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 31-MAR-2025, A CUSTOMER FROM SRI LANKA NOTIFIED BIOMÉRIEUX OF OBTAINING OVERESTIMATED RESULT WHEN TESTING PATIENT SAMPLE WITH VIDAS ESTRADIOL II (REF. 30431, LOT: 1011091550, EXPIRY DATE: 02-DEC-2025) COMPARED TO OTHER METHODS. ON (B)(6) 2025, AFTER PERFORMING THE CALIBRATION OF VIDAS ESTRADIOL II (REF. 30431, LOT: 1011091550 THAT WAS VALID, THE CUSTOMER RAN A COMPARISON OF A PATIENT SAMPLE (SERUM, COLLECTED ON (B)(6) 2025) ACROSS DIFFERENT ANALYZERS. THE RESULTS WERE AS FOLLOWS: WITH VIDAS ESTRADIOL II (REF. 30431, LOT: 1011091550) ON MINI VIDAS ANALYZER: 2878.31 PG/ML WITH DIASORIN LIAISON ANALYZER: 1716 PG/ML. WITH CLIA LAB ANALYZER PERFORMED BY ANOTHER LABORATORY: 1753 PG/ML TO FURTHER INVESTIGATE, THE SAME SAMPLE WAS STORED AT -25°C AND REANALYZED ON (B)(6) 2025 ON MINIVIDAS ANALYZER WITH VIDAS ESTRADIOL II (REF. 30431, LOT: 1011091550) AND THE RESULT WAS 2702.71 PG/ML. THE PATIENT (WOMAN, 33 YEARS OLD) WAS UNDERGOING IVF AND WAS ON MENSTRUAL DAY 7 WHEN THE INITIAL SAMPLE WAS TESTED. THE MEDICATIONS ADMINISTERED WAS GONAL F 300 PEN (7 UNITS) AND IVF M 75 IU (1 UNIT). THE ULTRASOUND FINDINGS WAS FOR THE RIGHT OVARY: 9 FOLLICLES (LARGEST MEASURING 11.8 X 12.1 MM) AND FOR THE LEFT OVARY: 6 FOLLICLES (LARGEST MEASURING 11.9 X 11.9 MM). TO BE NOTED THAT THE PATIENT IS NOT TAKING ORAL ESTROGEN IN ANY FORMS. 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. 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 SRI LANKA REGARDING OVERESTIMATED RESULT WHEN TESTING PATIENT SAMPLE WITH VIDAS ESTRADIOL II (REF. 30431, LOT: 1011091550, EXPIRY DATE: 02-DEC-2025) COMPARED TO OTHER METHODS. A BIOMÉRIEUX INTERNAL INVESTIGATION HAS BEEN COMPLETED WITH THE FOLLOWING RESULTS: CUSTOMER MATERIAL: NO SAMPLE AVAILABLE. INVESTIGATION OUTCOMES: COMPLAINT ANALYSIS: THE ANALYSIS OF COMPLAINTS RECORDED AGAINST THIS LOT DID NOT REVEAL ANY QUALITY ISSUE FOR THIS LOT OR ANY SYSTEMIC QUALITY ISSUE. QUALITY CONTROL RECORDS: THERE IS NEITHER CAPA NO NON-CONFORMITY NOR QUALITY EVENT LINKED TO THIS ISSUE ON THIS VIDAS ASSAY. 3-3) ANALYSIS AND TESTS CONDUCTED BY COMPLAINTS LABORATORY. CONTROL CHART ANALYSIS: THE COMPLAINTS LABORATORY ANALYZED THE CONTROL CHART OF INTERNAL SAMPLES WITH OESTRADIOL CONCENTRATIONS CLOSE TO THE ONES OBSERVED ON VIDAS AND DIASORIN METHODS (RESPECTIVE TARGET AT 1406 / 1479 / 1697 AND 2721 PG/ML) FOR SEVEN (7) LOTS OF VIDAS ESTRADIOL II REF.30431 INCLUDING THE LOT MENTIONED BY THE CUSTOMER (LOT 1011091550). ALL THE RESULTS COMPLIED WITH SPECIFICATIONS AND NO SPECIFIC TREND WAS OBSERVED OF VIDAS ESTRADIOL II REF.30431 LOT 1011091550 COMPARED TO THE OTHER LOTS. TEST ON INTERNAL SAMPLES: THE COMPLAINTS LABORATORY TESTED THREE (3) INTERNAL SAMPLES WITH A TARGET AT 1405.51 / 1771 AND 