APTIMA

Additional Manufacturer Narrative

THE LABORATORY THAT CALLED IN THE COMPLAINT INDICATED THAT THE PATIENTS WHO ARE FROM AN ADULT INDUSTRY, WENT TO ANOTHER LABORATORY THAT WAS RUNNING THE ORIGINAL VERSION OF THE APTIMA COMBO 2 ASSAY AND GOT NEGATIVE RESULTS, AND LIKELY NOT TREATED. HOLOGIC DID A PRELIMINARY ASSESSMENT OF PREVALENCE IN THE UNITED STATES. AS OF (B)(6) 2022, HOLOGIC IS AWARE OF SIX CONFIRMED CT VARIANT SAMPLES WITH A MUTATION IN THE RRNA REGION UTILIZED IN THE ORIGINAL VERSION OF THE APTIMA COMBO 2 ASSAY IN THE UNITED STATES. FOR PERSPECTIVE ON POTENTIAL PREVALENCE, HOLOGIC HAS SOLD OVER 130,000,000 TEST OF THE ORIGINAL VERSION OF APTIMA COMBO 2 ASSAY IN THE UNITED STATES SINCE JANUARY 2019.

Description of Event or Problem

CUSTOMER CONTACTED HOLOGIC ON (B)(6) 2022 QUESTIONING AC2 ASSAY RESULT FROM LOT 327730. CUSTOMER WAS RUNNING THE UPDATED APTIMA COMBO 2 ASSAY. CUSTOMER PROVIDED SAMPLES TO HOLOGIC FOR EVALUATION. HOLOGIC PERFORMED TESTING OF THE SAMPLES USING THE UPDATED APTIMA COMBO 2 ASSAY AND CONFIRMED THE POSITIVE RESULTS. THE RESULTS ARE CONSISTENT WITH A CT VARIANT, ALTHOUGH SEQUENCING HAS NOT YET BEEN PERFORMED TO CONFIRM IF THE SAMPLE ARE A CT VARIANT(S).

Description of Event or Problem

FOLLOW-UP REPORT, SEE H10.

Additional Manufacturer Narrative

THE FOLLOWING IS A RESUBMISSION THAT WAS INITIALLY SUBMITTED AS A FOLLOW UP MDR (2024800-2022-01101) ON (B)(6) 2022 BY HOLOGIC. CUSTOMER CONTACTED HOLOGIC ON (B)(6) 2022 QUESTIONING AC2 ASSAY CT POSITIVE RESULTS WHEN USING LOT NUMBER 327730, WHICH IS THE UPDATED APTIMA COMBO 2 ASSAY. THE CUSTOMER INDICATED THAT THE AFFECTED PATIENTS OBTAINED CT NEGATIVE RESULTS FROM A DIFFERENT DIAGNOSTIC SITE. HOLOGIC RECEIVED SAMPLES FROM LAB DIAGNOSTICS FOR EVALUATION ON (B)(6) 2022. INTERNAL TESTING OF THESE SAMPLES WITH THE UPDATED AC2 ASSAY CONFIRMED THE CUSTOMER¿S CT POSITIVE RESULTS. IN ADDITION, HOLOGIC PERFORMED TESTING WITH THE ORIGINAL VERSION OF THE AC2 ASSAY AND THE APTIMA CHLAMYDIA TRACHOMATIS (ACT) ASSAY. THE SAMPLES THAT YIELDED CT POSITIVE RESULTS WITH THE UPDATED AC2 ASSAY YIELDED CT NEGATIVE RESULTS WHEN TESTED WITH THE ORIGINAL VERSION OF THE AC2 ASSAY AND YIELDED CT POSITIVE RESULTS WHEN TESTED WITH THE ACT ASSAY. THESE SAMPLE DATA ARE CONSISTENT WITH CT VARIANT SAMPLES. HOLOGIC SUBSEQUENTLY SEQUENCED THE SAMPLES THAT WERE CT POSITIVE AND THE SEQUENCING RESULTS MATCHED THE SEQUENCE OF THE PREVIOUSLY IDENTIFIED (B)(6) VARIANT. OF NOTE, HOLOGIC PREVIOUSLY IDENTIFIED A PATIENT SAMPLE THAT CONTAINED THE (B)(6) VARIANT IN THE U.S. AND REPORTED THE FINDING TO THE FDA IN MANUFACTURER REPORT NUMBER (MRN) 2024800-2021-00011. A CT VARIANT WITH A MUTATION IN THE ORIGINAL VERSION OF THE AC2 ASSAY CT TARGET SEQUENCE MAY LED TO AN INCORRECT RESULT (FALSE NEGATIVE) OR A CT EQUIVOCAL RESULT. BEGINNING IN 2019, CT VARIANTS WERE IDENTIFIED THAT CONTAIN A MUTATION IN THE ORIGINAL VERSION OF THE AC2 ASSAY CT TARGET SEQUENCE. AS A RESULT, HOLOGIC COMMUNICATED WITH THE FDA REGARDING THE PRESENCE OF THESE CT VARIANTS. SEVERAL RECENT PUBLICATIONS HAVE DEMONSTRATED COMPARABLE PERFORMANCE OF THE ORIGINAL VERSION OF THE AC2 ASSAY WITH OTHER MANUFACTURERS¿ ASSAYS. OF NOTE, HOLOGIC HAS PREVIOUSLY COMMUNICATED TO U.S. LABS ALERTING THEM OF THE UPCOMING TRANSITION TO THE UPDATED AC2 ASSAY VIA (B)(4). HOLOGIC PRODUCT IS PERFORMING AS DESIGNED. THERE WERE NO ISSUES DURING THE MANUFACTURE OF THE PRODUCT.

Description of Event or Problem

FOLLOW-UP REPORT. SEE SECTION H10.

Additional Manufacturer Narrative

SECTION B5: STATED, "FOLLOW-UP REPORT. SEE SECTION H10:." WHEN IT SHOULD HAVE REFERENCED SECTION H11:.

Description of Event or Problem

SEE SECTION H11:.