The intent of the proposed revisions to the existing European Medical Device Directives is to better protect public health, ensure free and fair trade of goods, and adapt the legislation to the technological advancements observed throughout the industry.1 These revisions have been in process since 2008, when the EU Commission initiated a public forum to collect comments on the existing European medical device directives.TUV In 2010, the need for change was even more apparent with the discovery of the French PIP breast implant scandal. Emergo In 2012, the European Commission released the initial draft of the proposed regulations. The directive on active implantable medical devices (90/383/EEC) and on medical devices (93/42/EEC) was combined into one proposed regulation on medical devices, referred to as MDR. A proposed regulation on in-vitro diagnostic (IVD) medical devices, referred to as IVDR, is intended to replace the existing directive (98/79/EC). The European Parliament and the European Council amended the proposed regulations, and final texts were released in June 2016.1
The regulatory approach utilized in the MDR and the IVDR is a life-cycle approach, rather than pre-approval path as outlined in the existing directives. Guidance documentation related to Authorized Representation, Clinical Evaluation, Vigilance, and Post-Market Clinical Follow-Up were essentially incorporated into the regulations.
The major changes included in the final texts of the MDR and IVDR are described below and the subsequent affects on manufacturers, notified bodies, regulatory agencies and patients are outlined.
The MDR and IVDR include a revised medical device definition, which broadens the application of the regulation to include products not currently covered under the existing directives. For example, the MDR will apply to products used for cleaning, disinfection or sterilization. Under the current directive, these types of products were considered accessories to medical devices and thus were out of the scope of the Directive.Emergo Other product groups now within scope of both the MDR and IVDR include devices that do not have a medical intended purpose, such as colored contact lenses, cosmetic implant material, lifestyle and nutritional diagnostic tests. TUV, BSI MDR/IVDR The definition of a medical device accessory was also revised, to include products that “assist” devices, which will cover additional products.
Classification rules in MDR and IVDR changed as well. The MDR increased classification for some devices or requires heightened oversight by the Notified Body but did not change the actual classification of the device. Rather than utilizing the list-based classification system in the Directive, IVDs will be classified per the system developed by the Global Harmonization Task Force into four risk-based classes using seven distinct rules. For IVD devices that do not fit into the classification rules and were self-certified under the existing Directive, the IVDR will classify these devices into a higher risk class which will require Notified Body certification. This is a pivotal shift for the IVD industry since approximately 80-90% of IVDs will now require Notified Body certification to sell in the EU.BSI MDR/IVDR
Placing Products on the Market
The number of Essential Requirements increased, as well as the number of detail for each requirement. The concept of common specifications was added to the MDR. Referred to as common technical specifications in the IVD Directive, common specifications are documents (not standards) that describe technical or clinical requirements and provide a method of conformity to a requirement of the Regulation. Manufacturers are generally required to comply with common specifications, unless justification can be adequately demonstrated to ensure the same level of safety and performance. The regulations require common specification compliance for aesthetic products.
Clinical Evaluation & Clinical Investigation
The requirements for clinical evaluation and clinical investigation are more rigorous under the new regulations. Clinical investigations may be required for class III and implantable devices if the existing clinical evidence does not fulfill the new requirements.
Clinical performance studies will be required and significantly more evidence will be required for IVDs.BSI IVDR Both the MDR and IVDR control the conduct of interventional and other clinical performance studies and require the use of good clinical practices, including informed consent. Another major change is the Post-Market Clinical Follow-up requirement as part of the clinical evaluation cycle for the device.
For clinical evidence that relies on equivalence with another predicate device, there are several additional requirements that will likely limit the path to market for this type of clinical justification. In order to leverage equivalence to another device the manufacturer must scientifically justify technical, biological and clinical similarity. There needs to be no significant difference in the clinical performance and safety of the device and the predicate. The manufacturer must be able to demonstrate access to the data on the predicate device in order to substantiate this claim. Since that data is typically proprietary between market competitors, this requirement will likely severely limit the use of comparator equivalence justifications.
Supply Chain Enhancements
Both the MDR and the IVDR implement new supply chain requirements that affect each step of the medical device supply chain. Each supply chain participant, including importers and distributors, will be responsible for verifying regulatory compliance. Better definition on roles and responsibilities is defined between the authorized representative, distributor and importer. Vigilance reporting of adverse events and subsequent implementation of corrective action (as required) will be expanded to include importers and distributors as well as the manufacturer. All members of the supply chain must be able to maintain traceability of devices and retain those records for at least five years after the last device is supplied to the EU market. The regulations define the financial liability of the manufacturer as well as the authorized representative in the case of injury caused by the device.
