Process Qualification - Stage of Continuous process validation

Stage 2-Process Qualification :
process qualification (PQ) is the stage of process validation, the process design is evaluated to determine if it is capable of reproducible commercial manufacture. 

This stage has two elements:
 (1) Design of the facility and qualification of the equipment and utilities and
 (2) Process performance qualification (PPQ).

During Stage 2, CGMP-compliant procedures must be followed. Successful completion of Stage 2 is necessary before commercial distribution. Products manufactured during this stage, if acceptable, can be released for distribution.

1.     Design of a Facility and Qualification of Utilities and Equipment:

-It is essential that activities performed to assure proper facility design and commissioning precede Process performance qualification.

-The term qualification refers to activities undertaken to demonstrate that utilities and equipment are suitable for their intended use and perform properly.These activities necessarily precede manufacturing products at the commercial scale.

-Qualification of utilities and equipment generally includes the following activities:

-Selecting utilities and equipment construction materials, operating principles, 

-performance characteristics based on whether they are appropriate for their specific uses. 

-Verifying that utility systems and equipment are built and installed in compliance with the design specifications (e.g., built as designed with proper materials, capacity, and functions, and properly connected and calibrated). 

-Verifying that utility systems and equipment operate in accordance with the process requirements in all anticipated operating ranges. 

-This should include challenging the equipment or system functions while under load comparable to that expected during routine production. It should also include the performance of interventions, stoppage, and start-up as is expected during routine production. Operating ranges should be shown capable of being held as long as would be necessary during routine production.

The plan should identify the following items:

The studies or tests to use,

2. the criteria appropriate to assess outcomes,

3. the timing of qualification activities,

4. the responsibilities of relevant departments and the quality unit, and

5. the procedures for documenting and approving the qualification.

2. Process Performance Qualification

-The process performance qualification (PPQ) is the second element of Stage 2, process qualification. 

-The PPQ combines the actual facility, utilities, equipment (each now qualified), and the trained personnel with the commercial manufacturing process, control procedures, and components to produce commercial batches. 

-A successful PPQ will confirm the process design and demonstrate that the commercial manufacturing process performs as expected. 

-The approach to PPQ should be based on sound science and the manufacturer’s overall level of product and process understanding and demonstrable control. The cumulative data from all relevant studies (e.g., designed experiments; laboratory, pilot, and commercial batches) should be used to establish the manufacturing conditions in the PPQ.
 

-To understand the commercial process sufficiently, the manufacturer will need to consider the effects of scale. However, it is not typically necessary to explore the entire operating range at commercial scale if assurance can be provided by process design data. 

-In most cases, PPQ will have a higher level of sampling, additional testing, and greater scrutiny of process performance than would be typical of routine commercial production. The level of monitoring and testing should be sufficient to confirm uniform product quality throughout the batch. 

-The increased level of scrutiny, testing, and sampling should continue through the process verification stage as appropriate, to establish levels and frequency of routine sampling and monitoring for the particular product and process. Considerations for the duration of the heightened sampling and monitoring period could include, but are not limited to, volume of production, process complexity, level of process understanding, and experience with similar products and processes. 

-The process design stage and the process qualification stage should focus on the measurement system and control loop for the measured attribute. Regardless, the goal of validating any manufacturing process is the same: to establish scientific evidence that the process is reproducible and will consistently deliver quality products.