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.

Fred Ohsiek, Cleaning Validation Expert

Fred Ohsiek has performed cleaning validation for 22 years for small and large molecule API and finished-product manufacturing for 7 major pharmaceutical companies. This experience gave Fred a good perspective on industry best practices and practical solutions.

His experience covers every stage of the CV life cycle – from cleaning optimization to cleaning validation to continued process verification (CPV).

His experience includes legacy and startup facilities. Therefore, he is experienced in defending, remediating, or optimizing legacy facilities or building a CV program from the ground up.

He was one of the authors on the ISPE Guide: Cleaning Validation Lifecycle – Applications, Methods, and Controlsand the CV acceptance criteria chapter lead. This was a three-year project which included weekly meetings with industry SMEs to discuss very topic within the cleaning validation sphere.

Fred also has experience with cleaning challenges and issues. While working for Ecolab Life Sciences, Fred conducted site surveys; solved cleaning problems; assisted in optimizing cleaning processes; and conducted onsite CV training for major pharmaceutical and biotech corporations.

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