Finding Your Way Through the Woods
(or through the new European Medical Device Directive)

Great changes are occurring in European regulation of medical devices.  On March 21, 2010, European Medical Device Directive 2007/47/EC becomes the new law of the land, and any sales or uses of medical devices in Europe occurring after this date are subject to the many new requirements of the new rules. It doesn’t matter when your devices were first approved and/or sold in Europe – the new Directive applies to you.

Does this mean that “the party’s over” for European sales under a CE mark? Of course not. But what it does mean is that every company having or contemplating European medical device sales has only a few more months to ensure that their internal systems and practices comply with the new rules. If you were unaware of the new Directive, you have little time left to understand how these rules will affect your business, let alone implement the many changes mandated for continued selling in Europe. 

Most of the changes, taken individually, are relatively manageable. With a little prior planning and investigation, you can lead your company through a smooth transition when the new rules take effect.

What’s Changed at Grandma’s House?
This is the first significant revision to the EU Medical Device Directives in many years. There are many amended provisions that apply to every medical device manufacturer, no matter what class of device you make.  Moreover, it doesn’t matter if you sell your devices, or give them away for free – these new rules still apply to you. They will require you to modify or supplement many of the records and/or practices in your current manufacturing and quality control system, so it’s best if you identify and make the required changes now, rather than discover problems in the middle of a CE mark inspection.

Some of the more significant changes to the Directive include:

• “Clinical” data is now required for all medical devices.
• A post-market vigilance and reporting system is now required.
• Documentation requirements have increased.
• “Single Use” devices must be justified and consistent.
• A single European Authorized Representative must be appointed.
• Records retention rules have changed.
• Inspections will be more thorough and comprehensive.

Clinical Data
One of the most comprehensive changes in the Directive is the new requirement that ALL medical devices, regardless of classification, must include clinical safety and performance data in their supporting documents. If your device does not have a “clinical data evaluation” in its technical file, you need to create one as soon as possible. Even if you have existing documentation on safety and efficacy, you should review it to ensure that the data and analysis it contains are acceptable under the standards of the new Directive, because the new clinical data requirements are much more restrictive than the old requirements.

In creating a “clinical data evaluation” document, the Directive limits manufacturers to three sources of acceptable clinical data: (1) published clinical results on your medical device, (2) published clinical results on an “equivalent” device, or (3) published or unpublished clinical experience with your device or an “equivalent” device. Where your device has already been on the market for a while, this clinical data should already exist in the form of actual use and safety data. If you take steps now to collect and analyze this data, it should be a compelling justification to support continued European marketing of your device.

Where your device has only recently been placed on the market, or where you are currently in the approval process for a new device, there may not be enough actual performance data available to justify clinical use under the new rules, even when including unpublished data on your device. Such limited actual data means that you will need to collect as much additional data on “equivalent devices” as you can find. While this can be done internally, it is often best to hire an outside third-party to conduct the clinical literature review and analysis for your device and its reasonable “equivalents,” to avoid any appearance of a conflict of interest. [A very good explanation of the clinical literature review process is available here.] 

The Directive also requires manufacturers to create systems for post-market surveillance and reporting on the performance of their devices, and then to use their post-market data to periodically update their clinical data evaluation. An important part of your review should include verification that that the required post-market data is being proactively collected and is being used to periodically update this clinical data analysis.

Whatever the status of your device, the most important thing is that the collection and evaluation of device and “equivalent” data can take weeks or longer to accomplish, so it’s critical to begin this process as soon as possible. So start now. Remember: a well organized and coherent “clinical data evaluation” document in the technical file for each of your devices (including any available assessment of actual clinical experience with your devices) will go a long way to assuring your inspector that you are well aware of and complying with the requirements of the new rules.  

Documentation Changes
The new rules require many changes of documentation, a few of which will be explained here. For example, all manufacturers must now place an issue or last-revision date on their “Instructions for Use” (“IFU”). Also, there is now a requirement to document a device’s phthalate content, if it contains such material. “Single-use” (disposable) medical devices must now include an explanation of the characteristics and technical factors that could pose a risk to the patient if the device were re-used–this explanation would typically be included in the IFU. It is also important to note that the indication of “single use” for a given device must now be consistent across the entire EU (you can’t also sell the device as reusable somewhere else in the EU)–and your IFUs or other safety documentation (i.e., FMEAs) will need to reflect this. Other changes to the documents required in your technical file can include an evaluation of the ergonomic features of the device relating to potential users, as well as a statement of the potential users’ required knowledge and education level.

