| Catalog Number 06P02-55 |
| 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 10/02/2022 |
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Event Type
malfunction
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Event Description
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The customer observed a false nonreactive alinity s hbsag result for one patient that was nat positive.The following data was provided: sid (b)(6) initial result = 0.48 s/co (nonreactive), repeats = 0.52 s/co and 0.52 s/co (nonreactive), diasorin liaison = 0.23 (reactive), biorad monolisa = 10.48 (reactive), nat hbv = 33.93 (positive), nat hbv from pool of 6 samples = positive.Additional laboratory data was provided: alinity s results: syphilis = 0.06 (negative), hiv ag/ab = 0.09 (negative), anti-hcv ii = 0.03 (negative).Public health institute results: anti-hbc total = 8.01 s/co (reactive), anti-hbc igm = 14.79 s/co (reactive).No impact to patient management was reported.
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Manufacturer Narrative
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An evaluation is in process.A follow-up report will be submitted when the evaluation is complete.Note: this report is being filed on an international product, alinity s hbsag, list number 6p02-55, that has a similar product distributed in the us, list number 06p02-60.
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Manufacturer Narrative
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The complaint investigation for false nonreactive alinity s hbsag results included a review of data and information provided by the customer, search for similar complaints, ticket trending review, labeling review, device history record review, and in-house testing.Ticket searches determined that there is a normal complaint activity for the product and lot numbers 41014fn00 and 36338fn00.Trending review did not identify any trends for the issue for the products.Device history record review did not identify any non-conformances, potential non-conformances or deviations associated with lot numbers 41014fn00 and 36338fn00 and the complaint issue.In-house sensitivity testing was completed with lot numbers 41014fn00 and 36338fn00.The sensitivity panels produced the expected reactive results, and no false nonreactive result was obtained.Further a commercially available seroconversion panel (zeptometrix hbv seroconversion panel hbv11003) was tested.The seroconversion panel results were compared to historical data of alinity s hbsag.Reagent lots 36338fn00 and 41014fn00 detected the same bleeds as reactive for the seroconversion panel.Labeling was reviewed and sufficiently addresses the customer's issue.Based on our investigation, no systemic issue or deficiency with the alinity s hbsag reagent for lots 41014fn00 and 36338fn00 was identified.Note: the complaint investigation also included lot 36338fn00 that generated the false nonreactive alinity i hbsag results at the other laboratory during troubleshooting of the patient sample.Section b5 describe event or problem was updated to include additional data that was provided by the customer on 27oct2022.
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Event Description
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Additional data was provided by the customer on 27oct2022: the sample was sent for repeat testing on another alinity (serial (b)(6), lot 36338fn00) at a different laboratory for troubleshooting purposes only: alinity s hbsag initial result = 0.52 s/co (nonreactive) siemens centaur results = 4.99 s/co, 5.19 s/co, and 4.95 s/co (reactive).
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Event Description
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Additional information was provided by the customer on (b)(6) 2022.The patient was redrawn on (b)(6) 2022 and generated the following results: alinity s hbsag initial result = 0.52 s/co (nonreactive) biorad monolisa hbsag ultra = 0.59 (nonreactive) anti-hbc igm = 5.38 s/co (positive) anti-hbc total = 9.94 s/co (positive) anti-hbs = 3.14 miu/ml (negative) genotyping hepatitis b virus = positive (genotype d, hbsag subtype ayw2) no impact to patient management was reported.
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Manufacturer Narrative
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Section b5 describe event or problem was updated to include new patient information that was provided by the customer on 01dec2022.
