Application of a Decision-Support Tool to Assess Pooling Strategies in Perfusion Culture Processes under Uncertainty

Abstract

Biopharmaceutical manufacture is subject to numerous risk factors that may affect operational costs and throughput. This paper discusses the need for incorporating such uncertainties in decision-making tools in order to reflect the inherent variability of process parameters during the operation of a biopharmaceutical plant. The functionalities of a risk-based prototype tool to model cost summation, perform mass balance calculations, simulate resource handling, and incorporate uncertainties in order to evaluate the potential risk associated with different manufacturing strategies are demonstrated via a case study. The case study is based upon the assessment of pooling strategies in the perfusion culture of mammalian cells to deliver a therapeutic protein for commercial use. Monte Carlo simulations, which generate random sample behaviors for probabilistic factors so as to imitate the uncertainties inherent in any process, have been applied. This provides an indication of the range of possible output values and hence enables trends or anomalies in the expected performance of a process to be determined.

A new, integrated, continuous purification process template for monoclonal antibodies: Process modeling and cost of goods studies

“…SuperPro was combined with SchedulePro ® , a scheduling software package by the same company, and used to model a real antibody facility (Toumi et al, 2010), with the focus and strength of the work being on sizing shared resources and evaluating capacity scenarios. A sophisticated research tool was introduced early on from the laboratory at University College London, UCL (Farid et al, 2000) and was subsequently used extensively to generate both upstream (Lim et al, 2005) and downstream (Mustafa et al, 2004) case studies. A distinguishing attribute of the evolving UCL tool is its ability to introduce uncertainty in the simulations through stochastic Monte Carlo algorithms that address both business and process aspects of facility operation.…”

Evaluating and Visualizing the Cost‐Effectiveness and Robustness of Biopharmaceutical Manufacturing Strategies

“…Hence, it is important to be able to assess the robustness of alternative strategies under uncertainty. This will be exemplifi ed with case studies on fed -batch versus perfusion culture for commercial manufacture by Lim et al [1,2] and on the robustness of legacy purifi cation facilities to higher titer processes by Stonier et al [4] (Section 22.3 ).…”

Ultra scale‐down approach to correct dispersive and retentive effects in small‐scale columns when predicting larger scale elution profiles

“…1,2 This can mean that substantial feed volumes can often still be required for laboratory studies 3 -potentially on the order of many 10s to 100s of millilitres-limiting the number of early stage experiments that can be carried out and delaying optimization until late on in development when adequate amounts of feed become available. The need for alternative approaches coupled to growing financial pressures in the pharmaceutical industry 4,5 have increased interest in using ultra scale-down (USD) methods for acquiring process data. 6 These combine the use of small volumes of process material with mimics of the engineering environment in larger-scale equipments to enable the rapid evaluation of potential full-scale operating conditions.…”