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Pharmaceutical Technology Europe BIO/PHARMA OUTSOURCING INNOVATION eBOOK 2022 29 With gradual innovations, mRNA began to be considered a safe and efficient therapeutic tool in vaccine development. However, it was not until recently, with the onset of the COVID-19 pandemic, that the mRNA vaccine field quickly expanded. The need for a rapid response drove the swift adoption of these new technologies in vaccine and treat- ment development. CDMOs were increasingly becoming more heavily relied upon to support the development and manufacturing of these new drug technologies. This necessitated CDMOs to rapidly prepare for improvements to accommodate mRNA manufacturing and overcome any challenges they faced in an unprecedented amount of time. Adapting existing capabilities quickly. With an upsurge in demand for this new wave of technolog y, manufactur- ers needed to make necessary changes to their facilities and processes for them to be optimized to the product characteristics. Cold chain capabilities had to be expanded and opti- mized to suit the temperature-sensitive nature of mRNA molecules. This has been achieved by investing in different types of capabilities, from blast rate freezers to control rate freezers, and offering a wide range of container storage types to best fit the needs of the product. The necessary standard operating procedures (SOPs) have also had to be put in place for each new storage capability. The lipid nanoparticles used to encapsulate the mRNA were also unfamiliar to many manufacturers that predom- inantly worked with water-like solutions. Time was needed to determine how the nanoparticles would behave and how processing conditions could impact the characteristics of the mRNA products. Balancing new and existing projects. Not only did CDMOs need to accommodate a nd suppor t COVID-19-based projects, including vaccines, but t hey a lso needed to maintain the production of other medications requiring similar facilities. Ensuring sufficient capacity was, there- fore, one of the greatest challenges to CDMOs during the COVID-19 pandemic. Careful management was needed to avoid delays due to bottleneck processes and ensure sufficient capacity for the increased level of demand. Balancing these require- ments also necessitated both f lexibility and scalability to successfully support the development of a wide variety of essential products. Accelerating speed to market was essential. Speed was essen- tial in the delivery of products to patients in a short time frame, especially during the COVID-19 pandemic, and presented another challenge to manufacturers. To facilitate speed to market, regulatory approaches to accelerate the availability of vaccines and treatments were heavily relied upon. These included the US Food and Drug Adminis- tration's Emergency Use Authorization (2) and Priority Review (3) approaches and emergency conditional market authorization in the European Union (4). To successfully shorten timelines and meet capacity demand, CDMOs needed to expand facilities to of fer improved scalability and increase efficiency of existing processes. This required all aspects of development and manufacturing to be highly optimized. Throughout this process, the high quality had to be balanced with deliver- ing at an unprecedented speed. Managing supply chains to avoid disruptions. Manufactur- ers had to also ensure they maintained a reliable supply of raw materials and consumables. Many projects, both COVID-related and not, relied on much of the same equip- ment, processes, and raw materials. However, with the onset of the COVID-19 pandemic, biomanufacturers were waiting up to a year for supplies and equipment. Despite vendors responding to increased demand by expanding capacity, projects still took months to come online (5). Essential materials for making vaccines were in short supply—exposing how the supply chain is reliant on only a handful of countries, and even companies when it came to the sterile bags used for cell cultivation in bioreactors (6). Despite the rise of globalized supply chains in the past de- cade, the COVID-19 pandemic has highlighted the need to proactively monitor and quickly react to potential delays. Manufacturers had to identify several potential sources of equipment and consumables to have alternative options in the event of delays from their primary source. Identi- fying alternative suppliers close to the production facility for localization of materials helped to minimize risks as- sociated with delays. Additional time also had to be taken to ensure that the alternative equipment and consumables identified were suitable and optimized for the manufac- turing needs. The potential of mRNA The growing interest in mRNA technology is in part because of its ability to be easily edited, providing the potential for it to be used in the treatment of countless possible diseases. In this way, mRNA technologies have the ability to be used as a "plug-and-play" platform, offering unprecedented versa- tility. Recent advances in mRNA vaccine technologies have further improved translatability. Carriers have also been developed to prolong antigen expression in vivo, further increasing its potential. The pandemic has highlighted that foresight, careful preparation, and agility continue to be essential traits for CDMOs. Contin. on page 31