What documentation needs to be submitted to the IRB for an IND exemption request?

Question:

Can you share what type of documentation or rationale may be needed to justify an Investigational New Drug (IND) exemption with an IRB? We’ve read the FDA guidelines and fit within the exemption criteria as stated but want to be prepared for our IRB review. Specifically, we are working with commercially available and legally marketed cannabinoids, which may have their own unique considerations.
—Director, Biopharmaceutical Sponsor

Response:

For purposes of this answer, it is presumed that you have already determined that the product in question is a drug, and that the research constitutes a clinical investigation as defined by FDA regulations, and laid out in FDA guidance titled “Investigational New Drug Applications (INDs) – Determining Whether Human Research Studies Can Be Conducted Without an IND,” and that the criteria you are looking for an IND exempt determination are those within 21 CFR 312.2(b)(1).

Once those determinations have been made, then the IRB must determine if the product meets the requirements within the regulation. Some of the criteria are not within the IRB’s purview for determination, specifically items (i), (ii) and (v) of 21 CFR 312.2(b)(1) are items that are solely under the control of the sponsor and we expect the content of those to be pre-determined by the sponsor to be met. In addition, criteria (iv) is satisfied by the fact that the study has been submitted for review by the IRB, presuming the submission is complete, the standard criteria for approval are met, and an appropriate consent form or waiver of consent request are also submitted.

This leaves the IRB with needing to have sufficient information to affirm that the product is lawfully marketed within the United States and that the criteria within item (iii) are met: 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.

In regard to the confirmation that the product is lawfully marketed within the United States, generally just the product name is sufficient, as the IRB can confirm drug approvals on the FDA’s approved drugs database. However, if the product is marketed in any other way outside of a standard FDA approval, additional documentation of the product’s marketing status should be submitted.

In regards to information to support that criteria within item (iii) are met, generally the IRB can utilize the approved package labeling for drugs that appear on the FDA’s approved drugs database and determine if the use(s) in the proposed study are within the approved labeling, and if not, if the IRB believes that the criteria in item (iii) are met. However, if the use(s) within the proposed study are outside of the approved labeling, it would be helpful to the IRB if the submission contained a justification as to why the criteria in item (iii) are met. The justification should provide specific information about the potential risks and acceptability of the risk in the population to be studied. A change to the route of administration or population, such as pediatrics, may necessarily require FDA review. In addition, if the product does not appear on the FDA’s approved drugs database, then additional information, similar to FDA approved product labeling, would need to be submitted regarding what the product is lawfully marketed for, in addition to justification why the criteria in section (iii) are met.