The MDCG has issued new guidance on significant changes for legacy IVD devices under the IVDR Article 110(3): MDCG 2022-6

Background

Most IVDD CE marked devices have been granted an IVDR transition period and can continue to be placed onto the market after the IVDR’s date of application: 26 May 2022.

Specifically, the devices eligible for the transition period are those that were self-certified (“other IVDs”) under the IVDD but have been up-classed under the IVDR, and now require Notified Body issued CE marking certificates. These devices are referred to as ‘legacy’ devices.

IVDD devices with Notified Body issued CE marking certificates (e.g., self-test devices) that will be valid after 26 May 2022 are also legacy devices.

Only IVD medical devices that are classified as Class A non-sterile under the IVDR, require immediate compliance on 26 May 2022. Class A non-sterile devices are self-certified by the manufacturer under the IVDR.

However, legacy devices are subject to certain conditions.

What are the conditions for IVDD CE marked legacy devices to be placed on the market?

1. Some aspects of the IVDR will apply to IVDD CE marked legacy devices. These include the sections related to post-market surveillance, market surveillance, vigilance and registration of Economic Operators and devices.
2. The device must have IVDD CE marking before the IVDR date of application. This includes having signed the Declaration of Conformity and registered the devices with the relevant Competent Authorities prior to 26 May 2022.
3. No significant changes to the design or intended purpose of the device can occur after 26 May 2022.

What constitutes a ‘significant change’ to the design and/or intended purpose?

This is where the new MDCG document is helpful. Some highlighted examples are provided below.

We have only extracted a subset of examples from the guidance for reference. We strongly recommend bookmarking this document (and/or referencing it in your change procedure) for future help in determining if a change is significant or not. It is the manufacturer’s responsibility to document changes and justify that the change was not significant. Including, providing it to a Competent Authority upon request.

• • Extension of the intended purpose, such as:
    • additions regarding what is detected and/or measured, such as addition of a new genotype to a human papillomavirus assay, necessitating new primers
    • additional functions of the device, such as screening, monitoring, diagnosis
    • for companion diagnostics: extension of the target population(s) or of the tissue type or associated medicinal products
    • addition of specimen type(s)
  • Any other major change of the intended purpose, such as:
    • change of assay type, e.g. from screening assay to confirmatory assay or from qualitative to quantitative assay
    • change of operation from automatic to manual or vice versa
    • change of specimen type(s)
  • Changes that alter the device’s operating principle
  • Changes that adversely affect the safety or performance and negatively affect the risk/benefit ratio of the device, even if they do not alter the device’s operating principle:
    • change of instructions for use to refer to reduced sensitivity of the device based on data obtained as a result of post-market surveillance
    • alteration of assay-specific cut-off values resulting in decreased specificity
  • Software changes:
    • new or major change of operating system or any component
    • new or major modification of architecture or database structure, change of algorithm
    • presentation of medical data in a new format or by a new dimension or measuring unit
  • Changes of an ingredient or material that is essential for the operating principle of the device:
    • primers for PCR
    • capture antibodies / antigens for immunoassay
    • detection marker (e.g. fluorescent, chromogenic, chemiluminescent marker) for chromatography

What are examples of non-significant changes to the design and/or intended purpose?

Per Section 4.3, the following are examples provided of non-significant changes. Only a subset has been provided below, the full guidance should be read if/when a change determination is needed.

• • Limitation of the intended purpose, such as restricting the target population, specimen type, specimen location
  • Changes of the design that do not alter the device’s operating principle, that do not adversely affect the safety or performance and that do not negatively affect the risk/benefit ratio of the device:
    • changes in the processing steps of the method (e.g. a new washing step)
    • extension or reduction of shelf life of a non-sterile device
    • clarifications of labelling or instructions for use
    • change of number of tests in the kit configuration
  • Software changes*:
    • correction of an error which does not pose a safety or performance risk (bug fixes)
    • security update (e.g. cyber-security enhancements, longevity calculations)
    • appearance of the user interface (e.g. new languages, layouts or graphics)
    • changes to enhance the user interface without changes in performance
  • Changes of an ingredient or material that is not essential for the device’s operating principle, that do not adversely affect the safety or performance and that do not negatively affect the risk/benefit ratio of the device:
    • replacing a preservative
    • use of a new buffer whose pH is slightly different and more adapted to the assay
    • substitution of a chemical substance in order to comply with the REACH Regulation (EC) No 1907/2006
  • Change of the sterilisation cycle parameters under the approved QMS
  • Change of the shelf life validated by protocols approved by the notified body

*Note: These examples are valid only provided that the change does not adversely affect the safety or performance and that it does not negatively affect the risk/benefit ratio of the device.

How do I determine if a change is significant or not?

This MDCG document is a strong resource. In addition to a list of examples, it includes several flowcharts to help you determine if changes are significant or not. Please see an example below:

What happens if I have a ‘significant change’ to my legacy device?

If a significant change is being made to your IVDD legacy device, then that iteration of the device must undergo IVDR CE marking.

If this is the case, then you must engage with a Notified Body and obtain IVDR CE marking. Upon completion, you may market that changed device.

What are examples of general changes that do not risk the legacy device IVDD CE marking?

Per Section 4.2, examples of changes that do not impact the legacy device standing are:

• Changes to the manufacturer’s name, address or legal form, including merger or acquisition involving the manufacturer;
• Changes in relation to the authorized representative;
• Relocation or addition of a new manufacturer site, including when it affects subcontractors or suppliers;
• Changing the supplier of a material, ingredient or component, provided the specifications of the new material, ingredient or component do not change;
• Adding or replacing a new material number for logistic reasons without changing the material;
• Changes to outer packaging (e.g. size, material, layout) that do not adversely affect the stability, sterility or microbiological state of the device;
• New process validation as part of manufacturing improvements or scale-up of manufacturing.

Changes of the QMS, such as changes in the monitoring and control of production and operations environment, generally do not impact the design or intended purpose either, provided that the conditions for which the conformity assessment certification was granted are maintained.

What are the IVDR transition deadlines for legacy devices?

• • Class A non-sterile (‘self-certified’) – no change, must comply with the IVDR on its date of application, 26 May 2022
  • Class A sterile – compliance date of 26 May 2027
  • Class B – compliance date of 26 May 2027
  • Class C – compliance date of 26 May 2026
  • Class D – compliance date of 26 May 2025

Read more about this here: IVDR Progressive Roll-out Approved

Which countries require compliance to the IVDR?

The IVDR is mandatory in the European Single Market, which is comprised of: the 27 European Union member states, Iceland, Liechtenstein, Norway, Northern Ireland and Turkey.

Switzerland also requires IVDR CE Marking; however, since Switzerland is no longer part of the European Single Market, additional conditions apply.

Read more about Switzerland’s additional IVDR requirements here: CONFIRMED: Switzerland adopts IvDO/IVDR

Great Britain (England, Scotland, Wales) accepts CE marking for the moment. However, note that as of 1 July 2023, Great Britain no longer recognizes CE marking and instead will require UKCA marking in order to legally place devices onto their market.

Read more about UKCA Marking here: MHRA UKCA Marking Overview