MAUDE Adverse Event Report: SIEMENS HEALTHCARE DIAGNOSTICS, INC. ADVIA CENTAUR XP CA 19-9; IMMUNOLOGICAL TEST FOR CA 19-9 ANTIGEN

Model Number N/A

Device Problems Off-Label Use (1494); High Readings (2459); No Apparent Adverse Event (3189)

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

Event Date 05/01/2019

Event Type  Injury  

Manufacturer Narrative

The customer performed a dilution row.Results are the following: 1:2, 361; 1:4, 240; 1:8, 344; 1:16, 382.Siemens healthcare diagnostics is investigating.The 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." the ifu states in the limitations section: warning "do not use the advia centaur ca 19-9 assay as a screening test or for diagnosis.Do not predict disease recurrence solely on levels of advia centaur ca 19-9.Normal levels of advia centaur ca 19-9 do not always preclude the presence of disease.Note do not interpret serum levels of ca 19-9 as absolute evidence of the presence or the absence of malignant disease.Before treatment, patients with confirmed gi carcinoma frequently have levels of ca 19-9 within the range observed in healthy individuals.Additionally, elevated levels of ca 19-9 can be observed in patients with nonmalignant diseases.Measurements of ca 19-9 should always be used in conjunction with other diagnostic procedures, including information from the patient's clinical evaluation.The concentration of ca 19-9 in a given specimen determined with assays from different manufacturers can vary because of differences in assay methods, calibration, and reagent specificity.Ca 19-9 determined with different manufacturers' assays will vary depending on the method of standardization and antibody specificity.Therefore, it is important to use assay-specific values to evaluate quality control results." mdr 1219913-2019-00161 (sample (b)(6) 2019), mdr 1219913-2019-00162 (sample (b)(6) 2019), mdr 1219913-2019-00163 (sample (b)(6) 2019), mdr 1219913-2019-00164 (sample (b)(6) 2019), mdr 1219913-2019-00166 (sample (b)(6) 2019), and mdr 1219913-2019-00167 (sample (b)(6) 2019) were filed for the same event.

Event Description

Advia centaur xp ca 19-9 discordant high results were obtained for seven samples from the same patient.The results were reported to the physician and questioned.Repeat testing was performed using different samples on two alternate methods and the results were negative.The customer does not know which result is correct.The patient was in the intensive care unit.It is unknown if patient treatment was prescribed or altered.There was no report of adverse health consequences due to the discordant ca 19-9 results.

