‫بسم هللا الرحمن الرحيم‬

VALIDATION OF WATER
SUPPLY SYSTEM
Dr. Ahmad Abdallah Taha
Ain Sudan PVT .LTD.CO
General manger
February 2023
CONTENTS
 Objectives.
 Introduction.
 Validation System Qualification.
 Monitoring.
 Maintenance.
 Revalidation Change control.
 Validation documentation.
 Summary.
OBJECTIVE
 To understand
 Different types of water supply systems.
 Validation requirements.
 Qualification inspection requirement
INTRODUCTION
 High-quality water is essential for the manufacturing of pharmaceuticals. Water is
the most commonly used raw material in pharmaceutical manufacturing.

 water is directly or indirectly used in the pharmaceutical manufacturing such as a

major component in injectable products and in cleaning of manufacturing
equipment.

 It is one of the raw material that is usually processed by the pharmaceutical

manufacturer prior to use because it cannot be supplied by the vendor.

 Water is thus an important raw material in GMP and in validating the

manufacturing process.
INTRODUCTION
 Why purification?
 Although tap water is reasonably pure, it is always variable due to
seasonal variations, regional variation in quality.
 One must remove impurities and control microbes to avoid
contamination of products.
 Pretreatment depends on quality of feed water.
INTRODUCTION
 Quality of water should be specific for product
quality.
 Water contains,
 Organic and inorganic impurities
 Microbial contamination
 Endotoxin
 Particulate contamination
 Low quality of water can lead to
 product degradation
 product contamination
 loss of product and profit
TYPES OF WATER
 Different grades of Water for Pharmaceutical Purposes.
 each type has its own characteristic for all parameters.
1. Potable water
2. Purified water
3. Water for injection (WFI)
DIFFERENT TECHNIQUES USED FOR WATER TREATMENT

 De-chlorination (Sodium Bisulphite, Carbon Filter)

 Filtration

 Ultra Filtration

 Softening

 Demineralization

 Reverse Osmosis

 UV Treatment

 Deionization

 Ozonization
DIFFERENT EQUIPMENTS AND COMPONENTS FOR WATER SYSTEM

 Piping
 Valves
 Pumps
 Pressure gauges
 Heat exchangers
 Distillation unit
 Filters
 Deionizers
 Sensors
 Auxiliary equipment
WATER STORAGE AND DISTRIBUTION CONSIDERATIONS
 Materials of Construction (Chemical and Heat
Compatibility)
 Stainless Steel (316 or 316L)
 Teflon, Silicone, etc.
 Minimize Dead Legs ( 3 pipe diameters)
 Smooth Surfaces (Mechanical Polish ,
Electropolish)
 Clean joints (sanitary TriClamp, automatic
orbital welding)
 Passivate interior surfaces to form barrier
between water and free iron.
Conti.
 Design of the following should be appropriate to
prevent recontamination after treatment-
 Vent filter
 Tank UV light
 Steam sterilization
 Combination of on-line (TOC, Conductivity meter
etc.) and off-line monitoring (lab testing by
proper sampling) to ensure compliance with water
specification.
 VALIDATION CONCEPT
 It is essential to demonstrate that the proess or system consistently produce the
specified quantity and qualitywhen operated and maintained according to specific
written operating and maintenance procedure
 validation involves proving-
1. Engineering design
2. Operating procedures and acceptable ranges for control parameters
3. Maintenance procedures to accomplish it.
Conti..
 the system must be carefully,
 Designed

 Installed

 Tested during processing, after construction, and under all

operating conditions.
 Variations in daily, weekly and annual system
usage patterns must be validated.
WHY VALIDATION OF WATER SYSTEM?
 Most widely used and sometimes most expensive ingredient
 Drug component even if not in product
 Generally reviewed in depth by Regulators
 Many recalls water related
 Always considered direct impact system
 To ensure reliable, consistent production of
water of required quality
 To operate system within design capacity
 To prevent unacceptable microbial, chemical and
physical contamination during production, storage
and distribution
 To monitor system performance, storage and
distribution systems
VALIDATION CYCLE

