(504g) Towards Cost-Effective, Sustainable and Flexible Pharmaceutical Supply Chains: Single-Use Vs Stainless Steel Technology

The biopharmaceutical industry is uniquely placed to create value for society, by improving disease outcomes and make ground-breaking therapies available for those in need. As products reach market approval, manufacturers in the sector are pressured to carefully orchestrate and expand resources to meet forecasted demands. In this context, capacity planning activities are typically driven towards manufacturing strategies that decrease therapy costs and maximize product availability. Awareness of environmental sustainability of supply chain operations in life sciences and pharma is becoming increasingly relevant, with recent governmental and industrial initiatives to comply with Net Zero targets by 2030 [1].

Currently, established biopharmaceutical processes may rely on stainless steel equipment which are water and energy intensive [2]. Recent industrial trends for emerging therapeutics and vaccines undergoing scale-up propose instead a shift towards plastics-based equipment to minimize upfront capital investment and help meet global demands faster, which results in a high degree of solid contaminated waste [3]. In this space, computer-aided decision-making can help the benefits and drawbacks of adopting single-use equipment and help compare end-to-end supply chain performance with respect to their cost-effectiveness, environmental impact and scalability.

We present a framework for the quantification and optimization of supply chain sustainability (Figure 1) and illustrate tool capabilities for selected biopharmaceutical products. Firstly, flowsheets are developed to quantify the techno-economic performance of upstream (USP), downstream (DSP) and fill & finish (F&F) process sections of each manufacturing platform. Scale-dependent environmental impacts on midpoint and endpoint indicators are quantified through life cycle assessment (LCA) using ReCiPe 2016. Secondly, a multi-period mixed-integer linear programming (MILP) optimization problem is formulated. The optimization considers a set of candidate network nodes, costs, scale-dependent operational capabilities and demand scenarios and selects candidate supply chain structures, operational plans and suitable process equipment technologies. By fixing network structures and equipment technologies a priori, the optimization can generate a range of candidate solutions which can be compared in terms of (i) supply chain cost, (ii) environmental footprint, (iii) service level and (iv) upfront capital investment.

We consider a range of demand scenarios and biopharmaceutical products to understand product- and process-specific trends. First, the techno-economic analysis and life cycle assessment highlights that, for a given manufacturing scale, the use of single-use technologies in manufacturing may reduce both cost and environmental footprint compared to stainless steel facilities, given the substantial water usage reductions which outweigh the increased plastic waste. Second, the supply chain optimization problem is solved to compare optimal manufacturing configurations with respect to (i) cost, (ii) endpoint indicators vs midpoint indicators, (iii) product service level, through single- and multi-objective optimization methods. Given time-varying demands, the multi-period formulation is solved for fixed manufacturing designs based on stainless steel vs single-use equipment to identify a potential optimal technology switch throughout the scale-up process and the benefit of adopting single-use only in specific process steps.

In this fashion, we demonstrate how the tool can support decision-makers in the sector in developing cost-effective and eco-efficient scale-up strategies that ensure therapy availability from clinical trials to commercialization.

[1] HM Government (2021) Life Sciences Vision

[2] Budzinski K, Constable D, D’Aquila D, Smith P, Madabhushi SR, Whiting A, Costelloe T, Collins M (2022) Streamlined life cycle assessment of single use technologies in biopharmaceutical manufacture. N Biotechnol 68:28–36. https://doi.org/10.1016/j.nbt.2022.01.002

[3] Samaras JJ, Micheletti M, Ding W (2022) Transformation of Biopharmaceutical Manufacturing Through Single-Use Technologies: Current State, Remaining Challenges, and Future Development. https://doi.org/10.1146/annurev-chembioeng