HPAPI Cleaning validation considerations – Part 2

INTRODUCTION
This article not only applies to the HPAPI production, but also to pharmaceutical production with HPAPIs. Therefore, the term “HPAPI manufacturing” and “HPAPI product” applies to both types of production.
It is important that the requirements for the finished manufacturing companies are not transferred back in the process to active pharmaceutical ingredient manufacturers without consideration for the different processes (i.e., carry-over risk) that take place at this stage (1).

The main processes or activities in the three stages of validation (development, CV, and maintenance of the CV program) were evaluated. The evaluation of stage 1 is discussed in HPAPI Cleaning Validation Considerations Part 1 (2).
HPAPI Cleaning Validation Considerations Part 2 discusses Stage 2 and Stage 3 activities. There are no significant additional requirements or activities for stage 2 and stage 3, but the below discussion provides additional guidance on each activity.
For stage 2, it is critical that CV documents are complete and accurate, and execution are performed and documented accurately.
For stage 3, it is common practice in industry not to overcomplicate or overperform activities. Because of the high risk when manufacturing HPAPI manufacturing, stage 3 is a very critical stage.
Though most of the topics discussed apply to all pharmaceutical and biopharma industry, in HPAPI manufacturing any CV program failure (strategy or approach) or mismanaged situation (equipment selection, protocol deviations, …) could easily result in product loss, product recall, patient injury or death; instead of just a regulatory finding or loss of production time.
This article is not meant to discourage cleaning equipment instead of utilizing single use. It is simply to provide guidance and perspective on validating the cleaning on HPAPI manufacturing equipment.
Even though HPAPI products are usually manufactured at lab scale or a significantly smaller scale than non-HPAPI manufacturing, the concepts and principles are the same.