Sit! – Stay! – No IND Needed as Part of Guidance Document is Stayed

Last Friday, FDA published a Notice in the Federal Register (here) relative to staying a portion of its September 2013 Guidance Document titled Investigational New Drug Applications (INDs) – Determining Whether Human Research Studies Can Be Conducted Without an IND.  The Agency indicated that, based on comment received on various sections of the final Guidance, they are staying the requirement and will not take regulatory action if human studies are undertaken in the narrow scope of the stayed portion of the Guidance document without an IND being filed.

Subsection VI.D.2 is the target of the stay.  FDA says the following:

“Specifically, we are staying portions of subsection VI.D.2, ‘Conventional Food,’ and all of subsection VI.D.3, ‘Studies Intended to Support a Health Claim,’ except as to studies intended to evaluate whether a food substance reduces the risk of a disease in individuals less than 12 months old, those with altered immune systems, and those with serious or life-threatening medical conditions. Subsections VI.D.2 and VI.D.3 discuss, respectively, conventional food studies generally and studies intended to support a health claim for a conventional food or dietary supplement. The portions of subsection VI.D.2 that are being stayed are the third paragraph (which pertains to clinical studies intended to evaluate a food’s effect on the structure or function of the body) and a sentence in the fourth paragraph concerning clinical studies intended to evaluate a non-nutritional effect on the structure or function of the body. In subsection VI.D.3, a text box inserted below the subsection heading explains that clinical investigations intended to evaluate whether a food substance may reduce the risk of a disease in three categories of medically vulnerable subjects (individuals less than 12 months old, those with altered immune systems, and those with serious or life-threatening medical conditions) are excluded from the stay, and that subsection VI.D.3 is in effect for such investigations.

The stay of portions of subsection VI.D.2 and all of subsection VI.D.3 (subject to the exclusion for studies in the medically vulnerable populations described in this document) of the final guidance is effective immediately. All other parts of the final guidance remain in effect. We are republishing the guidance with the stayed material clearly identified so readers can distinguish parts of the guidance that remain in effect from parts that are subject to the stay.”

FDA generally does not intend to seek INDs for studies in the stayed categories while the stay is in effect. This stay does not, however, preclude enforcement of any provision of the FD&C Act or other relevant Federal statutes or regulations other than IND requirements (e.g., human subject protection laws and regulations). This stay does not affect investigations of conventional foods or dietary supplements studied for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. Products intended for such uses meet the definition of a “drug” at section 201(g)(1)(B) of the FD&C Act; such investigations will continue to be subject to IND requirements. For example, dietary supplements containing bacteria have been given to infants born prematurely for prevention of necrotizing enterocolitis. The investigation of such use, and similar uses of conventional foods or dietary supplements to diagnose, cure, mitigate, treat, or prevent a disease, continues to require an IND.

In summary, while the partial stay of the final Guidance is in effect, FDA does not consider clinical investigators or study sponsors to be under any obligation to obtain an IND for the following types of studies evaluating the effects of a product marketed as a conventional food or dietary supplement:

For conventional foods:

  • Clinical studies designed to evaluate whether a conventional food may reduce the risk of a disease, intended to support a new or expanded health claim, and conducted in a population that does not include individuals less than 12 months old, those with altered immune systems, or those with serious or life-threatening medical conditions;
  • Clinical studies designed to evaluate a non-nutritional effect of a conventional food on the structure or function of the body.

For dietary supplements:

  • Clinical studies designed to evaluate whether a dietary supplement may reduce the risk of a disease, intended to support a new or expanded health claim, and conducted in a population that does not include individuals less than 12 months old, those with altered immune systems, or those with serious or life-threatening medical conditions.”

The Federal Register Notice outlines the types of studies for which INDs are still necessary for conventional foods, dietary supplements and cosmetics and that is also further explained in the Guidance document (here).

It appears that FDA may be in somewhat of a standoff with food, dietary ingredient and cosmetic groups relative to FDA’s original interpretation outlined in the 2013 final Guidance.  Perhaps the groups are asserting that the relative statutes preclude the FDA’s previously outlined IND requirements.  Please keep your eye on this situation and if there is any question, it is suggested that you contact the appropriate review division at FDA if there is a doubt as to whether an IND may need to be filed for a human study, as outlined in the Guidance.