The medical device industry in America and perceived shortcomings in the US Food and Drug Administration's ("FDA") approval process have recently come under scrutiny in popular media.
An often-cited concern with the FDA's approval process relates to the 510(k) pathway, whereby a medical device may reach the market with a lesser amount of clinical testing. Through this regulatory pathway, a medical device may be approved if the manufacturer can demonstrate that their device is "substantially equivalent" to another device already on the market.
In this article, we take a look at the current regulatory regime in Canada as it pertains to medical devices, as well as what Health Canada is doing to implement regulatory reforms.
What is a Medical Device?
In Canada, medical devices are regulated by the Medical Device Bureau ("MDB") of Health Canada's Therapeutic Products Directorate ("TPD") in accordance with the Medical Device Regulations (the "Regulations"). Enacted on May 7, 1998, pursuant to the Food and Drugs Act, the Regulations define a medical device as "an instrument, apparatus, contrivance or other similar article, or an in vitro reagent, including a component, part or accessory of any of them, that is manufactured, sold or represented for use in":
(a) diagnosing, treating, mitigating or preventing a disease, disorder or abnormal physical state, or any of their symptoms;
(b) restoring, modifying or correcting body structure or the functioning of any part of the body;
(c) diagnosing pregnancy;
(d) care during pregnancy or at or after the birth of the offspring, including caring for the offspring; or
(e) preventing conception.
The Regulations apply only to medical devices for use in humans and not animals.
Medical devices are classified according to Health Canada's risk-based system. Devices are assigned one of four device classifications according to a set of 16 rules set out as Schedule 1 to the Regulations. In vitro diagnostic devices (i.e. devices and accessories used to perform tests on bodily samples) are subject to their own set of 9 rules. Each rule defines the classification based on how it is used, whether it is invasive, what system of the body it primarily affects, and whether energy, either electrical or other, may be used and/or transferred in a potentially hazardous way.
Class I represents the lowest risk to the patient while Class IV represents the highest risk. Pursuant to the Regulations, where a medical device can be classified into more than one class, the class representing the higher risk applies. Examples of each class are set out in Table 1, below:
Reusable surgical instruments, dressing and bandages, toothbrushes, wheelchairs and hospital beds.
Single use surgical instruments, short-term catheters, contact lenses, blood pressure monitors, MRI equipment, and dentures.
Long-term indwelling catheters, intraocular lens, pancreatic stents, hip implants, glucose monitors, ventilators, and intrauterine contraceptive devices (IUDs)
Intra-aortic balloon catheters, coronary stents, pacemakers, implanted spinal cord stimulators for pain relief, mechanical heart valves, and fetal pH monitor
How are Medical Devices approved in Canada?
The risk-based classification system determines the applicable approval process – with more demanding approval requirements for higher-risk devices.
Class I medical devices do not require licensing for the actual device. However, the Regulations require that any person, partnership or association involved in the importation or sale of such devices hold a Medical Device Establishment License ("MDEL"). An MDEL certifies that an establishment involved in the Canadian distribution of a Class I device meets the applicable standards of manufacture, but requires no evidentiary or clinical documentation.
In addition to basic contact and manufacturing information, an application for an MDEL requires an attestation by a senior official that the establishment has procedures in place to assure compliance with safety requirements and to protect the public should a problem with a device be identified. MDEL holders must submit an application for the review of their license on a yearly basis.
For Class II, III or IV devices, the actual device requires licensing before it can be sold in or imported into Canada. Manufacturers of these classes of devices must obtain a Medical Device License ("MDL") as certification of the device's quality, safety and efficacy. Applications for an MDL require a quality management system certificate issued by a Health Canada Registrar.
As lower-risk devices, Class II devices must provide an attestation by a senior official of the manufacturer of the device's compliance with safety and effectiveness requirements, but do not require clinical evidence.
For a Class III device application, summary evidentiary information must be provided. Approvability requirements for Class III devices also include:
- a description of the materials used in its manufacture and packaging;
- sale numbers in countries other than Canada and a summary of problems reported therein;
- studies relied upon to ensure compliance with safety and effectiveness requirements; and
- all published reports dealing with the use, safety and effectiveness of the device.
As they pose the highest risk, licensing applications for devices under Class IV are the most demanding and require detailed evidence as to their safety. In addition to the application requirements for Class III devices, licensing of Class IV devices notably require the following:
- a risk assessment comprising an analysis and evaluation of the risks, and the risk reduction measures adopted to satisfy safety and effectiveness requirements;
- a quality plan setting out the specific quality practices and resources;
- the manufacturing process of the device;
- detailed information of the studies relied on to ensure compliance with safety and effectiveness requirements (e.g. pre-clinical and clinical studies, process validation studies and literature studies); and
- objective evidence of the biological safety of devices incorporating human or animal tissue.
Does Canada have a 510(k) Equivalent?
In Canada, there is no equivalent to the FDA's 510(k) process. The 510(k) clearance pathway requires that a sponsor demonstrate that there is substantial equivalence to products already approved in the US market and that the difference between the "new" and existing device is immaterial. This regulatory pathway is available for both Class I and II medical devices in the US.
In Canada, all devices except Class I require a MDL before they can be sold. Therefore, Health Canada's requirements for Class II, III and IV devices are higher than the standards employed in the US.
What Post-market safety requirements exist?
While much recent discussion of the medical device industry has focused on pre-market approval process, a potentially larger issue exists in the under-reporting of adverse events. An adverse event is any unintentional, unfavourable clinical sign, symptom, or complication occurring as a result of treatment.
David Kessler, the FDA Commissioner from 1990 to 1997, notes that while a system for reporting complications exists there is "tremendous underreporting because it's a voluntary system" Rita Redberg, the Editor of Internal Medicine for the Journal of the American Medical Association, echoes this concern:
If a physician observes an adverse event, they do not have to report it. The only bodies that are required to report adverse events are the companies. It's estimated that only 3-4% of adverse events are reported to the FDA.
As in the US, the Regulations in Canada provide that device manufacturers must report adverse events to Health Canada. However, aside from obligations imposed on manufacturers, the reporting of adverse events is not mandatory. Health care providers are under no obligation to report adverse events to the FDA or Health Canada and would be well-served by a redesign of the regulatory framework so as to clarify and facilitate reporting of adverse events.
It has been estimated that only 5% of all adverse drug reactions and adverse events are reported to Health Canada. Even with a stronger pre-market approval process, this begs the question of how Health Canada and other regulatory bodies can adequately regulate marketed devices in the absence of accurate statistics regarding the prevalence of adverse events.
What Steps is Health Canada Taking?
Health Canada has been actively taking steps to reform the regulatory framework available to health care providers. On June 15, 2018, Health Canada published proposed regulations in the Canada Gazette, Part I which seek to amend the Food and Drug Regulations and Medical Devices Regulations to require hospitals to report serious adverse drug reactions and adverse medical device events.
Under the proposed regulations, hospitals would be required to report all adverse events to Health Canada, in writing, within 30 days of the incident. While the proposed regulations would only require "serious" adverse drug reactions to be reported, no such limitation is placed on medical device incidents.
For now, these regulations would only apply to hospitals and not to other healthcare facilities or providers. Canadians and other stakeholders have been invited to provide comments on this regulatory proposal by August 29, 2018.