A proposed delay in the transition to the Medical Device Regulation (MDR) is now officially in place in the European Union (EU), providing much-needed clarity as to the fate of legacy medical devices. An updated guidance from the Medical Device Coordination Group (MDCG) explains the modifications that can be made to devices certified under the legacy regulatory system, a document that manufacturers and developers should read carefully to ensure that any changes don’t render the device ineligible for the EU market.
As we explained earlier this year, the European Commission had proposed to delay the implementation dates to at least May 26, 2026, depending on the device type. The European Parliament and the European Council have now agreed to the delayed implementation framework. However, this is not the time to relax because the notified bodies (NB) that are licensed to do business in the EU have a severely limited capacity for reviews of device applications.
New Manufacturing Site, Suppliers Not Necessarily Significant
By definition, a legacy device must continue to comply with the Medical Devices Directive (MDD) or the Active Implantable Medical Devices Directive (AIMDD), and this updated version of MDCG 2020-3 incorporates some of the experience gained over the past three years. Broadly speaking, a certificate under the MDD or AIMDD would no longer be valid upon a significant change to a device’s design or intended purpose (intended purpose is analogous to the device’s intended use as described by the FDA).
The obvious question is how to determine what constitutes a significant change, but it might be helpful to first describe the kinds of changes that would not be deemed significant. Among the changes that would not constitute significant changes are:
- Relocation or addition of manufacturing sites, including subcontractors or suppliers;
- The addition of a new supplier of a material, substance, or device component, assuming that the specification of that product is the same as in the legacy device’s certificate; and
- A new validation of the manufacturing process as part of an effort to improve manufacturing or to scale up the volume of manufacturing.
For the most part, a change in the quality management system (QMS) need not constitute a significant change, a provision that will prove helpful to manufacturers that seek to adopt a dual Part 820/ISO 13485 approach to quality management. A corporate merger/acquisition would not constitute a change to the device, either, so long as the entity that holds the CE mark continues to exist in some form in a merger/acquisition scenario.
New Restriction of Intended Purpose Steers Clear of Significance
Restrictions of the device’s intended purpose typically do not constitute a significant change, such as a deletion of an indication for use, a restriction of the target population, or a restriction in how the device is deployed. However, the addition of a new indication for use would obviously constitute a significant change, as would the addition of a user population, such as making a device available for lay use when such was not previously included in the label.
A new delivery pathway or deployment method would also constitute a significant change under the MDCG policy. The manufacturer must document its assessment of changes that it believes do not constitute a significant change and must inform the NB of record of any such changes. The NB will have to document whether it concurs with any such conclusions. Less obvious is that a change in the device’s use per the stage of disease or disease severity would also constitute a significant change, something for developers and manufacturers to bear in mind when considering a change to enhance a product’s prospects.
As for design changes, the MDCG guidance states that non-significant changes might include:
- The modification of a part or component to align with a new or revised performance standard;
- A change in a component that falls within the range already certified for the device (e.g., a new variant of screw that is within the current range of length/diameter); and
- A change to the grip of a steerable ablation catheter undertaken to improve ergonomic comfort so long as functionality is unaffected.
These are deemed non-significant changes only insofar as the risk/benefit ratio of the device remains unaffected, a point the guidance reiterates several times. Changes to packaging may also constitute an insignificant change so long as the altered package size was previously validated for sterilization, but a change that alters a device’s operating principle, energy source, or alarm mechanisms would likely be seen as a significant change, thus invalidating that legacy device’s existing certification. Among the other examples given are:
- A change from an analogue to a digital controller;
- The introduction of software to a device when used to drive device function;
- The introduction of a pacing lead that is narrower in diameter than the existing lead; and
- The replacement of sensors with a sensor that operates on a different principle.
There is a significant context to consider for a device that has a place on both the U.S. and European markets. The FDA’s 2017 guidance for when to file a new regulatory submission for a 510(k) device is perhaps the most important of these, as it applies to hardware-only devices and to the non-software components of devices that incorporate both hardware and software.
One of the more important points to bear in mind regarding the FDA guidance is that any change that could significantly affect the safety or effectiveness may require a new 510(k), which applies even if the change is intended to “significantly improve clinical outcomes.” The FDA’s 2017 software changes guidance is also relevant, given that MDCG 2020-3 makes a point of declaring that any change to an algorithm that affects the operating principle or the control of the device would constitute a significant change.
This drawn-out transition period for the MDR … may force companies to make some difficult decisions about inventory.
The same can be said for any change that might alter the diagnosis or the delivery of therapy, and thus any artificial intelligence (AI) or machine learning (ML) algorithms are especially susceptible to a problem with significant changes. It is also important to point out that a change of the computer operating system (OS) would not be a significant change unless the software in question has to be modified to account for the OS switch.
This drawn-out transition period for the MDR – and the In Vitro Diagnostic Regulation (IVDR) as well – may force companies to make some difficult decisions about inventory, particularly given that obtaining a new MDR certificate is going to be challenging. One example of this is whether it makes sense to alter a class II device for the U.S. market if you have to maintain two versions of the device to avoid being temporarily forced out of the EU market. The FDA will typically turn around your new 510(k) application within 90 days, but things are moving much more slowly in the EU. Whatever you decide, it’s best to know in advance what a modification will do to your access to the EU market before making those changes, not after.