New FDA probiotic draft guidance accepts CFUs as unit of measure

September 24, 2018

In September, FDA released new draft guidance for probiotics indicating the agency will accept CFUs as a unit of measurement.

One of the most significant discussions in the probiotics industry is how manufacturers should label probiotic products and which unit of measurement they should use to list probiotic content. There has been a push to move away from listing probiotic content in metric weight (usually milligrams) and instead to use colony-forming units (CFU), which is a measure of the number of viable, live, active bacteria in a product. FDA regulations require that dietary supplement products list ingredients by weight, but in September, FDA released new draft guidance for probiotics indicating the agency will accept CFUs as a unit of measurement.

FDA’s labeling regulations for dietary supplements -specifically, 21 CFR 101.4(a)- have long required that ingredients be listed “in descending order of predominance by weight.” But when it comes to probiotics, a weight-based measurement is not an accurate reflection of how much of the live microorganism is viable at the time the supplement is consumed.

FDA released its draft guidance after the International Probiotics Association (IPA) filed a citizen’s petition in 2016 asking FDA to change dietary supplement regulations to require probiotic content to be listed as the number of CFUs present per serving at the end of a product’s shelf life, instead of by weight. IPA pointed out that, unlike with probiotics, milligram measurements are adequate for most vitamins, minerals, and botanical ingredients. Listing those ingredients by weight usually provides “consumers the information they need to evaluate how much ‘effective’ ingredient is in the product.” In its citizen’s petition, IPA used ginseng to illustrate this point: “For example, a consumer who wants to supplement their diet with ginseng can examine the labels of various products to compare how many milligrams of ginseng each provides, and knows that each milligram contributes to the efficacy of the product and/or is something he/she wants to consume.”

In the case of probiotics, however, a weight-based measurement doesn’t provide information about how much of the organism in a probiotic product is live and active-and only live, active organisms will confer a probiotic benefit on the host. In addition, the number of milligrams present does not necessarily uniformly correspond with the number of CFUs in a product; simply put, the number of milligrams in a product cannot be relied on to indicate how many CFUs are in the product. As IPA explained in its petition, “Due to various cell concentrations of the probiotics, the same number of milligrams could represent very different CFU counts. Hence, declaring probiotic ingredients by weight does not provide consumers with relevant information on the amount of effective ingredient they are consuming in a dietary supplement.”

While groups like IPA have said they would like to see FDA actually change its dietary supplement regulations to allow probiotics to sidestep the weight-measurement rule, changing regulations is a significant and lengthy process requiring a proposed rule, a comment period, and many years in between. In its draft guidance, FDA said it would not change the regulations at this time to require labeling in CFUs. (The agency did, however, say, “We recognize that manufacturers are using a number of different units of measure for probiotics, enzymes, and other dietary ingredients…Because of the complexity of these labeling concerns, we plan to issue information related to this subject at a later date.”)

FDA declined to change its regulations, but in the draft guidance, the agency made clear that companies can in fact label their probiotic products in CFUs. While draft guidance is nonbinding and is only meant to represent to the public what FDA’s thoughts are on the topic, the draft guidance indicates that FDA will not consider including CFUs on a probiotic’s Supplement Facts panel a violation of supplement labeling rules. It is important that the agency made its position known, since technically, according to official FDA labeling regulations, CFUs are not an official measurement allowed to appear on the Supplement Facts panel; only weight measurements are allowed by law.

In fact, in the draft guidance, FDA points out the benefits of labeling probiotic products per CFUs and the drawbacks of using weight measurements. “The weight of microbial dietary ingredient in a product represents the product’s total cellular mass, consisting of both live and dead microorganisms, and therefore does not necessarily correlate with the number of viable microorganisms in that product,” the agency wrote. Later, it wrote, “For the reasons articulated in this document, we have determined that consumers would benefit from permitting the label of dietary supplement products to accurately represent the quantity of live microbial dietary ingredients in the Supplement Facts label in terms of CFUs.”

Industry leaders welcomed the draft guidance’s acknowledgement of CFU labeling, which two associations, the  IPA and the Council for Responsible Nutrition (CRN; Washington, DC), encouraged as a best practice in a joint probiotic-labeling guideline they released last year. However, many say they still wish FDA would remove probiotics from the requirement to label content by weight. But while labeling by weight remains a supplement-labeling rule, it’s likely that companies will end up listing probiotic content in both CFUs and milligrams. As Duffy MacKay, ND, senior vice president, scientific and regulatory affairs for CRN, explains, because the number of milligrams present does not consistently correspond with the number of CFUs in a product, including both measurements on a label is a problem. As MacKay points out, due to the way bacteria behave, even if companies standardize the number of CFUs in their product, the weight of those products can vary with each batch. “So by requiring both [CFU and milligram measurements], you’re introducing a technical snag for manufacturers because if you keep your CFUs consistent every time, your weight is going to vary just slightly,” he says. The preference would be that labeling include only CFUs, and not milligrams, he says.

Still, he, like others, says he is pleased to see FDA acknowledging the benefits of CFU labeling. MacKay says CRN plans to submit comments to the agency pushing to remove weight-based labeling for probiotics altogether, but he acknowledges that this drastic step might not be a high priority for FDA at this point. “We’re going to push FDA…and see where they go,” he says.

And even if the regulations don’t change, he says, “We got halfway there. Consumers will still have the information they need” with CFU counts listed. He says issuing draft guidance was FDA’s expedient way of permitting CFU labeling even as the labeling regulations stay the same.

“I don’t think we’re going to die on our sword over this issue, but we want to continue to make it clear that this would be the best for consumers,” he adds.