Abstract
We provide an overview of the regulatory framework, pathways and underlying regulatory
authority for cell, gene and tissue-engineered therapies in Canada. Canada's regulatory
approach uses three sets of regulations, namely, the Cells, Tissues and Organs Regulations,
the Food and Drug Regulations and the Medical Devices Regulations. We provide an overview
of each these sets of regulations as they apply to clinical investigation to post-market
product lifecycle stages. Information is provided on the current sources of relevant
Health Canada guidance documents. We highlight several regional success stories including
Prochymal, a cell therapy product that achieved Canadian regulatory approval using
the conditional marketing approval system. We also examine the perceived gaps in the
Canadian regulations and how those gaps are being addressed by interactions between
the government, stakeholders and international bodies. We conclude that the risk-benefit
approach used by Health Canada for regulatory approval processes is sufficiently flexible
to enable to development of novel cell and gene therapy products in Canada, yet stringent
enough to protect patient safety.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to CytotherapyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells.Nature. 1963; 197: 452-454
United States National Institutes of Health. https://clinicaltrials.gov/. [Accessed April 4, 2019].
- Food and Drugs Act (R.S.C., 1985, c. F-27).Minister of Justice: Department of Justice, Ottawa2016
- Food and Drug Regulations (C.R.C., c. 870).Minister of Justice: Department of Justice, Ottawa2016
- Medical Devices Regulations (SOR/98-282).Minister of Justice: Department of Justice, Ottawa2016
- Safety of Human Cells, Tissues and Organs for Transplantation Regulations (SOR/2007-118).Minister of Justice: Department of Justice, Ottawa2015
- Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use.Food and Drug Administration. Center for Biologics Evaluation and Research, 2017
The International Society for Stem Cell Research. ISSCR letter to Health Canada on Regulation of Cell Therapies 14 Jun 2018.
- Workshop to address gaps in regulation of minimally manipulated autologous cell therapies for homologous use in Canada.Cytotherapy. 2017; 19: 1400-1411https://doi.org/10.1016/j.jcyt.2017.08.015
- Revised Fee Proposal for Drugs and Medical Devices.Government of Canada, 2018https://www.canada.ca/en/health-canada/programs/consultations-revised-fee-proposal-drugs-medical-device/document.htmlDate accessed: February 13, 2019
- Biologics and Genetic Therapies Directorate, Health Products and Food Branch. Guidance Document for Cell, Tissue and Organ Establishments - Safety of Human Cells, Tissues and Organs for Transplantation.Minister of Health: Health Canada, Ottawa2013
- Canada's Blood Supply Ten Years After the Krevner Commission.Library of Parliament, 2008
- Final report.Commission of Inquiry on the Blood System in Canada, 1997
- Therapeutic Products Directorate, Health Products and Food Branch. Guidance for Industry: Management of Drug Submissions.Minister of Health: Health Canada, Ottawa2013
- Guidance Document: Preparation of Clinical Trial Applications for use of Cell Therapy Products in Humans.Minister of Health: Health Canada. Health Products and Food Branch, Ottawa2015
- Notice to Industry: Aligned reviews between Health Canada and health technology assessment organizations.Government of Canada, 2018
- Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Huma or Animal Origin (Q5A(R1)).in: International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use. 1999
- General Principles to Address Virus and Vector Shedding.in: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. 2009
- General Principles to Address the Risk of Inadvertent Germline Integration of Gene Therapy Vectors.in: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. 2006
- Oncolytic Viruses.in: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. 2009
- Design and Analysis of Shedding Studies or Virus or Bacteria-Based Gene Therapy and Oncolytic Products.Food and Drug Administration. Center for Biologics Evaluation and Research, 2015
- Guidance for Industry: Guidance for Human Somatic Cell Therapy and Gene Therapy.Center for Biologics Evaluation and Research: Food and Drug Administration. Center for Biologics Evaluation and Research, Rockville1998
- Reflection paper on management of clinical risks deriving from insertional mutagenesis.European Medicines Agency: Committee for Advanced Therapies, London2013
- Draft Guideline on the Quality, Nonclinical and Clinical Aspects of Gene Therapy Medicinal Products.European Medicines Agency: Committee for Advanced Therapies, London2015
Government of Canada. New Substances Notification Regulations (Organisms). 2005.
