Development of an Integrated Continuous Manufacturing Process for the rVSV-Vectored SARS-CoV-2 Candidate Vaccine.

The administration of viral vectored vaccines remains one of the most effective ways to respond to the ongoing novel coronavirus disease 2019 (COVID-19) pandemic. However, pre-existing immunity to the viral vector hinders its potency, resulting in a limited choice of viral vectors. Moreover, the basic batch mode of manufacturing vectored vaccines does not allow one to cost-effectively meet the global demand for billions of doses per year. To date, the exposure of humans to VSV infection has been limited. Therefore, a recombinant vesicular stomatitis virus (rVSV), which expresses the spike protein of SARS-CoV-2, was selected as the vector. To determine the operating upstream process conditions for the most effective production of an rVSV-SARS-CoV-2 candidate vaccine, a set of critical process parameters was evaluated in an Ambr 250 modular system, whereas in the downstream process, a streamlined process that included DNase treatment, clarification, and a membrane-based anion exchange chromatography was developed. The design of the experiment was performed with the aim to obtain the optimal conditions for the chromatography step. Additionally, a continuous mode manufacturing process integrating upstream and downstream steps was evaluated. rVSV-SARS-CoV-2 was continuously harvested from the perfusion bioreactor and purified by membrane chromatography in three columns that were operated sequentially under a counter-current mode. Compared with the batch mode, the continuous mode of operation had a 2.55-fold increase in space-time yield and a reduction in the processing time by half. The integrated continuous manufacturing process provides a reference for the efficient production of other viral vectored vaccines.

Supply chain mapping: a proposed construct

During COVID-19, supply chain (SC) mapping has appeared as one of the critical supply chain capabilities that could make a striking difference in organisations' supply chain performance. Despite its crucial role in responding to SC disruptions, there is a void in the literature on this topic. In this context, the prime objective of the current study is to introduce a comprehensive measure of SC mapping accounting for its various dimensions. A review of the literature is conducted to identify the relevant dimensions and sub-dimensions of SC mapping. Next, two rounds of focused group discussions are conducted in order to refine the identified dimensions and to add any relevant dimensions of SC mapping. Third, we employ exploratory factor analysis to develop the construct of SC mapping. The findings reveal that SC mapping has three major dimensions, namely upstream mapping, downstream mapping, and midstream mapping, with a total 25 items. The developed construct can be used to operationalise the SC mapping and to examine its antecedents and precedents.

Enhancing supply chain agility through e-procurement in a volatile frontier market

Background: The business environment is increasingly becoming volatile, uncertain, complex and ambiguous (VUCA) because of globalisation, increased competition, random consumer tastes changes and environmental factors. Traditional procurement strategies are becoming increasingly redundant because of the volatility of the global business environment. The market has thus called for increased agility to conquer the VUCA nature of the supply chain environment. Objectives: The study sought to examine the role that e-procurement plays in augmenting the agility of supply chains. The four determinants of e-procurement, that is, e-design, e-sourcing, e-evaluation and e-negotiation, were linked directly with supply chain agility. Method: A census approach was taken to gather data from 219 supply chain and procurement employees of Zimbabwe's telecommunications and technology industry. A self-administered survey questionnaire was used based on a scientifically developed and validated supply chain agility measurement scale from the extant literature. Results: Using structural equation modelling (SEM), the study's results confirmed that e-procurement significantly predicts supply chain agility. All determinants of e-procurement were statistically significantly explaining supply chain agility in a volatile business environment. Conclusion: The study concludes that e-procurement augments the agility of the supply chain in volatile business environments, as e-procurement can increase swiftness and agility as it fosters ubiquitous business processes on a seamless real-time basis. It emerged from the study that the supply chain vulnerabilities volatile industries face could be eliminated through supply chain agility, augmented through e-procurement systems. The study's findings also implore supply network members from upstream to downstream to adopt e-procurement. Contribution: The study has practical implications for all supply network members from upstream to downstream. It implores these members to adopt e-procurement to revive supply networks amid environmental volatility and alleviate miscommunication. Study also offers theoretical implications for e-procurement and supply chain management. The study also contributes to the body of knowledge by extending the existing theories on e-procurement and supply chains in the context of environmental volatility.

