Integrated upstream and midstream processing with scalable pre-configurated single- use assemblies for accelerated commercial reach

The growth of single-use technologies (SUT) has revolutionized the bioprocess industry. The implementation of such technologies was motivated by a substantial reduction in processing time and operational costs compared to their stainless-steel counterparts. Integrated within automated platforms such as the NevoLine™ Upstream, SUT reveal their full potential by offering an increased flexibility and supporting continuous processing. With 100s of different SU configurations the NevoLine platform can accommodate most upstream and midstream processes by integrating four unit-operations in a single manufacturing solution. Cell culture and viral production steps lie in scalable SU bioreactors (SUBs) available in various sizes optimal for process development, as well as clinical and commercial GMP production of viral vaccines, viral vectors for gene therapy and other emerging applications. The SUBs are featured in a range of scale-down automated manufacturing systems that ease scalability. The improved sterility assurance and controls offered by SUT enable predictable batch-to-batch performances and release. The pre-gamma eradiated SU assemblies integrated in Univercells Technologies’ manufacturing systems open the door to ready-to-use solutions reducing installation time and easing sterile continuous processing. This study will demonstrate how the NevoLine Upstream integrated platform relying on SU assemblies can support continuous processing and accelerate commercial reach. It will focus on the following points: Intensified cell growth and viral production in the SU scale-X™ bioreactor with up to 100-times increase in titer compared to traditional technologies with experimental results in various gene therapy and vaccine applications. Bioreactor characterization with scalability demonstration from scale-X hydro 2.4 m² to nitro 200 m² cell growth surface by maintaining fluid flow homogeneity, gradient, and volume to surface ratio across scales. Homogeneity within the fixed-bed will be demonstrated by sampling experiments with confident results. The scalability will be demonstrated by similar cell growth and viral titers per m² of growth surface profiles across scales. Increased process flexibility at commercial scale with the integrated and automated NevoLine Upstream platform adapted to multi-product facilities and variability in production capacity demand. A significant reduction in operational footprint (up to 3-times) enabled by intensified and integrated SU assemblies

A dual platform revolutionizing gene therapy manufacturing

Advanced therapies enable for many indications with no current treatment a significant improvement in quality of life and in some cases a chance at life altogether. The commercialization of those breakthrough therapies rely on manufacturing technologies primary developed for the mAbs industry. Indeed, the commercialization of mAb products was accompanied by technology advances reaching high-capacity and cost-effective processes within integrated and continuous solutions. Nevertheless, in contrast with mAbs where the annual demand (in the US) can be estimated between hundreds of grams to hundreds of kilograms, GT products show an annual demand variability of over 7 logs. Currently used technologies present some limitations in reaching the capacity required by high-demand GT indications resulting in process scale-out and related overall performance decrease. As GT developers often endeavor to target numerous indications, the significant variability in annual demand has pushed them to adopt technologies depending on the types of applications, rather than adopting a single flexible technology. As lessons learn from the mAbs industry the development of a flexible technology accommodating most process requirements adapted to GT products could facilitate viral vector manufacturing while accelerating the availability of advanced therapies at reduced costs. Please click Additional Files below to see the full abstract

The NevoLineTM manufacturing system: Intensification & integration of upstream and downstream processing in a low-footprint, automated platform for viral production

These guidelines have been prepared in the format that should be used for the abstract submission. Authors should replace the text of this template in order to prepare their abstracts. Fonts, sizes and spacing should be used as they are used in this document. Page size is US 8.5 inch x 11 inch, top and bottom margin 0.8 inches, left and right margin 0.8 inches. Body text should be written in Arial, 10 pt, single spacing. The Abstract, in English, should introduce the proposed paper’s subject, summarize its contents, explain any unique aspects, and clearly indicate the specific relevance to the themes of the Conference. Do not sub-divide the text into separate sections. References may be included at the bottom. The world is facing an under-supply of some key vaccines due to poor synergies between growing market demands and aging production models. In this light, we have developed a proof of concept of a vaccine manufacturing platform aiming at increasing availability and affordability of vaccines - the NevoLineTM system. This simulated continuous and automated platform integrates both USP[1] and DSP[2] processes and is encapsulated into an isolator, making it a self-contained production unit (6m²). The technology relies on a single-use, high-density fixed-bed bioreactor operated in perfusion chained with downstream filtration, clarification and polishing steps to (a) decrease batch time, (b) reduce equipment utilization, (c) optimize utilities consumption and (d) intensify operations. By optimizing single-use technologies we are able to drastically reduce CAPEX[3], CoGs[4] and footprint and increase production capacity. Such manufacturing platform can easily be implemented into flexible facilities with simplified infrastructure, increasing adaptability in production and capacity for record time-to-market. This study will present the platform proof of concept on Vero line and trivalent inactivated polio vaccine (sIPV) production, achieving low CoGs (0,28$/dose for a trivalent sIPV) and large capacity. The presentation will feature the description of engineering development, but also results of cell growth, infections and product quality, as well as a description of the CAPEX, CoGS and capacity calculations. This manufacturing platform is undergoing sIPV process scale-up and pre-clinical bulk production. The NevoLine system is expected to produce any type of viral vaccine at a very low cost and large capacities to face global health challenges. [1] Upstream [2] Downstream [3] Capital expenditure [4] Cost of good

A rapid response vaccine manufacturing platform as a countermeasure to epidemic threats

The preparedness and rapid response to emerging infectious diseases outbreaks remains challenging due to limited market incentives. The development and manufacturing of vaccines are today facing bottlenecks in development time as well as in cost-effectiveness in order to be able to react rapidly and deliver low-cost, high-quality vaccines. Please click Download on the upper right corner to see the full abstract