 It includes four major steps-

 Determination of Quality Attributes
 The Validation Protocol
 Steps of Validation
 Control during routine operation
DETERMINATION OF QUALITY ATTRIBUTES
 The quality attributes, is gaining a clear understanding of the required
quality of water and its intended use
 Should be determined before starting the
validation.
 Without defining required quality attributes, we
cannot establish validation protocols.
THE VALIDATION PROTOCOL
 A written plan stating how validation will be conducted and defining acceptance criteria for
quality.
 For example, the protocol for a manufacturing process-
 it identifies -process equipment
1. critical process parameters
2. product characteristics,
3. sampling,
4. test data to be collected,
5. number of validation runs
6. acceptable test results
STEPS OF VALIDATION
 Establishing standards for quality attributes

 Defining system and subsystem

 Designing equipment, control, monitoring technologies

 Establishing standards for operating parameters

 Developing an IQ stage OQ stage

 Establishing alert and action levels

 Developing a prospective PQ stage

 Completing protocols and documenting each steps

ALERT AND ACTION LEVELS
 Alert and action levels are distinct from process parameters and product
specifications.
 They are used for monitoring and control rather than accept or reject decisions.
 The levels should be determined based on the statistical analysis of the data
obtained by monitoring at the PQ step.
 Alert levels are levels or ranges that when exceeded indicate that a process may
have drifted from its normal operation condition.
 Alert levels indicate a warning and do not necessarily require a corrective action.
Exceeding an action level indicates that corrective action should be taken to
bring the process back into its normal operating range.
SYSTEM QUALIFICATION
 Validation Master Plan
 User Requirement Specification
 Design Qualification
 Installation Qualification
 Operation Qualification
 Performance Qualification
 Re- Qualification.
DESIGN QUALIFICATION OF WATER SYSTEM
 Based on the URS, supplier designs the equipment.
 This is 1st step in the qualification of new water supply systems.
 Define process schematically by use of PFD and PIDs.
 It is documented the design of the system will include
 Functional Specification.(Storage, purification, etc)
 Technical/Performance specification for equipment.(requirements of water volume
and flow, define pumps and pipe sizes ).
 Detailed layout of the system.
 Design must be in compliance with GMPs and other regulatory requirements.
INSTALLATION QUALIFICATION
 IQ is in the form of checklist and it should include-
 Instrumentation checked against current engineering drawings and
specifications
 Review of PID
 Verification of materials of construction
 Installation of equipment with piping
 Calibration of measuring instruments
 Collection and collation of supplier operating and working
instructions and maintenance
requirements
Conti
 Installation of system as per Design requirements.
 Installation Verification-
 Systematic range of adjustments, measurements
and tests should be carried out to ensure proper
installation.
 Documentation include details of completed
installation.
Conti
 IQ Document should contain,
 Instrument name, model, I.D. No., Personnel
responsible for activities and Date.
 A fully verified installation that complies with
the documented design. (all deviations will have
been recorded and assessed.)
 All equipment documentation and maintenance
requirements would be documented.
 Completed calibration of measuring
instruments.
 Verification of Materials of construction.
OPERATION QUALIFICATION

 Definition The purpose of OQ is to establish, through documented testing, that all

critical components are capable of operating within
established limits and tolerances.
 it is the functional testing of system components mainly the critical components.
 The purpose of OQ is also to verify and document that the water supply system
provides acceptable operational control under at-rest conditions.
Conti
 Operation Qualification Checks-
 Ability to provide water of sufficient quality and quantity
to ensure achievement of specifications.
 Abilityto maintain general parameters like temperature,
pressure, flow at set points.
 Abilityto maintain any critical parameters(pH, TOC,
endotoxin, microbial level, conductivity etc. ).
Conti

 Includes
the tests that have been developed from
knowledge of processes, systems and equipment.
 Tests include a condition or a set of conditions
with upper and lower operating limits, sometimes
referred to as worst case conditions.
PERFORMANCE QUALIFICATION

 The purpose of PQ is to verify and document that

water supply system provides acceptable control
under Full Operational conditions.
 PQ should follow successful completion of IQ and OQ.
 PQ verifies that over time, the critical parameters, as defined in the
DQ are being achieved.
Conti

