How drugs are approved in Canada
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 companies 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 company according to strict procedures. Even if a drug is approved for use in Canada, monitoring 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 following outlines the various steps involved in developing a drug:
Chemical and biological researchLaboratory 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 company will proceed to the next step of development.
Pre-clinical developmentThe drug is given to animals in various amounts and over different periods of time. These animal “models” are typically rats or mice that have been genetically engineered to have the human genes that cause the familial form of Alzheimer’s disease (FAD). If it can be shown that the drug causes no serious or unexpected harm at the doses required to have an effect relevant to the disorder in question, the company will proceed to clinical trials. These preclinical studies often take two to three years.
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 company 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. The study must also be approved by a Research Ethics Board (REB). 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 finding out how high the dosages can be before adverse side effects occur. Phase 1 studies generally take at least one year to complete. If they look promising, they go into Phase 2 trials.
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 and Research Ethics Boards. 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 untreated or given another type of treatment. Side effects are identified and effective drug doses are determined. Usually it takes at least two years to obtain enough positive information to justify the much larger and more extensive Phase 3 trials.
Clinical trials – Phase 3
If the results from Phase 2 show promise, the drug company provides an updated Clinical Trial Application to the TPD, plus a new Research Ethics Board application, for any Phase 3 trials that will include Canadian sites. Hundreds or even thousands of people with Alzheimer's disease around the world will be involved, including those who have other medical conditions and those who are taking other medications. One group of patients receives the prospective treatment and a matching group receives a "placebo," a harmless inactive substance, or a comparable drug that is already on the market. It can take three years or longer to find out if the treated group does better than the untreated one and to confirm drug dosages that work without causing adverse side effects. If a drug successfully maintains its original promise right through to the end of the Phase 3 trial, it is submitted to the appropriate government agencies for their approval. Usually drugs are sent back for yet more study in Phase 4 trials on people with other medical conditions in addition to Alzheimer’s disease, or in different age or sex categories. This phase may take another two to four years.
In summary, the treatment may be approved for administration by doctors approximately eight to ten years after human studies first began.
New drug submission
If the results from Phase 3 continue to be favourable, the drug company can submit a New Drug Submission (NDS) to the TPD. A drug company 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 company. 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 company to market a drug with the condition that the drug company 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 safety and 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.
How to obtain a drug before it is approved
The HPFB can approve the release of a drug under the Special Access Program. Some drugs being investigated for the treatment of Alzheimer's disease may be obtained through this program. The individual's physician should contact the HPFB or the drug company directly to obtain information about access.
[The contents of this document are provided for information purposes only, and do not represent advice, an endorsement or a recommendation, with respect to any product, service or enterprise, and/or the claims and properties thereof, by the Alzheimer Society of Canada.]
Last Updated: 11/08/2017