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Patient 1
(B)(4), CONCOMITANT MEDICAL PRODUCTS: ANALYZER SERIAL# (B)(4). EXPLANATION OF OTHER CONCLUSION: 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 SYSTEM 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 (LIST 6L45 AND 8G62) 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 PRODUCT CORRECTION LETTER (FA10AUG2007) 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) STANDARD PREPARATION WAS IDENTIFIED AS A SOURCE OF VARIABILITY. THE (B)(4) STANDARD 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 (06L45 AND 08G62) 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 (LN 8G62 AND LN 6L45) WHICH DETERMINED THAT THE MATRIX OF THE SECONDARY STANDARD USED IN THE VALUE ASSIGNMENT OF THE CALIBRATOR IS SENSITIVE TO THE (B)(4) METHOD IN THE ABBOTT TOTAL BILIRUBIN REAGENTS (LN 8G62 AND LN 6L45). 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 THE (B)(4) FOR NEONATAL PROFICIENCY SURVEY SAMPLES. ACCURACY OF THE NEW PROCESS WAS CONFIRMED USING THE (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) STANDARD, (B)(4) STANDARD, 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) STANDARD. THE CAUSE OF THIS ISSUE WAS CONFIRMED THROUGH TESTING PERFORMED USING AN EXTERNAL REFERENCE (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 (FA12SEP2008 REVISION 01). 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) STANDARD PREPARATION AND INCREASING REPLICATES TO IMPROVING ACCURACY; REVALIDATED THE PROCEDURE. REASSIGNED OF (B)(4) STANDARDS USING IN-HOUSE PREPARED (B)(4) STANDARD TO ALLOW FOR LESS VARIABILITY FROM ONE ASSIGNMENT TO ANOTHER. ASSIGNED THE VALUES FOR BILIRUBIN CALIBRATOR USING REASSIGNED (B)(4) STANDARDS BY IN-HOUSE PREPARED (B)(4) METHOD. THIS IS THE FINAL REPORT.