COBAS TAQSCREEN MPX TEST

Description of Event or Problem

A CUSTOMER LAB FROM (B)(6) REPORTED THAT A (B)(6) DONOR SAMPLE GENERATED A (B)(6) MPX RESULT IN BOTH POOLS OF 6 AND INDIVIDUAL DONATION TESTING USING THE COBAS TAQSCREEN MPX TEST-CE-IVD (M/N 0458244190; BATCH 085458). NO DONOR INFORMATION HAS BEEN PROVIDED. THE SAMPLE WILL BE SENT FOR SEQUENCING ANALYSIS.

Additional Manufacturer Narrative

A DEFINITIVE CONCLUSION CANNOT BE DRAWN AT THIS TIME, AS THE INVESTIGATION INTO THIS ISSUE IS ONGOING. THE OUTCOME OF THE INVESTIGATION WILL BE COMMUNICATED THROUGH A FOLLOW-UP REPORT. THE ASSOCIATED US KIT IS M/N 04584252190, BL 125255. (B)(4).

Additional Manufacturer Narrative

DEVICE EVALUATED BY MANUFACTURER: YES. RESULT: DEVICE PERFORMED ACCORDING TO SPECIFICATION. CONCLUSION: NO FAILURE DETECTED AND PRODUCT WITHIN SPECIFICATIONS. THE CUSTOMER CLAIMS TO HAVE GENERATED A (B)(6) RESULT WITH THE COBAS TAQSCREEN MPX ASSAY FOR BOTH POOLS OF 6 AND POOLS OF 1. THE CUSTOMER STATES THE SAMPLE WAS (B)(6) FOR (B)(6) BY SEROLOGY. UPON REVIEW OF THE CUSTOMER'S DATA, THERE ARE NO TARGET CT VALUES FOR THE SAMPLES IN QUESTION AND THERE IS NO TARGET GROWTH AT ALL OBSERVED. FOR THE RUN USING POOLS OF 6, PERFORMED ON (B)(6) 2012, AN IC CT OF 31.21 WAS OBTAINED. THE RUN PERFORMED ON (B)(6) 2012 WAS WITH THE SAMPLE TESTED AS AN INDIVIDUAL DONATION, AND HAD AN (B)(6). BOTH GROWTH CURVES OF THE IC ARE TYPICAL IN SHAPE AND ARE IN THE TYPICAL RANGE. THE CUSTOMER PERFORMED VIRAL LOAD TESTING USING AN ASSAY WITH A LIMIT OF DETECTION (LOD) OF 40 COPIES/ML AND RECEIVED A RESULT OF "TARGET NOT DETECTED" (TND). THE LOAD OF THE COBAS TAQSCREEN MPX ASSAY IS (B)(6). RETAIN TESTING WAS PERFORMED ON THE COMPLAINT KIT LOT AND MET SPECIFICATION. THE SAMPLE IN QUESTION WAS NOT TESTED WITH THE COMPLAINT KIT, AS THERE WAS INSUFFICIENT VOLUME FOR BOTH REPEAT TESTING USING THE COBAS TAQSCREEN MPX KIT AND PERFORMING SEQUENCING. ALSO, A VIRAL LOAD TEST USING THE COBAS AMPLIPREP/COBAS TAQMAN (CAP/CTM) PLATFORM COULD NOT BE PERFORMED, AS THERE IS NO QUANTIFICATION TEST FOR (B)(6) . ADDITIONAL INVESTIGATION OF NUCLEIC ACID SEQUENCING WAS PERFORMED FOR THE SAMPLE THAT WAS RETURNED. THE SEQUENCING REPORT CONCLUDED THAT NO (B)(6) SEQUENCE DATA COULD BE OBTAINED FROM THE SAMPLE. THE REPORT ALSO STATES THE LACK OF (B)(6) SEQUENCE DOES NOT NECESSARILY MEAN THAT THERE IS NO (B)(6) PRESENT IN THE SAMPLE, AS THE LACK OF VIRAL SEQUENCE COULD BE DUE TO SEQUENCE HETEROGENEITY UNDER THE PRIMERS USED FOR SEQUENCING OR DUE TO THE VIRAL TITERS IN THE SAMPLE BEING TOO LOW FOR AMPLIFICATION PRIOR TO SEQUENCING. BASED ON THE TOTALITY OF THE DATA FROM BOTH THE CUSTOMER SITE AND ROCHE'S INTERNAL INVESTIGATION, THE SAMPLE LIKELY HAS A VERY LOW TITER, AS IT WAS NOT ABLE TO BE DETECTED BY THE COBAS TAQSCREEN MPX ASSAY, THE VIRAL LOAD ASSAY PERFORMED AT THE CUSTOMER SITE, AND DURING SEQUENCING. THIS COULD BE THE REASON THAT THE SAMPLE WAS NOT DETECTED BY THE COBAS TAQSCREEN ASSAY ORIGINALLY, BUT IT IS ALSO POSSIBLE THAT THE SAMPLE MAY CONTAIN SEQUENCE MISMATCHES TO THE TEST'S PRIMERS / PROBES. A PROCEDURAL LIMITATION OF THE ASSAY IS LISTED ON THE COBAS TAQSCREEN MPX PACKAGE INSERT ( M/N 04788397001-05, 2/2009, REVISION 3.0) WHICH STATES "THOUGH RARE, MUTATIONS WITHIN THE HIGHLY CONSERVED REGIONS OF THE VIRAL GENOMES COVERED BY THE COBAS TAQSCREEN MPX TEST PRIMERS AND/OR PROBES MAY RESULT IN FAILURE TO DETECT A VIRUS." (B)(4).