RAPS Convergence 2023: IVDR and Clinical Evidence Requirements

By Ken Pilgrim and Evangeline Loh

Emergo by UL consultants attended Regulatory Affairs Professionals Society (RAPS) Convergence 2023 recently held in Montreal Canada, and are providing dispatches on key issues, trends and challenges discussed at the conference. Our previous RAPS Convergence 2023 report covered European notified bodies and Medical Devices Regulation (2017/745, MDR) compliance efforts.

Below, we cover ongoing European In Vitro Diagnostic Medical Devices Regulation (2017/746, IVDR) themes discussed by conference presenters and attendees.

Background

RAPS Convergence 2023 included sessions which examined the IVDR from the perspective of legacy IVD devices as well as in comparison to the MDR. Many of the fundamental concepts in the IVDR are identical to the MDR.

There are certainly unique aspects to IVDs which also supports the medical devices and IVD legislation promulgated as two regulations. There is no concept of indications for use per se, as this is related to clinical condition or disease state as explained in MDCG 2020-6 on legacy medical devices, though indications is used interchangeably with intended purpose in MDCG 2022-2.

Some basic concepts and differences with the MDR

One of the RAPS conference speakers noted that the IVDR doesn’t include the MDR Article 22 on systems and procedure packs or Article 23 on parts and components. However, by definition an IVD can be a kit or a system. The kit is treated as a single device which can consist of multiple products and possesses CE marking as the single device.

As outlined in IVDR Annex II 1.1c there are many parameters which establish the intended purpose including but not limited to: claims, diagnostic application, use environment, and type of users. Emergo by UL has a recorded webinar examining the importance of an IVD intended purpose for accurate classification of the IVD.

Similar to the MDR, manufacturers struggle with documenting clinical evidence

BSI data identified that the most common submission nonconformities for IVDs was clinical evidence -- performance evaluations – similar to issues with clinical evaluations found with medical devices.

Manufacturers are expected to document performance evaluation and clinical evidence in the Performance Evaluation Report (PER). The IVD needs to achieve its intended clinical benefit, safety requirements and the intended purpose. All three aspects of performance evaluation need to be included: scientific validity, analytical performance and clinical performance.

The PER process is similar to the medical device Clinical Evaluation Report (CER) process

The PER is the documented assessment of the performance evaluation and clinical evidence data (known as the methodical PER process, which is analogous to the medical device CER).  

Perhaps a newer activity for some IVD manufacturers involves performing and documenting literature searches for both the IVD and state-of-the-art (SOA), as SOA is also expected for IVDs. One of the conference presenters explained this as SOA related both to devices (Common Specifications (CS), standards, guidance) and to medicine (standard of care, disease state).

Reminder: it would be optimal if similar devices selected for SOA are compliant to the IVDR or legacy to the In Vitro Diagnostic Medical Devices Directive IVDD 98/79/EC.

Concluding remarks

While the IVDR Performance Evaluation Plan (PEP) and PER may be newer activities for many if not most IVD manufacturers, there is some guidance available. MDCG 2022-2 guides manufacturers on fundamental concepts related to clinical evidence.  There is also MedTech Europe guidance on the IVDR and Clinical Evaluation. Of course, MEDDEV 2.7/1, Rev. 4 provides guidance on the literature search process and protocol and some key aspects of the clinical evaluation process for medical devices, though still relevant to IVDs. Emergo by UL also offers a recorded webinar explaining IVDR PERs.

Meeting IVDR PER requirements is not a simple feat, though with practice, IVD manufacturers’ PERs will improve.