BEUDAMED
    FDA Adverse Event Malfunction Summary report: N

    RAPIDEC CARBA NP

    MDR report key: 10485074 · Received September 2, 2020

    Report

    Report Number
    9615754-2020-00143
    Event Type
    Malfunction
    Date Received
    September 2, 2020
    Report Date
    May 21, 2021
    Manufacturer
    BIOMÉRIEUX, SA
    Product Code
    PTJ
    PMA / PMN Number
    K162385
    Product Problem
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    CA
    Reporter Occupation
    OTHER HEALTH CARE PROFESSIONAL

    Narratives

    Additional Manufacturer Narrative · 0

    INFORMATION REQUESTED AND PROVIDED BY THE AUTHORS: THE FOLLOWING INFORMATION WAS REQUESTED FROM THE AUTHORS OF THE PUBLICATION FOR THE INVESTIGATION. THE INFORMATION PROVIDED IS DESCRIBED BELOW. THE DETAILS OF METHODOLOGY TO CONDUCT RAPIDEC® CARBA NP INCLUDING CULTURE MEDIA USED, INCUBATION TIME, PROFICIENCY TESTING IF ANY, AND THE ENDPOINT COLOR INTERPRETATION FOLLOWED: THE AUTHORS FOLLOWED THE PACKAGE INSERT INSTRUCTIONS (20584 E DATED 2016/03) FOR THE METHODOLOGY, INCUBATION TIME AND RECOMMENDED QUALITY CONTROL SAMPLES AND USED THE READING GUIDE SHOWN IN THE ATTACHED PICTURE ¿NEGATIVE CONTROL WITH READING GUIDE¿. TSA AGAR AS THE CULTURE MEDIA WAS USED. BECAUSE ALL OF THESE SAMPLES WERE NOT CLEARLY POSITIVE AT THE FIRST INCUBATION TIME, A SECOND READING WAS PERFORMED AT 1 ½ HOURS LATER. THREE DIFFERENT TECHNOLOGISTS READ/INTERPRETED ALL OF THE RESULTS. IF PICTURES OF THE SPECIFICITY PANEL (NEGATIVE CONTROLS) REACTIONS WERE TAKEN: PHOTOGRAPHS PROVIDED. IF THE SPECIFICITY PANEL (NEGATIVE CONTROLS) ISOLATES COULD BE SHARED WITH THE MANUFACTURER (BIOMÉRIEUX) TO RE-RUN THESE ISOLATES: DUE TO PATIENT PRIVACY AND ETHICS REGULATIONS, THE AUTHORS ARE NOT ABLE TO RELEASE OR SHARE THE SPECIFICITY ISOLATES. THE ORIGIN OF THE SPECIFICITY PANEL (NEGATIVE CONTROLS) ISOLATES: THEY WERE A COLLECTION OF CARBAPENEM RESISTANT CLINICAL ISOLATES AT APL THAT WERE ROUTINELY SENT FOR CARBAPENEMASE PCR AT THE NML IN WINNIPEG. THESE ISOLATES TESTED PCR-NEGATIVE AT NML. THE DETAILS OF THE PRIMERS: REFERENCE MATASEJE ET ALL; JAC 2012; 67:1359-67. THE VITEK® 2 REPORTS ON THE SPECIFICITY PANEL (NEGATIVE CONTROLS) ISOLATES: DUE TO PATIENT PRIVACY REGULATIONS THE AUTHORS ARE NOT ABLE TO RELEASE OR SHARE THE SUSCEPTIBILITY RESULTS. HOWEVER, ALL THE ISOLATES TESTED NON-SUSCEPTIBLE TO EITHER ERTAPENEM AND/OR MEROPENEM. THE PCR REPORTS ON THE SPECIFICITY PANEL (NEGATIVE CONTROLS) ISOLATES: DUE TO PATIENT PRIVACY REGULATIONS THE AUTHORS ARE NOT ABLE TO RELEASE THE PCR REPORTS FROM THE NML. THEY WERE ALL CONFIRMED AS PCR-NEGATIVE BY NML. IF THE PRODUCT IS BEING USED FOR RESEARCH-USE-ONLY OR IN THE ROUTINE FOR CLINICAL SAMPLES: THE TEST WAS NOT IMPLEMENTED FOR CLINICAL SAMPLES. IT WAS USED FOR THIS VERIFICATION STUDY ONLY. EXPERT INVESTIGATION DETAILS: THE AUTHORS OF THE PUBLICATION IN QUESTION REPORT FALSE POSITIVE RESULTS ON RAPIDEC® CARBA NP. INDEED, THE AUTHORS EXPLAIN THAT DARK ORANGE COLORED RESULTS WERE OBTAINED ON A LARGE NUMBER OF ENTEROBACTERALES INCLUDED AS NEGATIVE CONTROLS (37/46). ADDITIONAL INFORMATION ON THE PROTOCOL USED WAS NEEDED TO UNDERSTAND THE ISSUE AND TO TRY TO DETERMINE THE ROOT CAUSE. THE SET OF 46 STRAINS OF ENTEROBACTERALES EXPECTED TO BE NEGATIVE WOULD ALSO HAVE BEEN USEFUL TO TEST INTERNALLY, HOWEVER IT WAS NOT POSSIBLE TO OBTAIN ADDITIONAL INFORMATION AND THE NEGATIVE STRAINS TO TEST. NEVERTHELESS, THERE WERE EXCHANGES AT THE TIME OF THE STUDY BETWEEN THE AUTHORS AND BIOMÉRIEUX. SOME PHOTOGRAPHS WERE SHARED ON THE NEGATIVE STRAINS TO ILLUSTRATE THE DARK ORANGE COLOR ISSUE. AT THE TIME OF THIS EXCHANGE, BIOMÉRIEUX SHARED SOME ADVICE ON HOW TO INTERPRET THE TEST AND ESPECIALLY MENTIONED THAT THE DARK ORANGE COLOR WAS NOT SUFFICIENT IN TEST WELL "E" TO CONCLUDE ON POSITIVE RESULTS. THE COLOR SHOULD BE COMPARED TO CONTROL WELL "D" AND THERE SHOULD HAVE BEEN SOME DIFFERENCES IN THE COLOR. IN THE EXAMPLES SHARED, BIOMÉRIEUX MENTIONED THAT SOME RESULTS SHOULD BE CONSIDERED AS NEGATIVE AND NOT POSITIVE. RELATED TO THE INFORMATION SHARED WITH BIOMÉRIEUX FOR THIS STUDY, THE ISSUE ALSO SEEMS, AT LEAST PARTIALLY, LINKED TO THE METHODOLOGY USED TO READ AND INTERPRET THE TEST. ALSO WE CANNOT EXCLUDE AN ISSUE DURING THE INOCULUM PREPARATION STEP. NO ADDITIONAL INFORMATION IS AVAILABLE ON THE STRAINS TESTED; WITHOUT THIS INFORMATION AND WITHOUT THE STRAINS IN QUESTION, IT IS NOT POSSIBLE TO FURTHER INVESTIGATE THE PUBLISHED ISSUE. AS DESCRIBED IN THE PERFORMANCE SECTION IN THE PACKAGE INSERT, EXTERNAL STUDIES PERFORMED IN EUROPE AND IN THE UNITED STATES SHOWED VERY GOOD SPECIFICITY RESULTS FOR RAPIDEC® CARBA NP, (97.8% FOR STUDIES PERFORMED IN EUROPE, 3 FALSE POSITIVE RESULTS AMONG 139 NEGATIVE STRAINS TESTED ; 5 FALSE POSITIVE RESULTS OBSERVED DURING THE UNITED STATES STUDIES AMONG 192 NEGATIVE SAMPLES). COMPLAINT TREND ANALYSIS A COMPLAINT TREND ANALYSIS WAS PERFORMED ON RAPIDEC® CARBA NP, REFERENCES 415418, 417498, 417824, 417825, FROM 01 JAN 2018 TO 30 APRIL 2021. A TOTAL OF EIGHT COMPLAINTS WERE RECEIVED FOR FALSE POSITIVE RESULTS INCLUDING THIS PUBLICATION, THE SEVEN OTHER COMPLAINTS WERE RESOLVED BY TROUBLESHOOTING AND PRODUCT PERFORMANCE ISSUES WERE NOT IDENTIFIED. CONCLUSION: TO DATE, THERE IS NO EVIDENCE THAT THE PRODUCT, RAPIDEC® CARBA NP, IS OUTSIDE ITS EXPECTED LEVEL OF PERFORMANCE, THEREFORE NEITHER CORRECTIVE NOR PREVENTIVE ACTION WILL BE IMPLEMENTED. AS PART OF OUR POST-MARKET SURVEILLANCE PROCESS, PUBLICATIONS WILL CONTINUE TO BE MONITORED ON OUR PRODUCTS.

