Biosimilars Policy

Arthritis Consumer Experts (ACE) has been learning about biosimilars since 2009 and has become a national arthritis community thought leader, conducting biosimilar workshops and sharing education with multi-stakeholder groups across Canada. The ACE biosimilars dialogue across Canada has included patients, healthcare professionals and policy decision makers in government and private health insurance.

What are ACE's views on biosimilars policies in Canada?

As biosimilars research is published in peer reviewed medical journals and policies regulating them evolve, so do ACE’s organizational views. As always, ACE will follow the evidence.

ACE's mandate is to continue to provide the latest research-based education and information on biosimilars to its members, subscribers and the public, and our guiding principle has been, and continues to be, to follow the scientific evidence in our therapeutic area. Based on current biosimilars regulatory approvals, peer reviewed, well-designed research studies and current meta-analysis, our organization’s views are:

  • Treatment of patients living with inflammatory arthritis should ask for and expect the best care possible through shared decision-making between themselves, their rheumatologist and other healthcare providers;
  • Biosimilars may have advantages over their originators due to improvements in manufacturing processes, delivery devices, among others;
  • Similar to legislated generic drug savings in Canada, biologic biosimilars reimbursement policy has the potential to save public and private healthcare systems billions of dollars now and over the coming years;
  • More than 10 years of clinical experience shows that biosimilars approved through European Medicines Agency can be used as safely and effectively in all their approved indications as their originators;
  • Policy development related to biosimilars to treat inflammatory arthritis should include unbiased and credible patient and rheumatologist participation who fully disclose their sources of funding from the manufacturers of the drug products affected by the policy;
  • Patients should be able to assess treatment (or no treatment) risk against benefit, and have tools to enable them to discuss the pros and cons of all treatment options with their healthcare team;
  • Policy transition is appropriate if the prescribing physician and their patient have the education and information tools they need to support the patient in all aspects of accessing their biosimilar, from “care coach” to help with formulary or private insurance paperwork, to infusion clinic and pharmacy orientation, and adherence support;
  • Government should reinvest policy transition savings in a timely manner into innovative medicines on formularies for unmet patient needs, list biologics and tsDMARDs with revised/relaxed reimbursement criteria to make access more efficient, and implement other important aspects of inflammatory arthritis models of care, such as instituting rheumatology nursing billing codes;
  • Policy transitioned patients should be monitored as part of their routine care;
  • Treatment results should be collected on patients in whom multiple transitions are made between biosimilars and originators.

Policy framework and reimbursement access in Canada

Since 2015, provincial formularies and private health insurers have been providing reimbursement for the biosimilars approved in Canada for the treatment of inflammatory forms of arthritis. Both provincial and private payers are considering biosimilars as a key element in their mandates to list cost-effective medication treatment that is clinically meaningful to patients and contributes to long-term cost reductions and drug plan sustainability.

Determining the value to patients and the health care system

A biologic “biosimilar” enters the market after a biologic “originator’s” patent expires, like a small molecule generic medication does when the brand name medication’s patent expires. And just the way generic medications are much lower in price compared to their original versions, so too are biosimilars in comparison to their originators. They have the same safety and efficacy yet are significantly less expensive, and the cost savings to the health care system can result in positive benefits to patients and society not related to the medicines themselves.

Like legislated generic drug savings have in Canada, biosimilars reimbursement policy has the potential to improve access to biologics and save public and private healthcare systems billions of dollars now, and over the coming years.

As reported at a Health Canada Biosimilar Workshop on March 20, 2017:

“A competitive and sustainable market for biosimilar and innovator drugs could offer many benefits to the healthcare system, including broadening access to effective biologic treatments, reducing the cost burden and enabling savings to be re-directed across all areas of healthcare including funding of new innovative therapies.”

A study commissioned by the Patented Medicine Prices Review Board (PMPRB) and conducted by the National Prescription Drug Utilization Information System (NPDUIS), “Potential Savings from Biosimilars in Canada”, estimated potential savings for infliximab alone in Canada could range between $91M and $514M in the third year following biosimilar entry.

Biosimilars create three main benefits to patients, the healthcare system, and society:

  1. Savings from biosimilars use can modernize “special access criteria”. Currently, patients must try and fail treatment on older, less expensive medications. Because biosimilars are significantly less expensive, public and private drug formularies can remove the need for patients to fail on these older therapies before approving reimbursement for them;

  2. Savings from biosimilars use can be reinvested into public and private drug formulary budgets making it possible to add new innovative medications coming into the market place, and by doing so, expanding patient medication choice; and,

  3. Savings from biosimilars can be invested into non-medication elements of care that patients need, such as specialized nursing, counselling, physio and occupational therapy, among other important elements of a holistic inflammatory arthritis treatment plan. 

