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Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2019 31 consider commercialization issues, because strate- gies are planned and implemented from the earli- est stages of development. Production methods for most gene and cell therapies are lengthy, complex, and difficult to expand as production needs rise. Manufacturing and supply chain complexity More traditional therapies, including small mol- ecules and even monoclonal antibodies, generally involve a simpler and more straightforward pro- duction process than gene and cell therapies do. Such processes offer the potential for scalability and opportunities for cost efficiencies through economies of scale. The production methods for most gene and cell therapies, however, are lengthy, complex, and difficult to expand as production needs rise. For example, the manufacture of au- tologous therapies such as chimeric antigen recep- tor T (CAR-T) cells or stem cell therapies requires a process that must be replicated in individualized batches to meet demand at every stage. With allogeneic therapies, the patient-specific nature of production makes it extremely challeng- ing to scale up production. The administration of these therapies also creates challenges that can be affected by decisions in technology and engineer- ing. For autologous treatments, a sample is taken from the patient, sent away for processing and modification (often to a single location regardless of geographic origin), and then dispatched back to a designated treatment center for re-adminis- tration to the patient. This process requires strict traceability and a robust and reliable chain of tem- perature control. Planning for this process can face considerable regulatory hurdles related to licensing, monitoring, and troubleshooting. Production of gene and cell therapies can also require customized technologies and innovations in production that require the active review and contributions of regulators and experienced out- side consultants to achieve target goals in compli- ance with both regulatory standards and costs. In early clinical stages, the feedback from regulators and others on production procedures will typically focus more on safety and issues such as viral banks, raw materials, and serums. At later stages, feed- back tends to focus on the impact of manufactur- ing decisions on a therapy's potency, consistency, and variability. More efficient production platforms The rapid growth in development of gene and cell therapies in recent years means that there are now several examples of pharmaceutical companies developing much more efficient production ca- pabilities for these drugs. For example, Novartis and Kite have created systems that can produce individualized CAR-T cell therapies in 22 and 17 days, respectively (2). ZIOPHARM Oncology is advancing a non-viral platform called the Sleep- ing Beauty system that rapidly produces genetically modified T cells within two days with potential for rapid scalability. The highly customized nature of production, however, can often mean that innova- tions in manufacturing of one therapy may not be easily transferable to others. Considerations in production can also differ within the broad category of gene and cell thera- pies. For example, production of allogeneic thera-