White Paper Examining Manufacturing Readiness for Breakthrough Drug Development

In July 2012, Congress passed the Advancing Breakthrough Therapies for Patients Act as part of the Food and Drug Administration Safety and Innovation Act (FDASIA). Section 902 of FDASIA provides for designation of a drug as a breakthrough therapy Bif the drug is intended alone or in combination with one or more other drugs, to treat serious or life-threatening diseases or conditions and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies (1).^ Breakthrough designation is a mechanism that the U.S. Food and Drug Administration (FDA) can grant to sponsors to expedite the development of these promising therapies. As part of the program, the FDA and sponsor collaborate in a dynamic, multi-disciplinary, resource-intensive process to determine the most efficient path using an Ball hands on deck approach^ involving senior managers and experienced review staff and more frequent and interactive communications (2,3). The objective is to expedite design and review of the clinical development program so that trials are as efficient as possible, and the number of patients exposed to potentially less efficacious treatment is minimized. As a consequence, clinical development timelines involving the traditional three distinct phases could be reduced from 7–10 to 3–5 years. The shorter clinical development programs will have significant impact on product and process development timelines requiring the manufacturing organization to reconsider traditional approaches to product and process development and undertake their own resource-intensive, cross-functional team approach to ensure a sustained supply of safe and efficacious product at the time of approval. To ensure success, the manufacturing organization should have good communications with the clinical organization to facilitate identification of potential candidates for breakthrough designation early and help gate or accelerate the appropriate Chemistry, Manufacturing, and Controls (CMC) and current Good Manufacturing Practice (cGMP) development activities. It is important to understand that breakthrough drug development programs are resource intensive; sponsors need to be selective about which programs to take forward and ensure management support. Moreover, a collaborative, cross-functional approach between development, commercial, and regulatory operations, with early and robust discussions, is essential to ensure successful development and launch of a breakthrough drug product. In March of 2015, Friends of Cancer Research (Friends) convened a group of industry and FDA stakeholders familiar with developing breakthrough drugs to explore options, The opinions expressed in this manuscript are those of Earl Dye, Annie Sturgess, Gargi Maheshwari, Kimberly May, Colleen Ruegger, Usha Ramesh, Heow Tan, Keith Cockerill, John Groskoph, Emanuela Lacana, Sau Lee, and Sarah Pope Miksinski and do not necessarily reflect the views or policies of the FDA.