VIDAS® ESTRADIOL II

Description of Event or Problem

PRODUCT DESCRIPTION. VIDAS® ESTRADIOL II (E2II) IS AN AUTOMATED QUANTITATIVE TEST FOR USE ON THE VIDAS® FAMILY OF INSTRUMENTS FOR THE QUANTITATIVE MEASUREMENT OF TOTAL 17 -ESTRADIOL IN HUMAN SERUM OR PLASMA (LITHIUM HEPARIN), USING THE ELFA TECHNIQUE (ENZYME LINKED FLUORESCENT ASSAY). THE VIDAS® E2 II ASSAY IS INTENDED FOR USE AS AN AID IN THE DIAGNOSIS AND TREATMENT OF VARIOUS HORMONAL SEXUAL DISORDERS AND IN ASSESSING PLACENTAL FUNCTION IN COMPLICATED PREGNANCY. RANGE OF EXPECTED VALUES IN A CLINICALLY HEALTHY POPULATION, THE FOLLOWING VALUES WERE FOUND: MEN (N = 173): < 62PG/ML. WOMEN: FOLLICULAR PHASE (N = 129): 18 - 147 PG/ML. PRE-OVULATORY PEAK (N = 33): 93 - 575 PG/ML. LUTEAL PHASE (N = 131): 43 - 214 PG/ML. MENOPAUSE (N = 26): < 58 PG/ML. THESE RESULTS ARE GIVEN AS A GUIDE. IT IS RECOMMENDED THAT EACH LABORATORY ESTABLISH ITS OWN REFERENCE INTERVAL FROM A RIGOROUSLY SELECTED POPULATION. CONVERSION FACTORS: FROM PMOL/L TO PG/ML (NG/L), MULTIPLY BY 0.272. FROM PG/ML (NG/L) TO PMOL/L, MULTIPLY BY 3.67. ISSUE DESCRIPTION: ON 25-MAR-2025, A CUSTOMER FROM FRANCE NOTIFIED BIOMÉRIEUX OF OBTAINING A POTENTIAL OVERESTIMATED RESULT WHEN TESTING PATIENT SAMPLES WITH VIDAS ESTRADIOL II (REF. 30431, LOT: 1010844220, EXPIRY DATE: 25-JUL-2025) COMPARED TO ANOTHER METHOD. THE PATIENT (WOMEN, BORN IN 1984) IS UNDERGOING ASSISTED REPRODUCTIVE TECHNOLOGY (ART) TREATMENT WITH ORAL ESTROGENS (MOLECULE UNKNOWN) AS PART OF OVULATION STIMULATION. ON 18-MAR-2025, THE CUSTOMER TESTED THE SAME PATIENT SAMPLE WITH 2 DIFFERENT KITS OF VIDAS ESTRADIOL II (REF. 30431, LOT: 1010844220 AND 1010956330) AND OBTAINED THE FOLLOWING RESULTS: - LOT 1010844220 (PURE SAMPLE): > 3000.00 PG/ML. - LOT 1010956330 (DILUTED SAMPLE ½ WITH MAN SERUM): 5556.89 PG/ML. ON (B)(6) 2025, A NEW PATIENT¿S SAMPLE WAS TESTED WITH ANOTHER METHOD (COBAS) BY ANOTHER LABORATORY AND THE RESULT WAS: 639 PG/ML. THE SAMPLE COLLECTED BY THE CUSTOMER WAS ALSO ANALYZED BY THE OTHER LABORATORY WITH COBAS METHOD AND THE RESULT WAS: 713 PG/ML. TO BE NOTED THAT IT IS MENTIONED IN THE PACKAGE INSERT: "IN CASES OF ESTROGEN THERAPY, AND PARTICULARLY THAT OF HORMONE REPLACEMENT THERAPY (MENOPAUSE), OVERESTIMATED RESULTS MAY BE OBTAINED." BASED ON THE AVAILABLE INFORMATION AT THE TIME OF THIS ASSESSMENT, THERE IS NO DATA AVAILABLE REGARDING A POTENTIAL PATIENT¿S IMPACT OF THIS ISSUE, OR ANY DELAYED OF RESULTS. THE POTENTIAL OVERESTIMATED RESULT OBTAINED WITH THE KIT VIDAS ESTRADIOL II (REF. 30431, LOT: 1010956330) IS ASSESSED SEPARATELY ((B)(6)). A BIOMÉRIEUX INTERNAL INVESTIGATION WILL BE INITIATED. NOTE: REFERENCE 30431 IS NOT REGISTERED IN THE UNITED STATES. THE U.S. SIMILAR DEVICE IS PRODUCT REFERENCE 30431-01.

