ADVIA CHEMISTRY IMMUNOGLOBULIN M_2 REAGENTS (IGM_2)

Additional Manufacturer Narrative

A SIEMENS REGIONAL APPLICATION SPECIALIST (RAS) REVIEWED THE REACTION CURVES AND DATA PROVIDED BY THE CUSTOMER AND DETERMINED THAT THE FALSELY LOW IGM_2 RESULTS MAY HAVE BEEN PRODUCED BY SOME INHIBITORY AGENT PRESENT WITHIN THE SAMPLE. THE MANUAL PRE-DILUTION OF THE SAMPLE REDUCES THE EFFECT OF THE INTERFERENCE AND ALLOWS THE TRUE ELEVATED VALUE TO BE MEASURED. THE ADVIA 2400 INSTRUMENT DID NOT GENERATE ANY ERRORS ON THE INITIAL RESULT BECAUSE THE REACTION CURVE SHOWS NO ABNORMALITIES. IT ALSO SHOWS THAT THERE WAS NO PROZONE OR HOOK EFFECT AND THAT THE FALSELY LOW IGM_2 RESULTS WERE NOT OBTAINED DIRECTLY DUE TO AN ANTIGEN EXCESS. THE RAS SPECIALIST CONCLUDED THAT THE POSSIBLE CAUSES OF THE DISCORDANT RESULTS COULD BE STERIC HINDRANCE BY HIGH PROTEIN CONCENTRATION OR NON-SPECIFIC BINDING OF ANTIBODIES IN IGM_2 REAGENT TO SOME SPECIFIC AGENT PRESENT IN THE SAMPLE OR SOME OTHER PARA-PROTEIN SUCH AS PRESENCE OF HUMAN ANTI-GOAT ANTIBODIES. THE ADVIA 2400 IGM_2 METHOD USES GOAT ANTI-HUMAN IGM ANTIBODIES. IF THE PATIENT HAS BEEN EXPOSED TO GOATS THEY MAY HAVE ANTI-GOAT ANTIBODIES PRESENT IN THEIR BLOOD. IF THIS IS THE CAUSE, OTHER IGM_2 RESULTS ON THE ADVIA 2400 INSTRUMENT MAY ALSO BE FALSELY LOW. A REGIONAL SUPPORT CENTER SPECIALIST STATED THAT THE QUALITY CONTROLS AND OTHER PATIENT SAMPLES FOR IGM_2 HAVE BEEN RECOVERING REPRODUCIBLY. THEREFORE, THIS SAMPLE APPEARS TO BE AN ISOLATED INCIDENT. THE CAUSE OF THE DISCORDANT, FALSELY LOW IGM_2 RESULTS ON ONE PATIENT SAMPLE IS UNKNOWN. THE DEVICE IS PERFORMING WITHIN MANUFACTURING SPECIFICATIONS. NO FURTHER EVALUATION OF DEVICE IS REQUIRED.

Description of Event or Problem

DISCORDANT, FALSELY LOW IMMUNOGLOBULIN M_2 (IGM_2) RESULTS WERE OBTAINED ON ONE PATIENT SAMPLE WHEN RUN NEAT ON AN ADVIA 2400 INSTRUMENT, WHILE USING REAGENT LOT 411515. THE SAMPLE WAS MANUALLY DILUTED WITH 1:10 DILUTION FACTOR AND REPEATED TWICE IN DUPLICATE ON THE SAME INSTRUMENT, RESULTING HIGHER EACH TIME. THE DISCORDANT RESULTS WERE REPORTED TO THE PHYSICIAN(S), WHO QUESTIONED THEM. THE CORRECTED RESULTS WERE REPORTED TO THE PHYSICIAN(S). THERE ARE NO REPORTS OF PATIENT INTERVENTION OR ADVERSE HEALTH CONSEQUENCE DUE TO THE DISCORDANT, FALSELY LOW IGM_2 RESULTS.

