Water System Validation
Water System Validation
Water System Validation
CONTENTS
Objectives
Introduction
Validation & System Qualification
Monitoring
Maintenance Revalidation & Change control Validation documentation Summary
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OBJECTIVE
To understand:
1. 2. 3. 4. 5. 6.
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The need for water quality manual reason for usage of pharmaceutical water supply systems. The technical requirements for water supply systems. 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
INTRODUCTION
Why purification?
o Although tap water is reasonably pure, it is
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
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Carbon Filter) Filtration Ultra Filtration Softening Demineralization Reverse Osmosis UV Treatment Deionization Ozonization
Valves
Pumps Pressure gauges
Heat exchangers
Distillation unit Filters
Deionizers
Sensors
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Auxiliary equipment
of Construction (Chemical and Compatibility) Stainless Steel (316 or 316L) Teflon, Silicone, Viton (gaskets, diaphragms)
Heat
Minimize Dead Legs (<= 2 pipe diameters) Smooth Surfaces (Mechanical Polish , Electropolish) Clean joints (sanitary TriClamp, automatic orbital
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welding) Passivate interior surfaces to form barrier between water and free iron (0.5 to 1% alkali at 160F for 30 minutes followed by 1% Phosphoric Acid or Nitric Acid at 150F to 180 F for 10 minutes.)
Conti.
Design of the following should be appropriate to
prevent recontamination after treatmentVent filter Sanitary overflow Tank UV light Conical Bottom Steam sterilization
and off-line monitoring (lab testing by proper sampling) to ensure compliance with water specification
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VALIDATION CONCEPT
To prove the performance of processes or systems under
all conditions expected to be encountered during future operations. 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-
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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
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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
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quality attributes, is gaining a clear understanding of the required quality of water and its intended use
Should
be validation.
determined
before
starting
the
process-
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it identifies -process equipment -critical process parameters -product characteristics, -sampling, -test data to be collected, -number of validation runs -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
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Conti
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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.
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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.
INSTALLATION QUALIFICATION
IQ is in the form of checklist and it should include
Instrumentation checked against current engineering drawings and specifications Review of P&ID
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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
installation.
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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.
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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
the water supply system provides acceptable operational control under at-rest conditions.
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Conti
Operation Qualification Checks
Ability to provide water of sufficient quality and quantity to ensure achievement of specifications. Ability to maintain general parameters like temperature, pressure, flow at set points. Ability to maintain any critical parameters(pH, TOC, endotoxin, microbial level, conductivity etc ).
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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.
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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.
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Conti
According to the FDAs advice: The observed variability of the equipment between and within runs can be used as a basis for determining the total number of trials selected for the subsequent PQ studies of the process.
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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.
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QUALIFICATION PHASES
Three phase approach recommended according to
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
Conti
Demonstrate production and delivery of water of
completion of phase 1
Sampling scheme generally the same as in phase 1 Water can be used for manufacturing purposes during
this phase
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Conti..
Phase-2 demonstrates:
Consistent operation within established ranges. so
required quantity and quality when the system is operated in accordance with the SOPs.
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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
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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
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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
maintenance
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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
established SOP.
If any deviation from SOP observed, determine the change
and evaluation should be performed depending upon the impact of the change on system.
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VALIDATION REPORT
Written at the conclusion of the equipment IQ, OQ
regulatory inspection
Will serve as reference document when changes to
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VALIDATION REPORT
STANDARD FORMAT 1. 2. 3. 4.
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.
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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.
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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.
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REFERENCES
Validation in pharmaceutical industry ; edited by P.P.
Process Validation; An international 3rd edition; edited by R. A. Nash and A. H. Wachter; 401-442
Sci. Series, Vol. 129, 3rd Ed., edited by B. T. Loftus & R. A. Nash, Marcel Dekker Inc., N.Y. Pg. No. 440-460.
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THANK YOU
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