Integrated & continuous processing: A proven solution to tackle gene therapy manufacturing challenges

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Biomanufacturing technology advances enable rapid response to disease outbreaks

Outbreaks can have devastating socio-economic and mental health impacts if the spread of disease is not stopped. Particularly in the case of COVID-19 which has claimed thousands of lives across the globe, the importance of rapid response to disease outbreaks is paramount. In the past, response to pandemics was following very long licensing and development timeframes, whereas in the case of COVID-19 the response was immediate while approval and manufacturing timeframes were much shorter. The global COVID-19 pandemic has highlighted the important role that scalable and flexible manufacturing solutions play in enabling rapid response to new disease outbreaks. In this unprecedent situation the industry joined forces and accelerated the development of new vaccine candidates to rapidly respond to the pandemic. Following this the next hurdle was to ensure that scaling up the production capacity to respond to the global immunization demand was feasible. Indeed, manufacturing capacity often acts as a bottleneck in rapid development programs. Traditional manufacturing processes are highly complex, require extensive process development efforts, and tend to suffer from a lack of scalability to rapidly reach commercial scale capacity. Considering the short timelines, vaccines are developed and scale-up at risk, with companies deploying manufacturing facilities at very early stage. Therefore, it is important that manufacturers can rapidly adapt their existing equipment and facilities for alternative drug candidates. This requires manufacturers to have facilities and equipment that are truly flexible and can be adapted for different drug candidates and processes. Please click Download on the upper right corner to see the full abstract

A roadmap to successful commercialization of autologous CAR T-cell products with centralized and bedside manufacture

The availability of two CAR T-cell therapies on the market has cemented the therapeutic potential of these products to treat oncology patients. However, in order for CAR T-cell therapies to be available to a wide number of patients, cell therapy developers must carefully design their manufacturing and commercialisation strategy. This analysis must take into account multiple factors related to the target market characteristics (EU v USA), the product features (e.g. dose size), manufacturing process (e.g. automated v manual platforms) as well as facility network (e.g. centralised v bedside manufacture) and supply chain requirements (e.g. fresh v frozen products). This presentation aims at assessing the implications of the choices made for each of these critical factors to provide a clear framework for decision-making during early stages of the development process of autologous CAR T-cell products. The resulting roadmap enables the successful commercialisation of these powerful therapeutics. This analysis was carried out using an advanced decisional tool developed at University College London. The case study assesses the economic and operational effects of the decisions made at the different levels of manufacturing and commercialisation strategy by computing metrics such as cost of goods, fixed capital investment, net present value, personnel requirement and facility footprint, while considering potential constraints relating to technology capacity, viral vector stock availability, product shelf life, market access and reimbursement strategies. Cost of goods (COG), net present value, process economics, supply chain, reimbursement, centralised, decentralised, bedside, GMP-in-a-box, market acces

Uma revisão bibliográfica do tipo scopping/mapping sobre a Agricultura Urbana e Periurbana

The world is undergoing an accelerated urbanization process marked by social and environmental imbalances. In this context, urban and periurban agriculture (UPA) emerges as an alternative to sustainable urbanization mainly due to its contribution to food security, reduction of environmental impact, revitalization of urban areas, integration of households and physical and psychological well-being increasing. The purpose of this paper is to understand how academic literature deals with urban and periurban agriculture. For that, a scoping / mapping literature review was carried out and its results were presented after identification of relevant scientific studies on UPA, its main aspects, ways in which the term has been defined; and discussion about themes from the selected articles. After this review, the conclusions are: the scientific production on the subject is undergoing high growth rates in recent years; the relationship between UPA and urban dynamics is more important for the definition of UPA than the location of agriculture; and that the aspects that authors found most interesting are: concept and panorama, urban planning and governance, quantitative potential, environment, risk of contamination and techniques and productivity.O mundo passa por um acelerado processo de urbanização marcado por desequilíbrios sociais e ambientais. Nesse contexto, a agricultura urbana e periurbana (AUP) surge como uma alternativa para a urbanização sustentável devido, principalmente, à sua contribuição para o aumento da segurança alimentar, redução de impacto ambiental, revitalização de áreas urbanas, “desalienação” dos moradores e aumento do bem-estar físico e psicológico . O objetivo deste artigo é compreender como a literatura acadêmica trata o tema agricultura urbana e periurbana. Para tanto, foi realizada uma revisão bibliográfica do tipo scoping/mapping) e seus resultados foram apresentados a partir da identificação de trabalhos científicos relevantes sobre AUP, principais aspectos, formas como o termo vem sendo definido; discussão sobre os artigos selecionados. Após a revisão, conclui-se que a produção cientifica sobre o tema apresenta alto crescimento nos últimos anos, que na definição da AUP, mais importante do que a localização da agricultura é a sua relação com a dinâmica urbana e que os aspectos de mais interesse dos autores são: conceito e panorama, planejamento urbano e governança, potencial quantitativo, meio ambiente, risco de contaminação e técnicas e produtividade

Social Impact Bonds: a Review of their Strengths and Weaknesses.

This article analyses social impact bonds as an innovative instrument to finance projects in the social or environmental fields. These are instruments that require the collaboration of different stakeholders (multi-stakeholder approach), which may generate a new approach to social or environmental problems. When successful, they could save resources for States. They attract private capital to finance societal projects, allowing them, simultaneously, competitive remuneration and an effective impact. Since their remuneration/reimbursement is based on outcomes, there is a risk transfer (at least partially) from the public sector to the private sector. However, difficulties in articulation between the different participants and in the correct measurement of results/outcomes may limit the scope (size and timeframe) of the projects involved, as well as distract NGOs from their mission. Due to the growing importance of Social and Sustainable Finance in financial markets and public policies, the detailed study of these new instruments is highly recommended