An approach to rapid distributed manufacturing of broad spectrum anti-viral griffithsin using cell-free systems to mitigate pandemics.

This study describes the cell-free biomanufacturing of a broad-spectrum antiviral protein, griffithsin (GRFT) such that it can be produced in microgram quantities with consistent purity and potency in less than 24 h. We demonstrate GRFT production using two independent cell-free systems, one plant and one microbial. Griffithsin purity and quality were verified using standard regulatory metrics. Efficacy was demonstrated in vitro against SARS-CoV-2 and HIV-1 and was nearly identical to that of GRFT expressed in vivo. The proposed production process is efficient and can be readily scaled up and deployed wherever a viral pathogen might emerge. The current emergence of viral variants of SARS-CoV-2 has resulted in frequent updating of existing vaccines and loss of efficacy for front-line monoclonal antibody therapies. Proteins such as GRFT with its efficacious and broad virus neutralizing capability provide a compelling pandemic mitigation strategy to promptly suppress viral emergence at the source of an outbreak.

Manufacturing a chimpanzee adenovirus-vectored SARS-CoV-2 vaccine to meet global needs.

Manufacturing has been the key factor limiting rollout of vaccination during the COVID-19 pandemic, requiring rapid development and large-scale implementation of novel manufacturing technologies. ChAdOx1 nCoV-19 (AZD1222, Vaxzevria) is an efficacious vaccine against SARS-CoV-2, based upon an adenovirus vector. We describe the development of a process for the production of this vaccine and others based upon the same platform, including novel features to facilitate very large-scale production. We discuss the process economics and the "distributed manufacturing" approach we have taken to provide the vaccine at globally-relevant scale and with international security of supply. Together, these approaches have enabled the largest viral vector manufacturing campaign to date, providing a substantial proportion of global COVID-19 vaccine supply at low cost.

Build a Sustainable Vaccines Industry with Synthetic Biology.

The vaccines industry has not changed appreciably in decades regarding technology, and has struggled to remain viable, with large companies withdrawing from production. Meanwhile, there has been no let-up in outbreaks of viral disease, at a time when the biopharmaceuticals industry is discussing downsizing. The distributed manufacturing model aligns well with this, and the advent of synthetic biology promises much in terms of vaccine design. Biofoundries separate design from manufacturing, a hallmark of modern engineering. Once designed in a biofoundry, digital code can be transferred to a small-scale manufacturing facility close to the point of care, rather than physically transferring cold-chain-dependent vaccine. Thus, biofoundries and distributed manufacturing have the potential to open up a new era of biomanufacturing, one based on digital biology and information systems. This seems a better model for tackling future outbreaks and pandemics.

Community-driven PPE production using additive manufacturing during the COVID-19 pandemic: Survey and lessons learned.

This study presents a detailed analysis of the production efforts for personal protective equipment in makerspaces and informal production spaces (i.e., community-driven efforts) in response to the COVID-19 pandemic in the United States. The focus of this study is on additive manufacturing (also known as 3D printing), which was the dominant manufacturing method employed in these production efforts. Production details from a variety of informal production efforts were systematically analyzed to quantify the scale and efficiency of different efforts. Data for this analysis was primarily drawn from detailed survey data from 74 individuals who participated in these different production efforts, as well as from a systematic review of 145 publicly available news stories. This rich dataset enables a comprehensive summary of the community-driven production efforts, with detailed and quantitative comparisons of different efforts. In this study, factors that influenced production efficiency and success were investigated, including choice of PPE designs, production logistics, and additive manufacturing processes employed by makerspaces and universities. From this investigation, several themes emerged including challenges associated with matching production rates to demand, production methods with vastly different production rates, inefficient production due to slow build times and high scrap rates, and difficulty obtaining necessary feedstocks. Despite these challenges, nearly every maker involved in these production efforts categorized their response as successful. Lessons learned and themes derived from this systematic study of these results are compiled and presented to help inform better practices for future community-driven use of additive manufacturing, especially in response to emergencies.

Application of 3D printing and distributed manufacturing during the first-wave of COVID-19 pandemic. Our experience at a third-level university hospital.

BACKGROUND: 3D printing and distributed manufacturing represent a paradigm shift in the health system that is becoming critical during the COVID-19 pandemic. University hospitals are also taking on the role of manufacturers of custom-made solutions thanks to 3D printing technology. CASE PRESENTATION: We present a monocentric observational case study regarding the distributed manufacturing of three groups of products during the period of the COVID-19 pandemic from 14 March to 10 May 2020: personal protective equipment, ventilatory support, and diagnostic and consumable products. Networking during this period has enabled the delivery of a total of 17,276 units of products manufactured using 3D printing technology. The most manufactured product was the face shields and ear savers, while the one that achieved the greatest clinical impact was the mechanical ventilation adapters and swabs. The products were manufactured by individuals in 57.3% of the cases, and our hospital acted as the main delivery node in a hub with 10 other hospitals. The main advantage of this production model is the fast response to stock needs, being able to adapt almost in real time. CONCLUSIONS: The role of 3D printing in the hospital environment allows the reconciliation of in-house and distributed manufacturing with traditional production, providing custom-made adaptation of the specifications, as well as maximum efficiency in the working and availability of resources, which is of special importance at critical times for health systems such as the current COVID-19 pandemic.

Rapid development and deployment of high-volume vaccines for pandemic response.

Overcoming pandemics, such as the current Covid-19 outbreak, requires the manufacture of several billion doses of vaccines within months. This is an extremely challenging task given the constraints in small-scale manufacturing for clinical trials, clinical testing timelines involving multiple phases and large-scale drug substance and drug product manufacturing. To tackle these challenges, regulatory processes are fast-tracked, and rapid-response manufacturing platform technologies are used. Here, we evaluate the current progress, challenges ahead and potential solutions for providing vaccines for pandemic response at an unprecedented scale and rate. Emerging rapid-response vaccine platform technologies, especially RNA platforms, offer a high productivity estimated at over 1 billion doses per year with a small manufacturing footprint and low capital cost facilities. The self-amplifying RNA (saRNA) drug product cost is estimated at below 1 USD/dose. These manufacturing processes and facilities can be decentralized to facilitate production, distribution, but also raw material supply. The RNA platform technology can be complemented by an a priori Quality by Design analysis aided by computational modeling in order to assure product quality and further speed up the regulatory approval processes when these platforms are used for epidemic or pandemic response in the future.

Exploration of alternative supply chains and distributed manufacturing in response to COVID-19; a case study of medical face shields.

Quarantine conditions arising as a result of the coronavirus (COVID-19) have had a significant impact on global production-rates and supply chains. This has coincided with increased demands for medical and personal protective equipment such as face shields. Shortages have been particularly prevalent in western countries which typically rely upon global supply chains to obtain these types of device from low-cost economies. National calls for the repurposing of domestic mass-production facilities have the potential to meet medical requirements in coming weeks, however the immediate demand associated with the virus has led to the mobilisation of a diverse distributed workforce. Selection of appropriate manufacturing processes and underused supply chains is paramount to the success of these operations. A simplified medical face shield design is presented which repurposes an assortment of existing alternative supply chains. The device is easy to produce with minimal equipment and training. It is hoped that the methodology and approach presented is of use to the wider community at this critical time.