Are you considering expanding your medical device sales to Canada? Will passing Canadian regulations to market and sell your product be too challenging or worth your while from a business perspective?
The Canadian approach to medical device regulation has many similarities to FDA requirements in the US and even more differences. US-based medical device manufacturers are expected to fully understand the difference between Canada and the US. Some of the regulatory nuances are particular to Health Canada, Canada's governmental department responsible for public health, while other significant differences result from the structure of the Canadian medical system.
The chances are good that if you’ve already gained the FDA's stamp of approval, you'll find that satisfying Canada's Medical Devices Bureau of the Therapeutic Products Directorate (TPD) requirements will be easy. However, it’s important to build your quality management system carefully to meet Canadian requirements and understand the exact differences between FDA and TPD regulations. Let's look at the specifics.
How the Canadian Medical Device Regulations Differ from the US
It's common for US-based and global medical device manufacturers to view the regulatory framework for medical devices in Canada as a mystery. The market of potential patients is much smaller, considering Canada's population of 35.6 million people is just over one-tenth the size of the US population of 327 million. Another significant difference between the US market and Canada is the Canadian public healthcare system. Canadian healthcare organizations navigate a much different public structure and are frequently subject to greater budgetary scrutiny.
Canada’s current regulatory framework has been in place since 1998. The foundation of the regulations addresses:
- Classification for non in vitro and in vitro medical devices
- Safety and effectiveness principles for all medical devices
- Requirements for manufacturer quality management systems
Some of the most significant differences between FDA and Health Canada requirements for medical device approval surround device classification, ISO, and reviewer discretion. You can begin to evaluate if obtaining Canadian approval is worth your effort by understanding how these differences are likely to impact your organization.
In the United States, the FDA groups medical devices into 3 classes, according to risk level; Class I, II, and III. Class I medical devices constitute the lowest-risk devices such as bedpans and stethoscopes. 95% of the time, Class I devices are exempt from the regulatory process. 43% of medical devices are Class II, such as powered wheelchairs. Class III medical devices consist of higher-risk devices such as pacemakers or implants and constitute just 10% of the devices regulated by the US FDA.
Canada has four levels of classification according to risk, Classes I through IV. Class I devices are approximately 40% of approved devices. Similar to the US, each higher level of device class means your device is subject to greater regulatory scrutiny. The rules for device classification are slightly different and involve the use of criteria such as invasiveness, reliance on an energy source, or potential contact with a patient's nervous or cardiovascular system.
Class I devices do not require a license to be sold in Canada. Class II devices require a license application. To gain approval for a Class III device, organizations must submit a valid ISO 13485 certificate. Class IV device applicants must provide Health Canada with an application, an ISO 13485 certificate, and more extensive data on safety. Class IV devices are evaluated within 75 days.
The US FDA has an extensive list of fees for market approval. The Fiscal Year (FY) 2019 fees for pre-market approval (PMA), Product Development Protocol (PDP), Post-Marketing Requirements (PMR), and Biologics License Applications (BLR) are currently set to $322,147. This does not include the annual establishment registration fee of $4,884. Small and mid-sized businesses with gross annual sales of $30 million or less are eligible to have the fee waived on their first PMA, PDP, PMR, or BLA. The general small business fee for these same applications is significantly reduced from FDA enterprise rates and priced at $80,537.
In Canada, Class I medical devices are exempt from device license applications and are not required to pay any fee. The fees can vary significantly for Class II, III, and IV devices. According to Health Canada, the fees as of April 1, 2019, are as follows:
- Class II License Application $414 CAD ($315 USD)
- Class III License Application $5,922 CAD ($4,524 USD)
- Class IV License Application $13,770 (10,520 USD)
These fees can vary slightly. For example, the application fee for a near-patient diagnostic in vitro Class IV device is significantly higher at $23,473 CAD. Manufacturers must pay an additional fee of $1,492 to $6,319 depending on device class each time there is a significant change in "process, facility, equipment, or quality control procedures."
ISO 14155 vs. 21 CFR for Clinical Investigations
Health Canada expects that manufacturers conform to the Good Clinical Practices (GCP) of ISO 14155:2011, an international standard for the clinical investigation of medical devices for human subjects. With very few exceptions, ISO 14155 is consistent with Canadian regulations for medical device manufacturers. ISO 14155 is not the law in the United States, but it is recognized as a standard by the US FDA.
The FDA requires medical device clinical trials to comply with CFR 21, notably:
- Part 11 (Electronic Signatures) See our post: What's the Best 21 CFR Part 11 Compliant Software?
