Most of us are familiar with clinical evaluations for medical devices.
But when it comes to the equivalent for in vitro diagnostic medical devices, the performance evaluation, most of us are a little more in the dark.
Unless you are an IVD manufacturer, of course – you guys already have performance evaluations down!
The In Vitro Diagnostic Directive 98/79/EC (IVDD) from 1998 was relatively straightforward on the evidence needed to establish the analytical and clinical performance evaluation for CE certification for in vitro diagnostic medical devices.
When the European Union In Vitro Diagnostic Regulation (IVDR, 2017/746) was implemented in 2017, it expanded on the performance characteristics, guiding the manufacturer through the conformity assessment.
And although the actual concepts and requirements surrounding the performance evaluation have remained the same over the last few decades, the IVDR heavily upped the technical documentation required for in vitro diagnostic medical devices.
A particular requirement issued by the IVDR is the performance evaluation plan (PEP), equivalent to the clinical evaluation plan for medical devices.
This article reviews analytical and clinical performance evaluation plans for in vitro diagnostic medical devices, what you need to draft a good one, and how it aligns with the rest of your performance evaluation.
What is the performance evaluation plan, and why do I need it?
The performance evaluation plan is described in Annex XIII of the IVDR, so it is required to comply with the IVDR.
A.k.a., you need it to get your CE marking or re-certified.
However, it can also do many other cool things for your technical documentation and in vitro diagnostic medical devices as a whole.
The performance evaluation plan is a great tool to take performance and safety design input and criteria, along with risk management, and align them to the larger IVDR requirements.
The IVDR specifies safety, performance, risk, and stability requirements in Annex I, Section 1-9.
In the performance evaluation, they are all evaluated together to ensure the continued safety and performance of your in vitro diagnostic medical devices.
What is the clinical evidence for IVDs?
With medical devices, what constitutes clinical evidence and which General Safety and Performance Requirements (GSPRs) it supports is relatively straightforward.
In vitro diagnostic medical devices, however, are built differently.
Generating clinical performance and stability data is relatively clear.
However, generating clinical evidence for safety and risk is a more opaque process. Manufacturers need to think outside the box to find the real-world experience of IVDs to support safety and benefit-risk ratio evidence.
Performance Evaluation Plan (PEP) for IVDs
The performance evaluation plan is described in Annex XIII as part of the performance evaluation. It is the first step in the three-step performance evaluation process.
The performance evaluation plan defines the whole performance evaluation process and documents the scientific and clinical rationale of the methods used. It also includes the acceptance criteria for the methodologies used, how the benefit-risk ratio determination will occur, and how it is deemed acceptable.
It lays out all your information about your in vitro diagnostic device and how you plan to identify, collect, and analyze further data to support your performance evaluation.
Specific points to include in your PEP
According to Annex XIII of the IVDR, your performance evaluation plan should include at least the following:
- Intended purpose and intended use
- IVD characteristics
- The analyte or marker to be determined by the device
- Identification of certified reference materials or reference measurement procedures to allow for metrological traceability
- Identification of the target patient groups, including clear indications, limitations, and contra-indications
- Identification of the general safety and performance requirements (GSPRs) requiring support from the relevant scientific validity and analytical and clinical performance data
- Specification of methods, including appropriate statistical tools
- A description of the current state-of-the-art
- Benefit-risk ratio considerations
- For software, identification, and specification of reference databases and other sources of data used as the basis for its decision-making
- Outline of developmental phases
- Post-market performance follow-up (PMPF)
If these aspects are not included in the performance evaluation plan, you must justify why they are inappropriate.
The performance evaluation plan is your recipe for the performance evaluation report. It tells you what to do and how and when.
Most importantly, the performance evaluation plan proves that you have a systematic process that ensures objectivity and completeness.
Frequently Asked Questions (FAQ)
Is the Performance evaluation plan mandatory under the IVDR?
Yes. There is no way around it – you need a performance evaluation plan.
How long should my PErformance evaluation plan be?
Unfortunately, there is no definite answer for the length of your PEP. It depends entirely on your IVD, its risk classification, and the clinical evidence you gather.
Will my notified body review my performance evaluation plan?
Yes, the performance evaluation plan is essential to the conformity assessment. As such, you can expect a detailed review of the PEP by the notified body.
If your device is low-risk (Class A) and does not require a notified body conformity assessment, you do not need to provide the performance evaluation plan for review. However, you can be asked for it at any point by the regulatory authority, and it is required under the IVDR, so it is better to have it prepared and ready.
Do legacy devices require a performance evaluation plan?
Legacy devices also require performance evaluation plans, but their approach differs from new in vitro diagnostic medical devices.
Manufacturers must re-examine their previous clinical evidence to assess its suitability under the IVDR. If the previous clinical data does not meet the IVDR requirements, manufacturers should evaluate how any gaps can be filled in the performance evaluation plan.