Medical device “significant changes” under the EU MDR & IVDR

The transitional provisions in EU MDR and IVDR allow devices that are still CE-marked under the former Directives to remain as “legacy devices” under certain conditions, including that no “significant changes” be brought to their design or intended purpose.
If you manufacture or place on the market “legacy devices”, you must understand what changes are deemed to be significant, and integrate the concept in your change management process.

Replaces the version of 23.03.2020

Key takeaways

• Any “significant change” brought to a “legacy device” still CE-marked under the former Directives entails the loss of the legacy status and requires certification under the EU MDR or IVDR.
• Manufacturers must be cautious in differentiating “substantial changes” from “significant changes”, particularly when it comes to additional device variants. 
• Medical device software is typically subject to continuous updates that might fall under the criteria of “significant change” and hinder further placing on the market as a “legacy device”.
• The Swiss competent authority, Swissmedic, considers that EC Declarations of Conformity for “legacy devices” cannot be amended after the date of application of the corresponding Regulation (EU MDR or IVDR).

Contents

When is “significant change” important under the EU MDR or IVDR?

Article 120(3) of the EU MDR, last amended by Regulation (EU) 2023/607, and Article 110(3) of the IVDR allow that devices which continue to comply with the former Directives (MDD, AIMDD, or IVDD) may be placed on the market or put into service for some more years, provided some prerequisites are fulfilled. These devices are known as “legacy devices”.

In order to benefit from these transition periods, legacy devices may not undergo any “significant change” in the design or intended purpose after the date of application of the corresponding Regulations, i.e. 26 May 2021 for the EU MDR and 26 May 2022 for the IVDR.

Legacy devices that have undergone a significant change, no longer qualify as legacy and their certification must be upgraded under the EU MDR or IVDR, whichever applies. It is therefore important to understand and recognize what changes to legacy device design or intended purpose are considered to be “significant”.

Because the term “significant change” is not legally defined in either Regulation, manufacturers must refer to the applicable guidance document issued by the Medical Device Coordination Group (MDCG) on this topic:

• MDCG 2020-3 for medical devices still CE-marked under the former MDD or AIMDD
• MDCG 2022-6 for in-vitro diagnostic devices (IVDs) still CE-marked under the former IVDD.

The decision-making criteria behind MDCG 2020-3 and MDCG 2022-6 are easy to understand and will not come as a surprise to medical device manufacturers who were already familiar with the old guidance from Notified Bodies, NBOG BPG 2014-3, or with similar guiding principles published in other jurisdictions, e.g. US FDA’s when to submit a new 510(k) for a change to an existing device or Health Canada’s guidance on interpretation of significant change of a medical device.

Is a “significant change” the same as a “substantial change”?

No.

The EU MDR and IVDR refer to “substantial changes” in the context of those quality system or device range changes that must be notified to Notified Body in the post-certification phase. Upon such notification, the Notified Body assesses the changes and determines whether additional audits are needed. The approval of a substantial change to the quality management system or the device-range covered shall take the form of a supplement to the existing EU certificate.

This notification requirement also applied under the former Directives (MDD, AIMDD, and IVDD) and the old guidance from Notified Bodies, NBOG BPG 2014-3, detailed the expectations as to what type of changes would be viewed as “substantial”, thus needing notification. In practice, there was considerable variability in how Notified Bodies applied these expectations.

“Significant change”, as described in MDCG 2020-3 or MDCG 2022-6, concerns the type of changes that would entail loss of legacy status. As such, the criteria and examples in these guidance documents should not be extrapolated to substantial device changes and device-range changes that must be reported to the Notified Body after certification under the EU MDR or IVDR. And vice-versa.

A change within the device range covered by a MDD, AIMDD or IVDD certificate usually corresponds to a “significant change” with respect to the “legacy” status. This is particularly important for “private label” versions of a CE-marked legacy device.

“Significant change” concerns the type of changes that would entail loss of legacy status.

A “private label” version is exactly the same device as the original one with just a change in the name or trademark under which the device is placed on the market. The private label version needs a Declaration of Conformity, but it is not possible to generate a new EC Declaration of Conformity under the former Directives that are now withdrawn (see also Can manufacturers amend EC Declarations of Conformity upon non-significant changes?). It could therefore be argued that the private label version is a new device model not CE-marked prior to the date of application of the EU MDR or IVDR and thus not eligible as a “legacy” device.

