At the end of May, a new Medical Device Consortium Group (MDCG) document was published by the European Commission: MDCG 2022-6—“Guidance on Significant Changes Regarding the Transitional Provision under Article 110(3) of the IVDR.” This guidance covers important information regarding the implementation of EU Regulation 2017/746, also known as IVDR and discusses key areas such as timelines, as well as the background and purpose of MDCG 2022-6. In this blog post, we highlight what impact this new document has for IVD manufacturers wishing to comply with IVDR, and also what considerations should be taken into account when implementing MDCG 2022-6.
As of 26 May 2022, the EU In Vitro Diagnostic Regulation (IVDR), as amended by Regulation (EU) 2022/112 came into force. This new regulation replaces the IVD Directive 98/79/EC (IVDD), which has been in use for more than 20 years.
One important element of the IVDR is Article 110, dealing with the transition from the previous IVDD to the updated IVDR. More specifically, Article 110(3) of the IVDR states that under certain conditions, the following devices may be placed on the market—or put into service after the IVDR date of application (26 May 2022)—until the end of the various transition periods specified in Article 110(3):
- Devices that have a valid certificate issued by a Notified Body (NB) under the EU IVDD; and
- Devices for which a declaration of conformity was created prior to 26 May 2022 in accordance with the IVDD and for which the conformity assessment procedure pursuant to the IVDR (contrary to the IVDD) requires the involvement of an NB.
The conditions for the application of the transitional provisions in Article 110(3) IVDR are that:
- Devices continue to comply with the IVDD; and
- There are no significant changes in the design or intended purpose of the device after the IVDR date of application (26 May 2022).
Another important note is that the new MDCG 2022-6 is based on the previously published MDCG 2020-3 guidance regarding significant changes under Article 120 MDR, however, the latter document excludes IVD products. Where appropriate, the MDCG 2022-6 guidance is now tailored to the IVD sector and takes into account experience gained with the application of MDCG 2020-3.
Background of the MDCG 2022-6 Document
With the introduction of the IVDR, it also became clear that Article 110(3) of the transitional provisions would lead to many questions such as:
- What is considered a significant design change or intended purpose change of an In Vitro Diagnostic (IVD) product?
- And, would the design or intended purpose be defined by IVDD or IVDR?
- Or both?
Please bear in mind that a misinterpretation of these definitions could have grave consequences, since it may lead to certificate suspension or withdrawal—or even having an IVD device removed from the market. As the document notes, a ‘significant’ change in design or intended purpose requires a full conformity assessment procedure to be carried out by an NB for the “new” IVD.
Two important facts should be understood:
- Notified Bodies are scarce and thus, availability is limited.
- The average Notified Body conformity assessment procedure can take at least six (6) months to a year.
With this information, manufacturers can draw the following picture.
IVD manufacturers that have previous experience with NB certification of their devices under the IVDD (either through Annex II or through Annex III.6), have a good understanding of the concept of reporting significant changes to an NB. But, significant changes are related to a change in the approved design or substantial changes to the Quality Management System (QMS) or product range covered, per definition in the IVDD.
Since the IVDD is not in force as of 26 May 2022, the MDCG 2022-6 has made clear that changes in the approved design or substantial changes to a QMS system or covered product range are still to be appropriately handled and communicated to a NB. This is per the ruling in the certification agreement with a manufacturer’s specific NB. In other words, these types of changes cannot fall by the wayside and do require full attention as well.
Impacts to IVD Manufacturers Complying with IVDR
As already implied above, the MDCG 2022-6 document intends to only provide clarification on the concept of ‘significant changes in the design and intended purpose’ under IVDR Article 110(3). In doing so, it emphasizes providing important decision trees and examples of both significant and non-significant changes—both of which are equally important in NAMSA’s view.
