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. Our results demonstrate 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.

Biopharmaceutical manufacturing requires high investments and longterm production planning. For large biopharmaceutical companies, planning typically involves multiple products and several production facilities. Production is usually done in batches with a substantial set-up cost and time for switching between products. The goal is to satisfy demand while minimising manufacturing, set-up and inventory costs. The resulting production planning problem is thus a variant of the capacitated lotsizing and scheduling problem, and a complex combinatorial optimisation problem. Inspired by genetic algorithm approaches to job shop scheduling, this paper proposes a tailored construction heuristic that schedules demands of multiple products sequentially across several facilities to build a multi-year production plan (solution sequence in which the construction heuristic schedules the different demands is optimised by a genetic algorithm. We demonstrate the effectiveness of the approach on a biopharmaceutical lot sizing problem and compare it with a mathematical programming model from the literature. We show that the genetic algorithm can outperform the mathematical programming model for certain scenarios because the discretisation of time in mathematical programming artificially restricts the solution space.

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