Biosimilars Facts

An additional treatment choice for patients with inflammatory arthritis

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

Health Canada defines biosimilars as a “biologic drug that enters the market subsequent to a version previously authorized in Canada, and with demonstrated similarity to a reference biologic drug.” While Health Canada uses the term “subsequent entry biologic,” the term “biosimilar” is used in Europe and the US. Health Canada has informed stakeholders that it intends to announce its adoption of “biosimilar” this fall when it releases a new guidance document.

While relatively new to Canada, biosimilars have been approved for use in Europe for a decade and for use in arthritis since 2013.


Biosimilars are not generics of their originator biologics
Biosimilars are similar, but not the same, as their originator biologics

Medications made with small, chemically manufactured molecules (e.g. acetylsalicylic acid, the active ingredient in aspirin) are made through a relatively simple process. After a manufacturer's patent for a particular medication, like aspirin, expires, other companies can easily make exact copies of the active ingredient of the brand name version. These are known as generics.

Biologics, however, are large molecule medicines made from living cells in a complex manufacturing process that can have a significant impact on the final drug product. It is impossible to make an exact copy of an originator biologic drug because the living cell structures cannot be the same.


Biosimilar Naming
Patient and healthcare professional groups have called for uniquely different brand naming for all biosimilars entering the Canadian marketplace to minimize confusion about which medication was being prescribed and filled at the pharmacy counter or infusion clinic, or taken by the patient. Unique naming is also very important when tracking adverse events at the population level.
Health Canada has decided to follow the non-proprietary naming protocol for biologics (including biosimilars) that is ultimately recommended by the World Health Organization (WHO). At the request of a number of regulatory jurisdictions, the WHO is working to address the issue of non-proprietary naming for biosimilars.
In late 2015, the WHO and the United States American Food and Drug Association (FDA) both released similar proposed guidance on naming - to add a unique identification code, consisting of four random consonants, to the existing non-proprietary name (e.g. infliximab wxyz).  The WHO guidance also recommends that regulatory agencies like Health Canada, can add in two numerical digits as a “check-sum”.  Health Canada is currently reviewing the WHO proposed guidance.

http://www.who.int/medicines/services/inn/WHO_INN_BQ_proposal_2015.pdf

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformati...

 

In 2016, patient experience with biosimilars around the world, particularly Europe, continues to grow and research-to-date shows their safety and efficacy profiles compared to their originator biologic (also referred as “brand name” biologic) to be very similar. Biosimilars have more pre-clinical data to inform physicians and patients making choices about medication therapy; however, biosimilars have less clinical trial data.  Pre-clinical data for biosimilars is as, or more, robust than that for originators’, in order for biosimilar manufacturers to demonstrate to regulators that they are highly similar in structure and function to the originator biologic.

ACE wants to know what do you think about biologics?

What are your views about biologics?

Biosimilars FAQs

  What are biologics?

Some of today’s important medications are biologic medications often referred to as “biologics.” They 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.

Biologics are among the medications used to treat diseases such as rheumatoid arthritis, anemia, low white blood cell counts, inflammatory bowel disease, skin conditions such as psoriasis and various forms of cancer. 

Biologics are more complex in structure and have larger molecules or mixtures of molecules than conventional (small molecule) medications. Conventional medications are made of pure chemical substances and their structures can be identified.  Most biologics, however, are complex mixtures that are more difficult to identify or characterize.

  What are biosimilars?

The term biosimilar or subsequent entry biologic is used by Health Canada to describe a “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.”

Biosimilars are made from the same basic building blocks as the originator, however biosimilars are not considered identical to their originator biologics because their chemical characteristics cannot be precisely duplicated during the manufacturing process. While there are concerns that biosimilars may have unique efficacy, immunogenicity, and safety profiles that are distinct from their originator biologics, the approval of biosimilars in Canada relies on the demonstration that these measures are equal between them. This is demonstrated through clinical (equivalence) trials in at least one disease indication, such as rheumatoid arthritis.

Health Canada uses the term “subsequent entry biologic;” however, the term “biosimilar” is used in Europe and the US. Health Canada has informed stakeholders that it intends to announce its adoption of “biosimilar” this fall when it releases a new guidance document.

While relatively new to Canada, biosimilars have been approved for use in Europe for a decade and for use in arthritis since 2013. 

  What is an originator biologic (also referred to as “reference biologic” or “brand name” biologic) medication?

An “originator biologic” is a biologic drug authorized on the basis of a complete quality, non-clinical, and clinical data package, to which a biosimilar is compared in studies to demonstrate similarity.

  Will biosimilars work in the same way as the originator biologic they were compared to?

A biosimilar needs to have the same mechanism of action as the originator biologic it was compared to, which means it should work in a similar way.

Health Canada will only approve a biosimilar if it has the same mechanism of action, route of administration, dosage form, and strength as the originator biologic. Additionally, a biosimilar can only be approved for the indications and conditions of use that have been previously approved for the originator biologic.

Once a biosimilar has been approved by Health Canada, patients and health care providers will be able to rely upon the safety and effectiveness of a Health Canada approved biosimilar just as they would for the originator biologic that the biosimilar was compared to.

