Postmarket Obligations for U.S. Companies Marketing Medical Devices in Europe

Gaining CE mark approval in Europe for a medical device and in-vitro diagnostic (IVD) device is a complex process. Many non-European manufacturers are unaware of individual country requirements and that systems for vigilance and postmarket surveillance must be in place for all classes of IVDs and medical devices before marketing any device. 

In addition, any change made to a device after it has been placed on the market must be assessed by the manufacturer to determine the impact to safety and effectiveness of the product. 

Costly errors and time delays can create cost pressures on manufacturers who may not be fully cognizant of the complexity of the process versus partnering with experts in regulatory compliance to successfully maintain CE mark approval.

Customer Complaints & Vigilance
Manufacturers need to implement a system for reviewing and evaluating customer complaints and product issues for any safety concerns. Events that fall under the definition of an “incident” must be reported to the national competent authority of the country in which the incident occurred. For example, if the incident occurred in Sweden, the incident must be reported to the Medical Products Agency in Sweden.

An “incident” is defined in the European medical device directives as “any malfunction or deterioration in the characteristics and/or performance of a device, as well as any inadequacy in the labeling or the instructions for use which, directly or indirectly, might lead to or might have led to the death of a patient, or user, or of other persons, or to a serious deterioration in their state of health.”

Three specific criteria must be met for an event to constitute an incident: an event has occurred; the manufacturer’s device is suspected to be a contributory cause of the incident; and the event led, or might on reoccurrence lead, to death or serious deterioration in the state of health of a patient, user or other person.

Additionally, incidents must be reported by the manufacturer or its European Union (EU) authorized representative to the competent authority within the defined timelines—immediately, or within two calendar days for a serious public health threat; within 10 calendar days where death or serious deterioration in the state of health of a patient, user or other person has occurred; and within 30 calendar days for all other incidents.

Incidents that occur within the 33 European countries that have adopted the medical device directives (28 EU members; three European Economic Area members—Norway, Iceland and Liechtenstein; one EU candidate country—Turkey; and Switzerland) must be reported to the relevant national competent authority under the European medical device vigilance system. Incidents that occur outside of this jurisdiction do not need to be reported to the European competent authorities.

Postmarket Surveillance to Mitigate Product Risks
Postmarket surveillance programs are expected to provide ongoing feedback to the manufacturer relating to the quality of the manufactured product, its safety and customer satisfaction. Product risks can never be completely eliminated. Therefore, manufacturers need to continually monitor feedback through postmarket surveillance activities to ensure risk is maintained at an acceptable level.

For example, some postmarket surveillance activities include clinical literature searches, search of regulatory agency databases for adverse events and field actions for similar products, feedback forms/questionnaires to healthcare professionals; analysis and trending of internal processes, i.e. corrective and preventative actions, complaints, non-conformances, servicing issues; and review of adverse event reports.

A formal postmarket surveillance review is necessary to understand how the device is performing in real-life situations. Typically an initial postmarket surveillance review meeting may be held six months to a year after the device has been launched or undergone a significant design change.

Product-related data from the various sources is analyzed and reviewed by a cross-functional team. Actual or potential safety and performance issues are reviewed, and any necessary actions for improvement or mitigation are agreed upon. A postmarket surveillance review program typically can be set at a frequency of one to three years. However, medical products that pose a higher risk or have significant product safety and/or quality issues should be formally reviewed more frequently. From a safety perspective, the manufacturer must ensure that following a risk-benefit review, the benefits continue to outweigh the risks throughout the life cycle of the product.

Efficient Change Control
Similar to the need for effective vigilance and postmarket surveillance systems, it is essential that device firms implement an efficient and effective change control system. It is accepted that process and product improvements may be required; manufacturing lines get moved, suppliers, equipment and raw materials change; and regulations constantly be updated or revised. Manufacturers are responsible for assessing product changes to determine their impact on safety and effectiveness. From a quality perspective, that means manufacturers need to ensure that where necessary, appropriate risk assessment is documented and verification and validation testing is performed prior to change implementation.

From a regulatory perspective, manufacturers also need to assess if the change has an impact on the contents of the CE technical file or design dossier.

The following factors should be considered when performing a regulatory impact assessment of a product change:

• Impacted products and markets
• Device classification
• Impact to:

– Essential requirements checklist
– List of standards
– Risk analysis
– Product labels and use instructions
– Biocompatibility
– Shelf life
– Product specification
– Clinical evaluation

Many modifications will require an update to the product CE technical file or design dossier, which can be handled by the manufacturer internally. Where a notified body has been involved in the conformity assessment, the manufacturer must determine if the notified body should be informed and/or approve of the product change. 

According to the Coordination of Notified Bodies Medical Devices on Council Directives guidance, the manufacturer must inform the notified body of “substantial” changes. The guidance document also provides some examples of “substantial” design and quality system changes, and the rationale behind the categorization of such changes. Manufacturers should develop a system for categorizing substantial changes relevant to their device.

Cutting Through the Clutter
Clearly, there are myriad regulatory requirements a manufacturer must face when attempting to obtain and maintain their CE mark in Europe. As in the United States, the regulatory environment constantly is changing with new regulations, re-regulation and sometimes confusing compliance issues. This is made even more perplexing when trying to comply with each European country’s specific requirements. Even one small error can result in significant cost impacts and time delays.

Seeking a partner whose role it is not only to stay current on the changing regulations but who also is knowledgeable in all areas of postmarket compliance can make a major difference in eliminating errors or delayed filings of updated information that could impact the viability or accessibility of the product in the market—and eliminate significant cost impacts. 

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Paula McCarthy has been a senior regulatory affairs advisor with Acorn Regulatory (www.acornregulatory.com) since 2013. She holds a bachelor of science degree and a master’s degree in biochemistry. She has worked for more than 20 years in the medical device industry, where she held management positions in R&D, quality and regulatory affairs.