General information about generic drugs
What are generic drugs?
Generic drugs are essentially copies of brand name drugs. They can be sold as soon as the equivalent brand name drug's patent has expired. They contain the same active ingredients, in the same amounts, as their brand name equivalents and must meet the same strict federal standards, notably with regard to product manufacturing and quality control. Therefore, a generic drug is considered the therapeutic equivalent of the original product. The presentation of the drug may be different, such as its shape, format, colour or taste, because the two products do not necessarily have the same inactive ingredients (colourant, flavour, preservative). However, generic drug manufacturers must demonstrate that these differences in no way affect the product's quality, efficacy and safety.
Are generic drugs inferior to brand name drugs?
No. Health Canada is the federal regulator responsible for authorizing the sale of all drugs and reviewing their safety and quality, whether the product in question is a brand name or generic drug. The active ingredients in a generic drug and its corresponding brand name drug must meet the same scientific standards established by the Therapeutic Products Directorate of the Health Products and Food Branch. The excipients (inactive ingredients) used in generic and brand name drugs come from a limited range of products. When Health Canada issues a Notice of Compliance, this means the product meets Food and Drug Regulations standards concerning efficacy, safety, purity and production quality.
Why do generic drugs cost less if they meet the same quality standards?
The primary reason for the cost difference between brand name drugs and their generic counterparts is the fact that generic drug manufacturers spend a lot less time and money on research and development than innovative companies. In fact, to be granted a patent to protect an innovative new drug molecule, the patent holder must publish all the critical information concerning said molecule. Once this patent expires, the "recipe" can then be used by anyone. Promoting an innovative product also contributes to its higher cost. The fact that generic drugs cost less than their brand name equivalents does not mean that they have lower quality standards. On the contrary, all drugs must meet the same rigorous scientific standards.
What does "bioequivalence" mean?
According to Health Canada, bioequivalence is defined as a high degree of similarity in the bioavailabilities of two pharmaceutical products that contain the same concentration of the same active ingredient (for example, a brand name drug and its generic equivalent). The bioavailability of a product is a measurement of the rate and extent to which its active substance is absorbed into the bloodstream. This means that two bioequivalent products are absorbed in a similar fashion and are unlikely to produce clinically significant differences in therapeutic effects and adverse reactions.
To determine whether two products are bioequivalent, studies are conducted to measure the blood concentrations of the active ingredient in healthy volunteers. Each study participant receives both the brand name drug and the generic drug. By looking at the results of multiple blood samples, the study determines whether the generic drug is absorbed the same way as the branded version.
When INESSS evaluates a generic drug, does it require proof of bioequivalence with the brand-name counterpart?
Yes. Proof of bioequivalence is one of the required items in a registration application for a generic drug. This document demonstrates that the generic product meets Health Canada standards with regard to its bioequivalence to the brand-name product. Proof of equivalence may be, for example, the Notice of Compliance that mentions the Canadian reference product or the summary report of the bioequivalence study findings submitted to Health Canada to obtain the Notice of Compliance.
How does Health Canada establish bioequivalence between a generic and brand name drug?
Given the numerous elements considered by Health Canada when establishing bioequivalence between generic and brand name drugs, you are invited to consult the Health Canada Website and search the term "bioequivalence" for details on the bioequivalence standards for various product categories.
What, exactly, is the "80% to 125% rule" we sometimes hear about?
The 80% to 125% rule refers to the Health Canada standards that must be met when determining the bioequivalence of two products. In a bioequivalence study, the findings must demonstrate that certain parameters describing the absorption of the generic product are similar to those of the brand name product, that is:
- The 90% confidence interval of the relative mean area under the concentration versus time curve (AUC) of the test to reference formulation should be within 80% and 125% inclusive.
- The relative mean maximum observed concentration (Cmax) of the test to reference formulation should be between 80% and 125% inclusive.