Understanding biosimilar terminology: transitioning, interchangeability, and substitution

In 2016 and the first half of 2017, as discussion around biosimilars in Canada has intensified, ACE has identified the need for clarifying issues and concerns related to policy terminology. From our discussions with stakeholders and our attendance at public and private sector biosimilars forums and workshops, ACE has observed that “transition” or “switch,” “therapeutic substitution” and “interchangeability” were all being used to describe transitioning a patient from an originator to its relevant biosimilar. At the same time, Health Canada, the US Federal Drug Administration and the European Medicines Agency have all issued further guidance on regulating biosimiliars in their countries. In all three environments, policy makers are increasingly aligning their policies, based on scientific evidence on safety and efficacy, on physician-led transitioning.

Comparing Biosimilars Policies: Canada, U.S. and the European Union

Starting with Canada, ACE provides you the following summary of biosimilars policy positions in Canada, the U.S. and the European Union as they continue to evolve.

Current Canadian Biosimilars Policies

While Canada has lagged behind Europe in terms of approving biosimilars, where regulators have approved 28 biosimilars between 2006 and 2016, Health Canada is beginning to narrow the gap.  Seven biologic biosimilars are currently approved by Health Canada: infliximab (Inflectra), infliximab (Renflexis), etanercept (Brenzys), etanercept (Erelzi), somatropin (Omnitrope); insulin glargine (Basaglar); and filgrastim (Grastofil).

In 2017, Health Canada revised its fact sheet on biosimilars. In line with changes to Health Canada’s Guidance Document, the Fact Sheet has been substantially rewritten and contains an overview and description of the regulatory framework for biosimilars. The Fact Sheet also includes a new section on drug and patient access and further defines transitioning or switching and interchangeability.

In December 2016, Health Canada released its revised Guidance Document on the approval pathway for biosimilars - Information and Submission Requirements for Biosimilar Biologic Drugs - based on experience gained as well as international developments in the regulation of biosimilars.

Health Canada on transitioning

Health Canada considers well-controlled switches from reference biologic drug to biosimilar in an approved indication to be acceptable. Health Canada recommends that a decision to switch a patient being treated with a reference biologic drug to a biosimilar, or between any biologics, be made by the treating physician in consultation with the patient and take into account any policies of the relevant jurisdiction.

Health Canada on 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 biologic originator. 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.

International Biosimilars Policy Perspectives

United States

In October 2017, the US Food and Drug Administration (FDA) published educational materials to help health care providers gain a better understanding of these important products and the approval process they undergo. This includes fact sheets and graphics for health care professionals, as well as materials for organizations to use in disseminating this information to their interested members.

In these educational materials, the FDA provided important guidance on whether a biosimilar or interchangeable product can be used in patients who have previously been treated with the reference product. According to the FDA, biosimilars and interchangeable products can be used in patients who have previously been treated with the reference product (treatment-experienced), as well as in patients who have not previously received the reference product (treatment-naïve).

Before approval of the biosimilar product, FDA may request additional data that looks at safety information for treatment-experienced patients who undergo a single transition (single switch) from a reference product to a biosimilar product

As part of the approval process for interchangeable products given more than once, manufacturers must show that patients can be switched back and forth between the reference product and the proposed interchangeable product without an increased risk in terms of safety or diminished efficacy.

In January 2017, the FDA released its draft guidance, which was initially expected to be published before the end of 2015, on biosimilar interchangeability with its biologic originator. This new regulatory framework sets the bar high for manufacturers of biosimilars. In the US, seven biosimilars have been approved to-date, none of which are considered to be interchangeable with their biologic originator.

According to the FDA, biosimilars will need to demonstrate the same clinical results (e.g. safety, purity, potency) as biologic originators for all approved indications, in order to be considered interchangeable. According to the FDA guidance, post-marketing studies for already-approved biologics will not be sufficient to support an application for interchangeability. The FDA guidance recommends that sponsors looking to get a biosimilar approved as interchangeable with its biologic originator conduct one or more switching studies to show that patients can alternate between a biosimilar and its biologic originator two or more times safely and without diminished efficacy.

ACR Response

The American College of Rheumatology (ACR) responded to the FDA guidance stating that the document addresses many of the safety and efficacy concerns physicians and patients have raised.

“The ACR is pleased to see the FDA issue draft guidance on biosimilar interchangeability,” expressed Dr. Angus Worthing, MD, FACP, chair of the ACR’s Government Affairs Committee. “This guidance brings us one step closer to the shared goal of lowering prices in the biologics marketplace. While the ACR is still reviewing the document and will provide detailed comments to the FDA in the coming weeks, our initial reaction is that the draft guidance strikes a good balance between ensuring safety and efficacy while also getting biosimilar products to market as efficiently as possible.”

