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www.biopharminternational.com Emerging Therapies 2022 eBook BioPharm International ® 7 Development e t h a nol , a h i g h ly f l a m m a ble s ubs t a nce. M a n- u fac t u rers w i l l need to h ave t he capabi l it ies to ensure the safe use of these materials or use an ex- perienced contract development and manufactur- ing organization. Additionally, the lipids currently in use were developed for small interfering thera- pies. Investing in the development of better lipid nanoparticle formulations or alternative deliver y technologies that improve conditions required for storage stability could have a significant impact on the delivery of mRNA therapeutics. Currently approved mRNA vaccines have a degree of temperature sensitivity, and cold chain logistics are required to deliver these life-saving therapeu- tics around the world. There is ample room for im- provement here, and researchers can assess different formulation technologies to achieve better stability (and already are). The future promise of personalized medicine One approach to cancer immunotherapy involves the use of personalized vaccines designed specifically for individual patient's tumors. The speed and flexibility of the mRNA platform make this a promising technol- ogy for personalized therapies. As the population is one patient, the manufacturing is a small batch. This is an area where we can expect to see future innovation that will intensify and collapse the workflow into micro-fac- tories, efficiently producing one product to one patient. Though the manufacturing processes can be similar for personalized medicine, individual small-batch scales will have some different manufacturing re- quirements. Large population vaccines are usually large-scale manufacturing, but those targeting a smaller patient population will most likely need a flex- ible manufacturing line, which can handle multiple products and offer the ability to scale out if needed. With the scope of such a wide range of scales, it's im- portant to recognize that this broad spectrum of ap- plications and their needs will have an impact on the manufacturing strategy adopted. Despite the challenges, mRNA therapeutics—more than any other drug modality—have the potential to go from mass population therapies, like the pandemic response, to truly personalized vaccines based on the ge- nome of a given patient. While this brings a spectrum of risks and initially high costs, this could transform the way chronic diseases are treated. If small batches are needed for personalized medi- cine as opposed to research, then traceability becomes a major concern. Hence, the needs of medicine makers become more focused on quality control (QC), patient tracking, and automating the process to control as much as possible. In small-batch manufacturing, the cost of goods will be a hurdle for many manufacturers. mAb ~5 nm Adeno- associated virus (AAV) ~25 nm Adenovirus ~90 nm Plasmid 100–300 nm Exosome (EV) 30–200 nm Enveloped virus (lentivirus) Enveloped virus (other) 80–120 nm 80–450 nm Lipid nanoparticle (LNP) 50–1000 nm mRNA 20–40 nm Option 2D FIGURE 1. Approximate sizes of a range of molecules used in therapeutic development. The elements of process, facility, resources, and infrastructure are integrated and influence each other. FIGURE COURTESY OF THE AUTHOR.