetics.

6. Temperature.
• Hot (65-80 c ) systems are self-sanitizing.
• Circulating water systems.
• One way water systems – “dead leg”

7. Risk assessment or level of quality.
• Parental requires very pure water with no
endotoxins.
• Topical and oral products – purified water
but preservatives in antacids are marginally
effective. Hence more stringent
microbial limits required.
• Add a microbial reduction step –
ultrafilteration.

8. System validation.
• Parental association technical report no.4
titled “design concept for validation of a
water for injection system”
- use of an appropriate challenge. In this
situation it would be undesirable to
introduce micro organisms into an online
system.

9. System validation.
• Hence reliance is placed on
- periodic testing for microbial quality
- installation of monitoring equipments at
specific check-points

10. Design qualification.
• Supply water source and specification
- periodic monitoring for inorganic and
radioactive traces.
• General environment – clean and tidy.
• System – leak and rust free, well
maintained.

11. Design qualification.
• System controls – electrical panels and
switches well protected.
• Access to the system restricted.
• Material of construction – pipes, tanks.
• Vender qualification – selection and
acceptance of specification.

12. Design qualification.
• Description of the system along with a
print.
• Drawing showing all the equipments from
water feed to point of use.
• Specifications for all the parts of system.
• Sampling points and their locations.

13. Design qualification.
• The print should be compared to the actual
systems annually to ensure its accuracy.
• To detect unreported changes.
• To confirm reported changes.

14. Installation qualifications.
• To ensure that all the design qualification
parameters are verified and confirmed
during actual installation of the system.
• All the changes during installation are
covered with change control system and
documented.
• All SOP’s are developed and authorised.

15. Operational qualifications.
• To demonstrate that system will
consistently produce the desired water
quality when operated in conformance with
SOP’s.
• The sampling and testing is performed for
initial phase and for the same time period.
• Data evaluated for its specification.

16. Performance qualifications.
• To demonstrate the water system is
operated in accordance to SOP’s over a
long period of time ( 1 year ).
• Variation in quality of feed water.
• Sampling and testing is performed
according to procedure and frequencies.
• Daily from one point of use with all points
of use tested weekly.

17. Performance qualifications.
• There must be a data to support SOP’s.
• There must be data demonstrating that
SOP’s are valid.
• There must be a data to support that
seasonal variations in feed water do not
adversely affect the operation of the system
or water quality.

18. Performance qualifications.
• Compilation of the data with conclusions
into the final report.
• Final report must be signed by the
appropriate people responsible for operation
and quality assurance of the water systems.

19. Review of validation.
• Validation performed according to schedule
protocol.
• Report indicates that the system is operating
in repeatable and reliable manner.
• Any non conformities indicated in the
report, explained and suitably authorized.

20. Microbial limits. (water for
injection)
• Essentially sterile.
• Occasionally low level count due to
sampling error may occur.
• Less than 10cfu/100ml is acceptable action
limit.
• None of the limits for water are pass / fail.
• All are action limits.

21. Microbial limits.
• When action limits are exceeded
- investigate the cause of problem.
- take action to correct the problem.
- asses the impact on product.
- document the results of investigation.
- prepare action plan.

22. Microbial limits.
• Sampling volume 100-300 ml preferred.
• Less than 100 ml unacceptable.
• Monitor for both endotoxins and
micro-organism.

23. Microbial limits ( purified water)
• Federal environmental protection agency
regulation for drinking water
- 500 micro-organisms / ml.
• USP action guideline – not greater than 100
organisms / ml.
• Purified water used to manufacture drug
products by cold process – free of
objectionable organisms.

24. Microbial limits.
• Objectionable organism
- can cause infections.
- capable of growth in drug products.
• As per guide to inspection of
microbiological pharmaceutical quality
control lab, the specific contaminants rather
than the number is more significant.

25. Microbial limits.
• Organisms exist in water systems.
- free floating.
- attached to the walls of pipes and
tanks – biofilm.
• Contamination not uniformly distributed.
• Pre treatment of feed water is recommended
for distillation equipment and is definitely
required for RO units.

26. Still.
• Malfunctioning of feed water wall and level
control results in droplets of feed water
being carried over in the distillate.
• 50 ltr of WFI in condenser remains at the
startup.
This leads to contamination.

27. Heat exchanger.
• Methods for preventing contamination due
to leakage.
- monitoring pressure differential to ensure
high pressure is always on the clean fluid
by gauges.
- double tube sheet type of heat exchanger.
• When not in use heat exchanger not to be
drained to avoid pinhole formation.

28. • Holding tank – vent filter integrity testing, readily
accessible.
• Pump – static or periodically operational –
accumulation of water in reservoir leads to
microbial contamination.
• Piping – high polished stainless steel.
- PVDF ( polyvinylidene fluoride ) requires
support, when heated tends to leak, deal legs and
no threaded fittings.

29. Reverse osmosis.
• Cold system.
• Filters are not absolute – at least two filters
be in series.
• No ball valves to be used – stagnant water.
• Ultrafiltration to be added.
• Filters are to be used with stated purpose.

30. Purified water system.
• Ozone utilization – for optimum effectiveness
dissolved ozone residue remains in the system.
- employee safety and use problem
• 0.2 micron line filter housing provides good
environment for contamination.
• UV light to be kept on continuously, glass sleeve
around the bulb must be kept clean – kills only
90% of the organisms entering the system.

31. Purified Water SystemPurified Water System