| Catalog Number 731774 |
| Device Problem
False Negative Result (1225)
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| Patient Problem
No Clinical Signs, Symptoms or Conditions (4582)
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| Event Date 08/10/2023 |
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Event Type
Injury
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Event Description
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On 25feb2024, grifols customer, (b)(6) hospital (pakistan), reported three specimens collected from august (b)(6) 2023 that were confirmed hcv serology positive but were nonreactive in ultrio elite discriminatory hcv assay (dhcv) using master lot (ml) 706519.Two of the three specimens were also quantified in "roche pcr" with result 'detected'.None were tested in the ultrio elite screening assay (ue).The customer requested an explanation for the discrepant results noting that "detection limits of pcr (15 iu/ml) is higher than that of dnat (2.4 iu/ml)." the record states no patient was at risk because the serology was positive.No specimens remain for investigation.Information was requested including results reports, assay names used, and specimen handling information, and not all was provided.On 19mar2024, grifols received information indicating the customer was testing known positives rather than screening normal donors.On 20mar2024, gds product quality committee meeting determined the complaint was not reportable as an mdr to the fda for the following reasons: "regarding the "cobas 6800 pcr" result "detected", grifols believes this assay is the cobas hcv assay.A result of "detected" with no associated quantitation in this assay indicates hcv rna is detected but below the lower limit of quantitation of the assay, which is 15 iu/ml hcv.It would not be unexpected for a sample below the limit of detection of the ue dhcv assay of 2.4 iu/ml to be detected in cobas hcv and not detected in ue dhcv.Previous events search and qc release testing do not indicate an hcv sensitivity issue with the ue dhcv assay, and there is no indication that any ue dhcv assay reagent lot is not performing as expected.Testing with the dhcv assay without a ue screening result is outside the ue instructions for use.The same customer ((b)(6) hospital) previously reported unexpected results in 2022 from similar testing (ue discriminatory assay was performed without ue screening assay).Grifols reported the events as an mdr (3500a_2032600-2022-00004) to prioritize caution but reiterated in the mdr report that "instructions in the package insert regarding discriminatory testing (initially screening with the ultrio elite multiplex assay and testing samples with reactive results in the discriminatory assays) were not followed by the customer." there is no risk of release of unidentified hcv infected donations due to potential false negative dhcv results because the customer was testing samples already identified as hcv positive by other assays.From the information available, the assay is working as designed." grifols continues to monitor unexpected results regularly to identify true assay malfunction.This event is not reportable in the us as an mdr due to the above assessment." however, on 02apr2024 and 11apr2024 grifols received additional information on testing results, especially, the pcr results (vs 'detected' as of 19mar2024).Testing information is summarized below.Sample (b)(6) 08aug2023: serology positive (b)(6) 2023: dhcv nonreactive (s/co 0.05) not tested by pcr sample (b)(6) (b)(6) 2023: serology positive (b)(6) 2023*: roche pcr: 694 iu/ml (b)(6) 2023: dhcv nonreactive (s/co 0.00 and 0.02) sample (b)(6) (b)(6) 2023: serology positive (b)(6) 2023*: roche pcr: 262 iu/ml (b)(6) 2023: dhcv nonreactive (s/co 0.00 and 0.00) *actual date is unknown but confirmed to be before dhcv testing in both specimens since the pcr results revealed significantly higher hcv titers (694 iu/ml and 262 iu/ml) compared to the dhcv lod of 2.4 iu/ml, the issue is determined to be reportable to the fda as an mdr on 12apr2024 due to the discrepant results between the ue dhcv and pcr assays.There is no risk of release of unidentified hcv infected donations due to potential false negative dhcv results because the customer was testing samples already identified as hcv positive by other assays.Despite the additional info, grifols believe there is no hcv sensitivity issue with ue ml 706519 or any ue lot, supported by previous events search and lot history with the customers.The lot ml 706519 has been in use with this customer since aug 2023 or even earlier, and with other customers also, without any additional complaints regarding hcv sensitivity.The device history record review identified no issues with hcv sensitivity with ml 706519.Grifols reviewed the dhcv run reports and did not observe any indications of instrument or assay malfunction.Based on the available information, there is no indication of hcv sensitivity issues with ultrio elite ml 706519 or the ultrio elite assay in general.Investigation is still ongoing.Follow-up information for this report will be provided when available.
