Snapshot

The FDA Real Time Oncology Review-RTOR pathway has been developed by the US Food and Drug Administration of United States.

This pathway can be used where Oncology drug applications, including New Drug Applications (NDAs) for new molecular entities (NMEs) submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA), original Biologics License Applications (BLAs) submitted under section 351(a) of the Public Health Service (PHS) Act, and supplemental NDAs and BLAs, may be eligible for RTOR. Acceptance into the RTOR program does not guarantee or influence approvability of the application, which is subject to the same statutory and regulatory requirements for approval as applications that are not included in RTOR. Participation by the applicant in this program is voluntary. NB: RTOR may not be suitable for certain biological products, such as cell and gene therapies, for which complex manufacturing and product characteristics need to be considered in evaluating the safety and efficacy of the product. For these types of products, USFDA recommend that a discussion of whether the product is suitable for RTOR take place with the appropriate review division. .

This pathway accelerates the regulatory review process.

It is an abridged review (a reliance pathway).

Target time assessment is RTOR involves early engagement with the applicant to discuss the submission timelines for RTOR components and the full application submission. To determine eligibility for RTOR, FDA would need the top-line efficacy and safety results from the pivotal clinical trial(s). At this stage, the applicant should have already completed the database lock for the clinical trial. At the time top-line results of a pivotal trial(s) are available and the database has been locked, an applicant may apply for review under RTOR by submitting a request to the Investigational New Drug Application (IND). The applicant should include their top-line results and submit RTOR Request information, which includes information such as the justification explaining how their application demonstrates that it is appropriate for RTOR, and a proposed timeline of when it will submit the various components of the RTOR 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 RTOR. This decision will generally be made within 20 business days of receipt of the request and communicated to the applicant via email. If the application is not accepted into RTOR, the applicant should follow routine application submission procedures. Once an application is selected, a teleconference with the applicant may be scheduled if necessary (generally within 20 business days). The OOD clinical division director/deputy director, the review team, and OCE staff may participate in this meeting. FDA and the applicant will discuss the plan for RTOR and reach tentative agreement on proposed submission timelines for the drug application. During the pre-NDA/BLA meeting to discuss the proposed application, FDA may share preliminary key review questions or issues and critical analyses needed. If FDA requests additional analyses, the applicant may submit them before or at the time of submission of the complete marketing application. In some cases, if FDA agrees, the applicant may submit the requested additional analyses after the marketing application is submitted. These discussions may be documented in the meeting minutes under the section, “Agreement of a Complete Application” for NDA NMEs or original 351(a) BLAs. For supplemental applications, RPMs may capture agreements discussed under “Additional Items Discussed” or under discussion of specific questions as appropriate in the official meeting minutes. When FDA receives the final component, the application is considered complete, and the review clock will start. A study by de Claro et al found that the median interval between the first RTOR submission to the complete application submission is 5.7 weeks, with a range of 1.7–16.2 weeks. The same study also reports that the median time from the clinical trial data cutoff to application submission is 6.1 months with a range of 2.7–15.7 months. Additionally, the median time from application submission to approval was 3.3 months, with a range of 0.4–5.9 months.