One rule, new rationale
Revision 5 of document MDCG 2020-16 concerns only Rule 7 of Annex VIII to the IVDR. The MDCG has clarified its rationale and amended the examples. The remainder of the document has not changed since Revision 4, which covered, amongst other things, Rules 1, 3(m), 4(a) and 6.
When is a value provided by the manufacturer not an assigned value?
Rule 7 is straightforward: controls without an assigned quantitative or qualitative value belong to class B. The problem was that manufacturers of standalone QC materials often specify ranges of analyte concentrations in the instructions for use. The guidance now unambiguously state that such information does not constitute an assigned value. The laboratory sets its own target values anyway, as it must constantly monitor the validity of examination results and validate the performance of its equipment. The data provided by the manufacturer is intended solely to facilitate the selection of the material for the method.
A standalone QC material remains in class B if the instructions for use clearly limit its intended purpose to monitoring the validity of laboratory examination procedures. It cannot replace the mandatory QC materials used to verify the performance of the IVD itself.
Control with or without an assigned value?
| Control with an assigned value | Control without an assigned value | |
|---|---|---|
| Basis | implementing rule 1.6 | Rule 7 |
| Class | the same as the device it controls (B, C or D) | B, unless other rules apply |
| Typical example | assay kit validity controls | standalone (third-party) control serum |
What materials does the MDCG cite as examples of class B?
- unassigned control sera,
- control materials used to verify migration in immunochromatographic assays,
- unassigned heterozygous quality control to monitor analytical performance of nucleic acid extraction, amplification and detection,
- non-assay-specific control plasma for use in coagulation,
- non-assay-specific control serum containing multiple biochemical analytes,
- a DNA or RNA probe supplied as a non-assay-specific normal control for in situ hybridisation (ISH).
The guidance also remind us that internationally certified reference materials and materials used for external quality assessment schemes are not IVDs at all (Article 1(3)(c) and (d) of the IVDR).
Where might a manufacturer go wrong?
Most commonly in the way the instructions are worded. The intended purpose is derived from the label, instructions for use, performance evaluation and promotional materials. Ambiguous claims may lead to a higher classification (Annex VIII, implementing rule 1.9). Therefore, if the description of the value ranges suggests that the material controls a specific test, the notified body may apply implementing rule 1.6. In that case, the material’s class follows that of the reagent, up to class D. It is therefore advisable to review the instructions and product data sheets now, before the notified body does so, and to explicitly refer to Revision 5 in the technical documentation when justifying the classification.
Link to the document: MDCG 2020-16 rev.5