Performance evaluation according to IVDR: Scientific validity
Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) has significantly tightened the requirements for the performance evaluation of in vitro diagnostic medical devices (IVD). Manufacturers are required to provide comprehensive evidence of the scientific validity, analytical performance and clinical performance of their products. This article provides a structured overview of the scientific validity requirements under the IVDR.
Overview and definition of scientific validity
The scientific validity of an analyte describes its suitability for detecting a clinical or physiological condition – in other words, it proves that the methodology with which the product is labelled actually has a scientific basis and can function accordingly. In accordance with IVDR Annex XIII Part A 1.2.1, the manufacturer must demonstrate scientific validity using one or more of the following methods:
- Scientific literature
- Expert reports/opinions from relevant professional organisations
- Results from studies to prove the mode of action
- Results from clinical performance studies
- Relevant information on the scientific validity of products measuring the same analyte
The scientific validity is verified and documented in the Scientific Validity Report (SVR).
However, it is only one part of the performance evaluation and must be considered in combination with analytical and clinical performance. Even after market launch, scientific validity should be continuously reviewed, especially as new scientific evidence becomes available.
Methodological approach – overview
According to IVDR, Annex XIII Part A 1.2, the manufacturer must systematically assess the scientific validity of his device. This includes the following steps:
- Systematic evaluation of the scientific literature to identify all relevant data relating to the intended purpose of the product.
- Evaluating and analysing the identified data with regard to its suitability for assessing the safety and performance of the product.
- Determination and preparation of additional data if relevant questions cannot be answered adequately.
Two central documents are required for the structured documentation of the literature search:
- A Literature Search Protocol (LSP):
It contains the methodological planning and documentation of the research carried out, including the search strategy, databases used, inclusion and exclusion criteria and the search results.
- A Literature Search Report (LSR):
It builds on the LSP and evaluates the included publications in terms of their scientific relevance and validity.
Methodological approach in detail
Manufacturers should take a systematic approach to literature research or other data procurement methods:
- Definition of the intended purpose and other central product properties
- Definition of a clear search strategy in relation to the analyte
- Execution of multiple, focussed search queries with consolidated search criteria
- Documentation of the methodology to ensure traceability, reproducibility and verifiability
If the relationship between the analyte and a clinical condition or physiological state is well established, existing evidence may be of sufficient quality and quantity to support scientific validity.
Examples of existing evidence:
- Evaluated literature data
- Peer review data
- Available clinical data (e.g. Summary of Safety and Performance – SSP, registers, authority databases)
- Information on the scientific validity of similar products
- Proof-of-concept studies
- Consensus-based expert opinions and position papers
However, if there is insufficient evidence, if the evidence is incomplete or if, for example, the analytes are novel, a scientific justification is required. In this case, additional evidence must be generated. A gap analysis should be carried out by the manufacturer to determine the additional data required.
Examples of generating new evidence:
- Conducting clinical performance studies
- Conducting other studies, e.g. analytical performance studies or PMPF studies (Post-Market Performance Follow-up)
However, it is important to emphasise that clinical performance studies primarily serve to demonstrate clinical performance rather than scientific validity. The need for such studies may also arise primarily from the evaluation of clinical performance data as part of the preparation of the Clinical Performance Report (CPR). This topic and the requirements for performance studies are discussed in detail in separate blog articles.
Relevance of the MDCG 2022-2 Guidance Document
The MDCG 2022-2 Guidance document “Guidance on general principles of clinical evidence for In Vitro Diagnostic medical devices (IVDs)” provides recommendations for the implementation of the scientific validity assessment as well as a graphical overview with different steps the manufacturer can take to fulfil the scientific validity requirements. The guidance document also serves as a general orientation aid for manufacturers to efficiently fulfil regulatory requirements for performance evaluation.
MDCG 2022-2 defines clearer requirements for systematic literature searches. It contains detailed specifications on how to conduct a literature search in a methodologically correct manner in order to meet regulatory requirements. A central element is the precise intended purpose of the product, as this is crucial for the correct assessment of scientific validity. The guidance also sets out specific requirements for various product classes – stricter requirements apply in particular to higher-risk in-vitro diagnostics (IVDs) in order to ensure a higher level of safety and evidence.
Differentiation from analytical and clinical services
Scientific validity is an essential component of performance evaluation, but is only the first of three central pillars. To fully demonstrate the safety and performance of an IVD, analytical and clinical performance must also be considered and documented.
- Scientific validity refers to the fundamental relationship between the analyte and a clinical or physiological condition.
- Analytical performance comprises the technical ability of the IVD to measure the analyte correctly – for example, in terms of sensitivity, specificity, linearity or detection limit.
- Clinical performance, on the other hand, assesses whether the measurement results in the real clinical application actually allow a reliable statement to be made about the clinical condition of the patient – for example, whether a test can reliably distinguish between healthy and sick patients.
All three components – scientific validity, analytical performance and clinical performance – are interrelated and together they form the basis for a robust and regulatory compliant performance evaluation.
Special challenge: Class A IVDs without analytes
A particular challenge in the assessment of scientific validity arises with class A products that do not have a specific analyte – such as centrifuges, sample containers, buffer solutions or incubators. As no direct association between an analyte and a clinical or physiological condition can usually be established for these products, scientific validity cannot be established in the traditional way by demonstrating an analyte mode of action.
Instead, the scientific validity of these products could be based on the basic functional principle of the product – for example, the principle of centrifugation, thermal incubation or chemically defined buffer reactions in the context of in vitro diagnostic sampling and analysis. Even if no specific analytes are available, it is essential to scientifically demonstrate the relevance and appropriateness of the product for the intended diagnostic application.
In such cases, the scientific validity can be documented as a chapter within the State of the Art Report (SOTA), either as a separate document or as part of the Performance Evaluation Plan (PEP)/Performance Evaluation Report (PER). Clear structuring and argumentation are crucial here.
There are currently no specific MDCG guidelines or normative specifications that regulate this special case. It is therefore the manufacturer’s responsibility to provide a comprehensible and regulatory justification based on the current state of science and technology.
Conclusion
Scientific validity is a central component of the performance evaluation of IVDs according to Regulation (EU) 2017/746 . Manufacturers must provide scientific evidence through a systematic literature search, comparison with existing scientific evidence and, if necessary, additional studies. A structured approach to planning and reporting facilitates the collection and documentation of relevant information. Regulatory requirements such as the IVDR and the MDCG 2022-2 document are essential for correct implementation. seleon can support you in planning and creating an IVDR-compliant performance evaluation!
Please note that all details and listings are not intended to be exhaustive, are without guarantee and are for information purposes only.
