A shared scalable suspension platform for cost effective manufacture of novel AAV gene therapies

“基因治疗药物产品（GTMPs）的快速发展需要新的制造工艺和设施。Gyroscope Therapeutics有限公司和Freeline Therapeutics有限公司是总部位于英国的中小企业，开发针对不同适应症的基因疗法，但都是通过腺相关病毒（AAV）载体传递的。Gyroscope和Freeline打算共同开发一种创新的、基于悬浮的病毒载体制造工艺，这将为两家公司的GTMP产品制造提供一个共享平台。基因疗法商业化面临的主要挑战是产品的商业规模生产和供应。陀螺仪和Freeline将开发一个专有的、无血清的、可扩展的、基于悬浮的制造平台，这将提高产品质量、安全性、稳健性，并在商业规模上降低产品成本。与临床生物技术中心（CBC）和工艺创新中心（CPI）、陀螺仪和Freeline等伙伴组织的工艺开发专家合作，将：1 .建立降低质粒起始物料遗传不稳定风险的综合方法；2 .建立专有的无动物成分和“化学定义”悬浮细胞培养制造工艺，该工艺可扩展，在最大限度地提高安全性、质量和产量的同时，最大限度地减少产品异质性；提供材料批次，以确认使用悬浮平台材料生产的产品与当前贴壁细胞培养平台生产的产品的可比性，从而使工艺变更得以实施4。生成数据，以促进以代表性规模将已开发的工艺技术转移到GMP生产设施，以便随后确认为GMP生产工艺。最终，一个成功的结果将解决gtmp面临的重大制造挑战，加强英国在科学创新方面的领导地位，为英国制药制造业提供投资和就业机会，并为患者带来医疗保健福利。”

"The rapid development of Gene Therapy Medicinal Products (GTMPs) requires new manufacturing processes and facilities. Gyroscope Therapeutics Ltd and Freeline Therapeutics Ltd are UK-based SMEs developing gene therapies for different indications but which are both delivered via adeno-associated viral (AAV) vectors. Gyroscope and Freeline intend to co-develop an innovative, suspension-based viral vector manufacturing process, which will provide a shared platform for the manufacture of each company's GTMP products. The major challenge facing commercialisation of gene therapies is the manufacture and supply of products at a commercial scale. Gyroscope and Freeline will develop a proprietary, serum-free, scalable, suspension based manufacturing platform, which will improve product quality, safety, robustness and reduce the costs of goods at commercial scale. Working together with process development specialists at partner organisations the Centre for Clinical Biotechnology (CBC) and the Centre for Process Innovation (CPI), Gyroscope and Freeline will:1. Establish ways to reduce risk of genetic instability of plasmid starting materials in an integrated approach;2. Establish a proprietary animal component free and 'chemically defined' suspension cell culture manufacturing process which is scalable and which minimises product heterogeneity while maximising safety, quality and yield;3. Supply batches of material to confirm comparability of product made using suspension platform material to that produced by current adherent cell culture platforms and so enable process changes to be implemented4. Generate data to facilitate technology transfer of the developed process at a representative scale to GMP manufacturing facilities for subsequent qualification as a GMP manufacturing process.Ultimately, a successful outcome will address a significant manufacturing challenge for GTMPs, strengthen the UK position as a leader in scientific innovation, offer scope for investment and employment into UK Pharmaceutical manufacturing and bring healthcare benefits to patients."