Skip to content

CAR-T and Cell Therapy Manufacturing in Canada

Canada stands as a formidable hub for CAR-T manufacturing, offering clients a comprehensive suite of capabilities that span upstream and downstream processing, automation, closed system bioreactors, and a commitment to regulatory compliance. The Nation’s collaborative spirit, coupled with a dedication to sustainability, positions Canada at the forefront of the global cellular therapy landscape, providing clients with a reliable and innovative partner in the development and production of advance CAR-T therapies.

Genetically modified T cells are powerful new drugs, offering the hope of a curative response in cancer patients. Chimeric antigen receptors (CARs) are a class of engineered synthetic receptors that reprogram lymphocyte specificity and function which can recognize, target, and eliminate cells with specific surface antigens, and they have demonstrated remarkable potency in B-cell malignancies and acute lymphoblastic leukemia (Villeneuve et al., 2023), and this technology is also applicable in principle to many cancers. Currently, six CAR-T cell products are approved for commercial use and are available on the U.S. and Canada market: three for B-cell leukemia and lymphoma (tisagenlecleucel, axicabtagene ciloleucel, lisocabtagene maraleucel), one for mantle cell lymphoma (brexucabtagene autoleucel), and two for multiple myeloma (idecabtagene vicleucel, and ciltacabtagene autoleucel) (Wang et Al, 2023; Health Canada website).

Further processes to identify appropriate target antigens, to overcome immunosuppressive tumor microenvironments, to reduce toxicities, and to prevent antigen escape are still required (Sadelain et al., 2017) but currently being studied on multiple clinical studies. Moreover, advances in optimal T-cell selection, genetic engineering and cell manufacturing are currently poised to expand T-cell-based therapies by fostering new applications for infectious diseases, autoimmunity (Sadelain et al.,2017), different types of cancers, but also raises hope in a wide range of non-malignant diseases (Sledz et al., 2023).

The Canadian landscape for cellular therapies, particularly CAR-T (Chimeric Antigen Receptor T-Cell) manufacturing, has witnessed significant advancement, positioning Canadian as a key player in the field. For clients seeking cutting-edge capabilities in CAR-T production, Canada offers a robust infrastructure encompassing state of the art facilities, advance technologies, and commitment to regulatory compliance.

In the Area of cell therapy and CAR-T manufacturing, Clinical Development & Manufacturing Organization (CDMO), have specialized facilities equipped with cutting-edge bioprocessing technologies. These facilities are designed to handle the intricate and highly regulated process involved in CAR-T cell production. Clients benefit from a tailored approach, ensuring that the manufacturing process aligns seamlessly with the unique specifications of each CAR-T therapy. In the Canadian landscape there are currently several companies advertising to providing manufacturing cell and gene therapy services, from product development through commercial manufacturing and packaging, such as Adare pharma Solutions, uBriGene, Eurofins, OmniaBio and C3i Center (The biopharmguy.com, and companies’ websites). There are also several academic groups, scientists, clinical research organization, but also physicians and programs across Canada including McGill University Health Centre Stem Cell Transplant and Immune Effector Cell Therapy Program, Hamilton Health Sciences, Cellular Therapy and Transplantation, The Ottawa Hospital Research Institute’s Biotherapeutics Manufacturing Center, and the Northern Alberta Blood and Marrow Transplant Program, which are working on CAR-T cell manufacturing therapies for patients (Alberta Cancer Foundation, Facebook video, and FACT Institution listing). Furthermore, for cellular therapy and/or cord blood transplant there are currently 22 Canadian organizations (Facilities and programs) listed and which have been FACT-accredited, on the official web site of the Foundation for the Accreditation of Cellular Therapy (FACT).

Notable Features of the Canadian Landscape

One of the notable features of CAR-T manufacturing in Canada is the utilization of closed-system bioreactors. These advance bioreactors provide a controlled and sterile environment for the expansion and cultivation of CAR-T cells, minimizing the risk of contamination and ensuring the production of high-quality cellular therapies (Levine et al.,2017). This closed-system approach aligns with global regulatory standards, offering clients assurance in the safety and consistency of their CAR-T products.

Furthermore, Canada’s CAR-T manufacturing capabilities extend to automated cell processing technologies. Automation plays a pivotal role in enhancing efficiency, reducing variability, and ensuring reproductivity in CAR-T production (Smith et al.,2020). Clients can rely on the precision and reliability afforded by automated systems, contributing to the scalability and commercial viability of CAR-T therapies.

In terms of upstream processing, Canada’s CAR-T manufacturing facilities excel in cell isolation and genetic modification techniques. Cutting-edge technologies are employed for efficient extraction and modification of patient-derived T-cells, a critical step in CAR-T production (Fesnak et al., 2016). Clients benefit from the expertise of skilled professionals utilizing advanced techniques that comply with rigorous regulatory requirements.

Downstream processing capabilities of Canadian CAR-T manufacturing facilities are equally impressive. Purification and formulation processes are meticulously executed to ensure the final CAR-T product meets the highest quality standards (Levine et al.,2017). This commitment to quality extends to rigorous testing and characterization protocols, providing clients with a comprehensive understanding of the therapeutic potency and safety of their CAR-T cell product.

Regulatory compliance is a cornerstone of CAR-T manufacturing in Canada. Facilities adhere to Good Manufacturing practice (GMP) guidelines, and their processes are designed to meet the stringent regulatory requirements set forth by health authorities (Elsallab et al.,2020). Client can have confidence in the robust quality assurance and regulatory frameworks in place, essential for navigating the complex landscape of cellular therapy manufacturing.