 PQ is used to demonstrate consistent achievement of

critical parameters over time.
 (such as pH, TOC, conductivity)
 PQ and OQ tests are sometimes performed in conjunction
with one another.
PERFORMANCE QUALIFICATION PHASES
 Three phase approach recommended according to WHO Technical
Report Series 929 to prove reliability and robustness.
Phase 1 (investigational phase)

 A test period of 2-4 weeks monitor the system

 System to operate continuously without failure or performance
deviation
 Chemical and microbiological testing should
include in accordance with a defined plan
Conti
 Sample daily from- incoming feed-water
 after each step in the purification process
 each point of use and at other defined sample points
 Develop appropriate operating ranges
 and finalize operating, cleaning, sanitizing and maintenance
procedures
Conti

 Demonstrate production and delivery of water of

the required quality and quantity
 Useand define the standard operating procedures
(SOPs) for operation, maintenance, sanitization and troubleshooting
 Verify provisional alert and action levels
 Develop and define test-failure procedure
Phase 2(verification step)

 A further test period of 2-4 weeks further intensive monitoring of the

system
 Utilization of all the SOPs after the satisfactory completion of phase 1
 Sampling scheme generally the same as in phase 1
 Water can be used for manufacturing purposes during this phase.
Conti..
 Phase-2 demonstrates
 Consistent operation within established ranges.
so it demostrate that the system is in control.
 Consistent production and delivery of water of
the required quantity and quality when the system is
operated in accordance with the SOPs.
Phase 3
 Over 1 year after the satisfactory completion of phase 2
 Water can be used for manufacturing purposes during this phase
 Demonstrate
 extended reliable performance
 that seasonal variations are evaluated
 Sample locations, sampling frequencies and tests
should be reduced to the normal routine pattern
based on established procedures proven during
phases 1 and 2
MONITORING
 Monitoring and feed back data are important in maintaining the performance systems.
Monitoring parameters include
 Flow, pressure, temperature, conductivity, TOC
 Samples taken From points of use, and specific sample points in a similar way how
water is used in service
 Tests should include physical, chemical and microbial attributes
 For example, stable state can be achieved by applying automatic continuous
monitoring of TOC and conductivity of the water system. They are the major quality
attributes of water by which organic and inorganic impurities can be determined.
MAINTENANCE

 A controlled, documented maintenance covering

 Defined frequency with plan and instructions
 Calibration programme
 SOPs for tasks
 Control of approved spares
 Record and review of problems and faults during
maintenance
MAINTENANCE
 System sanitization and bioburden control
 Systems in place to control proliferation of
microbes
 Techniques for sanitizing or sterilization
 Consideration already during design stage then
validated
 Special precautions if water not kept in the
range of 70 to 80 degrees Celsius
REVALIDATION CHANGE CONTROL

 Once the validation is completed, the standard

operating procedures (SOPs) are formalized.
 Routine operation should be performed according
to the established SOP.
 If any deviation from SOP observed, determine the
change and their impact on whole system
 Revalidation and evaluation should be performed
depending upon the impact of the change on system.
VALIDATION REPORT
 Written at the conclusion of the equipment IQ, OQ
and at completion of process validation.
 Will serve as primary documentation for regulatory inspection
 Will serve as reference document when changes to
the system are occurred and revalidation is
needed.
VALIDATION REPORT
 STANDARD FORMAT
 Executive summary
 Discussion
 Conclusions recommendation
 List of attachment
 Topic should be presented in the order in which
they appear in the protocol.
 Protocol deviation are fully explained
justified.
 The report is signed dated by designated
representatives of each unit involved in water
system validation.
Complete Documentation
 Verification of design documentation, including
 Description of installation and functions
 Specification of the requirements
 Instructions for performance control
 Operating procedures
 Maintenance instructions
 Maintenance records
 Training of personnel (program and records)
 Environmental records
 Inspection of plant
 Finally certification (Sign Off) by
Engineering, User (Production) and QA Heads.
SUMMARY

 Water supply systems,

 Play
a major role in the quality of
pharmaceuticals.
 Must be designed properly by professionals.
 Must be validated as a critical system.
THANK YOU