BEUDAMED
    FDA Adverse Event Malfunction Summary report: N

    CLINICAL CHEMISTRY BILIRUBIN CALIBRATOR

    MDR report key: 1190264 · Received October 9, 2008

    Report

    Report Number
    2018433-2008-00189
    Event Type
    Malfunction
    Date Received
    October 9, 2008
    Date of Event
    September 11, 2008
    Report Date
    September 11, 2008
    Manufacturer
    ABBOTT MANUFACTURING, INC.
    Product Code
    JIX
    PMA / PMN Number
    K981706
    Removal / Correction Number
    2018433-09/19/08-004-C
    Product Problem
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    WI, US
    Reporter Occupation
    HEALTH PROFESSIONAL

    Narratives

    Additional Manufacturer Narrative · 1

    (B)(4). CONCOMITANT MEDICAL PRODUCTS: ANALYZER (B)(4), TOTAL BILIRUBIN REAGENT (B)(4). EVALUATION, OTHER RESULT EXPLANATION: ABBOTT CLINICAL CHEMISTRY BILIRUBIN CALIBRATOR VALUE ASSIGNMENT PROCESS WAS INADEQUATE CAUSING LOW AND HIGH RESULTS ON PATIENT SAMPLES AND (B)(4) SURVEYS. ABBOTT CLINICAL CHEMISTRY BILIRUBIN CALIBRATOR IS USED ON THE AEROSET AND ARCHITECT CSYSTEM TO CALIBRATE TOTAL AND DIRECT BILIRUBIN. ABBOTT CUSTOMERS REPORTED THE FOLLOWING ISSUES FOR CLINICAL CHEMISTRY BILIRUBIN CALIBRATOR: LOW BIAS FOR TOTAL BILIRUBIN QUALITY CONTROL (QC) AND PATIENT RESULTS WITH BILIRUBIN CALIBRATOR LOT NUMBER CHANGE RESULTS TRENDING LOW WITH PROFICIENCY SURVEY SAMPLES. INVESTIGATION OF THESE ISSUES DETERMINED THAT THE CALIBRATOR VALUES ASSIGNED TO THE TOTAL BILIRUBIN REAGENT ((B)(4) AND (B)(4)) CAUSED RESULTS TO TREND DOWNWARD OVER THE PAST SEVERAL CALIBRATOR LOT NUMBERS. WITH A CHANGE FROM CALIBRATOR LOT 38436M100 TO LOT 41456M100 A BIAS OF (-) 7% TO 3% WAS OBSERVED. WITH A CHANGE FROM CALIBRATOR LOT 38436M100 TO LOT 42396M100 A BIAS OF (-) 4% TO 2% WAS OBSERVED. WITH A CHANGE FROM CALIBRATOR LOT 38436M100 TO LOT 48616M100 A BIAS OF (-) 5.5% TO 3.2% WAS OBSERVED. ON (B)(4) 2007 A (B)(4) LETTER ((B)(4)) WAS ISSUED TO ADDRESS BILIRUBIN LOW RECOVERY COMPLAINTS AND PROVIDED CUSTOMERS WITH NEW BILIRUBIN VALUES FOR ALL ON-MARKET CALIBRATOR LOTS. THE NEW BILIRUBIN VALUES WERE ASSIGNED USING THE SECONDARY STANDARD ((B)(4)). (B)(4) PREPARATION WAS IDENTIFIED AS A SOURCE OF VARIABILITY. THE (B)(4) MINIMIZED LOT-TO-LOT VARIABILITY IN THE VALUE ASSIGNMENT PROCESS. FOLLOWING THE USE OF (B)(4) AS A STANDARD FOR THE ASSIGNMENT FOR THE BILIRUBIN CALIBRATOR, AN INCREASE IN CUSTOMER COMPLAINTS FOR HIGH RESULTS FOR TOTAL BILIRUBIN REAGENTS ((B)(4) AND (B)(4)) WAS OBSERVED: HIGHER THAN EXPECTED RESULTS ON PROFICIENCY SURVEY SAMPLES, HIGHER THAN EXPECTED QUALITY CONTROL (QC) RECOVERY, HIGHER THAN EXPECTED PATIENT RESULTS. AN INVESTIGATION WAS INITIATED FOR THE TOTAL BILIRUBIN REAGENTS ((B)(4) AND (B)(4)) WHICH DETERMINED THAT THE MATRIX OF THE SECONDARY STANDARD USED IN THE VALUE ASSIGNMENT OF THE CALIBRATOR IS SENSITIVE TO THE (B)(4) IN THE ABBOTT TOTAL BILIRUBIN REAGENTS ((B)(4) AND (B)(4)). THE MATRIX OF THIS SECONDARY STANDARD CAUSED A POSITIVE BIAS. BECAUSE OF THESE FINDINGS, A NEW TOTAL BILIRUBIN CALIBRATOR VALUE ASSIGNMENT PROCESS WAS IMPLEMENTED FOR USE WITH THE TOTAL BILIRUBIN REAGENTS. THE REVISED VALUES LOWERED TOTAL BILIRUBIN RESULTS UP TO 18%. THERE IS NO ESTABLISHED REFERENCE METHOD FOR TOTAL BILIRUBIN, HOWEVER LITERATURE REFERENCES DOCUMENT ONGOING EFFORTS OF STANDARDIZATION. ABBOTT HAS SELECTED A TOTAL BILIRUBIN CALIBRATOR VALUE ASSIGNMENT PROCESS USED BY (B)(4) FOR (B)(4) SURVEY SAMPLES. ACCURACY OF THE NEW PROCESS WAS CONFIRMED USING THE (B)(4) MODIFIED BY (B)(4). THE IMPROVED VALUE ASSIGNMENT PROCEDURE REMAINS TRACEABLE TO (B)(4) AND DEMONSTRATES MINIMAL SENSITIVITY TO MATRIX VARIABILITY. ALIGNMENT OF THE STANDARDIZATION DIRECTLY TO THE (B)(4) WITH CONFIRMATION OF TOTAL BILIRUBIN COMMUTABILITY TO THE (B)(4) METHOD IMPROVES THE VALUE ASSIGNMENT ACCURACY. THE ROOT CAUSE WAS DETERMINED TO BE MATRIX ISSUES FOR TOTAL BILIRUBIN REAGENT ((B)(4)) RELATED TO THE COMMUTABILITY OF VARIOUS SAMPLES ((B)(4), (B)(4), BILIRUBIN CALIBRATOR, AND PATIENT SAMPLES) DUE TO THE PRODUCTION MATERIALS USED, E.G. HUMAN SERUM ALBUMIN (HSA) VS. BOVINE SERUM ALBUMIN (BSA). THIS MATRIX EFFECT WAS RESPONSIBLE FOR THE OVER-RECOVERY OBSERVED BY CUSTOMERS DURING THE CONVERSION TO THE (B)(4). THE CAUSE OF THIS ISSUE WAS CONFIRMED THROUGH TESTING PERFORMED USING AN EXTERNAL REFERENCE (B)(4) AND (B)(4) METHOD. AS A CORRECTIVE/PREVENTIVE MEASURE ALL ON-MARKET BILIRUBIN CALIBRATOR LOTS WERE RE-VALUE ASSIGNED PER THE NEW VALUE ASSIGNMENT PROCEDURE PROVIDING IMPROVED ACCURACY FOR TOTAL BILIRUBIN REAGENTS. THESE VALUES WERE COMMUNICATED IN THE CUSTOMER LETTER THAT WAS ISSUED ON (B)(4) 2008 ((B)(4)). IN ADDITION, ABBOTT (B)(4) HAS RE-WRITTEN AND VALIDATED THE PROCEDURE FOR BILIRUBIN CALIBRATOR. VALUE ASSIGNMENT AND VALUE VERIFICATION THAT INCLUDE: CLARIFIED PROCEDURE FOR PRIMARY (B)(4) PREPARATION AND INCREASING REPLICATES TO IMPROVING ACCURACY; REVALIDATED THE PROCEDURE. REASSIGNED OF (B)(4) USING IN-HOUSE PREPARED (B)(4) TO ALLOW FOR LESS VARIABILITY FROM ONE ASSIGNMENT TO ANOTHER. ASSIGNED THE VALUES FOR BILIRUBIN CALIBRATOR USING REASSIGNED (B)(4) BY IN-HOUSE PREPARED (B)(4) PER (B)(4) AND (B)(4) METHOD. THIS IS THE FINAL REPORT.

