In the United States 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:Scientific development.
The process begins with research. Scientists develop a new molecular entity targeted at a specific disease, symptom, or condition.Patenting.
The manufacturer applies for a patent, which prevents other drug companies from manufacturing a chemically identical drug. Patent protection lasts 17 years in the United States and 20 years in Canada. After the patent expires, any manufacturer can make generic versions of the chemical; generics typically cost much less than the brand-name drug.Pre-clinical testing.
Before the drug is taken by human subjects, pre-clinical testing of the chemical is performed on animals. Testing helps identify drug action, toxicity effects, side effects, adverse reactions, dosage amounts and routes, and administration procedures. This phase can take 3 to 5 years.Permission to begin clinical testing.
Once the drug is found to have demonstrable positive health effects and to be safe for animals, the manufacturer applies for permission to begin clinical studies on human subjects. In the United States, this is called New Drug Application (NDA) and is administered by the Food and Drug Administration (FDA). In Canada, this is called a Clinical Trial Application (CTA) and is administered by Health Canada.Clinical trials.
Clinical trials are initiated to establish the potential benefits and risks for humans. Several sub-phases are required in the clinical trials phase whereby increasingly larger sample sizes are used.
A new designation for first-in-human trials, which are designed to assess whether the drug affects humans in the manner expected.
Between 20 and 80 healthy volunteers are recruited to assess safety, tolerance, dosage ranges, pharmacokinetics, and pharmacodynamics.
Up to 300 patients with the disease are enrolled to assess efficacy and toxicity. Variables from Phase I trials may also be assessed.
Between 1000 and 3000 patients are entered into a randomized, double-blind study designed to confirm effectiveness, compare the new treatment with existing treatments, and study side effects further.
Ongoing surveillance of the drug after it receives approval and is marketed to assess for rare or long-term effects.Approval.
The results of the clinical studies are reviewed by Health Canada in Canada and by the FDA in the United States. These regulatory bodies assess every aspect of the drug, including the labeling. The approval process has been deemed excessively long by physicians and patients anxious to try new remedies for refractory or terminal diseases, and efforts have been made to shorten the process in both countries. Although approval times for new drugs were found to be significantly longer in Canada, it has been noted that significantly fewer drugs have been pulled from the market for safety reasons. Statistically, Canadians remove 2% of new drugs for safety reasons, whereas 3.6% of new drugs are taken off the market in the United States.Marketing.
Once a drug has been approved, it can be prescribed to consumers or, if it does not require a prescription, purchased by them.Post-Marketing Surveillance.
More clinical data become available when the 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.
Differences Between Canadian and U.S. Drug Pricing and Marketing
One major difference between the two countries is pricing. In Canada, the Patented Medicine Prices Review Board (PMPRB) regulates the prices manufacturers can charge for prescription and nonprescription medicines. This is to ensure that prices are not excessive. No such controls exist in the United States, which is why many citizens purchase their medications from Canadian online pharmacies. One study found that U.S. citizens can save approximately 24% if they buy their medications from Canadian pharmacies rather than from a U.S. chain pharmacy.
Another difference is in advertising. In the United States, manufacturers can market drugs directly, and forcefully, to consumers, a controversial privilege that has resulted in consumers requesting specific medications despite not necessarily understanding the complete 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 United States, the Institute of Medicine (IOM) has recommended that the FDA ban direct-to-consumer advertising for 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.
Drug Schedule, Availability, and Pregnancy Category Differences
Most Canadian provinces (with the exception of Québec) use drug schedules similar to U.S. schedules of controlled substances. Canada uses four categories, whereas the United States uses five (see for controlled substance schedules). The Canadian drug schedules are:
Schedule I: : Available only by prescription and provided by a pharmacist.
Schedule II: : Available only from a pharmacist; must be kept in an area with no public access.
Schedule III: : Available via open access in a pharmacy (over-the-counter).
Unscheduled: : Can be sold in any store without professional supervision.
Another difference is in availability. Some potentially dangerous drugssuch as heparin, insulin, and codeine-containing cough medicinesare available only with a prescription in the United States but are available over-the-counter in Canada. Similarly, some Canadian drugs are available in combinations not found in the United States (see for new Canadian combination drugs).
Although Canada currently does not have pregnancy categories like the United States, it is developing them. Canadian prescribers practice under the premise that no drug should be given to a pregnant woman unless the benefits to the mother clearly outweigh the potential risks to the fetus. Canadian health care providers may refer to a drug's FDA pregnancy category for guidance (see ).
Rawson N. "Canadian and U.S. Drug Approval Times and Safety Considerations." Ann Pharmacother. 37(10):14031408, 2003. Published Online, August 1, 2003. http://www.theannals.com. DOI 10.1345/aph.1D110 (accessed 15 December 2007).Quon B., Firszt R., Eisenberg M. "A Comparison of Brand-Name Drug Prices Between Canadian-Based Internet Pharmacies and Major U.S. Drug Chain Pharmacies. Ann Intern Med. 143(6):397403, 2005. http://www.annals.org/cgi/content/abstract/143/6/397 (accessed 10 December 2007).ADDITIONAL REFERENCES
Canadian Pharmacists Association. "From Research Lab to Pharmacy Shelf." http://www.pharmacists.ca/content/hcp/resource_centre/drug_therapeutic_inf
... (accessed 15 December 2007).
Health Canada. http://www.hc-sc.gc.ca/ahc-asc/index_e.html
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Tomalin A. "Drugs Used in Pregnancy: The Regulatory Process." Can J Clin Pharmacol. 14(1):e5e9, 2007. http://www.cjcp.ca/pdf/CJCP2007_e5_e9.pdf
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U.S. Food and Drug Administration. http://www.fda.gov
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