Additional Manufacturer Narrative

THIS REPORT WAS INITIALLY SUBMITTED FOLLOWING NOTIFICATION FROM A CUSTOMER IN FRANCE REGARDING OVERESTIMATED RESULTS FOR ONE (1) PATIENT WHEN USING VIDAS®ESTRADIOL II (REFERENCE 30431) WITH TWO DIFFERENT LOTS (LOT 1010844220 REPORTED IN MEDWATCH 8020790-2025-00004 AND LOT 1010956330 REPORTED IN MEDWATCH 8020790-2025-00005) WHEN COMPARED TO A COMPETITOR METHOD. IT IS TO BE NOTED THAT ANOTHER CUSTOMER ALSO REPORTED A SIMILAR ISSUE FOR TWO (2) PATIENTS WITH VIDAS® ESTRADIOL II 60 TESTS (REF. 30431, LOT: 1010956330) (REPORTED UNDER MEDWATCH 8020790-2025-00007 AND 8020790-2025-00008). A BIOMÉRIEUX INTERNAL INVESTIGATION HAS BEEN COMPLETED WITH THE FOLLOWING RESULTS: 1.COMPLAINT ANALYSIS: THE COMPLAINT ANALYSIS DID NOT REVEAL THIS ISSUE AS A SYSTEMIC QUALITY ISSUE. 2. DEVICE HISTORY RECORDS: THE REVIEW DID NOT HIGHLIGHT ANY ISSUE DURING THE MANUFACTURING PROCESS OF VIDAS® ESTRADIOL II 60 TESTS (REF. 30431, LOT 1010844220 AND LOT 1010956330). 3. ANALYSIS AND TESTS CONDUCTED BY COMPLAINTS LABORATORY. 3.1 CUSTOMER MATERIAL. A FROZEN SAMPLE WAS RECEIVED ON 10-APR-2025 - HEPARINIZED PLASMA: 1.5 ML, FROM THIS CUSTOMER. 3.2 CONTROL CHART ANALYSIS: THE COMPLAINTS LABORATORY ANALYZED THE CONTROL CHART OF INTERNAL SAMPLES FOR EIGHT (8) LOTS OF VIDAS® ESTRADIOL II 60 TESTS (REF. 30431) INCLUDING THE LOTS MENTIONED BY THE CUSTOMER (LOT 1010844220 AND LOT 1010956330). ALL THE RESULTS COMPLY WITH SPECIFICATIONS, AND NO SPECIFIC TREND OF VIDAS® ESTRADIOL II 60 TESTS (REF. 30431, LOT 1010844220 AND LOT 1010956330) WAS OBSERVED COMPARED TO THE OTHER LOTS. 3.3 TESTS PERFORMED BY THE COMPLAINTS LABORATORY. 3.3.1 TESTS ON INTERNAL SAMPLE. THE COMPLAINTS LABORATORY TESTED INTERNAL SERUM SAMPLES WITH EXPECTED ESTRADIOL CONCENTRATIONS AT 268, 724, 1479 AND 2105 PG/ML ON THE TWO (2) BATCHES MENTIONED BY THE CUSTOMER (LOT 1010844220 AND LOT 1010956330), AND THE ESTRADIOL LEVELS WERE FOUND WITHIN THE ACCEPTABLE RANGE FOR BOTH LOTS. FURTHERMORE, THERE IS NO SIGNIFICANT DIFFERENCE BETWEEN THE RESULTS OBTAINED BY THE COMPLAINTS LABORATORY AND THOSE OBSERVED BEFORE THE BATCH RELEASE. 3.3.2 TESTS ON THE RETURNED SAMPLE: THE RETURNED PATIENT SAMPLE WAS TESTED USING THE VIDAS® ESTRADIOL II 60 TESTS (REF. 30431, LOT 1010844220) AS WELL AS TWO (2) OTHER METHODS: COBAS AND RIA METHOD. THE RESULTS OBTAINED WITH VIDAS AND RIA WERE SIMILAR, WHEREAS THE VALUE MEASURED WITH COBAS WAS LOWER. 