- Canadian Environmental Protection Act, 1999 (S.C. 1999, c. 33).Minister of Justice: Department of Justice, Ottawa2016
Government of Canada. Policy: Drug/Medical Device Combination Products. Ottawa: Minister of Health: Health Canada; 1999.
- Inspection Strategy for Cells, Tissues and Organs Establishments (POL-0057).Minister of Health: Health Canada, Ottawa2012
- Cells, Tissues and Organs (CTO) Inspections.2016
- Guidance Document For Clinical Trial Sponsors: Clinical Trial Applications. 2016;
- Medical Device Inspections.2016
- Protecting Canadians from Unsafe Drugs Act (Vanessa's Law) (S.C. 2014, c. 24).Minister of Justice: Department of Justice, Ottawa2014
- Guidance on Evidence to Demonstrate Drug GMP Compliance of Foreign Sites (GUI-0080).Minister of Health: Health Canada. Health Product and Food Branch Inspectorate, Ottawa2009
Government of Canada. Quality Systems ISO 13485. n.d.
- GD210: ISO 13485:2003 Quality Management System Audits Performed by Health Canada Recognized Registrars.Minister of Health: Health Canada. Medical Devices Bureau, Ottawa2007
- Guidance Document GD211: Guidance on the Content of Quality Management System audit reports.Minister of Health: Health Canada. Medical Devices Bureau, Ottawa2011
- Policy for the Inspection of Medical Device Companies (POL-0035).Minister of Health: Health Canada, Ottawa2012
- Current practices and reform proposals for the regulation of advanced medicinal products in Canada.Regenerative Medicine. 2015; 10: 647-663https://doi.org/10.2217/rme.15.28
- Guidance Document: Notice of Compliance with Conditions (NOC/c).Minister of Health: Health Canada. Therapeutic Products Directorate. Bureau of Policy, Science and International Programs, Ottawa2011
United States Food and Drug Administration. Regenerative Medicine Advanced Therapy Designation 2 Feb 2018. https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ucm537670.htm (Accessed February 13, 2019).
- Guidance for Industry - Priority Review of Drug Submissions.Minister of Health: Health Canada. Therapeutic Products Directorate, Ottawa2009
- Guidance for Industry and Practitioners: Special Access Programme for Drugs. 2013;
- Efficacy and safety of ex vivo cultured adult human mesenchymal stem cells (Prochymal) in pediatric patients with severe refractory acute graft-versus-host disease in a compassionate use study.Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 2011; 17: 534-541https://doi.org/10.1016/j.bbmt.2010.04.014
- A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment.Blood. 1990; 76: 1464-1472
- Poor outcome in steroid-refractory graft-versus-host disease with antithymocyte globulin treatment.Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 2002; 8: 155-160
United States Food and Drug Administration. FDA announces comprehensive regenerative medicine policy framework 2017.
