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The MycoMEIA® Aspergillus Assay (MycoMEIA) is an enzyme immunoassay (EIA) for the in vitro qualitative detection of Aspergillus antigens in human urine from adults (>/= 18 years old) with suspected invasive aspergillosis (IA). The assay is not intended for use in lung transplant recipients. The results should be interpreted by trained healthcare professionals, incorporating other diagnostic procedures such as microbiological culture, histological examination of biopsy samples, and radiographic evidence to support the diagnosis of IA.

The MycoMEIA® Aspergillus Assay (MycoMEIA) is a sandwich enzyme immunoassay (EIA) that detects Aspergillus antigens in urine. The assay uses two mouse monoclonal antibodies that recognize galactofuranose (galf) epitopes. Both monoclonal antibodies are used to coat the wells of the microplate to bind the antigen, and to detect the antigen bound to the sensitized microplate as horseradish-peroxidase conjugates.

The design of the assay is in 96-well plates to enable large-volume testing in clinical laboratories.

Urine is first processed through Sample Processing Columns to eliminate an inhibitor of antibody-antigen recognition. The processed urine samples are added to the plate wells coated with the antibodies, incubated, and washed to remove unbound material. The bound antigen is incubated with antibodies linked to horseradish peroxidase and washed to remove the unbound material.

Next, the peroxidase substrate solution is added, which reacts with the complexes bound to the well to form a blue color reaction. The enzyme reaction is stopped by the addition of acid, which changes the blue color to yellow. The absorbance (optical density) of specimens and controls is determined with a spectrophotometer set at 450 and 620 nm wavelengths.

The amount of antigen in the clinical sample is determined by optical density (OD) using a spectrophotometer and interpreted as an OD index relative to the mean OD of a threshold control provided in the kit.

The MycoMEIA-ASP kit contains the following components:

• Microwell Plate
• Negative Control (NC) Sample (green)
• Threshold Control (TC) Sample (blue)
• Positive Control (PC) Sample (red)
• Conjugate (100X) (white)
• Conjugate Diluent (white)
• Chromogen Solution (yellow)
• Stop Solution (blue)
• Column Rinse
• Plate sealers

25X Concentrated Wash Solution and Sample Processing columns are required to perform the assay and are provided separately from the kit.

If a partial plate is used, empty ELISA plates to fill in the ELISA frame are available to customers as a separate product.

Each laboratory will be required to test positive and negative controls provided in the kit to confirm or authenticate the assay results and to determine the sample index factor that is calculated using the assay ODs. Calculations can be performed manually or using the WS001 MycoMEIA Calculation Worksheet, which is available separately.

The provided FDA 510(k) clearance letter and summary for the MycoMEIA Aspergillus Assay details the device's analytical and clinical performance. Here's a breakdown of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" for clinical performance in a pass/fail manner. Instead, it presents the determined performance characteristics. For several analytical aspects, the criteria are implicitly defined by standard guidelines (e.g., CLSI EP17-A2 for LoD, CLSI EP05-A3 for precision and reproducibility).

