RD internationalization, domestic technology alliance, and innovation in emerging market.

Although R&D internationalization plays an important role in enterprises' globalization, few studies explore the mechanism of R&D internationalization and emerging market companies' innovation, or the relationship between R&D internationalization, domestic technology alliances and absorptive capacity. How does the R&D internationalization of emerging market enterprises affect the innovation of those enterprises? Under fierce market competition, do absorption capacity and domestic technology alliances have a significant impact on enterprise innovation? From the perspective of the knowledge-based view, this paper studies 185 enterprises undergoing R&D internationalization in China from 2012 to 2017, using high-dimensional Poisson fixed effects model, we use instrumental (HDFE IV) estimation to explain the impact of R&D internationalization on the innovation of the parent company and the mechanism behind it. The study finds that R&D internationalization positively promotes the parent company's innovation, and domestic technology alliances and absorptive capacity play a partial mediator role in R&D internationalization. In the face of fierce market competition, domestic technical alliances play a significant role in promoting enterprise innovation, while absorptive capacity plays a negative role in promoting enterprise innovation with the moderating effect of market competition.

An Implementation Research Approach to Re-orient Health Supply Chains Toward an Equity Agenda in the COVID-19 Era.

The Covid-19 pandemic has exposed critical inequities in global healthcare supply chains and the need for these systems to be analyzed and reoriented with an equity lens. Implementation research methodology can guide the use of evidence-based interventions to re-orient health supply chains towards equity and optimize health outcomes. Using this approach, private and public sector entities can adapt their strategies to focus not just on efficiency and cost savings but ensuring that vulnerable populations have access to essential medications, vaccines, and supplies. Findings can inform regulations that address supply chain inequities at the global level, strengthen existing systems to fill structural gaps at the national level, and address contextual challenges at the subnational level. This methodology can help account for historical practices from prior health initiatives, identify contemporary barriers and facilitators for positive change, and have applicability to the Covid-19 pandemic and ongoing vaccine distribution efforts. An implementation research approach is critical in equipping health supply chains with a path for more resilient and equitable distribution of necessary supplies, vaccines, and delivery of care.

Process Control and Energy Efficiency.

We review the impact of control systems and strategies on the energy efficiency of chemical processes. We show that, in many ways, good control performance is a necessary but not sufficient condition for energy efficiency. The direct effect of process control on energy efficiency is manyfold: Reducing output variability allows for operating chemical plants closer to their limits, where the energy/economic optima typically lie. Further, good control enables novel, transient operating strategies, such as conversion smoothing and demand response. Indirectly, control systems are key to the implementation and operation of more energy-efficient plant designs, as dictated by the process integration and intensification paradigms. These conclusions are supported with references to numerous examples from the literature.

Optimal Decisions for Two Risk-Averse Competitive Manufacturers under the Cap-and-Trade Policy and Uncertain Demand.

With the increasingly serious problem of environmental pollution, reducing carbon emissions has become an urgent task for all countries. The cap-and-trade (C&T) policy has gained international recognition and has been adopted by several countries. In this paper, considering the uncertainty of market demand, we discuss the carbon emission reduction and price policies of two risk-averse competitive manufacturers under the C&T policy. The two manufacturers have two competitive behaviors: simultaneous decision making and sequential decision making. Two models were constructed for these behaviors. The optimal decisions, carbon emission reduction rate, and price were obtained from these two models. Furthermore, in this paper the effects of some key parameters on the optimal decision are discussed, and some managerial insights are obtained. The results show that the lower the manufacturers' risk aversion level is, the higher their carbon emission reduction rate and utilities. As the carbon quota increases, the manufacturers' optimal carbon reduction rate and utilities increase. Considering consumers' environmental awareness, it is more beneficial for the government to reduce the carbon quota and motivate manufacturers' internal enthusiasm for emission reduction. The government can, through macro control of the market, make carbon trading prices increase appropriately and encourage manufacturers to reduce carbon emissions.

A multiscale simulation framework for the manufacturing facility and supply chain of autologous cell therapies.

BACKGROUND AIMS: Autologous cell therapy (AuCT) is an emerging therapeutic treatment that is undergoing transformation from laboratory- to industry-scale manufacturing with recent regulatory approvals. Various challenges facing the complex AuCT manufacturing and supply chain process hinder the scale out and broader application of this highly potent treatment. METHODS: We present a multiscale logistics simulation framework, AuCT-Sim, that integrates novel supply chain system modeling algorithms, methods, and tools. AuCT-Sim includes a single facility model and a system-wide network model. Unique challenges of the AuCT industry are analyzed and addressed in AuCT-Sim. Decision-supporting tools can be developed based on this framework to explore "what-if" manufacturing and supply chain scenarios of importance to various cell therapy stakeholder groups. RESULTS: Two case studies demonstrate the decision-supporting capability of AuCT-Sim where one investigates the optimal reagent base stocking level, and the other one simulates a reagent supply disruption event. These case studies serve as guidelines for designing computational experiments with AuCT-Sim to solve specific problems in AuCT manufacturing and supply chain. DISCUSSION: This simulation framework will be useful in understanding the impact of possible manufacturing and supply chain strategies, policies, regulations, and standards informing strategies to increase patient access to AuCT.

