Biosimilars in Canada: What Patients Should Know About the Big Switch

Provincial biosimilar switching mandates have sparked patient anxiety across Canada. Here's what the clinical evidence actually shows.

Molecular structure representing biologic drug complexity and biosimilar development

When British Columbia told 40,000 patients in 2019 that their biologic medications were being switched to biosimilars, the backlash was fierce. Patient advocacy groups warned of unknown risks. Online forums filled with reports of new side effects. A petition gathered thousands of signatures. Seven years later, BC’s data tells a different story: $732 million saved, no increase in hospitalizations, and adoption rates above 91% across every drug class in the program. Almost every other province has since followed BC’s lead, and the gap between patient fear and clinical reality has become one of the most consequential disconnects in Canadian healthcare.

Not Your Grandmother’s Generic

The confusion starts with a bad analogy. People hear “biosimilar” and think “generic biologic,” which is close enough to be dangerous. A generic version of, say, metformin contains the exact same molecule as the brand-name drug. The active ingredient is identical down to the atom. You can verify this with straightforward chemical analysis, and that’s why Health Canada approves generics based on bioequivalence studies rather than full clinical trials. The manufacturing process doesn’t matter much when you’re assembling 21 atoms into a small molecule.

Biologics are a different beast entirely. These are large, complex proteins produced inside living cells, and a single molecule of a monoclonal antibody like infliximab can contain more than 25,000 atoms arranged in intricate three-dimensional structures. The protein’s shape determines its function, and that shape depends on how the cells were grown, what nutrients they received, what temperature they were kept at, and dozens of other manufacturing variables. No two production batches are perfectly identical, not even from the same manufacturer using the same cell line. Each batch is a population of slightly different molecules, a controlled range rather than a single chemical entity. This is why the term “generic biologic” doesn’t quite work, and why regulators invented a new word for the concept.

A biosimilar manufacturer can’t simply copy a chemical formula. They must develop their own cell line, optimize their own manufacturing process, and then demonstrate through extensive analytical, preclinical, and clinical comparison that their product is “highly similar” to the reference biologic with “no clinically meaningful differences” in safety, purity, or potency. The development process typically takes seven to eight years and costs upward of $100 million, compared to roughly $1 to $4 million for a traditional generic. This isn’t a shortcut. It’s a different kind of proof.

How Health Canada Decides What Counts as “Highly Similar”

Health Canada uses what it calls a “totality of evidence” approach to evaluate biosimilar applications. The process begins with extensive analytical studies comparing the biosimilar’s molecular structure, biological activity, and physicochemical properties to the reference product. These studies form the foundation of the submission, and they’re far more detailed than anything required for generics. Differences in glycosylation patterns, charge variants, aggregate levels, and binding affinity all get scrutinized.

On top of the analytical package, manufacturers submit comparative nonclinical studies (animal data) and clinical studies, traditionally including pharmacokinetic trials and at least one comparative clinical efficacy trial. The clinical trial isn’t designed to re-prove that the drug works; the reference product already did that. Instead, it’s designed to confirm that any residual differences seen in the analytical comparison don’t translate into clinically meaningful differences in patients. Health Canada has approved more than 40 biosimilars through this pathway since 2009, covering treatments for rheumatoid arthritis, inflammatory bowel disease, psoriasis, diabetes, cancer, and several other conditions (1).

The regulatory picture shifted in mid-2025 when Health Canada proposed draft guidance that would eliminate the requirement for comparative clinical efficacy trials “in most cases,” aligning with a similar move by the European Medicines Agency earlier that year (2). Under the proposed framework, clinical evidence would generally be limited to a comparative pharmacokinetic study that also collects safety and immunogenicity data. The rationale is that after more than fifteen years of biosimilar approvals worldwide, the analytical tools have become sensitive enough to detect clinically relevant differences without a full efficacy trial. This isn’t a lowering of standards so much as a recognition that the most informative evidence comes from the lab bench, not the clinic. Critics worry it opens the door to corner-cutting, but proponents point out that the European track record with abbreviated pathways has been spotless.

The NOR-SWITCH Trial and What Came After

For patients already stable on a biologic, the central question isn’t whether a biosimilar works; it’s whether switching to one is safe. The landmark study on this question remains the Norwegian NOR-SWITCH trial, published in The Lancet in 2017. It randomized 482 patients across six different inflammatory diseases to either continue on originator infliximab or switch to the biosimilar CT-P13, and followed them for 52 weeks in a double-blind design. Disease worsening occurred in 26% of the originator group and 30% of the biosimilar group, well within the pre-specified non-inferiority margin. Adverse event rates were nearly identical: 70% versus 68% (3). The open-label extension, published in 2019, confirmed these findings held up over an additional 26 weeks (4).

