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Review
. 2022 Dec:136:105266.
doi: 10.1016/j.yrtph.2022.105266. Epub 2022 Oct 4.

Considerations for determining safety of probiotics: A USP perspective

Amy L Roe  1 , Marie-Eve Boyte  2 , Chris A Elkins  3 , Virginia S Goldman  4 , James Heimbach  5 , Emily Madden  4 , Hellen Oketch-Rabah  4 , Mary Ellen Sanders  6 , Jay Sirois  7 , Amy Smith  8
Affiliations
Review

Considerations for determining safety of probiotics: A USP perspective

Amy L Roe et al. Regul Toxicol Pharmacol. 2022 Dec.

Abstract

A history of safe use is a backbone of safety assessments for many current probiotic species, however, there is no global harmonization regarding requirements for establishing probiotic safety for use in foods and supplements. As probiotic manufacturers are increasingly seeking to use new strains, novel species, and next-generation probiotics, justification based on a significant history of use may be challenged. There are efforts underway by a variety of stakeholders, including the United States Pharmacopeia (USP), to develop best practices guidelines for assessing the quality and safety of probiotics. A current initiative of the USP seeks to provide expert advice specific to safety considerations for probiotics. Toward this goal, this review provides a helpful summary guide to global regulatory guidelines. We question the suitability of traditional animal toxicology studies designed for testing chemicals for relevance in assessing probiotic safety. This includes discussion of the use of excessive dose levels, the length of repeated dose toxicity studies needed, and the most suitable animal species used in toxicology studies. In addition, the importance of proper manufacturing practices with regard to final product safety are also included. Thus, an outline of essential parameters of a comprehensive safety assessment for a probiotic are provided.

Keywords: Animal testing; Dietary supplements; Next-generation probiotics; Probiotics; Safety; Toxicology; United States Pharmacopeia.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
Phenotypic and Genotypic analysis of antimicrobial resistance genes for consideration of strain safety.
Fig. 2.
Fig. 2.
A proposed testing tier to guide data needs and studies for assessing probiotic safety.
See this image and copyright information in PMC

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Further reading

    1. European Medicines Agency (Ema), 1996. ICH topic Q5C quality of biotechnological products: stability testing of biotechnological/biological products. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-topic-q-.... (Accessed 6 June 2021).
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    1. European Pharmacopeia, 2019b. Microbiological Examination of Live Biotherapeutic Products: Tests for Specified Micro-organisms, 04/2019/20638.
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