COVID-19 as a trigger for dynamic capability development and supply chain resilience improvement

A firm's ability to manage risk and resilience in supply chains has turned out to be an invaluable capability during the COVID-19 pandemic. Fast responsiveness, quick decision-making, and the ability to reconfigure the resource base have helped firms during the pandemic, which caused rapid disruptive effects for which they were unprepared. This research applies the dynamic capability view as a theoretical framework to study the impact of the COVID-19 pandemic on firms' dynamic capabilities and, the influence of dynamic capabilities on supply chain resilience. These capabilities are highly needed to survive during the pandemic. Using the survey data, we found that the impacts that COVID-19 had on a firm's upstream supply chain influence firms' capabilities to seize opportunities or neutralise threats. Furthermore, we found that reconfiguring ability has a strong influence on supply chain resilience. Thus, the impacts of COVID-19 on the downstream supply chain pushed firms to realign resources to respond better to demand. Upstream disruptions pushed companies to react to threats and opportunities in the supply market, while downstream disruptions leveraged reconfiguring capabilities.

The Achilles heel of the U.S. food industries: Exposure to labor and upstream industries in the supply chain

The modern‐day food industries are part of a complex agri‐food supply chain, where food production has become efficient yet potentially vulnerable to supply chain risks. The COVID‐19 pandemic is a testament to that end. This article measures and identifies the U.S. food manufacturing industries' vulnerability to upstream industries and labor occupations by (a) calculating a food industry's diversification of intermediate input purchases across upstream industries, (b) quantifying the relative exposure of food manufacturing in a given industry and location to upstream input suppliers and labor occupations, and (c) estimating each food industry's gross output elasticity of inputs. This article also explores geographic heterogeneity in food industries' vulnerability. Among our results, we find evidence that the animal processing industry's output is relatively vulnerable to production labor, consistent with the observed disruptions to the meatpacking sector during COVID‐19, which were largely caused by labor issues. Our results may help academics and practitioners to understand food industries' vulnerabilities to upstream industries and labor occupations.

Designing a generic, adaptive protocol resource for the measurement of health impact in cash transfer pilot and feasibility studies and trials in high-income countries.

INTRODUCTION: In the context of the COVID-19 pandemic, upstream interventions that tackle social determinants of health inequalities have never been more important. Evaluations of upstream cash transfer trials have failed to capture comprehensively the impacts that such systems might have on population health through inadequate design of the interventions themselves and failure to implement consistent, thorough research measures that can be used in microsimulations to model long-term impact. In this article, we describe the process of developing a generic, adaptive protocol resource to address this issue and the challenges involved in that process. The resource is designed for use in high-income countries (HIC) but draws on examples from a UK context to illustrate means of development and deployment. The resource is capable of further adaptation for use in low- and middle-income countries (LMIC). It has particular application for trials of Universal Basic Income but can be adapted to those covering other kinds of cash transfer and welfare system changes. METHODS: We outline two types of prospective intervention based on pilots and trials currently under discussion. In developing the remainder of the resource, we establish six key principles, implement a modular approach based on types of measure and their prospective resource intensity, and source (validated where possible) measures and baseline data primarily from routine collection and large, longitudinal cohort studies. Through these measures, we seek to cover all areas of health impact identified in our theoretical model for use in pilot and feasibility studies. RESULTS: We find that, in general, self-reported measures alongside routinely collected linked respondent data may provide a feasible means of producing data capable of demonstrating comprehensive health impact. However, we also suggest that, where possible, physiological measures should be included to elucidate underlying biological effects that may not be accurately captured through self-reporting alone and can enable modelling of long-term health outcomes. In addition, accurate self-reported objective income data remains a challenge and requires further development and testing. A process of development and implementation of the resource in pilot and feasibility studies will support assessment of whether or not our proposed health outcome measures are acceptable, feasible and can be used with validity and reliability in the target population. DISCUSSION: We suggest that while Open Access evaluation instruments are available and usable to measure most constructs of interest, there remain some areas for which further development is necessary. This includes self-reported wellbeing measures that require paid licences but are used in a range of nationally important longitudinal studies instead of Open Access alternatives.