However, MDCG 2020-3 accepts as non-significant changes, additions within the currently certified device range, for device variants that fall inside certified worst case or accepted bracket validations, provided the benefit/risk ratio is not negatively affected, and provides the following examples:

• “new screw variant within current range of lengths and diameter;
• new catheter variant, with length and diameter within current range and worst case in sterilisation performance;
• new stent lengths which are intermediate between the previously certified stent lengths.”

This would be the case for “private label” versions.

Similar examples are not mentioned for IVDs in their corresponding guidance document, MDCG 2022-6, but the types of design changes that are considered “significant” for IVDs are less extensive.

Who shall determine whether or not a change is “significant”?

Medical device and IVD manufacturers shall assess any changes affecting their legacy devices against the criteria in MDCG 2020-3 or MDCG 2022-6 in order to determine whether or not the changes might be viewed as “significant”.

The manufacturer is responsible for documenting the decisions, with appropriate evidence and justification, that a change is non-significant. 

For legacy devices not subject to Notified Body oversight under the former Directives (i.e. Class I devices that are not sterile, not surgically reusable and not with measuring function, and self-declared IVDs), the documented decisions must be made available to competent authorities upon request.

For devices subject to Notified Body oversight, the changes and their implementation are verified by the Notified Body at the periodic surveillance audits or, where applicable, upon change notification submissions. The Notified Body verification shall determine whether an existing EC certificate under the former Directive (MDD, AIMDD or IVDD) remains valid or a new certificate under EU MDR or IVDR is required. The verification outcome is confirmed in writing by the Notified Body. The manufacturer shall number the Notified Body’s confirmation letters and keep them along with the corresponding EC certificate at the disposal of competent authorities.

What changes are “significant” under the EU MDR and IVDR?

MDCG 2020-3 is the guidance document that explains the criteria for considering a change “significant” under the EU MDR, using a series of flowcharts that manufacturers shall follow in their decision making.

In May 2023, MDCG 2020-3 was revised to align with the corresponding guidance under the IVDR, MDCG 2022-6, and with Regulation (EU) 2023/607 amending the transitional periods for legacy devices under the EU MDR. In this version, many useful details and examples have been added and are summarized below.

For IVDs, MDCG 2022-6 is the corresponding guidance document.

Because the approaches in MDCG 2020-3 and MDCG 2022-6 are identical and the criteria very similar, they can be described together.

The guidance documents are using a series of flowcharts that manufacturers shall follow in their decision making.

The flowcharts in both documents encompass:

• A main chart with an overview of the types of changes
• Chart A on changes of the intended purpose
• Chart B on changes of the design
• Chart C specifically on software changes
• Chart D on changes of a substance (ingredient, for IVDs) or material, and
• Chart E on changes of terminal sterilization method or on packaging design that impacts sterilization

A change under either MDCG 2020-3 or 2022-6 is to be considered non-significant when the answer to every question in all flowcharts leads to “non-significant change”.

Main Chart

The starting point is changes related to corrective actions. If the corrective action has been assessed and accepted by the relevant competent authority, the change is not considered to be significant. For changes due to corrective actions not assessed/accepted by the competent authority and for changes not related to corrective actions, the assessment of the change needs to continue by moving on to the following questions in the flowchart relative to intended purpose and device design.

If the change affects the device’s intended purpose, design/performance specification, software (whether embedded or standalone), materials (of any nature), or sterilization (incl. packaging design with impact to sterilization), the manufacturer must further assess the type of change using the specific secondary flowcharts that apply.

Chart A – Intended purpose changes

Intended purpose is to be understood as the use for which the device or IVD is intended according to its manufacturer, which includes the indications and contraindications, the intended user, the intended patient population, and the intended environment of use. Read more about the intended purpose.

