|
Intended use.Vidas sars-cov-2 igg (9cog) is an automated qualitative assay for use on the vidas family of instruments, for the detection of immunoglobulin g (igg) specific for sars-cov-2 in human serum or plasma (lithium heparin) using the elfa (enzyme linked fluorescent assay) technique.This assay is intended for use as an aid to determine if individuals may have been exposed and infected by this virus and if they have mounted a specific anti-sars-cov-2 igg immune response.Interpretation of results according to test value (i) is as follows: index interpretation i less than 1.00 negative, i = 1.00 positive.Description of the issue: on (b)(6) 2021, a customer in (b)(6) notified biomerieux of false negative result when testing with vidas sars-cov-2 igg (9cog) 60t (ref.(b)(4), lot # 1008397990, expiry date: 04-nov-2021) in context of external quality control (qc) labquality.The issue observed by the client happened with the sample s002, which was expected to be positive.There is no patient associated with this external survey sample; therefore, there is no adverse event related to any patient's state of health.Biomerieux internal investigation has been initiated.Note: reference (b)(4) is not sold or distributed in the united states.However, u.S-only product reference, (b)(4) has the same formulation and physical properties as reference (b)(4).
|
|
An internal investigation was performed following notification from a customer in poland that they experienced an eqa failure in association with vidas® sars cov-2 igg ref.(b)(4)/ lot 1008397990) with sample (b)(6) from labquality program.The result for sample (b)(6) was expected positive and was instead found negative by the vidas sars cov-2 igg peer group.Quality control records: there is neither capa nor non-conformity recorded on this vidas assay in link with the object of this complaint.Tests/analysis performed in the complaint laboratory: control chart analysis.The analysis was performed for: 4 internal samples with a positive target.7 batches of vidas sars cov-2 igg including the customer lot.All the samples results comply with the specifications and the lot of vidas sars cov-2 igg mentioned in the complaint is in the trend compared to the other lots.Analysis of results issued by labquality: program from (b)(6) 2021 lq775821022, sample (b)(6).One hundred and forty one (141) participants were involved in this challenge and forty five (45) reported a negative interpretation including vidas peer group (19 participants) and eight (8) reported a borderline result.Analysis of results issued from different external quality assessment programs since year 2020, the biomérieux complaints laboratory has subscribed to a (b)(6) program of external quality assessment and tested quality sample as any clinical laboratory involved in the program (blind test).According to the reports issued by this program, the complaint laboratory has obtained an excellent score for all the samples tested: eight samples included 6 with an expected positive result and 2 with an expected negative result.All the results complied with the expected interpretation and the indexes obtained were within the acceptable ranges.Test on vidas sars cov-2 igg: testing on internal samples: three positive samples were tested on the batches 1008397990 and 1008674550 of vidas sars cov-2 igg.The results obtained complied with the expectations with no significant difference between them and no evolution over time compared to the results observed before the batches release.Testing quality control sample (b)(6): this quality control sample was tested on vidas sars cov-2 igg lot 1008674550.The sample gave a negative result with 0.75 tv (positive threshold= 1 tv).This quality control sample was also tested on a competitor method (euroimmun anti sars cov2 elisa igg ref (b)(4)).The sample gave also a negative result with a ratio of 0.77 (positive threshold= 1.1).Tests performed by out characterization department: the sample (b)(6) was also tested with an in-house western blot: using the same main raw materials as those used in the manufacturing of vidas sars cov-2 igg assay (rbd antigen and conjugate).Using a nucleocapsid antigen and an external rbd protein.The revelation were done using human immunoglobulin igm and igg.The samples showed to have mainly an immune reactivity of igg antibodies against nucleocapsid antigen.Regarding the immune reactivity of igg antibodies against rbd antigen, the intensity is comparable (slightly lower) to the reactivity of an internal sample close to the cut off on vidas sars cov-2 igg (slightly below: 0.97 tv).This result could explain the negative result observed with euroimmun method and the vidas result based on the investigations outcomes, there is no reconsideration of vidas sars cov-2 igg performances.The sensitivity of this vidas assay is not 100% and some discrepancies can be observed especially in case of mild covid 19.The results are in favor of a low level of igg antibodies with mainly antibodies against nucleocapsid antigen and a low level of igg antibodies against rbd antigen with an immune reactivity below the positive threshold of some methods.This aligns with the results observe on the report provided by labquality, a distribution of results between positive, borderline and negative interpretation.Feedback from labquality organization: labquality organization does not have any clinical information regarding the donor that gave the sample involved in the manufacturing of the quality control sample (b)(6).However, according to their feedback, the level of igg antibodies is very low, certainly close to the detection capability of the different methods.Conclusion: according to the investigation, no anomaly was highlighted with the control chart analysis and the analysis of quality data.The complaints laboratory did not reproduce negative results when testing positive internal samples on vidas sars cov-2 igg lots 1008397990 and 1008674550.The complaints laboratory obtained also a negative result when testing the quality control sample (b)(6) from labquality on vidas sars cov igg lot 1008674550.The sample (b)(6) gave also a negative interpretation using a competitor method (euro immun anti sars cov-2 igg).According to in-house western blot method, it seems that the sample (b)(6) shows to have igg antibodies against nucleocapsid antigen and a level of igg antibodies against spike protein/rbd just below the positive threshold of vidas sars cov-2 igg method and euroimmun method.The investigation did not manage to identify any obvious root cause but according to the investigation outcomes, it seems that we are facing to a quality control sample with a low level of igg antibodies below the positive threshold of vidas sars cov-2 igg assay ref.(b)(4).It is mentioned in the clsi guideline ep14-a3 that processed samples used as qc material (e.G eqa) can have matrix effect.¿current scientific data suggest that such use of pt/ eqa results is not always feasible because of matrix effects.These processed materials us as pt/ eqa samples sometimes do not behave like patient samples routinely analyzed in the laboratory.Biases not generally seen with fresh biological fluids, are frequently seen with pt / eqa samples¿; according to the investigation, there is no reconsideration of any lots of vidas sars cov-2 igg ref (b)(4).
|
