FDA has issued draft guidance, Expedited Programs for Serious Conditions: Drugs and Biologics, to facilitate and expedite development and review of new drugs to address unmet medical need in the treatment of a serious or life-threatening condition: fast track designation, breakthrough therapy designation, accelerated approval, and priority review designation. The purpose of this guidance for industry is to provide a single resource for information on FDA’s policies and procedures for these four programs as well as threshold criteria generally applicable to concluding that a drug is a candidate for these expedited development and review programs.
In outlining the information, FDA also detailed in the draft guidance considerations a sponsor company should make in its manufacturing development program for a product under accelerated review. FDA specified that the sponsor of a product that receives an expedited drug development designation may need to pursue a more rapid manufacturing development program to accommodate the accelerated pace of the clinical program. The draft guidance specifies that a sponsor’s product quality and CMC (chemistry, manufacturing, and control) teams should initiate early communication with FDA to ensure that the manufacturing development programs and timing of submissions meet the agency’s expectations for licensure or marketing approval. The draft guidance specifies that when sponsors receive an expedited drug-development designation, they should be prepared to propose a commercial manufacturing program that will ensure availability of quality product at the time of approval. The draft guidance specifies that the proposal should consider estimated market demand and the commercial manufacturing development plan. The proposal should also consider manufacturing facilities and a lifecycle approach to process validation. Additionally, the proposal should include a timeline for development of the manufacturing capabilities with goals aligned with the clinical development program. After the initial discussion following designation, frequent communication during development will generally facilitate meeting manufacturing development goals and product quality goals.
The draft guidance specifies that sponsors of such products should allow for an earlier submission of the CMC section (including product quality information) for timely review, and, critically, for inspection activities Coordination with the sponsor and contract manufacturers may be necessary to ensure that manufacturing facilities and equipment are ready for inspection during review of the clinical section of the application. A comprehensive meeting with FDA’s product quality review groups in advance of submission may facilitate the quality assessment of products designated for expedited programs.
Although sponsors must ensure the availability of quality product at the time of approval, FDA may exercise some flexibility on the type and extent of manufacturing information that is expected at the time of submission and approval for certain components (e.g., stability updates, validation strategies, inspection planning, and manufacturing scale-up). The draft guidance specifies that the level of flexibility will be determined on a case-by-case basis after consideration of factors such as the following: (1) product characteristics, (2) seriousness of the condition and medical need, (3) manufacturing processes, (4) the robustness of the sponsor’s quality system, and (5) the strength of the sponsor’s risk-based quality assessment. FDA’s consideration of the sponsor’s proposal for an integrated postmarketing plan will also take into account whether elements of the plan may be appropriately executed as a postmarketing commitment or requirement.