Significant changes to the intended purpose include:

• intended purpose extension (a limitation in intended purpose not being considered significant), and
• For non-IVDs, per MDCG 2020-3:
  • new user or patient population, and
  • new way of clinical application (e.g. change in anatomical site, change in delivery pathway or clinical deployment method).
• For IVDs, per MDCG 2022-6:
  • Other major changes of intended purpose (e.g. change of assay type, change of specimen types, change of intended user, change from automatic to manual operation or vice versa).

NOTE: Labeling changes should be assessed to ensure they do not qualify as significant relative to the intended use (e.g. modifications to contraindications or warnings).

Chart B – Design changes

Significant changes include any of the below:

• change in operating principles, or
• any design change that may adversely affect safety or performance and negatively affect the benefit/risk ratio of the device.
• And for non-IVDs only, per MDCG 2020-3:
  • change of built-in control mechanism, 
  • change in source of energy,
  • change in alarm systems.

NOTE: Changes in design should be assessed regardless of how they are achieved (i.e. hardware, software,…).

Chart C – Software changes

Significant changes include any of the below:

• new or major change of operating system or any component,
• new or major modification of architecture or database structure
• change in algorithm,
• required user input replaced by closed loop algorithm,
• new presentation of medical data (e.g. in new format, new dimension or measuring unit), or
• any software change that may negatively affect the benefit/risk ratio of the device.
• And for non-IVDs only, per MDCG 2020-3:
  • new user interface (incl. changes that impact the way data is read or interpreted by the user)
  • new medical feature or functionality, 
  • new channel of interoperability.

NOTE: Examples of non-significant changes include: bug fixes (for errors that do not pose a safety risk) and security updates (e.g. cybersecurity enhancements, longevity calculations). For non-IVDs, also changes in appearance or enhancements of the user interface, and operating inefficiencies, provided they do not negatively affect usability, safety or performance. 

In brief, most software changes are viewed as significant. And software constantly evolves. Hence, medical software manufacturers should be extremely cautious in their software maintenance to avoid significant changes during the transitional period. Read more about medical device software (MDSW) under the EU MDR or IVDR here.

Chart D – Material or substance/ingredient changes

The criteria for non-IVDs, per MDCG 2020-3, and IVDs, per MDCG 2022-6 differ in this flowchart due to the different nature of the devices.

For non-IVDs significant changes include any of the below:

• change to or addition of a new material of human/animal origin,
• change to the excipient of a medicinal substance or to the medicinal substance itself,
• change to materials or substances that are in contact with patient tissue or fluid for more than 30 days or that are part of a surgically invasive device which is absorbed, or 
• the change affects safety or performance and negatively affects the benefit/risk ratio of the device.

For IVDs significant changes include any of the below:

• change to an ingredient or material essential for the operating principle (e.g. primers for PCR, antigens for immunoassays, detection markers), or 
• the change affects safety or performance and negatively affects the benefit/risk ratio of the device.

NOTE: material changes within the same specifications are not considered significant, including the substitution of a chemical substance in order to comply with REACH, provided the change does not negatively impact the benefit/risk ratio.

Chart E – Sterilization changes

Significant changes include any of the below:

• change in terminal sterilization method (e.g. ETO to Gamma, but also from non-sterile to sterile),
• change adversely affecting the sterility assurance level (per the corresponding international standards),
• changes in packaging design affecting sterility, stability or microbiological state of the device, including seal integrity,
• shelf-life extensions, when not validated according to protocols approved by the Notified Body.

NOTE: changes to storage or transportation conditions which could adversely affect sterility or stability of sterile device should also be considered significant.

What changes do not entail the loss of “legacy” status?

Even if they might still require submission to the Notified Body (for devices other than Class I and self-declared IVDs), the following changes would not require upgrading certification to EU MDR or IVDR:

• Administrative changes, in principle, are considered non-significant. This would include a change in EU Authorized Representative for a non-EU based manufacturer, or changes in legal manufacturer’s name, address or legal form for a given legal entity. However, a change in legal manufacturer (to a different legal entity) would not be considered an administrative change.
• Quality management system process changes that do not impact design or intended purpose, e.g. relocation or addition of a manufacturing site (incl. for subcontractors and suppliers), and certain changes to the quality management system that do not impact the conditions of the existing MDD, AIMDD or IVDD certificate.
• Device (incl. labelling) changes not restricted by MDCG 2020-3 or MDCT 2022-6 flowcharts, e.g. certain like-for-like material changes, appearance changes without usability impact.

