Development of live biotherapeutic products: a position statement of Asia-Pacific Microbiota Consortium

Abstract

Objective: Live biotherapeutic products (LBPs) are biological products composed of living micro-organisms, developed to prevent, treat, or cure diseases. Examples include cultured strains of Akkermansia muciniphila and Christensenella minuta, as well as treatments using purified Firmicutes spores for recurrent Clostridioides difficile infections. There is a need for guidelines over the increasing interest in developing LBPs. A panel of microbiome experts from Asia-Pacific countries articulates their perspectives on key considerations for LBP development.

Design: Experts in microbiome research, microbiology, gastroenterology, internal medicine and biotherapeutics industry were invited to form a panel. During the 2023 Inauguration Conference of the Asia-Pacific Microbiota Consortium, an organised, iterative roundtable discussion was conducted to build expert consensus on critical issues surrounding the development of LBP.

Results: The consensus statements were organised into three main aspects: (a) rationales of LBP development, (b) preclinical studies and (c) preparation for clinical studies. The panel strongly recommended to prioritise human-derived and food-sourced strains for development, with indications based on clinical need and efficacy shown in studies. Preclinical evaluation should involve thorough screening, genotyping and phenotyping, as well as comprehensive in vitro and animal studies to assess functional mechanisms and microbiological safety. Rigorous cell banking practices and genetic monitoring are essential to ensure product consistency and safety throughout the manufacturing process. Clinical trials, including postmarketing surveillance, must be carefully designed and closely monitored, with robust safety and risk management protocols in place.

Conclusions: The development of LBP should be approached with a strong emphasis on microbiological evaluation, clinical relevance, scientific mechanisms and safety at every stage. These measures are essential to ensure the safety, effectiveness and long-term success of the product.

Keywords: ENTERIC BACTERIAL MICROFLORA; MICROBIOME; PROBIOTICS.

Figure 1. Examples of single-strain, composite and engineered LBPs. The sources of LBPs are provided in parentheses, along with a summary of their modes of action and beneficial outcomes to health. Xla1 and SYNB1618 are in clinical trials, and VowstTM is FDA-approved. Image icon credits go to Flaticon.com, with acknowledgments to the icon artists: monkik, I Wayan Wika and Freepik. FDA, Food and Drug Administration; HFC, high-fat diet; LBPs, live biotherapeutic products.

Figure 2. Panel statements on the development of LBPs. The consensus statements are organised into three aspects: (a) rationale, (b) preclinical studies and (c) preparation for clinical studies. They are serially numbered as A1, A2, B1–B6 and C1–C6. Image icon credits go to Flaticon.com, with acknowledgments to the icon artists: Freepik, surang, Iconjam and Uniconlabs. LBPs, live biotherapeutic products.