Massachusetts Initiative to Improve Contraception Services: A Tale of Two Programs

Upstream selected clinical sites for recruitment based on patient volume, current state of contraceptive care, regional variation, patient demographics, and health center buy-in to implement Upstream's program with fidelity. Programming content for both teams included the following: 1. educating and coaching clinicians and support staff on how to provide patient-centered contraceptive counseling that is free of bias or coercion;2. providing technical assistance to stock the full range of contraceptive methods;3. supporting billing and coding to optimize reimbursement ofcontraceptive services and methods;4. revising or creating department or agency policies to enable highquality, sustainable practice change related to contraceptive care;5. incorporating a pregnancy intention screening or contraceptive needs assessment question, contraceptive counseling, and documentation of contraceptive method use into clinical workflows, often including the hospital's or agency's electronic health record (EHR) system;6. establishing strategies to ensure that a patient can receive their desired contraceptive method on the same day as their visit, including long-acting reversible contraceptive (LARC) methods;and 7. enhancing emergency contraception services. The additional programming areas and technical assistance of the Upstream intervention with partner health practices included: (1) training all agency staff on current best practices and clinical knowledge of high-quality contraceptive care;(2) coordinating clinician precepting for LARC placement and removal;(3) where necessary, providing funding to stock the full range of contraceptive methods;and (4) providing patient education materials for use during clinical visits. EVALUATION STRATEGIES AND EARLY FINDINGS At the outset of the Massachusetts initiative, both teams and representatives from the Massachusetts Department of Public Health and Massachusetts' Medicaid program worked collaboratively to design an evaluation plan for the fiveyear project.

Risk analysis of shallot upstream supply chain in Malang during COVID-19 pandemic

A sustainable supply scenario becomes an important part of supply chain management for agricultural products in a conjuncture situation. In order to invent sustainable agriculture product supply, it is necessary to ensure that the existing upstream supply chain is sufficiently resilient with minimum disruption. This research aims to analyze risk in the shallot upstream supply chain in Malang during the Covid-19 pandemics. In this study, 8 shallots farmers and 3 intermediaries/traders were interviewed as key informants, and the purposive method was used. Upstream supply chain risk analysis is carried out in two stages to analyze risks from farmers and traders. Analysis was done by using a risk matrix. The result shows that the main risk of sustainable aspects within the upstream level is economic aspects. The distribution level needs to be paid more attention to because it has more risks than the farmers’ level.

Public Health and Public Safety: Converging Upstream

Though aspirational, such framing sends a clear message: although medical care can blunt or reverse an individual's physical and mental illness, only by adelree·sing core upstream determinants of health- from fundamental (racism, poverty) to social and envirermKmtal (peer education and housing, air pollution) causes-is progress toward im;1 1 lth at the population fevel achievable. .erthe United States temini ies to spend more on health care, and prepertionally less on addressing 1 inderlying causes of ill health, than any other wealthy country. [...]guided by local data and knowledge, resources must be allocated to catalyze measurable gains in public safety, broadly construed. The Healthcare Anchor Network is working with health care systems across the country to lend the economic power ofthe hospital sector to strengthening community health through purposeful investment in social determinants of health.

Monitoring of SARS-CoV-2 in sewersheds with low COVID-19 cases using a passive sampling technique.

Monitoring SARS-CoV-2 RNA in sewer systems, upstream of a wastewater treatment plant, is an effective approach for understanding potential COVID-19 transmission in communities with higher spatial resolutions. Passive sampling devices provide a practical solution for frequent sampling within sewer networks where the use of autosamplers is not feasible. Currently, the design of upstream sampling is impeded by limited understanding of the fate of SARS-CoV-2 RNA in sewers and the sensitivity of passive samplers for the number of infected individuals in a catchment. In this study, passive samplers containing electronegative membranes were applied for at least 24-h continuous sampling in sewer systems. When monitoring SARS-CoV-2 along a trunk sewer pipe, we found RNA signals decreased proportionally to increasing dilutions, with non-detects occurring at the end of pipe. The passive sampling membranes were able to detect SARS-CoV-2 shed by >2 COVID-19 infection cases in 10,000 people. Moreover, upstream monitoring in multiple sewersheds using passive samplers identified the emergence of SARS-CoV-2 in wastewater one week ahead of clinical reporting and reflected the spatiotemporal spread of a COVID-19 cluster within a city. This study provides important information to guide the development of wastewater surveillance strategies at catchment and subcatchment levels using different sampling techniques.

Identification of G-quadruplex DNA sequences in SARS-CoV2.

G-quadruplex structure or Putative Quadruplex Sequences (PQSs) are abundant in human, microbial, DNA, or RNA viral genomes. These sequences in RNA viral genome play critical roles in integration into human genome as LTR (Long Terminal Repeat), genome replication, chromatin rearrangements, gene regulation, antigen variation (Av), and virulence. Here, we investigated whether the genome of SARS-CoV2, an RNA virus, contained such potential G-quadruplex structures. Using bioinformatic tools, we searched for such sequences and found thirty-seven (forward strand (twenty-five) + reverse strand (Twelve)) QGRSs (Quadruplex forming G-Rich Sequences)/PQSs in SARS-CoV2 genome. These sequences are dispersed mainly in the upstream of SARS-CoV2 genes. We discuss whether existing PQS/QGRS ligands could inhibit the SARS-CoV2 replication and gene transcription as has been observed in other RNA viruses. Further experimental validation would determine the role of these G-quadruplex sequences in SARS-CoV2 genome function to survive in the host cells and identify therapeutic agents to destabilize these PQSs/QGRSs.

