BEUDAMED
    FDA Adverse Event Malfunction Summary report: N

    ONCOMINE¿ DX EXPRESS TEST

    MDR report key: 25166741 · Received May 13, 2026

    Report

    Report Number
    3003335080-2026-00001
    Event Type
    Malfunction
    Date Received
    May 13, 2026
    Date of Event
    May 11, 2026
    Report Date
    May 13, 2026
    Manufacturer
    LIFE TECHNOLOGIES CORPORATION
    Product Code
    PQP
    UDI-DI
    10190302017305
    PMA / PMN Number
    P240040
    Removal / Correction Number
    3003335080-2026-001C
    Product Problem
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    MD, US
    Reporter Occupation
    003

    Narratives

    Additional Manufacturer Narrative · 0

    THE OVERALL POPULATION USING THE DEVICE INCLUDES ALL INDIVIDUALS TESTED WITH ODXET. FOR THOSE WHO DO NOT HAVE THE FGFR3 VARIANTS PRESENT, THERE ARE NO ASSOCIATED HEALTH RISKS, AND THE RISK ESTIMATE IS "UNLIKELY." THEREFORE, AT THIS TIME CANCERS OTHER THAN BLADDER CANCER WILL BE ASSUMED TO HAVE NO CLINICAL CONSEQUENCES FOR FN FGRF3 ALTERATIONS. THERE IS A POTENTIAL FOR PATIENT HARM WITHIN THE HIGHEST-RISK POPULATION THAT THE DETECTION OF AN FGFR3 C.746C>G P.S249C (COSM715) VARIANT IN THE PATIENT'S TUMOR MAY BE IMPACTED BY LOW TUMOR CONTENT, LOW VARIANT ALLELE FREQUENCY, OR SUBOPTIMAL NUCLEIC ACID QUALITY, THESE OUTCOMES CAN RANGE FROM NO ADVERSE CONSEQUENCES TO EXPERIENCING A NEGATIVE OUTCOME THAT COULD LEAD TO SUBOPTIMAL ONCOLOGIC MANAGEMENT, INCLUDING MISSED OPPORTUNITY FOR TARGETED THERAPY WITH FGFR INHIBITORS, RESULTING IN CONTINUED EXPOSURE TO INEFFECTIVE TREATMENTS, UNNECESSARY TOXICITY AND POTENTIALLY SHORTER SURVIVAL. THEREFORE, THE PROBABILITY OF MEDICALLY REVERSIBLE OR SERIOUS ADVERSE EVENTS AMONG INDIVIDUALS WITH A FALSE NEGATIVE FGFR3 MUTATION RESULT FOR THOSE BLADDER CANCER PATIENTS (THE POPULATION AT GREATEST RISK) IS CONSIDERED TO BE REMOTE. AS IMMEDIATE MITIGATION, CURRENT CUSTOMERS WILL BE WARNED OF THE FGFR3 (COSM715) VARIANT CALLING ISSUE AS WELL AS A RECOMMENDATION TO ENRICH FOR TUMOR CONTENT WHENEVER FEASIBLE. INCREASING TUMOR CONTENT IN THE SAMPLE WILL MINIMIZE THE CHANCE OF A VARIANT NOT BEING DETECTED AS THE AF WILL MORE LIKELY BE HIGHER AND ABOVE THE EXISTING VARIANT CALLING THRESHOLD. LASTLY, AS FGFR3 (COSM715) IN BLADDER CANCER IS A TIER 2 MUTATION, RECOMMENDATIONS WILL BE GIVEN TO CUSTOMERS TO CONSIDER ORTHOGONAL CONFIRMATION OF ANY BLADDER CANCER SAMPLE, ESPECIALLY NON-MUSCLE INVASIVE BLADDER CANCER, THAT IS NEGATIVE FOR ANY VARIANT RESULTS AND TUMOR CONTENT IS NOT ABLE TO BE ENRICHED.FGFR3 S249C IS LESS COMMON IN OTHER CANCER TYPES. (< 0.1% IN BREAST AND LUNG). A LIMITATION/WARNING STATEMENT WILL BE ADDED TO THE USER GUIDES (UGS) TO INFORM CUSTOMERS OF THE POSSIBILITY OF A FALSE-NEGATIVE RESULT FOR THE FGFR3 VARIANT: DETECTION OF AN FGFR3 C.746C>G P.S249C (COSM715) VARIANT IN THE PATIENT'S TUMOR MAY BE IMPACTED BY LOW TUMOR CONTENT, LOW VARIANT ALLELE FREQUENCY, OR SUBOPTIMAL NUCLEIC ACID QUALITY. IN SUCH CASES, THE VARIANT MAY BE PRESENT BELOW THE DETECTION THRESHOLD OF THE ASSAY WHICH WILL RESULT IN A FALSE-NEGATIVE FINDING. AND SHOULD BE FOLLOWED BY ADDITIONAL CONFIRMATORY TESTING. FOR LONGER-TERM MITIGATIONS, WHICH REQUIRE DATA-DRIVEN JUSTIFICATION, REGULATORY ASSESSMENT AND APPROVAL, THE SOFTWARE AND BIOINFORMATICS TEAMS ARE ASSESSING WHETHER LOWERING THE DETECTION THRESHOLD FOR FGFR3 COSM715 FROM 2.5% TO 1% TO IMPROVE DETECTION SENSITIVITY FOR THIS TARGET. IF PROVEN, A RE-EVALUATION OF THE ESTIMATED LOD WILL NEED TO BE PERFORMED AND A PANEL-WIDE ASSESSMENT IMPACT AND ANY POTENTIAL INCREASED RISK FOR FALSE POSITIVES FOR THIS TARGET. IF SUFFICIENT DATA JUSTIFICATION IS PROVIDED AND REGULATORY APPROVAL FOR THE STRATEGY IS APPROVED, A NEW HOTSPOT FILE/ASSAY DEFINITION FILE (ADF) AND POTENTIALLY UPDATED PRODUCT LABELING WILL NEED TO BE DEVELOPED AND IMPLEMENTED FOR CUSTOMERS. SHOULD AN ALTERNATE LONG-TERM SOLUTION BE REQUIRED, THERE ARE ADDITIONAL ITEMS THAT CAN BE ASSESSED.

