“Probiotics: Achieving a Better Regulatory Fit”

In the past, I have addressed regulatory issues regarding probiotics.(1) A recent paper, ‘Probiotics: Achieving a Better Regulatory Fit,’ in the Food and Drug Law Journal is a worthwhile summary of some problem areas in the regulation of probiotics.(2) I’d like to share some of the key conclusions from this article.

This article is the result of a project funded by the National Institutes of Health as part of the Human Microbiome Project (HMP). This project fell under the umbrella of ‘ethical, legal, and social implications’ of the HMP’s scientific goals. The project was awarded to a group at the University of Maryland, who approached this task by assembling a diverse working group consisting of HMP scientists, physicians, legal academics, government regulators, industry and consumer representatives, bioethicists, food and drug lawyers, and health policy makers to address the adequacy of the current regulatory framework for probiotics in the United States. An extensive white paper summarized the three meetings of the working group, and delineated recommendations;(3) this current article is a more focused report on the working group findings.

The article sets the stage with a summary of approaches in the United States to regulation of probiotic products. Then the authors discuss several key issues:

• Safety
• Need for INDs to conduct human research
• Characterization
• Claims

In my opinion, the topics surrounding safety and characterization – although certainly able to benefit from additional research and refinement – are mostly straightforward and reasonable paths exist for dealing with them. However, significant challenges persist with the need for INDs to conduct human research and substantiation of food and supplement claims in the United States.

This article makes several reasonable recommendations:(4)

  1. FDA should adopt clear guidelines for when an IND is or is not required for human research on probiotics. Clarity is a worthwhile pursuit; however, I think the FDA has already accomplished this in their September 2013 guidance. The problem with this guidance isn’t lack of clarity. The problem is the FDA’s failure to acknowledge that not all human studies on probiotics should be considered drug studies. Some studies on the physiological function of foods and supplements should not require an IND.
  2. Regulatory oversight and burden should be proportional to risk of the probiotic. If a particular probiotic is judged safe by the local institutional review board for an intended study endpoint, research on that probiotic should not be hindered by unnecessary regulatory requirements. This would enable investigator-initiated studies on commercially available products. It would facilitate innovative research. It would result in consumers and healthcare providers getting access to research that helps them decide what foods and supplements are useful. This leads directly to the next recommendation.
  3. FDA should adopt guidelines establishing an abbreviated IND process that would allow researchers, in certain situations, to bypass safety studies.(6) It makes no sense to waste scare research resources and unduly delay needed efficacy studies in the conduct of unnecessary safety studies. When research is proposed on products that are commercially available or for which an adequate case can be made for safe use for the intended study population, safety studies should not be required. Instead, it should be possible to proceed directly to efficacy studies, which include adverse incident reporting.
  4. FDA should encourage the study of acceptable ways to: 1) demonstrate modulation of a condition— for example, cholesterol level—in healthy individuals without making a disease claim, and 2) measure homeostasis. Probiotics marketed as foods or dietary supplements are intended for use by the general population. Studies designed to demonstrate effects of probiotic foods and supplements must be conducted in populations that are representative of the general population. Basic research that advances an understanding of ways to measure health could provide useful targets for future studies on probiotic foods and supplements.
  5. There should be a publicly available mechanism through which consumers can obtain more information on the underlying evidence supporting a particular product. This is not a problem unique to probiotics. Consumers have a difficult time sorting through all the marketing hype and technical jargon to understand what any number of functional foods and dietary supplements might be able to do for them. Common questions about probiotics from consumers and healthcare provides alike seem to center on “which probiotics do what for whom?” The answer requires a rigorous and unbiased review of the totality of evidence, with appropriate conclusions offered.

This paper asks some important questions and provides some useful recommendations regarding the regulatory approach to probiotics in the United States. The task at hand seems to be to develop a regulatory approach that is efficient, meets legally imposed mandates, assures consumer and study participant safety, and facilitates, not hinders, research progress.

1. These posts address regulatory issues with probiotics in the United States:
Human research, functional foods and the FDA
Conducting human research on probiotics in the United States: legal perspectives
How FDA’s actions are guaranteeing research on probiotic foods is not conducted in the USA
Rocky Road Ahead for Probiotics
2. Hoffmann DE, Fraser CM, Palumbo F, Ravel J, Rowthorn V, Schwartz J. 2014. Probiotics: achieving a better regulatory fit. Food and Drug Law Journal 69(2):236-272.
3. Hoffmann, et al. 2013. Final Report. Federal Regulation of Probiotics: An Analysis of the Existing Regulatory Framework and Recommendations for Alternative Frameworks. NIH Grant Number: 5R01HG005171
4. Hoffmann, et al. 2014. Page: 253
5. See: Human research, functional foods and the FDA
6. Hoffmann DE, et al., Probiotics: Finding the Right Regulatory Balance, 342 Science 314 (2013).