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

The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and evidemiological information:

· For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.

· To provide epidemiological information for surveillance of circulating influenza viruses.

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A Subtyping Kit (VER 4)

The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

· For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture:

· To provide epidemiological information for surveillance of circulating influenza viruses.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza B Lineage Genotyping Kit (VER 1.1 and 2)

The Influenza B Lineage Genotyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic realtime PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• For the determination of the genetic lineage of human influenza B viruses as B/Victoria or B/Yamagata lineage from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) from human patients with signs and symptoms of respiratory infection and/or from viral culture;

· To provide epidemiologic information for surveillance of circulating influenza viruses.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/H5 Subtyping Kit (VER 4)

The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

· For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens, conjunctival swabs, and viral culture in conjunction with clinical and epidemiological risk factors;

· To provide epidemiologic information for surveillance of circulating influenza viruses.

Device Description

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel consists of four real-time RT-PCR (rRT-PCR) assays used on IVD-labeled real-time PCR instruments that has been FDA-cleared for use with this device. The panel is configured in four separate kits: Influenza A/B Typing kit, Influenza A/H5 Subtyping kit, and Influenza B Genotyping kit. Each kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection of influenza virus RNA in respiratory and conjunctival specimens from patients presenting with influenza-like illness (IL). Oligonucleotide primers and probes for detection of influenza A, influenza B, and 2009 influenza A (swine origin) were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization and differentiation of influenza A(H3) and A(H1)pdm09 viruses, genetic lineages of influenza A(H5) viruses were selected from highly conserved regions of their HA genes. Oligonucleotide primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens are also included in the panel.

AI/ML Overview

The provided text describes the acceptance criteria and study proving the device meets those criteria for the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/H5 Subtyping Kit (VER 4), specifically concerning the addition of conjunctival swabs as a specimen type.

Here’s a breakdown of the requested information based on the provided text:

1. Table of acceptance criteria and the reported device performance:

The document does not explicitly present a table of acceptance criteria in terms of specific quantitative thresholds (e.g., minimum sensitivity/specificity percentages) for clinical performance. Instead, it describes an evaluation based on demonstrating successful detection capabilities and similarity to a predicate device. The performance is reported descriptively based on the clinical study results.

Reported Device Performance (for Influenza A/H5 Subtyping Kit (VER 4) on conjunctival swabs):

Performance Measure	Value/Description	Context/Details
Limit of Detection (LoD)	10^-5 EID50/ml	Confirmed for conjunctival swab specimens.
Interfering Substances	No interference observed	Tested with two common over-the-counter eyedrops (containing olopatadine hydrochloride and naphazoline hydrochloride respectively). Tested at 2x LoD in contrived specimens (conjunctival matrix and simulated respiratory matrix) and by adding directly to RT-PCR reaction.
Clinical Performance (on Confirmed Cases with Conjunctivitis Symptoms)	26/33 (78.8%) positive, 3/33 (9.1%) inconclusive	For A/H5 on Conjunctival Swab (CS) specimens.
Clinical Performance (on Confirmed Cases with Conjunctivities but URT Positive Only)	4/33 (15.2%) positive	For A/H5 on Upper Respiratory Tract (URT) specimens only.
Clinical Performance (on Confirmed Cases without Conjunctivitis Symptoms)	1/2 (50%) positive on CS, 1/2 (50%) positive on URT only	One case had CS sample, other had URT only.
Clinical Performance (on Probable Cases with Conjunctivitis Symptoms)	2/2 (100%) negative on CS
Subject Matched Paired URT and CS Specimens (Confirmed Cases)	10/32 (31.3%) positive on at least one URT and CS specimens
	15/32 (46.9%) positive in CS specimens only
	4/32 (12.5%) positive in at least one URT specimen only
	3/32 (9.4%) CS inconclusive, URT negative
Subject Matched Paired URT and CS Specimens (Probable Cases)	All URT and CS specimens tested negative	From 1 probable human case.

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

Clinical Test Set Sample Size:
- 46 total cases (44 confirmed, 2 probable) initially considered.
- 35 confirmed cases were assessed for performance due to exclusion of 9 cases where not all necessary assay reagents were used.
- 2 probable cases were assessed.
- The document also specifies the number of clinical specimens available for testing: e.g., 32 confirmed cases had subject-matched paired URT and CS specimens, 3 confirmed cases had only CS specimens, 1 probable case had subject-matched paired URT and CS specimens, and 1 probable case had only a CS specimen.
Data Provenance:
- Country of Origin: US (from public health investigations in the US).
- Retrospective or Prospective: The data was collected from specimens from March to November 2024 as part of public health investigations into outbreaks. This indicates a retrospective collection of existing specimens from human cases.

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

The ground truth for confirmed/probable cases of A/H5N1 was established based on "the criteria described in the current Council of State and Territory Epidemiologists (CSTE) document 24-ID-09." The document does not specify the number of individual experts or their qualifications directly. This refers to established public health guidelines rather than individual expert consensus.

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

The ground truth was established by adherence to existing CSTE criteria, not through a human reader adjudication process of the device's output. The device results were compared against these established "confirmed or probable case status."

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, an MRMC comparative effectiveness study was not done. This document describes the validation of a laboratory diagnostic kit (RT-PCR) with specific specimen types and does not involve human readers interpreting images or AI assistance.

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

Yes, this is effectively a standalone performance study. The device itself is an RT-PCR diagnostic panel. The "performance" described is that of the kit (reagents and controls run on a PCR instrument) in detecting viral RNA, without human interpretation of raw data beyond reading the instrument's output based on established cut-offs (e.g., Ct values). It's an "algorithm only" in the sense that the test results in a definitive positive, negative, or inconclusive outcome based on chemical reactions and signal detection.

7. The type of ground truth used:

The ground truth for the clinical performance evaluation was based on "confirmed or probable case status for each case on the criteria described in the current Council of State and Territory Epidemiologists (CSTE) document 24-ID-09." This can be categorized as outcomes data/epidemiological criteria as determined by public health authorities.

8. The sample size for the training set:

The document describes the validation of a diagnostic panel (PCR-based), not an AI algorithm. Therefore, there is no specific "training set" in the machine learning sense. The device's components (primers, probes) and their performance characteristics are established through analytical studies (e.g., LoD, interfering substances) and clinical validation with patient samples. The development of such a kit is based on extensive prior knowledge of influenza virus genetics and PCR technology, but not a "training set" in the context of supervised learning for AI.

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

As there is no "training set" in the AI sense, this question is not applicable to the device described. The "ground truth" for the analytical development of the RT-PCR panel would be based on well-characterized viral samples (e.g., BPL inactivated virus with known concentrations) and established laboratory techniques for nucleic acid detection.

Summary

Regulation Number and Section

§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.

(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.