- Part 50 (Informed Consent)
- Part 54 (Financial Disclosure)
- Part 56 (Institutional Review Boards)
- Part 812 (Investigational Device Exemptions)
FDA 21 CFR has many similarities with ISO 14155 standards, as well as a few differences. In general, ISO 14155 is a more stringent and comprehensive set of standards. To obtain a license for a Class II, III, or IV medical device in Canada, the clinical trial systems must be designed for compliance with ISO 14155. Some key differences between ISO 14155 and 21 CFR include, but aren’t limited to:
Investigational Plans and Regulations
ISO requires investigations are conducted according to the clinical investigation plan. FDA regulations require investigations to be done according to signed investor agreements, FDA regulations, and conditions of the institutional review board (IRB).
Deviations from Protocol
Deviations from protocol must be reported to the sponsor and ethics committee under ISO 14155 "as soon as possible." FDA regulations require the report of emergency use situation in five working days or fewer. In this case, the FDA requirement is more intensive.
ISO requires signatures, printed dates, and electronic case report forms (CRFs) from a principal. ISO also requires a signed, dated statement on printed, electronic documents which attests it's an accurate reproduction of the digital original and the use of a delegation log. FDA 21 CFR requires the retention of records for two years, and that organizations must notify the FDA of records transfer within ten working days. In this case, following both ISO and FDA requirements is a necessity for dual compliance.
21 CFR requires that organizations record all the names of individuals who are involved in the receipt, use, or disposal of medical devices and a collection of times and dates when the device was used. ISO requires expiration date records. In this case, it is necessary to meet both requirements.
ISO requires a signed and dated informed consent document from each subject, and the confirmation of the receipt of new information by trial subjects. ISO 14155 also requires organizations to report serious adverse events to the sponsor, ethics committee, and regulatory requirements, while the FDA has no provision for regulatory reporting. FDA requirements dictate the reporting of adverse events within ten working days. To meet both requirements, organizations must adopt ISO's stricter standards and the FDA's timeline for reporting.
The FDA has made significant strides toward fixing issues with reviewer discretion following complaints from medical device manufacturers about how hard it was to obtain approval. The general public wanted faster, more streamlined, and lower-cost access to innovative medical devices. The system is still far from perfect. Reviewers are still tasked with interpreting FDA guidance, but a committee instead of an individual always review device approvals. These teams are much more accessible for face-to-face meetings, and their first and foremost interest is public safety. The goal of the review teams is to make device products available for the good of the public interest, including innovations or orphan disease treatments.
Canada's regulations were introduced in 2008, but have changed little in the past 20 years. They're frequently referred to as the "new regulations." Their laws closely mirror ISO 13485, with some precise tweaks around approvals, required safety data, and the timelines for reporting issues in the field.
In the Canadian regulatory framework, one exciting current change is regarding the Medical Device Single Audit Program (MDSAP). Health Canada was reportedly "flooded" by applications by the January 1, 2019 deadline. Participation in the MDSAP program is mandatory for manufacturers of Class II, III, and IV medical devices. The MDSAP program is the idea for a harmonized, global model for audits, which allows medical device manufacturers to meet regulatory requirements in multiple global jurisdictions. While the US FDA is a member of the MDSAP consortium, it has indicated they do not intend to enforce MDSAP participation. MDSAP consortium members also include Japan, Brazil, and Australia.
The requirements for postmarket reporting on medical devices are, in general, less stringent in Canada. The current US postmarket requirements under the FDA address:
- Tracking systems
- Device malfunction reporting
- Serious injuries or deaths
- Establishment registration
In addition to these requirements, postmarket surveillance studies are required by the FDA for specific Class II or III devices, which are:
- Life-sustaining or life-supporting
- Implanted for more than one year
- Significantly used in pediatric populations
- Whose failure would cause adverse consequences
Under Health Canada, medical device manufacturers are required to meet Canadian Medical Devices Regulations (CMDR) postmarket requirements which cover:
- Maintenance of distribution records
- Complaint handling
- Mandatory problem reporting
Postmarket surveillance is a given in both Canadian and US markets. However, the requirements can vary significantly for Class II, III, or IV medical devices, depending on how your device is classified in each jurisdiction. For example, a Class III medical device in Canada may not require postmarket surveillance studies, though it would be subject to these requirements in the United States.
Meeting Canadian Device Regulations
While there are many similarities between the US FDA and Health Canada requirements for medical device manufacturers, there are also significant differences between the two regulatory frameworks. For manufacturers of devices classified by the FDA as Class II or III, the decision to pursue licensure for sale in Canada should be taken carefully. The Canadian patient market is smaller, and healthcare and reimbursement systems are structured very differently. Also, varying requirements for quality systems and clinical investigations require your organization to build in Canadian compliance before applying for a license.
If the decision to apply for a license in Canada makes financial sense for your organization, it's important to start understanding specific requirements and building in compliance as early as possible. A robust life sciences eQMS software can enable your organization to meet various requirements, including ISO 14155, FDA 21 CFR, and MDSAP.