FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

CLEARinse CTS is intended to collect and transport clinical nasal wash aspirate specimens that may contain influenza A or influenza B virus, by health care professionals, from the collection site to a laboratory or testing site. CLEARinse CTS specimens are suitable for use with legally marketed lateral flow immunoassays and molecular assays. CLEARinse CTS is for professional in-vitro diagnostic use.

Device Description

The product is an extension of the CLEARinse Pro device, a 510(k)-cleared (K082762) professional use medical device with indications for nasal lavage as well as mucus sample collection for subsequent testing. The CLEARinse Pro Handle and Instructions for Use are required for use of the CLEARinse CTS.

The CLEARinse CTS is comprised of two component assemblies: a revision to the 510(k)cleared Wash Head and a Transport Container to protect the Wash Head and specimen during transit. The CLEARinse CTS. used with the CLEARinse Pro Handle, will allow a nasal wash aspirate specimen to be collected by a medical professional, protected for transit, and ground shipped to a testing site. The user mounts the CLEARinse CTS Wash Head onto the CLEARinse Pro Handle and adds sterile saline as directed. The tip of the Wash Head is inserted into the patient's nostril and sterile saline is introduced. The irrigated saline and nasal secretions are then aspirated back into the Wash Head, collecting the specimen to be tested. The CLEARinse CTS Wash Head is removed from the Handle and placed into the Transport Container assembly (Container Cup, Filter Seal, Silicone Seal, and Container Lid) and then back into the CLEARinse CTS box for ground transportation of the specimen to a laboratory for testing.

The Wash Head is manufactured from inert, biocompatible plastics and is supplied as a sterile, single use device. The Transport Container is also manufactured from inert, biocompatible plastics and is a single use device but is not supplied sterile.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the CLEARinse CTS Specimen Collection and Transport System, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance:

Acceptance Criteria Category	Specific Criteria	Reported Device Performance/Results
Limit of Detection (LoD) - PCR	Recovery of target analyte from transport media > 95% accuracy. Ct values within +/- 3 Ct of the mean for confirmatory tests.	Influenza A (H1N1):
Preliminary: 1X LoD (4.0E-03 TCID50/mL) showed 100% positive (3 of 3 replicates).
Confirmatory: 1X LoD (4.0E-03 TCID50/mL) showed 19 out of 20 results within acceptance range for FluA1.
Influenza A (H3N2):
Preliminary: 1X LoD (8.7E-02 TCID50/mL) showed 100% positive (3 of 3 replicates).
Confirmatory: 1X LoD (2.6E-01 TCID50/mL) showed 20 out of 20 results within acceptance range for FluA1.
Influenza B:
Preliminary: 0.1X LoD (4.0E-03 TCID50/mL) showed 100% positive (3 of 3 replicates).
Confirmatory: 1X LoD (4.0E-03 TCID50/mL) showed 20 out of 20 results within acceptance range for FluB.
Established PCR LoDs: FluA (H1N1) 4.0 x10^-3 TCID50/mL, FluA (H3N2) 2.6 x10^-1 TCID50/mL, FluB 4.0 x10^-3 TCID50/mL.
Limit of Detection (LoD) - LFA	Lowest concentration producing >= 19 positives out of 20 samples (95%) in confirmatory testing.	Influenza A (H1N1):
Confirmatory: 0.25X (2.63E+01 TCID50/mL) showed 100% positive (20 of 20).
Influenza A (H3N2):
Confirmatory: 40X (3.98E+03 TCID50/mL) showed 100% positive (20 of 20).
Influenza B:
Confirmatory: 20X (3.98E+02 TCID50/mL) showed 100% positive (20 of 20).
Established LFA LoDs: FluA (H1N1) 2.6 x10^1 TCID50/mL, FluA (H3N2) 4.0 x10^3 TCID50/mL, FluB 4.0 x10^2 TCID50/mL.
Sample Stability - PCR	Deviation of no more than +/- 3 Ct for each target at a given time point from T=0.	Samples for viral nucleic acid testing are stable when stored for 48 hours at room (27°C) and refrigerated (4°C) temperatures. All average Ct values across time points (0-hr, 4-hr, 6-hr, 24-hr, 48-hr) for FluA H1N1, FluA H3N2, and FluB at both temperatures were within +/- 3 Ct of the baseline.
Sample Stability - LFA	Sufficient positive results maintained over time (implied by 3 of 3 positive replicates for 2.5X LoD samples).	Samples for antigen testing are stable when stored for 24 hours at room (27°C) temperature or 48 hours refrigerated (4°C). All replicates (3 of 3) were positive for FluA H1N1, FluA H3N2, and FluB at 2.5X LoD across tested time points (0-hr, 4-hr, 6-hr, 24-hr, 48-hr). Note: "24-hr" for room temp for LFA stability is implied as stability is reported as "24 hours at room temperature or 48 hours refrigerated."

