FDA Publishes Final Guidelines for Real-time Review of Oncology Drugs

The FDA originally published a draft of the guidelines on July 22, 2022, which stated that the program was meant to aid in quickly identifying possible cancer treatments that could qualify to be reviewed early by the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER).

The FDA has published its final guidelines that explain the eligibility and submission requirements for applicants interested in submitting biologics license applications (BLAs) or new drug applications (NDAs) for its real-time oncology review pilot (RTOR), according to a news release by Regulatory Focus regarding the finalization.¹

The final version of the guidelines state that eligible submissions must demonstrate significant benefits over available treatment options, must not require an advisory committee meeting or a new Risk Evaluation and Mediation Strategy (REMS), and must include clinical trial end points that can be “easily interpreted.”² These end points consist of overall survival and response rates as determined by the FDA Oncology Center of Excellence (OCE) and the review division.

“In a typical FDA drug review process, efficacy and safety data are submitted at the same time as other elements of a drug application (eg, administrative information, summary documents, clinical study reports, manufacturing information, and nonclinical study reports, etc.) for a complete application,” the FDA stated in the final guidance of the RTOR. “However, the process of assembling a drug application for submission usually takes at least several months. 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 (eg, parts of the clinical module, etc.) may be submitted at separate times.”

The FDA originally published a draft of the guidelines on July 22, 2022, which stated that the program was meant to aid in quickly identifying possible cancer treatments that could qualify to be reviewed early by the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER).³

The current approval has not altered much of the draft but rather clarified terminologies, the eligibility for drug applications, and the submission process. The draft originally stated that eligibility is based on “straightforward study designs as determined by the review division and the OCE.” New changes in the guidelines come after Pfizer’s suggestions to clarify what the OCE considered straightforward and noted that it would “be helpful for FDA to include several examples of the types of study designs that the review division and OCE consider straightforward.”⁴

The current guidelines state that, in order to be considered for RTOR, submissions should demonstrate: “Clinical evidence from adequate and well-controlled investigation(s) indicates that the drug may demonstrate substantial improvement on a clinically relevant endpoint(s) over available therapies; easily interpreted clinical trial endpoints (eg, overall survival, response rates), as determined by the review division and OCE; no aspect of the submission is likely to require a longer review time (eg, requirement for new REMS, advisory committee, etc.).”⁵

The RTOR was originally founded in 2018 to expedite potential new treatments for patients with cancer. The guidelines state that applications can continue to follow routine submission procedures if they are not accepted into RTOR.

References

1. Eglovitch JS. FDA finalizes guidance on real-time review of oncology drugs. News release. Regulatory Focus. November 7, 2023. Accessed November 16, 2023. https://tinyurl.com/2p86u6r6
2. Real-time oncology review (RTOR) guidance for industry. FDA.gov. November 2023. Accessed November 16, 2023. https://tinyurl.com/yc6ectma
3. Al-Faruque F. FDA explains the ins and outs of real-time oncology review program in new guidance. News release. Regulatory Focus. https://tinyurl.com/5em36n3e
4. Comment on “Real-Time Oncology Review.” Pfizer Inc. September 19, 2022. https://tinyurl.com/3ya6zp2e
5. Real-Time Oncology Review (RTOR). US Food and Drug Administration. Published November 7, 2023. Accessed November 16, 2023. https://tinyurl.com/3ywtss8u