Dynamic Scheduling of Multi-Product Continuous Biopharmaceutical Facilities: a Hyper-Heuristic Framework

Folarin B. Oyebolu, Richard Allmendinger, Suzanne S. Farid, Jürgen Branke

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The biopharmaceutical industry is increasingly interested in moving from batch to semi-continuous manufacturing processes. These continuous bioprocesses are more failure-prone and process failure is more consequential. In addition, the probability of failure is dependent on process run time which generally is determined independent of scheduling considerations. This work presents a discrete-event simulation of continuous bioprocesses in a scheduling environment. Dynamic scheduling policies are investigated to make operational decisions in a multiproduct manufacturing facility and react to process failure events and uncertain demand. First, different scheduling policies are adapted from the stochastic lot sizing literature and a novel look-ahead scheduling policy is proposed. Then, policy parameters (including process run time) are tuned using evolutionary algorithms. The benefit of policy parameter tuning is demonstrated and shows that the tuned policies perform much better than a policy that estimates policy parameters based on service level considerations and a policy based on a fixed cyclical sequence.
Original languageEnglish
Pages (from-to)71-88
Number of pages18
Issue number9
Publication statusPublished - 2 Mar 2019


  • Biopharmaceutical manufacture
  • Hyper-heuristics
  • Machine failure
  • Perfusion
  • Simulation optimisation
  • Stochastic economic lot scheduling problem


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