Collaboration is a key element of CAR-T manufacturing in Canada, with academic institutions, research organizations and industrial partners actively engaged in advancing the field. This approach ensures that CAR-T manufacturing facilities remain at the forefront of scientific and technological advances (Shah et al.,2018). Customers benefit from the interdisciplinary expertise and innovative solutions that arise from these partnerships, as the patient-specific nature of CAR-T therapies can present a challenge for scale-up and distribution, leading to a change in the status quo of the manufacturing and supply chain, highlighting the need for a more holistic approach to the manufacturing and supply chain. This underlines the need for smaller, more agile, and often regional manufacturing, resulting in distribution networks closer to the patient (Sarkis, M., et all., 2021).

Moreover, Canada’s commitment to sustainability is reflected in its CAR-T manufacturing practices. Facilities prioritize environmentally conscious approaches, incorporating green technologies and minimizing waste in line with evolving sustainability standards (Miehe, R. et all., 2019 and Sarkis, M., et all., 2021). The eco-friendly stance resonates with clients seeking socially responsible and sustainable manufacturing solutions.

Interested in Learning More About the Canadian Landscape for Oncology Clinical Research?

At Scimega, we are proud to say that the over 50 sites and Canadian PIs we work with are often top enrollers in the global oncology studies on which we collaborate with Sponsors.

As a niche Canadian CRO acting in Canada for the conduct of global cutting-edge oncology trials sponsored by mid-size biotechs, our team is skilled in collaborative vendor teaming. With a proven track record of 25 years unparalleled Canadian oncology experience Scimega guarantees sponsors the quickest site start-up and highest patient recruitment rate, without sacrificing premium quality data. With an optimal operations design robust enough to address an ever-changing clinical trial landscape, Scimega’s team of Lean Coached oncology experts go above-and-beyond for your study.

Our Lean Coached oncology experts work with your team to devise innovative solutions specific to the unique challenges of your oncology clinical trial. If you’re interested in learning more about the Canadian opportunity, explore an expansion with us!

Contributed by: Wilkinson Narcisse, MSc., Clinical Trial Leader

 

References:
- Villeneuve, P.J.A.; Bredeson, C. CAR-T Cells in Canada; Perspective on How to Ensure We Get Our Value’s Worth. Curr. Oncol. 2023, 30, 4033–4040. https://doi.org/ 10.3390/curroncol30040305
- Sadelain, M., Rivière, I., & Riddell, S. (2017). Therapeutic T cell engineering. Nature, 545(7655), 423–431.
- Levine, B. L., Miskin, J., Wonnacott, K., Keir, C., & Suhoski, M. M. (2017). Global manufacturing of CAR T cell therapy. Molecular Therapy - Methods & Clinical Development, 4, 92–101.
- Sledz, M., Wojciechowska, A., Zagożdżon R., Kaleta, B. (2023). In Situ Programming of CAR‑T Cells: A Pressing Need in Modern Immunotherapy. Archivum Immunologiae et Therapiae Experimentalis (2023) 71:18
- Wang V., Gauthier M. Decot V., Reppel L., Bensoussan D., Systematic Review on CAR-T Cell Clinical Trials Up to 2022:Academic Center Input. Cancers (Basel). 2023 Feb; 15 (4); 1003.
- Smith, T. T., Stephan, S. B., Moffett, H. F., McKnight, L. E., Ji, W., Reiman, D., Bonagofski, E., & Wohlfahrt, M. E. (2020). In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers. Nature Nanotechnology, 16(5), 522–529.
- Fesnak, A. D., June, C. H., & Levine, B. L. (2016). Engineered T cells: The promise and challenges of cancer immunotherapy. Nature Reviews Cancer, 16(9), 566–581.
- Elsallab, M., Levine, B. L., Wayne, A. S., Abou-El-Enein, M., & Jeyapalan, S. A. (2020). CAR T-cell product performance in haematological malignancies before and after marketing authorisation. The Lancet Oncology, 21(3), e104–e116.
- Shah, N. N., Fry, T. J., & Mechanisms of resistance to CAR T cell therapy. (2018). Nature Reviews Clinical Oncology, 16(6), 372–385.
- Miehea, R., Fulla J., Scholzb, P., Demmerb, A., Bauernhansla, T., Sauer, A., Schuhb, G., The Biological Transformation of Industrial Manufacturing – Future Fields of Action in Bioinspired and Bio-based Production Technologies and Organization. Procedia Manufacturing 39 (2019) 737–744.
- Sarkis, M., Bernardi, A., Shah, N., Papathanasiou, M.M., Emerging Challenges and Opportunities in Pharmaceutical Manufacturing and Distribution. Processes 2021, 9, 457. https:// doi.org/10.3390/pr9030457.
- Tanveer M., Rehman Khan S.A., Umar M., Yu Z., Sajid M.J., Haq I. U., Waste management and green technology: future trends in circular economy leading towards environmental sustainability. Vol.:(0123456789)1 3https://doi.org/10.1007/s11356-022-23238-8, Environmental Science and Pollution Research (2022) 29:80161–80178.
- The biopharmguy.com website, https://biopharmguy.com/links/company-by-location-canada.php.
- Alberta Cancer Foundation, Dr. Michael Chu and Dr. Irwin Sandhu are leading the charge in CAR T-cell therapy in Alberta. https://www.facebook.com/albertacancerfoundation/videos/dr-michael-chu-and-dr-irwin-sandhu-are-leading-the-charge-in-car-t-cell-therapy-/355503440276858/.
- Foundation for the Accreditation of cellular therapy (FACT) website. Search for Fact Accredited Organization. https://www.factglobal.org/about/.
- Health Canada website. Drug and Health Product Portal. Information on drugs and health products authorized by Health Canada. https://dhpp.hpfb-dgpsa.ca/dhpp/search.
Back To Top
Search