    Additional Manufacturer Narrative · 1

    THIS IS AN INITIAL REPORT. AN INVESTIGATION IS IN PROCESS. A FINAL REPORT WILL BE SUBMITTED WHEN THE INVESTIGATION IS COMPLETE.

    Description of Event or Problem · 1

    THE CUSTOMER STATED THAT PHYSICIANS HAVE NOTED THAT NEONATAL TOTAL BILIRUBIN RESULTS HAVE BEEN HIGH, RUNNING IN THE TEENS. BILIRUBIN REAGENT LOT NUMBER 6L45 AND BILIRUBIN CALIBRATOR LOT NUMBER 57919M100 WERE IN USE. THE CUSTOMER WAS USING HIS OWN CALIBRATOR ASSIGNMENT VALUES BECAUSE THE ASSIGNMENTS PROVIDED TO HIM AS PART OF 2007 WERE TOO HIGH. THE CUSTOMER IS AWARE THAT HE IS RUNNING NEONATE TOTAL BILIRUBIN OUTSIDE LABEL CLAIMS. OTHER BILIRUBIN ASSAYS AND QUALITY CONTROL MATERIALS ARE PERFORMING AS INTENDED. HOWEVER, THE CUSTOMER STILL FEELS THAT RESULTS ARE STILL ABOUT 10 PERCENT TOO HIGH BASED ON HIS OWN VALUE ASSIGNMENTS. NO PATIENT DATA IS AVAILABLE, AND SAMPLES HAVE NOT BEEN RUN WITH AN ALTERNATE METHODOLOGY. THE CUSTOMER HAS ALERTED PHYSICIANS THAT ANY RESULTS IN THE 20S WILL BE SENT OUT FOR CONFIRMATION IF REQUESTED. THE CUSTOMER FOLLOWED UP WITH ABBOTT TO REPORT THAT HE HAS MADE ADJUSTMENTS TO THE BILIRUBIN CALIBRATOR VALUES ISSUED AS PART OF 2008 AND HAS SINCE HAD NO ISSUES WITH BILIRUBIN RESULTS. NO FURTHER IMPACT TO PATIENT MANAGEMENT WAS REPORTED.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    1 CLINICAL CHEMISTRY BILIRUBIN CALIBRATOR FOR USE IN THE CALIBRATION OF THE CLINICAL CHEMISTRY BILIRUBIN ASSAY JIX ABBOTT MANUFACTURING, INC. NA 57919M100

    Patients

    Seq Age Sex Outcome Treatment
    1 NI ARCHITECT C8000 ANALYZER (B)(4)| ARCHITECT C8000 ANALYZER (B)(4)