COBAS AMPLIPREP / COBAS TAQMAN HCV, CE IVD

Description of Event or Problem

A CUSTOMER SITE IN (B)(6) REPORTED THAT TWO PATIENT SAMPLES WERE UNDER-QUANTITATED WITH THE COBAS AMPLIPREP / COBAS TAQMAN HCV TEST, CE IVD (CAP/CTM HCV) WHEN COMPARED TO THE TEST RESULTS GENERATED WITH THE (B)(4).

Additional Manufacturer Narrative

DEVICE EVALUATED BY MANUFACTURER: TESTING OF THE RETENTION MATERIAL WAS NOT PERFORMED FOR THE FOLLOWING REASONS: QUALITY CONTROL KIT RELEASE TESTING WAS VALID AND MET SPECIFICATIONS, A COMPLAINT HISTORY ANALYSIS INDICATED THAT NO OTHER COMPLAINTS WERE FILED AGAINST THE COMPLAINT KIT LOT FOR THIS REPORTED ISSUE AND THE PROBLEMATIC SAMPLES WERE NOT RETURNED FOR EXAMINATION. METHOD: QUALITY CONTROL KIT RELEASE TESTING DATA WAS REVIEWED AND A COMPLAINT HISTORY ANALYSIS WAS PERFORMED. THE INTENDED USE OF THE PRODUCT IS FOR THE MONITORING OF HCV-RNA VIROLOGIC RESPONSE IN PATIENTS RECEIVING ANTIVIRAL THERAPY, IN CONJUNCTION WITH OTHER CLINICAL AND LABORATORY MARKERS. THERE ARE TWO POTENTIAL MEDICAL RISKS ASSOCIATED WITH THE DISCREPANT RESULTS OBSERVED WITH THESE SAMPLES. THE FIRST RISK WOULD BE ASSOCIATED WITH AN INACCURATE BASELINE ASSESSMENT OF HIGH VIRAL LOAD (HVL) VERSUS LOW VIRAL LOAD (LVL), BASED ON THE THRESHOLDS ESTABLISHED IN THE CURRENT TREATMENT GUIDELINES (400-800,000 IU/ML). DISCREPANT DETERMINATION OF BASELINE VIRAL LOAD STATUS COULD RESULT IN A CLINICIAN INAPPROPRIATELY ALTERING THE DURATION OF THERAPY IN CERTAIN SUBSETS OF PATIENTS, BASED ON SOME OF THE TREATMENT GUIDELINES AND THE EMEA LABELING OF PEGINTERFERON/RIBAVIRIN TREATMENT. THE RISK ASSOCIATED WITH THIS SCENARIO WOULD BE EITHER EARLY TERMINATION OF TREATMENT POSSIBLY COMPROMISING TREATMENT RESPONSE OR UNNECESSARY EXPOSURE TO MEDICATIONS WITH SIGNIFICANT TOXICITY. SAMPLE C327 COULD FALL INTO THIS CATEGORY. THE SECOND RISK IS ASSOCIATED WITH INACCURATE DETERMINATION OF A 2 LOG REDUCTION FROM BASELINE AT WEEK 12 (EARLY VIROLOGIC RESPONSE OR EVR). AGAIN, DISCREPANT DETERMINATION OF EVR COULD RESULT IN A CLINICIAN INAPPROPRIATELY ALTERING THE DURATION OF THERAPY OR UNNECESSARY EXPOSURE TO TOXIC MEDICATIONS. BOTH SAMPLES COULD FALL INTO THIS CATEGORY DEPENDING ON THE BASELINE VIRAL LOAD. IT IS UNKNOWN WHETHER THE PATIENTS FROM WHOM THE SAMPLES WERE OBTAINED WERE RECEIVING ANTIVIRAL TREATMENT. ANY USE OUTSIDE THE CONTEXT OF MONITORING ANTIVIRAL THERAPY IS NOT WITHIN THE INTENDED USE OF THE PRODUCT AND MEDICAL RISK CANNOT BE ASSESSED FOR THESE SITUATIONS. FOR BOTH OF THESE SAMPLES, THE CUSTOMER INDICATED THAT THEY REPORTED THE CAP/CTM HCV TEST RESULTS TO THE PHYSICIAN; HOWEVER, IT IS UNKNOWN IF THESE TEST RESULTS RESULTED IN ANY CHANGE TO PATIENT TREATMENT. THERE WAS NO PATIENT HISTORY INFORMATION PROVIDED; THEREFORE, THE EXPECTED PATIENT RESULTS ARE UNKNOWN. NO RAW DATA WAS PROVIDED FOR CAP/CTM HCV ASSAY, SO THERE WERE NO GROWTH CURVES TO EVALUATE FOR POSSIBLE SUPPRESSION OR GROWTH CURVE ANOMALIES. ADDITIONALLY, NO SAMPLES WERE SUBMITTED FOR INVESTIGATION TO NO DETERMINATION OF SEQUENCE MISMATCHES COULD BE PERFORMED. THE CAP/CTM HCV PACKAGE INSERT INCLUDES THE FOLLOWING 2 KNOWN PROCEDURAL LIMITATIONS: THOUGH RARE, MUTATIONS WITHIN THE HIGHLY CONSERVED REGIONS OF THE VIRAL GENOME COVERED BY THE TEST'S PRIMERS AND/OR PROBE MAY RESULTS IN UNDER-QUANTITATION OF OR FAILURE TO DETECT THE VIRUS. DUE TO INHERENT DIFFERENCES BETWEEN TECHNOLOGIES, IT IS RECOMMENDED THAT, PRIOR TO SWITCHING FROM ONE TECHNOLOGY TO THE NEXT, USERS PERFORM METHOD CORRELATION STUDIES IN THEIR LABORATORY TO QUANTIFY TECHNOLOGY DIFFERENCES. ALTHOUGH THE CUSTOMER REPORTED THAT DISCREPANT RESULTS (UNDER-QUANTITATED) WERE GENERATED, THERE WAS NO INDICATION OF A PRODUCT NON-CONFORMANCE DURING INVESTIGATIVE TESTING, QC RELEASE TESTING, STABILITY TESTING OR COMPONENT TESTING. AS ADDITIONAL INFORMATION REGARDING TREATMENT, CUSTOMER USE, SAMPLE SEQUENCE AND RAW DATA WERE UNAVAILABLE, FURTHER INVESTIGATION WAS NOT POSSIBLE. (B)(4).