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In-house IVDs (also referred to as Laboratory Developed Tests, LDTs) manufactured and used within a single health institution are regulated products under the IVDR. While a CE mark is still not necessary, in-house IVD manufacturers are required to establish an “appropriate” Quality Management System by the crucial deadline of 26 May 2024. Let’s look deeper at the EU’s QMS requirements for in-house IVDs.

In the pre-IVDR era, in-house IVDs were typically designed and manufactured by entities compliant with or certified to ISO 15189, ISO/IEC 17025 or other national provisions. However, the IVDR has brought about significant changes. While the IVDR still requires compliance with these standards in article 5(5)(c), the MDCG Guidance 2023-1 makes it clear that “ISO 15189 alone does not constitute an appropriate QMS for the manufacture of in-house IVDs”. This prompts the question, what other measures should be implemented? Here, the MDCG 2023-1 seems to adopt a contradictory approach that requires further clarification.

On the one hand, it refers to the IVDR article 10(8) as a “guidance”. On the other hand, it lists examples of areas to be covered by an “appropriate” QMS without specifying whether the listed examples are exhaustive. Considering article 10(8) as a “guidance” will likely lead to creating a complete ISO 13485 QMS. While this approach certainly is a fail-safe positioning, it represents quite a shift for institutions used to the ISO 15189 framework! The pragmatic approach, therefore, takes a closer look at those examples. Looking at them through a device lifecycle lens, we can identify the following IVDR-specific processes that should be implemented:

  • Qualification/classification, justification for in-house IVDs and (if required by national law) notification
  • Design, manufacturing and risk management, including labeling and traceability management
  • Conformity assessment
  • Device monitoring, incl. similar CE-marked devices monitoring
  • Serious incidents reporting

The graph below shows a proposed QMS process map for in-house IVD manufacturers, along with additional elaborations on the processes:

Blog QMS IVDR readiness

The qualification process is of utmost importance as it enables clear identification of which devices, instruments, procedures, or reagents in the medical laboratory portfolio of analyses should be considered in-house IVDs, which ones should not, and why.  To establish internal rules for qualification, it is worthwhile to look at MDCG 2023-1 and guidance from medical laboratory associations such as the Dutch IVDR task force.

The classification process, guided by the pivotal IVDR Annex VIII, is to be done and can be supported by MDCG 2020-16. Authorities may require this information. Also, depending on the jurisdiction, some requirements will only apply to Class D devices.

Justification must be documented that no similar already CE-marked devices can be used as a substitute for the in-house IVDs. This requires comparing key characteristics, such as the device target patient group, related specific need(s) to be met and the required level of performance. This requirement will become applicable only from 26 May 2028. This date will be changed to 31 December 2030 once the European Commission proposal to amend the transitional provisions of the IVDR is published in the Official Journal of the European Union.

Some national laws require that Class D in-house devices' design and manufacturing processes are governed by an appropriate QMS and documented. We recommend a critical review of QMS requirements for design, development and production relevant to all in-house IVDs, described in ISO 13485 chapter 7 and their implementation. For design control, at minimum, the laboratory should document the intended purpose, performance requirements, and any other functional or user requirements for the in-house IVD and compare this to what the device achieves. A manufacturing flowchart illustrating the manufacturing process and a detailed description of the manufacturing facility will also be necessary. Design changes should be managed and tracked, ensuring a comprehensive and well-documented process.

As part of the design process, labeling and traceability needs are assessed and documented according to ISO 13485. It's important to consider the specific requirements of IVDR Annex I, chapter III. While many requirements may not be applicable or are covered by the laboratory's SOP for running the assay, the laboratory plays a crucial role in ensuring the in-house IVD can be identified. This includes ensuring information on expiry dates, batches, storage and handling conditions, and relevant warnings are readily available to users.

Risk management shall be conducted throughout the in-house IVD lifecycle (from design to manufacturing, use, and disposal). ISO 14971 represents the state-of-the-art. Alternatively, ISO 22367 (in which Annex A is of particular interest for in-house IVD manufacturers) may be considered.

For in-house IVDs, the conformity assessment does not require the involvement of a Notified Body. The laboratory should assess and document compliance with the relevant GSPRs and draw up an appropriate public declaration. MDCG 2023-1 provides a public declaration template.

National competent authorities, such as Swissmedic, may require notification of in-house IVDs. The timelines for notifications depend on the device classification.

The use of in-house IVDs in a clinical context (e.g., sample collection, handling, examination, and reporting of test results) should be appropriately covered by an ISO 15189-compliant QMS.

Device monitoring is required to review experience gained from “clinical” use of in-house IVDs and monitor the market for new similar CE-marked devices that may challenge the need for an in-house IVD. While an ISO 15189 QMS may already cover the collection of feedback, monitoring similar devices is a new activity.

Serious incidents identified (e.g. through monitoring activities) may have to be reported according to the IVDR timelines (dependent on local Competent Authority requirements). This requires the QMS to consider both the systematic evaluation of feedback/complaints against the serious incident qualification criteria and the incorporation of appropriate reporting mechanisms and timelines.

Conclusion

In-house IVD manufacturers shall ensure that their QMS is aligned with the requirements of the IVDR by 26 May 2024. ISO 15189 / ISO 17025 will not be sufficient to demonstrate compliance. While some advocate that the QMS adjustments may be limited mainly to design, manufacturing and IVDR GSPR compliance, a deeper dive into the requirements indicates more comprehensive requirements. On top of considering design, manufacturing and risk management frameworks such as ISO 13485 and ISO 14971, IVDR-specific processes are required related to qualification, classification, justification, notification, labeling, monitoring, serious incidents reporting and conformity assessment.

Valentin Chapuis
Senior Quality & Engineering Support

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