Biosimilars Resources

Biosimilars Library

Health Canada Biosimilars Landing Page

https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/biosimilar-biologic-drugs.html

  • Provides information about biosimilars including a fact sheet, relevant guidance documents, scientific advice meetings and links to approved drugs.

 

Biosimilars Fact Sheet

https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/fact-sheet-biosimilars.html

  • provides information about biosimilars and their regulation in Canada.

 

Health Canada Guidance Document: Information and Submission Requirements for Biosimilar Biologic Drugs

https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/information-submission-requirements-biosimilar-biologic-drugs-1.html

  • Communicates the regulatory framework for biosimilars and is intended to help manufacturers follow the laws and regulations governing the authorization of biosimilars in Canada

 

Dorner, T, Kay J. Biosimilar agents in rheumatology: current perspectives and lessons learnt. Nat Rev Rheumatol. 2015; 11:713-724

https://www.researchgate.net/profile/Jonathan_Kay/publication/281096426_Biosimilars_in_rheumatology_Current_perspectives_and_lessons_learnt/links/56658c2308ae4931cd623f1a/Biosimilars-in-rheumatology-Current-perspectives-and-lessons-learnt.pdf

 

Kay J. Biosimilars: New or déjà vu? Arthritis Rheumatol. 2016; 68: 1049-1052

http://onlinelibrary.wiley.com/doi/10.1002/art.39568/full

 

Kay J, Schoels MM, Dorner T, Emery P, Kvien TK, Smolen JS, Breedveld FC. Consensus-based recommendations for the use of biosimilars to treat rheumatologic diseases Ann Rheum Dis. 2017 September 2. doi: 10-1136/annrheumdis-2017-211937.

http://ard.bmj.com/content/early/2017/09/04/annrheumdis-2017-211937

Biosimilars Glossary

Biologic

Biologic medications are made from living organisms. The material they are made from can come from many sources, including humans, animals and microorganisms such as bacteria or yeast. Biologic medications are manufactured through biotechnology, derived from natural sources or, in some cases, produced synthetically.

Biosimilars

Biosimilars describe a group of biologic medications that are administered by subcutaneous injection or intravenous infusion and are similar, but not the same, as their originator biologics (also referred to as “brand name” biologics).

Health Canada defines a biosimilar as “biologic product that would enter the market subsequent to, and similar to, an approved innovator biologic, which would rely in part, on prior information regarding safety and efficacy that is deemed relevant due to the demonstration of similarity to a reference biologic product (originator biologic).”

Equivalence

According to Health Canada, “authorization of a biosimilar is not a declaration of pharmaceutical equivalence, bioequivalence or therapeutic equivalence to the originator biologic.” Biosimilars are highly similar to the originator biologic they were compared to, but have allowable differences because they are made from living organisms. Biosimilars also have no clinically meaningful differences in terms of safety, purity, and strength from the originator biologic.  Health Canada also states: “the demonstration of similarity does not signify that the quality attributes of the two products being compared are identical, but that they are highly similar with two consequences:

  1. that the existing knowledge of both products is sufficient to predict that any differences in quality attributes should have no adverse impact upon safety or efficacy of the biosimilars; and

  2. that non-clinical and clinical data previously generated with the reference biologic drug are relevant to the biosimilar.”

Extrapolation 

Health Canada may approve a biosimilar to treat a disease without any clinical trial data to support its use in that disease. Once “biosimilarity” to the originator has been demonstrated, it is no longer a requirement to re-study the biosimilar in all indications previously studied with the originator product. This is called "indication extrapolation." Approval of a biosimilar is not a declaration of bioequivalence with the originator biologic. Post-approval, biosimilars are regulated like any new biologic medicine.

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 approval of biosimilars. In addition, biosimilar manufacturers are responsible to monitor the immunogenicity potential of the biosimilar after it is on the Canadian market.

Interchangeability

In Canada, interchangeability often refers to the ability for a patient to be changed from one drug to another equivalent drug 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 drugs that are off patent and have been deemed interchangeable with their generic equivalent.