Exploring Supply Chain Collaboration for Green Innovations: Evidence from the High-Tech Industry in Poland

The purpose of this article is to investigate whether the wide scope of supply chain collaboration including both customers and suppliers (Upstream–downstream External Collaboration) determines the greening of innovation more significantly than the scope limited only to suppliers (Upstream External Collaboration) or customers (Downstream External Collaboration). This goal was achieved as part of extensive research on the impact of relational capital on the innovativeness of high-tech companies in Poland. The results of the research were analysed using fuzzy conversion scales and descriptive statistics based on triangular fuzzy numbers. The application of the achievements of the fuzzy sets theory made it possible to test the hypotheses presented in the article with the use of fuzzy analysis of variance (fuzzy ANOVA). The findings confirm that the subjective scope of collaboration in the supply chain is important for greening innovation. Companies that cooperate with both suppliers and customers (Upstream–downstream External Collaboration) declared a greater tendency to green their innovations than those that cooperate with only one group of partners. The research findings contribute to the literature on the role of collaboration in the ecological responsibility and environmental performance of supply chain partners. The conclusions may have practical implications for the design and implementation of strategies in sustainable supply chain management. The study provides important lessons for SC managers facing the challenge of sustainable management during and after the COVID-19 outbreak.

The impact of Covid-19 on global upstream and downstream supply chain management activities

COVID-19 pandemic has affected thousands of people worldwide;with significant economic changes in the past and to the changes to be made for future. Many organisations especially;The Intergovernmental economic organisation (OECD - The Organisation for Economic Co-operation and Development) warned the companies and industries on the global economic cut, the corona virus will be boarding. The global economy and international markets pitched down with the spread of corona virus spreading from China which is the world's second largest economy to other countries including Asia;Europe;Australia;Europe;America and the Middle East. Many economies came up with many policies to prevent the further spread of this virus;including restrictions on travel and quarantines;which has disrupted international supply chains affecting a lot of business operations and dwindle revenues. About 75 percent of business including Wholesale;Manufacturing;Retail and Services in China and about 51,000 companies have this impact at a global level according to data from Dun and Bradstreet. The success or failure of every Business depends on how well they manage their supply chain management activities. The impact of corona virus on supply chain activities is twofold. One is;Upstream Supply chain management where companies should monitor the backward integrated activities in procuring the inventory;which has accommodated a loss in the production because of closure of factories and a slowdown in the economy. Second is;Downstream Supply chain management where the intermediaries and middlemen face a lot of problems because of scarcity in inventory and many quarantine measures taken by many economies. Many disruptions in both Upstream and Downstream Supply chains lead to severe scarcity of inventory which was experienced globally by all the economies. This situation has made many economies to think of the inter connectivity and inter dependency among global nations in terms of supply chain. This article is aimed to highlight the effects and changes COVID-19 pandemic has brought in the supply chain industry from both Upstream and Downstream perspective. © 2022 Author(s).

Disruptions in the Upstream Palm Oil Supply Chain: A Case of COVID-19's Impact on Upstream Intermediaries in Malaysia

The COVID-19 pandemic had a global impact since it was first discovered in late 2019, in Wuhan, China. According to the World Health Organization (WHO), COVID-19 has affected over 179 million people and killed approximately 3.9 million people in more than 200 countries across the globe (WHO,2021). This outbreak has not only affected people’s lives but also disrupted global supply chains. It has shown significant effects on businesses, consumers, and the global economy. Fear of the virus has led to many companies scrambling to respond regarding employees’ job security, ensuring supply security, risk mitigation strategy, and addressing market uncertainties that are driving down demand. Broadly, the objective of this article is to highlight issues faced by the upstream palm oil supply chain actors during this pandemic. Based on the problem, the study concluded that some forms of actions (short-term & long-term) have been proposed to ensure an agile palm oil supply chain.

