Purpose of the RTOR Pilot
The Oncology Center of Excellence Real-Time Oncology Review (RTOR) pilot program aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible, while maintaining and improving review quality and balancing the review team’s workload through data and analysis standardization, and early iterative engagement with the applicant.
For the pilot program, multiple supplemental New Drug Application (NDA) and supplemental Biologic License Application (BLA) submissions will be selected from each clinical division (Division of Oncology Products 1, Division of Oncology Products 2, and Division of Hematology Products) to evaluate the feasibility and optimize the process for RTOR. Some original NDA or BLAs may be selected as well. Acceptance into the RTOR pilot does not guarantee or influence approvability of the supplement, which is subject to the usual benefit-risk evaluation by FDA scientists.
Submissions to be considered for the RTOR pilot should meet the following criteria:
- Drugs likely to demonstrate substantial improvements over available therapy, which may include drugs previously granted Breakthrough Therapy Designation for the same or other indications.
- Straight forward study designs, as determined by the review division and the OCE.
- Studies conducted exclusively outside the United States and neoadjuvant and prevention studies will be excluded.
- Endpoints that can be easily interpreted (for example, overall survival in a randomized trial).
- Supplements with CMC formulation changes will be excluded.
Submissions with greater complexity, including those with companion diagnostics, may also be excluded for the purposes of the pilot program.
At the time of top-line results of a pivotal trial, if the eligibility criteria above is met, an applicant can apply for the RTOR pilot by notifying the appropriate division Regulatory Project Manager. The clinical division director/deputy director, the review team (including reviewers, team leaders, and management from all relevant review disciplines) and OCE management will jointly decide whether the application can be selected for the RTOR pilot program.
sNDA/sBLA Timeframe of Real-Time Oncology Review (RTOR)
Q1. Will there be a formal analysis of the pilot and how well it is working? If so, when will this analysis be available?
Yes, analysis will be conducted after each CDER Office of Hematology and Oncology review division has completed the pilot.
Q2. How long will the pilot last before it becomes routine practice?
There is no definite timeline for the pilot program.
Q3. What are the main differences between this and how the FDA currently treats NDAs and BLAs?
RTOR allows the FDA to review much of the data earlier, before the applicant formally submits the complete application. First, the applicant will present topline data for the FDA to determine whether RTOR would be appropriate for the supplement. If the agency determines RTOR is an appropriate review pathway, the applicant can start sending pre-submission data to the agency, under the original NDA/BLA, 2-4 weeks after all patient data has been entered and locked by the applicant in their database and the applicant decides to request FDA approval. This pre-submission package should include key raw and derived (ADaM) datasets, including safety and efficacy tables and figures, the study protocol and amendments, and a draft of the prescribing information. In addition, the applicant should also submit key results, analysis, and datasets for other disciplines (e.g., clinical pharmacology), if applicable. The FDA will start evaluating the pre-submitted data for sufficiency and integrity. This informed pre-analysis gives FDA reviewers and applicants an early opportunity to address data quality and potential review issues. The FDA can provide early feedback to the applicant regarding the most effective way to analyze data to properly address key regulatory questions. By the time the applicant submits the application with the FDA, the agency’s review team has completed the analysis and is in a better position to conduct a more efficient review.
Q4. Does this program impact when the application fee is due/assessed?
For supplemental applications, no fees are necessary. For new molecular entities, PDUFA fees (when applicable) will be due when the first component of the RTOR is submitted.