3.3.3 INTERFERENCE TESTING: THE COMPLAINTS LABORATORY PERFORMED INTERFERENCE STUDIES BY SPIKING SAMPLES WITH WEAK ESTRADIOL CONCENTRATION WITH ESTRONE MOLECULE (CROSS REACTIVITY DESCRIBED IN THE PACKAGE INSERT OF VIDAS® ESTRADIOL II 60 TESTS (REF. 30431)). ON A MALE SAMPLE AND A POOL OF SERA SPIKED WITH ESTRONE (ELEVATED CONCENTRATION) A HIGHER CONCENTRATION OF ESTRADIOL THAN EXPECTED WAS OBSERVED. THE VIDAS METHOD SHOWS A MORE PRONOUNCED OVERESTIMATION OF ESTRADIOL COMPARED TO COBAS, WHICH IS ALSO AFFECTED BUT TO A LESSER EXTENT. THE CROSS REACTIVITY DESCRIBED IN THE PACKAGE INSERT WAS REPRODUCED. AS THE RETURNED PATIENT SAMPLE WAS EXHAUSTED IN PREVIOUS TESTING, IT WAS NOT POSSIBLE TO MEASURE ITS ESTRONE LEVELS AND NEITHER TO PURSUE THE INVESTIGATION TO DETERMINE THE ROOT CAUSE OF THE ELEVATED VIDAS ESTRADIOL II RESULTS REPORTED BY THE CUSTOMER. WITHOUT THIS MEASUREMENT, IT CANNOT BE CONFIRMED WHETHER ESTRONE MAY HAVE CONTRIBUTED TO THE HIGH ESTRADIOL RESULT. IT IS TO BE NOTED THAT ESTRONE AND OTHER ESTROGEN CAN BE BROUGHT BY FOOD (E.G THERE ARE NUMEROUS PHYTO-OESTROGEN IN SOY). ESTRONE IS ALSO PRODUCED BY ADRENAL GLANDS AND IS A RELATIVELY ABUNDANT HORMONE WIDELY DISTRIBUTED IN TISSUES OF ANIMAL AND PLANT ORIGIN. ACCORDING TO MEDICAL AFFAIRS ADVISOR, IN THE CONTEXT OF IN VITRO FERTILIZATION, ESTRADIOL IS ONE ELEMENT OF THE MEDICAL HISTORY OF THE PATIENT TESTED BUT THERE IS ALSO ULTRASOUND IMAGING (FOR COUNT AND SIZE EVALUATION OF FOLLICLES AND SELECTION OF THE OVARY). AN INAPPROPRIATE ESTRADIOL RESULT SHOULD ALERT THE CLINICIAN. 4. ROOT CAUSE ANALYSIS AND CONCLUSION: THE ELEVATED ESTRADIOL RESULTS OBSERVED BY THE CUSTOMERS WERE NOT REPRODUCED WHEN TESTING INTERNAL AND BIOBANK SAMPLES. HOWEVER, THE PATIENT¿S RETURNED SAMPLE FROM THE CUSTOMER SHOWED A SIMILAR ELEVATION, CONFIRMING THE CUSTOMER'S OBSERVATION OF HIGHER ESTRADIOL LEVELS WITH VIDAS COMPARED TO COBAS. THIS SAMPLE WAS TESTED USING VIDAS ESTRADIOL, COBAS, AND RIA METHODS; RESULTS FROM VIDAS AND RIA WERE COMPARABLE, WHILE THE VALUE OBTAINED WITH COBAS WAS LOWER. SAMPLES ARTIFICIALLY SPIKED WITH HIGH CONCENTRATIONS OF ESTRONE ALSO SHOWED ELEVATED ESTRADIOL LEVELS, AS DESCRIBED IN THE PACKAGE INSERT, SUGGESTING POTENTIAL INTERFERENCE. HOWEVER, IT WAS NOT POSSIBLE TO MEASURE ESTRONE LEVELS IN THE PATIENT¿S SAMPLE, AS IT WAS NO LONGER AVAILABLE FOR FURTHER TESTING. AS A RESULT, THE INVESTIGATION CANNOT BE PURSUED FURTHER, AND IT IS NOT POSSIBLE TO DETERMINE THE DEFINITIVE ROOT CAUSE OF THE ISSUE OBSERVED BY CUSTOMERS. ACCORDING TO THE ABOVE DATA, THE PERFORMANCE OF THE VIDAS® ESTRADIOL II 60 TESTS (REF. 30431, LOT 1010844220 AND LOT 1010956330) IS CONFORM TO THE EXPECTED SPECIFICATIONS.