Confused about the need to file an IND? Think your study may be exempt? Not sure where to start?
Any drug that does not currently have FDA approval for marketing requires an IND before it can be administered as a part of a research study. In some cases an FDA-approved (marketed) drug must also be conducted under an IND.
According to Food and Drug Administration (FDA) regulations 21 CFR 312.2, the clinical investigation of a drug product that is lawfully marketed in the United States is exempt from IND requirements if all the following apply:
- The investigation is not intended to be reported to FDA as a well-controlled study in support of a new indication for use nor intended to be used to support any other significant change in the labeling for the drug;
- If the drug that is undergoing investigation is lawfully marketed as a prescription drug product, the investigation is not intended to support a significant change in the advertising for the product;
- The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product;
- The investigation is conducted in compliance with the requirements for institutional review set forth in part 56 and with the requirements for informed consent set forth in part 50; and
- The investigation is conducted in compliance with the requirements of 21 CFR 312.7.
The FDA will not accept an IND application for an investigation that is exempt under the provisions noted above.
Typically the greatest challenge in determining exemption from IND regulations is deciding whether the investigation significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the investigational drug.
The FDA maintains that “because the assessment of risks involved in a therapeutic procedure is an everyday part of the practice of medicine, the individual investigator should usually be able to determine the applicability of the exemption”, meaning that a formal FDA determination of exemption is not required. Note, however, that support of an assertion that the research use of a drug does not increase subject risk most commonly requires scientific data (i.e. simply citing investigator clinical care experience with the off-label use of the drug is not adequate). It is critical to understand whether the proposed trial increases the risk to the target patient population in comparison with the patient population for which this drug is currently approved.
For studies involving marketed drugs in oncology patients refer to FDA’s guidance “IND Exemptions for Studies of Lawfully Marketed Drugs or Biological Products for the Treatment of Cancer, January, 2004”.
For guidance on determining whether an IND is required, or compiling an IND for submission to the FDA, contact the SOM Clinical Trials Office at 434-924-8570 or email@example.com.