Getting or Keeping CE Marketing

In just under 18 months, if you manufacture medical devices that are placed on the European Market, changes are coming that can affect companies that currently have CE Marking, or are trying to achieve the marking. In order to avoid unnecessary delays or even lose certification, Claire McKenna, medical device program manager with the National Standards Authority of Ireland (NSAI), helps make sense of these changes.

It is well known that if a company wants to sell a medical device in the United States, they need FDA approval; if that device is to be sold in Europe, it requires CE Marking. "In order to obtain CE Marking – unless the device you want to market is very low-risk – you need a Notified Body to approve the product so you can achieve CE Marking," McKenna explains. "NSAI, being a Notified Body, works with companies that are seeking CE Marking for their products."

Understanding Directives

Directives are issued by the European Commission – there's a requirement for each country in the EU to take that directive and transpose it into national law in order for it to become a legal requirement.

There are three main medical device directives. The first is the Active Implantable Medical Devices Directive (AIMD) – 90/385/EEC. This directive is specific because it covers devices that are powered and placed in the body and are intended to remain there for a period of time; for example; a pacemaker. "All medical devices covered under this directive are high risk devices," McKenna says. The next directive 98/79/EC is the In-Vitro Diagnostic Devices Directive (IVD) which addresses devices used to test human samples outside of the body. Some basic examples would be devices used for blood type testing and pregnancy testing. Finally, 93/42/EEC Medical Devices Directive (MDD) is the one that most devices would fall under.

The manner in which EC Directives are changed is rather complex, McKenna explains, and is not always obvious. This is because changes are made through the publication of other Directives.

There has been a major revision to the AIMD and the MDD. After many years and drafts, in September 2007 a new directive was published: 2007/47/EC. While clarification is primarily the main aspect of this new Directive, some of the areas of change will significantly affect companies in the area concerning clinical data, definition, post-market surveillance, and for devices falling under the MDD, classification. Since Directive 2007/47/EC is making a significant change to both the AIMD and the MDD, a Notified Body, such as NSAI, can help ease the pain and help ensure compliance.

Classification Know-How

You can have a very simple, low-risk device, or a very high-risk device; it does not make sense to put the same rules in place for all devices, so classification for devices is risk-based.

"Class 1 is the lowest risk and Class 3 is the highest risk," McKenna explains. "If it is a Class 1 device that is not sterile and does not perform a measurement function, the risk to the patient or user is remote, so the level of control is minimal. In these cases it is really up to the manufacturer to declare, ‘I meet the applicable requirements of the directive and no Notified Body involvement is required.' This is referred to as ‘self-declaration.'"

However, if it is a high risk device, the manufacturer needs a Notified Body who is more involved in making sure that the product and the systems that are used to produce the product are acceptable and that they meet requirements of the directive.

Here is where the changes in the directive can affect manufacturers: If a manufacturer currently has a low-risk device, certain changes in the new directive may reclassify it into a higherrisk device, then different steps have to be taken in order to obtain, or maintain, the CE Marking.

According to McKenna, there are five device classifications in the MDD: Class I, Class I sterile/measuring function, Class IIa, Class IIb, and Class III. A Notified Body starts getting involved for anything other than a Class I (nonsterile/non-measuring). As mentioned above, "the way the Directive is structured, the higher the risk, the higher the class, the more that is required for certification, which in turn will mean greater attention to the detail and a greater amount of documentation that needs to be supplied," McKenna says.

Closing Loopholes

Many of the changes to the MDD are really fixing loopholes or clarifying areas that were somewhat overlooked or interpreted. For example, the rules that covered surgically-invasive devices, something that is going into the body through a manmade opening, for example piercing through the skin with a needle, and those for transient use – meaning it is only used for up to 60 minutes at a time – these devices are generally Class IIa, but there are exceptions if it is used in certain areas of the anatomy.