    Description of Event or Problem · 0

    IT HAS BEEN DISCOVERED THAT THE ONCOMINE DX EXPRESS TEST (ODXET) MAY NOT DETECT THE FGFR3 C.746C>G P.S249C (COSM715) VARIANT WHEN PRESENT IN A SAMPLE AT VERY LOW ALLELIC FREQUENCIES (AFS) DUE TO A SECONDARY STRUCTURE FORMATION THAT INHIBITS AMPLIFICATION OF THE MUTANT ALLELE, WHICH MAY RESULT IN FALSE-NEGATIVE RESULTS FOR THIS SPECIFIC FGFR3 VARIANT DUE TO AF MEASUREMENT FALLING BELOW THE VARIANT CALLING THRESHOLD. PREDICTIVE MODELING INDICATES THIS IS DRIVEN BY HIGH GUANINE AND CYTOSINE (GC) CONTENT AROUND THE MUTATION SITE AND THE SHORTER AMPLICONS USED IN THE ODXET PANEL, WITH THE SPECIFIC C-TO-G CHANGE OCCURRING WITHIN A GC-RICH REGION THAT PROMOTES SUCH STRUCTURES. THIS EFFECT IS NOT OBSERVED IN WILDTYPE SAMPLES. THERMO FISHER HAS NOT BEEN MADE AWARE OF ANY DEATH, SERIOUS INJURY OR PERMANENT BODILY IMPAIRMENT OCCURRED FROM THE USE OF THE PRODUCT.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    390177 ONCOMINE¿ DX EXPRESS TEST NEXT GENERATION SEQUENCING ONCOLOGY PANEL, SOMATIC OR GERMLINE VARIANT DETECTION PQP LIFE TECHNOLOGIES CORPORATION 3155346US,3335701US 10190302017305

    Patients

    Seq Age Sex Outcome Treatment
    1 NA Unknown