(88 days)
The Panther Fusion Flu A/B/RSV assay is a multiplex real-time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and differentiation of influenza B virus, influenza B virus, and respiratory syncytial virus (RSV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection.
This assay is intended to aid in the differential diagnosis of influenza A virus, influenza B virus and RSV infections in humans and is not influenza C virus infections. Negative results do not preclude influenza A virus, influenza B virus or RSV infections and should not be used as the sole basis for treatment or other management decisions. This assay is designed for use on the Panther Fusion system.
Performance characteristics for influenza A were established when influenza A(H1N1)pdm09 were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging. performance characteristics may vary. 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 any culture specimens.
The Panther Fusion Flu A/B/RSV assay is a multiplex real-time reverse transcriptase PCR (RT-PCR) in vitro diagnostic test developed for use on the fully automated Panther Fusion system to detect and differentiate influenza A, influenza B, and respiratory syncytial virus (RSV) directly from the nasopharyngeal swab specimens.
The Panther Fusion Flu A/B/RSV assay involves the following steps: Sample lysis, nucleic acid capture and elution, and multiplex RT-PCR where analytes (when present) are simultaneously amplified, detected and differentiated. Nucleic acid capture and elution takes place in a single tube on the Panther Fusion system. The eluate is transferred to the Panther Fusion system reaction tube containing the assay reagents. Multiplex RT-PCR is then performed for the eluted nucleic acid on the Panther Fusion system.
Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:
Acceptance Criteria and Device Performance: Panther Fusion Flu A/B/RSV Assay
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly list "acceptance criteria" in a separate table, but rather presents the performance study results as evidence that the device meets the necessary standards for clearance. Based on the "Performance Data" section, the key performance metrics evaluated are Sensitivity and Specificity. The acceptance criteria are implicitly those demonstration of high accuracy for the detection and differentiation of Influenza A, Influenza B, and RSV.
| Performance Metric | Target (Implicit Acceptance Criteria) | Reported Device Performance |
|---|---|---|
| Influenza A | High Sensitivity & Specificity | Sensitivity: 99.2% |
| Specificity: 97.9% | ||
| Influenza B | High Sensitivity & Specificity | Sensitivity: 97.9% |
| Specificity: 99.7% | ||
| RSV | High Sensitivity & Specificity | Sensitivity: 98.7% |
| Specificity: 95.1% | ||
| Analytical LoD | Detection at low concentrations | Varies by strain (Table 4) |
| Analytical Reactivity | Detects multiple strains | 100% detection for tested strains (Table 5) |
| Analytical Specificity | No cross-reactivity | 100% against 52 organisms (Table 8) |
| Interfering Substances | No interference at clinically relevant concentrations | No observed interference (Table 6) |
| Competitive Interference | No interference from co-infection | 100% detection for both targets (Table 7) |
| Carry-Over/Contamination | Low rate | 0.4% |
| Assay Precision | Consistent results | Low %CV (Tables 9, 10, 14, 15) |
| Reproducibility | Consistent results across sites/operators | 100% agreement for negative/moderate positive, ≥97.8% for low positive (Table 13) |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: 2869 evaluable specimens for the clinical performance study.
- Data Provenance:
- Country of Origin: The study was conducted at "four participating US pediatric/adolescent, private and/or university hospitals." This indicates data from the United States.
- Retrospective or Prospective: The study was prospective, using "leftover, remnant nasopharyngeal (NP) swab specimens from male and female individuals of all ages exhibiting signs and/or symptoms of a respiratory tract infection."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The document does not specify the number or qualifications of experts used to establish the ground truth for the clinical test set. It states that "reference viral culture followed by direct fluorescent antibody (DFA) identification" was used, with "A validated PCR assay" for discordant resolution testing. This implies standard laboratory practices rather than requiring expert consensus for direct interpretation of results as might be seen for imaging studies.
4. Adjudication Method for the Test Set
The adjudication method for the clinical test set was:
- Initial ground truth: reference viral culture followed by direct fluorescent antibody (DFA) identification.
- Discordant Resolution: "A validated PCR assay was used for discordant resolution testing."
There's no mention of expert human adjudication of the results themselves, but rather reliance on a secondary, confirmatory laboratory method (PCR) for samples where the initial reference method (culture/DFA) and the device result disagreed.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study evaluates a diagnostic assay, not an AI-assisted interpretation by human readers. The comparison is between the device's performance and established laboratory reference methods (culture/DFA and PCR), not human reader performance.
6. If a Standalone Performance Study Was Done
Yes, a standalone performance study was done. The entire clinical performance section (pages 16-18) details the evaluation of the Panther Fusion Flu A/B/RSV assay directly against reference methods without human intervention as an interpretive component. This is an algorithm-only (device-only) performance evaluation for an in-vitro diagnostic (IVD) test.
7. The Type of Ground Truth Used
The ground truth used for the clinical performance study was a combination of:
- Viral Culture / Direct Fluorescent Antibody (DFA) identification: This served as the primary reference method.
- Validated PCR Assay: Used for discordant resolution. This means that if the Panther Fusion assay result disagreed with the culture/DFA result, an independent, validated PCR assay was used to determine the true status of the sample.
8. The Sample Size for the Training Set
The document does not specify the sample size for a training set. This is a diagnostic device clearance submission, and typically, the "training" (development and optimization) of such assays involves analytical studies (e.g., LoD, inclusivity, specificity) and internal validation, rather than a distinct "training set" in the machine learning sense. The clinical performance study serves as the independent validation of the finalized device.
9. How the Ground Truth for the Training Set Was Established
As no explicit "training set" in the machine learning context is mentioned for this IVD, the concept of establishing ground truth for it is not directly applicable in the provided information. The analytical studies (LoD, inclusivity, specificity, etc.) described earlier in the document involve preparing samples with known concentrations of viral strains or challenging the assay with specific organisms, where the "ground truth" is established by the controlled preparation and spiking of these materials.
§ 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.