Additional Manufacturer Narrative

THE INITIAL MDR WAS FILED ON JULY 20, 2017. ADDITIONAL INFORMATION (08/04/20170): ADDITIONAL INFORMATION HAS BEEN RECEIVED REGARDING PATIENT DATA. THERE WAS AN ADDITIONAL VALUE OBTAINED ON THE ADVIA 2400 INSTRUMENT UPON DILUTION, RESULTING AS 22 G/L. ALSO, THE CUSTOMER HAD TESTED THE SAMPLE ON THE ALTERNATE METHODOLOGY, WHICH RESULTED HIGH. . ADDITIONAL INFORMATION (08/08/2017): A SIEMENS HEADQUARTERS SUPPORT CENTER SPECIALIST REVIEWED THE EVENT DATA AND CONCLUDED THAT THIS IS NOT A METHOD OR REAGENT LOT ISSUE. THE SYSTEM IS FUNCTIONING AS DESIGNED. QUALITY CONTROL WAS WITHIN ACCEPTABLE RANGE AND ONLY ONE SAMPLE WAS IMPACTED. THIS DATA IS CONSISTENT WITH INTERFERENCE, HOWEVER, THE INTERFERENCE COULD NOT BE DETERMINED WITH THE INFORMATION AVAILABLE. AS PER ADVIA CHEMISTRY IMMUNOGLOBULIN M_2 (IGM_2) INSTRUCTIONS FOR USE STATE, A NUMBER OF SUBSTANCES CAUSE PHYSIOLOGICAL CHANGES IN SERUM ANALYTE CONCENTRATIONS. AS WITH ANY CHEMICAL REACTION, THE CUSTOMER MUST BE ALERT TO THE POSSIBLE EFFECT ON RESULTS OF UNKNOWN INTERFERENCES FROM MEDICATIONS OR ENDOGENOUS SUBSTANCES. THE LABORATORY AND PHYSICIAN MUST EVALUATE ALL PATIENT RESULTS IN LIGHT OF THE TOTAL CLINICAL STATUS OF THE PATIENT. THE SYSTEM AND ASSAY IS WORKING AS SPECIFIED. CORRECTED INFORMATION (08/04/2017): THE INITIAL REPORT STATED THAT THE "DATE OF EVENT" AND "DATE RECEIVED BY MANUFACTURER" WERE (B)(6) 2017. THE CORRECT DATES ARE (B)(6) 2017 AND (B)(6) 2017 RESPECTIVELY. CORRECTED INFORMATION (08/23/2017): THE INITIAL MDR, STATED THAT THE NEAT RESULTS OBTAINED ON THE PATIENT SAMPLE FOR IGM_2 ON THE ADVIA 2400 INSTRUMENT WERE 2.27 AND 2.32 G/L. THERE WAS ANOTHER NEAT VALUE OBTAINED WITH THE NEAT RUN I.E. 2.8 G/L. . MDR 2432235-2017-00505 WAS FILED FOR THE SAME EVENT.

Description of Event or Problem

ON (B)(6) 2017, A DISCORDANT, FALSELY LOW IMMUNOGLOBULIN M_2 (IGM_2) RESULT WAS OBTAINED ON ONE PATIENT SAMPLE WHEN RUN NEAT ON AN ADVIA 2400 INSTRUMENT, WHILE USING REAGENT LOT 411515. ON (B)(6) 2017, THE SAMPLE WAS ANALYZED USING AN ALTERNATE METHODOLOGY, RESULTING HIGH AND INDICATIVE OF HIGH PARAPROTEIN BAND. THE CUSTOMER CONFIRMED THE HIGH RESULT BY REPEATING THE SAMPLE ON THE ALTERNATE METHODOLOGY. THIS PROMPTED THE CUSTOMER TO REPEAT THE SAMPLE AS NEAT AND WITH DILUTION ON THE ADVIA 2400 INSTRUMENT. THIS IS WHEN THE CUSTOMER DETERMINED THAT THE NEAT RESULTS AND A RESULT OBTAINED UPON INITIAL DILUTION ON THE ADVIA 2400 INSTRUMENT WERE DISCORDANT. THE RESULTS FROM THE ELECTROPHORESIS AND THE RESULTS OBTAINED ON THE ADVIA 2400 INSTRUMENT UPON MANUAL DILUTION WERE CONSIDERED CORRECT. THE DISCORDANT RESULT WAS REPORTED TO THE PHYSICIAN(S), WHO QUESTIONED IT. THE CORRECTED RESULTS WERE REPORTED TO THE PHYSICIAN(S). THERE ARE NO REPORTS OF PATIENT INTERVENTION OR ADVERSE HEALTH CONSEQUENCE DUE TO THE DISCORDANT, FALSELY LOW IGM_2 RESULTS.

Additional Manufacturer Narrative

THE INITIAL MDR 2432235-2017-00432 WAS FILED ON JULY 20, 2017. THE FIRST SUPPLEMENTAL MDR 2432235-2017-00432_S1 WAS FILED ON SEPTEMBER 1, 2017. ADDITIONAL INFORMATION (07/06/2017): A SIEMENS CUSTOMER SERVICE ENGINEER (CSE) WAS DISPATCHED TO THE CUSTOMER SITE. THE CSE PERFORMED A TOTAL SERVICE CALL AND PREVENTIVE MAINTENANCE ON THE INSTRUMENT. THE CSE REPLACED THE SEALS AND SERVICED SAMPLING PUMP, DILUTION DISCHARGE PUMP, SAMPLING WASH PUMP, AND REAGENT DISPENSING PUMP 1. THE CSE ALSO REPLACED THE DRAIN PUMP TUBING AND SERVICED THE VACUUM VALVES. THE CSE FOUND THAT THE SOLENOID VALVE WAS NOT OPENING CORRECTLY, SO HE REPLACED THE VALVE. THE CSE CLEANED THE WASH PORTS AND ION-SELECTIVE ELECTRODE DRAIN, CHECKED THE REACTION WASHER AND DILUTION WASHER ASPIRATIONS AND CLEANED LINES WITH BLEACH. THE REAGENT TEMPERATURES WERE WITHIN RANGE. THE CSE RAN A CLEANING PROCEDURE AND ADDED ADDITIONAL DELTA CHECK MEASURES INTO THE CUSTOMER'S HOST LABORATORY INFORMATION SYSTEM. THE CAUSE OF THE DISCORDANT, FALSELY LOW IGM_2 RESULTS ON ONE PATIENT SAMPLE IS UNKNOWN. ADDITIONAL INFORMATION (09/05/2017): THE RESULT OF 22 G/L WAS OBTAINED WITH MANUAL DILUTION.