Water is the most widely used raw material or starting material in the production, processing and formulation of pharmaceutical products.  Planned, well-defined, successful and well-documented commissioning and qualification is an essential precursor to successful validation of water systems. 

  • A Three-Phase Approach should be used to satisfy the objective of proving the reliability and robustness of the water system.
  • This guidance does not define the standard requirements for the conventional qualification stages like DQ, IQ and OQ, but concentrates on the particular PQ (Performance Qualification) approach that should be used for WPU (Water for Pharmaceutical use) systems to demonstrate their consistent and reliable performance.
  • Tests on the source water must be included within the validation programme and continued as part of the routine monitoring.
  • The source water should meet the requirements for drinking-water as per WHO guideline and any internal specification.

Phase 1 of Performance Qualification

  • Sample daily or continuously monitor the incoming feed-water to verify its quality.
  • A test period of Two Weeks should be spent monitoring the system intensively.
  • During this period, the system should operate continuously without failure or performance deviation.
  • Usually water is not used for finished pharmaceutical product (FPP) manufacturing during this period.
  • Following activities should be included in the testing approach.
  1. Undertake chemical and microbiological testing in accordance with a defined plan.
  2. Sample or continuously monitor the incoming feed-water daily to verify its quality.
  3. Sample or continuously monitor after each step in the purification process.
  4. Sample or continuously monitor at each point of use and at other defined sample points.
  5. Develop appropriate operating ranges.
  6. Develop and finalize operating, cleaning, sanitizing and maintenance procedures.
  7. Demonstrate production and delivery of product water of the required quality and quantity.
  8. Use and refine the standard operating procedures (SOPs) for operation, maintenance, sanitization and troubleshooting.
  9. Verify provisional alert levels.
  10. Develop and refine test-failure procedure.

Phase 2 of Performance Qualification

  • A further test period of Two Weeks should be spent carrying out further intensive monitoring while deploying all the refined SOPs after the satisfactory completion of phase 1.
  • Sampling scheme should be generally the same as in Phase-1.
  • Use of the water for FPP manufacturing purposes during this phase may be acceptable, provided that both commissioning and phase 1 data demonstrate appropriate water quality and the practice is approved by QA.
  • The approach should also:

-Demonstrate consistent operation within established ranges;

-Demonstrate consistent production and delivery of water of the required quantity and quality when the system is operated in accordance with the SOPs

Phase 3 of Performance Qualification

  • Phase 3 typically runs for One Year after the satisfactory completion of phase 2.
  • Water can be used for FFP manufacturing purposes during this phase which has the following objectives:
    -To demonstrate reliable performance over an extended period;
    -To ensure that seasonal variations are evaluated.
  • The sample locations, sampling frequencies and tests should be reduced to the normal routine pattern based on established procedures proven during phases 1 and 2.

Abbreviations :

  • DQ : Design Qualification
  • IQ : Installation Qualification
  • OQ : Operation Qualification
  • PQ : Performance Qualification
  • FPP : Finished Pharmaceutical Product
  • WPU : Water for Pharmaceutical Use
  • WHO : World Health Organization
  • SOP : Standard Operating Procedure

Reference : WHO Guidelines
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