For example, say a patient self-administers a biologic medication by injection to treat their rheumatoid arthritis. To receive the biosimilar instead of the reference product, the patient needs a prescription from a rheumatologist written specifically for that biosimilar. However, once a product is approved by Health Canada as interchangeable, the patient may be able to take a prescription for the reference product to the pharmacy and, depending on the Province or Territory, the pharmacist could substitute the interchangeable product for the reference product without consulting the rheumatologist. 

At present and as it relates to biosimilars, Health Canada has declared biosimilars not to be interchangeable with their originator biologic. 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 drugs. According to the new guidance from Health Canada, interchangeability decisions rest with provincial or territorial governments. They also regulate pharmacy substitution practices.

Medical Transitions

In the case of a patient not doing well on their current originator biologic or biosimilar of choice, a transition to another originator biologic or biosimilar, or other non-biologic medicine, with a different molecular action is then considered by the patient and their rheumatologist. Transitioning when medically required is important to achieving the best disease control and outcomes.

New Starts

New starts are patients who have been newly prescribed a biologic medicine. For example, infliximab (Inflectra) has been approved for patients newly prescribed infliximab (“new starts”) on public drug plans across Canada.

Policy Transitions

Policy transition (“non-medical switching”) occurs when a public or private drug plan’s reimbursement policy necessitate patients move from their current biologic originator to its biologic biosimilar, usually because it is significantly less expensive. Policy transition is not medically related.

Biosimilars FAQs

Biosimilars Workshop

Arthritis medication naming system

In light of the recent arrival of new classes of medicines for certain types of inflammatory arthritis, such as biosimilars and Janus kinase (JAK) inhibitors, a new naming system for disease-modifying anti-rheumatic drugs (DMARDs) is being adopted in Europe and North America.

Essentially, there are two categories of medications: a group that treats disease symptoms and a group that treats the underlying disease process.

1. Medications to treat symptoms

- non-steroid anti-inflammatories (NSAIDs)

- pain relievers, like acetaminophen (Tylenol®)

- steroids

- opioids (narcotics)

Glucocorticoids (GC such as steroids like prednisone): steroids are often used as a “bridging therapy” or to treat life-threatening or organ-threatening complications of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, systemic lupus erythematosus, and vasculitis.

Non-steroidal anti-inflammatory drugs (NSAIDs such as aspirin, naproxen and celecoxib): these medications help to reduce the inflammation and pain caused by rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and osteoarthritis. Some NSAIDs are available over the counter like ibuprofen (e.g. Motrin or Advil) or naproxen (Aleve) while others require a prescription.

2. Medications to treat the underlying disease

The term “disease-modifying anti-rheumatic drugs” (DMARDs) is used to categorize certain medicines that suppress the disease process that causes the worsening of rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, among many other types of inflammatory arthritis. They alter the natural course of the disease. DMARDs suppress the inflammation, slow joint damage, decrease autoantibody levels and have positive effects on long-term functional outcome.

DMARDs now come in all “shapes and sizes” and can be taken by pill, self-injection and infusion (IV). Each DMARD works in a unique way and the decision about which one(s) is best for you is perhaps the most important conversation you can have with your rheumatologist.

In the new naming system for disease-modifying anti-rheumatic drugs (DMARDs), there are classifications for:

Synthetic (or chemical) DMARDs are now divided into:

csDMARDs: Conventional synthetic DMARDs include traditional medications such as methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, gold salts and others.

tsDMARDs: Targeted synthetic DMARDs include only those medications that were specifically developed to target a particular molecular structure such as tofacitinib, baricitinib or apremilast, or agents not focused primarily on rheumatic diseases, such as imatinib or ibrutinib.

Biological DMARDs are now divided into:

boDMARDs: Biological original DMARDs include abatacept, adalimumab, anakinra, certolizumab peogl, etanercept, golimumab, infliximab-Remicade, rituximab or tocilizumab

bsDMARDs: Biosimilar DMARDs include infliximab-Inflectra