FRED OHSIEK
Validation Manager, Ecolab Life Sciences, USA

Abstract

In general, cleaning validation (CV) is a 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 not specifically to any industry. Therefore, deciphering and implementing their recommendations or expectations is often difficult.
Because high potent active pharmaceutical ingredient (HPAPI) manufacturing (API or finished product) is very high-risk from a patient safety perspective, every stage of the cleaning validation (from development to periodic monitoring) requires additional considerations and evaluation.
Every stage of the cleaning validation was assessed in respect to HPAPI manufacturing. 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).

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.

The main processes or activities in the three stages of validation (development, CV, and maintenance of the CV program) are evaluated. Stage 1 requires the most consideration, preparation, and planning. Accordi ...