In the United States (U.S.) and Canada, most drugs are prescribed and used similarly. However, certain processes and actions of the U.S. and Canadian pharmaceutical industries differ in significant ways, affecting both consumers and health care providers. Safety, marketing, and availability are three of these issues.
Controversy related to the importation of medications from Canada by U.S. consumers has sometimes raised concerns about the safety of these drugs. These fears are unfounded; in fact, the Canadian approval and manufacturing processes are very similar to U.S. processes. Both countries have pharmaceutical-related standards, laws, and policies to ensure that chemical entities marketed for human diseases and conditions are safe and effective. The process of taking a new drug from the laboratory to the pharmacy shelves includes:
The process begins with research. Scientists develop a new molecular entity targeted at a specific disease, symptom, or condition.
A manufacturer applies for a patent, which prevents other drug companies from manufacturing a chemically identical drug. Patent protection lasts 17 years in the U.S. and 20 years in Canada. After a patent expires, any manufacturer can make generic versions of the chemical; generic drugs typically cost much less than the brand-name drugs.
Before a drug is taken by human subjects, preclinical testing of the chemical is performed first on animals. Testing helps identify drug action, toxicity effects, side effects, adverse reactions, dose amounts and routes, and administration procedures. This phase can last anywhere from 3 to 5 years.
Once a drug is found to have demonstrable positive health effects and is safe for animal consumption, a manufacturer seeks permission to begin clinical studies with human subjects. In the U.S., this process is called New Drug Application (NDA) and is administered by the Food and Drug Administration (FDA). In Canada, the process is referred to as a Clinical Trial Application (CTA) and is administered by Health Canada.
Clinical trials are initiated to establish the potential benefits and risks for humans. Several subphases are required in the clinical trials phase whereby increasingly larger sample sizes are necessary.
Phase 0:
A new designation for first-in-human trials, which are designed to assess whether the drug affects humans in a manner that is expected.
Phase 1:
Between 20 and 80 healthy volunteers are recruited to assess safety, tolerance, dose ranges, pharmacokinetics, and pharmacodynamics.
Phase 2:
Up to 300 patient volunteers with the drug-targeted disease are enrolled to assess efficacy and toxicity. Variables from Phase I trials may also be assessed.
Phase 3:
Between 1000 and 3000 patient volunteers are entered into a randomized, double-blinded study designed to confirm drug effectiveness, comparability with existing treatments, and further exploration of potential and real side effects.
Ongoing surveillance of a drug for rare or long-term effects, or Phase 4 in Canada, continues after approval is received and marketing begun.
The results of the clinical studies are reviewed by Health Canada in Canada and by the FDA in the U.S. These regulatory bodies assess all aspects of a drug, including the labeling. The approval process is often deemed excessively long by physicians and patients who are anxious to try new remedies for refractory or terminal diseases. Efforts are ongoing to shorten the process in both countries. For example, Health Canada is collaborating with the FDA to develop a harmonized system for new drug submissions. A jointly planned Common Electronic Submissions Gateway (CESG) has been developed to allow submissions to be sent to both Canada and the U.S. in a common platform, while the review of these submissions continues to be a separate process.
Once a drug has been approved, it can be prescribed to consumers or, if it does not require a prescription, purchased by them.
More clinical data become available when a drug is marketed and used by many people for longer periods of time. Pharmacovigilance is the term used to refer to the process of ongoing assessment of a drug’s safety and effectiveness during this phase. In Canada, this includes Adverse Drug Reaction reporting by consumers and health professionals as described in "Detecting and Managing Adverse Drug Reactions."
One major difference between Canadian and U.S drug regulatory processes is pricing. In Canada, the Patented Medicine Prices Review Board (PMPRB) regulates the prices that manufacturers can charge for prescription and nonprescription medicines. This is to ensure that prices are not excessive. No such control exists in the U.S., with postrebate prices for medications in the U.S. being approximately 10–15% higher than in Canada.
Another difference is in advertising. In the U.S., manufacturers can market drugs directly, and forcefully, to consumers, a controversial privilege that has resulted in consumers requesting specific medications despite not necessarily understanding all of the risks and benefits. In Canada, such advertising is limited and subject to the approval of the Advertising Standards Canada (ASC) agency and the Pharmaceutical Advertising Advisory Board (PAAB). To address this issue in the U.S., the Institute of Medicine (IOM) has recommended that the FDA ban direct-to-consumer advertising during the first 2 years after a drug is marketed. Such a delay may help to prevent large numbers of people experiencing side effects not observed in the clinical trials, such as occurred with sildenafil (Viagra) when several patients died or developed vision problems in the first months after marketing began.
In Canada, Natural Health Products (NHPs) are regulated by Health Canada under the Natural Health Products Regulations. All NHPs must have a product license, and the Canadian sites that manufacture, package, label, and import these products must have a site license. A Natural Product Number (NPN) or Homeopathic Medicine Number (DIN-HM) is issued for the product only after it has been reviewed by Health Canada for its safety and efficacy. The term "Natural Product" refers to vitamins and mineral supplements, herbal remedies, traditional and homeopathic medicines, probiotics and other products such as amino acids, enzymes, essential fatty acids, protein supplements, or personal care items for consumption that contain natural ingredients.
In the U.S., the FDA classifies natural products as food products under the Dietary Supplements Health Education Act, so claims about the ability of a supplement to diagnose, prevent, treat, or cure a disease is prohibited. It is not necessary, however, for natural products to undergo review or approval or for testing to be done for identity and purity of active ingredients.
In Canada, drug schedules are used to classify medication according to accessibility. The Canadian drug schedules as defined by NAPRA (the National Pharmacy Regulatory Authorities) are:
The U.S., in contrast, categorizes medications according to two general classes:
As a result of these differences in accessibility some potentially dangerous drugs (such as insulin and codeine-containing cough medicines) are available only with a prescription in the U.S. and available without a prescription but in consultation with a pharmacist in Canada. Similarly, some Canadian drugs are available in combinations not found in the U.S. (see Appendix [not included in this PDA edition] for new Canadian combination drugs). There can also be significant variation within Canada due to each province and territory independently scheduling drugs, with the exception of narcotics and controlled substances. Other differences also exist with respect to drug availability between the two countries.
SOURCES CITED
ADDITIONAL REFERENCES
Common Electronic Submissions Gateway. https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/applications-submissions/guidance-documents/common-electronic-submissions-gateway.html (accessed 10 October 2023).
Health Canada. https://www.canada.ca/en/health-canada.html (accessed 10 October 2023).
Natural and Non-Prescription Health Products. https://www.canada.ca/en/health-canada/services/drugs-health-products/natural-non-prescription/regulation.html (accessed 10 October 2023).
U.S. Food and Drug Administration. http://www.fda.gov (accessed 10 October 2023).