Earlier this year, the United States Food and Drug Administration (FDA) released draft guidance, Real-Time Oncology Review (RTOR) Guidance for Industry. The RTOR program is focused on identifying promising new cancer treatments that might qualify for early review by the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER). Importantly, the guidance notes that it does not address the FDA’s expedited programs, including the Fast Track Designation, Breakthrough Therapy Designation, or Priority Review Designation.
The RTOR program was started in 2018 by the FDA’s Oncology Center of Excellence (OCE) and the Office of Oncologic Diseases (OOD), to allow sponsors to submit clinical trial top-line results and data of their cancer drugs in development sooner, hopefully allowing FDA reviewers the opportunity to not only review the data before an official submission of the premarket application, but also provide feedback on the clinical trial.
“The OCE developed RTOR to facilitate earlier submission of critical efficacy and safety data to initiate FDA’s evaluation of the application, whereby components of individual modules (e.g., parts of the clinical module, etc.) may be submitted at separate times,” the agency notes. “RTOR is different than the existing mechanisms for rolling review in which, generally, complete modules (e.g., the complete clinical module) are submitted prior to a complete application submission. The intent of RTOR is to provide FDA reviewers earlier access to data, to identify data quality and potential review issues, and potentially provide early feedback to the applicant, which can allow for a more streamlined and efficient review process.”
For sponsors to qualify for the program, they must provide the FDA with three pieces of information: (1) that their drug is likely to demonstrate substantial improvement over other available treatments; (2) if the drug is not likely to demonstrate substantial improvement over other available treatments, it would need to qualify for the agency’s Expedited Programs; and (3) the sponsor must have a straightforward study design as determined by the review division and OCE.
The FDA notes that when a drug qualifies for the RTOR program, it does not “alter the review performance goals and timelines associated with the applications, including as described in the Prescription Drug User Fee Amendments,” and while “early approvals have occurred with applications included in the RTOR, this may not be feasible for all applications due to specific issues that may be identified with the application or overall workload considerations.”
Additionally, FDA notes that just because a drug qualifies for the RTOR program, it “does not guarantee or influence approval of the application.”
The draft guidance lists the proposed process that the RTOR program will take, starting with submission of the top-line results from a pivotal trial, when available. Sponsors can submit their request to be considered for the program to their assigned Regulatory Project Manager and to the Investigational New Drug Application via email. Included in the email should be the top-line results along with a written explanation as to why they should be included in the program.
FDA notes that upon receipt of the application, “the review division director/deputy director, with input from the review team (including reviewers, team leaders, and management from all relevant review disciplines), will decide whether the application will be selected for the RTOR program. This decision will generally be made within 20 business days of receipt of the request and communicated to the applicant via email.”
As is always the case with guidance documents, it does not have the force and effect of law and do not bind the public in any way. It is only meant to provide clarity to the public regarding existing requirements under the law.