2105 PG/ML ON VIDAS ESTRADIOL II REF.30431 LOT 1011091550 (RETAIN KIT OF LOT MENTIONED BY THE CUSTOMER) AND VIDAS ESTRADIOL II REF.30431 LOT 1011239440 (LOT USED AS A REFERENCE). VIDAS ESTRADIOL II REF.30431 LOT 1011091550 GAVE RESULTS WITHOUT ANY SIGNIFICANT DIFFERENCE COMPARED TO THOSE OBSERVED BEFORE THE BATCH RELEASE. NO EVOLUTION OVER TIME OF THE SAMPLES' ACTIVITY WAS OBSERVED. MOREOVER, SIMILAR RESULTS WERE OBTAINED BETWEEN BOTH LOTS TESTED. TEST ON SAMPLES FROM BIOMERIEUX BLOOD BANK (BIOBANK). THREE (3) SAMPLES WERE TESTED FROM THE BIOBANK WITH KNOWN VALUES OF OESTRADIOL DETERMINED BY COATRIA METHOD. THE SAMPLES GAVE SIMILAR HIGH CONCENTRATIONS USING VIDAS ESTRADIOL II REF.30431 LOT 1011091550 COMPARED TO THE ONES OBSERVED USING COATRIA METHOD. A POOL OF SERA WAS PREPARED (EACH INDIVIDUAL SERUM HAS A KNOWN WEAK CONCENTRATION OF OESTRADIOL DETERMINED BY MASS SPEC METHOD). THE OBJECTIVE WAS TO HAVE ENOUGH VOLUME FOR DIFFERENT TESTING. A SIMILAR RESULT WAS OBSERVED WHEN TESTING THE POOL ON VIDAS ESTRADIOL II REF.30431 LOT 1011091550 COMPARED TO THOSE OBTAINED ON INDIVIDUAL UNITS USING MASS SPEC METHOD. INTERFERENCE TESTING: IT WAS NOT POSSIBLE TO RETRIEVE THE SERUM, SO INTERFERENCE STUDIES WERE PERFORMED BY SPIKING SAMPLES WITH WEAK OESTRADIOL CONCENTRATION WITH ESTRONE MOLECULE (CROSS REACTIVITY DESCRIBED IN THE PACKAGE INSERT OF VIDAS ESTRADIOL II REF.30431). ON THE MALE SAMPLE AND POOL OF SERA SPIKED WITH ESTRONE (ELEVATED CONCENTRATION) A HIGHER CONCENTRATION OF OESTRADIOL THAN EXPECTED WAS OBSERVED. THE CROSS REACTIVITY DESCRIBED IN THE PACKAGE INSERT WAS REPRODUCED. HOWEVER, AS IT WAS NOT POSSIBLE TO TEST THE PATIENT¿S SAMPLE, IT CANNOT BE STATED THAT IT IS THE ROOT CAUSE OF ELEVATED RESULTS OBSERVED BY THE CUSTOMER. MOREOVER, THIS SAMPLE WAS NOT TESTED FOR ESTRONE. ESTRONE AND OTHER OESTROGEN 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, OESTRADIOL IS ONE ELEMENT OF THE MEDICAL HISTORY OF THE PATIENT BUT THERE IS ALSO ULTRASOUND IMAGING (FOR COUNT AND SIZE EVALUATION OF FOLLICLES AND SELECTION OF THE OVARY). AN INAPPROPRIATE OESTRADIOL RESULT SHOULD ALERT THE CLINICIAN. MOREOVER, IN THE CONTEXT OF LIFECYCLE MANAGEMENT AND IVDRF PROCESS, THE REAGENT PERFORMANCE IS CONTINUOUSLY MONITORED. CONCLUSION: THE ELEVATED OESTRADIOL RESULTS OBSERVED BY THE CUSTOMER WERE NOT REPRODUCED WHEN TESTING INTERNAL SAMPLES AND SAMPLES FROM OUR BIOBANK. THE ELEVATED OESTRADIOL RESULTS WERE OBSERVED WHEN TESTING SAMPLES SPIKED WITH ELEVATED ESTRONE CONCENTRATIONS. WITHOUT THE PATIENTS SAMPLE AVAILABLE, FURTHER INVESTIGATION CANNOT BE PURSUED AND THE ROOT CAUSE OF THE ISSUE OBSERVED BY THE CUSTOMER CANNOT BE IDENTIFIED. ACCORDING TO THE DATA MENTIONED ABOVE, THERE IS NO RECONSIDERATION OF VIDAS ESTRADIOL II REF.30431 LOT 1011091550.