Up until now exceptions covered the central circulatory system. However, in the revision to the MDD, the central nervous system has now been added as an exception. So come 2010, such a device will no longer be Class IIa, but will be considered a Class III. As a result, it is important for manufacturers start looking at making sure that they can support the revised requirements.

The conformity assessment routes available (ways for pursuing CE marking) may change after 2010, due to the fact that as the risk of the device increases and manufacturers may not have as many options as before. "What NSAI is currently doing to assist its customers with conformity is as their currently-approved products come up for renewal, we are reviewing the devices against the new standards to see if the classification will be changing," McKenna explains. "In the case where there is a change in class, clients can begin to take the proper steps to demonstrate that it now meets the added requirements.

Clinical Data

Aside from the changes in classification for the MDD, probably the most significant impact of the revision to manufacturers is the entire area of clinical data. The new Directive provides a clearer definition of what constitutes clinical data. Basically, it is the clinical information used to support the product's safety when it is used in or on humans. So obviously the manufacturer will have to do testing first to make sure that they have taken every precaution, so that it won't break and injury somebody. The current Directive always had the intent that the manufacturer would supply clinical data; the higher the risk, the more data required. However, manufacturers also had the option to go down the literature route – where the manufacturer would piggy-back on another devices' clinical data.

"The important thing, when the device is being compared to other devices, is that the manufacturer has to be able to demonstrate equivalence, and that's very important – it must be comparing apples to apples," McKenna states. It has to be the same materials, the same area in the anatomy, and the same intended use. All the variables will need to be the same, otherwise the company won't be able to use that data to demonstrate that their device is safe.

Broadened Scope

Another change is broadening the definition of a medical device, and what that encompasses. The current MDD does mention software, which is part of a medical device. "Now, the new Directive has come out and defined stand-alone software as a medical device when it is intended by its manufacturer to be used specifically for diagnosis and/or therapeutic and necessary for the proper application," McKenna says.

"Bear in mind that things evolve, and software is used much more often. For example, you may have had a device that took certain readings and recorded them. Today, software takes those readings, then uploads them into a database for a physicians review. In this case, the software is being classified because it can impact diagnoses." In this case, if the software fails it may lead to misdiagnosis.

The MDD change has been made so that any software used for diagnosis or therapeutic purposes, is now considered a medical device and must go through the process for CE Marking.

Post-Market

Currently with CE Marking there's a vigilance system that requires that a manufacturer who receives a complaint about a device must investigate the complaint. The vigilance system is not just for something that actually happened, but also for something that could happen. In these situations, it is considered a reportable incident or event, and that's pretty common in any regulatory system.

This vigilance system has always been in place, but what is now required for all devices is that the manufacturer needs to have a plan in place for following up on incidents once a product has been placed on the market. This plan must be ready as part of the product's release plan. Manufacturers have to plan to follow up to see how things are doing rather than just waiting for people to report issues. McKenna explains that the directive says if you do not take a proactive approach, you are going to have to justify why not. "NSAI is working with our customers to make sure this is yet another area where they will be prepared come 2010 – taking the proactive approach," she adds. "There will be significantly more emphasis placed on post-market clinical follow-up as a part of the post-market surveillance plan. Companies will have to keep close tabs on their products and have a system in place to report, and react, to any unexpected changes once the product is released in the marketplace."

Keeping the CE Mark

McKenna suggests that the first step a company should take prior to 2010 is to talk to their Notified Body. Next the manufacturer really needs to get a feel for these changes in order to determine what, if any, impact they will have on their products. Finally, the manufacturer should make sure they have the latest Directive to refer, this is because there have been a few directives and one regulation that have already impacted the MDD.

After reviewing all the changes to the Directives that will take affect in 2010, U.S. companies that export their products to Europe will be required to provide additional steps to conform – specifically in the areas of the definition of a medical device, clinical data, classification and post-market steps. "Working with a Notified Body now, in 2008, will help avoid many stumbling blocks come 2010. The last thing a manufacturer would want to do is be caught offguard when the new Directive takes effect," McKenna concludes.