Risk Evaluation of Foreign Direct Investment in Petroleum Projects in Peru

In the coming decades the world economy will continue depending on hydrocarbons. Foreign direct investment (FDI) for oil exploration and exploitation will be important and necessary to meet energy demand. These investments are associated with risks and uncertainties inherent to this sector due to the fact that large amounts of initial investment are required, long periods of recovery of the investment, exhaustibility of oil and natural gas resources, crude oil price volatility, geological risk and socioenvironmental risk. South American countries have significant potential of non-renewable energy resources that need to be exploited to support their development and economic growth after the devastation caused by the COVID-19 crisis. There is currently a shortage of international oil companies (IOC) in this region due to political instability associated with a high rate of corruption, poor-quality institutions, and overestimated rate tax regimes. The purpose of this research is to perform a classification of countries from low risk to high risk within the South American continent;as a favorable place to invest in its upstream sector. Six risk categories were preliminarily identified (political risk, macroeconomic risk, technical risk, investment climate risk, potential risk of oil resources and risk of environmental limitations);and ten indicators associated with these six risks of foreign investment in oil projects. The information of these indicators is collected to carry out the analytical hierarchy process (AHP) and obtain the weighting index of these ten indicators that are later used in the order preference technique by similarity to ideal solution (TOPSIS) in order to obtain the ranking of these countries. Countries with low-risk investments were ranked;as a result, Peru is in third place. Likewise, it is concluded that the countries with the highest amount of proven oil reserves and the lowest percentage of Government Take are the most favorable as a destination for foreign investment. © 2021 Latin American and Caribbean Consortium of Engineering Institutions. All rights reserved.

Towards integrated production of an influenza A vaccine candidate with MDCK suspension cells.

Seasonal influenza epidemics occur both in northern and southern hemispheres every year. Despite the differences in influenza virus surface antigens and virulence of seasonal subtypes, manufacturers are well-adapted to respond to this periodical vaccine demand. Due to decades of influenza virus research, the development of new influenza vaccines is relatively straight forward. In similarity with the ongoing coronavirus disease 2019 pandemic, vaccine manufacturing is a major bottleneck for a rapid supply of the billions of doses required worldwide. In particular, egg-based vaccine production would be difficult to schedule and shortages of other egg-based vaccines with high demands also have to be anticipated. Cell culture-based production systems enable the manufacturing of large amounts of vaccines within a short time frame and expand significantly our options to respond to pandemics and emerging viral diseases. In this study, we present an integrated process for the production of inactivated influenza A virus vaccines based on a Madin-Darby Canine Kidney (MDCK) suspension cell line cultivated in a chemically defined medium. Very high titers of 3.6 log10 (HAU/100 µl) were achieved using fast-growing MDCK cells at concentrations up to 9.5 × 106 cells/ml infected with influenza A/PR/8/34 H1N1 virus in 1 L stirred tank bioreactors. A combination of membrane-based steric-exclusion chromatography followed by pseudo-affinity chromatography with a sulfated cellulose membrane adsorber enabled full recovery for the virus capture step and up to 80% recovery for the virus polishing step. Purified virus particles showed a homogenous size distribution with a mean diameter of 80 nm. Based on a monovalent dose of 15 µg hemagglutinin (single-radial immunodiffusion assay), the level of total protein and host cell DNA was 58 µg and 10 ng, respectively. Furthermore, all process steps can be fully scaled up to industrial quantities for commercial manufacturing of either seasonal or pandemic influenza virus vaccines. Fast production of up to 300 vaccine doses per liter within 4-5 days makes this process competitive not only to other cell-based processes but to egg-based processes as well.

Confronting the Upstream Causes of COVID-19 and Other Epidemics to Follow.

The upstream causes of the COVID-19 pandemic have received little attention so far in public health and clinical medicine, as opposed to the downstream effects of mass morbidity and mortality. To resolve this pandemic and to prevent even more severe future pandemics, a focus on upstream causation is essential. Convincing evidence shows that this and every other important viral epidemic emerging in the recent past and predictably into the future comes from the same upstream causes: capitalist agriculture, its destruction of natural habitat, and the industrial production of meat. International and national health organizations have obscured the upstream causes of emerging viral epidemics. These organizations have suffered cutbacks in public funding but have received increased support from international financial institutions and private philanthropies that emphasize the downstream effects rather than upstream causes of infectious diseases. Conflicts of interest also have impacted public health policies. A worldwide shift has begun toward peasant agricultural practices: Research so far has shown that peasant agriculture is safer and more efficient than capitalist industrial agricultural practices. Without such a transformation of agriculture, even more devastating pandemics will result from the same upstream causes.