The RAPS San Francisco Bay Area Chapter kicked off 2014 with a 7 March conference focused on the proposed EU medical device regulations. Topics covered both near-term and long-term changes in key requirements critical to demonstrating compliance to existing directives and impending changes as proposed. The message was clear-change is underway in the EU and the medical device industry needs to be ready sooner than anticipated.

A BSI Healthcare medical device expert team presented at the chapter event. A brief summary of each conference segment follows.

Proposed Medical Device Regulation (MDR) and IVD Regulation (IVDR)

Paul Brooks, senior vice president, Healthcare Solutions, BSI Healthcare, told attendees that in October 2013, the EU Parliament completed its first reading of the proposed Medical Device Regulation and In Vitro Diagnostic Regulation, which were initiated by the European Commission (EC) in September 2012. The outcome, according to Brooks, was that the EU Parliament "added a few edits to the draft regulation that are challenging" for the industry overall from BSI's perspective.He emphasized the regulations are not yet final, so further revision is likely. But, there is no doubt the requirements and expectations are increasing for both Notified Bodies (NBs) and industry entering the EU market. Here are some key regulatory proposals, according to Brooks.

Three directives (Medical Devices Directive (MDD), Active Implantable Medical Devices Directive (AIMDD), and In Vitro Diagnostics Directive (IVDD)) will be consolidated into two regulations-the Medical Device Regulation (MDR) and the In Vitro Diagnostic Regulation (IVDR). The proposed MDR, with 10 Chapters, 97 Articles and 15 Annexes, is a larger document than the MDD but has a similar structure. The IVDR also is larger and more detailed, similar to the proposed MDR.

Each NB likely will have tighter scopes of designation defined by the Competent Authorities (CAs). All NBs must apply for new designations under the proposed regulations. As a result, Brooks believes industry may observe a reduction in the number of NBs, particularly smaller ones, pulling out of the medical device space due to the greater demands for in-house competence imposed by the new regulations, combined with the potential for a narrower scope of business opportunity.

New delegated entities under the proposed regulations may add time to the EU review process. These include:

• Medical Device Advisory Committee (MDAC)-This is an expert committee of stakeholders providing important guidance to the EC and the Medical Device Coordination Group (MDCG) and will play a role in supporting the review of high-risk products.
• MDCG-The committee of EU Member State representatives will play a significant role in how regulations are implemented.
• Assessment Committee for Medical Devices (ACMD)-The committee will assist the MDCG with the review of high-risk devices.
• Special Notified Bodies (SNBs)-These are NBs with specific expertise that will be designated by the CAs to evaluate high-risk (Class III MDR and Class D IVDR) and novel technologies.

For the proposed MDR, Brooks pointed out the more contentious aspects of the proposed regulation:

• Chapter VIa introduces more prescriptive labeling requirements for medical devices, including Unique Device Identification (UDI), and enhanced controls for the safe reprocessing of medical devices. Industry should be wary of this, said Brooks, and BSI anticipates this may change prior to the final rule being published.
• Single-use devices must be approved and included in the proposed list on single-use devices as agreed upon by the EC in conjunction with MDAC.
• There will be an increased control of the supply chain including NB audits of critical suppliers.

Medical device classifications, the EUDAMED database and UDI requirements, technical documentation, common technical specifications (CTS), Declarations of Conformity, and annual safety and clinical performance reports (Class III and active implantable devices) are just a few areas of change in store within the proposed regulations.

The proposed IVDR is a "quantum leap" from the existing IVDD, Brooks said, introducing a new IVD classification scheme (including genetic tests) and other major changes such as new conformity assessment paths. Moving forward, 80-90% of all IVDs on the market now will require NB involvement.

Regulation now encompasses language from European Commission Medical Devices Guidance Documents (MEDDEVs) concerning postmarket surveillance, vigilance and clinical evaluation. The role of the MEDDEVs now will need to be reassessed.

The next step in the EU regulatory process is the first reading of the regulations by the EU Council, followed by second readings by all parties (EC, EU Parliament and EU Council). This is targeted for completion by end of the fourth quarter of 2014/first quarter of 2015. Once finalized as a regulation, the three-year transition period for both the MDR and IVDR is anticipated to begin by the third or fourth quarter of 2015.