NOR-SWITCH was important because of its rigor and its size, but it wasn’t an outlier. A 2022 systematic review in Frontiers in Pharmacology examined the evidence across multiple biosimilar switches and found no consistent signal of harm, including in studies involving multiple switches between products (5). A 2020 systematic review comparing double-blinded and open-label switching studies found something telling: discontinuation rates due to adverse events ran about 5.6% in open-label studies but only 3.1% in blinded ones (6). Patients who knew they were being switched reported more problems than patients who didn’t know. The drug wasn’t the variable. The knowledge was.

The Nocebo Problem Is Real, and So Is the Anxiety Behind It

That gap between open-label and blinded discontinuation rates points to a phenomenon called the nocebo effect, which is the opposite of a placebo effect. When patients expect negative outcomes, they experience them, not because the treatment changed but because their perception did. A 2024 systematic review in Pharmaceutical Medicine identified thirteen distinct strategies for reducing nocebo responses during biosimilar switches, with positive framing and clear communication from healthcare providers showing the strongest evidence of effectiveness (7).

Dismissing patient concerns as “just nocebo” would be both inaccurate and unhelpful, though. The anxiety is real, and it comes from reasonable places. Patients with chronic inflammatory diseases have often spent years finding a treatment that works. Many went through multiple failures before landing on a biologic that gave them their life back. Being told by a provincial government that their medication is changing, often with limited explanation and a hard deadline, triggers legitimate fear. That the evidence strongly supports the safety of switching doesn’t mean the process has been handled well. Several patient advocacy organizations, including the Gastrointestinal Society and Arthritis Society Canada, have criticized the communication strategies used during early switching mandates, noting that patients often learned about the change from a pharmacist or a letter rather than from their prescribing specialist.

The good news is that provinces appear to be learning. More recent switching programs, including Ontario’s 2024 rollout and Manitoba’s program that launched the same year, have included longer transition periods, clearer exemption processes for patients with documented medical reasons to stay on the originator, and better educational materials (8). Most programs also exempt specific populations such as pregnant patients and children under 18.

The Provincial Patchwork

As of early 2026, ten of thirteen Canadian jurisdictions have biosimilar switching policies in place. British Columbia was first in May 2019. Alberta followed in late 2019. Quebec, New Brunswick, Nova Scotia, Saskatchewan, and several territories implemented their own programs over the following years. Ontario, the largest province, launched its biosimilar designation policy on July 31, 2024, giving patients six months to transition. Manitoba became the final major province to act, with its Biosimilar Initiative taking effect on August 1, 2024 (9).

The general structure is consistent across provinces, though the details vary. Once a biosimilar is listed on the provincial formulary, the public drug plan stops covering the originator biologic for new patients, and existing patients are given a transition window of typically six months. Patients who have documented medical reasons for staying on the originator, such as a previous adverse reaction to the biosimilar or a contraindication, can apply for an exemption through their prescriber. Private insurance plans have increasingly followed suit, though the timelines and specific products covered differ by insurer.

The economic results from BC, the jurisdiction with the longest track record, have been striking. The province reported $732 million in direct drug cost savings over five years, with $226 million of that coming in the 2023-2024 fiscal year alone (10). Those savings weren’t simply pocketed. BC reinvested the money into expanded PharmaCare coverage, funding continuous glucose monitors for diabetes patients, broadening access to COPD inhalers, adding heart failure medications as regular benefits, and expanding coverage of Trikafta for cystic fibrosis. The argument for biosimilar switching isn’t abstract; it’s that money saved on equivalent drugs goes directly toward treatments that patients couldn’t previously access.

What the Safety Data Actually Shows

The strongest piece of Canadian evidence on post-switch safety came in early 2026, when a study published in Arthritis Care & Research examined whether BC’s nonmedical switching policy led to increased healthcare utilization among patients with inflammatory arthritis. The researchers found no evidence of increases in physician visits, hospital services, emergency department visits, or concomitant drug use after the switch (11). This wasn’t a small signal being waved away; there was simply no signal at all.

The BC government’s own monitoring data, covering all 40,000-plus patients who switched, showed that people who moved from reference biologics to biosimilars had the same health outcomes as those who were on reference biologics before the policy took effect (10). Emergency room visits didn’t rise. Hospitalizations didn’t rise. The use of additional medications to manage breakthrough disease didn’t rise. For a program that generated significant patient anxiety, the clinical reality has been remarkably uneventful.

