title: Regulatory Oversight of Cell and Gene Therapy Products in Canada.
abstract: 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 (CGTPs) 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 CGTPs, 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 harmonisation at an international level are essential for progress in the development and commercialisation 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.
authors.affiliation: Centre for Evaluation of the Radiopharmaceuticals and Biotherapeutics, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Health Canada, 100 Eglantine Driveway, A/L 0603C, Ottawa, ON, Canada, K1A0K9. anthony.ridgway@hc-sc.gc.ca.
authors.forename: Anthony
authors.initials: A
authors.lastname: Ridgway
authors.affiliation: Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Health Canada, 100 Eglantine Driveway, A/L 0603C, Ottawa, ON, Canada, K1A0K9.
authors.forename: Francisca
authors.initials: F
authors.lastname: Agbanyo
authors.affiliation: Clinical Evaluation Division - Haematology/Oncology, Centre for Evaluation of Radiopharmaceuticals and Biotherapeutics, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Health Canada, 100 Eglantine Driveway, A/L 0603C, Ottawa, ON, Canada, K1A0K9.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Stem Cell Research Lab, Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Health Canada, 251 Sir Frederick Banting Driveway, A/L 2201E, Ottawa, ON, Canada, K1A0K9.
authors.forename: Michael
authors.initials: M
authors.lastname: Rosu-Myles
mesh_terms: D000818:Animals; D001688:Biological Products / Q000627:therapeutic use; D002170:Canada; D064987:Cell- and Tissue-Based Therapy / Q000941:ethics* / Q000379:methods; D004274:DNA, Recombinant / Q000627:therapeutic use; D017277:Drug Approval; D004335:Drug and Narcotic Control / Q000331:legislation & jurisprudence*; D015316:Genetic Therapy / Q000941:ethics / Q000331:legislation & jurisprudence*; D005822:Genetic Vectors / Q000627:therapeutic use; D006801:Humans; D061214:Patient Safety / Q000331:legislation & jurisprudence; D017410:Practice Guidelines as Topic; D012107:Research Design; D057170:Translational Research, Biomedical / Q000941:ethics / Q000331:legislation & jurisprudence*; D054928:Validation Studies as Topic
chemical_list: D001688:Biological Products; D004274:DNA, Recombinant
keywords: CTO Regulations; Health Canada; More than minimally manipulated; Regulation of cell therapy; Regulation of gene therapy; Safety of Human Cells, Tissues and Organs for Transplantation Regulations