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Manufacturer Narrative
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Updated 10mar2023: section h10 addtl mfg narrative updated to include return sample testing results.Sample return was received after the original complaint investigation.The returned sample, id (b)(6), was re-tested in-house with alinity s hbsag and showed a nonreactive result of 0.46 s/co.Further, the sample was tested with alinity i hbsag next, alinity i hbsag next confirmatory, architect core m (anti-hbc igm), architect core (anti-hbc total) and architect anti-hdv (anti-hdv, delta prototype assay) assays.The results were as follows: alinity i hbsag next: 24.65 s/co, 25.38 s/co, 23.74 s/co, 23.64 s/co and 25.15 s/co.Alinity i hbsag next confirmatory: neutralization of 100 (confirmed positive).Architect core (anti-hbc total): 6.57 s/co and 6.66 s/co (repeat reactive).Architect core m (anti-hbc ig m): 13.53 s/co and 13.64 s/co (repeat reactive).Architect anti-hdv (anti-hdv, delta prototype assay): 121 rlu, 0.2 s/co (nonreactive).Hbv dna testing by pcr and sequencing to identify potential variation in the sample material was performed using a very sensitive, established sequencing method.Summary of results: dna from the complaint sample was extracted in 7 replicates, 0.5 ml sample each, total from 3.5 ml.All extracted dna was used as template for two rounds of pcr to amplify s-gene, total 14 pcr reactions.2 of 14 pcrs had very faint bands of approximately correct size on agarose gel suggesting non-specific amplification from a sample without hbv-specific template.The two pcr products were sanger sequenced using hbv primers, and generated sequence fragments were confirmed to be human sequences.The blast showed 99% identity to the human dna sequence.There were no hbv-specific dna identified in the sample.The review of all results indicates the first sample was taken during the late phase of an acute primary infection with low concentration of hbv dna and hbsag, and high levels of igm antibodies against the hbv core protein.The results of the second sample support this interpretation, with hbv dna and hbsag negative by all assays, anti-hbv igm signal reduced and anti-hbc increasing.The reason why the alinity s hbsag assay and architect hbsag qual ii assay did not detect the first sample as hbsag reactive was not conclusively determined; however, given the fact that the analytical sensitivity of the abbott assays are equal to, if not better, than the comparator assays, for the wildtype of the virus there may be variation within the dna in the a-determinant region that may have been hidden due to the low level of hbv dna present which negatively affects the binding of the abbott hbsag assays reducing the analytical sensitivity for this specific sample.Overall, the results of return sample testing do not change the outcome of our initial investigation; no systemic issue or deficiency with the alinity s hbsag reagent for lots 41014fn00, 36338fn00,42658fn00 or with the architect hbsag qualitative ii reagent for lot 37293fn00 was identified.
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Event Description
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Updated on 05feb2023: additional clarifying information was received on 13jan2023: the last sample collected from the patient was drawn on 27oct2022 and not on 17oct2022.The sample also had nat testing completed (nat on roche cobas mpx) and generated negative results.
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Manufacturer Narrative
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Section b5 describe event or problem was updated on 05feb2023 to include clarifying information that was provided on 13jan2023.Section b5 describe event or problem was updated on 05feb2023 to correct the date the last sample was collected from the patient.
