The idea of a rolling submission, or rolling review, for a Biologics License Application (BLA) or New Drug Application (NDA) is not new. In fact, the concept was introduced as the U.S. Food & Drug Administration (FDA) implemented the Modernization Act of 1997.
A rolling submission is done in waves. Sponsors submit completed sections for review, as opposed to waiting for the entire application to be finished. Smaller portions, as opposed to one large submission, are well suited for projects granted accelerated review timelines. We’re seeing that the means to pull off a rolling submission are available and the awarding of expedited pathway designations is motivating sponsors to proceed with a sense of urgency.
Technology is vastly superior today compared to the era of dial-up internet when the rolling submission concept was born. The adoption of eCTD and availability of the Electronic Submissions Gateway (ESG) make it much easier to achieve a rolling submission. The final tipping point in favor of rolling submissions is a regulatory one, spelled out in the guidance document Expedited Programs for Serious Conditions – Drugs and Biologics.
If your drug program meets criteria set by the FDA, you are entitled to certain benefits. Permission to proceed with a rolling submission is one such benefit. A product receiving a Fast Track designation is eligible for a rolling submission, as is a product granted a Breakthrough Therapy designation.
How exactly does a rolling submission work? As an example, a sponsor submits their non-clinical portion in the first wave, followed by a chemistry, manufacturing and controls (CMC) wave and then a final wave containing clinical. In another instance, you might submit CMC in the first wave and place final stability in the last wave.
Module 1 components can be submitted in each wave. For example you may want to submit your letters of authorization and debarment certifications in wave 1, while waiting to place labeling in the final wave. There is no set way to operate. Each program is unique and merits its own roadmap/plan.
The review clock typically does not begin until everything is submitted. Nevertheless it is an advantageous concept for both parties – sponsor and Agency. Considering these breakthrough programs are expeditious in nature, it behooves the agency to commence preliminary review as opposed to waiting and receiving one big NDA/BLA bolus. Sponsors are also working with a greater degree of efficiency by sending finished parts while other aspects of their application, such as the clinical portion, are still in progress.
If you are interested in pursuing this type of submission, speak with your FDA regulatory project manager and submit an official rolling review request. The request should be placed in Module 1, specifically section 1.7.3. Any subsequent correspondence you receive regarding the rolling submission should be housed in 1.7.4.
The beauty of eCTD is the manner in which the standard classifies files as new, replaced, or deleted. If you are working on a rolling submission, eCTD accounts for all the components, interdependencies, linkages and lifecycle. The final wave is marked as the original application.
The FDA’s eCTD Technical Conformance Guide, posted in October 2015, is a great resource and represents FDA’s current thinking on technical specifications. The document includes a section on rolling submissions and is a logical starting point if you’re planning to pursue such a project.