Guest Editorial from Robert Packard, Sr. Manager, Regulatory Affairs at Delcath Systems, Inc.:
In February, at a press conference in Brussels, Commissioner John Dali requested immediate measures by the member states to ensure patient safety and restore the public’s confidence in the current system. Initially there was discussion about adopting a pre-market approval process similar to the FDA’s PMA process. As more information became available, it became clear that a European PMA process was unlikely. The European Commission does not support a PMA-like process, and a Dutch report from April of this year indicated that only France was in favor of a PMA system.
The FDA recently issued an internal report that was highly critical of the European approach to regulating medical devices.
In this report there are five key areas where the two systems are compared (reproduced in the table below).
First, the Standards for approval in Europe are Standards developed by device industry experts—including the US FDA. For example, resurfacing joint implants must pass simulated wear testing to ensure that the patient will not require revision surgery prematurely (i.e. – 90% of knee implants must last longer than 10 years). This type of long-term durability testing is not practical as an endpoint for clinical studies. This is why the Europeans require Post-Market Surveillance Plans and Post-Market Clinical Follow-up. The Eucomed plan calls for strengthening these Standards further.
Second, the clinical evaluation of literature referred to in the US FDA report was recently revised and updated by issuing a guidance document (MEDDEV 2.7.1 rev 3). This document is 46 pages long and requires that Notified Bodies complete a 17 page checklist for high-risk devices. Furthermore, it is increasingly difficult for companies to get CE Marking approval for Class IIb and Class III devices without performing clinical trials. There is also a revised ISO Standard for conducting clinical trials, ISO 14155, which has narrowed the gap between these two levels of clinical data quality.
Third, although the FDA is a central regulatory authority, there is no independent “watchdog” process for reviewing competency of FDA reviewers or the agency itself. The EU Commission’s approach is to urge member states to review the Notified Bodies they have designated and determine if the Notified Bodies are competent to perform these high-risk reviews. In addition, the Commission is emphasizing the need for competent authorities to act jointly—as though it were a single “central regulatory authority.”
Fourth, approvals are typically communicated by posting the CE Certificate and/or the Design Examination Certificate for a product on a company’s website. This documentation is also required as part of the registration process in each member state. Although the average citizen may not know where to get this information, the average citizen wouldn’t be able to navigate the US FDA approvals database either. Notified Bodies have no difficulty verifying authenticity of a CE Certificate with other NBs. Competent authorities and accreditation bodies also audit the Notified Bodies annually to verify that approvals are appropriate and justified. In fact, the competent authorities actually observe individual auditors on a rotating basis and audit reports are sampled even more frequently. The transparency of the PMA process is also questionable. Any documentation presented by a company is heavily redacted—thus eliminating the perceived benefits of public disclosure.
Fifth, post-approval reporting is required by the EU in several forms—albeit different from the US FDA’s requirements. Vigilance reporting is required to be submitted to the Competent Authorities. This vigilance is also shared with the Notified Body—who will review the documentation and ensure that appropriate corrective actions are implemented. Post-market surveillance is required by the ISO 13485 Standard (Clause 8.2.1) and the European Medical Device Directive (MDD). Post-Market Clinical Follow-up (PMCF) is also required in Annex X, 1.1c of the MDD. The EU Commission is calling for improved effectiveness of the vigilance process and tools for traceability of long-term device performance—including Unique Device Identification (UDI), which the US FDA recently issued as a draft document.
In summary, both of these systems have their strengths and weaknesses. However, the EU is striving to make some radical improvements to their system in the next two years and the US FDA is making its own big improvements. In the next two years, we can expect these two systems to become more alike than different—despite all the finger-pointing about which system is worse.
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