Manufacturer Narrative

Siemens filed the initial mdr (b)(4) on (b)(6)2019.(b)(4) additional information: the results of the measurements with hbt (heterophilic blocking tube) were provided by the customer.The customer had three aliquots of the sample (serum (th 19153311s), hep-plasma (th 19153311hp), plasma (th 191533a).Sid measurements without hbt measurement with hbt th 19153311s 394.45 and 359.96 270.08 and 271.91 th 19153311hp 316.45 and 373.33 244.05 and 240.34 th 191533a 349.41 and 342.92 261.09 and 250.95 (b)(6)2019 correction: the initial mdr was filed as product problem in section b1 and malfunction in section h1 based on the information provided at the time.Based on the additional information received on (b)(6)2019 (see below) section b1 is corrected to adverse event, section b2 is corrected to other serious (important medical events), and section h1 is corrected to serious injury.(b)(6)2019 additional information: per siemens' customer, the general practitioner used the advia centaur xp ca19-9 assay as a screening test while it is not labeled for that intended use.Patient had different medical examinations, for example endocrinology, sonography, endoscopic retrograde cholangiopancreatography (ercp).Details of these tests were not provided by the customer.Due to the higher ca 19-9 results, the patient had a gall bladder operation.Date and details of surgery are unknown.Latest cea results for the siemens method were 13.4 and with the alternate method 18.2.Unit of measure not provided.(siemens was unable to obtain clarification on whether this is meant to be cea or ca19-9).Customer has no information about the patient's medications.Advia centaur xp ca19-9 dilutions were performed and dilute in a relatively linear fashion.Neat 426.9 u/ml 1:2 361.2 u/ml 1:4 240.4 u/ml 1:8 344.0 u/ml 1:16 382.4 u/ml (b)(6)2019 additional information: siemens investigated to identify possible root cause for a repeatable high discordant result with the advia centaur xp ca 19-9 assay versus alternate methods.The falsely elevated ca19-9 assay result is likely due to heterophilic interference.Siemens reviewed test results for the sample neat and hbt treated.Hbt had a -28% effect on lowering the dose.An extremely high titer of heterophilic interference may likely be the cause of the -28% effectiveness in lowering the ca 19-9 result.Per the scantibodies laboratory ifu limitations statement "there may be some samples with extremely strong heterophilic interference.In such cases the hbt may not be able to block all of the assay interference." per the advia centaur ca 19-9 ifu limitations statement: "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." (b)(6)2019 additional information: the customer (laboratory physician) will not be providing any further information and has declined anything further from siemens.The instructions for use (ifu) states in the intended use section: "for in vitro diagnostic use in the quantitative, serial determination of ca 19-9 in human serum and to aid in the management of patients with gi carcinoma using the advia centaur®, advia centaur xp, and advia centaur xpt systems.The test is intended for use as an aid in monitoring patients previously treated for gi cancer.Serial testing for ca 19-9 in the serum of patients who are clinically free of disease should be used in conjunction with other clinical methods used for the early detection of cancer recurrence.The test is also intended for use as an aid in the management of gi cancer patients with metastatic disease by monitoring the progression or regression of disease in response to treatment." the 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." the ifu states in the limitations section: "warning do not use the advia centaur ca 19-9 assay as a screening test or for diagnosis.Do not predict disease recurrence solely on levels of advia centaur ca 19-9.Normal levels of advia centaur ca 19-9 do not always preclude the presence of disease.Note: do not interpret serum levels of ca 19-9 as absolute evidence of the presence or the absence of malignant disease.Before treatment, patients with confirmed gi carcinoma frequently have levels of ca 19-9 within the range observed in healthy individuals.Additionally, elevated levels of ca 19-9 can be observed in patients with nonmalignant diseases.Measurements of ca 19-9 should always be used in conjunction with other diagnostic procedures, including information from the patient's clinical evaluation.The concentration of ca 19-9 in a given specimen determined with assays from different manufacturers can vary because of differences in assay methods, calibration, and reagent specificity.Ca 19-9 determined with different manufacturers' assays will vary depending on the method of standardization and antibody specificity.Therefore, it is important to use assay-specific values to evaluate quality control results." the clinical history and current diagnosis of the patient are unknown.The intended use of the advia centaur ca19-9 assay is for managing/monitoring patients already diagnosed with gi cancer.As noted in the limitations of the ifu, the assay is not intended for diagnosis or screening, or use in isolation.The factors that lead to the decision to perform gallbladder removal surgery, including the results of other testing and imaging, as was performed in the current case and that would typically be used in conjunction with ca19-9 results, are unknown.Gallbladder surgery is not uncommon and carries only a small risk of complications.It may be performed laparoscopically or via a large incision.The risks of gallbladder surgery include bile leak, bleeding, infection, injury to nearby structures and risks of general anesthesia.The advia centaur xp instrument is performing within specifications.The falsely elevated ca19-9 assay result is likely sample specific and due to heterophilic interference.The complaint information confirms that the siemens customer (laboratory physician) understands intended use of the ca19-9 assay according to the ifu.The customer declined further assistance from siemens.No further evaluation of the device is required.Based on siemens' investigation results and findings, the event problem and evaluation codes in section h6 have been updated.Device codes are 1494 and 2459; result code is 213; conclusion code is 4315.Statements attributed to this event are derived from information submitted to the siemens complaint handling system and have not been verified.Mdr (b)(4) supplemental report 1 (sample (b)(6)2019 ), mdr (b)(4) supplemental report 1 (sample (b)(6)2019 ), mdr (b)(4) supplemental report 1 (sample(b)(6)2019 ), mdr (b)(4) supplemental report 1 (sample (b)(6)2019 ), mdr (b)(4) supplemental report 1 (sample (b)(6)2019 ), and mdr (b)(4) supplemental report 1 (sample (b)(6)2019 ) were filed for the same event.

• Brand Name: ADVIA CENTAUR XP CA 19-9
• Type of Device: IMMUNOLOGICAL TEST FOR CA 19-9 ANTIGEN
• Manufacturer (Section D): SIEMENS HEALTHCARE DIAGNOSTICS, INC.; 511 benedict avenue; tarrytown NY 10591 5097
• MDR Report Key: 9038475
• MDR Text Key: 214799515
• Report Number: 1219913-2019-00165
• Device Sequence Number: 1
• Product Code: NIG
• UDI-Device Identifier: 00630414574257
• UDI-Public: 00630414574257
• Combination Product (y/n): N
• PMA/PMN Number: K031393
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: foreign,health professional,u
• Type of Report: Initial,Followup
• Report Date: 11/01/2019

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 09/13/2019
• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: Yes
• Device Operator: Health Professional
• Device Expiration Date: 12/19/2019
• Device Model Number: N/A
• Device Catalogue Number: 10491379
• Device Lot Number: 64456445
• Date Manufacturer Received: 10/07/2019
• Patient Sequence Number: 1
• Patient Outcome(s): Other