Product changeovers (PCO): Acceptance Limits for the carryover of inactivated API Part I – The comparable quality approach

For multi-product biopharmaceutical facilities, setting the acceptable level of process residues following equipment cleaning is an important regulatory, business, product quality, and patient safety consideration. Conventional approaches for setting an acceptance limit for process residues have been based on the assumption that the active pharmaceutical ingredient (API) is chemically or functionally intact following the cleaning process. These approaches include Maximum Allowable Carryover (MAC) Health Based Exposure Limits and other “dose” or Permissible Daily Exposure (PDE)-based limits.

The concept for cleaning acceptance limits based on intact product originated from the manufacturing of small molecule pharmaceuticals. In contrast biopharmaceutical products are large molecules that are likely to degrade and become inactive when exposed to cleaning conditions. Therefore, an alternative approach to setting cleaning acceptance limits for biopharmaceutical products based on the actual process residues that could potentially be present on production equipment should be considered.

This paper, based on the work of the BioPhorum Multi-product facilities team and authored by Rizwan Sharnez and Angela To, describes the methodology to assess and verify API inactivation during cleaning