This article not only applies to high potent (HP) active pharmaceutical ingredient (API) manufacturing, but it also includes pharmaceutical manufacturing products with HP APIs; 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].
Because of the high risk of cross contamination, HPAPI product manufacturers often utilize single-use components for direct product contact equipment surfaces, not requiring cleaning validation. Single-use components come at a cost: they are expensive over time and have a heavy environmental impact. The decision to use single-use components may be due to patient safety, site logistics, or lack of site validation expertise.

The purpose of this article is to help a firm to evaluate if cleaning and validating the cleaning process is an option. Because of the higher risk to patient safety in HPAPI manufacturing (API or finished product), every stage of the cleaning validation (from development to periodic monitoring) requires focus and effort to reduce that risk and understand the cleaning and validation process. Although stage 2 (validation execution) and stage 3 (periodic monitoring) require it, they are created from the knowledge accumulated in stage 1. Therefore, the main focus of stage 1 is to understand the cleaning process and create a validation process that demonstrates the cleaning is effective to an acceptable level. Stage 2 (cleaning validation execution) and stage 3 (periodic monitoring) rely on stage 1 understanding and decisions.

Although the following discussion will explore concepts, considerations, and suggestions for performing stage 1 cleaning validation for HPAPI manufacturers, the information presented can also be used for non-HPAPI manufacturers.