Considerations and Regulatory Challenges for Innovative Medicines in Expedited Approval Programs: Breakthrough Therapy and Sakigake Designation.

Abstract

In the breakthrough therapy designation (BTD) and Sakigake designation programs, rolling submission and close communication between applicants and regulatory authorities enable the timely access of patients to innovative medicines. However, challenges in the quality development, including chemistry, manufacturing, and control (CMC), are expected during the accelerated timeline. This study focused on development with quality by design (QbD) concept, shelf life of drug product, and post marketing commitment (PMC) to clarify developmental strategies and regulatory challenges associated with expedited approval programs. QbD developments, shelf life of drug products, and PMC were surveyed in the review reports of the US Food and Drug Administration (FDA) and Pharmaceuticals and Medical Devices Agency (PMDA) websites. Overall, 86% of BTD products and two out of three Sakigake products were developed using a QbD approach. Furthermore, 92% of BTD products and two out of three Sakigake products were granted a shelf life of at least 18months. In the BTD pathway, 50% of PMCs concerned the reevaluation of specification and test method. For most BTD and Sakigake products, the control strategy was developed utilizing the QbD concept, and long shelf life was granted despite the accelerated timeline. No discount for specification setting was observed for assuring quality, based on the available data at the time of approval in the BTD and Sakigake programs, although PMCs were mainly required for reevaluation of the specification and test method in BTD programs. Further efforts should focus on creating/revising guidelines for CMC development.