None of this means that no individual patient has ever done worse after switching. In any large population, some patients will experience disease flares that happen to coincide with a medication change, and some may have genuine immunological responses to differences in excipients or formulation. The exemption process exists for these cases. But the population-level data, drawn from tens of thousands of patients followed over years, shows that these events occur at the same rate whether or not a switch happened.

Where Biosimilars Are Heading

The next frontier is oncology. Biosimilars of trastuzumab (Herceptin), bevacizumab (Avastin), and rituximab (Rituxan) are already approved in Canada and are being incorporated into provincial switching programs. The financial stakes are enormous, since cancer biologics represent some of the most expensive drugs in the formulary. The American Society of Clinical Oncology issued a policy statement supporting biosimilar use in oncology while calling for continued pharmacovigilance, and Canadian oncology groups have taken similar positions (12).

Farther out, researchers are exploring what biosimilar competition might look like for cell and gene therapies, a drug class where single treatments can cost over a million dollars. A 2024 analysis in the Journal of Law and the Biosciences argued that gene therapies are more amenable to the biosimilar model than cell therapies, since demonstrating “high similarity” is more feasible when the product is a defined genetic sequence delivered by a viral vector rather than a living cell population with inherent variability (13). This remains theoretical for now, but the regulatory and manufacturing frameworks being built for today’s biosimilars will shape how these future products are evaluated.

Health Canada’s proposed 2025 guidance changes, if finalized, will accelerate the pace of biosimilar approvals by reducing the clinical trial burden while maintaining the analytical rigor that has underpinned the safety record so far. For patients, the practical message hasn’t changed much: biosimilars are held to a high standard, the switching evidence is reassuring across multiple diseases and multiple products, and the savings fund treatments that weren’t previously covered. The anxiety around switching was understandable. The data that’s accumulated since should go a long way toward putting it to rest.

References

  1. Health Canada. “Biosimilar biologic drugs in Canada: Fact Sheet.” Canada.ca. www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/fact-sheet-biosimilars.html

  2. Health Canada. “DRAFT Guidance Document: Information and Submission Requirements for Biosimilar Biologic Drugs.” June 2025. www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/draft-information-submission-requirements-biosimilar-biologic-drugs.html

  3. Jorgensen KK, et al. “Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial.” The Lancet, 2017;389(10086):2304-2316. DOI: 10.1016/S0140-6736(17)30068-5

  4. Goll GL, et al. “Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial.” Journal of Internal Medicine, 2019;285(6):653-669. DOI: 10.1111/joim.12880

  5. Barbier L, et al. “Switching Among Biosimilars: A Review of Clinical Evidence.” Frontiers in Pharmacology, 2022;13:917814. DOI: 10.3389/fphar.2022.917814

  6. Pouillon L, et al. “The Biosimilar Nocebo Effect? A Systematic Review of Double-Blinded Versus Open-Label Studies.” Journal of Managed Care & Specialty Pharmacy, 2018;24(10):952-960. DOI: 10.18553/jmcp.2018.24.10.952

  7. Tan SS, et al. “Mitigating the Nocebo Effect in Biosimilar Use and Switching: A Systematic Review.” Pharmaceutical Medicine, 2024;38:467-487. DOI: 10.1007/s40290-024-00541-y

  8. Government of Ontario. “Biosimilar Policy Update: Transition from Originator.” OHIP InfoBulletin 240803, 2024. www.ontario.ca/document/ohip-infobulletins-2024/bulletin-240803-biosimilar-policy-update-transition-originator

  9. Smart & Biggar. “Update on biosimilars in Canada.” June 2025. www.smartbiggar.ca/insights/publication/update-on-biosimilars-in-canada-june-2025

  10. Government of British Columbia. “B.C.’s biosimilar initiative saves money, reinvests to expand drug coverage.” News release, June 2024. news.gov.bc.ca/releases/2024HLTH0081-000927

  11. Dang TT, et al. “Did a Non-Medical Biosimilar Switching Policy Cause an Increase in Non-Biologic/Biosimilar Health Care Resource Utilization or Cost in Patients With Inflammatory Arthritis?” Arthritis Care & Research, 2026. DOI: 10.1002/acr.25610

  12. Lyman GH, et al. “ASCO Policy Statement on Biosimilar and Interchangeable Products in Oncology.” JCO Oncology Practice, 2023;19(4):171-175. DOI: 10.1200/OP.22.00783

  13. Gitter DM, Gitter RJ. “Introducing biosimilar competition for cell and gene therapy products.” Journal of Law and the Biosciences, 2024;11(2):lsae015. DOI: 10.1093/jlb/lsae015