“We also applaud the FDA for suggesting clinical studies which switch back and forth, not just one-way from the reference drug to the biosimilar. The use of at least two exposure periods to each drug will mimic to some extent what our patients are likely to experience with changing formularies in a multi-payer, multi-state, ever-changing market."

European Union

While relatively new to Canada, biosimilars have been approved for use in the European Union (EU) for a decade and for use in arthritis since 2013.

The European Medicines Agency (EMA) has not experienced any concerns with the safety of the 28 biosimilars it has recommended.

According to a CADTH Environmental Scan report, the use of biosimilars in the EU is expected to result in overall savings of between €11.8 billion and €33.4 billion by 2020

EMA has published a guide to provide HCPs with information on the science and regulation underpinning the use of biosimilars: “Over the last 10 years, the EU monitoring system for safety concerns has not identified any relevant difference in the nature, severity or frequency of adverse effects between biosimilars and their reference medicines”.

Currently, in the EU, the definitions of transitioning-switching, interchangeability and substitution are as follows:

Transitioning-Switching – decision by treating physician to exchange one medicine for another medicine with the same therapeutic intent

Interchangeability – the medical practice of changing one medicine for another that is expected to achieve the same clinical effect in a given clinical setting and in any patient on the initiative, or with the agreement of the prescriber

Substitution – practice of dispensing one medicine instead of another equivalent and interchangeable medicine at the pharmacy level with consulting the prescriber

In the EU, like in Canada, the ruling regulatory body (European Medicines Agency comparable to Health Canada) leaves the decision on a policy framework guiding the use of biosimilars to individual member countries (comparable to provincial and territorial policy decision making in Canada).

EU member countries generally agree to the fact that EU authorized biosimilars are considered alternative therapeutic options to their respective biologic originators, under the supervision of a clinical decision maker. The majority of countries, including England, Norway, Denmark, Germany, Netherlands, Belgium, France, and Portugal support physician led switching or transitioning for biosimilars. As of March 2017, there is also convergence across EU countries that biologics should not be substituted at the pharmacy level with the involvement of the clinical decision maker.

EU Associations and Patient Group Organization Response

Here is a brief summary of positioning statements by leading EU Medical Associations and Patient Groups:

EU - Consortium of individual Regulators (2017)

  • Because of the high similarity, there is no reason to believe that the body's immune system would react differently to the biosimilar compared with the original biological upon a switch. This view is supported by the current experience with biosimilars on the market and by literature data. 

European League Against Rheumatism (EULAR) - Biosimilars – 2015 What do patients need to consider?

  • National arthritis patient group organizations across Europe work together via the EULAR Standing Committee of PARE. Each EU member country is represented with one delegate in the committee.

  • The PARE committee issued a position paper on biosimialrs in 2015 where they stated many patients consider that leaving open the possibility of switching or transitioning, interchangeability and substitution would introduce unacceptable uncertainties into that decision-making process.

European Crohn’s and Colitis Organisation (ECCO) – 2016 ECCO position statement: the use of biosimilar medicines in the treatment of inflammatory bowel disease (IBD)

  • Switching* from the originator to a biosimilar in patients with IBD is acceptable

  • Clinical studies of equivalence in the most sensitive indication can provide the basis for extrapolation. Therefore data for the usage of biosimilars in IBD can be extrapolated from another sensitive indication.

  • When a biosimilar product is registered in the EU, it is considered to be as efficacious as the reference product when used in accordance with the information provided in the Summary of Product Characteristics.

  • Studies of switching can provide valuable evidence for safety and efficacy. Scientific and clinical evidence is lacking regarding reverse switching, multiple switching, and cross-switching among biosimilars in IBD patients.

  • Switching from originator to a biosimilar should be performed following appropriate discussion between physicians, nurses, pharmacists, and patients, and according to national recommendation. The IBD nurse can play a key role in communicating the importance and equivalence of biosimilar therapy.

*Please note the European Crohn's and Colitis Organisation uses the term "switching". ACE uses the term "transitioning".

European Society for Medical Oncology (ESMO) – 2017 Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers

Interchangeability and switching should only be permitted if:

  • the physician is well-informed about the products;
  • the patient is fully briefed by the physician; and
  • a nurse is closely monitoring the changes and tracking any adverse events.
The first biosimilars in Canada

In 2014, the first biosimilar in Canada approved for inflammatory arthritis was infliximab (Inflectra®). It was launched to treat severe rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA). In 2016, infliximab (Inflectra®) is being added to many provincial drug plans and private health insurance plans for the treatment of these diseases.

