DIMENSION®

Additional Manufacturer Narrative

THE SIEMENS HEALTHCARE DIAGNOSTICS HEADQUARTERS SUPPORT CENTER (HSC) HAS EVALUATED THE INFORMATION PROVIDED BY THE CUSTOMER AND EXAMINED THE INSTRUMENT LOG DATA FOR THE DISCORDANT LOW TACROLIMUS (TAC) RESULTS. THE CUSTOMER LABORATORY REPORTED THAT THE ISSUE WAS ISOLATED TO THIS INDIVIDUAL PEDIATRIC PATIENT'S SAMPLES AND NOT SAMPLES FROM OTHER PATIENTS. NO INSTRUMENT ISSUES WERE REPORTED OR OBSERVED IN THE INSTRUMENT LOG DATA. SOME SAMPLE HANDLING ISSUES WERE OBSERVED IN THE INSTRUMENT LOG DATA, HOWEVER THEY COULD NOT BE CORRELATED WITH THE REPORTED ISSUE. THE CUSTOMER STATED THAT THIS PEDIATRIC PATIENT'S SAMPLES WERE COLLECTED IN 3 ML ETHYLENEDIAMINETETRAACETIC ACID (EDTA) TUBES. THE TUBES WERE CONSISTENTLY UNDERFILLED WITH APPROXIMATELY 1 ML OF BLOOD. THE VOLUME WAS ESTIMATED, NOT MEASURED, AND COULD BE 0.5 TO 1 ML. UNDER FILLING EDTA TUBES INCREASES THE CONCENTRATION OF EDTA IN THE ALIQUOT OF WHOLE BLOOD TESTED FOR TAC. INCREASED CONCENTRATIONS OF EDTA CAUSE FALSELY LOW TAC VALUES. THE TAC IFU STATES THE NON-INTERFERENCE LEVEL OF EDTA IS 3 MG/ML. THIS VALUE IS HIGHER THAN THE CONCENTRATION IN COMMERCIALLY AVAILABLE COLLECTION TUBES UNLESS THEY ARE UNDER FILLED. COLLECTION TUBE EDTA CONCENTRATION IS APPROXIMATELY 1.8 MG/ML FOR AN APPROPRIATELY FILLED COLLECTION TUBE. EDTA CONCENTRATIONS EXCEEDING 3 MG/ML WILL DEPRESS TAC RESULTS. A COLLECTION TUBE WITH 0.5 TO 1 ML OF BLOOD COLLECTED WOULD HAVE A EDTA CONCENTRATION IN THE RANGE OF 5.4 TO 10.8 MG/ML. THE DIMENSION® TACROLIMUS FLEX® REAGENT CARTRIDGE (TAC) INSTRUCTIONS FOR USE STATES: FOLLOW THE INSTRUCTIONS PROVIDED WITH YOUR SPECIMEN COLLECTION DEVICE FOR USE AND PROCESSING. WHOLE BLOOD CAN BE COLLECTED USING RECOMMENDED PROCEDURES FOR COLLECTION OF DIAGNOSTIC BLOOD SPECIMENS BY VENIPUNCTURE. THE FINAL CONCLUSION FROM SIEMENS IS THAT THE PRODUCT WAS PERFORMING AS DESIGNED AT THE TIME OF TESTING. FALSELY LOW TAC (TACROLIMUS) VALUES WERE CONSISTENTLY OBTAINED ON ONE PEDIATRIC PATIENT DUE TO PHLEBOTOMIST UNDER FILLING OF THE PATIENT'S EDTA COLLECTION TUBES DURING BLOOD COLLECTION. AS OF 2/6/2017 THE CUSTOMER REPORTED FURTHER INFORMATION ON THE STATUS OF THE PATIENT. THEY STATED THAT AFTER STOPPING THE ADMINISTRATION OF TACROLIMUS, THE 10 MONTH OLD BLOOD TUMOR PATIENT BECAME A COMPLETE REMISSION AND WAS DISCHARGED FROM THE HOSPITAL. IN ADDITION, THE CUSTOMER PROVIDED INFORMATION THAT THE SAMPLES WERE COLLECTED VIA THE LINE CONNECTED TO A PERIPHERAL CENTRAL VENOUS CATHETER.

Additional Manufacturer Narrative

INITIAL MDR 2517506-2016-00561 WAS FILED 28-DEC-2016. 2517506-2016-00561 SUPPLEMENT 1 WAS FILED 10-FEB-2017. 2517506-2016-00561 SUPPLEMENT 2 WAS FILED 31-MAR-2017. MDR 2517506-2016-00561 SUPPLEMENT 2 INADVERTENTLY DOCUMENTED IN ERROR THAT "SIEMENS HEADQUARTERS SUPPORT CENTER IS INVESTIGATING THE INCIDENT."

