Continuous manufacturing technologies in upstream pharmaceutical supply chains: Combining engineering and managerial criteria

Abstract

The COVID-19 pandemic exposed vulnerabilities in upstream pharmaceutical supply chains (PSC). One is that the global supply of active pharmaceutical ingredients (APIs) is overly dependent on few locations and large-scale batch manufacturing. Regulators hope to enable more dependable location decisions and improved processing quality with the adoption of advanced technologies such as process intensification through continuous manufacturing (CM). Conceptual work suggests that the benefits of shifting from batch to CM accrue end-to-end across the PSC. Yet detailed quantitative information about CM is limited at an early stage of evaluation, and too specialised to inform managerial decisions about PSC reconfiguration. Supply chain and engineering criteria are rarely combined in the early-stage evaluation of alternative CM technologies. Extant CM research typically overlooks implications for supply chain managers. To address the current gap, this paper evaluates, at an early stage of adoption, alternative CM reactor technologies for the synthesis of APIs in selected therapeutic areas. With evidence from secondary data, relevant technologies and criteria are identified, and their relative importance is evaluated in a semi-quantitative fashion following the Analytical Hierarchy Process (AHP) principles, ensuring that findings are intelligible to both engineers and managers. The proposed empirical work enriches previous conceptual frameworks predicated on volume-variety considerations. Specifically, findings suggest that microreactor technologies outperform alternatives all things considered. However, PSC managerial considerations introduce nuances in specific therapeutic areas e.g., antivirals where a tension between complex chemistry and the need for flexibility in unit operations may favour batch manufacturing. For analgesics the need to exploit the existing manufacturing base whilst addressing inventory reduction favour technologies that incorporate elements of batch and CM. The proposed analysis is in line with real-world decisions that global medicines manufacturers are increasingly facing, as governments seek to develop local health countermeasures to the COVID-19 pandemic in the absence of detailed information