MAUDE Adverse Event Report: SIEMENS HEALTHCARE DIAGNOSTICS, INC. ADVIA CENTAUR XPT CA15-3; CA15-3 IMMUNOASSAY

Model Number N/A

Device Problem No Apparent Adverse Event (3189)

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

Event Date 03/09/2020

Event Type  malfunction  

Manufacturer Narrative

Siemens healthcare diagnostics is investigating.The full context of the scenario above is unknown (e.G.Rationale for testing on 3 platforms, which results would be considered accurate, whether patients were re-baselined prior to implementation of a new tumor marker assay, etc).It is well known for tumor markers that results from different platforms/assays cannot be used interchangeably and this limitation is expressly stated in siemens ifus for tumor marker assays.The instructions for use states: "warning: the concentration of ca 15-3 in a given specimen, as determined by assays from different manufacturers, can vary because of differences in assay methods and reagent specificity.The results reported by the laboratory to the physician must include the identity of the assay for ca 15-3 used.Values obtained with different assay methods cannot be used interchangeably.If, in the course of monitoring a patient, the assay method used for determining serial levels of ca 15-3 is changed, the laboratory must perform additional serial testing to confirm baseline values.The advia centaur ca 15-3 assay is based on the df3 and 115d8 antibodies available through agreement with fujirebio diagnostics, inc." "measurements of ca 15-3 should always be used in conjunction with other diagnostic procedures, including information from the patient's clinical evaluation".Siemens has requested additional information mdr 1219913-2020-00100 was filed for samples with collection date (b)(6) 2020.Mdr 1219913-2020-00101 was filed for samples with collection date (b)(6) 2020.Mdr 1219913-2020-00103 was filed for samples with collection date (b)(6) 2020.

Event Description

A customer is questioning advia centaur xpt ca15-3 results for multiple patient samples tested with one reagent lot.This customer transitioned from immulite to the advia centaur xpt ca15-3 method.A patient correlation study was performed at the customer site during the transition; customer observed acceptable correlation results.The customer then observed discordant low advia centaur xpt ca15-3 results when they began reporting patient results.The customer provided atellica im ca15-3 results for troubleshooting.The customer is not questioning the atellica im ca15-3 results.There is no indication that patient treatment was prescribed, delayed or altered.There was no report of adverse health consequences due to the discordant ca15-3 results.

Manufacturer Narrative

Siemens filed initial mdr 1219913-2020-00102 on 04/10/2020.Additional information 04/13/2020: customer informed physicians regarding the changing of methods from immulite to advia centaur xpt before the go live date.Additional information from 04/23/2020: customer performed additional correlation testing for troubleshooting using advia centaur xpt ca153 lot 179 and immulite brm lot 302.In this study, 4 of the previous patient samples were tested neat and then diluted 1:4.The samples repeated with similar results as the original results for both advia centaur xpt and immulite instruments.Diluted results were lower, but without serial dilutions no interpretation about linearity can be made, however the immulite diluted results are only about 10% lower so it does not seem likely that this issue is related to an interferent.There is no claim that these methods should match and the methods are standardized differently.According to the method qc inserts, it can be seen that immulite expected results are higher than advia centaur xpt.Siemens looked into the release data of the advia centaur xpt and immulite kit lots and neither are showing a strong bias that would cause this customer observation.Siemens continues to investigate.Mdr 1219913-2020-00100 supplemental report 1 was filed for samples with collection date (b)(6) 2020.Mdr 1219913-2020-00101 supplemental report 1 was filed for samples with collection date (b)(6) 2020.Mdr 1219913-2020-00103 supplemental report 1 was filed for samples with collection date (b)(6) 2020.

