APTIMA COMBO 2 ASSAY

Additional Manufacturer Narrative

A NEW CHLAMYDIA TRACHOMATIS (CT) VARIANT HAS BEEN IDENTIFIED THAT AFFECTS THE DETECTION OF CT BY APTIMA COMBO 2® ASSAY ON BOTH TIGRIS® (CATALOG NUMBER 301130) AND PANTHER® INSTRUMENTS (CATALOG NUMBERS 302923 AND 303094). FURTHER, IT IS CONFIRMED THAT THE MUTATION RESIDES IN THE REGION OF THE GENOME DETECTED BY THE AC2 PROBE (IN THE 23S RRNA GENE) WHICH IS DISTINCT FROM THE REGION (16S RRNA GENE) TARGETED BY THE ACT PROBE. THEREFORE, THE PERFORMANCE OF THE ACT ASSAY IS NOT AFFECTED BY THIS MUTATION. THE COMPLAINT IS NOT RELATED TO A MALFUNCTION OF THE PANTHER INSTRUMENT NOR RELATED TO THE PRODUCTION METHODS OF THE ASSAY. HOLOGIC SUBMITTED A FIELD SAFETY CORRECTIVE ACTION (FSCA) IN EUROPE RELATED TO THIS INCIDENT. NO RELATED COMPLAINTS WERE REPORTED IN THE US.

Description of Event or Problem

A CUSTOMER, (B)(6) FROM (B)(6) REPORTED THAT THEY OBTAINED PATIENT SAMPLE RESULTS WITH ELEVATED RLU VALUES (RANGE: 23-35K), WHICH WERE CONSIDERED TO BE CT NEGATIVE/GC NEGATIVE USING THE APTIMA COMBO 2 (AC2) ASSAY. HOWEVER, WHEN SOME OF THESE SAMPLES WERE RETESTED USING THE APTIMA CT ASSAY, THEY PRODUCED CT POSITIVE RESULTS. THE AC2 ASSAY AND THE APTIMA CT ASSAY ARE TWO DIFFERENT ASSAYS. SOME OF THE SAMPLES THAT PRODUCED POSITIVE RESULTS USING THE APTIMA CT ASSAY WERE ALSO TESTED WITH ASSAYS FROM OTHER MANUFACTURERS AND ALSO PRODUCED CT POSITIVE RESULTS. HOLOGIC'S INITIAL REVIEW OF THE DATA IN THE COMPLAINT SUGGESTED THAT THE AFFECTED SAMPLES MAY BE BELOW THE LIMIT OF DETECTION (LOD). BOTH THE AC2 ASSAY PACKAGE INSERT ((B)(4)) AND THE APTIMA CT ASSAY PI ((B)(4)) INDICATE THAT THE LIMIT OF DETECTION (LOD) IS ONE INCLUSION-FORMING UNIT (IFU) PER ASSAY, OR 5 FG CT PER ASSAY. QC RELEASE TESTING FOR BOTH THE AC2 ASSAY AND THE APTIMA CT ASSAY REQUIRES THAT 0.5 FG CT SAMPLES PRODUCE A POSITIVE CT RESULT; THIS CONCENTRATION IS BELOW THE LOD FOR EACH OF THE ASSAYS. THUS, BOTH THE AC2 ASSAY AND THE APTIMA CT ASSAY ARE WORKING WITHIN PACKAGE INSERT CLAIMS. A RISK ASSESSMENT INDICATES THE SEVERITY ASSOCIATED WITH AN INCORRECT RESULT IS SERIOUS BUT PROBABILITY OF OBTAINING AN INCORRECT RESULT FOR A SAMPLE THAT HAS A CT CONCENTRATION AT THE LOD OR ABOVE IS REMOTE. THIS IS MITIGATED SINCE QC RELEASE TESTING REQUIRES THE TESTING OF SAMPLES BELOW THE LOD.

Description of Event or Problem

A CUSTOMER, (B)(6) REPORTED THAT THEY OBTAINED PATIENT SAMPLE RESULTS WITH ELEVATED RLU VALUES (RANGE: 23-35K), WHICH WERE CONSIDERED TO BE CT NEGATIVE/GC NEGATIVE USING THE APTIMA COMBO 2 (AC2) ASSAY. HOWEVER, WHEN SOME OF THESE SAMPLES WERE RETESTED USING THE APTIMA CT ASSAY, THEY PRODUCED CT POSITIVE RESULTS. THE AC2 ASSAY AND THE APTIMA CT ASSAY ARE TWO DIFFERENT ASSAYS. SOME OF THE SAMPLES THAT PRODUCED POSITIVE RESULTS USING THE APTIMA CT ASSAY WERE ALSO TESTED WITH ASSAYS FROM OTHER MANUFACTURERS AND ALSO PRODUCED CT POSITIVE RESULTS. HOLOGIC'S INITIAL REVIEW OF THE DATA IN THE COMPLAINT SUGGESTED THAT THE AFFECTED SAMPLES MAY BE BELOW THE LIMIT OF DETECTION (LOD). BOTH THE AC2 ASSAY PACKAGE INSERT (PI, 502183EN-IFU-PI, REV. 006) AND THE APTIMA CT ASSAY PI (502184EN-IFU-PI, REV. 006) INDICATE THAT THE LIMIT OF DETECTION (LOD) IS ONE INCLUSION-FORMING UNIT (IFU) PER ASSAY, OR 5 FG CT PER ASSAY. QC RELEASE TESTING FOR BOTH THE AC2 ASSAY AND THE APTIMA CT ASSAY REQUIRES THAT 0.5 FG CT SAMPLES PRODUCE A POSITIVE CT RESULT; THIS CONCENTRATION IS BELOW THE LOD FOR EACH OF THE ASSAYS. THUS, BOTH THE AC2 ASSAY AND THE APTIMA CT ASSAY ARE WORKING WITHIN PACKAGE INSERT CLAIMS. A RISK ASSESSMENT INDICATES THE SEVERITY ASSOCIATED WITH AN INCORRECT RESULT IS SERIOUS BUT PROBABILITY OF OBTAINING AN INCORRECT RESULT FOR A SAMPLE THAT HAS A CT CONCENTRATION AT THE LOD OR ABOVE IS REMOTE. THIS IS MITIGATED SINCE QC RELEASE TESTING REQUIRES THE TESTING OF SAMPLES BELOW THE LOD. AN ON-GOING INVESTIGATION IS IN PROCESS AT HOLOGIC REGARDING THIS COMPLAINT.