Continuing the First Steps in a European CE Marking Compliance Strategy

This article is the third in a series covering the differences and the areas needing to be addressed, when planning to market medical devices in Europe, that are already cleared for market under a U.S. Food and Drug Administration 510(k). If you haven’t already read part one and part two of this series, you should prior to this one.
 
This article addresses the issue of how to present existing U.S. Food and Drug Administration compliant clinical data in a manner that will help minimize the number of issues raised by the reviewing European Notified Body.
 
Clinical Data Requirement
The clinical evaluation process outlined here has been simplified, but it does cover and illustrate the main steps in the process. Clinical data, assessed and analyzed in accordance with the European MEDDEV, with the conclusions presented in the form of a Clinical Evaluation Report (CER), is a mandatory requirement for affixing the CE Mark in Europe. Simply submitting existing clinical data, even though it has been acceptable for a U.S. Food and Drug Administration market clearance, will NOT be acceptable on its own for Europe.
 
The CER must make reference to the relevant MEDDEVs and the data contained within the CER should follow the format recommended in the primary MEDDEV. The primary MEDDEV is 2.7.1 Revision 3 titled, “Clinical Evaluation: A Guide for Manufacturers and Notified Bodies,” but it should also be noted that there are several associated MEDDEVs dealing with the related issues of clinical trials/studies and the reporting of SAEs, etc., that need consideration.
 
Objectives and Scope
There are three distinct phases to the process. The first step is to identify and determine the essential safety and performance characteristics of the subject device. The objectives and scope of the clinical evaluation must be clearly stated and documented, in order for the “signed off” conclusion at the end of the process to be able to confidently ensure that the objectives within the defined scope have been met, the device performs as intended and is safe in use, and any risks are acceptable or mitigated.
 
Clinical Evaluation
Clinical evaluation is the process in Europe where the clinical safety and performance characteristics of a medical device are verified. Verification is accomplished by determining the safety and performance characteristics and then identifying pertinent existing published literature and clinical data, which is then assessed and analyzed in accordance with strict criteria, with the results then being used to arrive at a conclusion. The conclusion then confirms and verifies the safety and performance characteristics that were determined during the first phase.
 
Literature and Clinical Data
The data used in clinical evaluation consists of a combination of published literature, the results of clinical experience, and the results of clinical trials/studies. Every piece of clinical data used in the evaluation process has to be assessed for its suitability and ability to contribute to the evaluation process.
 
A distinct process must be established for reviewing all the potential literature and data. The process must include well-defined inclusion and exclusion criteria, including weighting of the reviewed data in accordance with its contribution to the evaluation process. Clinical data with a negative contribution to the process should also be included for balance.
 
Equivalence Criteria
It is fundamentally important that the inclusion criteria for any literature or clinical data takes account of the following aspects before committing the data for use in the clinical evaluation. If the cited device in the literature is NOT the subject device, then equivalence must be shown regarding the clinical, technical, and biological essential characteristics.

• Clinical: Same intended purpose, clinical condition, site of application, and indications/contraindications
• Technical: Mode of operation, environment of use, and specifications
• Biological: Biocompatibility of all materials in contact with the patient

 
If equivalence of all the clinical, technical, and biological characteristics cannot be fully demonstrated, the data may still be used in the evaluation, but a justification fully evaluating and justifying any differences or discrepancies must be documented.
 
Clinical Trial
If existing clinical data or published literature is unsuitable or is not available for any individual or specific characteristic of the subject device, then conduction of a formal clinical trial would need to be considered in order to confirm in the CER that all the essential characteristics have been verified. There are harmonized European EN standards (e.g., EN 14155-x) that mandate how a clinical trial must be conducted.
 
Clinical Evaluation Report
The final step in the process is the production of a CER. The purpose of the CER is to bring together all the data from the evaluation phase and make a judgment that the objectives within the scope determined at the start of the process have been met.
 
A judgment is also made that any risks associated with the clinical process for which the device is indicated are outweighed by the benefits to the patient.
 
Finally, a person who is qualified in the discipline for which the device is indicated signs off the CER.
 
Author Note: The European regulatory requirements for medical devices underwent a major change in February 2010 and a further major change is due to be implemented later this year. This major change is coinciding with the publication of ISO 13485:2016 and these significant changes will be covered in a future article in this series.
 

---

Bernard Tremaine is the former CEO of MDQAS Ltd. (1994 to 2015 August). Bernard has 40+ years experience in the healthcare industry, with half of this time being spent at MEI in Milwaukee, Wis., where he held various positions in MEI’s European operations.