- Direct-to-consumer marketing of stem cell interventions by Canadian businesses.Regen Med. 2018; 13: 643-658
- The involvement of Canadian physicians in promoting and providing unproven and unapproved stem cell interventions. - PubMed - NCBI.BMC Med Ethics. 2018; 19
- Stem cell tourism and public education: the missing elements.Cell Stem Cell. 2014; 15: 267-270https://doi.org/10.1016/j.stem.2014.08.009
- Athletes’ use of unproven stem cell therapies: adding to inappropriate media hype?.Molecular Therapy : The Journal of the American Society of Gene Therapy. 2012; 20: 1656-1658https://doi.org/10.1038/mt.2012.172
- Gordie Howe's “Miraculous Treatment” Case Study of Twitter Users’ Reactions to a Sport Celebrity's Stem Cell Treatment.JMIR Public Health and Surveillance. 2016; 2: e8https://doi.org/10.2196/publichealth.5264
- Gordie Howe's Stem Cell “Miracle” A Qualitative Analysis of News Coverage and Readers’ Comments in Newspapers and Sports Websites.Stem Cell Reviews. 2015; 11: 667-675https://doi.org/10.1007/s12015-015-9606-8
- Cellular transplants in China: observational study from the largest human experiment in chronic spinal cord injury.Neurorehabilitation and Neural Repair. 2006; 20: 5-13https://doi.org/10.1177/1545968305284675
- Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.PLoS Medicine. 2009; 6e1000029https://doi.org/10.1371/journal.pmed.1000029
- Angiomyeloproliferative lesions following autologous stem cell therapy.Journal of the American Society of Nephrology : JASN. 2010; 21: 1218-1222https://doi.org/10.1681/ASN.2009111156
- Bilateral Retinal Detachments After Intravitreal Injection of Adipose-Derived “Stem Cells” in a Patient With Exudative Macular Degeneration.Ophthalmic Surgery, Lasers & Imaging Retina. 2017; 48: 772-775https://doi.org/10.3928/23258160-20170829-16
- Vision Loss after Intravitreal Injection of Autologous “Stem Cells” for AMD.The New England Journal of Medicine. 2017; 376: 1047-1053https://doi.org/10.1056/NEJMoa1609583
Master Z, Caulfield T. Patient Booklet: What you need to know about stem cell therapies. 2014. http://www.hli.ualberta.ca/Research/Public_Outreach_Award.aspx
- Stem-cell tourism and scientific responsibility. Stem-cell researchers are in a unique position to curb the problem of stem-cell tourism.EMBO Reports. 2011; 12: 992-995https://doi.org/10.1038/embor.2011.156
- Stem cell tourism and Canadian family physicians.Canadian Family Physician Medecin de Famille Canadien. 2012; 58 (e182-5): 365-368
- Stem-cell therapy faces more scrutiny in China.Nature. 2009; 459: 146-147https://doi.org/10.1038/459146a
- Germany tightens law on stem cell treatments.Bmj. 2009; 339: b2967https://doi.org/10.1136/bmj.b2967
United States Food & Drug Administration. Owner of Arizona company charged and convicted of introducing an unapproved new drug—stem cells—into interstate commerce 2011.
The International Society for Stem Cell Research. Patient Handbook on Stem Cell Therapies. 2008.
International Society for Cellular Therapy. International Society for Cellular Therapy: Connect, Communicate, Translate. n.d.
- Stem Cell Treatments for Cerebral Palsy.Factsheet for patients and families. 2011;
CellCAN. What You Need to Know. 2016.
Article info
Publication history
Published online: June 10, 2019
Accepted:
March 13,
2019
Received:
November 23,
2018
Identification
Copyright
© 2019 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Forward for two review articles authored by ISCT's North American Legal & Regulatory Affairs Committee on the regulatory framework for cellular & gene therapy product approval in the U.S. and CanadaCytotherapyVol. 21Issue 7
- PreviewA major hurdle for worldwide development of Cellular & Gene Therapy Products (CGT) is the differing regulatory structures within various geographic jurisdictions. These differences impact patient access to innovative, potentially revolutionary and curative medical therapies. The International Society for Cell & Gene Therapy (ISCT)'s intent is to contribute to the improving development and regulatory approval of CGTs in all areas of the globe. The first and second reviews in this potential global series, authored by ISCT's North American Legal & Regulatory Affairs Committee, focus on North America, specifically U.S.
- Full-Text
- Preview
- Current state of U.S. Food and Drug Administration regulation for cellular and gene therapy products: potential cures on the horizonCytotherapyVol. 21Issue 7
- PreviewCellular & Gene Therapies (CGTs) are complex products, which have been key foci of the International Society for Cell & Gene Therapy (ISCT). For this ISCT North American Legal & Regulatory Affairs Committee review publication, CGTs include but are not limited to somatic cell-based therapies, pluripotent cell-derived cell-based therapies, gene- or non-gene-modified or gene edited versions of these cell-based therapies, in vivo gene therapies, organ/tissue engineered products, and relevant combination products.
- Full-Text
- Preview
