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 (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.
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Abbreviations
- AAV:
-
Adeno-Associated Virus
- Ab:
-
Antibody
- ABE:
-
Adenine Base Editor
- AD:
-
Alzheimer’s Disease
- AHR:
-
Assisted Human Reproduction
- ALL:
-
Acute Lymphoblastic Leukemia
- ALS:
-
Amyotrophic Lateral Sclerosis
- ATMP:
-
Advanced Therapy Medicinal Product
- ATP:
-
Advanced Therapeutic Product
- bAb:
-
Binding Antibody
- BCMA:
-
B-cell Maturation Antigen
- BioCanRx:
-
Biotherapeutics for Cancer Treatment
- BRDD:
-
Biologic and Radiopharmaceutical Drugs Directorate
- CADTH:
-
Canadian Agency for Drugs and Technologies in Health
- CAR:
-
Chimeric Antigen Receptor
- CBE:
-
Cytosine Base Editor
- CEPA:
-
Canadian Environmental Protection Act
- CGTP:
-
Cell and Gene Therapy Products
- CIHR:
-
Canadian Institutes of Health Research
- CNS:
-
Central Nervous System
- COVID:
-
Coronavirus Disease
- CQA:
-
Critical Quality Attributes
- CRISPR:
-
Clustered Regularly Interspaced Short Palindromic Repeats
- CRS:
-
Cytokine Release Syndrome
- CSA:
-
Canadian Standards Association
- CTA:
-
Clinical Trial Application
- CTD:
-
Common Technical Document
- CTO:
-
Cells, Tissues, and Organs
- CTP:
-
Cell Therapy Product
- DIN:
-
Drug Identification Number
- DMD:
-
Duchenne Muscular Dystrophy
- DSB:
-
Double-Stranded Breaks
- EMA:
-
European Medicines Agency
- eNOS:
-
Endothelial Nitric Oxide Synthase
- F & D:
-
Food and Drugs
- GCP:
-
Good Clinical Practices
- GMP:
-
Good Manufacturing Practices
- GTP:
-
Gene Therapy Product
- GvHD:
-
Graft versus Host Disease
- HD:
-
Huntington’s Disease
- HER2:
-
Epidermal Growth Factor Receptor 2
- HGPS:
-
Hutchinson-Gilford Progeria Syndrome
- HPFB:
-
Health Products and Foods Branch
- hRPE:
-
Human Retinal Pigment Epithelium
- HSC:
-
Hematopoietic Stem Cell
- HTA:
-
Health Technology Assessment
- ICH:
-
International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use
- IMPD:
-
Investigational Medicinal Product Dossier
- INESSS:
-
Institut National d’Excellence en Santé et en Services Sociaux
- IPRP:
-
International Pharmaceutical Regulators Programme
- iPSC:
-
Induced Pluripotent Stem Cell
- KO:
-
Knockouts
- LBCL:
-
Large B-cell Lymphoma
- LCA:
-
Leber Congenital Amaurosis
- LMNA:
-
Lamin A gene
- LNP:
-
Lipid-nanoparticle
- MSC:
-
Mesenchymal Stromal Cell
- nAb:
-
Neutralizing Antibody
- NCE:
-
Networks of Centres of Excellence
- NDS:
-
New Drug Submission
- NHP:
-
Non-Human Primates
- NIH:
-
National Institutes of Health
- NMD:
-
Non-sense-Mediated Decay
- NOC:
-
Notice of Compliance
- NOC/c:
-
Notice of Compliance with Conditions
- NSERC:
-
National Science and Engineering Research Council
- NSNR:
-
New Substances Notification Regulations
- OSE:
-
On-Site Evaluation
- PCR:
-
Polymerase Chain Reaction
- PMDA:
-
Pharmaceuticals and Medical Devices Agency
- QOS:
-
Quality Overall Summary
- R2D2:
-
Regulatory Review of Drugs and Devices
- RAC:
-
Recombinant DNA Advisory Committee
- REB:
-
Research Ethics Board
- SBD:
-
Summary Basis of Decision
- SCD:
-
Sickle Cell Disease
- SCN:
-
Stem Cell Network
- sgRNA:
-
Single-guide Ribonucleic Acid
- siRNA:
-
Small interfering Ribonucleic Acid
- SMA:
-
Spinal Muscular Atrophy
- SMN:
-
Survival Motor Neuron
- SNV:
-
Single Nucleotide Variant
- SPG50:
-
Spastic Paraplegia Type 50
- SSHRC:
-
Social Science and Humanities Research Council
- ssODN:
-
Single-stranded DNA Oligonucleotide
- TAC:
-
T cell Antigen Coupler
- TCR:
-
T cell Receptor
- TIL:
-
Tumor-Infiltrating Lymphocyte
- US:
-
United States
- USP:
-
US Pharmacopeia
- WGS:
-
Whole Genome Sequencing
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Wang, J. et al. (2023). Canadian Regulatory Framework and Regulatory Requirements for Cell and Gene Therapy Products. In: Galli, M.C. (eds) Regulatory Aspects of Gene Therapy and Cell Therapy Products. Advances in Experimental Medicine and Biology, vol 1430. Springer, Cham. https://doi.org/10.1007/978-3-031-34567-8_6
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