The procedures required to legally place a medical device on the market vary in Canada, the US and the EU. Different regulatory bodies are involved, requiring different types of submissions (Table 1) and review timelines depending on the classification of the device.
Table 1: Medical device submissions: Canada, the US and the EU1–7
|Jurisdiction||Submission||Device classification||Regulatory body|
|Canada||Establishment registration||Class I||Health Canada|
|Medical Device Licence Application||Classes II, III & IV|
|US||Establishment registration||Classes I, II & III||U.S. Food and Drug Administration (FDA)|
|Traditional, abbreviated or special 510(k)s||Class II, and some class I||
|De novo||Low- to moderate-risk devices that have been classified as class III because they were found not substantially equivalent to existing devices||FDA|
|EU||Technical documentation||Class I, and certain class IIa||Self-certification by manufacturer|
|Technical file||Class IIa & IIb||Notified Body|
|Design dossier||Class III||Notified Body|
|Consultation dossier (only for the medicinal ingredient used in the device)||Class III (a device with a medicinal ingredient)||Competent Authority (coordinated via the Notified Body)|
*PMA = Premarket authorization application
PDP = Product development protocol
The regulatory review process in Canada is straightforward. The sponsor (applicant) deals with a single regulatory agency, Health Canada. For class I medical devices, the manufacturer needs to apply for an establishment licence unless he or she imports or distributes it solely through someone who already holds an establishment licence. For medical devices that are classified as class II, III or IV, a Medical Device Licence Application must be submitted.
The higher the risk of the medical device, the more information is required in the licence application and the more the time is required to reach regulatory approval (for example, in the first screening and review cycle, the agency’s performance goals are 15 days for class II and 90 days for class IV).
The submission typically goes through an administrative screening, an application validation and a review. At each stage, the submission is checked to see if it meets Health Canada’s standards of acceptability and regulatory safety and effectiveness requirements. A medical device submission can be deemed unacceptable at any point in the review process. If this occurs, the sponsor will have to provide additional information or a clarification before the submission can advance. Otherwise, a refusal letter may be issued by Health Canada.1
When a submission reaches the end of the review process, a decision whether or not to provide regulatory approval will be made.
The type of review required by the FDA depends on the medical device classification. Devices that are exempt from the premarket notification or authorization requirements are subject to general controls, including the establishment registration and device listing and labelling, record-keeping and reporting requirements. For medical devices that are subject to the 510(k) notification process, the target review timeline is 90 days. For PMA applications for class III devices, the target review timeline is 180 days.2
For lower-risk medical devices that do not have a predicate device (which results in an automatic class III designation), a sponsor may request a de novo classification of the product in order to reclassify it as class I or II. The request must be in writing and sent within 30 days from the receipt of the Non-Substantial Equivalence (NSE) determination. The request should include all of the following:
The de novo process has a 60-day review period. If the FDA classifies the medical device as class I or II, the sponsor will then receive regulatory approval to market the medical device. This device can then be used as a predicate device for other firms to submit a 510(k).3
For certain medical devices, a sponsor may choose an FDA-accredited third party (an “Accredited Person”) to conduct the primary review of 510(k). After the primary review of the 510(k), the Accredited Person forwards their review, recommendation and the 510(k) to the FDA. The FDA then issues a final determination within 30 days.4
Before a medical device can be legally placed on the market in Europe, it must go through an appropriate “conformity assessment process” to establish that it meets all the essential requirements of the applicable EU Directives. This process ensures that the device as it is designed and subsequently manufactured will meet the essential requirements. This enables the manufacturer to make a formal declaration of conformity and apply the CE mark of conformityi to the device.
For low-risk medical devices (class I and some class IIa), such as a tongue depressor or a colostomy bag, the manufacturer can make a declaration of conformity with the essential requirements based solely on a self-assessment, without needing the involvement of a Notified Body.ii
For medium- to high-risk medical devices (Classes IIa, IIb and III), the manufacturer must call on a Notified Body to assess the conformity. The Notified Body may perform one or more tasks as listed in Table 2. To some degree, the manufacturer may choose their method for the conformity assessment of the device and/or manufacturing system, depending on the type of device and the level of associated risk (Tables 2 and 3). The end result is a certificate of conformity that enables the manufacturer to apply CE marking to the product.5,6
Table 2: Certification activities of Notified Bodies
|Quality system certification||Device certification|
Certification based on auditing against a quality system standard for design, production and final inspection (for example, ISO 13485)
Certification based on auditing against a quality system standard for production and final inspection (for example, ISO 13485―design control)
Certification based on auditing against a quality system standard for final inspection (for example, EN 46003)
Certification based on the examination of the design dossier versus standards/essential requirements (paperwork review)
Certification of the design based on testing of physical samples versus standards/essential requirements
Certification of individual production batches based on the testing of the whole batch or of batch samples versus standards/acceptance criteria
Table 3: Conformity assessment options available to manufacturers, based on device classifications per the Medical Device Directive 93/42/EEC6,7
|Device classification||Conformity assessment options available to manufacturers|
|EC Self Declaration (Annex VII)|
|Full QA (Annex II) minus EC Design-examination
EC Declaration of conformity (Annex VII)
|Full QA (Annex II) minus EC Design-examination
EC Type-examination (Annex III)
|Full QA (Annex II)
EC Type-examination (Annex III)
The majority of Notified Bodies are independent commercial organizations that are designated, monitored and audited by the relevant Member States (of the EU) via their national Competent Authorities. A company is free to choose any Notified Body to cover the particular class of medical device under review. After approval, post-market surveillance is the responsibility of a Member State via the Competent Authority.
Manufacturers not located in the EU must appoint an authorized representative within the EU. After a product obtains the CE marking, its manufacturers must comply with any additional local registration requirements in each relevant Member State (such as informing the Competent Authority of their registered place of business or of any device description being placed on the market).
iA designation that indicates a product meets EU safety, health and environmental protection requirements.
iiA Notified Body is a certification organization that the national authority (the Competent Authority) of an EU Member State designates to carry out one or more of the conformity assessment procedures described in the annex(es) of the EU Directives. It must be qualified to perform all the functions set out in any annex for which it is designated.8
The information presented in these articles is intended to outline the general processes, principles and concepts of the healthcare product development lifecycle. Since regulatory requirements are ever-changing, it is current only as of the date of publication and not intended to provide detailed instructions for product development. Every healthcare product is unique and therefore so is its associated product development lifecycle. Specific advice should be sought from a qualified healthcare or other appropriate professional.
Published: October 17, 2012