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

Funder: Support from the Engineering and Physical Sciences Research Council (EPSRC) Future Continuous Manufacturing and Advanced Crystallization (CMAC) Research Hub (Grant No. EP/P006965/1) is gratefully acknowledged.; Id: http://dx.doi.org/10.13039/501100000266The 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 informatio

Right-handed Sneutrino Dark Matter in Supersymmetric B-L Model

We show that the lightest right-handed sneutrino in TeV scale supersymmetric B-L model with inverse seesaw mechanism is a viable candidate for cold dark matter. We find that it accounts for the observed dark matter relic abundance in a wide range of parameter space. The spin-independent cross section of B-L right-handed sneutrino is consistent with the recent results CDMS II and XENON experiments and it is detectable in future direct detection experiments. Although the B-L right-handed sneutrinos annihilate into leptons, the PAMELA results can not be explained in this model unless a huge boost factor is considered. Also the muon flux generated by B-L right-handed sneutrino in the galactic center is smaller than Super-Kamiokande's upper bound.Comment: 16 pages, 7 figures; version accepted for publication in Journal of High Energy Physic

Trans-specialization understanding in international technology alliances: The influence of cultural distance

In the information age, the firm's performance hinges on combining partners' specialist knowledge to achieve value co-creation. Combining knowledge from different specialties could be a costly process in the international technology alliances (ITAs) context. We argue that the combination of different specializations requires the development of "trans-specialization understanding" (TSU) instead of the internalization of partners' specialist knowledge. This article examines the extent to which inter-firm governance in ITAs shapes TSU, and whether the development of TSU is endangered by cultural distance. We hypothesize that relational governance, product modularity, and cultural distance influence TSU development, which in turn influences firm performance. We collected data from 110 non-equity ITAs between software and hardware firms participating in the mobile device sector. We analyzed the data using partial least squares path modeling. Our findings suggest that TSU largely depends on product modularity and relational governance in alliances. However, while cultural distance negatively moderates the path from relational governance to TSU, it has no effect on the relationship between product modularity and TSU. Based on this, we conclude that product modularity can substitute for relational governance when strong relational norms are not well-developed in international alliances. Thus cultural distance does not invariably amount to a liability in ITAs

Multinationality and performance literature: a critical review and future research agenda

The literature on the relationship between the degree of multinationality (M) and performance (P) in the context of multinational enterprises (MNEs) has attracted a large volume of research in the past 50 years. Yet, the theoretical foundations and the empirical conclusions concerning the nature of M–P relationship vary greatly, thus call for a critical review and assessment. We examine 135 articles in 39 leading scholarly journals and classic books published during the period 1960–2015. We use an inductive approach and a qualitative content analysis methodology for our comprehensive and critical review of the literature. We incorporate international business, finance, and accounting perspectives in our analysis. We review the conceptualization and measurement of M, P, the findings on M–P relationships, methodologies, and geographic focus. We identify six key inconsistencies in the existing research, which cause ambiguity in the relevant findings. We make eight recommendations for future research to address these inconsistencies. Thus, our study contributes to the central debate in this research field

Evaluating the business case for continuous manufacturing of pharmaceuticals: A supply network perspective

This chapter addresses the challenges of evaluating the business case for continuous manufacturing of pharmaceuticals, looking beyond traditional technical assessments made at the unit operations or individual production facility level. It provides an overview of key concepts, approaches, and tools for the early assessment of supply network configuration opportunities enabled by continuous production processing interventions. Multiple levels of analysis are considered with the aid of examples based on major UK research programs on continuous production process technologies. Particular emphasis is placed on the potential for achieving enhanced product flexibility (in terms of volume and variety) and, depending on scale, the optimum number and location of manufacturing operations to support speed to market and system-level cost benefits. In the case of multiple manufacturing operations using continuous production process technologies, where production facility replication through digital twins is becoming a key enabler, the chapter sets out a supply network design and analysis approach that evaluates the commercial and operational viability of alternative manufacturing supply network scenarios