Guidance on medical device significant changes

The new Regulation (EU) No. 2017/745 on medical devices (EU MDR) will apply from 26 May 2021. This article provides guidance for the interpretation of significant changes to medical devices under MDR.

Transitional provisions in EU MDR Article 120 allow for medical devices lawfully placed on the market under the previous regulatory regime (i.e. Directive 93/42/EEC on medical devices, MDD, and Directive 90/385/EEC on active implantable medical devices, AIMDD), to remain subject to the MDD/AIMDD under certain conditions and until no later than 26 May 2024. Existing medical devices that will not be upgraded to compliance with the EU MDR by virtue of the transitional provisions are known as “legacy devices”.

One of the conditions for benefiting from the transitional provisions is that the legacy device does not undergo “significant changes in design or intended use”.

On 16 March 2020, the long-awaited guidelines on “significant change” were published by the Medical Device Coordination Group (MDCG), under guidance document MDCG 2020-3.

Contents:

What does MDCG 2020-3 build upon?

MDCG 2020-3 builds upon two relevant references:

• the Notified Body’s best practice guide NBOG BPG 2014-3 on the type of medical device design and Quality Management System (QMS) changes that would require reporting to the Notified Body, under the former MDD.
• the types of software changes triggering a new UDI, as provided for in Annex VI Part C, section 6.5 of the same EU MDR.

The resulting document is a lean and practical guide for manufacturers of “legacy devices” of any type and class.

Even if few examples are provided in MDCG 2020-3, the decision-making criteria are easy to understand and will not come as a surprise to medical device manufacturers who were already familiar with NBOG BPG 2014-3 or with similar guiding principles published in other jurisdictions, e.g. US FDA’s when to submit a 510(k) for a software change or Health Canada’s guidance on interpretation of significant change.

On 16 March 2020, the long-awaited guidelines on “significant change” were published by the Medical Device Coordination Group (MDCG), under guidance document MDCG 2020-3.

Moreover, although not part of the scope of MDCG 2020-3, this guidance document becomes a valuable basis for manufacturers to assess the significance of device changes in a consistent manner.

Who is responsible for determining whether a medical device change is significant?

Medical device manufacturers shall assess all changes against the criteria in MDCG 2020-3 in order to determine whether or not they are “significant changes” within the meaning of EU MDR Article 120.

For devices other than Class I, the changes and their implementation will be verified by the Notified Body at audits or upon change notification submissions, where applicable. The Notified Body verification will determine whether an existing MDD/AIMDD certificate remains valid, per EU MDR Article 120, or a new certificate under EU MDR is required. Such verification will be confirmed in writing by the Notified Body.

The manufacturer shall number the Notified Body’s confirmation letters and keep them along with the corresponding MDD/AIMDD certificate at the disposal of competent authorities.

Manufacturers of Class I devices that would require Notified Body involvement under the EU MDR (e.g. Class I surgically reusable, Class I devices that would be upgraded to Class IIa or above per EU MDR classification rules) shall document their decisions relative to changes and make such documentation available to competent authorities. Read more about class I medical device requirements for manufacturers here.

What changes do not trigger upgrading of certification to EU MDR?

Even if still subject to submission to the Notified Body (for devices other than Class I), the following changes would not require upgrading certification from MDD/AIMDD to EU MDR:

• Administrative changes, in principle, are considered non-significant. This would include a change in EU Authorized Representative (EAR) 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.
• QMS process changes that do not impact design or intended purpose, e.g. relocation or addition of a manufacturing sites (incl. for subcontractors and suppliers), and certain changes to the quality management system that do not impact the conditions of the existing MDD/AIMDD certificate.
• Device (incl. labelling) changes not restricted by MDCG 2020-3 flowcharts, e.g. certain like-for-like material changes, appearance changes without usability impact.

What are “significant changes in design or intended use”?

MDCG 2020-3 introduces 6 sequential flowcharts to guide the decision making, i.e. a main chart and 5 topic-specific secondary charts.

Main Chart

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 separate, specific flowcharts below are to be followed, as applicable.

If the change is related to corrective actions that have 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 next question, i.e. changes on design or performance specifications.

A schematic depiction of the main chart is shown below:

Secondary Charts

MDCG 2020-3 provides secondary charts with specific questions to support the assessment of changes.

Chart A – Intended purpose changes

Significant changes include:

• intended purpose extension or change (other than limitation, which is not considered significant),
• new patient/user population,
• change in clinical use (e.g. change in anatomical/access site, change in clinical deployment method).

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/performance specification changes

Significant changes include:

• changes that require further clinical/usability data to support safety/performance,
• new risks requiring mitigation or negative impact on existing risks,
• change in built-in controls,
• change in operating principle, source of energy or alarms.

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

Chart C – Software changes

Significant changes include:

• changes of operating system or any component,
• new or modified architecture/database structure/algorithm,
• user input replaced by closed loop algorithm,
• new diagnostic/therapeutic feature,
• new channel of interoperability,
• new user interface,
• new presentation of medical data (e.g. in new format, new dimension or measuring unit).

NOTE: Examples of minor changes without impact to diagnostic/treatment would include: bug fixes (for errors that do not pose a safety risk), security updates (e.g. cybersecurity enhancements, longevity calculations), appearance/enhancement of the user interface without performance changes, or operating inefficiencies.

Chart D – Material changes

Significant changes include:

• any changes to materials of human/animal origin
• any changes to medicinal substances contained (or to any process affecting the quality, safety or efficacy of such medicinal substances),
• new suppliers for other types of material/ingredient where the existing specifications are not met. However, if the existing specifications are met, the change in supplier needs to be assessed in terms of impact to the device design/performance specifications.

NOTE: Like-for-like material changes (same supplier and same specifications) are not considered significant.

Chart E – Sterilization changes

Significant changes include:

• changes in sterilization method (including from non-sterile to sterile, but excluding change in cycle parameters),
• changes in sterility assurance level (per the corresponding international standards),
• changes in a sterile device’s packaging design affecting functionality, safety, stability or seal integrity,
• changes in a sterile device’s shelf life (extension of shelf-life, in principle, is not considered significant).

What do medical device manufacturers need to do?

Manufactures are required to:

• Integrate the significant change decision-making process from MDCG 2020-3 in their QMS. This would typically mean updating the change management procedure, accordingly. It might also require links/updates to the notification/reporting procedure, regulatory strategy procedure (relative to the upgrading of “legacy devices” to EU MDR certification), and design control or software lifecycle procedures, as applicable.
• Collect all Notified Body confirmation letters relative to changes implemented, and store them along with the existing MDD/AIMDD certificates, as proof of their validity, per the transitional provisions in EU MDR Article 117.
• Document the justification relative to the significance of a change affecting Class I medical devices.

How can Decomplix help?

Please contact us for details, in case you are looking for expert assistance with any or all of the following:

• Determining the most appropriate regulatory strategy for your company’s “legacy devices”.
• Setting up or reviewing your QMS processes and procedures in conformity with EU MDR and MDCG 2020-3.
• Getting trained on EU MDR compliance.

You can find out more about our CE marking services here.

(last updated in April 2020)

Pictures: patpitchaya, garagestock/Shutterstock