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Scientists looking at a bottle of probiotic supplements.

Current issues in probiotic quality: An update for industry

/in ISAPP Science Blog /by KC

By Dr. Mary Ellen Sanders, ISAPP, Dr. Kit Goldman, USP, Dr. Amy Roe, P&G, Dr. Christina Vegge, Dr. Jean Schoeni, Eurofins

With probiotic dietary supplement use growing globally and an increasing array of products on the market, probiotic quality is an issue of perpetual relevance to industry. Best practices for producing high-quality probiotics change frequently, making it important for companies to stay informed.

ISAPP convened a webinar on this topic, available to ISAPP members only. The webinar took place November 16, 2021, and was hosted by Executive Science Officer, Dr. Mary Ellen Sanders. Speakers focused on the activities of the United States Pharmacopoeia (USP), a non-profit organization based in the US and operating globally, which for the past 200 years has worked to improve public health through development of quality standards for medicines, dietary supplements and foods. In 2017 USP formed an Expert Panel on probiotics.

Dr. Kit Goldman, Sr Director, Dietary Supplements and Herbal Medicines, USP, spoke about the origin of USP and the USP activities related to probiotic quality. USPs expert volunteers have determined the necessary parameters for probiotic quality standards, which include tests for identification, assay/enumeration and contaminants, and have created standards for a number of probiotic species/strains. In the course of doing so, the Probiotics Expert Panel identified specific areas where more information was needed to fully understand issues related to probiotic quality. This led to the formation of sub-teams to consider aspects of probiotic identification, enumeration and safety.

Dr. Amy Roe, Principal Scientist at P&G, spoke on appropriate regulatory requirements for probiotic safety. Currently, there is no global harmonization on the requirements for establishing probiotic safety for use in foods and supplements. Although ‘history of safe use’ has been central to safety assessments for many current probiotic species, probiotic manufacturers are increasingly seeking to use new strains, species, and next-generation probiotics; justification of safety based on a significant history of use may be challenged. USP and other stakeholders are looking 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 through reviewing global regulatory guidelines, evaluating appropriateness of traditional animal toxicology studies for studying the safety of probiotics, highlighting the importance of proper manufacturing practices with regard to final product safety, and outlining of essential parameters of a comprehensive safety assessment for a probiotic.

Dr. Jean Schoeni, Fellow at Eurofins, spoke on comparing probiotic enumeration methods. One challenge faced by the USP Probiotics Expert Panel is how to compare the increasing number of probiotic enumeration methods appearing in monograph submissions. A sub-team of the panel developed a solution that combines APLM (Analytical Procedures Lifecycle Management – a streamlined approach for determining the method’s fitness for intended use) with TI (tolerance interval) calculations. Schoeni encouraged companies to adopt this solution, highlighting tools that have been provided to the probiotics industry through publication of the sub-team’s work.

Dr. Christina Vegge spoke on quantification of multi-strain blends. For probiotic products comprising multiple strains, the viable numbers of each strain in these products would ideally be quantified. However, reliance on plate count methods creates analytical challenges regardless of whether the quantification of viable numbers of each strain in the blend is conducted prior to or after blending. Further challenges arise when addressing the reductions in potency over shelf life of the product. For multi-strain products, plate count procedures are insufficient—and currently no official guideline or general best practice exists to resolve this situation. Therefore, the USP Probiotics Expert Panel wants to conduct an explorative study to examine non-culture based technologies to quantify the viable composition of multi-strain blends.

A recording of this webinar is available for ISAPP industry members only. Please see here and email info@nullisappscience.org for the password to access this page.

Publications (open access) from USP Probiotics Expert Panel:

Jackson et al. Improving End-User Trust in the Quality of Commercial Probiotic Products. Front Microbiol. 2019 Apr 17;10:739.  doi: 10.3389/fmicb.2019.00739.

Weitzel MLJ, et al. Improving and Comparing Probiotic Plate Count Methods by Analytical Procedure Lifecycle Management. Front Microbiol. 2021 Jul 12;12: 693066. doi: 10.3389/fmicb.2021.693066.

 

 

Five things scientists should know about the future of probiotics and prebiotics

/in ISAPP Science Blog /by KC

By Marla Cunningham​, Metagenics Global R&D Innovation Manager and 2021 ISAPP Industry Advisory Committee representative

As anyone connected with probiotics and prebiotics knows – there’s a lot happening in this space.

After a well-attended discussion group at the 2019 ISAPP Annual Meeting in Antwerp, a collaboration of 16 industry and academic scientists came together to produce a broad overview of current and emerging trends that were covered in this discussion. Just released online by Trends in Microbiology, the open access paper identifies some top trends across multiple spheres of influence on the future of probiotics and prebiotics.

  1. Discovery: Prebiotics and probiotics are emerging from unexpected sources – naturally occurring as well as synthesised or engineered. Food, human and animal microbiome-derived probiotics feature heavily in probiotic development through top-down microbiome data-driven approaches as well as physiological target-driven screening approaches. Prebiotic sources have expanded beyond traditional plant sources to include food waste streams, animal gut-derived glycans and mammalian milk as well as increasingly sophisticated synthesis techniques, involving sonication, high pressure, acid, enzyme and oxidation treatments. A growing understanding of the implications of carbohydrate structure on microbial metabolism is driving the emergence of designer prebiotics, as specific substrates for microbes of interest or the production of target metabolites, such as polyphenol-derived bioactives.
  2. Evaluation: Calls for integrated systems biology -omic approaches to the evaluation of probiotic and prebiotics effects continue to increase, utilising whole genome and metabolite approaches, with a focus on better understanding of mode of action as well as differential host and microbial responses that serve to improve host health.
  3. Product development: Quality assurance techniques continue to undergo evolution as the challenges of divergent product formats and increasingly complex formulations necessitate innovation in the field. There is a focus on techniques beyond cell culture enumeration for probiotic product verification as well as on the identification of functional markers of probiotic and prebiotic activity, which can be applied in complex food matrices.
  4. Regulation: Recent regulatory challenges with claim approval are understood to have driven corresponding evolution in clinical science and an increased focus on mechanistic elucidation. However, the converse is also occurring, with the development of novel probiotic species, therapeutics for disease treatment and increasingly microbiome-driven modes of action having implications for regulatory frameworks. This ‘give and take’ between science and regulatory requirements will likely accelerate into the future as the field continues to evolve.
  5. Implementation: Interest continues to grow in precision and personalised approaches to nutrition and healthcare, especially in the field of microbiome-related interventions where there is significant appreciation of host-to-host variability. The identification of putative microbial signatures of health and disease continues to fuel the development of health-associated microbes as candidate probiotics and as targets for novel prebiotic substrates. Further, a focus beyond microbial composition and into microbial function is driving interest in interventions which can correct metabolomic profiles, such as probiotics with specific enzyme activity to boost synthesis or catabolism of key microbial metabolites in vivo, including purine and monoamine compounds.

These and other trends create a rich and evolving landscape for scientists within the field and provide the promise of a bright future for prebiotics and probiotics.

Read the full paper here

Reference:

Cunningham, M., Azcarate-Peril, M. A., Barnard, A., Benoit, V., Grimaldi, R., Guyonnet, D., Holscher, H. D., Hunter, K., Manurung, S., Obis, D., Petrova, M. I., Steinert, R. E., Swanson, K. S., van Sinderen, D., Vulevic, J., & Gibson, G. R. (2021). Shaping the Future of Probiotics and Prebiotics. Trends in microbiology, S0966-842X(21)00005-6. Advance online publication. https://doi.org/10.1016/j.tim.2021.01.003