FRED OHSIEK
Sr Global Technical Manager, Life Science (Cleaning Validation), Ecolab Life Sciences

Abstract

In general, Cleaning Validation (CV) is very complicated topic. The complexity is not only maneuvering within a site’s CV program, but also between industries (i.e., small molecule, biopharma, and API/finished product manufacturing). Regulatory guidelines discuss CV topics in general but specifically to any industry. Therefore, deciphering and implementing their recommendations or expectations is often difficult.
Because High Potent Active Pharmaceutical Ingredient (HPAPI) manufacturing is very high-risk from a patient safety perspective, every stage of the CV (from development to periodic monitoring (PM)) requires additional considerations and evaluation.
A thorough assessment of every stage of the HPAPI CV process was performed. This resulted in considerations, recommendations and solutions; which are published in this article.

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. ...