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Manufacturer Narrative
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Section b5 describe event or problem was updated to include additional information (new lot number 40599fn00) that was provided on 28mar2023.The new lot number was used for troubleshooting purposes only.Section h10 addtl mfg narrative was updated to include the investigation results of the lot numbers used for troubleshooting purposes only.The complaint investigation for false nonreactive alinity s hbsag results (and architect hbsag qualitative ii troubleshooting results and alinity i hbsag qualitative ii troubleshooting results) included a review of data and information provided by the customer, search for similar complaints, ticket trending review, labeling review, and device history record review.In-house testing was completed for the alinity s hbsag lot numbers and alinity i hbsag lot number.Field data review was performed for the architect hbsag qualitative ii assay.Additionally, return sample testing was completed.The returned sample, id 10121471, was re-tested in-house with alinity s hbsag and showed a nonreactive result of 0.46 s/co.Further, the sample was tested with alinity i hbsag next, alinity i hbsag next confirmatory, architect core m (anti-hbc igm), architect core (anti-hbc total) and architect anti-hdv (anti-hdv, delta prototype assay) assays.The results were as follows: alinity i hbsag next: 24.65 s/co, 25.38 s/co, 23.74 s/co, 23.64 s/co and 25.15 s/co.Alinity i hbsag next confirmatory: neutralization of 100 (confirmed positive).Architect core (anti-hbc total): 6.57 s/co and 6.66 s/co (repeat reactive).Architect core m (anti-hbc ig m): 13.53 s/co and 13.64 s/co (repeat reactive).Architect anti-hdv (anti-hdv, delta prototype assay): 121 rlu, 0.2 s/co (nonreactive).Hbv dna testing by pcr and sequencing to identify potential variation in the sample material was performed using a very sensitive, established sequencing method.Summary of results: dna from the complaint sample was extracted in 7 replicates, 0.5 ml sample each, total from 3.5 ml.All extracted dna was used as template for two rounds of pcr to amplify s-gene, total 14 pcr reactions.2 of 14 pcrs had very faint bands of approximately correct size on agarose gel suggesting non-specific amplification from a sample without hbv-specific template.The two pcr products were sanger sequenced using hbv primers, and generated sequence fragments were confirmed to be human sequences.The blast showed 99% identity to the human dna sequence.There were no hbv-specific dna identified in the sample.The review of all results indicates the first sample was taken during the late phase of an acute primary infection with low concentration of hbv dna and hbsag, and high levels of igm antibodies against the hbv core protein.The results of the second sample support this interpretation, with hbv dna and hbsag negative by all assays, anti-hbv igm signal reduced and anti-hbc increasing.The reason why the alinity s hbsag assay and architect hbsag qual ii assay did not detect the first sample as hbsag reactive was not conclusively determined; however, given the fact that the analytical sensitivity of the abbott assays are equal to, if not better, than the comparator assays, for the wildtype of the virus there may be variation within the dna in the a-determinant region that may have been hidden due to the low level of hbv dna present which negatively affects the binding of the abbott hbsag assays reducing the analytical sensitivity for this specific sample.Ticket searches determined that there is a normal complaint activity for the products and lot numbers 41014fn00, 36338fn00, 42658fn00, 37293fn00, and 40599fn00.Trending review did not identify any trends for the issue for the products.Device history record review did not identify any non-conformances, potential non-conformances or deviations associated with lot numbers 41014fn00, 36338fn00, 42658fn00, 37293fn00, and 40599fn00 and the complaint issue.Labeling was reviewed and sufficiently addresses the customer's issue.In-house sensitivity testing was completed with alinity s hbsag lot numbers 41014fn00, 36338fn00, 42658fn00, and alinity i hbsag lot number 40599fn00.The sensitivity panels produced the expected reactive results, and no false nonreactive result was obtained.Further a commercially available seroconversion panel (zeptometrix hbv seroconversion panel hbv11003) was tested.The seroconversion panel results were compared to historical data of alinity s hbsag.Reagent lots 36338fn00 and 41014fn00 detected the same bleeds as reactive for the seroconversion panel.The overall performance of the architect hbsag qualitative ii assay was reviewed using field data from customers worldwide.The median population result for lot 37293fn00 for the reactive population is comparable with all other lots in the field and falls within established baselines, confirming no systemic issue for the lot.The overall performance of the alinity i hbsag qualitative ii assay was reviewed using field data from customers worldwide.The median population result for lot 40599fn00 for the reactive population is comparable with all other lots in the field and falls within established baselines, confirming no systemic issue for the lot.Based on our investigation, no systemic issue or deficiency with the alinity s hbsag reagent for lots 41014fn00, 36338fn00,42658fn00 or with the architect hbsag qualitative ii reagent for lot 37293fn00 or with the alinity i hbsag qualitative ii reagent for lot 40599fn00 was identified.Overall, the results of the additional lot investigation do not change the outcome of the initial investigation.
