Applied Statistics for FDA Process Validation 2019

In Guidance for Industry Process Validation: General Principle and Practices, process validation is defined as, ""...the collection and evaluation of data, from the process design stage through commercial production.." The guidance further delineates the 'process design stage through commercial production' into three distinct stages of the product lifecycle:

Stage 1: Process Design: The commercial manufacturing process is defined during this stage based on knowledge gained through development and scale-up activities.

Stage 2: Process Qualification: During this stage, the process design is evaluated to determine if the process is capable of reproducible commercial manufacturing.

Stage 3: Continued Process Verification: Ongoing assurance is gained during routine production that the process remains in a state of control.

The first stage of process validation is process design. The Process Validation guidance document states, "A successful validation program depends on information and knowledge from product and process development. This knowledge and understanding is the basis for establishing an approach to control of a manufacturing process that results in products with desired quality attributes:

Manufactures should:

• Understand the sources of variation
• Detect the presence and degree of variation
• Understand the impact of variation on the process and ultimately on product attributes
• Control the variation in a manner commensurate with the risk it represents to the process and product."

The second stage of process validation is process qualification. Although stage 2 has two elements, this course will focus on recommendations for the second element, PPQ. 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." Additionally, the process validation guidance document that "Each manufacturer should judge whether it has gained sufficient understanding to provide a high degree of assurance in its manufacturing process to justify commercial distribution of the product. Focusing exclusively on qualification efforts without understanding the manufacturing process and associated variations may not lead to adequate assurance of quality."