Can manufacturers amend EC Declarations of Conformity upon non-significant changes?

While there is a clear, official position in MDCG 2020-3 and MDCG 2022-6 forbidding Notified Bodies to update EC Certificates for legacy devices after the date of application of the corresponding Regulations, i.e. 26 May 2021 for the EU MDR and 26 May 2022 for the IVDR, nothing in MDCG 2020-3 or MDCG 2022-6 forbids or restricts updates to EC Declarations of Conformity relative non-significant changes.

From a strict legal perspective, it is reasonable to consider that a manufacturer can no longer claim conformity to a Directive that has been withdrawn and is no longer valid, such as the MDD, AIMDD or IVDD. Yet, the transitional provisions in the EU MDR and IVDR require that legacy devices must continue to comply precisely with those withdrawn Directives, and compliance with the Directives requires a EC Declaration of Conformity.

Several Notified Bodies and EU competent authorities, still accept amendments to EC Declarations of Conformity for legacy devices, generating confusion in the Medtech industry.

To the best of our knowledge, Swissmedic is the only competent authority that has officially stated its position on this topic, via a note on its webpage relative to Frequently Asked Questions, as follows:

“For legacy devices, the declaration of conformity must have been drawn up before the date of application* of the respective new regulations. It is important to emphasize that the issuing of new declarations of conformity, including amended, adapted or supplemented declarations of conformity in accordance with Directives 93/42/EEC, 90/385/EEC and 98/79/EC is not permitted after the date of application* of the respective new regulations. A declaration of conformity can only ever be issued in accordance with the current law.

The manufacturer may list non-significant changes (MDCG 2020-3) affecting the content of a declaration of conformity issued under the old legislation on a document accompanying the declaration of conformity, in analogy to the procedure for non-significant changes affecting certificates issued under the old legislation.

* Medical devices (without IVD): MedDO and EU-MDR -> Date of Application: 26 May 2021; IVD: IvDO and EU-IVDR -> Date of Application 26 May 2022”

Today, this does not seem to be the position of several Notified Bodies and EU competent authorities, who continue to accept amendments to EC Declarations of Conformity for legacy devices, generating confusion in the Medtech industry. A clear, harmonized position at the MDCG level or by Team-NB would be welcome, in particular providing guidance on how to address cases where manufacturers had no choice but to update their EC Declarations of Conformity, e.g. upon request from their Notified Bodies.

What do manufacturers need to do?

As a first step, all manufacturers of legacy devices should appropriately integrate the significant change decision-making process from MDCG 2020-3 (for non-IVDs) or MDCG 2022-6 (for IVDs) in their quality management system, by making the necessary amendments to the change management procedure. Integration might also require updates to the procedure for change notification to the Notified Body, the regulatory strategy procedure (relative to the upgrading of “legacy devices” to EU MDR or IVDR certification), and the design control or software lifecycle procedures, as applicable.

Then, for every change brought to a legacy device that might impact the design or the intended purpose:

• For devices subject to Notified Body oversight:
  Collect all Notified Body confirmation letters relative to changes implemented, and store them along with the existing MDD/AIMDD/IVDD certificates, as proof of their validity, per the transitional provisions in EU MDR Article 120 or IVDR Article 110.
• For devices that do not require Notified Body involvement:
  Document the justification relative to the significance of a change affecting a Class I medical device or a self-declared IVDs.

How Decomplix can help

Decomplix stands by as a coach in compliance matters and as the customer’s close contact to Swiss authorities for medical device and in-vitro diagnostic companies all around the world. We can answer specific questions, provide expert assessment of your situation and support reviewing your change management process to ensure compliance under the EU MDR and IVDR. 

You can learn more about our services here.

Further reading

• “Legacy” medical devices and IVDs under EU legislation
• The intended purpose – or, what does your medical device do?
• Medical device regulatory strategy – EU vs. US
• Is my product a medical device in Europe? How to determine if your product requires medical device CE marking
• Medical device software (MDSW) under the EU MDR or IVDR