SIMPLEXA COVID-19 DIRECT ASSAY

Additional Manufacturer Narrative

DIASORIN MOLECULAR RECEIVED A COMPLAINT ON THE SIMPLEXA COVID-19 DIRECT ASSAY MOL4150 LOT# X19686N FOR A SUSPECTED FALSE NEGATIVE ON ONE (1) "RING" PROFICIENCY SAMPLE THAT REPEATED AS POSITIVE ON COMPETITOR ASSAY, BD MAX. RUN ANALYSIS OF THE SIMPLEXA RESULTS ARE AS FOLLOWS: RUN (B)(6) 2025 AT 0901 - SAMPLE ID (B)(6): S GENE (35.9), ORF1AB (33.4) - SAMPLE ID (B)(6): NOT DETECTED BOTH TARGETS - SAMPLE ID (B)(6): NOT DETECTED BOTH TARGETS - SAMPLE ID (B)(6): S GENE (25.0), ORF1AB (25.0) - SAMPLE ID (B)(6): S GENE (33.7), ORF1AB (32.4) RUN (B)(6) 2025 AT 0811 - SAMPLE ID (B)(6) (POSITIVE CONTROL): S GENE (27.2), ORF1AB (28.1) - SAMPLE ID (B)(6): S GENE (NOT DETECTED), ORF1AB (33.1) THE CUSTOMER STATED THE BD MAX RESULTS WERE DETECTED FOR COVID BUT NO BD MAX DATA WAS SHARED. THE SAMPLE ID (B)(6) WAS EXPECTED TO BE POSITIVE BUT WAS NOT DETECTED ON THE INITIAL RUN ON (B)(6) 2025 AND ONLY DETECTED FOR 1 TARGET IN THE REPEAT RUN ON (B)(6) 2025. A DETECTION OF ONLY 1 TARGET WITH A CT = 33.1 IS LATER THAN THE TYPICAL 22-32 CTS WITH DETECTED SAMPLES/CONTROLS. A POSITIVE CONTROL (SAMPLE 9999999902) WAS RUN ON THE REPEAT RUN WITH DETECTION OF BOTH THE S GENE (27.2) AND ORF1AB (28.1). IN ADDITION, THREE (3) OTHER KNOWN POSITIVE SAMPLES WERE DETECTED WITH 2 OF THE 3 SAMPLES ALSO SHOWING SLIGHTLY ELEVATED CTS. IT IS KNOWN THAT THE BD MAX ASSAY DETECTS THE N1 AND N2 GENES (DIFFERENT TARGETS THAN THE SIMPLEXA ASSAY) AND UTILIZES AN EXTRACTION OF THE SAMPLE (SIMPLEXA IS A DIRECT MODERATE COMPLEXITY ASSAY. BATCH RECORD REVIEW SHOWED THE CRITICAL COMPONENT, REACTION MIX MOL4151 LOT# X19688N, MET ALL QC RELEASE CRITERIA PRIOR TO KIT RELEASE. POS CTRLS WERE DETECTED WITH AN AVG CT = 26.3 (S GENE) AND 26.1 (ORF1AB). NO MALFUNCTIONS OCCURRED DURING QC RELEASE. RETAINS OF THE SUSPECTED DEVICE WERE TESTED ON (B)(6) 2025 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 = 26.5 / ORF1AB AVG CT = 27.1). 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. IT IS NOT KNOWN HOW THESE RING PROFICIENCY SAMPLES ARE COLLECTED, BUT IT IS LIKELY THE SPECIFIC SAMPLE 9833711800 IS NEAR THE LIMIT OF DETECTION OF THE SIMPLEXA ASSAY. 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."

Description of Event or Problem

DIASORIN MOLECULAR RECEIVED A COMPLAINT ON THE SIMPLEXA COVID-19 DIRECT ASSAY MOL4150 LOT# X19686N FOR A SUSPECTED FALSE NEGATIVE ON ONE (1) "RING" PROFICIENCY SAMPLE THAT REPEATED AS POSITIVE ON COMPETITOR ASSAY, BD MAX. THE CUSTOMER CONFIRMED THE SUSPECTED FALSE NEGATIVE RESULTS WERE ON A PROFICIENCY SAMPLE ONLY. NO ALLEGED HARM OCCURRED TO ANY PATIENTS.