Increasing Biomanufacturing Yield with Bleed-Feed: Optimal Policies and Insights

Abstract

Problem definition: Bleed-feed is a novel technology that allows biomanufacturers to skip intermediary bioreactor setups. However, the specific time at which bleed-feed is performed is critical for success. The process is stringently regulated, and its implementation involves unique trade-offs in operational decision-making. Our analysis formalizes the operational challenges related to bleed-feed decisions, and our results inform biomanufacturers and policy-makers on the potential impact of this technology on current practice. Academic/Practical Relevance: Operations Management (OM) methodologies have not yet been widely adopted in the biomanufacturing industry. This research presents one of the first attempts to demonstrate how OM can complement biomanufacturing to improve operational decisions. We present a practically-relevant problem and a rigorous solution approach that is relevant to both OM and biomanufacturing communities. Methodology: We develop a finite-horizon, discrete-time Markov decision process, and analyze the structural characteristics of optimal bleed-feed policies. Results: We show that optimal bleed-feed policies have a two-way control-limit structure under mild conditions that were validated with industry data. Unlike common industry opinions, our analysis reveals that regulatory requirements do not necessarily limit the potential benefits of bleed-feed. Managerial Implications: Our analysis (supported with an industry case study) shows that bleed-feed implementation can provide benefits. Slow growing and/or high-risk cell cultures benefit the most from the use of the bleed-feed technology. Real-world test runs at MSD (using one bleed--feed) resulted in 85% improvement in the batch yield.