MAY 2020, SPECIAL FEATURE
|Kusuma Mallikaarjun, PhD
Strategic Clinical Regulatory Consulting
Evidera, a PPD business
Brief Overview of CTAP
The Coronavirus Treatment Acceleration Program (CTAP)1 is a special emergency program instituted by the US Food and Drug Administration (FDA) in response to the COVID-19 pandemic. The primary goal of the program is to expedite the availability of new treatments and vaccines to COVID-19 patients as rapidly as possible by using every possible resource, applicable pathway, and process across the agency. The program also ensures that the safety and effectiveness of these treatments and vaccines are simultaneously evaluated. It is important to note that CTAP is not a separate, standalone review entity within the agency, but rather a program which helps prioritize and route COVID-19 programs rapidly to the appropriate FDA Centers and review staff to achieve the above goals.
The CTAP program is an extraordinary effort within the FDA to expedite COVID-19 programs, and its effective implementation includes the following actions:
- Establishing a multi-specialty, multi-disciplinary COVID-19 Product Development team in the Center for Drug Evaluation and Research (CDER), led by the Division of Antivirals in the Office of Infectious Diseases. This team is focused on tracking, managing, triaging, and expediting the review of all COVID-19 treatment development proposals within CDER and the Center for Biologics Evaluation and Research (CBER).
- Streamlining the process for COVID-19 treatment developers to send inquiries and requests to the FDA by establishing a dedicated CTAP mailbox ([email protected]). The requests sent to this email address are triaged by CDER’s COVID-19 Product Development Team. This dedicated mailbox also allows for allocation of COVID-19 programs to the appropriate center within the FDA in those cases where jurisdiction is unclear (i.e., CDER or CBER).
- Establishing clear landing pages on the FDA website to obtain center specific information and processes for COVID-19 program development and meeting requests.
- Drug Development Inquiries for Drugs to Address the COVID-19 Public Health Emergency2
- Coronavirus (COVID-19) | CBER-Regulated Drugs3
- Redeploying medical and regulatory staff to augment review teams that are dedicated to COVID-19 applications.
- Involving senior management in the review of COVID-19 submissions.
- Redeploying operations and policy staff to support the overall CTAP effort.
- Providing resources to healthcare providers and researchers to help them submit emergency single patient expanded access (compassionate use) requests to treat COVID-19 patients with investigational products.
- CTAP covers COVID-19 programs for drugs and biologics, with the following exceptions noted by CBER as not covered:
- Preventive vaccine programs
- Any biologic/vaccine COVID-19 program for an investigational product which has been previously assigned to CBER for any other indication, and/or if there have been prior communications with CBER for the product
- COVID-19 related device programs are not covered
CTAP Actions to Expedite COVID-19 Treatments and Trials
- Immediate triaging of requests from COVID-19 treat-ment developers and scientists to 1) route these to the appropriate CDER or CBER review staff expeditiously and 2) allow for rapid initiation of clinical trials
- Prioritization of proposed products and trials for FDA interactions by CDER or CBER based on completeness/quality of submission, scientific merits, stage of development, and potential benefit-risk profile
- Ultra-rapid and interactive review/input for:
- Development plans
- Single patient emergency/expanded access requests
- Expediting quality assessments for products
- Facilitating transfer of manufacturing to alternative or new sites to avoid supply disruption
- CTAP is currently processing the second wave of COVID-19 treatment proposals and inquiries
- As of April 16, 2020, CTAP had received 950 inquiries and proposals for the development of COVID-19 treatments
- As of May 11, 2020, there were 144 active trials of COVID-19 treatments and 457 COVID-19 development programs in the planning stages
- Turnaround time for CTAP requests is generally one day or less
- CTAP protocol review times occur within 24 hours from submission for some cases
- Single patient emergency/expanded access requests are being reviewed 24 hours a day and generally within three hours from request
Recommended Strategy for Pharmaceutical Companies with COVID-19 Programs
Companies wishing to pursue the CTAP approach for review of their proposed COVID-19 treatment protocol, or to seek FDA input for their program, should do so via the CTAP mailbox if the proposed COVID-19 treatment is:
- A drug, biologic or a treatment vaccine, and
- Is in the late Phase 1, Phase 2, or Phase 3 stage of development, and
- There is a clear signal of proof of concept (POC) and/or significant efficacy, and
- There is a favorable benefit-risk profile, or
- A product for which FDA jurisdiction is unclear
However, requests and inquiries should be submitted directly to the appropriate CDER, CBER, or Center for Devices and Radiological Health (CDRH) Review Divisions if the proposed COVID-19 treatment is:
- A device or
- A prophylactic vaccine, or
- A biologic that has already been allocated to CBER previously for another indication, or
- A biologic that has been previously discussed with CBER, or
- A drug, biologic or a treatment vaccine at a very early Pre-IND or Early-Phase 1 development stage, or
- There is no clear signal of POC and/or significant efficacy, and/or
- There is no favorable benefit-risk profile
While submission of requests and inquiries to the CTAP mailbox for COVID-19 programs at very early Pre-IND or Early-Phase 1 development phase is not precluded, such requests or inquires will be directed to the standard Pre-IND meeting path with the relevant CDER/CBER review division by the COVID-19 Product Development Team. Proposed COVID-19 treatment programs at later stages of development but with no clear POC, weak signals of efficacy, or less than ideal benefit-risk profile will be of low priority in the CTAP pipeline for agency review and interactions.
For the strategic assessment of proposed COVID-19 treatment programs or clinical trials, the existing evidence of POC/efficacy/safety/benefit-risk profile is a crucial pre-requisite for identifying the appropriate pathway to pursue at the FDA. It is important to note that irrespective of which regulatory path is used to obtain FDA review or input for a proposed COVID-19 treatment clinical trial or program, the agency is committed to expedited processing of COVID-19 programs as feasible, based on the completeness of the request/submission, scientific merit, stage of development, and the overall benefit-risk profile of the proposed investigational treatment.
- US Food and Drug Administration. Coronavirus Treatment Acceleration Program (CTAP). Available at: https://www.fda.gov/drugs/coronavirus-covid-19-drugs/coronavirus-treatment-acceleration-program-ctap. Accessed May 19, 2020.
- US Food and Drug Administration. Drug Development Inquiries for Drugs to Address the COVID-19 Public Health Emergency. Available at: https://www.fda.gov/drugs/coronavirus-covid-19-drugs/drug-development-inquiries-drugs-address-covid-19-public-health-emergency. Accessed May 19, 2020.
- US Food and Drug Administration. Coronavirus (COVID-19) CBER-Regulated Biologics. Available at: https://www.fda.gov/vaccines-blood-biologics/industry-biologics/coronavirus-covid-19-cber-regulated-biologics. Accessed May 19, 2020.