Skip to main content
Clinical Trials Resource Group

Clinical Trials Resource Group

Number2IND Process: Self-Determination of IND Exemption

Self-determination of IND exemption based on 21 CFR 312.2

Typically the greatest challenge to Academic Health Centers 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.  While guidances clarifiy that investigators “should usually be able” to appropriately assess the applicability of the exemption requirements, careful thought should be given by Academic Health Centers on how to best manage the variability in determining IND exemption status that is introduced by relying solely on individual investigator interpretation of the IND exemption regulations (From Hartman et al “IND/IDE support for Investigator-Initiated Clinical Research: The Clinical Translational Science Award (CTSA) Experience”)

Self-determination of IND exemption based on 21 CFR 312.2, outlined  in this template.  Walk through the requirements to self-determine your exemption status. Pay a particular attention to the Criteria #4.   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.   Based upon your review of the requirements, determine if your protocol is exempt or not exempt. Submit the letter to the IRB along with your IRB packet

Guidance for Industry Investigational New Drug Applications (INDs) Determining Whether Human Research Studies Can Be Conducted Without an IND 


Special Considerations for Lawfully Marketed Oncology Drugs 

In 2004, the FDA finalized a guidance document that was first drafted in 2002 to assist sponsors in determining whether research use of marketed drugs or biologics for the treatment of cancer met the regulatory requirements for exemption from the IND regulations.  The guidance provides examples of studies that generally are considered exempt from IND regulations, and examples of those that are not.  While the guidance specifically refers to studies using marketed products for the treatment of cancer, the guidance provides a useful framework for assessing whether other types of studies meet the IND exemption requirements. 

In cases where an IND application is submitted but the research use of the marketed drug noted in the application is considered exempt from IND regulations by the FDA, the FDA issues a letter of exemption to person or institution submitting the IND application

If Not Exempt, go to Step 3 

If Exempt, go to Step 4