IND guidance complicates research into immune health, forum participants told

Studying immune responses in the target population where an immune supporting supplement is meant to marketed is a key pillar in building a structure that will stand up to FDA and FTC regulatory scrutiny, attendees at the recent NutraIngredients-USA Trends in Immune Health Forum were told.

The forum, hosted by NutraIngredients-USA, brought together two researchers, a lawyer and a product developer/consultant, to discuss trends in the sector. Much of the discussion centered on how best to conduct research in the sector that can underpin product claims without stepping over a newly-defined line in the sand into Investigational New Drug (IND) territory.

The panelists on the forum, which aired on June 30 and is available on demand here, were Philip Calder, PhD, Susan Kleiner, PhD, Dr Refaat Hegazi, MD and attorney Ivan Wasserman.

The immune system, of course, is the body’s defense mechanism against infection, so products dealing with this, and the studies on those products, by their very nature will trend close to the supplement/drug divide as defined in US law. A fairly recent FDA guidance document on Investigation New Drug (IND) applications has complicated research in the field, said Wasserman, who is a managing partner at the Manatt law firm.

“For studies on dietary supplements and foods, really it’s the study endpoint that determines if you need an IND, not what the products is or how it will be marketed to the public,” said Wasserman. "FDA is saying that for dietary supplements, they don’t care if it might be an herbal product that has been on the market for 30 years or a probiotic or whatever. If the study is designed to evaluate the product’s ability to treat, prevent or cure disease—such as preventing colds or flus or whatever—poof! your product is a drug and you need to file an IND.” 

Wasserman added that keeping to the claim of ‘maintains/supports a health immune system’ is one way to stay within the regulators’ good graces.  Such claims have been viewed by the Federal Trade Commission is not implying to consumers that they will get fewer respiratory infections.  But claiming to ‘boost’ the immune could imply that effect, he said.

“In general your studies need to match your claims. If you say anything beyond ‘maintains,’ you need to have studies showing your product has that benefit in preventing colds or flu or whatever. But studying your product in that way makes your product a drug, so we get into this Catch 22,” Wasserman said.

Calder, who is a professor at the University of Southampton in the UK, said that it is important to study a product’s effect in the target population because immune system challenges, and therefore the corresponding configuration of the immune system itself, varies around the world.

“You want to study the immune system in the area where the application is going to be made because of the differences in the microbiome and immune competence,” Calder said.

In addition to micronutrients such as vitamins, minerals and antioxidants, it’s important to keep in mind the macronutrient needs of immune-challenged populations such as aging individuals or athletes engaged in serious training.  Kleiner, who is a nutritionist and product developer who has consulted with a number of professional sports teams and athletes, said that getting enough calories, and especially carbohydrates, is a key aspect of support athletes’ immune function.

“Athletes are notoriously under fueled and these days under carbed. Under fueling has classically been known to suppress the immune system. Not having enough carbohydrate is known to change the microbiome,” Kleiner said.

Another population that is potentially immune challenged are elderly, and here the effect is associated with a general wasting, said Hegazi, who is the medical director of Abbott Nutrition.

“There is this whole idea of lean body mass and the immune system, and how we can target lean body mass and immunity.  Sarcopenia is a loss of muscle mass, but it’s not just muscle. Sarcopenia is really a loss of lean body mass and it affects the bones, the organs and the immune system. I think we can do better if we come up with a holistic approach to meet the protein needs of these patients,” Hegazi said.