Accelerating Cancer Drug Approvals with the FDA Real-Time Oncology Review (RTOR)
The U.S. Food and Drug Administration (FDA) has introduced several innovative regulatory pathways to expedite drug approvals, especially in high-need areas like oncology. One such initiative is the Real-Time Oncology Review (RTOR), designed to enhance efficiency in the review process for cancer therapies. This article explores the objectives, criteria, process, and benefits of the RTOR program and how it supports faster access to life-saving treatments for patients with cancer.
What is the FDA RTOR Program?
The Real-Time Oncology Review (RTOR) program, launched by the FDA’s Oncology Center of Excellence (OCE) in 2018, allows the FDA to begin reviewing portions of a drug’s application (typically efficacy and safety data) before the entire New Drug Application (NDA) or Biologics License Application (BLA) is formally submitted. This rolling data submission model helps shorten the overall time to approval.
Objectives of RTOR:
- Enable early review of pivotal clinical data
- Reduce overall review timelines for oncology therapies
- Enhance communication and collaboration between the FDA and sponsors
- Improve FDA workload planning and data review sequencing
Eligibility Criteria for RTOR Participation:
Not all applications qualify for RTOR. The FDA typically selects candidates based on:
- Breakthrough Therapy
It’s important to note that sponsors cannot directly apply for RTOR. Instead, the FDA invites eligible sponsors to participate based on the application’s characteristics and prior interactions.
Key Features of the RTOR Process:
- Pre-Submission Planning:
Sponsors engage in early dialogue with the FDA to align on datasets, trial endpoints, and timelines. - Early Data Submission:
FDA begins reviewing selected datasets (e.g., efficacy tables, safety analysis) before the complete NDA/BLA is submitted. - Rolling Review and Communication:
Sponsors receive preliminary feedback during the rolling submission, enabling real-time issue resolution. - Full Submission and Labeling:
Upon completion of the full NDA/BLA, the FDA finalizes its review with labeling negotiations running in parallel.
RTOR vs Traditional Review Pathways:
| Parameter | RTOR | Traditional Review |
|---|---|---|
| Data Review Start | Before full application submission | After full application submission |
| FDA Communication | Continuous | Formal milestones |
| Review Duration | Potentially shorter | Standard review timelines (10 months) |
Examples of Drugs Approved Under RTOR:
- Atezolizumab (Tecentriq) – for triple-negative breast cancer
- Sotorasib (Lumakras) – for KRAS G12C-mutated NSCLC
- Mobocertinib – for EGFR exon 20 insertion mutations
These approvals demonstrate how RTOR has successfully facilitated quicker access to breakthrough therapies for oncology patients.
Integration with Other FDA Programs:
RTOR is often combined with other expedited programs such as:
- Breakthrough Therapy Designation
- Priority Review
- Accelerated Approval Pathway
This multi-program synergy allows regulators and sponsors to compress the time from development to patient access.
RTOR Submission Components:
Although formal FDA templates for RTOR submission do not exist, typical documents include:
- Annotated statistical analysis datasets
- Top-line efficacy tables
- Safety summary datasets
- Integrated Summary of Efficacy (ISE) and Safety (ISS)
- Clinical study reports (partial or draft)
Best Practices for Sponsors:
- Maintain active communication with the FDA during development
- Develop robust statistical and clinical summaries
- Use SOPs aligned with Pharma SOPs to manage RTOR documentation
- Employ advanced data analysis platforms for real-time dataset generation
- Train regulatory and QA staff with GMP audit process aligned protocols
Challenges with RTOR Implementation:
- Limited transparency in selection criteria
- Resource-intensive for sponsors and FDA reviewers
- Requires mature data management infrastructure
Comparison with EMA and CDSCO:
While the European Medicines Agency (EMA) does not have an exact RTOR equivalent, it offers rolling reviews in emergency contexts (e.g., COVID-19 vaccines). In India, the CDSCO is piloting faster review processes but lacks a dedicated oncology-specific RTOR framework.
Conclusion:
The FDA Real-Time Oncology Review (RTOR) is a game-changing initiative that aligns regulatory rigor with the urgency of cancer care. By enabling earlier data evaluation and iterative feedback, RTOR has redefined the speed of oncology drug development. For sponsors, leveraging RTOR requires readiness, strategic planning, and adherence to evolving regulatory expectations. Platforms like Stability Studies and comprehensive SOP frameworks can support seamless participation in this expedited review paradigm.