The new MDCG 2022-6 document does carry a “disclaimer” for all examples, and advises that significant changes identified during a regulatory assessment should always be established on a case-by-case basis. The examples are only valid provided the change:
- Does not adversely affect the safety or performance; and
- Does not negatively affect the risk/benefit ratio of the device.
So, there is certainly not a one-size-fits-all approach that can be applied here. In addition, all decisions in the decision tree must be appropriately answered. If the answer to every question in a sub-chart leads to ‘non-significant change,’ one should return to the main chart.
An interesting point to mention regarding the MDCG 2022-6, is that some important examples that were expected are actually missing. For instance, a transition from using polyclonal antibodies in an IVD kit to monoclonal antibodies used to detect particular analytes would certainly be expected. Alternatively, some examples that are mentioned as non-significant could very well be significant such as:
- Extension or reduction of shelf-life for a non-sterile device; or
- Change in sterilization cycle parameters.
In the grand scheme of things, the above is perhaps less relevant, since every change must be weighed on its own merits, irrespective of the examples given in the document.
Another important aspect is the potential impact the new guidance has on the certification of existing devices under IVDD. Any changes that impact the design and intended purpose should be controlled through existing design control procedures, as they will fall under scrutiny by a NB as part of surveillance activities (audits, off-site Technical Documentation, reviews, etc.). The outcome of these verification activities will determine whether a certificate in accordance with the IVDD remains valid according to Article 110, IVDR. Constraints and reporting of “significant” changes fall under the aforementioned contractual obligations an IVD manufacturer has with their NB. In the case of self-declared devices under Annex III, IVDD, these change justifications would need to be documented and made available to a Competent Authority on a request basis—and, Competent Authorities will also rollout surveillance activities.
Important Considerations when Implementing MDCG 2022-6
In summary, the MDCG 2022-6 document provides much clarity pertaining to the transitional IVDR provisions and is certainly worthwhile.
Some key takeaways that manufacturers should keep in mind related to MDCG 2022-6 are as such:
- Read the MDCG 2022-6 alongside what is mentioned in the IVDR. This is especially important following the amendment through Regulation (EU) 2022/112—the document will help you strategize your regulatory IVDR roll-out plan.
- Incorporate some of the decision sheets into your own documented procedures for change control; the authorities will expect you to do this.
- Use this information to your advantage to further improve your understanding of intended purpose and design control.
How can NAMSA Help?
At NAMSA, our European regulatory team can help guide you through this complex regulatory environment and help determine the correct regulatory pathway for your IVD product. We not only understand how to accurately interpret the complicated regulatory challenges that IVD manufacturers sometimes face, but we also help you simplify the development and implementation of effective development strategies. Whether supporting IVD regulatory assessments and submissions, developing IVDR compliant technical files, designing and managing clinical trials or building ISO 13485:2016 and 21 CFR part 820 compliant quality systems… we’ve got you covered.
To learn about NAMSA’s full suite of IVD services and solutions, including IVDR compliance planning, please visit: https://namsa.com/services/ivd/. Or, if you’re ready to set up a complimentary consultation, get in touch with one of our IVD experts here: https://namsa.com/namsa-expertise/subject-matter-experts.
Alex Laan has been in the IVD and Medical Device industry for a total of 20 years with 12 years spent working for a respectable EU Notified Body. Alex has held the position of Principal Certification Manager at DEKRA Certification BV, a Notified Body for IVDs and Medical Devices located in Arnhem, The Netherlands. Mr. Laan also worked for KEMA Quality, beginning in 2006, where he was qualified for Lead Assessor for Medical Devices and IVD devices, Device Specialist reviewer in IVDs and Medical Devices, including drug-device combinations. In these roles, Alex managed projects with large multinationals (e.g., Boston Scientific), as well as small start-up companies. Alex has been an active member of IVD working group within EU Notified Bodies and TEAM-NB and acting as direct contact for EU competent authorities and EMA on implementation of the EU IVDR (2017/746) and EU MDR (2017/745).