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Event Description
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Additional information was provided on 28mar2023: a sample from the same patient generated nonreactive results with alinity i hbsag qualitative ii assay (lot 40599fn00).No further information was provided.No impact to patient management was reported.
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Manufacturer Narrative
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Additional testing was completed on the returned sample, id (b)(6).The number of patient results depending on lot is between 1 to 21 for architect and between 1 and 6 for alinity i.This low number of samples is not sufficient for lot to lot comparison or comparison to the worldwide population.With patients being represented this low, the median results by lot can be influenced by a single result within the expected s/co range.The returned sample, id (b)(6), was tested in-house using the abbott realtime hbv 0.5 ml assay and m2000 instrument system (m2000sp for sample extraction and m2000rt for real-time pcr amplification/detection) to quantify viral loads in the specimen.Sample was detected by realtime hbv assay with viral load result < 10 iu/ml.Attempting to pcr and sequence partial s-gene aa 111-176 to determine if any escape mutations in the a-determinant are present.-the dna from the complaint sample was extracted in 9 replicates, 0.5 ml sample each.-successfully pcr amplified and sequenced s-gene fragment spanning amino acids 111-176 from three replicates.Sequences for all replicates were 100% identical.-identified three amino acid substitutions t118a, p120t and p127t vs genotype d consensus sequence.These were not observed in the belgrade sequence.-p120t is known as escape mutation.Frequency of the p120t in genotype d is rare 1.2% (67/5598) based on the hbv sequence data base.The sample collected on september 29, 2022, is representative of a late phase acute primary hbsag infection.This conclusion is based on review of the entire testing profile including the initial draw (9/29/22) exhibiting low level dna and hbsag in conjunction with high levels of igm antibodies against the hbv core protein.This conclusion is further supported by the results of the second sample draw (10/27/2022), demonstrating hbv dna and hbsag negative results, anti-hbc igm decreasing and anti-hbc increasing.The sequencing results from the medical faculty of microbiology and immunology of belgrade concluded there were no mutations in the a-determinant loop that could potentially impact the targeted region of detection by the abbott hbsag assays.The sequencing data generated at abbott matched the data from belgrade with the exceptions of mutations in three positions, specifically amino acids t118a, p120t, and p127t.This difference may be attributable to preferential amplification of a mixed population of viral isolates at low viral load (<10 iu/ml), as can be expected when viral isolates with different sequences exist in the same sample.Although none of these mutations are in the target epitopes of the abbott assay, the unique combination of three mutations near the target epitope of one of the monoclonals may have reduced the analytical sensitivity of the assay in this specific case which has not been described in the literature before.Notably, per the publication, lou et al., ¿an ultra-sensitive abbott architect assay for the detection of hepatitis b virus surface antigen (hbsag)¿, j clin virol, 2018 aug;105:18-25, have previously demonstrated detection of each of these individual mutations in other native samples with different mutation profiles using abbott hbsag assays, including the architect hbsag qual ii assay.The investigation concludes the most likely cause of the negative abbott hbsag results are hbsag mutation(s) adjacent to the assay¿s antibody binding region in conjunction with a very low viral load.We cannot however rule out potential impact from a secondary interfering factor within the sample.Abbott¿s investigation as well as alims conclusions support abbott¿s hbsag reagents are performing as intended per design.This case is related to the unique characteristics of this sample and not indicative of a systemic issue.While sample donations in this phase are infrequent, they can occur.No assay can detect all hbv positive specimens.Nat testing and/or testing with an hbcore assay provide additional protection for specimens in this phase of infection.
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Event Description
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Additional information was provided on 28mar2023: a sample from the same patient generated nonreactive results with alinity i hbsag qualitative ii assay (lot 40599fn00).No further information was provided.No impact to patient management was reported.
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Search Alerts/Recalls
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