  What is a generic medication?

A generic medication is chemically identical to a brand name drug in dosage, safety, strength, route of administration, quality, performance and intended use.

  Are biosimilars generic versions of their originator biologics?

No, biosimilars are not "generic biologics" and many characteristics associated with the authorization process and marketed use for generic pharmaceutical medications do not apply. Generic medications are copies of brand-name medications, have the same active ingredient, and are the same as those brand name medications in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use. That means the brand name and the generic are bioequivalent.  

According to Health Canada, “authorization of an SEB (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.”

 


Unlike generic medications, biosimilars are not identical to their originator biologics. Every biologic is made from living cells. To ensure that any minor structural differences of a biosimilar will not result in differences in the body, multiple tests called “assays” are conducted in the lab.
When those tests prove the biosimilar’s similarity to its originator biologic, it is then studied “head-to-head” against its originator biologic in clinical trials. Only then can it be confirmed as highly similar.

After the originator biologic patent expires, Health Canada reviews and may approve other manufacturers to introduce "similar" versions (like biosimilars) of the originator. Makers of biosimilars are expected to use the same building blocks (or “amino acid” sequence) as the originator biologic, but will use a different manufacturing process to form the final medication. In ACE surveys conducted across Canada, physicians and patients considered patient safety a primary concern in the use of biosimilars, or any marketed medication. They felt strongly that biosimilars be effectively tracked in the marketplace and that information should be made available for external review, as it is for their originator biologics.

  What is immunogenicity and why is it a special concern for biologics?

Immunogenicity is the ability to stimulate an immune response in the body of a human or animal. This ability generally protects people against pathogens by recognizing and reacting to foreign proteins. It is a specific concern for biologic medications because they are primarily protein medicines that may be seen as being foreign. An immune response to a biologic medication can range from development of detectable but not clinically significant antibodies to an immune response with significant impact on patient safety. A patient's immune response may also affect a treatment's effectiveness.


There are a number of ongoing studies, including “real world” tracking of patients, to monitor for any increase in immunogenicity when transitioning from an originator biologic to a biosimilar. This will help determine if transitioning patients can be considered a safe practice before it can be medically recommended or mandated through reimbursement policy.

  How is immunogenicity being addressed for biosimilars?

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.

  How are biosimilars regulated?

Biosimilars have a different approval pathway compared to originator biologics. Health Canada reviews the manufacturing process, data on the comparability of the biosimilar to the originator biologic and non-clinical and clinical data supplied by the biosimilar manufacturer, to establish whether it is similar enough to its originator biologic.

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.

  What is interchangeability or automatic substitution?

Interchangeability is a process that allows a pharmacist to automatically substitute one product for another 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.

At present and as it relates to biosimilars, Health Canada has declared biosimilars not to be interchangeable with their originator biologic. However, the provincial governments in Canada govern rules around the determination of interchangeability between an originator biologic and a biosimilar. They also regulate pharmacy substitution practices. Health Canada has stated: “SEBs (biosimilars) are not “generic” biologics and authorization of an SEB is not a declaration of pharmaceutical or therapeutic equivalence to the originator biologic.” Health Canada has expressed caution to the Provinces on the issue of interchangeability and has stated that physicians make only well-informed decisions on alternating or interchanging therapies.

  What is therapeutic substitution?

Therapeutic substitution, also referred to as “drug switching” or “therapeutic interchange”, is the practice of replacing the prescribed medication with a chemically different medication in the same class that is expected to have the same clinical effect. Therapeutic substitution usually occurs when the prescribed medication is substituted at the pharmacy counter with another due to cost differences. 

Health Canada has declared biosimilars are not declared to be pharmaceutically or therapeutically equivalent with their originator biologics, and this should inform decisions regarding interchangeability and substitutability. The authority to declare two products automatically substitutable by a pharmacist rests with provincial government. At this time, no provincial government in Canada has declared interchangeability between an originator biologic and a biosimilar and, therefore, there have been no cases of substititution in pharmacy practices across Canada."

  What does “switching” or “transitioning” mean?

“Switching” or “transitioning” means a patient is moved from one medication to another. In the case of biosimilars, there are two types of transitions:

Policy Transitions

Policy transitions (referred to as non-medical switching) necessitate patients to change their medicine of choice to another, typically less expensive, medicine, not for a medical reason.

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.

  Can a biosimilar be used to effectively treat the same diseases/conditions that its originator biologic drug treats?

A biosimilar may be granted any indications held in Canada by its originator biologic, but only if enough data is provided to support the claim. It can also be granted indications different from those of the originator biologic if a full clinical data package is submitted for those indications.

  What is 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.

Questions? We’ll find the answers for you.

As biosimilars research data continues to be published and policies regulating them evolve, ACE continues to provide information for the arthritis community and other chronic diseases such as diabetes, oncology and gastrointestinal diseases. As part of that commitment, we encourage you to send us questions. We will provide answers to you and add that content to our website. That’s what the Biosim•Exchange is all about.