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Event Description
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On (b)(6) 2024, grifols customer, (b)(6) hospital, reported three specimens collected from (b)(6) 2023 that were confirmed hcv serology positive but were nonreactive in ultrio elite discriminatory hcv assay (dhcv) using master lot (ml) 706519.Two of the three specimens were also quantified in "roche pcr" with result 'detected'.None were tested in the ultrio elite screening assay (ue).The customer requested an explanation for the discrepant results noting that "detection limits of pcr (15 iu/ml) is higher than that of dnat (2.4 iu/ml)".The record states no patient was at risk because the serology was positive.No specimens remain for investigation.Information was requested including results reports, assay names used, and specimen handling information, and not all was provided.On 19mar2024, grifols received information indicating the customer was testing known positives rather than screening normal donors.On 20mar2024, gds product quality committee meeting determined the complaint was not reportable as an mdr to the fda for the following reasons: "regarding the "cobas 6800 pcr" result "detected", grifols believes this assay is the cobas hcv assay.A result of "detected" with no associated quantitation in this assay indicates hcv rna is detected but below the lower limit of quantitation of the assay, which is 15 iu/ml hcv.It would not be unexpected for a sample below the limit of detection of the ue dhcv assay of 2.4 iu/ml to be detected in cobas hcv and not detected in ue dhcv.Previous events search and qc release testing do not indicate an hcv sensitivity issue with the ue dhcv assay, and there is no indication that any ue dhcv assay reagent lot is not performing as expected.Testing with the dhcv assay without a ue screening result is outside the ue instructions for use.The same customer ((b)(6) hospital) previously reported unexpected results in 2022 from similar testing (ue discriminatory assay was performed without ue screening assay).Grifols reported the events as an mdr (3500a_2032600-2022-00004) to prioritize caution but reiterated in the mdr report that "instructions in the package insert regarding discriminatory testing (initially screening with the ultrio elite multiplex assay and testing samples with reactive results in the discriminatory assays) were not followed by the customer." there is no risk of release of unidentified hcv infected donations due to potential false negative dhcv results because the customer was testing samples already identified as hcv positive by other assays.From the information available, the assay is working as designed." grifols continues to monitor unexpected results regularly to identify true assay malfunction.This event is not reportable in the us as an mdr due to the above assessment." however, on 02apr2024 and 11apr2024 grifols received additional information on testing results, especially, the pcr results (vs 'detected' as of (b)(6) 2024).Testing information is summarized below.Sample (b)(6).(b)(6) 2023: serology positive (b)(6) 2023: dhcv nonreactive (s/co 0.05) not tested by pcr.Sample (b)(6).(b)(6) 2023: serology positive (b)(6) 2023*: roche pcr: 694 iu/ml (b)(6) 2023: dhcv nonreactive (s/co 0.00 and 0.02) sample (b)(6).(b)(6) 2023: serology positive (b)(6) 2023*: roche pcr: 262 iu/ml (b)(6) 2023: dhcv nonreactive (s/co 0.00 and 0.00) *actual date is unknown but confirmed to be before dhcv testing in both specimens since the pcr results revealed significantly higher hcv titers (694 iu/ml and 262 iu/ml) compared to the dhcv lod of 2.4 iu/ml, the issue is determined to be reportable to the fda as an mdr on 12apr2024 due to the discrepant results between the ue dhcv and pcr assays.There is no risk of release of unidentified hcv infected donations due to potential false negative dhcv results because the customer was testing samples already identified as hcv positive by other assays.Despite the additional info, grifols believe there is no hcv sensitivity issue with ue ml 706519 or any ue lot, supported by previous events search and lot history with the customers.The lot ml 706519 has been in use with this customer since aug 2023 or even earlier, and with other customers also, without any additional complaints regarding hcv sensitivity.The device