Understanding FDA Regulatory Terminology During COVID-19

To update clinicians on the various terminology used by the FDA on treatments related to COVID-19 we have developed this reference guide.

Classification of Intended Use and Definitions

The classification of your intended use dictates which products can be used and what regulatory framework needs to be in place based on your intent.

For example, if you are treating a patient with an FDA-approved product, you can take it off the shelf and use it for both on-label and off-label treatment. For products in the pre-approval phase, they can be used to diagnose and treat patients based on FDA Expanded Access, the FDA Emergency Use Authorization, or Right-to-Try.

If your intended use is for purposes of science or regulatory marketing approval, when using an FDA-approved product, you can use it in a post-marketing study (if studying labeled use) or you must be part of a clinical trial (if studying off-label use). For products in the pre-approval phase and the intent us for science, it must be used as part of a clinical trial/clinical investigation.

On-Label Treatment

On-label treatment is treatment in accordance with the labeled use of the product.

Off-Label Treatment

Off-label treatment is treatment by use of approved products not in accordance with the labeled use. Off-label use can mean that the product is:

Used for a disease or medical condition that it is not approved to treat, such as when a chemotherapy is approved to treat one type of cancer, but healthcare providers use it to treat a different type of cancer.
Given in a different way, such as when a drug is approved as a capsule, but it is given instead in an oral solution.
Given in a different dose, such as when a drug is approved at a dose of one tablet every day, but a patient is told by their healthcare provider to take two tablets every day.

Off-label use by itself does not make the care “investigational,” and off-label use can even be the “standard of care” (many drugs used in pediatrics are not labeled for pediatric use). The lack of evidence is what determines whether the care is “investigational” and the intent contributes to whether it is a “clinical trial.”

Post-Marketing Study

A post-marketing study is a clinical investigation done to further the knowledge on the product’s labeled use. One may be done for many reasons, including it being an FDA requirement or commitment for marketing approval. The requirements for IRB oversight and a Research Consent Form will depend on a variety of factors, such whether there are additional interactions or interactions with the research subjects, or if the study is intended to support a marketing application with the FDA.

FDA Expanded Access/Compassionate Use

The FDA’s Expanded Access program, sometimes called “compassionate use,” is the use of an investigational product outside of clinical trials to diagnose, monitor, or treat patients with serious diseases or conditions for which there are no comparable or satisfactory approved therapy options available.

Expanded Access may be appropriate when all the following apply: (i) Patient has a serious disease or condition, or whose life is immediately threatened by their disease or condition; (ii) There is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; (iii) Patient enrollment in a clinical trial is not possible; (iv) Potential patient benefit justifies the potential risks of treatment; and (v) Providing the investigational medical product will not interfere with investigational trials that could support a medical product’s development or marketing approval for the treatment indication.

Right-to-Try

Right To Try is a new federal law (established 2018) that authorizes the use of unapproved medical products by patients diagnosed with a terminal illness in accordance with their State law (should they have one) instead of going through the FDA. These laws are essentially an alternative to FDA’s Expanded Access by allowing the distribution and administration of investigational drugs without any approval, consultation or prompt adverse event reporting with the FDA.

Emergency Use Authorization (EUA)

An EUA is the authority the FDA has to temporarily approve certain unapproved products to diagnose and respond to designated chemical, biological, radiological, and nuclear (CBRN) emergencies. An EUA bypasses the usual federal requirements until the EUA is terminated. Depending on the EUA details, IRB or consent requirements may exist.

Clinical Investigation/Trial

A clinical trial is a research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. While patients may directly benefit while volunteering in a clinical trial, the primary purpose is to answer hypothesis driven questions about safety and efficacy. Clinical trials require prior IRB approval, special consent forms and a lot of other regulatory and scientific requirements.

FDA Expanded Access

There are two main types of FDA Expanded Access to diagnose/treat patients with products in the pre-approval phase.

Emergency Exemptions

FDA Emergency Use Authorization

An FDA Emergency Use Authorizations is essentially a temporary marketing permit without the requirement of clinical trials. They are approved to diagnose and respond to designated chemical, biological, radiological, and nuclear (CBRN) emergencies and a list can be found on the FDA website.

Emergency IND/IDE

An emergency IND/IDE is usually more commonly known as “Compassionate Use” for Single Patient Expanded Access IND/IDEs. For an Emergency IND/IDE, all IND/IDE rules apply, including IRB prior approval, custom consent form that meets FDA standards, and an inability to charge for participation without permission from the FDA.

Emergency Use IRB Exemption

An Emergency Use IRB Exemption happens when a physician has to administer an investigational product before receiving IRB approval. Certain criteria must be met to exempt from prior IRB approval, including it must be a life-threatening situation, there must be no standard acceptable treatment available, and there must not be sufficient time to obtain IRB approval. The IRB must be notified in 5 working days.

Basic FDA Regulatory Requirement

Common Examples in COVID-19

Word of Caution

It is important to note this is not an exhaustive document, but is a high level overview. There are occasional situation-specific exceptions based on details of individual situations. Additionally, the inclusion of a product on the “Common Examples” list is not an endorsement.