Purpose of this notice: To request that IVD users monitor mutations of SARS-CoV-2 and their impact on diagnosis.
Description of the problem:
Following the detection of SARS-CoV-2 variants containing mutations, including SARS-CoV-2 VOC 202012/01, and SARS-CoV-2 501Y.V2, WHO reminds users of IVDs to monitor detection rates for SARS-CoV-2 at their site.
IVD users should routinely review test results to detect unexpected increases or decreases in test results, including positivity rate, target detection rate, invalid or unreturnable result rate, etc. These variations may be early indicators of impact on the safety, quality or performance of the IVD products. Certain mutations may increase the risk of delayed diagnosis (due to inconclusive or invalid results), and misdiagnosis.
Manufacturers of IVDs listed by WHO (through Emergency Use Listing) must proactively scan literature and other sources for any documented mutations that might impact the safety, quality or performance of their product. This should be incorporated as part of their post-market surveillance plan and will be supplemented by feedback reported by IVD users in the form of unexpected results, as well as other product problems and adverse events. All gathered information must be reviewed in a timely fashion, using risk management principles to determine any necessary actions.
Advice on action to be taken by IVD users:
IVD users should notify the IVD manufacturer in the following circumstances:
- Increased discrepancies in cycle threshold (Ct) values between different gene targets.
- Failure to detect specific gene targets, including those containing gene sequences that coincide with documented mutations.
- Misdiagnosis (for example, false negative).
See WHO website for reporting form for IVD users to give feedback to manufacturers
Contact person for further information:
Anita SANDS, Regulation and Prequalification, World Health Organization,