The Canadian Regulatory System for Cell and Gene Therapies

An increasing number of cell and gene therapy (CGT) products are approved by regulators around the world, including several therapies approved by Health Canada in recent years, as follows:

• Gilead’s Tecartus for mantel cell lymphoma (approved in 2021);
• Celgene’s Abecma for multiple myeloma (2021);
• Novartis’ Zolgensma for spinal muscular atrophy (2020);
• Spark Therapeutics’ Luxturna for a rare form of inherited vision loss (2020); and,
• Gilead’s Yescarta (2019) and Novartis’ Kymriah (2018), both CAR T cell-based gene therapies for the treatment of blood cancers.

In addition to these approvals, many CGT candidates are currently being evaluated in clinical trials in Canada.

How CGTs are Regulated in Canada

In Canada, CGT products are regulated under the existing regulatory frameworks developed for pharmaceutical and biologic drugs, human material for transplants, and medical devices. A majority of CGTs are classified as biological drugs and are regulated by the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) within Health Canada. As a biological drug, the sponsor of a CGT must submit a Clinical Trial Application (CTA) to Health Canada prior to commencing a clinical trial, and file a New Drug Submission (NDS) for review and approval prior to marketing a new therapy in Canada.

A few selected cellular therapies that meet specific criteria (i.e., minimally manipulated, for homologous use, allogeneic, non-systemic effect) or have an established safety profile and therapeutic use (i.e., bone marrow transplantation) are regulated as human cells, tissues, and organs (CTO) under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. A premarket application is not required for therapies regulated as CTOs, although registration of the organization manufacturing or manipulating the product is required with an emphasis on the prevention of disease transmission (such as HIV type 1 and 2, Hepatitis B and C, syphilis).

Harmonized Regulatory Framework

Although CGTs can vary widely in nature, the major regulatory systems around the world (e.g., U.S. Food and Drug Administration, Health Canada) are broadly similar. Like other major regulatory systems, Health Canada’s regulatory framework is risk-based, meaning that the level of regulatory control is established on the basis of defined risk categories. For low-risk CGTs regulated as CTOs, the regulations focus on the control of possible contaminations and disease transmission, whereas the regulatory expectation for CGTs as biological drugs are higher to address the risks of these highly manipulated novel therapies.

As an official member of the International Council for Harmonisation of Technical Requirements for Human Use (ICH), Health Canada adopts all ICH guidelines and standards and accepts data generated in other ICH member countries. This is reciprocated in that if a clinical trial is conducted in Canada, the sponsor can potentially use the trial data for other ICH member countries/regions such as the U.S. or EU. In addition, CGT developers can use existing regulatory guidance available in other ICH member countries to guide the development of their products in the absence of Canada-specific guidance.

Collaborative and Flexible Regulatory Environment

Health Canada encourages developers and manufacturers to engage early in the development process through consultations, including pre-CTA meetings. Engagement with Health Canada is available to all stakeholders (including those based outside of Canada) and is offered at no cost and with no limit on the number of consultations, thus allowing developers to gain early insight into the regulator’s expectations of their development programs.

CGTs often treat life-threatening or severely debilitating illnesses that require early access to promising new therapies. Like other major regulators, Health Canada has accelerated approval pathways and programs available to expedite the development and approval of CGTs. For example, the sponsor can apply for a notice of compliance with conditions (NOC/c). A NOC/c may grant conditional approval in situations where sufficient product safety has been established, where preliminary evidence is supportive of clinical efficacy, or where a particular patient population would benefit from the process of collecting additional clinical data from early market access. The conditions must be met within a defined period after the NOC/c is issued. The NOC/c status significantly shortens the standard premarket review period to a target of 200 days (from the standard 300 days). Priority review of New Drug Submissions is also available for products that meet the criteria for this procedure and shortens the premarket review period to just 180 days.

Navigating the Canadian Regulatory System

Although the Canadian regulatory system is broadly similar to other major systems, there are subtle differences between them, most of which are administrative in nature; for instance, the paperwork required for the Lot Release Program during clinical trials or Canada-specific language requirements (i.e., product labelling in both official languages, English and French). Another difference to note for viral vector use in human gene therapy is that the vectors are regulated as micro-organisms and subject to the New Substances Notification (NSN) Regulations (Organisms) in Canada. This requires that an environmental and human health risk assessment be conducted for new substances and micro-organisms that are not already on the Domestic Substances List.

CGT developers working with a Canadian partner or CDMO should leverage their regulatory expertise when navigating the regulatory system in Canada.

For a detailed overview of the regulation of CGTs in Canada, see CCRM’s recently published chapter on this topic, part of the first publication on Global Regulation of Regenerative Medicine titled Regulation of regenerative medicines: a global perspective published by the Regulatory Affairs Professional Society (April, 2022).

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