Drug: A substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. A substance (other than food) intended to affect the structure or any function of the body.
Biologic: Biologics include a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. A biologic can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues.
If your study involves a drug or biologic that is not being used for its approved use and during the course of medical practice (i.e., standard of care), then your study is subject to FDA regulations.
If physicians use a product for an indication not in the approved labeling, they have the responsibility to be well-informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product's use and effects. Use of a marketed product in this manner when the intent is the "practice of medicine" does not require the submission of an Investigational New Drug Application (IND). See FDA Guidance on "Off-Label" and Investigational Use Of Marketed Drugs, Biologics, and Medical Devices.
Clinical investigation means any experiment that involves a test article and one or more human subjects (21 CFR 56.102c). A project is not a clinical investigation if the drug/biologic is being used during medical practice and is not being used to diagnose, treat, cure, prevent, or mitigate a disease or condition.
Not all clinical studies need to operate under an IND. The FDA has outlined specific situations where the use of a drug or biologic in research is exempt from IND requirements. See WVU OHRP’s Drugs and Biologics Decision Tool (LINK) for more information.
A drug/biologic may be IND exempt if it meets all of the following criteria:
Or if it falls into one of the following categories:
According to FDA’s 2013 FDA IND Determination Guidance (page 12), whether an IND is needed for a study evaluating a dietary supplement is determined by the intent of the clinical investigation.
Expanded access refers to the use of an investigational drug when the primary purpose is to diagnose, monitor, or treat a patient’s disease or condition. The terms expanded access, access, and treatment use are used interchangeably. Expanded access allows for drugs that are investigational (i.e., not FDA approved) to be used for treatment use outside of a clinical trial. This is also sometimes referred to as compassionate use. Treatment use is not considered a clinical investigation, however, FDA submission and IRB review are necessary. The criteria for Expanded Access are largely determined by (1) the seriousness of a patient's condition, (2) other available FDA-approved treatment options, (3) patient population size needing treatment, and (4) drug status. This webpage is a summarized guide to the FDA regulations on Expanded Access to Investigational Drugs for Treatment Use, found in [21 CFR 312.300]. It does not provide full guidance for Expanded Access to Investigational Drugs; as such, FDA regulatory materials must also be consulted for full information.
Under FDA’s current regulations, there are three categories of expanded access:
Yes. Expanded access to an investigational drug for treatment use, including emergency use, requires informed consent as described in 21 CFR part 50. Investigators treating a patient(s) with an investigational drug under expanded access are responsible for ensuring that the informed consent requirements of part 50 are met (21 CFR 312.305(c)(4)). One of the purposes of informed consent is to ensure that the patient is informed that he/she will be treated with an investigational product and that there may be uncertainty about the safety and effectiveness of the product. See FDA Guidance on Expanded Access to Investigational Drugs for Treatment Use — Questions and Answers.
Emergency use is defined as the use of an investigational drug or biological product with a human subject in a life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval [21 CFR 56.102(d)]. The emergency use provision in the FDA regulations [21 CFR 56.104(c)] is an exemption from prior review and approval by the IRB. The exemption, which may not be used unless all of the conditions described in 21 CFR 56.102(d) exist, allows for one emergency use of a test article without prospective IRB review. FDA regulations require that any subsequent use of the investigational product at the institution have prospective IRB review and approval. FDA acknowledges, however, that it would be inappropriate to deny emergency treatment to a second individual if the only obstacle is that the IRB has not had sufficient time to convene a meeting to review the issue.
Life-threatening, for the purposes of section 56.102(d), includes the scope of both life-threatening and severely debilitating, as defined below.
If you believe you need to submit a request to administer a test article in an emergent situation in which there is no have time to obtain prior IRB approval, (see additional information below to be sure your situation qualifies), please complete and submit the Emergency Use Request Form.
The physician reviews the FDA definition of life threatening [21 CFR 56.102(d)] and can verify that the proposed use of an investigational drug or device meets that definition. The physician should contact the WVU OHRP or IRB for consultation regarding the potential emergency use. If the definition of life threatening is not met, emergency use procedures must not be followed. For additional options, consult the IRB guidance on Expanded Access for Investigational Drugs and Expanded Access for Unapproved Devices.
Visit WVU OHRP’s Emergency Use of a Test Article website for further guidance.