Infliximab (Inflectra®) is a biosimilar version of infliximab based upon the biologic originator infliximab (Remicade®). It was issued a Notice of Compliance (or “approved”) by Health Canada and recommended for listing on provincial formularies by the national Common Drug Review.

Health Canada has stated that biologic originators and biosimilars are not declared to be pharmaceutically or therapeutically equivalent. Health Canada does not support automatic substitution and does not recommend interchangeability of the biosimilar and the biologic originator; however, the decision to substitute one for the other is a provincial or private health insurer’s decision.

For information on Health Canada’s decision, please see the Summary Basis of Decision for infliximab (Inflectra®) available at:

https://health-products.canada.ca/noc-ac/info.do?lang=en&no=18169

Additional information may be found in the Inflectra® Product Monograph, approved by Health Canada and available here: 

https://pdf.hres.ca/dpd_pm/00035250.PDF

For Common Drug Review’s review and recommendation, please see: https://www.cadth.ca/sites/default/files/cdr/complete/cdr_complete_SE038...

The second biosimilar in Canada approved for inflammatory arthritis is etanercept (Brenzys®). It is a biosimilar version of etanercept based upon the reference product etanercept (Enbrel®). It was issued a Notice of Compliance by Health Canada on August 31, 2016 for the treatment of patients with rheumatoid arthritis and ankylosing spondylitis.

For information on Health Canada's decision, please see the Summary of Basis of Decision for etanercept (Brenzys®) availble at: https://health-products.canada.ca/noc-ac/info.do?lang=en&no=18480

Additional information may be found in the Brenzys® Product Monograph, approved by Health Canada and available here:

https://pdf.hres.ca/dpd_pm/00036407.PDF

For Common Drug Review's review and recommendation, please see: https://www.cadth.ca/sites/default/files/cdr/complete/SE0485_complete_Br...

The third biosimilar in Canada for inflammatory arthritis is etanercept (Erelzi®). It is a biosimilar version of etanercept based upon the reference product etanercept (Enbrel®). It was issued a Notice of Compliance by Health Canada on April 5, 2017 for the treatment of patients with rheumatoid arthritis, ankylosing spondylitis and juvenile idiopathic arthritis. 

For information on Health Canada's decision, please see the Summary Basis of Decision for etanercept (Erelzi®) available at: 

https://health-products.canada.ca/noc-ac/info.do?lang=en&no=19131

Additional information may be found in the Erelzi® Product Monograph, approved by Health Canada and available here: 

https://pdf.hres.ca/dpd_pm/00038823.PDF

For Common Drug Review's review and recommendation, please see: 

https://www.cadth.ca/sites/default/files/cdr/complete/SE0513_complete_Er...

Biosimilars Policy FAQs

Are patients taking infliximab (Remicade) or etanercept (Enbrel) and currently reimbursed by a provincial formulary or private drug plan required to transition to the biologic biosimilar versions of those two brand name biologics?

Health Canada recommends that physicians make well-informed choices when considering interchanging therapies. Currently, provincial and private drug plans are not mandating policy transition between a patient’s current biologic to an approved biosimilar.

In terms of “transitioning” or “switching,” Health Canada recommends those decisions should be made by the physician and their patient:

“Switching generally refers to a one-time change from a reference biologic drug to a biosimilar. Health Canada recommends that a decision to switch a patient being treated with a reference biologic drug (innovator product) to a biosimilar should be made by the treating physician in consultation with the patient and taking into account available clinical evidence and any policies of the relevant jurisdiction. For questions related to changing from one biologic drug to another, patients should speak to their doctor.”

Click here to see Health Canada's Fact Sheet: Biosimilars: https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/fact-sheet-biosimilars.html

Currently, provincial and private drug plans are not mandating policy transition between a patient’s current bioloigic to an approved biosimilar.

Except in Saskatchewan, there is convergence across Canadian provinces and territories that patients newly prescribed infliximab for rheumatoid arthritis, psoriatic arthritis, ankylosing arthritis and plaque psoriasis are reimbursed for the biosimilar in place of the originator biologic. There is convergence across Canadian provinces and territories that patients newly prescribed etanercept for rheumatoid arthritis and ankylosing spondylitis are reimbursed for the biosimilar in place of the originator biologic.

Current funding status of infliximab (Inflectra) with provincial formularies

Infliximab (Inflectra) has been listed in a number of provinces across Canada. Here is a summary of the reimbursement criteria in those provinces.

Have you been affected by new biosimilars policy?

Provincial formularies and private health insurers have begun providing reimbursement for the first biosimilar approved in Canada. Have you had experience gaining reimbursement for a biosimilar prescription with a provincial or private health insurance formulary?