Unannounced Visits

Brooks also discussed unannounced visits, which are being implemented in the EU quite soon. In September 2013, EU Commission Recommendation 2013/473/EU was published in response to the PIP Breast Implant fraud. Annex III of this recommendation requires NBs to make unannounced visits in addition to regular product and Quality Management System (QMS) assessments. Although the provision for unannounced visits exists currently within the MDD, NBs rarely put this into practice. Furthermore, these visits can be held at the manufacturer's facility, at a critical subcontractor or a crucial supplier, at a frequency of one visit per third year (more frequently for high-risk products). Who will pay for these visits? The manufacturer will, according to Brooks.

These audits will be focused visits, looking at ongoing manufacturing, technical documentation, product identification and traceability, verification of components and may involve witnessing tests. The audit team will not be the regularly assigned NB QMS or product auditors. NBs will be evaluated by their CAs to see how well they are implementing this new requirement come June 2014.

What can manufacturers do now to prepare? BSI recommends the following:

• Study Commission Recommendation 2013/473/EU published on 24 September 2013.
• Review critical subcontractors and crucial supplier contracts.
• Factor additional visit costs into hour budget processes for NBs.
• Draft processes/procedures for receiving unannounced visits.
• Communicate awareness across all staff and train staff.
• Perform mock audits. Be ready.

Understanding Clinical Equivalence

Caution: clinical equivalence may not be what a manufacturer thinks it is, according to Laurel Macomber, MS, PMP, RAC, BSI product expert, and Ronald Rakos, PhD, RAC, team leader, Vascular Devices, BSI Healthcare. For the EU market, it is not "substantial equivalence" as determined under US Food and Drug Administration (FDA) guidelines. This is a common trap into which manufacturers that sell in both markets fall. MEDDEV 2.7.1 defines "equivalent devices" for the EU as those devices that:

• have the same intended use
• have similar technical characteristics
• have similar biological characteristics

These characteristics should be similar to the extent that there would be no clinically significant difference in the performance and safety of the comparable device.

The message was clear: an FDA predicate device found to be substantially equivalent under 510(k) premarket notification policies may not meet the MEDDEV 2.7.1 definition for an equivalent device. FDA requirements allow for technological characteristic differences, such as different materials, provided the sponsor can demonstrate the change does not raise new safety and effectiveness issues. This may not be the case for the EU.

For the EU, the manufacturer of the newer device should focus on discussing the differences, rather than highlighting the similarities. Several practical examples were prepared by Macomber and Rakos and reviewed with audience participation.

Risk Management and the Impact of EN ISO 14971:2012

EN ISO 14971:2012 is the European harmonized standard based on ISO 14971:2007, Macomber and Rakos told the chapter meeting. It took effect 30 August 2012 and superseded former harmonized standard EN ISO 14971:2009. They emphasized that manufacturers should have updated all internal procedures by now to reference the 2012 harmonized standard for presumption of conformity to the directives.

What are the differences in the two standards? They are in the foreword and Annex Z only. Annex Z tries to provide greater clarity and alignment with the requirements of the three directives for risk management.

Macomber reviewed the general requirements of a risk management system, in addition to covering the seven content deviations between the international standard and the directives' requirements.

For example, ISO 14971 states the "manufacturer may discard negligible risks." However, the directives require that "all risks, regardless of their dimension, need to be reduced as much as possible." So, it is not sufficient to state that risks are acceptable, medical device manufacturers also must demonstrate the risks have been reduced as much as feasibly possible.

It is imperative for medical device manufacturers to understand what these content differences are in order to establish compliance with the harmonized standard and the applicable product directives.

Technical Files and Design Dossiers

Lastly, BSI HealthcareTechnical Director Ibim Tariah, PhD, confirmed current technical documentation requirements as well as some helpful interpretation of key sections such as the Essential Requirements, risk management, supplier management, postmarket surveillance (reactive and proactive PMS), postmarket clinical follow-up (PMCF) and Declarations of Conformity.

One of the common mistakes made by manufacturers regarding product-line extensions is providing the NB with an incomplete design dossier supplement. "Be sure to cover all the key elements of the content of a dossier-tell the complete story," Tariah said. "Consider what you would expect to see. Doing so will help to reduce the review time," he added.

About the Author

Lori A. DonDiego, RAC, is theRAPS San Francisco Bay Area Chapter co-chair for communications. She is a senior manager of regulatory affairs at Cerus Corp. in Concord, CA, and can be reached at loridondiego@comcast.net.

Cite as: DonDiego L. "Embracing Change in EU Medical Device Regulation - The Notified Body Perspective." Regulatory Focus. March 2014. Regulatory Affairs Professionals Society.