MAUDE Adverse Event Report: SIEMENS HEALTHCARE DIAGNOSTICS, INC. ADVIA CENTAUR XP ENHANCED ESTRADIOL (EE2) ASSAY; ENHANCED ESTRADIOL IMMUNOASSAY

Model Number N/A

Device Problem Adverse Event Without Identified Device or Use Problem (2993)

Patient Problem No Known Impact Or Consequence To Patient (2692)

Event Date 05/09/2017

Event Type  Injury  

Manufacturer Narrative

Additional information has been requested from the customer for investigation and clarification but was not obtained.The samples from the patients are not available for further testing and investigation.Internal data for the ee2 lot 036 and calibrator 30 lot 20 shows that the product is performing as intended.The customer was expecting lower ee2 results for the two patients.It is unclear if the product was used as intended by the customer.Current clinical guidance for the treatment of hormone receptor-positive metastatic breast cancer (er-positive mbc) recommends that treatment of premenopausal women with er-positive mbc include either ovarian suppression or ovarian ablation.When ovarian suppression is pursued with gnrh agonists such as lupron, suppression of ovarian production may be incomplete and may subsequently impact efficacy of treatment.For this reason, the american society of clinical oncology (asco) guidelines recommend that estradiol levels be monitored in these patients using a high-sensitivity assay.Because there are no data defining the optimal level of plasma estradiol and because tests from different manufacturers vary widely in sensitivity, asco recommends that the local laboratory definition of menopausal levels of estradiol using a high-sensitivity assay be used for monitoring effectiveness of ovarian suppression.The siemens advia centaur enhanced estradiol assay is not considered a high sensitivity estradiol assay.For patient 2, two estradiol values of 29.2 pg/ml ((b)(6) 2017) and 22.2 pg/ml ((b)(6) 2017) are provided and both are within the expected post-menopausal female range.Both results are in accordance with the asco recommendation that estradiol levels be maintained within the definition of menopausal levels (e.G.

Event Description

Advia centaur xp enhanced estradiol (ee2) results were questioned on samples from two patients when the customer received urgent medical device recall (umdr) cc-17.15.A.Us dated (b)(6) 2017.The customer said two clinicians called him about product not related to the recall and were concerned about the elevated estradiol levels reported and were concerned over the two patients who had ee2 run at this site.Both patients were breast cancer patients and had oophorectomies.It is unclear whether the oophorectomies were based solely or at all on the ee2 result.The patients were undergoing lupron therapy.Each patient had low fsh levels consistent with lupron effect.The estradiol and fsh levels are checked on these patients to ensure that the lupron therapy is achieving adequate ovarian function suppression.There was no clinical indication for ultrasound.According to the clinicians, the elevated estradiol levels suggested that adequate ovarian function suppression was not being achieved with lupron therapy.Bilateral oophorectomy was pursued.According to the clinicians, these patients are expected to have unmeasurable estradiol levels on lupron and aromatase inhibitor therapy.The clinicians were concerned for inadequate ovarian function suppression.The customer has not provided any other information for these patients.Multiple attempts have been made to obtain the information.Both patients underwent oophorectomies.These procedures were not reported as adverse health consequences to siemens.Statements attributed to the clinicians are derived from information submitted to the siemens complaint handling system and have not been verified.

