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On 28 January 2022, Regulation 2022/112 entered into force, amending the transitional provisions in Article 110 of the (EU) 2017/746. As a result,  the transition period for legacy devices under directive 98/79/EC (IVDD) to comply with the (EU) Regulation IVDR was extended. The new timelines according to Regulation 2022/112 are summarised in the following table:

*issued before 26 May 2022

In the past months, the MDCG has published several guidelines to support manufacturers and notified bodies to comply with the requirements outlined in Article 110 for legacy devices. The remarks included in these guidelines are summarized below:

What is a legacy device?

Legacy devices are IVDs that are placed in the market or put into service after 26 May 2022 and until the end of the respective transition period, including:

  • Devices for which a declaration of conformity was drawn up before 26 May 2022 under the IVDD and need an NB for the EC certification under IVDR.
  • Devices covered by a valid EC certificate issued by an NB under the IVDD before 26 May 2022.

Old devices are those IVDs placed on the market or put into service before 26 May 2022 under the IVDD and are still on the market or in use after 26 May 2022.

Source: MDCG 2022-8

What requirements must legacy devices fulfill during the transition period under Article 110?

Manufacturers of legacy devices shall comply with several IVDR requirements during the transition period. These requirements include:

  1. Set up a post-market surveillance (PMS) system based on a PMS plan, including the post-market performance follow-up (PMPF). A PMS report or PSUR would also be expected for legacy IVDs.
  2. Vigilance procedures (serious incidents reporting, field safety notices, and trend reporting).
  3. Market surveillance procedures.
  4. Registration of economic operators and devices. 

Source: MDCG 2022-8

What is considered a significant change?

Legacy devices can benefit from the extended transitional provisions under the conditions that they continue to comply with the IVDD and that there are no significant changes in the design and intended purposes of those devices after the date of application of the IVDR.

MDCG 2022-6 aims to clarify the concept of significant changes in the design and intended purpose. How can manufacturers determine if a change is significant?

Changes not impacting the design or intended purposes

Changes in areas other than the design and intended purposes will not impact the device’s status. These changes include administrative and manufacturing process changes (e.g., manufacturer name, authorized representative, new manufacturing sites, changing of suppliers, outer packaging changes, and new process validation).

Changes impacting the design or intended purposes

In this case, the manufacturer should assess the significance of each change case by case. If the change is non-significant, the justification should be documented. It is important to remark that manufacturers are responsible for providing evidence that the changes do not affect the design/intended purpose or are not significant. As part of their surveillance tasks, notified bodies will verify changes and their implementation, but if a manufacturer is unsure about the significance of a given change, it can ask their notified body and file the response.

Changes that can affect the design and intended purpose and are NOT significant include, for example:

  • Changes done as part of a CAPA action that have been assessed and accepted by a competent authority.
  • Corrections of spelling mistakes or editorial changes in the instructions for use (IFU) or label.
  • Updates of the information supplied by the manufacturer if required by law (other than the IVDR) and if the changes are related to clarifications and do not adversely affect the devices’ safety.
  • Limitation of the intended purpose.
  • Changes in design that do not alter the device’s operation principle, such as changes in incubation time and temperatures or changes in internationally agreed reference values.
  • Software security updates.
  • Enhancement of the user interface.
  • Changes in a material that is not essential for the device’s operating system.

These changes are non-significant, provided that they do not adversely affect the safety/performance of the device or its benefit/risk ratio.

Changes that can affect the design and intended purpose and ARE significant include, for example:

  • Extension or major change of the intended purpose, including more analytes, additional functions, an extension of the target population, specimen types, assay type, change of the intended user, etc.
  • Changes in design that affect the device’s operation principle (e.g., change from immunoturbidimetry measurement to colorimetric measurement)
  • Changes that adversely affect the device’s safety, performance, or risk/benefit ratio.
  • The MDCG also includes software changes, changes related to an ingredient or material, and changes in the sterilization process that can be significant:
    • Change of the software algorithm.
    • Changes in an ingredient or material that is essential for the device’s operating principle.
    • Changing a device from “non-sterile” to sterile.

MDCG 2022-6 contains additional examples and several flowcharts to assist stakeholders in deciding the change’s significance.

Source: MDCG 2022-6

How can manufacturers prepare for the upcoming NB surveillance?

MDCG 2022-15 includes guidance for NBs overseeing IVD legacy regarding the surveillance activities required during the transitional period. This guidance also covers certain manufacturers’ obligations, especially those related to updates needed in the quality management system.

