MAUDE Adverse Event Report: ROCHE MOLECULAR SYSTEMS, INC. - BRANCHBURG COBAS® EGFR MUTATION TEST V2; SOMATIC GENE MUTATION DETECTION SYSTEM

Catalog Number 07248563190

Device Problem False Positive Result (1227)

Patient Problems Cancer (3262); Solid Tumour (4552); No Clinical Signs, Symptoms or Conditions (4582)

Event Date 10/03/2022

Event Type  Injury  

Manufacturer Narrative

A supplemental mdr will be submitted to share the conclusion of the investigation.Facility name truncated due to character limit, full name: (b)(6).

Event Description

A customer from the united kingdom alleged discrepant results for one patient when using the cobas egfr mutation test v2.The sample was initially tested using the cobas egfr mutation test v2 and generated a "mutation detected" result for exon 19 deletion.A subsequent retest was performed using the same test and generated the same result.Two retests were performed, one using next generation sequencing (ngs) and another using sanger sequencing.Both did not detect exon 19 deletion.The result was originally reported as "egfr exon19 deletion/duplication mutation detected" but this was rescinded and an amended report was issued based on the ngs result (egfr negative).It has been communicated that the patient was administered osimertinib based on the cobas egfr mutation test v2 report.The patient's interval scan showed progression and therefore the treatment was discontinued.Further details are unknown at this time, including the timeframe between the initial cobas efgr mutation test v2 and the sequencing retests.An investigation is ongoing to evaluate the customer issue.

Manufacturer Narrative

Eval method code: added b11 - historical data analysis and b14 - analysis of production records.

Manufacturer Narrative

B1 - product problem: changed from yes to no b1 - adverse event: changed from no to yes b2 - outcomes attributed to adverse event: added c17649-other serious h1 - type of reportable event: changed from c25745-malfunction to c53569-serious injury updated imdrf codes ----- the original egfr cobas report stating that an exon 19 mutation had been detected was issued on 4th october 2022.The ngs result was then communicated to the patient¿s clinical team on 8th november 2022.The sample (dna isolation) was requested for internal investigation.However, the customer shared that they only have 4 ul left and need to keep some in storage with them so the customer will not be able to send sample to us.Patient medical history such as previous egfr results or treatments was also requested but no information was provided to date.The investigation included review of the provided data files from both, cobas egfr mutation test v2 and ngs.No abnormalities could be observed when reviewing the amplification curves generated with cegfrv2.Controls generated expected results indicating the assay is working as intended.Review of ngs bam files: no evidence of ex19del mutation nor anything that might have caused a false positive ex19del (such as a single nucleotide polymorphism (snp)).In addition, other exons were observed that are not represented in the cobas egfr v2 assay, and there was no exon 28 representation (cobas egfr v2 assay internal control) indicating a potential mutagenic test.Sanger sequencing: no mutation detected (data not provided).Based upon the ct values for ex19del mutation and rough estimates when compared to limit of detection study, this sample contains about 2.5-5% of ex19del mutation, which is a low percent mutation sample.The cause of the intra-assay discrepancy could not be identified.Based on the information provided, there are several potential causes: 1) due to differences in technologies, results between cobas egfr v2 and ngs or sanger sequencing will not correlate 100%, as documented in the method sheet of cobas egfr v2.In this case for ngs, the qiaseq targeted dna panels and qiaseq index kits were used.2) intended use differs between assays.The cobas egfrv2 test is indicated as a companion diagnostic to aid in selecting nsclc patients for treatment with egfr tyrosine kinase inhibitors.3) potentially, incorrect dna input was used during ngs workflow leading to inaccurate results.As the sample contained low percent mutation, the dna input would be critical in the detection and sensitivity of the assay.

Manufacturer Narrative

Updated e-clinical signs and symptoms codes and f-health impact codes.

• Brand Name: COBAS® EGFR MUTATION TEST V2
• Type of Device: SOMATIC GENE MUTATION DETECTION SYSTEM
• Manufacturer (Section D): ROCHE MOLECULAR SYSTEMS, INC. - BRANCHBURG; 1080 us highway 202 south; branchburg NJ 08876
• Manufacturer (Section G): ROCHE MOLECULAR SYSTEMS, INC. - BRANCHBURG; 1080 us highway 202 south; na; branchburg NJ 08876
• Manufacturer Contact: stacie-ann creighton ; 1080 us hwy 202 s; na; branchburg, NJ 08876 ; 9082537112
• MDR Report Key: 15974030
• MDR Text Key: 308102748
• Report Number: 2243471-2022-01037
• Device Sequence Number: 1
• Product Code: OWD
• UDI-Device Identifier: 00875197005448
• UDI-Public: 00875197005448
• Combination Product (y/n): N
• Reporter Country Code: UK
• PMA/PMN Number: P150047
• Number of Events Reported: 1
• Summary Report (Y/N): N
• Report Source: Manufacturer
• Source Type: Foreign,Health Professional
• Reporter Occupation: Other Health Care Professional
• Type of Report: Initial,Followup,Followup,Followup
• Report Date: 04/12/2023

1 Device was Involved in the Event

1 Patient was Involved in the Event

• Is this an Adverse Event Report?: Yes
• Is this a Product Problem Report?: Yes
• Device Operator: Health Professional
• Device Expiration Date: 08/31/2023
• Device Catalogue Number: 07248563190
• Device Lot Number: H31955
• Is the Reporter a Health Professional?: Yes
• Initial Date Manufacturer Received: 11/16/2022
• Initial Date FDA Received: 12/13/2022
• Supplement Dates Manufacturer Received: 03/08/2023; 03/08/2023; 04/11/2023
• Supplement Dates FDA Received: 03/30/2023; 03/31/2023; 04/12/2023
• Was Device Evaluated by Manufacturer?: Device Not Returned to Manufacturer
• Is the Device Single Use?: No
• Is This a Reprocessed and Reused Single-Use Device?: No
• Patient Sequence Number: 1
• Patient Outcome(s): Other