history record review identified no issues with hcv sensitivity with ml 706519.Grifols reviewed the dhcv run reports and did not observe any indications of instrument or assay malfunction.Based on the available information, there is no indication of hcv sensitivity issues with ultrio elite ml 706519 or the ultrio elite assay in general.Investigation is still ongoing.Follow-up information for this report will be provided when available.30may2024: investigational testing to confirm the ue and dhcv assay performance, grifols performed additional testing on hcv qc panels with ue ml 706519.The qc panels are used for master lot release testing.The sample size and acceptance criteria for qc release testing were applied to the investigational testing.Testing was completed on (b)(6) 2024.For ue, hcv 1a qc panels at 100 c/ml and 30 c/ml were 100% reactive (specification of 100% and >=70%, respectively).The hcv 2b qc panels at 300 c/ml and ~100 c/ml were also 100% reactive (specification of >=95% and >=70%, respectively).For dhcv, hcv 1a qc panels at 100 c/ml and 30 c/ml were 100% reactive (specification of 100% and >=70%, respectively).The hcv 2b qc panels at 300 c/ml and ~100 c/ml were also 100% reactive (specification of >=95% and >=70%, respectively).The investigational testing confirmed the ue and dhcv assays performed as expected.Interpretation of results the customer deferred specimens from transfusion/ transplant based on reactive serology results and roche pcr results.Grifols referenced the center for disease control "interpretation of results of tests for hepatitis c virus infection and further actions" for the three specimens under investigation.Sample (b)(6) was hcv serology reactive and dhcv nonreactive.This would be interpreted as "presumptive hcv infection".This indicates either past hcv infection that has resolved or active infection with titer below the lod of the dhcv assay.Additional testing of the specimens and information would be required to rule out issues with storage or handling of the specimen that could affect results.Sample (b)(6) and sample (b)(6) were hcv serology reactive and hcv rna detected in roche pcr (694 iu/ml and 262 iu/ml, respectively), and nonreactive in dhcv.These would be interpreted as "current hcv infection".In these cases, the dhcv results are unexpected.The concentrations detected in the roche assay would be detected in dhcv under normal circumstances.The dhcv tests were performed after the roche pcr testing, but storage and handling information was not available.Additional testing of the specimens and information would be required to rule out issues with storage or handling of the specimen that could affect results.Risk assessment: severity: minor.There is no risk of release of unidentified hcv infected donations due to incorrect dhcv results because the customer was testing specimens already identified as hcv positive in other assays.A discriminatory assay discordant result can cause additional testing and questioning of the result by the customer.Probability: remote.The probability of a dhcv result discordant with serology in any ue ml is remote based on the previous events search.Overall risk: negligible.Panther assay specific risk analysis for bloodbank assays ((b)(4)), gdss-(b)(4) version 2.0, and product safety risk management procedure, (b)(4) version 11.0 were reviewed to assess risk.New risk to patient safety was not identified.Product impact no impact to product was identified.Review of the qc release process and a previous events search in the grifols complaint system indicate that the assay is working as designed.Customer impact the impact to the customer was questioning the discord between dhcv and roche/ serology results.Following iso 14971, grifols risk assessment is based on severity of a harm or impact to human health and the probability of occurrence of harm or impact to human health.There is no risk of release of unidentified hcv infected donations due to incorrect dhcv results because the customer was testing specimens already identified as hcv positive in other assays.Based on the severity rating of ·minor· and probability rating of ·remote·, the overall risk posed by a discrepant dhcv result is determined to be negligible.
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Search Alerts/Recalls
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