(442 days)
The Spectral West Nile virus IgM STATus™ test is a rapid immunochromatographic lateral flow assay that utilizes recombinant West Nile virus (WNV) antigen (E glycoprotein) for the qualitative detection of IgM antibodies to WNV in human serum or plasma (sodium heparin or sodium citrate). This test is for the presumptive laboratory diagnosis of West Nile virus infection in patients having signs and symptoms of meningoencephalitis. Positive results must be confirmed by the PRNT (Plaque Neutralization Reduction Test), or by using the current CDC guidelines for diagnosis of this disease. The Spectral test is not intended for point of care testing, home use or in screening blood donor samples.
A Simple and Rapid Immunoassay for the Qualitative Detection of West Nile Virus IgM Antibodies in Human Serum or Plasma. The Spectral WNV IgM STATus™ test employs solid-phase immunochromatographic assay technology to qualitatively detect the presence of WNV IgM antibodies in serum or plasma. When the specimen to be tested is dispensed into the sample well of the Spectral device, anti-WNV IgM in the sample will bind to the recombinant WNV antigen (envelop glycoprotein (E) of West Nile virus, NY99 strain) to form a tertiary complex with gold-labeled monoclonal murine antibody against flavivirus family glycoprotein E. This tertiary complex will migrate through reaction strip and be captured by goat anti-human IgM antibodies at the Test area. Excess, unreacted gold complex detector is captured by immobilized anti-mouse IgG antibodies at the Control area. A visible pinkish-purple horizontal band will appear in the Test area within 15 minutes following the addition of a sample if the level of the WNV IgM antibodies in the human serum sample is above the cut-off level. A pinkish-purple band in the Control area indicates that the test is working properly and such a band must always appear, irrespective of the WNV IgM levels, in order for the test to be valid.
Acceptance Criteria and Device Performance Study for Spectral West Nile Virus IgM STATus™ Test
This document outlines the acceptance criteria and the studies that demonstrate the Spectral West Nile Virus IgM STATus™ Test meets these criteria, based on the provided 510(k) summary (K052519).
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria with specific numerical targets in a formal table. However, based on the performance data presented, the implicit acceptance criteria appear to be high agreement (sensitivity and specificity/negative agreement) with a legally marketed predicate device (Focus West Nile Virus IgM Capture ELISA) and reference methods like PRNT, along with robust reproducibility.
| Performance Metric | Implicit Acceptance Criteria (Derived from Predicate) | Reported Device Performance |
|---|---|---|
| Negative Agreement | High agreement with predicate device in non-flavivirus IgM samples. | Overall: 98.8% (95% CI: 97.1-99.7%) (n=346) |
| Site 1: 99.4% (95% CI: 96.5-99.9%) (n=158 out of 160) | ||
| Site 2: 98.2% (95% CI: 93.8-99.8%) (n=114) | ||
| Site 3: 98.6% (95% CI: 92.4-99.9%) (n=71 out of 72) | ||
| Serological Sensitivity (Acute) | High agreement with PRNT and CDC WNV IgM & IgG ELISA positive (acute). | Site 4: 95% (95% CI: 83.1%-99.4%) (n=40) |
| Site 5: 100% (95% CI: 88.3%-100%) (n=24) | ||
| Serological Sensitivity (Late) | High agreement with PRNT and CDC WNV IgM & IgG ELISA positive (late). | Site 5: 80% (95% CI: 59.3%-93.2%) (n=25) |
| Negative Agreement (CDC WNV IgM ELISA Negative) | High agreement with CDC WNV IgM ELISA negative. | Site 4: 96% (95% CI: 86.3%-99.5%) (n=50) |
| Site 5: 97% (95% CI: 82.8%-99.9%) (n=30) | ||
| Reproducibility | Consistent results across different sites, lots, and operators. | All sites and operators produced expected results for all 15 panel members on every day of testing. |
| Interfering Substances | No interference from common blood constituents at specified concentrations. | No interference observed up to the listed concentrations of human serum albumin, bilirubin, hemoglobin, triglycerides, and human IgM. |
| IgM Specificity | Confirmation of IgM class antibodies in positive samples. | All 14 DTT-treated samples produced negative results, while untreated paired samples remained positive. |
| Cross-Reactivity | Acceptable levels of cross-reactivity with other pathogens. | Varied results, specific percentages reported for each agent (e.g., Herpes Simplex: 10%, ANA: 39%, Rheumatoid Factor: 30%, Dengue Virus: 10%, Yellow Fever: 20%). |
2. Sample Size Used for the Test Set and Data Provenance
The test set consisted of several distinct groups of samples tested at different study sites.
- Non-flavivirus IgM samples (for Negative Agreement):
- Total Sample Size: 346 specimens.