2. Sample size used for the test set and the data provenance:

LoD Testing (PCR and LFA):
- Preliminary Test Set: Various concentrations were tested, typically with 3 replicates for each concentration.
- Confirmatory Test Set: 20 replicates were used for each influenza strain (H1N1, H3N2, FluB) at their respective 1X LoD (for PCR) or determined LoD (for LFA).
- Data Provenance: The data appears to be prospective as it involves controlled spiking of viral strains into a negative clinical matrix and subsequent testing with the device. The origin of the clinical nasal wash matrix (NWA) is not explicitly stated but is described as "pooled negative clinical nasal wash matrix." The tests were conducted using commercially available assays (Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV and PBM BioSign Flu A+B).
Sample Stability Testing (PCR and LFA):
- Test Set: Each stability study evaluated triplicate samples for each influenza strain (H1N1, H3N2, FluB) per time point (0-hr, 4-hr, 6-hr, 24-hr, 48-hr) and per storage condition (4°C, 27°C). This means, for PCR, 3 strains * 5 time points * 2 temperatures * 3 replicates = 90 tests. Similarly for LFA, though the 0-hr was a baseline, and some time points appear a little different in the table headers.
- Data Provenance: Similar to LoD, this is prospective testing using spiked contrived samples in a negative clinical nasal wash matrix.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

The study in this 510(k) summary focuses on analytical performance (Limit of Detection and Stability) rather than diagnostic accuracy against a clinical ground truth established by experts.
The "ground truth" for the test sets was derived from known concentrations of spiked viral strains (TCID50/mL) determined by established laboratory methods, and then assessed using commercially available and validated diagnostic assays (Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV for PCR and PBM BioSign Flu A+B for LFA).
No human experts (e.g., radiologists) were used to establish the ground truth for these particular analytical studies.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

For the analytical studies described, no adjudication method (like 2+1 or 3+1) was used or required.
The results for LoD and stability were primarily quantitative (Ct values for PCR) or categorical (positive/negative for LFA) based on the output of the reference diagnostic assays. The "ground truth" for the spiked samples was the known concentration of the viral load.

5. 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:

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was conducted or presented in this 510(k) summary.
The CLEARinse CTS is a specimen collection and transport system, not an AI-powered diagnostic imaging device or an AI-assisted detection tool where human reader performance would be a relevant metric. The studies focus on the ability of the device to preserve and recover viral nucleic acids and antigens for downstream testing.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

The performance described in this 510(k) is essentially standalone performance of the collection and transport system.
The device itself (CLEARinse CTS) is not an "algorithm" in the typical sense of AI/ML. Its performance is evaluated by its ability to maintain the integrity of spiked samples, which are then analyzed by already cleared in vitro diagnostic assays (the Cepheid PCR and PBM BioSign LFA). These assays operate independently to detect the target. The studies demonstrate the device's contribution to maintaining sample quality for these standalone diagnostic tests.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The ground truth for both the LoD and stability studies was based on contrived samples with known concentrations of viral pathogens. These concentrations were quantified using standard laboratory methods (TCID50/mL).
The "true" positivity or negativity of a sample at a given concentration was determined by the performance of the established reference nucleic acid (PCR) and antigen (LFA) diagnostic assays, and compared against their expected LoDs.

8. The sample size for the training set:

As this submission pertains to an in vitro diagnostic specimen collection and transport device and not an AI/ML algorithm that requires training, there is no "training set" in the context of machine learning.
The performance data provided is for verification and validation of the device's analytical capabilities.

9. How the ground truth for the training set was established:

Again, since this is not an AI/ML device, the concept of a "training set" and establishing its ground truth for machine learning does not apply.
The ground truth for the test samples used in the analytical studies was established by spiking known concentrations of influenza strains into a negative clinical matrix (as described in point 7).

Summary

Regulation Number and Section

§ 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.