By Bryan K. Braxton, Ph.D, Director Aseptic R&D
The early phases of drug development can be challenging for many reasons, especially with the pressure for speed to the clinic to prove value and preserve funding. That is why it is critical that a drug’s formulation and process are well understood for manufacture at the required scale, which is typically small in early development. This understanding of critical process parameters and impact on quality attributes related to the finished form can be especially challenging if you are working with a limited amount of API. This occurs when an API is expensive, potent, challenging to source, or even a highly regulated substance, such as a Schedule I drug, which requires permission from the Drug Enforcement Agency (potentially causing delays).
A multidiscipline team approach using strategic experimental design is needed to reduce the manufacturing risk of small scale batches. Information should be collected from as few experiments as possible to avoid wasting precious material. The data from these experiments should ideally identify confounding relationships and high risk scaling factors. The worst outcome is for GMP drug products at small scale to be unsuitable for clinical trials due to these API-consuming experiments producing data not useful for de-risking the manufacturing process. Avoiding this scenario requires not only the right expertise and equipment but also experience with successful GMP manufacturing at scales as small as a few liters. A risk-based investment in understanding at these small scales can prevent costly issues during scaling development that ultimately affect the timely delivery to patients in need.