Euro News

Busy December Yields New Regulatory Documents

We often welcome the holidays with a slower pace at the office, vacation time, seemingly long and extended holiday visitors, and copious amounts of delicious, yet artery-insalubrious and somnolence-inducing food.

In contrast to our slow and semi-gluttonous month, the climate in the offices of the European Commission (EC) was bustling with efficiency. December was astonishingly busy and productive, with two guidelines revised, a Web site overhaul and redesign and the implementation of Directive 2007/47/EC on the near horizon. Perhaps it was the brink of a new decade, or in the face of the

weakened economy, an attempt to start the New Year off with gusto. Perhaps it simply was the weather. Nonetheless, the issuance of revised guidelines merits a review of the current regulatory status in Europe.

Directive 2007/47/EC

As you should now be well aware, the implementation date of Directive 2007/47/EC, which will affect all medical devices (except IVDs) marketed in Europe, is fast approaching. By March 21, manufacturers’ devices must be compliant with the modified directive (Directive 2007/47/EC). An important housekeeping note is that since Directive 2007/47/EC is an amending directive, it will automatically be assumed that your devices are in compliance after March 21, at which point you will only need to reference the Medical Devices Directive MDD 93/42/EEC, and not both directives. Notified bodies are scrambling to work with their clients to identify the device subcategories and generic device groups, and, similarly, manufacturers also are working furiously to update their clinical data.

Clinical Data

An essential change of Directive 2007/ 47/EC is that clinical data requirements are necessary on ALL devices, including Class I. We covered this topic in detail in the January/February 2008 issue of Medical Product Outsourcing. The directive imposes more stringent requirements as to what constitutes “clinical evidence” and mandates stronger enforcement by authorities and notified bodies. The definition of “clinical data” is included in Article 1 (k): “The safety and/or performance information that is generated from the use of a device. Clinical data are sourced from:

• clinical investigation(s) of the device concerned; or

• clinical investigation(s) or other studies reported in the scientific literature, of a similar device for which equivalence to the device in question can be demonstrated; or

• published and/or unpublished reports on other clinical experience of either the device in question or a similar device for which equivalence to the device in question can be demonstrated.”

In addition, the essential requirements of the directive call for clinical evaluation according to Annex X, which has been significantly amended. In particular, the essential requirements of Annex I added ER 6a: “Demonstration of conformity with the Essential Requirements must include a clinical evaluation in accordance with Annex X,” and Annex X specifically references a clinical evaluation report that must be documented. The onus is on the manufacturer to demonstrate that there is sufficient clinical data on its medical devices. The following excerpt from MEDDEV 2.7.1 (see below) stipulates:

“Similarly, it may be possible to use compliance with recognized standards to satisfy the clinical evidence requirements for devices based on technologies with well-established safety and performance characteristics.”

In keeping with the productive December atmosphere, a third revision of MEDDEV 2.7.1, titled “Guidelines on Medical Devices, Clinical Evaluation: A Guide for Manufacturers and Notified Bodies,” was issued.

The issuance of this revision aligns the European guidance with GHTF guidance document GHTF SG5/N2R8 of August 2007. This revision of MEDDEV 2.7.1 links the two documents. In fact, certain sections have been transposed verbatim, and the format is nearly identical.

The two documents, GHTF SG5/N2R8 August 2007 and MEDDEV 2.7.1, rev 3 December 2009, are available online.

MEDDEV 2.12.1, Rev 6 Vigilance

The European MEDDEV 2.12.1 titled “Guidelines on a Medical Devices Vigilance System” also has been revised.

Revision 6 includes minor “technical” modifications to the Incident Report Form, Annex 3. These modifications include the following and will be de facto expected after March 20:

• Inserts query if the incident is a serious public health threat

• Separates “death” from “unanticipated serious deterioration in state of health, serious public health threat” for classification of incident

• Includes one field for device manufacturing date and one field for expiration date, which was previously a single field

• Adds implant and explant dates, for implants only

• Adds a question about number of similar incidents

Please note that the link to MEDDEV 2.12.1, Rev 5 on the European Commission Web site no longer functions because it has been superseded by Rev 6.

European Commission EuropaWeb Site Redesign

The European Commission Europa Web site (http://ec.europa.eu/enterprise/sectors/ medical-devices/index_en.htm) has been redesigned, and some of the changes are likely to impact links referenced in your documents and procedures. As a result of the new design, some links are now obsolete and will render an error message if accessed. It is important that all of the Web sites referenced in your documents and procedures be checked.

From an aesthetic standpoint, the user interface of the site has been modernized, and the sidebars have been updated to better organize documents and links.

The left-hand sidebar, for example, is now divided into the following sections: enterprise and industry, policy highlights, industry sectors, reference documents, useful links, questions and terms, enterprise e-services portal and multimedia portal. There also is a dropdown menu for quick links to EC databases. These enhancements have helped to create a more user-friendly site, a sharp contrast from the old site, which had vague sidebar items, including links such as the one for “some other related policies.”

Italian Registrations Delayed

The December bustle also reached the Italian Ministry of Health, but in a different way. The registration deadline pursuant to the legislative decrees Decreto del Ministero della Salute 20 Febbraio 2007 and 20 Marzo 2007, which required manufacturers (or a firm’s designated entity) to register their medical devices in the Italian Ministry of Health Database if the medical devices are to be sold in Italy, has been postponed.

The legislative decrees called for manufacturers of devices that were placed on the Italian market to register their devices. The manufacturer may register directly or give the authorization to another entity to do so. The registration provides a unique number for each device (or device family), and if the manufacturer wishes to list its devices on the database accessed by the National Health Service hospitals, a fee is required per device.

A variety of regulatory documents for the device and forms need to be submitted, including the Global Medical Device Nomenclature Code, Italian labeling, etc. Once compiled and posted to the Italian Ministry of Health Database, the review process by the Italian Ministry of Health may take up to 30 days. The entry would then be “published” to the Italian Ministry of Health database so that it could be accessed by purchases in hospitals.

The registration deadline recently was postponed until March 31 to simplify the process and modify the requirementsfor registration.

Evangeline Loh, P.h.D, R.AC., is vice president of regulatory affairs for Emergo Group, an international consulting firm providing regulatory, quality assurance and distribution consulting services. Sage Farrar is a regulatory research associate at Emergo Group. Emergo has offices in the United States, Europe, Japan, China, Canada and Australia. Evangeline can be reached at evangeline@ emergogroup.com.