Part IV: Qualification of Water and Air Handling Systems

3. Steps of Validation

Validation plans for water and air systems typically include the following steps:

1. Establishing standards for quality attributes of water and air to manufacture pharmaceuticals.

2. Defining systems and subsystems suitable to produce the desired water and air by considering the quality grades of water and air.

3. Designing equipment, controls, and monitoring technologies.

4. Establishing standards for operating parameters of the selected equipment of the system.

5. Developing an IQ stage consisting of instrument calibrations, inspections to verify that the drawings accurately depict the as-built configuration of the system, and special tests to verify that the installation meets the design requirements. These items include pipe and instrument drawings, air pressure differentials, air velocities, and airflow patterns.

6. Developing an OQ stage consisting of tests and inspections to verify that the equipment, system alerts, and controls are operating.

7. Establishing alert and action levels for the operational standards and routine control. This phase of qualification may overlap with aspects of the next step.

8. Developing a prospective PQ stage to confirm the appropriateness of critical process parameter operating ranges. System reproducibility is to be demonstrated in this stage over an appropriate time period.

During this phase of validation, alert and action levels for key quality attributes of water, such as TOC, pH, particulates and microbes, and operating parameters for an air system (e.g., temperature, time, air pressure differential, airflow velocity, and air exchange rate) are verified.

9. Supplementing a validation maintenance program (also called continuous validation life cycle) that includes a mechanism to co ntrol changes to the system and establishes and carries out scheduled preventive maintenance, including recalibration of instruments.

10. Instituting a schedule for periodic review of the system performance and re-qualification.

11. Completing protocols and documenting steps 1 through 10.