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The FDA’s view on the term “probiotics”

By James Heimbach, Ph.D., F.A.C.N., JHEIMBACH LLC, Port Royal, VA

James Heimbach, food and nutrition regulatory consultant

Over the past 20 years as a food and nutrition regulatory consultant, I have filed about 40 GRAS notices with the United States Food and Drug Administration (FDA), including 15 strains of probiotic bacteria and 5 prebiotics. This fall I submitted notices dealing with 4 strains of bacteria and on January 16 received a telephone call from FDA that surprised me and initially infuriated me, but which I have come to understand.

The essence of the call was that FDA was declining to file my probiotic notices because the notices had identified the subject bacteria as “probiotics” or “probiotic bacteria.” FDA suggested that I resubmit without calling the subject microorganisms “probiotics.”

 

 

As I said, I was surprised and frustrated, and I still would prefer that when FDA makes a policy swerve they would do it in a way that does not make extra work for me and delay my clients’ ability to get to market in a timely manner.

What I have had to do here is remove my advocate’s hat and put on my regulator’s hat. (I worked for FDA for a decade . . . long ago [1978 to 1988], but I still remember how to think like a regulator.) And here is the issue. Recall that GRAS is concerned with safety, not efficacy (generally recognized as safe, or GRAS), and the information provided in a GRAS notice is focused on safety (although benefits may be more-or-less incidentally covered). The reviewers at FDA are charged with assessing whether the notice provides an adequate basis to conclude that there is a reasonable certainty that no harm will result from the intended use. They are not charged, and they are not equipped, to evaluate what benefits ingestion of the substance or microorganism might provide. So they are not in a position to say whether the subject microorganism will “confer a health benefit on the host,” which is to say, they are not in a position to say whether or not it may be regarded as a probiotic. Remember, probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (Hill et al. 2014).

Given that the FDA reviewers cannot say whether the notified microorganism is rightly called a probiotic, they are reluctant to sign off that they have no questions about a notice that calls it one. Regulatory agencies have to be careful; things sometimes come back to haunt them. Those who have been following FDA’s GRAS-notice response letters for a couple of decades will be aware that the agency is putting more and more disclaimers into the letters—about standards of identity, about potential labeling issues, about benefits shown in clinical trials, and about Section 201(II) of the FD&C Act.

One concern that FDA likely has is that if some issue comes up in the future regarding a claim made for benefits from use of a product containing the subject bacterium, someone may make the argument that FDA had accepted that the strain is indeed a probiotic and so it presumably confers probiotic benefits. In the case of probiotics, there are also some internal FDA politics. As ISAPP meeting attendees may already be aware, FDA’s Center for Biologics Evaluation and Research (CBER) would like to claim jurisdiction over all administration of live microorganisms, and the Center for Food Safety and Applied Nutrition (CFSAN) does not seem willing to have a confrontation.

I suspect that a similar situation obtains with the term “prebiotic.” Although I have filed a number of GRAS notices for prebiotics, they haven’t been called that; they have been called fructooligosaccharides, or tamarind seed polysaccharide, or polydextrose, or 2’-O-fucosyllactose. I don’t know how FDA would respond if a GRAS determination were filed with the substance labeled as a prebiotic.

So, I’ve decided that my sympathies lie with FDA. Until and unless a microorganism has been confirmed by competent authority to have probiotic properties when used as intended in a GRAS notice, FDA is probably correct in rejecting its right to be labeled a probiotic. If it’s any consolation, this new position by the FDA has its origin in their acknowledgment of the official scientific definition of the word “probiotic”.

When Mary Ellen Sanders (ISAPP’s Executive Science Officer) reviewed my first draft of this note, she asked what I had in mind by “competent authority,” to which I don’t have a good answer at the present time except to insist that it is not FDA’s Division of GRAS Notice Review. Thirty years ago, when I was at FDA, I was in the Office of Food Science and Nutrition, and that office was charged with making determinations of that type (although I don’t recall anything about probiotics coming before us). But FDA no longer has such an office. Until it does, or until it agrees on another source of authority on designation of microorganisms as non-CBER-domain probiotics, I suspect that CFSAN will continue to be very cautious in this area.

Minimum criteria for probiotics: ISAPP perspectives

By Mary Ellen Sanders PhD, Executive Science Officer, ISAPP

During its 2018 annual meeting (June 5-7), ISAPP convened a group of 30 participants from 13 countries to address issues associated with global harmonization of regulations for probiotics and prebiotics. This topic was of interest due to the broad international presence at this meeting, ISAPP’s first in Asia. The goal of this group was to provide regulators guidance derived from this assemblage of experts regarding the minimum criteria a probiotic food or supplement should meet. Drs. Seppo Salminen, Yuan-Kun Lee, and Gabriel Vinderola, who chaired this group, recently completed a summary titled “ISAPP position statement on minimum criteria for harmonizing global regulatory approaches for probiotics in foods and supplements”.

In December of 2017 the International Probiotic Association (IPA) presented a proposal to Codex Alimentarius – a recognized body that develops global standards and guidelines related to foods – regarding establishment of guidelines for probiotic foods. Codex Alimentarius accepted this proposal and requested that Argentina prepare draft guidelines to be considered in the 2018 session of the Codex Alimentarius  Committee on Nutrition and Foods for Special Dietary Use. ISAPP representatives and group coordinators (Sanders, Salminen and Vinderola) took part along with IPA in a scientific meeting in Argentina to present the ISAPP views to local authorities and experts.  IPA hopes that these efforts will lead to harmonized regulations since “this lack of harmonization in industry practice and legislation remains and often leads to serious issues and concerns for the probiotics industry, regulators, and even consumers in regard of quality, safety and labelling.” (Page1 of the proposal)

As the efforts of harmonization of regulations for probiotic foods through Codex progresses, ISAPP offers – through this summary document – its perspectives on minimum criteria for probiotics. The ISAPP group’s conclusions echo the principles outlined in the IPA proposal. Our hope is that this ISAPP document will provide useful perspective to local regulators. As of this writing, Prof. Salminen has delivered this document to the Codex representative at the Finnish Ministry of Agriculture and Food. We hope that further dissemination of the perspectives in this document will contribute to a science-based approach to global harmonization of regulations for probiotics.

See the document for the list of minimum criteria.