G.

PULLA REDDY COLLEGE OF PHARMACY

(Affiliated to Osmania university, Approved by PCI and AICTE, Accredited by NAAC)
SEMINAR IN PHARMACEUTICAL VALIDATION

VALIDATION OF PHARMACEUTICAL WATER SYSTEM AND PURE STEAM

PRESENTED BY : ASMA BEGUM

ROLL NO : 1701228850001
COURSE : M .PHARMACY 1ST YEAR , 1st semester
DEPARTMENT : PHARMACEUTICAL ANALYSIS
CONTENT:

• INTRODUCTION
• VALIDATION CONCEPT
• SYSTEM QUALIFICATION
• VALIDATION SEQUENCES FOR WATER SYSTEM
• VALIDATION OF PHARMACEUTICAL PURE STEAM
• CONCLUSION
• REFERENCE
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.
 Water
system 

Pure
Compr-
essed air Utilities steam
system

HVAC
system
VALIDATION OF WATER
SYSTEM
VALIDATION CONCEPT
To prove the performance, one must demonstrate (document) that the processes or
systems consistently produce the specified quantity and quality of water when
operated and maintained according to specific written operating and maintenance
procedures.

validation involves proving-

1. Engineering design
2. Operating procedures and acceptable ranges for control parameters
3. Maintenance procedures to accomplish it
 The system must be carefully,
1.Designed
2.Installed
3.Tested during processing, after construction, and under all operating conditions.
System usage patterns must be validated daily, weekly and annually.
 SYSTEM QUALIFICATION
Validation Master Plan

 User Requirement Specification

 Design Qualification 

 Installation Qualification

 Operation Qualification

Performance Qualification 

Re- Qualification
 VALIDATION SEQUENCES :
A) DESIGN QUALIFICATION
• Piping
• Holding tanks
• Valves
• Filters
• Deionisers and reverse osmosis (RO)
• Ultraviolet (UV) lights
• Distillation stills
B) INSTALLATION QUALIFICATION
C) OPERATIONAL QUALIFICATION
D) PERFORMANCE QUALIFICATION
• Phase 1
• Phase 2
• Phase 3
 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.
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.
 They are used as biocidal.
 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.
 PERFORMANCE QUALIFICATION
Demonstrate the effectiveness and reproducibility of the total integrated process.

Phase 1 Phase 2 Phase 3

 2-4 weeks for monitoring  2-4 weeks should be spent  3 typically runs for one
the system intensively. carrying out further year after the completion
 Chemical and microbial intensive monitoring of phase 2
testing  Sampling same as phase 1  Demonstrate extended
 Sampling in the reliable.
purification  Ensure that seasonal
 Develop and finalize- variation are evaluated
operating, cleaning,
sanitizing & maintenance
 Demonstrate production
and delivery of product
water of the required
quality and quantity
VALIDATION OF PURE STEAM
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 analyzed within 2 hours of sampling, store sample
at 2-8°C
Types of steam system in pharmaceutical industries
House steam
contains steam generator and
distribution system made of
iron or steel.
Constructed with rusting
material.
This system is usually treated
with various substances like
amines, hydrazine or other
boiler additives to arrest
corrosion.
Clean steam
It established when steam is used
for directly treating the product or
product contact surfaces.
Constructed with non-rusting
material. E.g.: stainless steel.
 This system use either purified
or distilled water as feed water.
Steam System
Steam system validation include the following steps:

Make a process diagram and identify major process steps.

Define major equipment in the process.

Carry out IQ, OQ, PQ. 

Process outline of clean steam 

 Water Distillation
water pre treatment  equipment 

Steam Holding
generator   Tanks

  Distribution
system 
Major equipment in the process

STEAM GENERATOR DISTRIBUTION SYSTEM

INSTALLATION QUALIFICATION
1. For clean steam generator
 Connect the generator to the required utilities and verify on to their
correctness
 Tighten flanges or other fittings, clean generator chemically and
passivate generator after installation. Label the utilities feeding the
generator
 Carry out pressure testing and record the results.
 Check and calibrate all critical processes instruments
2. Distribution system [IQ]

• Confirm than distribution system is as per the specification of the

company
• Compare the design drawing ,make note of modifications and record
• All branches of the system should be appropriately labelled.
• Clean the distribution system and record it.
• Carry out pressure test and record the result.
 OPERATIONAL QUALIFICATION
1.Clean steam generator 
According To SOP, start up and run the clean steam generator

Check that all instruments and alarms are working correctly. Record
their status.

 Check that the generated steam meet the specifications and can be
produced in quantities required
 2. Distribution system  [OQ]
 Test all the use points of the system for adequate supply of steam
under maximum load or other production condition.

 Quality of steam should be tested at all the use points.

 Use point should also be tested to find out that excess condensate is
not present under operating conditions..
PERFORMANCE QUALIFICATION
Consist of required testing specified in the protocol.

A typical protocol would include several tests under defined load

conditions.

Testing consists of condensing steam at various use point and subject

condensate for testing WFI.
CONCLUSION
Water and pure steam systems must be operated within regulatory
guidelines 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
optimization, safety, efficacy and assurance of quality. Such validation
protocols also fulfill regulatory requirements and provide good business
sense.
References

1. Nash A.P, watcher M.A pharmaceutical process validation; validation

of water system and air handling systems
2. P.P Sharma .Validation In Pharmaceutical Industry ,chapter 7,page 227
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