Diasorin molecular received a complaint on (b)(6) 2022 on the simplexa covid-19 direct assay mol4150 lot# 13999n for a suspected false negative on two (2) patient samples during a correlation study that were negative on the simplexa assay, but positive on the cepheid competitor assay.Run analysis of the simplexa results are as follows: "sample 6:" simplexa, instrument 1d0448: s gene (31.6) orf1ab (32.1).Simplexa, instrument 1d0591: negative 2x.Cepheid: postiive (39.5)."sample 7:" simplexa, instrument 1d0448: s gene (0), orf1ab (36.6).Simplexa, instrument 1d0591: s gene (27.7) orf1ab (30.1).Cepheid: positive (28.8)."sample 8:" simplexa, instrument 1d0448: negative run 1, run 2 s gene (32.5) orf1ab (32.3).Simplexa, instrument 1d0591: s gene (33.9) orf1ab (35.2).Cepheid: positive (33.5).Ample 7 was interpreted correctly by the software as detected/positive even with no s gene detection since the simplexa assay is qualitative.Samples 6 and 8 performed differently depending on the instrument.It is known that the cepheid assay has different targets (e gene, n2) and uses extracted samples compared to the simplexa assay (s gene, orf1ab, direct samples).The customer stated the samples were collected a week before testing, but the samples were not provided for investigation.It is not known how the samples were stored or setup between repeats runs.The customer's device was not provided for investigation.Batch record review showed the critical component, reaction mix mol4151 lot# 13748n, met all qc release criteria prior to kit release.Mol4151 lot# 13748n was tested using positive controls and no-template controls (ntc).Positive controls were tested in quadruplicate and resulted in zero (0) occurrences of false negatives in any of the covid-19 targets.All positive controls were detected at an average ct = 27.9 (s gene), 27.2 (orf1ab), and the internal control avg ct = 31.4.No malfunctions occurred during qc release testing.Retains of the suspected device were tested on (b)(6) 2022 with 14 replicates (2 discs of 7 pc each) of mol4160 positive control.Both times the targets were detected on all replicates (s gene = 27.1, 27.5 / orf1ab = 27.1, 27.7).No false negatives occurred.No malfunctions occurred.Potential causes for the false negative results may be an instrument failure or error, an operator error, incorrect handling of reagents during testing or storage, or deviation from the assay procedure outlined in the package insert.It is not possible to determine a definitive root cause at this time.As stated in the instructions for use, ifuk.Us.Mol4150, "negative results do not preclude sars-cov-2 infection and should not be used as the sole basis for patient management decisions.Negative results must be combined with clinical observations, patient history, and epidemiological information" and per the limitations section, item 5 "false-negative results may occur if the viruses are present at a level that is below the analytical sensitivity of the assay or if the virus has genomic mutations, insertions, deletions, or rearrangements or if performed very early in the course of illness." this is the 1st complaint on mol4150 lot# 13999n for false negative results.
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