Prompted by rapid advances in medical device technologies and in part by recent findings of safety issues with previously approved devices, the regulation of medical devices in the European Union (EU) is undergoing a sweeping transformation. Current changes include an expanded scope of regulated devices, greater oversight and control of notified bodies, unannounced audits of suppliers and more. For most medical device manufacturers, these changes will directly impact the product review and certification process, and are likely to increase the investment of time and resources required for product approval.
The proposed regulatory changes are likely to have the greatest impact on manufacturers of in vitro diagnostic medical devices. In vitro diagnostics, which include chemicals and reagents, consumables and analyzers used in the evaluation of human specimens such as blood and urine, represent an annual global market value of approximately $50 billion (USD), and are projected to exceed $22 billion (USD) in Western Europe alone by 2018.
Under the proposed changes, nearly 80 percent of in vitro diagnostic medical devices sold in the EU could be subject to notified body approval, up from just 20 percent currently.
This article, excerpted from a white paper from UL, offers an overview of the recent and proposed changes to regulations applicable to medical and in vitro diagnostic devices sold in the EU. Click here to read the white paper in its entirety, covering possible impact on device manufacturers, and how device makers can effectively navigate the changing EU regulatory landscape.
Proposed changes to EU device regulations
Although specific aspects of the EU’s proposed medical device regulations are subject to further modification prior to their final publication, the proposed regulations do provide some insight into changes likely to affect manufacturers, importers and distributors of medical devices once the new regulations take effect. While some of the anticipated changes will affect the approval and post-market surveillance of all medical devices, the largest impact is expected to fall on manufacturers of in-vitro diagnostic medical devices.
Each of the proposed medical device regulations includes a number of annexes that detail general health and safety requirements, classification rules, clinical evidence requirements, and the role of notified bodies. Some of the specific, anticipated changes from the current medical device directives include:
• Extension of regulatory scope: Both 2012/0266 (medical devices and active implantable medical devices) and 2012/0267 (in vitro diagnostic medical devices) will extend the scope of medical and in vitro diagnostic devices currently regulated by the EU. Newly regulated products are expected to include implants for aesthetic purposes, genetic testing products, dedicated medical software and some high-risk devices manufactured for use within a single health institution.
• Implementation of classification structure for in vitro devices: In vitro diagnostic medical devices will now be subject to classification rules that allocate products to one of four risk classes, similar to the classification structure that already exists for medical devices in the EU. Notified body approval will be required for the majority of in vitro diagnostic devices, with the exception of those that pose a low risk to patients.
• Reinforced regulations covering clinical investigations: 2012/0267 will require manufacturers to provide a summary of safety and clinical performance in support of pre-market applications for in vitro diagnostic medical devices posing medium to high risk or high risk to patients, and to maintain post-market data for continuous assessment of potential safety risks.
• Implementation of unique device identification requirements: Both 2012/0266 and 2012/0267 propose requirements regarding the use of unique device identification (UDI) mechanisms to increase traceability of devices through the supply chain, and to facilitate effective product recalls in the event of safety concerns.
• Role of “qualified persons”: Manufacturers will be required to have within their organization at least one individual responsible for all aspects of regulatory compliance. This “qualified person” must possess the experience and/or skills appropriate to this task.
•Expanded registration database of devices: Both regulations propose to expand the use of the European Databank on Medical Devices (Eudamed) to provide a centralized repository of information on approved medical devices for regulators and consumers. This change is expected to increase EU-wide access to product information, thereby increasing transparency and improving overall safety.
• Increased regulation and oversight of notified bodies: Notified bodies will be subject to new minimum requirements to achieve and maintain designation, and more rigorous monitoring by national authorities through witnessed audits and other mechanisms.
• Stronger post-market vigilance and surveillance: Notified bodies will be granted increased authority to conduct post-market product testing and sample checks, including unannounced factory inspections at manufacturing locations. Increased vigilance issues, reported field complaints or other product concerns may result in additional unannounced audits.
• Greater coordination of regulatory efforts: The proposed regulations call for the formation of a medical device coordination group (MDCG) composed of members representing national authorities. The goal of the MDCG is to facilitate coordination between EU member states of medical device egulation and surveillance, with scientific, technical and logistical support provided by the EU Commission.
• Other changes: Both proposed regulations clarify key definitions and terms used to avoid confusion or misinterpretation. The regulations also clarify the legal responsibilities of medical device distributors and importers as well as those who sell or market medical devices via the Internet.
Recent changes in Notified Body audits and assessments
As noted previously, EU member states are responsible for transposing the essential requirements of directives into national law, leaving open the possibility for interpretive differences. In addition competent authorities in member states can apply different criteria in the appointment and operation of notified bodies. The gaps between individual member states in the transposition of product requirements and the criteria applied to notified bodies can ultimately compromise the goal of achieving uniform levels of patient safety across the EU.
To help narrow these gaps, the EU Commission has also issued a Recommendation addressing the performance of audits and assessments by notified bodies. Commission Recommendation No 2013/473/EC 11 clarifies the current Directives in terms of conducting product assessments, assessments of a manufacturer’s quality system, and unannounced audits.
Specific guidelines are detailed in the Recommendation’s three Annexes, with product assessments addressed in Annex I, quality system assessments addressed in Annex II, and unannounced audits addressed in Annex III.
The Commission’s guidance on unannounced audits has been the focus of much of the attention being given to this Recommendation. It calls on notified bodies to carry out unannounced audits at least once every third year. More frequent unannounced inspections are recommended in cases involving high risk devices, if devices of the type in question are frequently found to be non-compliant, or when specific information gives cause for concerns regarding a product’s safety. The guidance also specifies the length of unannounced audits (at least a day), and the minimum number of auditors (at least two).
The Commission’s Recommendation on audits and assessments is applicable to the Commission’s current medical device regulatory framework and is not dependent on the approval of the Regulations discussed earlier in this paper. Although the guidance has been published as a Recommendation only, it is expected that notified bodies will comply with the guidelines regarding audits and assessments.
Failure to do so could be interpreted by national authorities as a derogation by the notified body of the essential requirements of current directives and regulations, potentially resulting in the loss of its notified body designation.
Further changes can be found in Commission Implementing Regulation No 920/2013,12 which came into force at the end of 2013. The Implementing Regulation establishes EU-wide criteria for the designation of notified bodies, as well as provisions governing the extension and renewal of notified body designation. The Regulation also requires designating authorities in EU member states to monitor the performance of notified bodies within its jurisdiction through file reviews, on-site assessments and audits. Finally, under the terms of the Regulation, the Commission reserves the right to investigate individual cases of notified body competence.