Manufacturer Narrative

Siemens filed the initial mdr 1219913-2017-00187 on august 22, 2017.08/23/2017 additional information: the customer told siemens that at cornell, some of the doctors use the results of the siemens' assays outside of ifu claims and feels this is an incorrect practice.According to the customer, the ee2 issue with the two patients of concern is one example of wrongful use of the advia centaur results.As such, the codes have been updated based upon this new information.The advia centaur ee2 assay is performing as intended.Siemens communicated the following information to the customer on (b)(4) 2017: based on siemens investigation, it was concluded that the product (ee2 calibrator lot 20) met specifications.Siemens believes that the test results were used in a way that is not in accordance with our instructions for use.We want to provide further background regarding our conclusion: siemens advia centaur xp ee2 is indicated for in vitro diagnostic use in the quantitative determination of estradiol in human serum and plasma (heparinized and edta) using the advia centaur®, advia centaur xp, and advia centaur xpt systems.Consistent with this, the ifu for the advia centaur assay does not state that the assay is indicated for monitoring er positive mbc patients or that any detectable level of estradiol should be interpreted as indicative of residual ovarian function when monitoring er-positive mbc patients undergoing ovarian suppression.The ifu does say: in the interpretation of results section: "results of this assay should always be interpreted in conjunction with patient's medical history, clinical presentation and other findings." in the limitations section: "heterophilic antibodies in human serum can react with reagent immunoglobulins, interfering with in vitro immunoassays.Patients routinely exposed to animals or to animal serum products can be prone to this interference and anomalous values may be observed.Additional information may be required for diagnosis.The drug fulvestrant (faslodex®)* may cause falsely elevated estradiol results in immunoassays.For patients being treated with fulvestrant, an alternate method that is not expected to show cross reactivity to fulvestrant, such as liquid chromatography-mass spectrometry (lc-ms), should be used.With the advent of new steroid based medications (analogues) with similar chemical structures to estradiol, there is the possibility of cross-reactivity and results inconsistent with the patients clinical history.For diagnostic purposes, the results should always be assessed in conjunction with the patient's medical history, clinical examination and other findings.If the estradiol results are inconsistent with clinical evidence, additional testing is suggested to confirm the result." of course, an assay result is also only one potentially relevant data point in a clinician's assessment of a patient.Siemens healthineers assays should be used in accordance with the applicable instructions for use (ifu).We also want to reinforce that the enhanced estradiol ifu states in the interpretation of results section: "results of this assay should always be interpreted in conjunction with patient's medical history, clinical presentation and other findings." no further evaluation of the device is required.Mdr 1219913-2017-00185 supplemental report 1 for patient 1 sid (b)(6) was filed for a different patient from the same complaint.Mdr 1219913-2017-00186 supplemental report 1 for patient 2 was filed for additional patient results from a different date.

• Brand Name: ADVIA CENTAUR XP ENHANCED ESTRADIOL (EE2) ASSAY
• Type of Device: ENHANCED ESTRADIOL IMMUNOASSAY
• Manufacturer (Section D): SIEMENS HEALTHCARE DIAGNOSTICS, INC.; 511 benedict avenue; tarrytown NY 10591 5097
• Manufacturer (Section G): SIEMENS HEALTHCARE DIAGNOSTICS, INC.; 333 coney street; e. walpole MA 02032
• Manufacturer Contact: eiman sulieman ; 333 coney street; e. walpole, MA 02032 ; 5086604603
• MDR Report Key: 6811347
• MDR Text Key: 83271242
• Report Number: 1219913-2017-00187
• Device Sequence Number: 1
• Product Code: CHP
• UDI-Device Identifier: 00630414573342
• UDI-Public: 00630414573342
• Combination Product (y/n): N
• Reporter Country Code: US
• PMA/PMN Number: EXEMPT
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: company representative,health
• Reporter Occupation: Other Health Care Professional
• Type of Report: Initial,Followup
• Report Date: 09/19/2017

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 08/22/2017
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: No
• Device Operator: Health Professional
• Device Expiration Date: 07/27/2017
• Device Model Number: N/A
• Device Catalogue Number: 10490889
• Device Lot Number: 036
• Was Device Available for Evaluation?: No
• Is the Reporter a Health Professional?: Yes
• Date Manufacturer Received: 08/23/2017
• Was Device Evaluated by Manufacturer?: Device Not Returned to Manufacturer
• Date Device Manufactured: 09/27/2016
• Is the Device Single Use?: No
• Type of Device Usage: Initial
• Patient Sequence Number: 1
• Patient Outcome(s): Other
• Patient Age: 46 YR