Emerging technologies & companies in cell & gene therapy manufacturing

Abstract

Cell and gene therapy (CGT) offers the potential of new curative treatments for patients in great medical need in oncology, inheritable diseases, immune conditions, and other therapeutic areas. This rapid transformative development of the therapeutic armamentarium must be accompanied by effective manufacturing to deliver these sophisticated therapies to patients diligently at scale. As this new industry grows, we identify innovations that could structure its transformation. Approved CGT products, which at the moment collectively benefit a few thousand patients annually, are produced using costly, inefficient, largely manual and often not fit-for-purposes processes primarily inherited from the manufacture of structurally simpler biologics. There is also much room for improvement in analytical methods. New techniques are emerging to make nucleic acids, vectorize them into viruses or non-viral vehicles, and transfer them into cells inside or outside the patient’s body. Together, they could generate better-defined biochemical entities and thus more precise medicine while reducing costs and time to market. This would result in lower doses, reduced toxicities, higher efficacy, improved accessibility and, ultimately, greater clinical impact. The ability to personalize treatments and the shape of the production infrastructure are also likely to be transformed as manufacturing processes designed specifically for CGT are rolled out. Developing these new techniques are a small set of large multinational companies now joined by a cohort of about a hundred start-ups and small and medium-sized enterprises (SMEs) listed in Table 1– who are seeking to improve every step of CGT manufacturing processes by repurposing methods developed for other applications or by leveraging bespoke innovations in biology, engineering, physics, chemistry, and data science. These innovations include new nucleic acid formats and viral biosynthesis methods, non-viral gene therapy ‘printers’, cell therapy ‘GMP boxes’, microfluidics or encapsulation-based cell culture, in vivo cell therapy, non-chromatographic separations, advanced GMP cell sorting and new optical methods for nanoscale analytics. In the next few years, as an industry, we will need to produce thousands of drug candidates for clinical trials and, hopefully, dozens of new drugs at vastly increased scale. This will require important process improvements in both quality and productivity. The product is the process: we must continue to improve both.