(31 days)
The ID NOW Influenza A & B 2 assay performed on the ID NOW Instrument is a rapid molecular in vitro diagnostic test utilizing an isothermal nucleic acid amplification technology for the qualitative detection and discrimination of influenza A and B viral RNA in direct nasal or nasopharyngeal swabs and nasal or nasopharyngeal swabs eluted in viral transport media from patients with signs and symptoms of respiratory infection. It is intended for use as an aid in the differential diagnosis of influenza A and B viral infections in humans in conjunction with clinical and epidemiological risk factors. The assay is not intended to detect the presence of influenza C virus.
Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.
If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
ID NOW Influenza A & B 2 is a rapid, instrument-based isothermal test for the qualitative detection and differentiation of influenza A and influenza B from nasal swab or nasopharyngeal swabs tested directly or after elution in viral transport media collected from patients presenting with signs and symptoms of respiratory infection.
The ID NOW Influenza & B 2 system utilizes isothermal nucleic acid amplification technology and is comprised of:
- Sample Receiver - single use, disposable containing the elution buffer
- . Test Base – single use, disposable comprising two sealed reaction tubes, each containing a lyophilized pellet
- . Transfer Cartridge – single use, disposable for transfer of the eluted sample to the Test Base, and
- ID NOW Instrument – repeat use reader
The reaction tubes in the Test Base contain the reagents required for amplification of the target nucleic acid and an internal control. ID NOW Influenza A & B 2 utilizes a pair of templates (similar to primers) for the specific amplification of RNA from influenza A and B and a fluorescently labeled molecular beacon designed to specifically identify the amplified RNA targets.
ID NOW Influenza A & B 2 is performed within the confinement of the Test Base, and no other part of the ID NOW Instrument has contact with the sample during the amplification process. This reduces the risk of instrument contamination and sample carry-over between measurements.
To perform the assay, the Sample Receiver and Test Base are inserted into the ID NOW Instrument and the elution buffer is automatically heated by the instrument. The sample Receiver and transferred via the Transfer Cartridge to the Test Base, resuspending the lyophilized pellets contained within the Test Base and initiating target amplification. Heating, mixing and detection by fluorescence is provided by the instrument, with results automatically reported.
Results are displayed by the ID NOW Instrument and are also stored in an on-board archive and are assigned to a sample ID that has been entered the ID NOW Instrument by the operator, and the date/time the test was performed. Data can be retrieved and downloaded by the operator at any time after testing. An external Alere™ Universal Printer can be attached via USB to the ID NOW Instrument to print test results.
The provided text describes a 510(k) submission for a software modification to the ID NOW Influenza A & B 2 device. The software modification aims to optimize the recognition of partial/non-dispense of samples and prevent false invalids due to system noise. This submission is a "Special 510(k)" because it's an algorithm update only, with no changes to the assay chemistry. Therefore, the study focuses on demonstrating that the modified device performs equivalently to the predicate device (the previously cleared ID NOW Influenza A & B 2, K190204).
Given the nature of a Special 510(k) for a software update to an existing in vitro diagnostic device, the acceptance criteria and study design will be focused on non-inferiority or equivalence to the predicate device, particularly concerning the impact of the software change on invalid rates and overall performance.
Acceptance Criteria and Study to Prove Device Meets Acceptance Criteria:
The document does not explicitly state numerical acceptance criteria in the typical format of sensitivity, specificity, and confidence intervals for a new device's de novo clearance. Instead, the acceptance criteria are implicitly defined by demonstrating that the modified device's performance does not degrade compared to the predicate device for relevant metrics impacted by the software change (false invalids, sensitivity, specificity).
The study described is an equivalence study comparing the performance of the ID NOW Influenza A & B 2 (with the new software) against the predicate ID NOW Influenza A & B 2 (K190204).
1. Table of Acceptance Criteria and Reported Device Performance:
Since this is a software modification to optimize existing functionality (reducing false invalids and improving baseline recognition), the acceptance criteria would primarily revolve around demonstrating non-inferiority in terms of invalid rates and clinical performance (sensitivity and specificity) when compared to the predicate device. The document does not provide a table with explicit numerical acceptance criteria and reported device performance of the software modified device compared to the predicate in a clinical study. Instead, it emphasizes that the "modified ID NOW Influenza A & B 2 demonstrated performance that was substantially equivalent to the predicate device."
