SPADA Meeting Book

6.3 Assay Stewardship – when new viral or bacterial strains are discovered, will the existing 708 assay work? 709 After an assay is designed and validated, it is relatively common for the scientific community 710 to discover a new strain of a pathogen that has a mutation at a site that causes the assay to fail. 711 This process is termed “signature erosion” (9). To date, there have not been any good methods 712 for anticipating new mutations. One general recommendation is to design primers to be a little 713 longer than needed for a perfect match. In the event that a single or double mutation occurs at a 714 later time, the primers will still work as long as the new mutation does not occur at the 3’-end of 715 either primer. In addition, there is a need to have software that can computationally test any new 716 sequenced isolate against existing validated assays to predict if the new isolate is likely to be 717 “covered” by the existing assay (i.e. if the existing assay is predicted to give an amplicon for the 718 new isolate with high efficiency), or if the existing assay is likely to fail for the new isolate (i.e. 719 the existing assay is predicted to give an amplicon for the new isolate with low efficiency). Even 720 better would be for software to constantly monitor existing databases for new entries and to 721 automatically alert a user or agency if a new isolate is “high risk” for assay failure. This 722 capability would allow for real-time monitoring of assays to alert agencies in charge of 723 protecting the public about potential assay failures. The agencies could then focus their ongoing 724 validation efforts on those assays that have a high likelihood of failure rather than using their 725 limited resources on potentially unnecessary redundant validations. Funding, development, and 726 implementation of such an assay stewardship approach is highly recommended by the SPADA 727 working group.

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