2. INTRODUCTION
Water is mostly used substances, raw material, or ingredient in the
production, processing, and formulation in pharmaceutical industries
Water is a component of every pharmaceutical product, so water system
must be validated
Proper pharmaceutical water system must have
Achieve & maintain compliance with pharmacopoeia requirements.
Have proper sampling system from correct points with appropriate
frequency.
Troubleshoot common contamination problems.
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5. DESIGN QUALIFICATION
It includes general information regarding various components or parts of water
treatment systems
PIPING
Selected material: stainless steel, It should be designed for reliability, pressure
control, and avoidance of extractable contaminants.
Holding tanks
7500-15000 litres
Valves
Commonly used valves: gate, ball, butterfly and diaphragm
Ozone process water system: Teflon should be employed
Filters
Prefiltration- granular or cartilage filters are used.
Carbon beds- 10-50 µ pore size.
Membrane filters- 0.2 µ pore size.
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6. Deionisers and reverse osmosis (RO) units
Ion exchanger resins used to remove charged particles
Resins are periodically regenerated
Carbon beds
To remove Organic chlorine and low molecular weight carbon
Ultraviolet (UV) lights
Wavelength for microbial reduction: 254 nm
Distillation stills
It effectively inactivates various micro organisms
Ozone and Heat sterilants
Strong oxidizing agent with powerful disinfecting property
Both are used as biocidal.
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7. INSTALLATION QUALIFICATION
All the unit components are installed as per the specifications and according
the design drawings.
It involves instrument connections, review the instrumentation drawings,
review and verify the MOC, examination and documentation of welds,
inspection for dead legs and pipe lopes, verification of stainless steel
passivation and leaks
OPERATIONAL QUALIFICATION
OQ verifies the capabilities of processing units to perform satisfactorily within
the operational limits.
Alarm controlling of utilities, like steam pressure (high/low), pressure
differential limits shall be checked.
Verify all the functional and operational parameters are as per acceptance
criteria, complete the OQ documents.
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8. PERFORMANCE QUALIFICATION
Demonstrate the effectiveness and reproducibility of the total integrated process.
Phase 1
2-4 weeks for monitoring the system intensively.
Chemical and microbial testing
Sampling in the purification
Develop and finalize- operating, cleaning, sanitizing & maintenance
Demonstrate production and delivery of product water of the required quality and quantity.
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9. Phase 2
2-4 weeks should be spent carrying out further intensive monitoring.
Sampling same as phase 1
Phase 3
3 typically runs for one year after the completion of phase 2
Demonstrate extended reliable.
Ensure that seasonal variation are evaluated
REVALIDATION
SANITIZATION
ALERT & ACTION LEVEL
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10. VALIDATION OF PHARMACEUTICAL PURE STEAM
Pure steam is used in sterilization is very common in pharmaceutical
manufacturing.
Sampling of pure steam
Bacterial Endotoxin Test and chemical test should be done separately.
Depyrogenated tubes or bottles are used
Allow the steam to drain
Open the cap of the bottle and fill
Tighten the cap of the bottle
If the sample not analysed within 2 hours of sampling, store sample at 2-
8°C
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11. ANALYSIS OF PURE STEAM
Non-condensable gases
It should not be more than 3.5%
Steam dryness value
It should not be less than 90%
pH
At 25°C It should be 5-7
Conductivity
It should not be more than 1.3 µs/cm
Microorganism
Steam condensate is tested for microbial contamination
Endotoxin test
It should not be more than 0.25 EU/ml as in water for injection
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12. CONCLUSION
Water and pure steam systems must be operated within regulatory
guidelines as with pharmaceutical production facilities. To validate these
systems, there must be documented evidence that the system is operating
consistently and according to the desired specifications. Validation is a tool
for total quality management and it is necessary for process optimisation,
safety, efficacy and assurance of quality. Such validation protocols also
fulfill regulatory requirements and provide good business sense.
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13. REFERENCES
1. V.M. Jadhav et al; journal of pharmacy research 2009, 2(5)
2. Nash A.P, watcher M.A pharmaceutical process validation; validation of
water system and air handling systems
3. ICH guidelines, Good Manufacturing Practice guide for active
pharmaceuticals Ingredients, Q7A (March 15, 2000)
4. Rakesh Pahwa et al; Tropical Journal of Pharmaceutical Research, February
2010; 9 (1): 81-90, Review Article on Validation Aspects of Water
Treatment Systems for Pharmaceutical Products
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