Suggested criteria for using the term ‘probiotic’
Written by Dr Bruno Pot, Science Director at Yakult Europe
The term “probiotic” was defined in 2002 by a WHO/FAO Expert Committee as “Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”1, a definition grammatically revised by Hill et al. in 2014, stipulating also that probiotics must have a defined content, provide appropriate viable counts at the end of shelf life, be supported by suitable evidence for the claimed health benefits and, in relation to these benefits, must be safe for its intended use.2 The intended use aspect is important as it discriminates between probiotics for healthy people, regulated as foods or food supplements, and probiotics intended to treat or cure disease, regulated as drugs.
While the definition of probiotics is clear, simple and easy to use, the regulatory climate for probiotics remains less so and the broad character of the definition may be contributing to this confusion at a regulatory level. Scientific communities have been working to help clarify the situation, and the two recent publications discussed below are examples of this.
The first is a common initiative of IPA-Europe* and ISAPP*, two organisations that support science and communication on probiotics, and is entitled “Criteria to Qualify Microorganisms as ‘Probiotic’ in Foods and Dietary Supplements”, defining the minimum criteria applying to probiotic strains used in foods and food supplements.3 The experts state that a probiotic strain must be:
1. Sufficiently characterised (identified at strain level, free of virulence factors and antibiotic resistances)
2. Safe for the intended use (e.g. be listed on the QPS* list of EFSA*)
3. Supported by human clinical trial research, conducted according to generally accepted scientific standards (or matching the recommendations of local authorities), and
4. Alive in the product at the end of the shelf life, at the level used in the supporting clinical research.
A second paper soon to be published in Experimental & Molecular Medicine4, was an initiative of the PRI*, and focusses on the term and regulatory situation of “Live Biotherapeutic Products” (LBP), a category defined by the FDA* as “a biological product that contains live microorganisms, such as bacteria, is applicable to the prevention, treatment, or cure of a disease or condition of human beings, and is not a vaccine”, and therefore includes probiotics for pharmaceutical applications.5 Since 2019, the quality requirements for this category of drugs has also been accepted and clarified by the European Pharmacopoeia.6 Similar to all products intended to prevent or treat diseases, LBPs have to be registered as medicinal products before going to the market in the US and in Europe. The paper clarifies that for this category, in absence of specific guidelines in Europe, regulatory authorities and the pharmaceutical industry will routinely use the most relevant guidelines from the ICH*. Therefore the research behind this type of pharmaceutical product will be different as, in addition to safety, the impact of the type of product, in terms of quality, production method and, e.g. the acceptance of side effects, is clearly different from food or food supplements.7
In conclusion it can be stated that while a broad and formal definition of probiotics has been very useful to describe and accommodate the wide variety of current and future applications of probiotics in intestinal, oral, vaginal or skin health, the respective regulatory situations that match these different applications are still being further developed. While recent discussions have highlighted the need for clear regulation(s), the papers mentioned here show that big steps forward have been set and that the future of probiotics remains very promising.
EFSA: European Food Safety Authority
FDA: U.S. Food and Drug Administration
ICH: International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use
IPA-Europe: International Probiotic Association, part of IPA-global
ISAPP: International Scientific Association of Probiotics and Prebiotics
PRI: Pharmabiotic Research Institute (https://www.pharmabiotic.org/)
QPS: Qualified Presumption of Safety
1. FAO/WHO (2002). Guidelines for the Evaluation Of Probiotics in Food. Paris: FAO, 1–11 (https://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf).
2. Hill et al. (2014) Nature Reviews Gastroenterology & Hepatology 11: 506–514.
3. Binda et al. (2020) Frontiers in Microbiology 11: 1662.
4. Cordaillat-Simmons et al. (in press) Experimental & Molecular Medicine
5. FDA. (2016). Early Clinical Trials with Live Biotherapeutic Products: Chemistry, Manufacturing, and Control Information. Guidance for Industry. https://www.fda.gov/files/vaccines,%20blood%20&%20biologics/published/Early-Clinical-Trials-With-Live-Biotherapeutic-Products--Chemistry--Manufacturing--and-Control-Information--Guidance-for-Industry.pdf.
6. Council of Europe. (2019). Live Biotherapeutic Products (LBPs): unprecedented quality requirements by the Ph. Eur. Commission https://www.edqm.eu/en/news/live-biotherapeutic-products-lbps-unprecedented-quality-requirements-ph-eur-commission.
7. Rouanet et al. (2020) Frontiers in Medicine 7: 237.