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  1. CDER Small Business & Industry Assistance (SBIA)

Transcript: Real-Time Review of Drug Applications is Now a Reality

Welcome to the CDER Small Business and Industry Assistance (SBIA) Podcast Series

Today’s topic is Real Time Review of Drug Applications.

The FDA has started using real-time review of drug applications to evaluate clinical data as soon as trial results become available. This means that FDA can approve a new indication soon after an applicant files a marketing application. Currently, this approach is only being implemented by FDA’s Oncology Center of Excellence or OCE, through two pilot programs for supplemental applications to already-approved cancer drugs. However, this could later expand to new drugs and biologics.

FDA was able to start analyzing data for the recently approved supplemental application for the cancer drug Kisqali before it was submitted, and help guide the applicant’s analysis of the top-line data to tease out the most relevant information. The supplemental application received approval under the pilot less than one month after the submission date, and several months ahead of the goal date.

The two pilot programs aim to approve supplements much sooner than the standard review times. The goal is to increase the efficiency of the development and review of cancer drugs and improve FDA’s rigorous standards for evaluating efficacy and safety by enhancing the process for evaluating the data submitted to us.  

What does this mean? It’s a win-win situation across the board for industry, FDA, health care providers and patients. FDA will have more time to engage with applicants and focus on the key aspects of drug reviews, and health care providers and patients will benefit from the availability of drug products.

The first pilot program being utilized by FDA, the Real-Time Oncology Review or RTOR Program, focuses on early submission of data that are the most relevant to assessing the product’s safety and effectiveness. RTOR allows the FDA to review much of the data earlier, after the clinical trial results become available and the database is locked, before the information is formally submitted to the FDA.

 Eligibility criteria used for a supplemental new drug application to be selected for RTOR include:

  • Drugs likely to demonstrate substantial improvements over available therapy
  • Straight forward study designs and
  • Endpoints that can be easily interpreted

Studies conducted exclusively outside the United States, adjuvant, neoadjuvant, and prevention studies, supplements with chemistry, manufacturing and control formulation changes and supplements with pharmacology/ toxicology data will be excluded.

Submissions with greater complexity, including those with companion diagnostics, may also be excluded from the pilot program.

At the time of top-line results of a pivotal trial, if the eligibility criteria are met, an applicant can apply for the RTOR pilot by notifying the appropriate FDA Regulatory Project Manager.

Once FDA determines that RTOR is an appropriate review pathway, the applicant can start sending pre-submission data to the agency under the original new drug application (NDA) or biologics license application (BLA) two to four weeks after all patient data has been entered and locked in the database and the applicant is ready to request FDA approval. This pre-submission package should include key raw data and derived datasets, study protocol and amendments, and a draft of the package insert. The applicant should also submit key results, analysis, and datasets for other disciplines, if applicable.

FDA will start evaluating the pre-submitted data for sufficiency and integrity. This pre-analysis gives the agency an early opportunity to address data quality and potential review issues and provide early feedback regarding the most effective way to analyze data to properly address key regulatory questions.  By the time the applicant submits the application, the FDA review team will already have completed the analysis and can conduct a more efficient, timely, and thorough review. Early engagement with the sponsor can potentially improve the quality of the NDA/BLA submission, and FDA’s evaluation of the application.

The second pilot is a new Assessment Aid, a structured template that the applicant uses to organize its submission into a structured format to facilitate FDA’s review of the NDA or BLA including supplements.

This creates a more efficient and streamlined review process and reduces the administrative burden on FDA reviewers by allowing them to focus on key results and perform critical analyses that may have been omitted by the applicant.

During the Investigational New Drug or IND stage, the Assessment Aid template is sent to the applicant. The applicant can send a notification of interest to the FDA Regulatory Project Manager prior to application submission or at the pre-NDA or pre-BLA meeting. If participating in the RTOR program, the applicant may submit the Assessment Aid before or around the time of the NDA/BLA submission.

The applicant will add their position concisely once top-line data are received in anticipation of an original or supplemental NDA or BLA submission, and the FDA review team will add their assessment, which will focus on whether FDA agrees with the applicant’s position along with any additional findings and analyses.  By using a structured template, the FDA can layer its assessment into the same file submitted by the sponsor.

Applicants who do not wish to participate in the Assessment Aid pilot will follow the usual submission process. Note that there is no definite timeline for the pilot programs. An analysis will be conducted after each CDER Office of Hematology and Oncology review division has completed the pilot. In addition, there are no user fees since the pilot is for supplemental applications only. If expanded to original drugs and biologics, the FDA will determine when to assess the PDUFA fees.

As FDA and applicants embark on this exciting new venture, we hope to improve regulatory review efficiency and further solidify our review standards, while reducing administrative burdens that can add to the time and cost of the review process. Our ultimate goal is to ensure that safe, effective and quality treatment options are available to patients as early as possible.

A link to the full SBIA Chronicles article and more information about CDER’s SBIA Program can be found at: www.fda.gov/cdersbia. Thanks for tuning in!

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