Impact of failure rates, lot definitions and scheduling of upstream processes on the productivity of continuous integrated bioprocesses

Abstract

BACKGROUND: The failure rates and the scheduling of bioprocesses have a substantial impact on process performance and economics but are often overlooked and neglected. Integrated continuous biomanufacturing is more flexible in respect to scheduling and the impact of failures can be reduced by appropriate scheduling and lot definitions. RESULTS: In this work, we used a Monte Carlo approach on an integrated continuous biomanufacturing process with varying daily failure rates in the upstream and scheduling scenarios for seed fermentation (N-1 stage) to quantify the impact on the actual productive uptime of the integrated process. The optimum targeted production time in the continuous upstream ranges between 45 and 90 days depending on the daily failure rate and the lot definition used for the process. We showed that a minimal flexibility for planning of the seed fermentation is necessary to harvest the full potential of integrated continuous biomanufacturing. A comparison with batch manufacturing in the upstream processing showed a higher productive uptime for continuous biomanufacturing regardless of daily failure rates. Computation of productive uptime for different lot definitions showed that a daily lot definition only shows a loss of 3% to a maximum of 5% productivity, depending on the daily failure rate, compared to a real-time release approach. CONCLUSIONS: With this study, we provide a decision-making tool for the scheduling of upstream processes and implementation of integrated continuous biomanufacturing taking failure into account, showing the extent to which planning of flexibility and batch definitions influence the productivity of continuous integrated bioprocesses. © 2020 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.