Requirements to be covered by manufacturers to comply with IVDR Article 110 (3): The QMS approved under the directive needs to be maintained and updated to comply with the IVDR requirements regarding the following:

  • Vigilance
  • PMS
  • Market surveillance
  • Registration of economic operators and devices

During the transition period, legacy devices do not need to comply with other articles, including the requirements related to Person Responsible for Regulatory Compliance (PRRC, Art15),  Unique Device Identifier (UDI, Art 24), or Summary of Safety and Performance (SSP, Art 29).

Surveillance according to IVDR Article 110(3):

The MDCG 2022-15 emphasizes that NB surveillance activities need to include the new requirements resulting from the IVDR transitional provisions, even for NB designated under IVDD.

NBs need to ensure that their contracts remain applicable after the IVDR date of application and cover surveillance activities for legacy devices. NBs should also review the QMS documentation to verify the following:

  • The scope of the devices covered by the certificate.
  • The QMS has been updated regarding the requirements related to significant changes, PMS, market surveillance, vigilance, and registration of economic operators and devices.
  • All appropriate processes feed into the PMS plan.

Based on the findings from the QMS review, the NB can adjust the audit program, including individual and unannounced audits, which should focus on the new requirements. If major non-conformities that may compromise the device’s safety are identified, the NB should inform the relevant competent authority.

When thinking about on-site audits, NBs can find four possible scenarios:

Thus, IVD legacy device’ manufacturers need to start (if they have not done it yet) updating their QMS to comply with the requirements stated in Article 110 (3).

Source: MDCG 2022-15

What can manufacturers (and other EO) do until EUDAMED is fully functional?

As mentioned above, one of the requirements for legacy devices is registering economic operators and devices in EUDAMED. Currently, the EUDAMED modules to fulfill this requirement are operative. However, other EUDAMED modules have not yet been released.

The MDCG 2022-12 guides the administrative process and provides technical solutions to comply with the IVDR requirements until the EUDAMED database is fully functional. It is expected that manufacturers follow this guidance and apply those principles to their QMS.

Source: MDCG 2022-12

NBs have no capacity; how can manufacturers ensure a spot?

On August 2022, following a request from European Health Ministers, the MDCG published a position paper (MDCG 2022-15) proposing solutions to improve the efficiency of the IVDR application and ensure a continuous supply of IVDs in Europe:

  • The MDCG proposes to increase NB’s capacities by using hybrid audits, leveraging evidence from previous IVDD assessments, or using the flexibility described in MDCG 2022-4 regarding surveillance for legacy devices. The MDCG also proposes to eliminate unnecessary administrative workload for NBs, speed up the development of the EUDAMED database to ensure a more efficient sharing system, modify the frequency of NB reassessment, or accelerate the NB designation process.
  • The MDCG also highlights the need to improve NB accessibility by increasing fee transparency and allocating capacity for small and medium enterprises and first-time applicants.
  • The MDCG encourages dialogue between the NB and manufacturers to enhance manufacturers’ preparedness. NBs are also encouraged to provide “training” to manufacturers through webinars, workshops, or guidelines regarding the application process and common non-conformities.
  • Other actions include reducing the complexity of conformity assessment for legacy devices, including orphan devices, and taking a more pragmatic approach.

Source: MDCG 2022-12

How can AKRN support your company in the IVDD to IVDR transition?

If you are a manufacturer with a legacy IVD who can benefit from Article 110, AKRN can support you in several phases of the IVDD to IVDR transition. Our extensive portfolio covers the following:

  • Quality Management services: AKRN quality team supports manufacturers in the development and update of the QMS documentation, with a focus on the IVDR requirements (post-market surveillance, market surveillance, vigilance, and registration of economic operators).
  • Regulatory Consulting & Medical Writing services: Our regulatory consultants are experienced in performing Technical Documentation and Performance Evaluation gap assessments, implementing the gaps to ensure full compliance with IVDR requirements, and developing the PMS Plan, PMPF Plan, and associated reports to comply with Article 110.
  • Clinical performance studies: AKRN provides clinical services to cover the entire clinical performance study phase, from design to execution, including:
    • Selection of KOL, laboratories, and biobanks
    • Preparation of essential documentation
    • Site initiation, monitoring, and close-out
    • Data management and Biostatistics
    • Report preparation

Sources

Subject Matter Experts

Ariadna Navarro Aragall, Ph.D. Associate Director RA & QA LinkedIn

José Velazquez, M.Sc.
Quality Assurance Manager LinkedIn

Arancha López-Pérez, Ph.D.
Regulatory Affairs Scientist LinkedIn

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