Bill and Melinda Gates Foundation: Global Grande Challenges – Manufacturing Gut Microbial Biotherapeutics

The Challenge – New Approaches for Manufacturing Gut Microbial Biotherapeutics seeks fundamentally new strategies for manufacturing gut microbial biotherapeutics to achieve manufacturing efficiency and cost reductions necessary for global health applications. The Foundation is particularly open to high risk, unproven concepts that could yield novel systems. The Foundation also encourages approaches that may be carried out in low- and middle- income countries (LMIC) and proposers currently working in these settings.

Strategies could include (but are not limited to or constrained by) the following ideas:

• Different reactor designs including continuous stirred-tank, multistage, and/or multiphasic bioreactors with small footprints
• Disposable or low capital cost bioreactor designs
• Spatial structuring or immobilization at varying length scales, spatial gradients, media viscosity (i.e. liquid or solid state)
• Dynamically changing growth conditions and inoculation strategies reducing batch-to-batch variability
• Various growth conditions including temperature, gas composition, mixing, and dilution rate
• Novel, low-cost media components

Proposals should specifically detail how they will demonstrate a prototype process operating at lab-scale or greater enabling the manufacture of a diverse health-associated gut microbiota as may be expected in a live biotherapeutic product, specifically 1) production of at least 10 distinct strains derived from the healthy human gut 2) including at least two strains from the Firmicutes phylum of which at least one strain is highly oxygen-sensitive, at least two strains from the Bacteroidetes phylum and at least two strains from the Actinobacteria phylum. These strains could be obtained from commercial culture collections (i.e. ATCC or DSMZ) or may be novel isolates. It is likely that growth of multiple strains together simultaneously may be required for efficiency although other strategies can be pursued.

In addition, proposals should include how they will address all the following three key criteria:

• Low cost: How does the strategy enable a significant cost reduction over current batch fermentation and mixing practices towards an eventual target cost of ~$0.10 USD per dose, where each dose consists of ~109 bacteria?
• Scalability: Could the strategy be easily scaled up in the future, for example to a pilot scale of tens of thousands of doses per week of clinical grade material? Can potential risks in scale-up be addressed up front? How is the batch-to-batch production variability and risk of contamination minimized to meet purity, potency and consistency standards acceptable by the US Food and Drug Administration and other regulatory agencies for live biotherapeutic products?
• Universality: How can the strategy be easily adapted for the production of live biotherapeutic products representing diverse health-associated gut microbes and composed of larger or smaller numbers of strains than specified here?

Amount: Phase I grants for $100,000 will be awarded for a period of 18 months. Phase I projects that show promise will be eligible to apply for follow-on Phase II funding. Approximately 50 awards are made each round.

Eligibility: Private and public organizations. Individuals must be affiliated with an organization to apply.

Link: https://gcgh.grandchallenges.org/challenge/manufacturing-gut-microbial-biotherapeutics

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