The concept of putting live organisms in foods or capsules has never sat very well with the Food and Drug Administration. It’s an underlying current that surfaced in the recently released draft guidance on New Dietary Ingredients with a section that takes square aim at the category.
“This is reflective of FDA’s longstanding concern about putting live organisms into the food supply,” said Marc Ullman, an attorney who consults with natural products companies on regulatory affairs.
It’s symptomatic of a standing debate at FDA about where probiotics should fit in the regulatory scheme. Should they, in fact, be regulated under the Center for Biologics Evaluation and Research (CBER), which regulates things like vaccines?
“There is a series of triggers that cause FDA to view probiotics with a higher degree of interest,” said Loren Israelsen, executive director of the United Natural Products Alliance. “They’re fermented. They come from source materials that FDA has traditionally viewed as biologics. The risks of contamination are higher. FDA has spent quite amount of time on issues surrounding probiotics. Are they really biologics or not?
“Relative to any other category they spend more time talking about probiotics than anything else,” he said.
The issue with identification
The study of probiotic bacteria has a long history dating back to Russian scientist Elie Metchnikoff in the early twentieth century. And some individual strains have a long history, too; for example, Dr. Khem Shahani of the University of Nebraska Lincoln discovered the DDS-1 strain of lactobacillus acidophilus in 1959 and worked with it for decades thereafter.
The history of NDI notifications up to this point shows that one of the ways in which companies typically fall down is in failing to precisely indentify the ingredient that is the subject of the filing. That’s more of a challenge with a probiotic that with, say, a botanical.
“How do you identify the stain or species? If you go back into the genealogy of these things, it is really hard to figure if you really dealing with lactobacillus-whatever. If you have to go back to pre-94 to establish ODI status, some will be O.K., others will have a really hard time doing that. And as you speciate and create new strains FDA’s view is that as you do that you have clearly triggered the NDI process. And they are concerned about other, possibly pathogenic strains getting into your material.”
Israelsen said this last concern could make filing NDI notifications on probiotic ingredients trickier than for, say, a botanical ingredient. The agency, he said, does not have a high degree of confidence that manufacturers can positively identify the strains they are working with. Nor is FDA reassured that manufacturers can say with certainty that their ingredient or supplement contains only the species stated on the label and no others.
If, for example, a given sample of a probiotic supplement were grown out in a Petri dish and yielded 10 billion individuals of the species stated on the label and some small fraction of unidentified organisms, be they pathogenic or no, that’s unlikely to pass muster. And an argument that a similar broad spectrum of organisms is present in commonly available fermented foods won’t fly, either; the guidance specifically excludes organisms that were “inadvertently present in foods as contaminants.”
Asleep at the wheel?
Leading European probiotics manufacturers have long been alert to changing regulatory winds. The industry there has been in a long (mostly losing) wrestling match the European Health and Saftey Authority over the evaluation of health claims connected to probiotics. So it's no wonder manufacturers there seemed better prepared for the release of the NDI guidance. In May, a coalition of three primarily European industry associations released a position paper on probiotics and NDIs arguing that the safety of these ingredients should be based on evaluations on the genus and species level, not the strain.
But when Israelsen posed the question of how many were concerned about the status of probiotics to a room of about 170 people at the recent NDI seminar held by the UNPA in Salt Lake City, it stirred little reaction or debate. And when a midsized North American probiotics supplier was contacted for reaction for this story, an executive there said he wasn’t aware enough of the guidance to comment.
“I strongly suspect that there is a very poor understanding among those that should know about what is going on,” Israelsen said.
“You are going to have a lot of companies in the industry just not paying attention. I just find that unacceptable. “