The FDA has acknowledged (see Federal Register notice) that human research on foods should be possible without an Investigational New Drug (IND) filing. (Comments may be submitted to the FDA on this notice here.) On October 30, the FDA responded to complaints from stakeholders regarding the September 2013 final guidance, which stipulated that human research on foods needed to be conducted under an IND. An IND would be required regardless of the safety or availability in the marketplace of the test product and even if the research endpoints were:
- Structure/function (with the exception of taste, aroma or nutritive value), or
- Reduction-of-risk-of-disease endpoints (already approved food/disease claims could be further studied without an IND)
- Dietary management of a disease
I specifically mention these endpoints because these constitute legal functions of foods. The FDA position was that studying the impact of a food on such endpoints in human subjects turned that food into a drug (or more specifically, an investigational new drug).
Stakeholders complained (see previous post) that there should be a path to conduct human research on these endpoints – as foods, not drugs.
The FDA reconsidered. Rather than scrap the entire guidance or issue a revised one, the FDA chose to highlight sections of the guidance that would be ‘stayed’. Presumably, this means that the FDA has determined to stop or suspend these sections. By its nature, a stay can be lifted. This terminology is usually used for court or legal proceedings, so its use here on a guidance document – which are never legally binding* – looks a bit out of place. But by doing so, the FDA seems to realize that IRBs and NIH often treat guidance as law.
The stayed sections include an exception for studies intended to reduce the risk of disease in medically vulnerable populations (individuals less than 12 months of age, those with altered immune systems, and those with serious or life-threatening medical conditions).
From the point of view of research designed to investigate physiological functions of foods and supplements, this seems to be a positive action by the Agency. Perhaps the biggest concern from the perspective of the probiotic field is that the section of the guidance on ‘Live Organisms’ was not stayed. This guidance states that an IND is required for studies of a live organism administered to study host response to an organism. (The reference for this section is Part 312 of the FDC Act, which deals with drugs.) Here the guidance acknowledges an exemption for dietary supplements or foods. But then a parenthetical reference is added after the exemption, stating that food or drink is “primarily for taste, aroma, or nutritive value, rather than for some other effect on the structure or function of the body”. So does this mean that a structure/function endpoint for human research with a live microbe (probiotic) in a food would require an IND? If so, would this result in the guidance being stricter on a probiotic food than other food?
The FDA has for years required that probiotic studies in human populations be conducted under INDs. I remain baffled by the entire premise of this uniquely American problem. It seems that safety of study subjects should be FDA’s primary concern. To best manage that in the drug arena, the IND process has been developed. The IND assures that a very strict process is followed so that all the necessary details are in place for a drug to be marketed if efficacy and safety are adequately substantiated. But this is not the goal for food research. It seems that the focus should be on safety of any given study, not whether the study addresses structure, function, host response, or cure/treatment/prevention of disease. If a study is safe on a product not intended to be a drug, why impose the IND rubric at all? At the 2015 ISAPP meeting, one attorney commented that research endpoints do not dictate a product’s regulatory category; vendor intent does. It seems this challenges the whole basis for IND requirements for foods and supplements.
For more details, see an excellent post from the FDA Law Blog on this stay: “Should I Stay or Should I Go” to FDA for an IND? FDA Issues a Stay for Certain Food Provisions of the Final IND Guidance
*FDA guidance documents include this text: “This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations.”