Chimeric antigen receptor-T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods.

Cell and gene therapies have demonstrated excellent clinical results across a range of indications with chimeric antigen receptor (CAR)-T cell therapies among the first to reach market. Although these therapies are currently manufactured using patient-derived cells, therapies using healthy donor cells are in development, potentially offering avenues toward process improvement and patient access. An allogeneic model could significantly reduce aggregate cost of goods (COGs), potentially improving market penetration of these life-saving treatments. Furthermore, the shift toward offshore production may help reduce manufacturing costs. In this article, we examine production costs of an allogeneic CAR-T cell process and the potential differential manufacturing costs between regions. Two offshore locations are compared with regions within the United States. The critical findings of this article identify the COGs challenges facing manufacturing of allogeneic CAR-T immunotherapies, how these may evolve as production is sent offshore and the wider implication this trend could have.

Costs and effectiveness of hearing conservation programs at 14 US metal manufacturing facilities.

OBJECTIVE: This study characterised overall and specific costs associated with hearing conservation programmes (HCPs) at US metal manufacturing sites, and examined the association between these costs and several noise-induced hearing loss (NIHL) outcomes. DESIGN: We interviewed personnel and reviewed records at participating facilities. We also measured noise for comparison to the ten-year average of measurements made by each facility. NIHL outcomes assessed included rates of standard threshold shifts (STS) and high-frequency hearing loss, as well as prevalence of hearing impairment, for each participating facility. We used linear regression to identify per-person HCP costs that best predicted the NIHL outcomes. STUDY SAMPLE: We evaluated 14 US metal manufacturing facilities operated by a single company. RESULTS: Annual HCP costs ranged from roughly $67,000 to $397,000 (average $308 ± 80 per worker). Our full-shift noise measurements (mean 83.1 dBA) showed good agreement with the facilities' measurements (mean 82.6 dBA). Hearing impairment prevalence was about 15% overall. Higher expenditures for training and hearing protector fit-testing were significantly associated with reduced STS prevalence. Higher training expenditures were also related to lower hearing impairment prevalence and high-frequency hearing loss rates. CONCLUSIONS: HCP costs were substantial and variable. Increased workplace spending on training and fit-testing may help minimise NIHL.

Manufacturing costs of HPV vaccines for developing countries.

BACKGROUND: Nearly all of the 500,000 new cases of cervical cancer and 270,000 deaths occur in middle or lower income countries. Yet the two most prevalent HPV vaccines are unaffordable to most. Even prices to Gavi, the Vaccine Alliance, are unaffordable to graduating countries, once they lose Gavi subsidies. Merck and Glaxosmithkline (GSK) claim their prices to Gavi equal their manufacturing costs; but these costs remain undisclosed. We undertook this investigation to estimate those costs. METHODS: Searches in published and commercial literature for information about the manufacturing of these vaccines. Interviews with experts in vaccine manufacturing. FINDINGS: This detailed sensitivity analysis, based on the best available evidence, finds that after a first set of batches for affluent markets, manufacturing costs of Gardasil for developing countries range between $0.48 and $0.59 a dose, a fraction of its alleged costs of $4.50. Because volume of Cervarix is low, its per unit costs are much higher, though at comparable volumes, its costs would be similar. INTERPRETATION: Given the recovery of fixed and annual costs from sales in affluent markets, Merck's break-even price to Gavi could be $0.50-$0.60, not $4.50. These savings could support Gavi programs to strengthen delivery and increase coverage. Outside Gavi, prices to lower- and middle-income countries, with profit, could also be lowered and made available to millions more adolescents at risk. These estimates and their policy implications deserve further discussion.

Optimal multi-floor plant layout based on the mathematical programming and particle swarm optimization.

In the fields of researches associated with plant layout optimization, the main goal is to minimize the costs of pipelines and pumping between connecting equipment under various constraints. However, what is the lacking of considerations in previous researches is to transform various heuristics or safety regulations into mathematical equations. For example, proper safety distances between equipments have to be complied for preventing dangerous accidents on a complex plant. Moreover, most researches have handled single-floor plant. However, many multi-floor plants have been constructed for the last decade. Therefore, the proper algorithm handling various regulations and multi-floor plant should be developed. In this study, the Mixed Integer Non-Linear Programming (MINLP) problem including safety distances, maintenance spaces, etc. is suggested based on mathematical equations. The objective function is a summation of pipeline and pumping costs. Also, various safety and maintenance issues are transformed into inequality or equality constraints. However, it is really hard to solve this problem due to complex nonlinear constraints. Thus, it is impossible to use conventional MINLP solvers using derivatives of equations. In this study, the Particle Swarm Optimization (PSO) technique is employed. The ethylene oxide plant is illustrated to verify the efficacy of this study.