How Drugs Are Approved in Canada
(Reproduced with permission from the Alzheimer Society of Canada, www.alzheimer.ca)
It is the responsibility of the Therapeutic Products Directorate (TPD) of the Health Products and Food Branch (HPFB), Health Canada, to ensure that all drugs used by the public are safe and effective for specific conditions, and of high quality. This responsibility includes ensuring that drug manufacturers have tested the drugs they wish to market and that the public is protected during each stage of the drug’s development.
Before being approved, a drug for the treatment of Alzheimer’s disease must be tested by the manufacturer according to strict procedures. Even if a drug receives approval for use in Canada, the monitoring of its effectiveness and side effects continues. For example, some side effects can be uncommon and do not show up during clinical trials, but are found once the drug is marketed and given to a greater number of people. The average time between initial laboratory work and marketing of a drug is 12 years. The following outlines the various steps involved in developing a drug:
Chemical and Biological Research
Laboratory tests are carried out in tissue cultures and with a variety of small animals to determine the effects of the drug. If the results are promising, the manufacturer will proceed to the next step of development.
Pre-Clinical Development
The drug is given to animals in various amounts and over different periods of time. If it can be shown that the drug causes no serious or unexpected harm at the doses required to have an effect, the manufacturer will proceed to clinical trials.
Clinical Trials — Phase 1
The objective of Phase 1, the first administration in humans, is to test if people can tolerate the drug. If this testing is to take place in Canada, the manufacturer must prepare a Clinical Trial Application for the TPD. This includes the results of the first two steps and a proposal for the testing in humans. If the information is sufficient, the HPFB grants permission to start testing the drug, generally first on healthy volunteers. These trials typically consist of single doses given at one time, under carefully monitored conditions. This testing starts the process of identifying common side effects, as well as the dose range that can be tolerated.
Clinical Trials — Phase 2
Phase 2 trials are carried out on people with Alzheimer’s disease, who are usually otherwise healthy, with no other medical condition. Trials carried out in Canada must be approved by the TPD. In Phase 2, the objective of the trials is to continue to gather information on the safety of the drug and begin to determine its effectiveness. Trials are designed and carried out by highly qualified investigators with expertise in Alzheimer’s disease. The drug is given for sufficient time to determine if it makes a difference, compared to people who are given another type of treatment. Side effects are identified and effective drug doses are determined.
Clinical Trials — Phase 3
If the results from Phase 2 show promise, the drug manufacturer provides an updated Clinical Trial Application to the TPD for any Phase 3 trials, which will include Canadian sites. Many more people with Alzheimer’s disease will be involved, including those who have other medical conditions and those who are taking other medications. The objectives of Phase 3 include determining whether the drug can be shown to be effective, and have an acceptable side effect profile, in people who better represent the general population. Further information will also be obtained on how the drug should be used, the optimal dosage regimen and the possible side effects.
New Drug Submission
If the results from Phase 3 continue to be favourable, the drug manufacturer can submit a New Drug Submission (NDS) to the TPD. A drug manufacturer can submit a NDS regardless of whether the clinical trials were carried out in Canada. The TPD reviews all the information gathered during the development of the drug and assesses the risks and benefits of the drug. If it is judged that, for a specific patient population and specific conditions of use, the benefits of the drug outweigh the known risks, the HPFB will approve the drug by issuing a Notice of Compliance. The HPFB will also review and edit the Product Monograph submitted by the manufacturer. This document helps to ensure that the drug is used properly by providing physicians with the information they need.
For conditions that are life-threatening or cause severe impairment (such as Alzheimer’s disease), the HPFB can authorize a drug manufacturer to market a drug with the condition that the drug manufacturer undertake additional studies to verify the drug’s benefit. This authorization is a Notice of Compliance with condition (NOC/c). A NOC/c is given to an eligible drug which has demonstrated promising clinical effectiveness in clinical trials. The product must be of high quality and possess an acceptable benefit. The conditions include a requirement to closely monitor the drug for adverse reactions and to provide HPFB with regular updates. Once the conditions are met, the designation is removed.