Manufacturer Narrative

Siemens filed mdr 1219913-2020-00102 on 04/10/2020.Siemens filed mdr 1219913-2020-00102 supplemental report 1 on 05/05/2020.Additional information from 05/06/2020: siemens acquired and tested 8 patient samples using advia centaur xp ca 15-3 lot 181 and immulite 2000 brm lot 302.The sample result differences ranged from 1.85 to 30.1 u/ml absolute difference between testing on the systems on the same patient and simple regression slope of 1.4.All samples are clinically concordant based on each systems reference range.Both tests use mouse monoclonal antibodies.The concentration of ca 15-3 in a given specimen determined with assays from different manufacturers can vary because of differences in assay methods, calibration, and reagent specificity.Ca 15-3 determined with different manufacturers' assays will vary depending on the method of standardization and antibody specificity.Additional information from 05/11/2020: the customer observed a bias for samples using advia centaur xpt ca 15-3 vs immulite 2000 brm of > +/-30% on some samples.Samples overall were approximately 43% different with the immulite 2000 results positively biased.Siemens reviewed information provided to determine probable root cause.Qc was in range for both methods; the original method comparison performed during advia centaur xpt install had a slope of 0.982 between the methods on patient samples, however it was determined that these were not all native samples but were control material and spiked/contrived samples.The customer performed a dilution on 4 of the samples however this did not lower the result appreciably so an interferent is not suspected cause for the higher immulite 2000 results.Siemens reviewed the release data of the advia centaur systems ca 15-3 and immulite 2000 brm kit lots used by the customer for comparisons and there was no positive bias observed with immulite 2000 lot 302 that would account for the patient samples running this much higher.Siemens performed a study with 8 patient samples tested in duplicate on both methods.Immulite 2000 brm lot 302 (same lot as customer) and advia centaur xp/xpt ca15-3 reagent lot 181/ calibrator lot 62 were used as they were the only lots available for testing at the lab.The sample result differences ranged from 1.85 to 30.1 u/ml absolute difference between testing on the systems on the same patient.Overall the immulite 2000 brm results were 42.8 % higher which is consistent with what the customer observed.All of the samples were concordant based on each methods cutoff/reference range: immulite 2000 brm 95th percentile of the observed results =38.7 u/ml; advia centaur xp/xpt ca15-3 99th percentile of the observed results= 32.4 u/ml.The advia centaur xp/xpt ca 15-3 and immulite 2000 brm assays are not standardized the same way; they are both standardized to an internal standard and there is no claim that results will match.Per the advia centaur xp/xpt ca 15-3 instructions for use, "the concentration of ca 15-3 in a given specimen determined with assays from different manufacturers can vary because of differences in assay methods, calibration, and reagent specificity.Ca 15-3 determined with different manufacturers' assays will vary depending on the method of standardization and antibody specificity." siemens' investigation is complete.No product performance issue is confirmed.The method code, result code and conclusion code have been updated to reflect the additional information.Reference section h6 of this report for the updated codes.Mdr 1219913-2020-00100 supplemental report 2 was filed for samples with collection date (b)(6) 2020.Mdr 1219913-2020-00101 supplemental report 2 was filed for samples with collection date (b)(6) 2020.Mdr 1219913-2020-00103 supplemental report 2 was filed for samples with collection date (b)(6) 2020.

• Brand Name: ADVIA CENTAUR XPT CA15-3
• Type of Device: CA15-3 IMMUNOASSAY
• Manufacturer (Section D): SIEMENS HEALTHCARE DIAGNOSTICS, INC.; 511 benedict avenue; tarrytown, ny
• MDR Report Key: 9950965
• MDR Text Key: 203691126
• Report Number: 1219913-2020-00102
• Device Sequence Number: 1
• Product Code: MOI
• UDI-Device Identifier: 00630414461311
• UDI-Public: 00630414461311
• Combination Product (y/n): N
• PMA/PMN Number: K012357
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: foreign,health professional,u
• Type of Report: Initial,Followup,Followup
• Report Date: 06/01/2020

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Date FDA Received: 04/10/2020
• Is this an Adverse Event Report?: No
• Is this a Product Problem Report?: Yes
• Device Operator: Health Professional
• Device Expiration Date: 04/29/2020
• Device Model Number: N/A
• Device Catalogue Number: 10327620
• Device Lot Number: 179
• Was Device Available for Evaluation?: No
• Date Manufacturer Received: 05/06/2020
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1