(651 days)
The Sample Preservative Fluid is intended for the stabilization, and inactivation of infectious, unprocessed, upper respiratory specimens suspected of containing Influenza A virus. Specimens transported in the Sample Preservative Fluid are stable refrigerated (2-8°C) and at room temperature (20-25°C). The Sample Preservative Fluid is suitable for use with compatible legally marketed molecular diagnostic devices.
Sample Preservative Fluid is a medium for stabilization of Influenza A RNA during sample transport/storage. The fluid is composed of quanidine thiocyanate, Triton X-100, and nuclease-free water. Sample Preservative Fluid is provided in a labeled screw-cap tube.
Sample Preservative Fluid configuration:
- BSC82X1-A1: a screw-cap tube filled with 2 mL of Sample Preservative Fluid liquid ● and a prepackaged nasopharyngeal swab for sample collection
- Nasopharyngeal swab: regular size, sterile disposable sample swab (80mm . breakpoint)
Here's a summary of the acceptance criteria and study details for the Sample Preservative Fluid, based on the provided document:
Acceptance Criteria and Device Performance
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Shelf-life: | Shelf-life: |
| No bacterial or fungal growth | No bacterial or fungal growth observed for 24 months. |
| No obvious change in appearance | No change in appearance observed for 24 months. |
| No tube leakage at -0.08 MPa for ten minutes | No tube leakage observed for 24 months. |
| Media density of 1.06 ± 0.04 g/mL | No change in density over time observed for 24 months. |
| Detection Limit (LoD): | Detection Limit (LoD): |
| Lowest concentration detected with ≥ 95% detection rate | 0.08 TCID50/mL for Influenza A H3N2 (A/California/2/2014, VR-1938) with 100% detection rate. |
| Specimen Stability: | Specimen Stability: |
| All Ct values fall within a 3.0 Ct range of Day 0 | All Ct values for Influenza A H3N2 in nasal matrix preserved at 2-4°C and 20-25°C for 35 days fell within a 3.0 Ct range of Day 0, indicating no significant degradation. |
| Cytotoxicity (for viral inactivation assay): | Cytotoxicity (for viral inactivation assay): |
| No significant cytotoxicity to cell monolayer | No toxicity to MDCK cell monolayer observed when Sample Preservative Fluid was diluted to ≥ 1:3500. A 1:4000 dilution showed normal cell morphology/growth in preliminary tests, and 1:3500 in confirmatory tests. |
| Viral Inactivation: | Viral Inactivation: |
| Successful inactivation of Influenza A virus | ≥4.7 logarithmic reduction in Influenza A after 30 and 60 seconds of incubation in the Sample Preservative Fluid, demonstrating viral inactivation of >99.99%. No cytotoxicity observed in the cell monolayer from samples exposed to inactivated virus. |
Study Details
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Sample size used for the test set and the data provenance:
- Shelf-life: 3 lots of Sample Preservative Fluid. Data provenance is not explicitly stated but is implicitly from an in-house study conducted by the applicant (Hangzhou Bioer Technology Co., Ltd). The study appears to be proprietary/internal rather than retrospective or prospective clinical data.
- Detection Limit (LoD):
- Preliminary LoD: 5 replicates for each of 5 concentrations (0.32, 0.16, 0.08, 0.04, 0.02, 0.01 TCID50/mL) for a total of 30 replicates (though actual testing for 0.02 and 0.01 TCID50/mL ceased if a certain number of negative results were observed).
- Confirmatory LoD: 20 replicates at 0.08 TCID50/mL (initially attempted at 0.04 TCID50/mL).
- Data provenance is from an in-house laboratory study.
- Specimen Stability: Replicates of four for each of three reagent lots, tested at 6 timepoints (Day 0, 1, 8, 15, 22, 35) at two different temperatures (2-4°C and 20-25°C). Total number of Ct values reported is 144 for each temperature condition (3 lots * 4 reps * 6 timepoints). Data provenance is from an in-house laboratory study.
- Cytotoxicity Study: Not explicitly stated, but multiple dilutions (from 1:10 up to 1:8000 for preliminary, and from 1:1000 for confirmatory) were tested against a cell monolayer. This is an in-house laboratory study.
- Viral Inactivation Study: Influenza A H3N2 virus combined with Sample Preservative Fluid and negative nasal matrix, incubated for 30 and 60 seconds. Each mixture diluted 3500x and plated into 8 wells in triplicate (total of 24 wells per condition). Positive and negative controls were also used. This is an in-house laboratory study.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. The studies described are laboratory-based performance studies (shelf-life, LoD, stability, inactivation) using controlled experimental conditions and quantitative measurements (e.g., bacterial/fungal growth, leakage, density, PCR Ct values, viral titers, cell morphology), not expert interpretation of clinical data.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set: Not applicable, as expert adjudication is not used for these types of laboratory performance studies.
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If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance: Not applicable. This device is a sample preservative fluid, not an AI-powered diagnostic or imaging system involving human readers.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: Not applicable. This is a physical device (fluid) and does not involve an algorithm.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Shelf-life: Physical and chemical property evaluations (e.g., visual inspection, pressure tests, density measurements) and microbial growth assays.
- Detection Limit (LoD): Defined concentration of target virus (Influenza A H3N2) in negative nasal matrix, assayed by a cleared molecular diagnostic device (Cepheid Xpert Xpress Flu/RSV Assay).
- Specimen Stability: Defined concentration of target virus (Influenza A H3N2) in negative nasal matrix, assayed by a cleared molecular diagnostic device (Cepheid Xpert Xpress Flu/RSV Assay). Comparison of Ct values over time to a baseline (Day 0).
- Cytotoxicity Study: Observation of cell morphology and growth status on a cell monolayer (MDCK cells).
- Viral Inactivation Study: Measurement of viral titers (TCID50/mL) and observation of cytopathic effects on MDCK cells. Reduction in culturable virus compared to controls.
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The sample size for the training set: Not applicable. This device does not use machine learning or AI, and therefore does not have a training set.
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How the ground truth for the training set was established: Not applicable, as there is no training set.
§ 866.2950 Microbial nucleic acid storage and stabilization device.
(a)
Identification. A microbial nucleic acid storage and stabilization device is a device that consists of a container and reagents intended to stabilize microbial nucleic acids in human specimens for subsequent isolation and purification of nucleic acids for further molecular testing. The device is not intended for preserving morphology or viability of microorganisms.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of microorganisms and types of human specimens intended to be preserved.
(2) The labeling required under § 809.10(b) of this chapter must include the following:
(i) A detailed device description, including all device components;
(ii) Performance characteristics from applicable analytical studies, including nucleic acid stability and microorganism inactivation;
(iii) A limiting statement that erroneous results may occur when the transport device is not compatible with molecular testing; and
(iv) A limiting statement that the device has only been validated to preserve the representative microorganisms used in the analytical studies.
(3) Design verification and validation must include the following:
(i) Overall device design, including all device components and all control elements incorporated into the analytical validation procedures;
(ii) Thorough description of the microorganisms and methodology used in the validation of the device including, extraction platforms and assays used for the detection of preserved nucleic acids; and
(iii) The limit of detection (LoD) of the molecular test used to establish microorganism nucleic acid stability.