SIMPLEXA COVID-19 DIRECT ASSAY

Description of Event or Problem

DIASORIN MOLECULAR RECEIVED A COMPLAINT ON THE SIMPLEXA COVID-19 DIRECT ASSAY MOL4150 LOT# X18870N FOR A SUSPECTED FALSE NEGATIVE ON ONE TWO (2) PATIENT SAMPLE THAT RESULTED NOT DETECTED ON THE SIMPLEXA ASSAY, BUT DETECTED UPON REPEAT ON A DIFFERENT METHOD (FILMARRAY MELT CURVE ANALYSIS). NO FALSE RESULTS WERE REPORTED OUT TO THE CLINICIAN. NO ALLEGED HARM OCCURRED.

Additional Manufacturer Narrative

DIASORIN MOLECULAR RECEIVED A COMPLAINT ON THE SIMPLEXA COVID-19 DIRECT ASSAY MOL4150 LOT# X18870N FOR A SUSPECTED FALSE NEGATIVE ON ONE TWO (2) PATIENT SAMPLE THAT RESULTED NOT DETECTED ON THE SIMPLEXA ASSAY, BUT DETECTED UPON REPEAT ON A DIFFERENT METHOD (FILMARRAY MELT CURVE ANALYSIS). RUN ANALYSIS OF THE THE SIMPLEXA RESULTS ARE AS FOLLOWS: RUN (B)(6) 2023 SAMPLE ID (B)(6): NOT DETECTED, IC CT = 28.5. SAMPLE ID (B)(6): NOT DETECTED, IC CT = 30.9. THE CUSTOMER STATED THEY ARE USING COPAN AS THE TRANSPORT MEDIUM AND REPEATED THE TWO NOT DETECTED SAMPLES ON A "FILMARRAY MULTIPLEX PCR SYSTEM" WHICH UTILIZES A MELT CURVE ANALYSIS METHOD. IT IS NOT KNOWN WHAT ARE THE PARAMETERS AND GENE TARGETS OF THIS OTHER PCR METHOD. THE CUSTOMER ALSO NOTED THAT THEY ARE GETTING SEVERAL INVALID RESULTS ON THE SAME RUNS DUE TO EC515 ERRORS WHICH IS INDICATIVE OF POSSIBLE AMPLICON CONTAMINATION ISSUES. THE CUSTOMER DID NOT REPORT THE ALLEGED FALSE NEGATIVE RESULTS DUE TO THE EC515 ERRORS THAT OCCURRED ON THE SAME RUN. THE CUSTOMER'S SAMPLES WERE NOT PROVIDED FOR ANALYSIS. BATCH RECORD REVIEW SHOWED THE CRITICAL COMPONENT, REACTION MIX MOL4151 LOT# X18871N, MET ALL QC RELEASE CRITERIA PRIOR TO KIT RELEASE. MOL4151 LOT# X18871N WAS TESTED USING POSITIVE CONTROLS AND NO-TEMPLATE CONTROLS (NTC). POSITIVE CONTROLS WERE TESTED IN QUADRUPLICATE AND RESULTED IN ZERO (0) OCCURRENCES OF FALSE NEGATIVES IN ANY OF THE COVID-19 TARGETS. ALL POSITIVE CONTROLS WERE DETECTED AT AN AVERAGE CT = 26.4 (S GENE), 26.4 (ORF1AB), AND THE INTERNAL CONTROL AVG CT = 30.6. NO MALFUNCTIONS OCCURRED DURING QC RELEASE TESTING. RETAINS OF THE SUSPECTED DEVICE WERE TESTED ON 01/09/24 WITH 14 REPLICATES (2 DISCS OF 7 PC EACH) OF MOL4160 POSITIVE CONTROL. BOTH TIMES THE TARGETS WERE DETECTED ON ALL REPLICATES (S GENE AVG CT = 27.0 / ORF1AB AVG CT = 27.4). NO FALSE NEGATIVES OCCURRED. NO MALFUNCTIONS OCCURRED. POTENTIAL CAUSES FOR THE FALSE NEGATIVE RESULTS MAY BE AN INSTRUMENT FAILURE OR ERROR, AN OPERATOR ERROR, INCORRECT HANDLING OF REAGENTS DURING TESTING OR STORAGE, OR DEVIATION FROM THE ASSAY PROCEDURE OUTLINED IN THE PACKAGE INSERT. THE CUSTOMER'S DEVICE AND SUSPECTED FALSE NEGATIVE SAMPLE WAS NOT PROVIDED FOR INVESTIGATION. IT IS NOT CONFIRMED TO BE AN ASSAY REAGENT ISSUE AT THIS TIME. AS STATED IN THE INSTRUCTIONS FOR USE, IFUK.EN.MOL4150, "NEGATIVE RESULTS DO NOT PRECLUDE SARS-COV-2 INFECTION AND SHOULD NOT BE USED AS THE SOLE BASIS FOR PATIENT MANAGEMENT DECISIONS. NEGATIVE RESULTS MUST BE COMBINED WITH CLINICAL OBSERVATIONS, PATIENT HISTORY, AND EPIDEMIOLOGICAL INFORMATION" AND PER THE LIMITATIONS SECTION, "FALSE-NEGATIVE RESULTS MAY OCCUR IF THE VIRUSES ARE PRESENT AT A LEVEL THAT IS BELOW THE ANALYTICAL SENSITIVITY OF THE ASSAY OR IF THE VIRUS HAS GENOMIC MUTATIONS, INSERTIONS, DELETIONS, OR REARRANGEMENTS OR IF PERFORMED VERY EARLY IN THE COURSE OF ILLNESS." THIS IS THE 1ST COMPLAINT FOR FALSE NEGATIVE ON MOL4150 LOT X18870N.