Decentralised manufacturing of cell and gene therapies

Decentralised manufacturing of cell and gene therapie

Enhancing cell and gene therapy manufacture through the application of advanced fluorescent optical sensors

Cell and gene therapies (CGTs) are examples of future therapeutics that can be used to cure or alleviate the symptoms of disease, by repairing damaged tissue or reprogramming defective genetic information. However, despite the recent advancements in clinical trial outcomes, the path to wide-scale adoption of CGTs remains challenging, such that the emergence of a “blockbuster” therapy has so far proved elusive. Manufacturing solutions for these therapies require the application of scalable and replicable cell manufacturing techniques, which differ markedly from the existing pharmaceutical incumbent. Attempts to adopt this pharmaceutical model for CGT manufacture have largely proved unsuccessful. The most significant challenges facing CGT manufacturing are process analytical testing and quality control. These procedures would greatly benefit from improved sensory technologies that allow direct measurement of critical quality attributes, such as pH, oxygen, lactate and glucose. In turn, this would make manufacturing more robust, replicable and standardized. In this review, the present-day state and prospects of CGT manufacturing are discussed. In particular, the authors highlight the role of fluorescent optical sensors, focusing on their strengths and weaknesses, for CGT manufacture. The review concludes by discussing how the integration of CGT manufacture and fluorescent optical sensors could augment future bioprocessing approaches

Automating decentralized manufacturing of cell and gene therapy products.

Decentralized, or redistributed manufacture, is likely to be the manufacturing approach of choice for some cell- and gene-based therapies, in particular, personalized therapies. Such an approach will ultimately depend on the business model and will take into account the regulatory and supply chain factors. Advances in technology and integration of automated production platforms have demonstrated the potential for decentralized manufacturing, however there is a need to extend the scope of automation across the entire process including the cell isolation, distribution, tracking, administration, quality management systems and development of automated analytical techniques to facilitate real-time release. For decentralized manufacture to be successfully integrated for cell and gene therapy production, lessons from other accepted healthcare-associated models of manufacture can provide useful insights and perspectives to make informed decisions. Such models share similar characteristics to decentralized manufacture in that they are patient-specific and have a limited time-frame for administration. These existing approaches, which have successfully incorporated aspects of automation, can provide a blueprint for success and may expedite the decentralization of patient-specific cell and gene therapy manufacture

Informed decision-making for decentralised manufacturing of cell and gene therapies

Informed decision-making for decentralised manufacturing of cell and gene therapie

Decentralized manufacturing of cell and gene therapies: Overcoming challenges and identifying opportunities

Decentralized or “redistributed” manufacturing has the potential to revolutionize the manufacturing approach for cell and gene therapies (CGTs), moving away from the “Fordist” paradigm, delivering health care locally, customized to the end user and, by its very nature, overcoming many of the challenges associated with manufacturing and distribution of high volume goods. In departing from the traditional centralized model of manufacturing, decentralized manufacturing divides production across sites or geographic regions. This paradigm shift imposes significant structural and organisational changes on a business presenting both hidden challenges that must be addressed and opportunities to be embraced. By profoundly adapting business practices, significant advantages can be realized through a democratized value chain, creation of professional-level jobs without geographic restriction to the central hub and a flexibility in response to external pressures and demands. To realize these potential opportunities, however, advances in manufacturing technology and support systems are required, as well as significant changes in the way CGTs are regulated to facilitate multi-site manufacturing. Decentralized manufacturing is likely to be the manufacturing platform of choice for advanced health care therapies—in particular, those with a high degree of personalization. The future success of these promising products will be enhanced by adopting sound business strategies early in development. To realize the benefits that decentralized manufacturing of CGTs has to offer, it is important to examine both the risks and the substantial opportunities present. In this research, we examine both the challenges and the opportunities this shift in business strategy represents in an effort to maximize the success of adoption

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

Decentralised manufacturing of cell and gene therapy products: learning from other healthcare sectors

Decentralised or 'redistributed' manufacturing represents an attractive choice for production of some cell and gene therapies (CGTs), in particular personalised therapies. Decentralised manufacturing splits production into various locations or regions and in doing so, imposes organisational changes on the structure of a company. This confers a significant advantage by democratising supply, creating jobs without geographical restriction to the central hub and allowing a more flexible response to external pressures and demands. This comes with challenges that need to be addressed including, a reduction in oversight, decision making and control by central management which can be critical in maintaining quality in healthcare product manufacturing. The unwitting adoption of poor business strategies at an early stage in development has the potential to undermine the market success of otherwise promising products. To maximise the probability of realising the benefits that decentralised manufacturing of CGTs has to offer, it is important to examine alternative operational paradigms to learn from their successes and to avoid their failures. Whilst no other situation is quite the same as CGTs, some illustrative examples of established manufacturing paradigms are described. Each of these shares a unique attribute with CGTs which aids understanding of how decentralised manufacturing might be implemented for CGTs in a similar manner. In this paper we present a collection of paradigms that can be drawn on in formulating a roadmap to success for decentralised production of CGTs

Corrosion of magnesium and magnesium–calcium alloy in biologically-simulated environment

A study of biocompatibility and corrosion of both metallic magnesium (Mg) and a magnesium alloy containing 1% calcium (Mg-Ca) were investigated in in vitro culture conditions with and without the presence of bone marrow derived human mesenchymal stem cells (hMSCs). Chemical analysis of the degraded samples was performed using XRD and FEGSEM. The results from the XRD analysis strongly suggested that crystalline phase of magnesium carbonate was present on the surface of both the Mg and Mg-Ca samples. Flame absorption spectrometry was used to analyse the release of magnesium and calcium ions into the cell culture medium. Magnesium concentration was kept consistently at a level ranging from 40 to 80. mM for both Mg and Mg-Ca samples. No cell growth was observed when in direct contact with the metals apart from a few cells observed at the bottom of culture plate containing Mg-Ca alloy. In general, in vitro study of corrosion of Mg-Ca in a biologically-simulated environment using cell culture medium with the presence of hMSCs demonstrated close resemblances to in vivo corrosion. Although in vitro corrosion of Mg-Ca revealed slow corrosion rate and no immediate cytotoxicity effects to hMSCs, its corrosion rate was still too high to achieve normal stem cell growth when cells and alloys were cultured in vitro in direct contact

Approaches and challenges for the manufacture and scale-out of autologous cell therapies

Approaches and challenges for the manufacture and scale-out of autologous cell therapie

Advancing Tissue and Regenerative Engineering in UK Medicine (ATREUM) abstracts booklet

Advancing Tissue and Regenerative Engineering in UK Medicine (ATREUM) abstracts bookle