IVDR Transition and Significant Change…… What’s a Significant Change?

Regulation (EU) 2017/746, IVDR, is in place, and the market is in a 2nd phase of transition. But what should manufacturers know about this period of transition? And what are the new challenges that are introduced because of the conditions put in place?

In this series we will break down the challenges and conditions of IVDR transition arrangements and what manufacturers must be aware on to keep their products on the market.

What are the relevant transition arrangements?

Article 110(3) as amended by Regulation (EU) 2022/112 states that under certain conditions the following devices may be put on the market or put into service after the date of application (DOA) of the IVDR, 26 May 2022, until the end of specified transition periods which are aligned to the classification of the IVD under IVDR.

· Devices which have a valid certificate issued by a notified body under Directive 98/79/EC on in vitro diagnostic medical devices (IVDD)

· Devices that have a valid declaration of conformity (DoC), drawn up prior to the 26 May 2022 in compliance to Directive 98/79/EC on in vitro diagnostic medical devices (IVDD) and for which the classification and resultant conformity assessment procedure according to IVDR requires the involvement of a notified body.

Now, what does this mean? This means that if your product has a CE certificate issued by a notified body under IVDD or a DoC in compliance to the IVDD, drawn up prior to the 26 May 2022, and if the classification of the device under IVDR means that a notified body is required for conformity assessment then there is more time to transition to IVDR.

So, this is good news right?

Yes, this means there is some more time, however……………..

Significant Changes

The transition provisions above are conditional on the fact that the product must continue to be compliant to IVDD and there MUST NOT be any significant changes to the design or intended purpose of the device after the DOA. Guidance, released by the Medical Device Coordination Group (MDCG), MDCG 2022-6 Guidance on significant changes regarding the transitional provision under article 110(3) of the IVDR, provides information and examples on what is, and is not, considered a significant change. MDCG-2022-6

An interesting observation is that section 4.2 provides scenarios of changes that are not considered changes to the design or intended purpose of the device in the meaning of Article 110(3) of IVDR, and therefore does not affect a manufacturers ability to continue to place the product on the market under the IVDD compliance, however they may well be considered significant changes within the Quality Management System (QMS) of the manufacturer and also may also be notifiable to the notified body. For example:

· Relocation or addition of new manufacturing sites, including when it affects subcontractors or suppliers.

· Changes of the manufacturers name, address or legal form, including a merger or acquisition involving the manufacturer

· New process validation as part of manufacturing improvements or scale up of the manufacturing

Changes in Intended Purpose

MDCG 2022-6 makes a very helpful distinction here. If an intended purpose is being limited by restricting its use, for example, through in different target populations, reducing the number of specimen types then this is not considered a significant change.

Changes to the intended purpose that are an extension to the intended purpose, for example, an addition of a specimen type, or other major changes of the intended purpose, for example, change of operation from automated to manual and vice versa are considered significant changes.

Changes in Design

Section 4.3 states that not all changes concerning the design or intended would automatically be considered significant. MDCG 2022-6 provides flowcharts for different scenarios to determine whether a change is regarded as significant.

Changes of the design that do not alter the devices operating principle, that do not adversely affect the safety or the performance and that do not negatively affect the risk/benefit ratio of the device should not be considered significant.

Examples of design changes that would NOT be considered significant are:

· Changes in incubation times and temperatures

· Changes in processing steps of the method (e.g. a new wash step)

· Use of a new PCR Cycler which is more efficient.

In Summary

Based on MDCG 2022-6, its clear that the internal processes for change, a manufacturers ability to affectively manage product risk through the life cycle of the product and how the risk benefit ratio is affectively articulated in the technical documentation are all important factors to manufacturer remaining compliant to the transitional provisions in Article 110(3) of the IVDR.

Manufacturers will need to ensure that their QMS supports effective processes in establishing whether product change is considered significant, and then ultimately determine whether a product can continue to be made available on the market under the existing transitional arrangements.

IVDR transition does enable manufacturers to continue to use the IVDD as a route to market. However, as we can see there are further regulatory requirements that manufacturers must follow to take advantage.