Biologics (original-brand biologics and biosimilars)

Biologic medicines come from living organisms or from their cells and are often made using biotechnology. They are used to treat diseases and medical conditions including anemia, hormone deficiency, inflammatory arthritis, certain types of cancer, diabetes, inflammatory bowel disease and psoriasis. Biologics are generally larger and more complex than chemically produced medicines.

Biosimilars

As patents expire for originator medicines, manufacturers may produce new versions of the biologic medicines called biosimilars.

To receive Health Canada's authorization for sale, a biosimilar must demonstrate that there are no clinically meaningful differences in terms of physiochemical structure, function, efficacy and safety and immunogenicity. Clinical efficacy studies must demonstrate that the therapeutic effects of the biosimilar (both risk and benefit) are consistent.¹¹

After a medicine is authorized for sale, post-market analyses and studies can further demonstrate no meaningful differences in clinical efficacy between a biosimilar and the original-brand biologic.¹²

Since 2009, Health Canada has authorized for sale 37 biosimilars of 15 original-brand medicines.

Original-brand biologic

Original-brand biologics are biologic medicines already authorized for sale (also known as the reference biologic). When the patent of an original-brand biologic expires, pharmaceutical manufacturers are allowed to make a biosimilar version or follow-on medicine of the original-brand biologic.

Authorization

Medicines are authorized for sale in Canada once they have successfully gone through the drug review process. This process involves the review of a drug application by scientists in the Health Products and Food Branch of Health Canada, and on occasion, outside experts, to assess the safety, efficacy and quality of a medicine.¹³

Throughout the process, the safety and well being of Canadians is the paramount concern.

Generics

Generic medicines are small molecules that are chemically synthesized and are equivalent to the original-brand name products both pharmaceutically and therapeutically. In other words, they feature the same amount of active ingredient(s) and the same dosage forms and also meet the same applicable (and other) standards of strength, quality, purity and identification. They are also administered, usually in pill form, in the same way as the original medications.

Switching

For the past five years, provincial drug plans across Canada have listed biosimilar brands ahead of original-brand biologics for treatment-naïve patients (patients who have not previously received the original-brand biologic). Since 2019, some provincial formularies have begun implementing “switch” policies that change coverage for specific biologic medicines.¹⁴

Under a switch policy, patients and their prescribers have a certain period to discuss switching from an originator brand to a biosimilar brand. Patients unable to switch or who have an adverse response to the biosimilar can seek exceptional “special authority” coverage for the original-brand biologic.¹⁵

In the context of biosimilar use, Health Canada “considers switching between authorized products to refer to a change from routine use of one specific product to routine use of another specific product. Patients and healthcare providers can have confidence that biosimilars are effective and safe for each of their authorized indications. No differences are expected in efficacy and safety following a change in routine use between a biosimilar and its reference biologic drug in an authorized indication.”¹⁶

Prior to switching, both physicians and their patients must be fully informed and have all available information about the biosimilar medicine, such as details about the reimbursement policy, patient support program information, including contact names and phone numbers.

Immunogenicity

The immune system has evolved to recognize foreign proteins in the body. Biologics are usually injected into the body and the immune system often reacts to them. This reaction is referred to as the immunogenicity of the product.

Sometimes immunogenicity can only be detected using sophisticated laboratory tests and has no impact on the patient. In other cases, immunogenicity can impact patient safety or how well the medication works.

Health Canada is addressing immunogenicity as part of the comparative clinical trials required for authorization of biosimilars. In addition, biosimilar manufacturers are responsible to monitor the immunogenicity potential of the biosimilar after it is on the Canadian market.¹⁷

Interchangeability

In Canada, interchangeability often refers to the ability for a patient to be changed from one medicine to another equivalent medicine by a pharmacist, without the intervention of the doctor who wrote the prescription when it has been deemed interchangeable by a Provincial or Territorial regulatory body. For instance, this is a common practice for medicines that are off patent and have been deemed interchangeable with their generic equivalent.

At present and as it relates to biosimilars, Health Canada has declared biosimilars not to be interchangeable with their originator biologic.¹⁸ Health Canada's authorization of a biosimilar is independent of provincial, territorial, or private drug plan decisions regarding its formulary listing and reimbursement or any decision as to interchangeability between these medicines.

According to the new guidance from Health Canada, interchangeability decisions rest with provincial or territorial governments, which also regulate pharmacy substitution practices.

Extrapolation

Once studies show that the biosimilar is highly similar to the reference biologic medicine with no clinically meaningful differences, Health Canada can authorize the biosimilar for the same indications as the reference biologic medicine, based on the previously established efficacy and safety of the reference biologic medicine in each indication.¹⁹

This concept is often called extrapolation or extension of indications, and it avoids the unnecessary repetition of clinical studies.

An indication is a term that means the use of a medicine to treat a specific disease or medical condition. Many biologic medicines are authorized for more than one indication.

Authorization of each indication is also supported by scientific knowledge and the medical literature about the:

• biosimilar
• reference biologic medicine
• mechanism of action of the medicine in the specific diseases or medical conditions involved

Patients and prescribers can have confidence in the use of a biosimilar in each indication authorized by Health Canada.

Post-marketing surveillance

After a medicine is authorized for sale, post-market analyses and studies can further demonstrate no meaningful differences in clinical efficacy between a biosimilar and the originator.

Health Canada monitors the safety of all medicines on the market, including biologics (original-brand and biosimilar).²⁰

Health Canada:

• Conducts market surveillance
• Monitors adverse reaction reports
• Investigates complaints and problem reports
• Takes action as appropriate

Health Canada also requires medicine manufacturers to monitor for biologics (original-brand and biosimilar) safety:

• Set up a system to 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 approval for any major changes to
• the manufacturing process,
• dose regimen, or
• recommended uses of the medicine²¹

Health Canada also receives drug safety information from other jurisdictions including the United States and the European Union.