For manufacturers located outside of the EU, the new rules require that the manufacturer designate a single authorized representative in the EU for all medical devices. The Directive also requires the manufacturer to designate a single authorized representative for each class of medical devices it sells. Although the Directive does not require the manufacturer to choose the same representative for both functions, it is often easiest to unify the two functions in a single representative. This representative is authorized to act for the manufacturer, and can be contacted with regards to the manufacturer’s compliance with the requirements of the Directive. The authorized representative(s) must be identified somewhere on the device or its packaging.

While the above change examples appear to be relatively simple and minor changes on their surface, you should remember that the revision of any controlled document requires a significant level of time and effort. Additional delays can occur with documents such as labels and/or IFUs, which often require foreign language translation, printing of multiple copies, and then whatever time is takes to package (or repackage) the revised documents with the appropriate medical devices. Addressing these issues as early as possible, therefore, can significantly lessen your risk of violating the Medical Device directives after the new rules are in effect.

Records Retention
The new rules require that all medical device manufacturers maintain their manufacturing and quality records for the “useful life” of the medical device (which should be defined by every manufacturer), or for a minimum of five years from the date of manufacture, whichever is longer. Moreover, the new rules require records on implanted devices to be maintained for a minimum of 15 years after the last product is manufactured.

Manufacturers should take care to ensure that the document retention requirements in their quality systems, as well as corporate document retention policies, reflect the new changes. It is also important to ensure that documents required under the new rules, but eligible for destruction under the old rules, are not destroyed in the months leading up to the implementation date.

Inspection Standards
Starting on March 21, 2010, the new rules will take full effect-there is no “phase in” period, and inspections for granting or renewing CE mark status will be conducted under the new rules. You, as the manufacturer, are responsible for complying with these changes to the European regulations, and you don’t get a “free pass” simply because your product was approved under the old regulations.

During CE mark renewal inspection, it is highly likely that the inspecting body will pay particular attention to the areas of clinical data evaluation, design documentation, user considerations, and manufacturer’s controls on third party design and manufacturing. These areas are particularly highlighted in the new rules, and thus the inspecting body is certain to focus its efforts in these various areas during their visit.

You’re not out of the woods yet, Red…
Even if you’ve accounted for many or all of the previous changes, you could have additional work to do if you are selling one or more types or classes of medical devices having specific additional requirements under the new rules. Under the new Directive, some devices have been assigned to a higher risk classification, which can even require “prior approval” from your notified body before you can continue selling the device after March 21, 2010. Obviously, it is HIGHLY recommended in such cases that you consult a regulatory expert familiar with many of the new changes to help you navigate the new rules.

Some specific areas of change in the new rules include:

1. Medical software – If you make stand-alone software, or if software is incorporated into your medical device, the software must be validated and may be regulated as an active medical device
2. Device risk classifications – a number of devices will change their risk classification under the new rules, including:

• Devices will now be classified by their primary mode of action, and not their intended use
• Devices that contain human tissue, blood or plasma are now classified in relation to that characteristic
• Devices used to disinfect invasive medical devices now have an increased risk classification
• The usage period for removed/replaced invasive devices is now cumulative. That is, the risk classification now relates to total usage period (the total duration of contact with the body), whether or not the individual device has been replaced. 
• The definition of the high risk “circulatory system” has been expanded to include the vessels all the way to the aortic bifurcation.
  

Revising Your Certificate of Conformity
After you take the necessary steps to comply with the requirements of the new Directive, you will be able to document this fact in your Certificate of Conformity. Specifically, you can note that your Document of Conformity states compliance with 90/385/EEC or 93/42/EEC, respectively, as amended by Directive 2007/47/EEC. Although various guidance documents have stated that such compliance will be assumed after March 21, 2010, it is a good idea to fully document the fact that your medical devices comply with the new rules.

My…What big TEETH you have…
If you remember only one thing from this article, remember that the new rules apply to everyone–if you sell a medical device in Europe after March 21, 2010, that medical device, and all the supporting documentation behind it, must comply with the new rules. If you leave the changes to the last minute, you may find yourself without approval after your next CE inspection, barred from selling to your European markets. That could translate into possible months of missing revenues, while you frantically make last-minute changes, and waiting at the end of a long line of unhappy medical manufacturers awaiting re-inspection. Take the necessary steps now to ensure your compliance with the new rules, and you will ensure your continued medical device sales in the European market.