By: Stephen M. Hahn, M.D., Commissioner of Food and Drugs, Patrizia Cavazzoni, M.D., Acting Director, Center for Drug Evaluation and Research, and Peter Marks, M.D., Ph.D., Director, Center for Biologics Evaluation and Research
When the U.S. Food and Drug Administration learned of the novel coronavirus (COVID-19) and its potentially devastating effects, we acted swiftly to set the regulatory stage for drug and biologics manufacturers to develop products to treat this serious disease. To meet this urgent need, the FDA created the Coronavirus Treatment Acceleration Program (CTAP) to enable the FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) to leverage cross-agency scientific resources and expertise to bear on COVID-19 therapeutic development and review. We’re excited to say that there are now more than 510 drug development programs in planning stages, and as of today, the agency has reviewed more than 230 trials of potential therapies for COVID-19.
While the FDA is part of a whole of government approach to COVID-19, CTAP is a distinct component of this effort focusing specifically on therapeutics, not vaccines or devices. Another major initiative of the U.S. government, Operation Warp Speed (OWS), funds and rapidly develops or co-develops vaccines, therapeutics, and diagnostics, while the FDA, through CTAP, regulates therapeutic development. There is a clear delineation between OWS executive actions and FDA regulatory decision-making.
The FDA recognized that there would be a need for early and frequent discussions between the agency and potential therapeutic product developers. So early on, we set up an email inbox for COVID-19 therapeutic development inquiries, COVID19email@example.com. It helps researchers and developers get directed to the right person on the first try and enables us to track inquiries.
Each inquiry the FDA receives is reviewed by a triage team that is composed of experienced clinical reviewers, other scientific reviewers, policy experts and regulatory project management staff. The team strives to acknowledge receipt within 24 hours. These staff help those with proposals for potential COVID-19 therapeutics identify and add any information necessary to ensure that the proposal is complete enough for productive discussion. Then, the team sends the proposal with a brief synopsis to the right organizational unit within the FDA for review by disease area experts.
Teams of experienced clinical reviewers and regulatory affairs experts in CDER and CBER provide outreach and regulatory advice to less experienced inquirers. Preliminary, partially-formed inquiries go to them before they are assigned to product review teams to determine next steps for engaging with the FDA, including what regulatory submission is appropriate, what to include in that submission, and how to submit it.
Once individual inquiries develop into proposals, our discussions with sponsors can then meet several key milestones:
- Pre-Investigational New Drug (Pre-IND) Meetings, where sponsors seek initial advice on their proposed development programs. Information about Pre-INDs, including guidance on how to efficiently engage with the FDA and expedite clinical trial initiation, is available at Drug Development Inquiries for Drugs to Address the COVID-19 Public Health Emergency.
- INDs, to study therapeutics in humans. More information is available at CDER’s “Investigational New Drug (IND) Application” webpage. While the FDA is committed to moving products into clinical trials efficiently, we must also work to ensure patients are not exposed to an unreasonable and significant risk of illness or injury. More information is available at “Ensuring the Safety of Patients in Clinical Trials Studying Investigational New Drugs to Prevent or Treat COVID-19.”
- Emergency Use Authorizations (EUAs). Before a therapeutic is approved for use in COVID-19 patients, the FDA can issue an “emergency use authorization” for the product’s emergency use if certain statutory requirements are met, such as when there is no adequate, approved and available alternative therapy and the known and potential benefits of the product for the proposed use outweigh its known and potential risks. This is not a usual step in drug or biologic development, but can be a key step in facilitating patient access. More information is available on the FDA’s Emergency Use Authorization (EUA) webpage. For most new or repurposed potential therapeutics for COVID-19, pre-IND advice and submission of an IND is the recommended regulatory pathway.
- New Drug Applications (NDA) and Biologics License Applications (BLA), seeking FDA approval of drugs and biologics for use in COVID-19 patients.
We will continue to report the number of active drug development programs, studies underway, EUAs and approvals at our CTAP program dashboard monthly.
Behind the scenes of CTAP, office leaders within CDER and CBER align our efforts across therapeutic areas, scientific disciplines, and organizational units. Clinical, operations and policy supervisors meet regularly to discuss staffing support, trial design, endpoint selection, and consistency of practice and expectations for COVID-19 submissions. Clinical and biostatistical experts meet regularly to share information, advance our scientific understanding and develop consistent approaches. Senior leadership stay actively engaged on key drug and biologic development and review issues.
When CTAP started, we achieved extraordinary turnaround times for certain significant inquiries and proposals, to get key studies going rapidly. For therapeutic development programs with strong rationales and evidence, we continue to dramatically exceed standard timelines. We have found that a complete pre-IND submission is the key to expediting comprehensive pre-IND advice, more rapid review of the subsequent IND and more rapid clinical trial initiation.
While we have shortened our timelines, our regulatory review and decision-making processes have not changed. Interactions with review teams follow our usual stable, predictable, and flexible process. We give all researchers and developers our best advice, apply our legal and regulatory standards, and make decisions on the basis of the science and the data.
Safe and effective COVID-19 therapeutics and other medical products are a very high priority at the FDA. We understand the impact of this public health emergency and approach our role in facilitating the development and availability of important medical products with the strongest sense of urgency.