According to Health Canada legislative and regulatory provisions, a biosimilar is a biologic drug that was authorized to enter the market subsequent to a first innovative version previously approved in Canada and has demonstrated similarity to a reference biologic drug. Biosimilars are marketed chiefly to reduce the economic burden of patients and the third-party payer, whether public or private.
Health Canada’s biosimilar drug review procedures rest on thorough scientific analysis similar to that applied by other regulatory agencies, including the European Medicines Agency (EMA). The approval of any biosimilar medication requires demonstration of its similarity to the reference biologic drug in terms of molecular structure, physicochemical properties, biological activity and immunochemical properties. Once this first requirement is met, non-clinical and clinical data to compare biosimilar and reference drugs are analyzed to support the clinical indications requested by the drug manufacturer concerned. Following this procedure, the biosimilar drug sponsor can obtain approval for all the indications held by a reference biologic drug on market in Canada even though clinical studies are not conducted for each one of them. In such cases, approval is based on scientific evidence, which must factor in the following: drug’s action, physio-pathological mechanisms of the illness or health condition concerned, safety profile, dosage regimen, and clinical experience with the reference biologic drug.
INESSS Review Procedures for Biosimilars
As stipulated in the Act respecting the Institut national d’excellence en santé et en services sociaux, INESSS conducts a two-step drug analysis procedure. It assesses the therapeutic value of the medication; if the therapeutic value is not established to satisfaction, INESSS communicates a notice to that effect to the Minister of Health and Social Services; if INESSS considers that the therapeutic value of the medication has been established, it continues its assessment, taking into consideration all the aspects prescribed by the Act, which are listed below:
- The reasonableness of the price charged;
- The cost-effectiveness ratio of the medication;
- The impact that entering the medication on the list will have on the health of the general public and on other components of the health and social services system; and
- The advisability of entering the medication on the list, given the purpose of the basic prescription drug insurance plan.
The therapeutic value of a biosimilar drug is assessed on the basis of demonstration of its similarity with the reference product; in general, the reference product is the brand name drug marketed in Canada. For assessing a biosimilar drug, it is essential for the therapeutic value of the reference product to be recognized by INESSS.
Since the Notice of Compliance (NOC) from Health Canada confirms that the biosimilar drug and the reference product are similar and show no clinically significant difference in terms of safety and efficacy, the assessment of the therapeutic value of the biosimilar drug for a given indication relies on the NOC.
Moreover, INESSS conducts an assessment of the efficacity and safety data of a biosimilar medication used by patients who were previously prescribed the reference product.
Reasonableness of the price charged and cost-effectiveness ratio of the medication
Evaluation of the reasonableness of the price charged for a medicinal product and its cost-effectiveness ratio on the basis of the criterion of efficacy allows to appreciate the investment resources associated with drugs evaluated in relation to expected therapeutic results.
This evaluation is based on a pharmacoeconomic analysis conducted in the target population for the intended indication. Given the demonstration of the similarity in efficacy and safety between the biosimilar medication and comparator drug it is intended to substitute, the efficacy of the products is assessed by comparing prices only.
Impact of entering the medication on the list on the health of the general public and on other components of the health and social services system, and particular considerations (health economics, purpose of the basic plan, considerations of ethical nature)
A budget impact analysis is conducted to prove the financial capacity of the health and social services system to offer this drug. This analysis is used to estimate the impact of listing the biosimilar drug on the budget of the Régie de l’assurance maladie du Québec (RAMQ) – as regards the public portion of the prescription drug insurance plan – or on that of the health institutions.
- When INESSS receives a request to enter a first biosimilar drug on the list, the manufacturer of the reference product is notified and is given the opportunity to submit – within a prescribed time period – an application for exemption from application of the Lowest Price Method (LPM); this application must be scientifically documented.
- In cases where a reference biologic drug has not been assessed by INESSS or entered on the list of drugs, the biosimilar drug is assessed against the requirements for the brand name drug.
- INESSS reserves the right to conduct a comprehensive evaluation if it considers that significant issues of whatsoever nature so require.