Biosimilars – What You Need to Know – for Providers
Find answers to potential patient questions about biosimilars in our handout: Discussing Biosimilars with Patients: A Resource for Healthcare Providers.
What are biologics?
- Biologics are complex protein molecules created inside a living cell.
- Biologics have become mainstays in the treatment of many types of cancer, including breast, gastrointestinal, lung, ovarian and other cancers.
What are biosimilars?
- A reference biologic is the original branded product approved by Health Canada.
- When the patent for a reference biologic expires, manufacturers can sell highly similar copies of the reference biologic, known as biosimilars.
- A biosimilar is not necessarily identical to its reference biologic (see question below), but based on Health Canada’s guidelines and approval standards for the pharmacokinetics, pharmacodynamics, safety and clinical efficacy of biologics, the two are highly similar.
- As for all drugs, Health Canada’s authorization of a biosimilar requires meeting approval standards for manufacturing and controls.
- Health Canada says that there are no clinically meaningful differences between biosimilars and their reference biologic drugs.
How do biosimilars differ from generic drugs?
- The active ingredients in generic drugs are exactly the same as the brand name drug, while biosimilars are highly similar but not exact copies.
- The natural variability and more complex manufacturing of biologics does not allow an exact replication of a biologic molecule.
How are biologics and biosimilars manufactured?
- Since biologics and biosimilars are made inside living cells, every batch of biologics and biosimilars made is slightly different.
- When a manufacturer makes changes to the process of how a biologic is made, they need to prove that the product is highly similar to the previous product and that there is no adverse impact upon safety or efficacy.
How are biologics and biosimilars regulated in Canada?
- Biosimilars are regulated as new drugs under the Food and Drugs Act and the Food and Drug Regulations.
- For a drug to be called a biosimilar, the drug manufacturer must provide information to Health Canada to show that the biosimilar and the reference biologic drug are highly similar, and that there are no clinically meaningful differences in terms of safety and efficacy between them.
- Health Canada's decision to authorize a biosimilar for sale is based upon a benefit/risk assessment after considering all of the data submitted by the manufacturer.
- Health Canada's rigorous standards for authorization mean that patients and healthcare providers can rely upon the quality, safety and efficacy of a biosimilar, just as for any biologic drug.
Do biosimilars work as well as the reference biologic?
- Biosimilars have been shown to have no clinically meaningful differences from the reference biologic in properly designed clinical trials. These trials must have a sensitive and homogenous patient population, an appropriate clinical design and useful study endpoints.
- Biosimilars have been studied in large numbers of patients. As an example, trastuzumab biosimilars have been trialed in 6 independent Phase 3 clinical trials that had at least 500, and as many as 800 patients in each clinical trial.
- Biosimilars work in the same ways as their reference biologic. It is expected that if a patient is transitioned to, or started on, a biosimilar, they will have the same outcome as if they were treated with the reference biologic.
How are biologics and biosimilars monitored?
Health Canada monitors the safety of all drugs on the market, including biosimilars. Health Canada and manufacturers both play a role in monitoring drug safety.
- conducts market surveillance
- monitors adverse reaction reports
- investigates complaints and problem reports
- monitor reported side effects
- report any new information received about serious side effects to Health Canada
- notify Health Canada about any studies with new safety information
- request authorizations for any major changes to the manufacturing process, dose regimen or recommended use of the drug
What is switching?
- Switching generally refers to a change from the routine use of one specific product to the routine use of another specific product.
- No differences in efficacy and safety are expected following a change in the routine use between a reference biologic drug and its biosimilar in an authorized indication.
What does it mean to extrapolate indications?
- Once studies show that the biosimilar is highly similar to the reference biologic drug with no clinically meaningful differences, Health Canada can authorize the biosimilar for the same indications as the reference biologic drug, based on the previously established efficacy and safety of the reference biologic drug in each indication.
- This concept is often called extrapolation or extension of indications, and it avoids the unnecessary repetition of clinical studies.
- Authorization of each indication is also supported by scientific knowledge and the medical literature about the:
- reference biologic drug
- mechanism of action of the drug in the specific diseases or medical conditions involved
- As an example, rituximab (Truxima) was studied in non-Hodgkin’s lymphoma yet was also approved for chronic lymphocytic leukemia.
Can biologics and biosimilars be used “off-label”?
- Biologic or biosimilar drugs may be used for indications that were not submitted by the original manufacturer for approval by Health Canada if there is sufficient clinical evidence in the literature.
Is it safe to use a biologic for an indication that has not been approved by Health Canada?
- Health Canada does not make any safety recommendations for off-label use of approved medications. However, certain medications in Canada (e.g. bevacizumab (Avastin)) are used and provincially funded for indications where there is no Health Canada-approved indication (cervical cancer).
- In other regions (e.g., Europe) all indications for the reference biologic are extrapolated to the biosimilar.
How will biosimilars impact the health system in Canada?
- Biosimilars can support a more stable market supply of biologic drugs.
- Biosimilars can save money for the health system.
- Biologic drugs are very expensive to the health system. In 2018, Canada spent approximately $6.7 billion on all biologics.
- Biosimilars can be sold at a much lower price than the reference biologic.
- The money saved by using biosimilars can be put back into the cancer system to help pay for, and improve access to, new treatments.
Have any other jurisdictions successfully implemented biosimilars?
- Biosimilars have been in use for more than 10 years in Europe.
- As of January 2019, Europe has approved almost 60 different biosimilars.
- Europe has had more than 700 million patient treatment days and has not detected any signals that the products were less safe or efficacious than the reference biologic.
- The National Health Service has achieved almost 100% uptake of rituximab biosimilar.
When did oncology biosimilars enter the Canadian market?
- The first therapeutic oncology biosimilar received Health Canada Notice of Compliance in 2018, followed by public funding in 2019.
What cancer drugs will have biosimilars?
- As of February 2020, Health Canada has approved biosimilars for bevacizumab (Avastin), trastuzumab (Herceptin) and rituximab (Rituxan).