Biologic drugs (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, lymphoma, ovarian and other cancers. Since biologics are made from living cells, every batch is almost the same but not identical.

A reference biologic is the original branded product approved by Health Canada. When the patent for a reference biologic expires, manufacturers can make highly similar copies of the reference biologic, known as biosimilars. In Canada, biosimilars were previously called subsequent entry biologics (SEBs).

The active ingredients in generic drugs are exactly the same (identical) as the brand name drug, while biosimilars are highly similar but not exact copies. The natural variability and more complex manufacturing of biologics do not allow for exact replication of a biologic molecule.

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.

Yes. Biosimilars have been shown to be equivalent to their reference biologics 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 assessed in six independent Phase 3 clinical trials that had between 500 to 800 patients in each clinical trial.

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.

Switching generally refers to a one-time change from a reference biologic drug to a biosimilar but can also refer to a change from a biosimilar to a reference biologic or another biosimilar.

Extrapolation is often used to refer to the authorization (by a regulatory body, like Health Canada) of a drug for indications where clinical studies were not done. For example, subcutaneous rituximab was studied in follicular lymphoma, yet approved for all types of lymphoma. 

Extrapolation also refers to the use of a drug for indications that are not approved by Health Canada. In some instances, these indications are publicly funded. Health Canada may extrapolate biosimilar indications to indications where clinical studies were not done.

Yes. Health Canada states that a biosimilar can have an indication different from what was studied for its approval based on scientific rationale, although Health Canada does not make any safety recommendations for off-label use of approved medications. In Canada, some medications are occasionally used in cancers for which there is no Health Canada approval (e.g., bevacizumab in cervical cancer). In other regions (e.g., Europe) all indications for the reference biologic are extrapolated to the biosimilar.

Biosimilars can save money for the health system. Biologic drugs are very expensive to the health system. In 2016, Canada spent more than $3.6 billion on these drugs. Implementation of biosimilars creates cost savings that can be put back into the cancer system to pay for, and improve access to new treatments.

Biosimilars have been in use for more than 10 years in Europe. As of January 2019, Europe had approved almost 60 different biosimilars. Europe has had more than 700 million patient treatment days with biosimilars, and has not detected any signals that the products were less safe or efficacious than their reference biologics. The National Health Service has achieved almost 100% uptake of rituximab biosimilar.