Over the past few months, what have the main changes been to medical-device regulations in Canada, the U.S., and Europe?

The answer is as big as the question, and will usefully be divided into four sections: quality assurance, Canada, the United States, and Europe.

Quality Assurance

Over the course of the last few months, there have been no significant changes in quality-assurance regulations pertaining to medical devices. A new revision of the ISO 14971 standard for risk management was relaxed at the beginning of the year, but the modifications were minor. A change to the ISO 9001 standard is expected by the end of 2008, but there again, no significant changes are anticipated. The most notable change has likely been the revision to Health Canada’s GD207 directive in November, and there, too, the change was slight: this mainly clarified what scope statements are permitted for an ISO 13485 certificate.

Canada

Changes have all been minor or very specific.

United States

Several important recent changes in the U.S. and at the FDA have occurred.

• A new era seems to have dawned at end of May 2007 with the introduction between May and September of a number of new “consensus standards.” These demonstrate a larger effort by the FDA to recognize international and European standards. The FDA has, for example, recognized the European standard on EN980 symbols.
• The Food and Drug Administration Amendments Act was adopted on September 27, 2007. This law modifies the administrative fees for a number of FDA services. With the passage of this bill, certain types of services have been substantially modified. Among the important changes are the following:

• A reduction in fees for 510(k), premarket approval (PMA), PMA supplements, etc., of between 18% and 70%. The FDA lowered the rates because it was seeing fewer and fewer requests, since the costs were significant for small businesses.
• The introduction of a $1706 USD fee for the annual registration for manufacturing sites. Furthermore, registration forms 2891 and 2892 (for registering a manufacturing site and for registering products for sale, respectively) were replaced in October by an electronic database. Since 510(k) and PMA are now linked to manufacturing site and product category, it is now more difficult for a manufacturer to “forget” to produce a 510(k) or PMA before selling in the U.S. You can find more information here: http://www.fda.gov/cdrh/reglistpage.html.
• The introduction of a $1480 USD fee for small businesses, and a $2960 USD fee for larger ones, to obtain a Request for Information through a 513(g). Furthermore, the answer no longer is binding on the FDA.
• The introduction of a fee for 30-day PMA supplements and for Class III devices’ periodic reporting.
• Congress introduced new quantitative and qualitative objectives for the FDA to try to make the review and submissions process more transparent and efficient. The new guidelines are found in “Guidance for Industry and FDA Staff: Interactive Review for Medical Device Submissions: 510(k)s, Original PMAs, PMA supplements, Original BLAs [Biologic Licence Applications], and BLA Supplements” and in “Guidance for Industry and FDA Staff: Expedited Review of Premarket Submissions for Devices.”
• The coming-into-force on December 26, 2007, of the obligation to register all clinical trials in the National Institutes of Health database, and the obligation to confirm to the FDA that it was done in the context of the 510(k) and the corresponding PMA. (For more information, see the FDA’s web page at http://www.fda.gov/cdrh/news/121307.html.)
• The reduction of limitations on the Third-Party Inspections program.
• The coming-into-force of the Pediatric Medical Device Safety and Improvement Act to ensure the development of medical instruments will take children into account.

• A new project has been introduced to issue guidelines on the use of scientific articles to limit the risks of “off-labelling.” (You can find a provisional copy of the “Draft Guidance for Industry on Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices” for the purposes of comments at http://www.fda.gov/oc/op/goodreprint.html.)

Europe

• A revision of directive 93/42/CEE (MDD), directive 2007/47/CEE, was adopted on September 21, 2007, and came into effect October 11, 2007. Among other notable changes are:

• An expanded definition of a “medical instrument” to include software, for example.
• Annex I on essential requirements was altered to add a stipulation concerning independent validation of software. A requirement to take into account the level of experience and knowledge of the user was spelled out. Stricter demands on the characteristics of Class IIb and III medical devices were also introduced.
• A requirement to respect the strictest demands between the MDD (Medical Devices Directive) and directive 2006/42/CEE was added for instruments that are considered machinery for the purposes of Article 2(a) of directive 2006/42/CEE.
• A clarification of the demands surrounding the revision of technical records was brought in, as was a reclassification—upward, for a number of instruments—of different types of devices.
• Different changes have been introduced to clinical trials; in particular, clinical studies are now seen as part of a continuing process that includes studies after devices have been commercialized.
• Businesses must maintain no more than one authorized representative if they are not based in Europe.

Companies will have to investigate very quickly whether their products will be affected by these changes, especially by the reclassification that accompanies the combined demands.

• A new revision of the guidelines on a Medical Devices Vigilance System, MEDDEV 2.12-1 revision 5, was issued in April 2007 and came into effect on January 1, 2008. A free copy is available at: http://ec.europa.eu/enterprise/medical_devices/meddev/2_12_1-rev_5-2007-fin3.pdf.
• Although this is more specific than the preceding changes, it is useful to mention that manufacturers of medical instruments aimed at children will have to consult the paediatric regulation adopted by the European Parliament in December 2006.

Future questions:

This is the first of a series of questions Dr. Montini will answer on the regulation of medical devices. Please write to Medical Technology Watch Canada if you would like to suggest a theme for him to address in a future issue.

As an indication, in upcoming editions we hope to take on such topics as:

How do you define “medical instrument”? (Are medical devices defined similarly in all countries? How do you classify medical devices? What are the main differences between device classes in Canada, the U.S., Europe, and Japan? Is it possible to protest the class assigned to a medical device?)

Quality assurance systems (What are the similarities and differences among ISO 13485, Annex II of the Directive on Medical Devices, and CFR 21 part 820? Do you need ISO 13485 certification to export to Europe? If my device is ISO 13485–compliant, do I also have to get ISO 9001 or ISO 14001 certification? What is CMDCAS? What are EC and MDD markings?)

Risk management (How is risk management different from risk analysis? When is risk analysis necessary? Are standards useful?)

Labelling (What does labelling mean? what laws and regulations apply?)

The approval process (What steps need to be taken? Who can approve a medical instrument? What are the differences between 510(k), PMA, and an IDE in the U.S.? Do Canada and Europe follow the same approach? How about the rest of the world?)

Priority Reviews (What do they generally contain? What is “indicated use”? What are the main differences between Canada, the U.S., and Europe?)

Dr. Emmanuel Montini

Do you have questions on Regulatory Affairs? Send your questions to Adam Levin