Regulatory Considerations for Stability Studies of Co-Processed Active Pharmaceutical Ingredient.

A co-processed active pharmaceutical ingredient (CP API) is the combination of an active pharmaceutical ingredient (API) with non-active component(s). This technology has been demonstrated to offer numerous benefits, including but not limited to improved API properties and stability. The infrastructure requirements are such that the manufacture of a CP API is typically best suited for an API facility. CP API has been regulated as either an API or as a drug product intermediate (DPI). This variability in the designation has led to ambiguities on the regulatory CMC expectations in the CP API including the stability of CP API and CP API containing products which, in turn has hampered the broader application of this technology in the pharmaceutical industry. This difference in designation also resulted in challenges to the lifecycle management of the regulatory documentation for the CMC information of the CP API.This white paper represents the proposals for the regulatory requirements on stability studies related to CP API and to drug product containing CP API by the CP API Working Group (WG) of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ). Additionally, considerations and the WG's recommendations on the stability studies of CP API from different manufacturing sites or processes and post-approval changes for product containing CP API are described.