As we know that water is the most essential part of different pharmaceutical preparations & is used for the cleaning of machines, equipment’s and other accessories during manufacturing hence directly & indirectly it plays an vital role in building of product quality.
Why Water System Validation is Important :
1.The purpose of carrying out water system validation is to assure that the treatment process produces a high quality of water consistently.
2. Water system validation is mandatory in order to study the reproducibility, consistency & effectiveness of water system.
3. Regulatory Guideline requirements
4. In order to achieve desired chemical and microbiological quality as per international guidelines.
5. Validation is a complete documented evidence which gives the surety that any specified process consistently gives the end product having predetermined quality parameters and specifications.
6. Establishing the reliability of pharmaceutical water purification, storage, and distribution systems requires demonstrating control of the process through an appropriate period of monitoring and observation.
Water Validation different Steps :
Pharmaceutical water treatment system validation consists of three steps which are: DQ (Design Qualification) IQ (Installation Qualification) OQ (Operational Qualification) & PQ (Performance Qualification)
DQ (Design Qualification) :
1. It includes all the information about various components of water treatment system.
2. It contains complete schematic diagram of mechanical, electrical and water flow in order to verify the appropriate installation.
3. It defines the purification units, safety of the system, control devices & alarm systems.
4. Specify the sampling plans and sampling point for microbiological and chemical testing, describe sanitization methods, define method of analysis and data plotting.
IQ (Installation Qualification) :
1.Installation qualification gives surety and proof that the water system has correctly installed & supplied & meets
2. It involves the development of Installation qualification Protocol, an inspection & test plan for water system.
3. It is necessary to document and certify all the installation parameters prior to perform operational qualification.
4. For the installation qualification of water system, key elements are : Verification of utilities required including compressed air, steam, electricity & feed water.
5. All these utilities must be checked thoroughly when performing installation of system.
6. All the controlling instruments must be calibrated and certified as per written procedures that they are accurate, precise, selective and specific.
OQ (Operational Qualification)
1.It consists of various inspection and tests in order to verify the reliable operation of equipment, system controls and alert.
2. It is complete documented verification of the system that it works throughout the process as per operating ranges consistently.
3. OQ check the operation of water system to provide sufficient quantity of water with specified high quality water, to maintain parameters like temperature, pressure, flow, TOC, endotoxin, pH, conductivity and microbial level.
PQ (Performance Qualification) :
1. When water system has operationally verified, performance qualification step comes.
2. It includes variety of tests designed in order to verify the consistent satisfactory system performance.
3. It is carried out by performing the necessary product test and intermediate test of the process to demonstrate reliable and accurate performance.
4. PQ documents that water quality consistently and continuously meets the predetermined required specifications
Water Validation Testing Phases :
Complete water system validation requires 1 year long time because of possible operating problems, maintenance errors which might occurs during this period, equipment failure etc. One more reason for such long time is to determine the seasonal change on the microbial quality of feed water and to determine the procedure of system sanitization effectiveness against microorganisms.
Water system validation has been categorized into 3 phases: Phase I,
Phase II and Phase III.
Phase I Validation :
1. This is preliminary phase and requires a 2 – 4 weeks (14 days minimum) testing period in order to monitor the system deeply.
2.The system is continuously operated in this phase without failure & extensive and frequent sampling is carried out with testing from various locations .
3. Microbiological and chemical testing is performed according to the defined plan.
4. Phase I finalize the sanitizing, cleaning and maintenance procedures along with operating ranges development.
5. Before the end of phase I, system is initiated to operate with some stress or tense conditions like start of system after failure of power or start up after emergency system shut down. System is simulated to operate under normal situation of maintenance like start up of system after regeneration of resin, filter changing, ozone generator failure etc. & in the last water system (Standard Operating Procedure )SOP’s produced.
Phase II Validation :
1.This phase is continuity of previous phase i-e phase I, it carries the sampling plan same as previous phase plan & it also facilitates the monitoring of system for 2 – 4 weeks (30 days) period.
2. In this phase, development of refined SOP’s after phase I completion is done.
3. During phase II, manufacturing can be done with that water.
4. This phase describes that the water system is within predetermine ranges and under control.
5. At phase II, testing also assures the continuous persistent and steady production of required quality and quantity when the water system as per (Standard Operating Procedure ) SOP’s operated.
Phase III Validation :
1.In this phase sampling locations and frequency reduced as compared to previous phases.
2. Phase III represents that the water system shows reliable under control attainment over such a long time period & Phase III typically runs for one year after the satisfactory completion of phase II.
3. Manufacturing can be done during phase III & Feed water seasonal variations also evaluated & monitored in this Phase.
4. Complete microbiological and chemical analysis must be carried out in phase III and results are required to be presented in graphs using computer imitations.
5. Whole validation report should be compiled, written, reviewed and approved as per company’s standard procedure.
6.chemical & microbiological analysis like pH , conductivity, Total organic carbon (TOC) & total bacterial count shall be done through out the above phases .
Post Validation Monitoring of Water :
1. It comprises of routine check and balance of the water system, normal sampling and routine analysis & maintenance of equipment.
2. All the phases should be monitored in order to assure that the required desired conditions are satisfactorily set as specification.
3. All these checks should be clearly documented in the respective log book as well as in the reference validation protocol & Report
4. Any deviation or change from this procedure should be documented and investigated.
5. There must be a written procedure or program for maintenance of equipment part should be defined in the protocol.
6. The procedure should have all the details of items required to check calibration and maintenance frequency.
Re-validation of Purified water System :
Re-validation is important which can occur due to various condition
Periodic Re-validation & Re-validation after any changes
Periodic Re-validation :
- over certain period of time water system need to be change &
Periodic Re-validation is done to evaluate the impact of the change.
- During periodic Re-validation some areas of water system should undergo changes like Standard Operating Procedure, Specification & calibration etc.
Re-validation after any changes :
1.It should be done to evaluate the quality & system of water after any changes.
2. Addition or deletion of any parts or utilities to the existing water system
3. Addition or deletion of any user point or expansion of distribution system
4. Any major change in the process equipment or any maintenance work performed after any major breakdown