2. Sample Size Used for the Test Set and Data Provenance

• Analytical Sensitivity (LoD): 60 determinations with low target analyte level replicates.
• Precision (Repeatability and Within-Laboratory): 80 replicates per sample (run twice daily for 20 days, by two operators, in duplicate). Samples included kit controls, contrived samples, and clinical sample pools.
• Reproducibility: 90 replicates per sample (run twice daily for 5 days, by two operators, in triplicate) across three sites. Samples included kit controls, contrived samples, and clinical sample pools.
• Interfering Substances: Endogenous and exogenous substances spiked into pooled healthy urine, and clinical samples from patients with known endogenous conditions.
• Cross-Reactivity (Microorganisms): Tested in duplicate (n=2) for each microorganism listed.
• Cross-Reactivity (Clinical Samples): Urine samples from people with various medical conditions, including fungal, viral, and bacterial infections.
  • Specific numbers for each condition are listed in the summary (e.g., 1 with histoplasmosis, 2 with streptococcus, etc.).
  • Additional cross-reactivity testing involved 21 subjects with documented bacterial pneumonia, 1 with mixed bacterial infection, 2 with mixed GI complications, 2 with histoplasmosis, 1 with blastomycosis, 1 with candidemia, and 1 with disseminated fusariosis.
• Clinical Performance:
  • Archived, Retrospective Study: 475 samples collected from 290 subjects. 226 samples from 50 subjects with proven (n=3) or probable (n=47) IA.
  • Prospective Study:
    • Initiated with 210 consented subjects providing 254 urine samples during 213 suspected infection episodes.
    • Excluded 34 lung transplant recipients, 2 pediatric subjects, 1 contaminated sample, 3 subjects without CT scans, and 4 subjects who received mold-active antifungal therapy.
    • Final analysis: 166 subjects and 169 infectious episodes for specificity.
    • "Possible" IA cases (n=106) were excluded from the analysis for specificity.
    • 38 subjects were adjudicated as having no invasive fungal infection.
    • 26 subjects were adjudicated as having mixed or other (non-IA) infections.

Data Provenance:

• Clinical Performance: Comprised of both archived, retrospective samples and prospectively collected samples.
• Cross-Reactivity, Interfering Substances, Analytical Sensitivity, Precision, Reproducibility: Laboratory-based studies using spiked samples, controls, and some clinical samples (origin of clinical samples not explicitly stated beyond "healthy urine" or "clinical samples from patients with known endogenous conditions" or "urine samples obtained from people with different medical conditions").

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

• Clinical Performance (Prospective Study): Clinical diagnoses were adjudicated by "a reviewer who was blinded to MycoMEIA test results."
• Qualifications: The specific qualifications of this reviewer (e.g., specialty, years of experience) are not specified in the provided text.

4. Adjudication Method for the Test Set

• Clinical Performance (Prospective Study): The adjudication method involved "a reviewer who was blinded to MycoMEIA test results." The reviewer applied the 2020 EORTC/MSG diagnostic criteria to establish diagnoses of proven IA, probable IA, and possible IA.
• No specific multi-expert adjudication method (e.g., 2+1, 3+1) is mentioned.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Human Improvement with AI vs. without AI Assistance

• The MycoMEIA Aspergillus Assay is an enzyme immunoassay (EIA), an in vitro diagnostic (IVD) device for detecting antigens.
• This is not an AI-powered device or imaging-based device that would involve human readers interpreting images with or without AI assistance.
• Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance was not conducted, and such data is not applicable here.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

• This is an in vitro diagnostic assay, which intrinsically provides a standalone (assay-only) result (an index value). The device itself is the algorithm/assay.
• The clinical performance section (sensitivity and specificity tables) represents the standalone performance of the MycoMEIA assay in detecting Aspergillus antigens in urine.
• While results are "interpreted by trained healthcare professionals, incorporating other diagnostic procedures," the reported sensitivity and specificity values reflect the assay's direct performance against the established ground truth.

7. The Type of Ground Truth Used

• Clinical Performance: The ground truth for Invasive Aspergillosis (IA) was established using 2020 EORTC/MSG diagnostic criteria for proven and probable IA. This is a consensus-based diagnostic standard.
• Analytical Studies (LoD, Precision, Reproducibility, Interfering Substances, Cross-Reactivity): Ground truth was based on known concentrations of Aspergillus antigen, specific microorganisms, or specific interfering substances as used in controlled spiking experiments.

8. The Sample Size for the Training Set

• The provided document describes a 510(k) submission for a clinical assay. It details analytical and clinical performance studies, which serve as validation.
• Unlike machine learning or AI-based devices, traditional IVDs typically do not involve a distinct "training set" in the same sense. The assay's design and optimization (analogous to training) would have occurred during its development phase, but specific "training set" sample sizes are not applicable or provided in this context. The study data presented are for validation/testing.

9. How the Ground Truth for the Training Set Was Established

• As explained above, a distinct "training set" with established ground truth in the context of machine learning is not relevant for this traditional immunoassay device. The ground truth for validation data was established as per point 7.

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