Understanding the Specific Evaluation Documentation Required for IVD Performance Under Article 56 of the IVDR

Specific IVD performance evaluation documentation required under Article 56 of the IVDR includes:

• •  Performance Evaluation Plan (PEP)
  •  Scientific Validity Report (SVR)
  •  Analytical Performance Report (APR)
  •  Clinical Performance Report (CPR)
  •  Performance Evaluation Report (PER)

Furthermore, where manufacturers utilize scientific (peer-reviewed) literature and other sources of data from literature and regulatory authority vigilance databases, the literature search and review protocol and report will also support the SVR and CPR. 

Can an IVD be exempt from specific evaluation documentation?

While the IVDR does not describe any scenarios where IVDs may be exempt from any of these documentation requirements, it states that the depth and extent of the performance evaluation shall be proportionate and appropriate to the characteristics of the device, including the risks, risk class, performance, and its intended purpose. 

It also establishes that it is up to the manufacturer to specify and justify the level of the clinical evidence necessary to demonstrate conformity with the relevant GSPR, with the level being appropriate in view of the characteristics of the device and its intended use. 

For reagent-based assays, it is relatively easy to determine the documentation necessary as they possess both specific analytical and clinical performance characteristics and are directly involved in analyte detection. Where manufacturers typically encounter challenges in determining the documentation necessary for their device is when their IVD falls under Rule 5 (e.g. products for general laboratory use, accessories that possess no critical characteristics, and specimen receptacles, etc.) or their devices are calibrators/control materials. 

Is it necessary to prepare an SVR evaluation documentation for an IVD?

Taking calibrators/control materials as an example, as these IVDs do not perform analyte detection, scientific validity is not required to support clinical evidence. However, in our experience, manufacturers must still prepare an SVR that demonstrates the scientific validity of the assay(s) they are supporting which, in the case of multi-parametric controls, would cover the scientific validity of each analyte corresponding with each parameter. 

The IVDR does not establish a definition for ‘analyte’, however in MDCG 2020-16, ‘analyte’ (as well as ‘marker’ and ‘measurand’) is defined as “a substance or material; something that is used to identify; a factor that establishes the nature of an entity or event; a constituent of a sample with a measurable property.” Based upon this definition, it can be understood that a ‘specimen’ is not an analyte, which is consistent with definitions established in the Clinical and Laboratory Standards Institute (CLSI) Harmonized Terminology Database. Therefore, for specimen receptacles, it is reasonable that scientific validity can be justified as not applicable. 

Are APRs necessary for evaluating IVD performance?

Regarding the APR, for specimen receptacles, while it may appear that these do not possess any specific analytical performance characteristics, a review of GSPR 9.1(a) lists the following, which is applicable to these types of IVDs, and indicate that an APR is necessary: 

• •  Determination of appropriate criteria for specimen collection and handling
  •  Control of exogenous interference (particularly in the case of sterile specimen receptacles)

Why do IVDs need to possess a clinical evaluation documentation?

Regarding the CPR, manufacturers may believe that if their IVD does not possess any of the specific clinical performance characteristics described under GSPR 9.1(b) then a CPR can be justified as unnecessary, particularly as ‘clinical performance’ is defined under the IVDR as “the ability of a device to yield results that are correlated with a particular clinical condition or a physiological or pathological process or state in accordance with the target population and intended user.” However, manufacturers are encouraged to gather all relevant clinical evidence in order to understand the clinical risks and benefits of their IVD. It should be noted that ‘existing clinical data’ to be included in investigator’s brochures for clinical performance evaluation studies includes “other relevant clinical data available relating to the safety, scientific validity, clinical performance, clinical benefits to patients, design characteristics and intended purpose of similar devices, including details of their similarities and differences with the device in question.” Therefore, clinical data related to the safety and intended purpose of the device or similar devices could be included as “other clinical data” in the CPR for IVDs that do not possess specific clinical performance characteristics. 

Why should manufacturers review clinical evidence for IVD devices?

Lastly, it is important to note that legacy device manufacturers should review the clinical evidence that they hold to determine its suitability under the IVDR. There may be scenarios where previous clinical performance studies performed under the IVDD do not meet clinical performance study requirements under the IVDR (and under ISO 20916:2019 (not yet harmonized)).

Learn more regarding IVD evaluation documentation with MedEnvoy

If you have any additional questions regarding performance evaluation or require relevant training/consulting services, get in touch. 

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