- Provenance: Prospectively collected from patients with a variety of non-flavivirus ailments (e.g., rash, febrile, bronchitis, diarrhea, drug, neuropathy, acute coronary syndrome) and from endemic normal populations.
- Country of Origin:
- Site 1: South-Western State of America (endemic region).
- Sites 2 & 3: South Eastern Provinces of Canada (endemic regions).
- WNV PRNT Confirmed / CDC WNV IgM ELISA Negative specimens (Study Site 4):
- Total Sample Size: 90 specimens (40 WNV PRNT confirmed; 50 CDC WNV IgM ELISA negative).
- Provenance: Randomized retrospective patient serum specimens from a provincial health laboratory, sent with suspected WNV infection.
- Country of Origin: South Eastern Province of Canada.
- Banked Panel of Clinical Serum Specimens (Study Site 5):
- Total Sample Size: 79 specimens.
- Provenance: Banked clinical serum specimens from patients with clinical symptomology consistent with WNV infection (including symptomatic acutely infected, neuro-invasive disease, and asymptomatic for previous exposures).
- Country of Origin: Prairie Province at Central Canada.
- Reproducibility Panel: 15 clinical specimens.
- Interfering Substances Panel: Positive and negative serum specimens spiked with specific substances.
- IgM Specificity Panel: 14 paired positive samples.
- Cross-Reactivity Panel: Varied number of samples for each potentially cross-reactive agent (e.g., 10 for HSV, 28 for ANA, 33 for Rheumatoid Factor).
- Provenance: Sera sero-positive to other potentially cross-reactive pathogens.
- Country of Origin: North Eastern USA (site 1), Mid-West Canada (site 3 for Dengue), in-house (site 2 for ANA/RF), CDC laboratory at Mid-West USA (site 4 for EEE).
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 test set. Instead, it relies on established reference methods and the comparator predicate device.
4. Adjudication Method for the Test Set
The document does not mention an explicit adjudication method for the test set (e.g., 2+1, 3+1). The "ground truth" was established by reference assays or clinical characterization of samples.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
There is no indication of a multi-reader multi-case (MRMC) comparative effectiveness study or any assessment of human readers improving with AI vs. without AI assistance. This device is a diagnostic assay (rapid immunochromatographic test) designed for laboratory use, not an AI-assisted diagnostic imaging or interpretation tool for human readers.
6. Standalone Performance Study
Yes, a standalone performance study was conducted. The "Method Comparison" section explicitly tests the Spectral device against a comparator device (Focus West Nile Virus IgM Capture ELISA) and other reference methods like PRNT and CDC WNV IgM ELISA. The reported performance metrics (e.g., negative agreement, serological sensitivity) are measures of the algorithm's (device's) performance without human-in-the-loop intervention beyond reading the visible bands.
7. Type of Ground Truth Used
The ground truth for the different test sets was established using a combination of the following:
- Reference Devices/Assays:
- Comparator device: Focus West Nile Virus IgM Capture ELISA (for negative agreement studies).
- PRNT (Plaque Neutralization Reduction Test): Considered a gold standard for confirming WNV infection. Used for characterizing positive WNV samples at Study Site 4 and 5.
- CDC WNV IgM ELISA and IgG ELISA: Used as reference assays for characterizing WNV positive and negative samples at Study Site 4 and 5.
- Clinical Characterization: Samples at Study Site 4 were from patients with "suspected WNV infection based on clinical signs and symptoms." Samples at Study Site 5 were from patients with "clinical symptomology consistent with the West Nile virus infection."
- Pathogen Sero-positivity: For cross-reactivity studies, samples were characterized as sero-positive to other potentially cross-reactive pathogens (e.g., Herpes Simplex Virus, Cytomegalovirus, Syphilis, Epstein Barr Virus, ANA, Rheumatoid Factor, HIV, certain Encephalitis viruses, Dengue Virus, Hepatitis B/C, Legionella, Yellow Fever, E. coli infection).
8. Sample Size for the Training Set
The document does not provide any information regarding a training set or its sample size. This is a rapid diagnostic test, and the reported studies focus on validation and performance characteristics as opposed to machine learning model development which would typically involve distinct training and test sets.
9. How the Ground Truth for the Training Set Was Established
Since no information on a training set is provided, the method for establishing its ground truth is also not available in the document.
§ 866.3940 West Nile virus serological reagents.
(a)
Identification. West Nile virus serological reagents are devices that consist of antigens and antisera for the detection of anti-West Nile virus IgM antibodies, in human serum, from individuals who have signs and symptoms consistent with viral meningitis/encephalitis. The detection aids in the clinical laboratory diagnosis of viral meningitis/encephalitis caused by West Nile virus.(b)
Classification. Class II (special controls). The special control is FDA's guidance entitled “Class II Special Controls Guidance Document: Serological Reagents for the Laboratory Diagnosis of West Nile Virus.” See § 866.1(e) for the availability of this guidance document.