Equivalently different....
When is equivalence not equal? When it's FDA vs EU MDR equivalence.
By Dr Will Brambley, Lead Medical Writer, Mantra Systems Ltd
Regulation (EU) 2017/745 on medical devices (MDR) gives manufacturers the ability to use clinical data related to an equivalent device to demonstrate conformity as part of their Clinical Evaluation. This principle is much like the concept of substantial equivalence of medical devices, first introduced by the FDA in a 1976 amendment to the Federal Food, Drug and Cosmetic Act.
The purpose of this article is to give an overview of both the respective regulatory pathways, to demonstrate their similarities and differences, and to explain how this impacts MDR compliance.
Let's start by looking at the FDA perspective.
Equivalence under FDA
While there are several routes for a device to be approved by the FDA, one of the most common is via the 510(k) program. This process allows a manufacturer to demonstrate that an existing device on the market (called the predicate) is substantially equivalent to their own device. If this can be successfully done, this can be sufficient to obtain approval for the device.
The FDA states that:
“The new device must have the same intended use as the predicate device and the same technological characteristics or different technological characteristics that do not raise different questions of safety and effectiveness than the predicate device.”
If the manufacturer’s device and the predicate device have different technological characteristics, then the device can still pass the 510(k) submission provided the application demonstrates that the differences do not raise new questions of safety and effectiveness compared to the predicate device.
While manufacturers can identify more than one predicate device, only one is required. Furthermore, the FDA encourages manufacturers to identify a single predicate to simplify and facilitate the decision-making process. ?
Common reasons for a negative 510(k) outcome of “not substantially equivalent” include:
This process is summarised in the flow chart below:
Equivalence in EU MDR
By contrast, the EU MDR requires that equivalence in biological and clinical characteristics is shown alongside similar technical characteristics. Equivalence must be shown in all three domains in order to be successful.
A summary of considerations relating to technical, biological and clinical characteristics is presented below.
To demonstrate equivalence of a device, the supporting evidence must show that there is no clinically significant difference in the safety and clinical performance of the device. ?This ensures that the assessment of equivalence is duly substantiated and based on proper scientific justification.
This evidence can be provided from the sources contained in the table below.
Manufacturers may identify more than one equivalent device, but each device must be proven to be equivalent to the subject device according to the above criteria. They must also specify the generation/version of a device being considered for equivalence.
FDA vs EU MDR equivalence - head-to-head comparison
So how do the two forms of equivalence stack up in practice? Take a look at the summary below:
Impact on the Clinical Evaluation Report for EU MDR submissions
When producing a Clinical Evaluation Report (CER) according to Article 61 of the MDR, the manufacturer must set out a robust, objective, and scientific analysis of clinical evidence relating to the subject device. If claiming equivalence, assuming the requirements for equivalence are met then that equivalent device must be shown to conform to relevant GSPRs as set out in their Clinical Evaluation Plan (CEP). Unlike under FDA, the 'job isn't done' just because equivalence is demonstrated.
If there is not a sufficient body of literature-based evidence for a device, or that device does not meet the standards of the GSPRs, then a device is essentially useless as an equivalent device. For this reason, it's important to always consider whether a device is worth including as an equivalent.
Summary
Under the MDR, manufacturers must meet additional criteria on top of those required to prove equivalence under the 510(k) process of the FDA. The most impactful of the additional criteria is the need for the devices to have the same biological and clinical characteristics. As with the subject device, manufacturers must also compare the data on clinical performance and safety for a claimed equivalent device with the benchmarks provided by a state-of-the-art literature review.
This video summarises the key points in this article. For more information on including claims of equivalence in your MDR submission, please contact a member of our team.