Canada's generic drugs: The basis for trust in their clinical efficacy

Jake Thiessen opened The Value of Generic Drugs Symposium with a discussion on the safety of generic drugs. Health Canada’s mandate, as Thiessen pointed out, is to ensure that all the medications that Canadians receive are therapeutically safe, effective and of high quality.

Thiessen, the founding director of the University of Waterloo’s Faculty of Pharmacy, helped his audience to understand the approval process for generic prescription medicines and the meaning of “bioequivalency.” He explained that, although some people may think generic drugs are inferior to brandname drugs, Health Canada’s leading edge standards requires that pharmaceutical manufacturers follow rigid scientific and clinical evidence to ensure brand-name and generic drugs are equally safe, effective and of high quality.

Brand-name drugs go through a number of stages before receiving approval from Health Canada: discovery; pre-/nonclinical studies; various phases of clinical studies and human testing; a National Drug Schedule review; and then, once approved, post-approval surveillance. Generic drugs don’t have to submit to the whole bank of clinical trials again but, rather, are required to undergo an equivalence testing study using what’s already known about the brand-name drug.

To be deemed “bioequivalent,” a manufacturer must show that a generic drug’s performance in delivering itself to the body is the same as that of the brand-name drug. The manufacturer then presents this evidence to Health Canada, which acknowledges that the generic shows a sufficiently high degree of similarity to the brand-name drug, and will be unlikely to produce clinically relevant differences in therapeutic effects, adverse effects or both.

“Every product must be evaluated comparatively, which means comparing the performance in the human body versus a product for which the clinical outcome is known,” explained Thiessen. “The known clinical outcome is always with the brand-name drug. Whether a generic manufacturer seeks to create competitive products or an brand-name firm wants to make changes in formulation, sites of manufacture or product extensions, the same bioequivalency requirements are applied to both brands and generics.”

Given that a certain amount of variability exists in the manufacturing process for both brand-name and generic drugs, and that people have different reactions to the same dose of medications, variations in the concentrations of a particular drug found in the body are expected. “Variability is a sobering and important part of all science, human performance and testing of medicines,” said Thiessen. “Variability must be factored into an equitable system of medicine approvals. For example, it’s impossible for the content of any manufacturer’s product, brand or generic, to be identical when tested repetitively, so there’s a commonly permitted range of plus or minus 10%. This is inevitable due to the natural manufacturing variability that exists … It’s also impossible for the absorption of any manufacturer’s product, brand or generic, to be identical on different occasions, so there’s a commonly permitted performance range of minus 20% to plus 25%. This takes into account the human variability that arises when people are tested repetitively.”

When the generic drug’s performance falls within an acceptable range, the product is approved by Health Canada as being bioequivalent. For patients, this translates into “interchangeability,” which means that products can be switched clinically without an adverse change in therapeutic response.

Thiessen cited numerous studies examining how patients reacted when switched from a brand-name to a generic drug. A Harvard-based study, for example, concluded that just the process of refilling a prescription, whether with the brand or the generic, was associated with a higher risk of a reaction. Symptoms may be related to anxiety, delays in refilling the prescription, temporary non-adherence, variations in medication use patterns, or intraproduct (batch) variations. “The researchers found that the residual of switching between different manufacturers of the medications was negligible,” he reported.

Thiessen summarized by stressing that Canadians should feel confident in the quality and safety of generic drugs: “Health Canada has stringent criteria to safeguard the best healthcare interests of Canadians, and it uses the best known quantitative testing for designating products as the same or bioequivalent.”