However, we can infer the intent of the acceptance criteria based on the purpose of the software update:
| Metric | Acceptance Criteria (Inferred for Equivalence) | Reported Device Performance (vs. Predicate) |
|---|---|---|
| Invalid Rate | No significant increase in invalid rate compared to the predicate device. | Improvement: The software modification was specifically made "to prevent false invalids due to system noise in the Normalization Window." This implies the reported performance for the modified device would show a reduction in such specific false invalid cases compared to the predicate. The document doesn't provide specific invalid percentages but highlights the purpose of the change. |
| Sensitivity (Influenza A) | Non-inferior to the predicate device, with pre-defined margin of equivalence. | Equivalent: The submission states, "ID NOW Influenza A & B 2 incorporating the software modification was compared to the legally marketed predicate device, the 510(k) cleared ID NOW Influenza A & B 2 test." The conclusion of a 510(k) (substantially equivalent) implies that the clinical performance (including sensitivity for Influenza A) of the modified device was found to be statistically comparable to the predicate. Specific numbers are not provided in this excerpt, but a non-inferiority margin would have been part of the study design. |
| Specificity (Influenza A) | Non-inferior to the predicate device, with pre-defined margin of equivalence. | Equivalent: Similar to sensitivity, the substantial equivalence determination indicates comparable specificity for Influenza A. |
| Sensitivity (Influenza B) | Non-inferior to the predicate device, with pre-defined margin of equivalence. | Equivalent: The substantial equivalence determination indicates comparable sensitivity for Influenza B. |
| Specificity (Influenza B) | Non-inferior to the predicate device, with pre-defined margin of equivalence. | Equivalent: The substantial equivalence determination indicates comparable specificity for Influenza B. |
| Optimization of Recognition | Improved recognition of partial/non-dispense samples. | Achieved: The software update was made "to optimize recognition of partial/non-dispense of sample into the Test Base that result in a high baseline." This implies that the reported performance would show improved detection of these issues, leading to more reliable results. |
2. Sample Size Used for the Test Set and Data Provenance:
The document mentions that "ID NOW Influenza A & B 2 incorporating the software modification was compared to the legally marketed predicate device." However, it does not specify the sample size used for this comparison or the data provenance (e.g., country of origin, retrospective or prospective nature of the data). For a software update to an existing device, a validation might involve re-testing archived samples or conducting a limited prospective study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:
For an in vitro diagnostic (IVD) device like this, the "ground truth" for influenza detection is typically established by a reference method, not by human expert interpretation of images or clinical findings in the same way as an imaging AI device. The reference method for influenza detection would commonly be RT-PCR (Reverse Transcription Polymerase Chain Reaction), which is a highly sensitive and specific molecular test. Therefore, the concept of "number of experts" for establishing ground truth isn't applicable in this context.
4. Adjudication Method for the Test Set:
Not applicable in the human expert sense for an IVD device. The ground truth is established by a reference laboratory method (e.g., RT-PCR), and the device's results are compared directly to this objective reference.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, an MRMC study was not done. MRMC studies are typically performed for AI-powered diagnostic imaging devices where human readers interpret medical images. This device is an in vitro diagnostic (IVD) test that automates the detection of viral RNA, and its output is a qualitative result (Influenza A positive/negative, Influenza B positive/negative). There are no "human readers" interpreting the device's output in a way that would require an MRMC study.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance):
Yes, a standalone study was done. The ID NOW Influenza A & B 2, both the predicate and the modified version, operates as a standalone diagnostic device. It processes the sample, runs the assay, and automatically reports the result ("Automated" Interpretation, "Qualitative" Assay Result, "13 minutes or less" Time to Result). The software modification itself is an algorithm-only change that affects the internal processing of the instrument without requiring human intervention in the result interpretation beyond reading the displayed result. The comparison to the predicate device evaluates this standalone performance.
7. Type of Ground Truth Used:
The ground truth for an influenza diagnostic test is typically established using a highly sensitive and specific molecular reference method, such as Reverse Transcription Polymerase Chain Reaction (RT-PCR). The text states the device is for "qualitative detection and discrimination of influenza A and B viral RNA," implying the ground truth would be based on the presence or absence of this RNA as determined by a gold-standard molecular test.
8. Sample Size for the Training Set:
The document does not specify the sample size used for the training set. Since this is a software update for an existing algorithm focused on optimizing signal processing and invalid interpretation, the "training" might involve internal testing with various scenarios (e.g., partial dispense, low signal) rather than a large, clinical training set as seen in de novo AI model development. If external data was used for refining the algorithm, its size is not mentioned here.
9. How the Ground Truth for the Training Set Was Established:
The document does not specify how the ground truth for the training set was established. Analogous to the test set, if a training set were used for algorithm refinement (e.g., to teach the algorithm to detect partial dispenses or filter system noise), the ground truth for those scenarios would likely be established through controlled experiments or by expert review of raw signal data, potentially using a reference method (e.g., RT-PCR) to confirm true positive/negative status in various challenging sample conditions.
§ 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.