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On 05oct2023, grifols customer, (b)(6) (mexico) reported one plasma sample tested (b)(6) 2023 that was nonreactive (s/co 0.10) with ultrio elite (ue) master lot (ml) 706866 but was reactive for hbsag and hbv reactive in "cobas 6800".The sample was also reactive for hbsag on (b)(6) 2023.The donation was not used.The customer drew a second sample from the same donor on or around (b)(6) 2023.This sample was reactive in ue (s/co 14.42), hbv reactive in "cobas 6800", and hbsag reactive.An aliquot of this second sample was also tested in a real time pcr quant assay for hbv; the result was hbv not detected.This complaint was originally registered as a non-complaint 'routine service' work order on 06oct2023 by the regional grifols diagnostic customer technical support team.The investigation was completed by the regional grifols diagnostic customer technical support team under the non-complaint work order with the conclusion that low titer hbv was the root cause of the discordant results.A customer letter was provided on 07dec2023.The mis-categorization of the complaint was identified during the quarterly audit of routine service and inquiry records completed by grifols diagnostic solutions (gds) qa complaints team on 20feb2024.A new work order for this issue was opened on 20feb2024 as a potential health and safety complaint so the issue could be evaluated by the gds product quality committee (pqc) for reportability, and investigation could be further performed by the gds qa complaints team.The pqc has determined the issue to be reported to the fda as an mdr.In the meanwhile, the pqc has requested a capa to be opened to retrain the personnel responsible for the mis-categorization to prevent reoccurrence.Capa 200040314 was opened for the retraining and to ensure the effectiveness of the retraining.The retraining was completed on 20mar2024 to reinforce knowledge for classifying complaints, especially potential health and safety complaints during the complaint case registration process.No sample remains for investigation.A previous events search for hbv sensitivity issues across all ue master lots was performed and no trends were identified that indicated a loss of sensitivity in any ue reagent master lot or ml 706866.Information was requested including results reports, assay names used, and sample handling information.Grifols also requested the customer testing protocol as it is suspected the customer was performing an evaluation of the ue assay and the "cobas 6800" assay rather than normal donor screening.No additional information was provided.It is suspected the "cobas 6800" assay used is the roche cobas mpx assay for use on the cobas 6800 system.This assay has a lower hbv sensitivity than the ue assay (mpx limit of detection for hbv is 1.3 iu/ml in serum and 1.4 iu/ml in plasma; ue limit of detection is 4.3 iu/ml), so it would not be unexpected for a low titer hbv sample to be reactive in mpx and nonreactive in ue.In addition, intermittent reactivity is expected in samples with low titer (at or below the 95% limit of detection for hbv of ue).The information provided for the real time pcr quant assay for hbv used states the assay has an lod of 20 iu/ml, which is above the ue hbv lod.Although the lod of the pcr was not low enough to justify the sample titer was at or below the lod of the ue assay, the varied results between assays are consistent with a sample around the lod of both the quant assay used and the ue assay.The serology information provided (hbsag reactive) was consistent with either acute or chronic hbv infection.Additional information would be required to differentiate between the two conditions.The root cause of the disagreement between ue and "cobas 6800"/ serology is likely low titer hbv, but this could not be confirmed due to lack of sample for investigation.Intermittent reactive results are expected in low titer samples (at or below the 95% lod of the ue assays).Based on the previous events search and qc release data for ml 706866, the ultrio elite assay is working as designed.A risk assessment was performed.The severity of a blood screening false negative result is critical, as use of an infected donation can cause multiple infections.The probability of a false negative result is remote based on the previous events search.False negative results do occur but are rare.New risk to patient safety was not identified.There were no related non-conformances noted in the manufacturing record or as part of a search of the nonconformance records for this lot number.Product impact no impact to product was identified.Review of the qc release data 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 the ultrio elite and cobas 6800/ 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.Based on the severity rating of ·critical· and probability rating of ·remote·, the overall risk posed by a false negative ultrio elite result is determined to be acceptable.This is the final report and no additional information is expected.
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