Clinical Evaluation Division - Oncology/Radiopharmaceuticals, Centre for Oncology, Radiopharmaceuticals and Research, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada.
Centre for Policy, Pediatrics and International Collaboration, Biologic and Radiopharmaceutical Drugs Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada.
Adv Exp Med Biol. 2023;1430:91-116. doi: 10.1007/978-3-031-34567-8_6.
Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations. Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. The manufacture and clinical testing of cell and gene therapy products (CGTP) presents many challenges beyond those for protein biologics. Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation. Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding. In addition, for many CGTP, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients. Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types. Regulatory cooperation and harmonization at an international level are essential for progress in the development and commercialization of these products. However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking. This chapter is dedicated to provide an overview of Health Canada regulatory oversight of CGTP.
加拿大卫生部根据《加拿大食品药品法》及其附属法规，将基因治疗产品和许多细胞治疗产品作为生物药物进行监管。符合某些标准的细胞产品，包括最小程度的操作和同源使用，可能会根据《人类细胞、组织和器官用于移植的安全法规》采用基于标准的方法。细胞和基因治疗产品（CGTP）的制造和临床测试提出了许多超出蛋白质生物药物的挑战。细胞不能进行病原体去除或失活程序，并且必须在最终配方后不久经常给药。病毒载体设计和制造控制对于整体产品质量至关重要，并通过复制能力、载体整合和载体脱落等问题与患者的安全性和疗效相关。此外，对于许多 CGTP，非临床研究的价值在很大程度上仅限于提供概念验证，并且与适当剂量、安全性参数以及疗效替代或真实决定因素的有效性相关的第一个有意义的数据必须来自患者精心设计的临床试验。应对这些众多挑战需要应用各种风险缓解策略，并满足专门针对产品类型的监管期望。在这些产品的开发和商业化方面，国际层面的监管合作和协调至关重要。然而，特别是在细胞治疗领域，可能需要新的监管模式，以便在缺乏追求典型药物产品批准途径的资源和动力的情况下，从临床进展中获益。本章旨在概述加拿大卫生部对 CGTP 的监管监督。
