Batch Culture Formulation of Live Biotherapeutic Products

Live biotherapeutic products (LBPs) are an emerging therapeutic modality that have been clinically investigated for treating pathogenic infections and inflammatory diseases. A major class of LBPs are feces-derived microbial consortiums which require numerous process development steps (e.g., separation, purification, blending) to facilitate LBP formulation into oral dosage forms. A subset of these LBPs circumvents the need for continuous fecal processing by batch culture for individual strains of microbes that are rationally defined and combined in the final LBP formulation. Separately, delivery formulations (e.g., polymer encapsulation) are being developed for LBPs to improve storage and intestinal engraftment; however, formulation requires additional manufacturing processes distinct from fecal processing or batch culture. Here, a streamlined approach termed batch culture formulation (BCF) is developed to combine the individual batch culture and formulation processes into a single-step process. Based on a previously described polymeric film formulation that encapsulates LBPs, BCF is shown to reduce the number of required processes to formulate LBP-films without altering LBP phenotype, function, or storage profiles compared to the standard LBP-film formulation approach. Additionally, it is demonstrated that BCF facilitates scaled-fabrication from the milligram to gram scale with predictable loading, highlighting the potential that BCF has for clinical translation.

Automated summary

LBPs are a new therapeutic modality, with feces-derived microbial consortiums being the main focus, but there are also subsets that use batch culture for individual microbial strains. Delivery formulations like polymer encapsulation are being developed for LBPs, requiring distinct manufacturing processes. A streamlined approach called BCF combines batch culture and formulation processes into a single step, reducing the number of required steps for LBP-film formulation.