Additional Manufacturer Narrative

INITIAL MDR WAS FILED ON 12/28/2016. SUPPLEMENT 1 WAS FILED ON 2/10/2017. UPDATE - SIEMENS HEALTHCARE DIAGNOSTICS HAS OBTAINED CORRECTED INFORMATION AFTER WE REQUESTED ADDITIONAL CLARIFICATION FROM OUR REGIONAL UNIT IN (B)(4) ON 3/13/2017. REQUESTED CLARIFICATION WAS RECEIVED BETWEEN 3/13/2017 AND 3/17/2017 THE FOLLOWING INFORMATION PROVIDED IN THE ORIGINAL MDR (SEE BELOW) WAS INCORRECT. FROM INITIAL MDR - TACROLIMUS RESULTS (B)(6) 2016 (NG/ML), INITIAL RESULT, (SAMPLE 1): LESS THAN 0.1 NG/ML, TACROLIMUS DOSAGE WAS INCREASED. RESULT ON NEW SAMPLE (SAMPLE 2): 5 NG/ML. THE FIELD ENGINEER COULD NOT CONFIRM THE DATES THAT THE RESULTS ABOVE WERE OBTAINED AND THE SAMPLE IDENTIFICATION NUMBERS ORIGINALLY PROVIDED AS SAMPLE 1 AND SAMPLE 2 FROM (B)(6) 2016 IN THE ORIGINAL MDR. THE REGIONAL UNIT HAS PROVIDED THE FOLLOWING CONFIRMED SAMPLE IDENTIFICATION NUMBERS (SIDS), DATES OF TESTING, AND RESULTS FROM THIS PATIENT: (B)(6). CORRECTION FROM PREVIOUS INFORMATION - THE PATIENT TACROLIMUS DOSAGE WAS INCREASED ON (B)(6) 2016 AND THEN AGAIN ON (B)(6) 2016. TACROLIMUS DOSING WAS DISCONTINUED (B)(6) 2016. IN ADDITION THE FIELD ENGINEER COULD NOT CONFIRM THE SID NUMBER FOR SAMPLE 1 THAT WAS TESTED BY LC/MS IN THE INITIAL INFORMATION SUBMITTED IN THE ORIGINAL MDR. THEY WERE ABLE TO DEFINE THAT SAMPLE 2 THAT WAS TESTED BY LCMS ON (B)(6) 2016 WAS (B)(6). THE RESULTS ON THE LC/MS WERE REGARDED AS CORRECT BY THE PHYSICIAN. PER INFORMATION PROVIDED BY THE EDTA TUBE MANUFACTURER CUSTOMER SUPPORT DEPARTMENT, THE EDTA TUBE CONTAINED LIQUID SOLUTION. THE EDTA TUBE CONTAINS 50 MICROLITERS OF A 15%W/V LIQUID SOLUTION OF EDTA-3K.2H2O. SIEMENS HEADQUARTERS SUPPORT CENTER IS INVESTIGATING THE INCIDENT.

Additional Manufacturer Narrative

THE CUSTOMER CONTACTED THE SIEMENS CUSTOMER CARE CENTER (CCC). THE CAUSE OF THE DISCORDANT, LOW TAC RESULTS IS UNKNOWN. THE ACCOUNT DISCONTINUED THE TAC DOSAGE ON THE BASIS OF THE HIGHER RESULTS OBTAINED BY THE ALTERNATE METHODOLOGY, LC/MS. ALTHOUGH THERE WAS AN INDICATION THAT SOME RENAL DYSFUNCTION HAD OCCURRED, THE LATEST UPDATE FROM THE ACCOUNT IS THAT THE STATUS OF THE PATIENT IS IMPROVING. SIEMENS HEADQUARTERS SUPPORT CENTER IS INVESTIGATING THE INCIDENT.

Description of Event or Problem

DISCORDANT, LOW TACROLIMUS (TAC) RESULTS WERE OBTAINED ON ONE PATIENT'S SAMPLES ON THE DIMENSION XPAND PLUS INSTRUMENT. THE RESULTS WERE REPORTED TO THE PHYSICIAN. THE SAMPLES WAS RETESTED BY AN ALTERNATE METHODOLOGY (LCMS) AND HIGHER RESULTS WERE OBTAINED. THE PATIENT TACROLIMUS DOSAGE WAS INCREASED ON THE BASIS OF THE INITIAL LOW RESULTS. THERE WAS SOME INDICATION THAT RENAL DYSFUNCTION OCCURRED DUE TO THE INCREASE OF DOSAGE.