Unique device identification (UDI) will also be required. The UDI is compromised of two parts, a device identifier(DI) and a production identifier (PI). The DI is a fixed portion of the UDI that identifies the model number of the device and links the device to the manufacturer. The PI is the variable portion of the UDI that identifies the lot/batch number, expiration date/manufacturing date or serial number for the device.
There are many changes to labeling and instructions for use requirements. All device labels, on all levels of packaging will likely be revised as a result of the new regulations. There are special labeling requirements for certain implant products. The patient must have easy access to all safety information, including warnings and precautions, expected lifetime of the device and any mandatory follow-up. With regards to the actual implanted device, the patient must receive identification of the device including UDI information.
Vigilance and Post Market Surveillance
There are substantial changes to the post-market surveillance and vigilance reporting requirements under the new regulations. Some reporting rules were changed, which will result in more reports. The timeline for reporting serious public health threats did not change, but the timeline for reporting all other adverse events decreased from 30 days to 15 days. The reduced time allowed for reporting will likely result in an increase in the number of follow-up reports in order to provide additional information. The combination of the change to reporting rules and the reporting timeline shift will result in an overall increase in the number of vigilance reports submitted by manufacturers.
A requirement for post-market clinical follow up was added as well as periodic (annual) safety update reports. These reports will summarize post-market data and analysis, a description of any actions taken as a result of post market trends and include sales volume data.
The Affect on Key Stakeholders
There is no provision for “grandfathering” of existing products under the new regulations. Therefore device manufacturers will need to review product portfolios to determine the affect of the new regulations and subsequent actions needed for both CE marked products and non-CE marked products. BSI MDR/IVDR
Due to the increased clinical and regulatory requirements, manufacturers may need to invest in additional resources to adequately satisfy the clinical and regulatory requirements. It is possible that new clinical data will need to be generated, which is a substantial undertaking, both from an economic and resource perspective. Under the new regulations, device manufacturers (and authorized representatives) are required to retain at least one person permanently and continuously who is responsible for regulatory compliance, regardless of the size of the organization. The one exception noted for this is for manufacturers of custom devices who are micro-enterprises.
One of the major role changes driven by the new regulations is the evolution of the notified body role from an industry partner under the Directives to a police-like extension of the Competent Authorities. In the new regulations, notified bodies are required to undergo a designation process and stricter requirements for notified body staff are defined. The demand for notified bodies will increase dramatically, as not all current notified bodies may seek or may not seek full designation for all services currently supplied to manufacturers. Further increasing the demand for notified bodies, is the classification changes, especially in the IVDR, which will require more resources from designated notified bodies.
Another major change in the MDR is that notified bodies will be required to submit their clinical evaluation assessment report to an expert panel appointed by the EU Commission prior to certifying a class III implantable device or class IIb device intended to intended to administer/remove a medical product.
The regulations will require notified bodies to conduct unannounced audits at least once every five years, which originated as a recommendation from the commission in 2013. Notified bodies are required to test manufacturing samples, or even market samples. However, the responsibility for the cost of this testing is not defined.
In an attempt to harmonize efforts between member states, a new regulatory body called the Medical Device Coordination Group (MDCG) is defined with a primary purpose of increasing collaboration between member states while allowing the EU Commission to act when required. The additional vigilance requirements will demand more resources to support processing data at the member state level. Member states will be need to work together in order to coordinate enforcement activities and report surveillance plans to be incorporated into the European Market Surveillance Plan. Member states also can begin applying fees to cover the costs associated with the new requirements.
One of the primary objectives of the new EU regulations is to better protect public health. Patient access to information is enhanced. The addition of UDI and vigilance reporting to the European database systems will help make essential device information and user experience data more readily available. UDI information will improve recall and field safety corrective action effectiveness. Additional labeling requirements will better inform the end user. One drawback is that due to the tightened clinical requirements, patients may experience a longer delay in access to new medical devices and technologies. However, more robust regulatory controls with the intent to improve overall patient safety should outweigh this risk.
The changes the new regulations bring to the European medical device community and vast. Although the new regulations will not go into effect until three years after formal publication in the Official Journal of the European Union (OJEU), it is important to begin preparing now for implementation.
Medtecheurope, European Unique Device Identification Database (EUDID), Accessed February 29, 2017
EU Commission Recommendation. n.d. //www.3ec.sk/fileadmin/user_upload/Product_Certification/UNANNOUNCED_AUDITS_2014.pdf.
2. Commission Recommendation. September 2013, 2013. //eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2013:253:0027:0035:EN:PDF.