In order to get a drug approved for sale in the United States, companies have to go through the FDA’s Center for Drug Evaluation and Research (CDER) – the main consumer watchdog for drugs in the US. The main function of the CDER is to evaluate new drugs before they can be sold to consumers to not only prevent inadequate drugs from making it to the shelves, but also to provide doctors and patients with information about how to properly use the drug. The goal in drug evaluation is to ensure that drugs marketed in the US are safe and effective – to make sure that the benefits outweigh the risks.
The FDA has established a standard protocol for getting a drug approved in the US, part of which includes the drug manufacturer conducting lab, animal and human clinical testing and then submitting that data to the FDA for review. As you might imagine, testing a brand-new drug in humans is very risky business – which is why the FDA requires the manufacturer to first perform lab and animal tests so that they can learn how the drug works and whether or not it seemingly safe for human use. After successful lab and animal testing, human trials can begin. The goal of the human trials is to determine if the drug can be safely used to treat a disease and if it provides a real health benefit to the patient. Typically, lab and animal testing take between 1- 3 years to complete, and human trials can take up to 10 years.
A team of CDER professionals (including physicians, statisticians, chemists, pharmacologists, etc.) will review the submitted data and the manufacturer’s proposed product labelling. It’s important to review the labelling to ensure the manufacturer isn’t making any misleading claims about the drug’s efficacy. So long as this review process determines the drug’s health benefits outweigh the known risks, the drug is approved for sale.
Medical countermeasures, or MCMs, are FDA-regulated products (biologics, drugs, devices) that may be used in the event of a potential public health emergency. In emergency situations, such as the global pandemic from COVID-19 that we are currently faced with, the FDA will make certain exceptions to fast-track vaccines and treatments. Through the FDA Medical Countermeasures initiative (MCMi), the FDA works with different government partners (local, state, national and international) to support public health preparedness and response efforts. They also work with non-government backed organizations such as universities and research centers to further the development of MCMs. During public health emergencies, it is possible that MCMs may be approved by the FDA and used during the response efforts. These MCMs may initially have been in the FDA pipeline for approval (but not officially approved yet) or they may have been previously approved, but not for the specific indication they are trying to treat during the emergency. FDA may need to use special authorities to allow the use of these emergency MCMs, such as the Emergency Use Authorization (EUA).
The FDA recognizes that the COVID-19 pandemic may affect the standard conduct of clinical trials on medical products, including possible vaccines and pharmaceutical products. New challenges from quarantines, site closings, travel limitations, interruptions in the supply chain of the investigational product or if site personnel or test subjects become infected with COVID-19, create difficulties in complying with the standard procedures. To act efficiently the FDA will need to enact protocol modifications as necessary, such as the following for ongoing clinical trials:
- Ensuring the safety of trial participants is paramount. Study decisions may include those related to continued trial recruitment, continued use of the investigational product for patients already participating in the trial, and the need to change patient monitoring during the trial, provided the patient is informed.
- Sponsors, in consultation with clinical investigators and Institutional Review Boards (IRB) / Independent Ethics Committees (IEC), can determine the type of protection regarding the safety, well-being and rights of the participant, depending on each case. , and can be modified throughout the trial.
- Participants in the trial may or may not attend the research site for the visits specified by the protocol due to their condition. In the event of not attending, sponsors should evaluate alternative methods for security evaluations, such as telephone contact, virtual visit, alternative location for evaluation, including local laboratories or imaging centers.
- In some cases, trial participants who no longer have access to the research product or research site may need additional safety monitoring (for example, withdrawal of an active research treatment).
- New processes or modify existing processes will vary according to the protocol and the local situation. Including delayed evaluations for ongoing trials or, if the study cannot be properly conducted according to the existing protocol.
- COVID-19 screening procedures that may be mandated by the health care system in which a clinical trial is conducted need not be reported as an amendment to the protocol, even if performed during clinical study visits, unless the sponsor incorporates the collected data as part of a new research objective.
- Changes to the research protocol or plan to minimize or eliminate immediate risks or to protect the life and well-being of research participants (for example, to limit exposure to COVID-19) may be implemented without IRB approval or before submitting an amendment to the IND or IDE, but must be informed afterwards. Sponsors and clinical investigators should document how restrictions related to COVID-19 led to changes in study behavior and the duration of those changes and indicate which trial participants were affected and how those participants were affected.
- Changes in study visit times, missed visits, or patient interruptions can lead to a lack of information (for example, for procedures specified by the protocol). It will be important to capture specific information in the case report form that explains the missing data base, including the relationship with COVID-19 for the information specified in the missing protocol (for example, missed study visits or study interruptions due to to COVID-19)
- If scheduled visits to clinical sites will be significantly affected, certain investigational products, such as those generally distributed for self-administration, may threaten alternative methods of safe delivery. In all cases, it must be documented.
- With respect to efficacy evaluations, the FDA recommends consulting with the appropriate review division regarding protocol modifications for collecting efficacy endpoints, such as the use of virtual evaluations, evaluation delays, and alternative collection of Specific research samples, if possible. For individual cases where efficacy endpoints are not collected, the reasons why the efficacy endorsement is not obtained should be documented (for example, identify the specific limitation imposed by COVID-19 that leads to inability to perform the evaluation specified by the protocol).
The FDA is doing everything possible to maintain the health of the American people and ensure all medical products that are being developed are safe and effective. It is a collaborative learning experience and the organization is aiming to keep the protocols flexible while still remaining safe for the patient and the population. For more information on the FDA's role in the fight against COVID-19, visit www.fda.gov.
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