The probiotics industry has joined the chorus of dissenters since the Food and Drug Administration released its New Dietary Ingredient draft guidance July 1.
The guidance—meant to help dietary supplement manufacturers know when a safety notification is needed prior to the release of their products—may only muddle the waters when it comes to probiotics products.
The draft document does not address probiotics by name. But the guidance does address bacterial microorganisms in the following passage:
Should I notify FDA about a microbial ingredient in my dietary supplement?
Yes, if it is a NDI that has not been present in the food supply as an article used for food in a form in which the food has not been chemically altered (21 U.S.C. 350b(a)(1)). However, not all bacterial microorganisms are dietary ingredients, and a microorganism that is not a dietary ingredient cannot be a NDI. For example, pathogenic species of bacteria, such as Salmonella species or E. coli, are not dietary ingredients even though they may have been inadvertently present in foods as contaminants. Bacteria that have never been consumed as food are unlikely to be dietary ingredients. A bacterial microorganism is a dietary ingredient if it is a dietary substance (an intentional constituent of food) or otherwise falls within one of the dietary ingredient categories listed in 21 U.S.C. 321(ff)(1). For example, bacteria that are used to produce fermented foods that are eaten without a cooking or pasteurization step (e.g., lactic acid bacteria used to produce cheese or yogurt) could be "dietary substances for use by man to supplement the diet by increasing the total dietary intake," which are defined as dietary ingredients in section 201(ff)(1)(E) of the FD&C Act (21 U.S.C. 321(ff)(1)(E)). FDA does not have a separate regulatory category or definition for dietary ingredients consisting of live or viable microorganisms.
What does this mean for 50-plus strains of beneficial bacteria currently being used in foods, beverages and supplements worldwide?
"There seems to be a fair degree of unclarity in the draft guidance, but not really a lot of news when it comes to how probiotics would be treated in the case of the NDI legislation," said Michael Oredsson, CEO of Probi.
The Swedish-based probiotics supplier has a big stake in the issue: The company reported sales increases of 16 percent in 2010 to $39.52 million (€27.77 million) from $32.85 million (€23.08 million) in 2009.
Meanwhile, over at Extracciones Naturales S.A. de C.V., technical director Marco Aurilio is scratching his head over the guidance's statement that the "FDA does not have a separate regulatory category or definition for dietary ingredients consisting of live or viable microorganisms."
"So yogurt and other fermented foods, which are chock full of bacteria, don't count as food?" he asked. "People have been eating bacteria in fermented foods way before we had food labels or packaging to scrutinize. Now the FDA is telling us that we cannot characterize the bacteria in fermented foods as healthy, naturally, occurring ingredients? Is Natto [a traditional Japanese fermented soybean food] adulterated unless supported by an NDI disclosure?"
Guidance likely to cause development delays
Probiotics supplier Chr. Hansen of Denmark expressed similar uncertainty.
"The draft guidance is vague in some areas, overly specific in others and does not fit the general intent and purpose of DSHEA," said Janet Balson, manager of regulatory affairs for Chr. Hansen. "As currently drafted, it is likely to be responsible for delays in the development and introduction of new probiotic cultures."
Her greatest concern is with the provision that declares that changes in fermentation or manufacturing can trigger the need for an NDI notification, as well as another passage that declares that a microbial food substance is chemically altered if the media is different than that used for conventional foods.
"We work continuously on improvement of media and production procedures in order to improve culture yield, performance and stability/survival under application conditions," Balson said. "Media and production parameter modifications do not impact the identity or phenotypic characteristics of a strain, and should not require a re-evaluation of safety and the need to apply for NDI notification. Media and production parameters applied in industrial fermentation of cultures are not constant."
Chr. Hansen is also concerned that a new submission would be required for combination products, even though the individual cultures are safe under the guidelines of DSHEA. "For probiotic cultures, there are no safety concerns when different probiotic cultures are used in combination," Balson said.
Manufacturer proposes alternative idea
Just how should the federal government ensure the safety of probiotics cultures, if not through this draft guidance?
Chr. Hansen has an idea: "Several leading probiotic associations have recently released a position paper on the safety of microbial cultures for probiotics," Balson said. "This paper demonstrates the safety history of microbial species, stating that 'If a strain/isolate of a Genus/species population is currently and appropriately used in dietary supplement applications in the US and that Genus/species has a safe history of use in food before October 15, 1994, then other strains/isolates of the Genus/species population should not be considered new and do not require a NDIN.'
"Chr. Hansen supports this position and believes it should be adopted as guidance for probiotic cultures used in dietary supplements."