It is important to understand that these two elements constitute only one part of the Health Canada standards on bioequivalence. Furthermore, this "80% to 125% rule" applies to most drugs. However, requirements may differ for certain drug categories, for example, those with a narrow therapeutic range (critical dose drugs).
There is a common misconception that the "80% to 125% rule" means the allowed variance in drug absorption between a generic product and its brand name equivalent is 45%. This is false.
What are the bioequivalence requirements for drugs with special pharmacokinetic properties?
Health Canada has special bioequivalence requirements, notably for combination drug products, long half-life drugs, drugs for which an early time of onset or rapid rate of absorption is important (rapid onset drugs) and drugs in modified-release formulations.
In addition, Health Canada qualifies certain drugs as "critical dose drugs." This category includes drugs for which comparatively small differences in dose or concentration can lead to potentially serious adverse reactions or therapeutic failures. This category currently includes the following drugs: cyclosporine, digoxin, flecainide, lithium, phenytoin, sirolimus, tacrolimus, theophylline and warfarin. For these drugs, Health Canada applies stricter bioequivalence standards between brand name and generic products, that is:
- The 90% confidence interval of the relative mean area under the concentration versus time curve (AUC) of the test to reference formulation should be within 90% and 112% inclusive.
- The 90% confidence interval of the relative mean maximum observed concentration (Cmax) of the test to reference formulation should be between 80% and 125% inclusive.
Furthermore, these requirements must be met in both the fasted and fed states.
For more information, search the term "bioequivalence" on the Health Canada Website.
Is it true that switching from a brand name drug to a generic product can cause variations in the drug's blood concentration?
Switching from a brand name drug to a generic product can cause variations in the drug's blood concentration. For this reason, bioequivalence studies are designed to ensure that these variations are minimal and clinically insignificant.
Does registration of a generic drug on the List of Medications mean that pharmacists can substitute a brand name product with the generic one without questioning?
No. The generic drugs registered on the List of Medications are usually bioequivalents of brand name products according to Health Canada standards. However, the purpose of the List of Medications is not to determine that a given drug is interchangeable with other products registered on the list. Instead, it looks at the classification of drugs whose cost is covered by the public plan, as well as the price and pricing method adopted by the Régie de l’assurance maladie du Québec. Pharmacists must observe the laws governing professions in Quebec when substituting products and inform patients about their prescribed medication.
Can a prescribing physician request that a patient receive the prescribed brand rather than another version?
Yes. Prescribing physicians can write on the prescription that they wish the patient to receive the prescribed brand and none other. This can be done for a brand name drug or generic drug.
With regard to the reimbursement of a brand name drug that costs more than its generic versions, the brand name drug will be reimbursed if the prescribing physician writes "no substitution" and indicates a reason code corresponding to recognized therapeutic concerns specific to the patient's condition. These concerns could include, for example, a documented allergy or intolerance to an ingredient in the drug other than the active substance, or a dosage form that is not suitable for the patient. In the absence of recognized therapeutic concerns, insured individuals may, if they wish, obtain the brand name drug despite the existence of a less expensive generic drug, but they will have to pay the cost difference between the brand name drug and the lowest priced generic version. The reimbursed cost will, in fact, correspond to the lowest price charged by the various brands containing the same active ingredient.
These new rules concerning the use of "no substitution" came into effect on April 24, 2015, for new prescriptions, and on June 1, 2015 for existing prescriptions.
|Generic name||Recognized indications for coverage (under certain conditions)||Products||Application of the lowest price method (LPMi)|
Chronic myeloid leukemia (CML) |
Acute lymphoblastic leukemia
Gastrointestinal stromal tumours
|Gastrointestinal stromal tumours||GleevecTM||
i The LPM is used to establish the price payable for certain drugs (generic names) registered on the List of Medications that are produced by two or more manufacturers. The lowest price is based on the lowest guaranteed selling price for pharmacists submitted by a manufacturer for a given package size.