(73 days)
Copan eNAT- molecular collection and preservation medium- is intended for the stabilization, transportation and inactivation of an unprocessed upper respiratory clinical specimen suspected of containing influenza A virus RNA. eNAT- molecular collection and preservation medium- is intended for use with compatible molecular assays.
The primary purpose of nucleic acids amplification techniques is to screen for a wide range of infectious diseases, so nucleic acid integrity of clinical specimens during transport and storage should be preserved.
eNAT® medium contains a detergent and a protein denaturant to prevent microbial proliferation and to maintains the integrity of the nucleic acids from cells or pathogens collected from patients and inactivates pathogen viability, thus eNAT® is not intended to be used for culture-based techniques.
Copan eNAT® has 3 different configurations:
Ref. 6U072S: a plastic screw-cap tube filled with 2 ml of Molecular Preservation and Transport medium.
Ref. 6U073S01: a plastic screw-cap tube filled with 2 ml of Molecular Preservation and Transport medium and a regular size tip nylon flocked swab for sample collection.
Ref. 6U074S01: a plastic screw-cap tube filled with 2 ml of Molecular Preservation and Transport and a minitip nylon flocked swab for sample collection.
The provided text details the 510(k) summary for the Copan eNAT® molecular collection and preservation medium. The document compares its performance to a predicate device, PrimeStore™ MTM, focusing on the inactivation and stabilization of Influenza A virus RNA.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria | Reported Device Performance (eNAT®) |
|---|---|---|
| Flu A Inactivation | >4.0 log reduction in concentration at 10 seconds (based on predicate device's criteria) | 4.5 log reduction (for Flu A in eNAT® at 10 seconds) |
| Flu A RNA Stability | +/- 3.0 Ct after 4 weeks storage at both 2-8°C and 25°C (compared to Time zero) | -0.2 ΔCt after 4 weeks at 2-8°C |
| -0.1 ΔCt after 4 weeks at 25°C |
2. Sample Size Used for the Test Set and Data Provenance
The text explicitly mentions the following sample sizes and aspects of data provenance for the performance studies:
-
Flu A Inactivation Study:
- Test Set Description: High concentrations of Flu A in nasal matrix were inoculated into eNAT® using Copan's regular nasal-type FLOQSwabs®.
- Sample Size: Not explicitly stated as a number of distinct "samples." The study describes inoculating "aliquots" onto MDCK cell lines.
- Data Provenance: The study design "followed the study design described by Longhorn in the PrimeStore MTM Decision Summary, DEN170029." This suggests an in-house laboratory study. The country of origin for the data is not specified, but the applicant is Copan Italia S.p.A.
- Retrospective/Prospective: These appear to be prospective laboratory studies designed to evaluate the eNAT® device.
-
Analytical Sensitivity Study (LoD):
- Test Set Description: Flu A was diluted to 0.180 TCID50/ml (in the matrix) for testing with eNAT® in combination with the Cepheid Xpert® Xpress Flu/RSV assay.
- Sample Size: 24 replicates for the eNAT® samples.
- Data Provenance: Not explicitly stated but implied to be an in-house laboratory study.
- Retrospective/Prospective: Prospective laboratory study.
-
Flu A RNA Stability Study:
- Test Set Description: Flu A spiked into eNAT® medium.
- Sample Size: 24 replicates for each storage condition (Time zero, 4 weeks at 2-8°C, 4 weeks at 25°C).
- Data Provenance: Not explicitly stated but implied to be an in-house laboratory study.
- Retrospective/Prospective: Prospective laboratory study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The provided text does not mention the involvement of experts (such as radiologists) to establish ground truth for the test sets. The studies described are analytical performance studies conducted in a laboratory setting, rather than clinical studies requiring expert interpretation of diagnostic images or results. The "ground truth" for these studies is based on quantitative laboratory measurements of viral load or RNA levels.
4. Adjudication Method for the Test Set
As the studies are analytical performance assessments based on quantitative laboratory measurements (e.g., log reduction, TCID50/ml, PCR Ct values), adjudication methods (like 2+1 or 3+1 often used in clinical image interpretation studies) are not applicable and therefore not mentioned. The results are determined by the outcome of the laboratory assays.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done or is described. The studies detailed are analytical performance evaluations of the device's ability to inactivate and stabilize viral RNA, not clinical studies involving human readers and their diagnostic accuracy with or without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The device itself is a molecular collection and preservation medium, not an algorithm. Therefore, the concept of "standalone performance" in the context of an algorithm does not apply here. The studies conducted evaluated the standalone performance of the medium in terms of its chemical and biological effects on the virus and its RNA.
7. The Type of Ground Truth Used
The ground truth used for these studies is analytical/laboratory-based:
- Flu A Inactivation: The ground truth for viral viability was determined by MDCK (Madin-Darby Canine Kidney) cell culture to measure cytopathic effect (CPE) and determine TCID50/ml (Tissue Culture Infectious Dose 50%).
- Analytical Sensitivity (LoD) and RNA Stability: The ground truth for the presence and quantity of Flu A RNA was established using a molecular assay (Cepheid Xpert® Xpress Flu/RSV assay), which provides quantitative PCR Ct values. The initial concentration of Flu A (TCID50/ml) was also a part of the ground truth for LoD.
8. The Sample Size for the Training Set
The provided text does not mention a training set as this device is a physical sample collection and preservation medium, not an AI/ML algorithm that requires training data. The studies are for performance validation of the medium itself.
9. How the Ground Truth for the Training Set Was Established
Since there is no training set mentioned for an AI/ML algorithm, this question is not applicable.
§ 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.