    Description of Event or Problem · 1

    AN INTERNAL COMPLAINT WAS INITIATED IN RESPONSE TO A REVIEW OF A SCIENTIFIC PUBLICATION TITLED ¿RAPID DETECTION OF ENTEROBACTERALES THAT PRODUCE CARBAPENEMASES ¿BY CHAN ET AL. THE STUDY EVALUATED THE PERFORMANCES OF THREE RAPID TESTS: RAPIDEC CARBA NP® (BIOMÉRIEUX), ¿-CARBA® (BIO-RAD), NG-TEST CARBA 5® (BIOTECH) AS WELL AS MODIFIED CARBAPENEM-INACTIVATION METHOD AND EDTA VERSION (ECIM) ASSAYS AGAINST A GLOBAL COLLECTION OF ENTEROBACTERALES (N = 216) WITH DIVERSE CARBAPENEMASES. FALSE POSITIVE RESULTS WERE REPORTED ON RAPIDEC CARBA NP® (REF. 415418). THE STUDY RESULTS FOUND THE RAPIDEC CARBA NP® ASSAY HAD A SENSITIVITY OF 98.6% AND SPECIFICITY OF 19.6%. THE LOW SPECIFICITY (19.6%) OF RAPIDEC CARBA NP® REPORTED BY CHAN ET AL. SHOWED FALSE PRESENCE OF CRE (CARBAPENEM-RESISTANT ENTEROBACTERIACEAE) IN THE ISOLATES NOT HARBORING SUCH GENES/ENZYMES. THERE IS NO INDICATION OF ANY SERIOUS DETERIORATION TO ANY PATIENT¿S STATE OF HEALTH RELATED TO THE EXECUTED STUDY IN THE PUBLICATION. BIOMÉRIEUX HAS INITIATED AN INTERNAL INVESTIGATION.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    949230 RAPIDEC CARBA NP RAPIDEC® CARBA NP PTJ BIOMÉRIEUX, SA

    Patients

    Seq Age Sex Outcome Treatment
    1