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The OraQuick Ebola Rapid Antigen Test is an in vitro diagnostic single-use immunoassay for the qualitative detection of antigens within the Ebolavirus genus but does not differentiate between these viruses. Testing with the OraQuick Ebola Rapid Antigen Test must only be performed when public health authorities have determined the need for this test. Testing for Ebola Virus Disease (EVD) must be performed in accordance with current guidelines provided by the appropriate public health authorities that address appropriate biosafety conditions, interpretation of test results, and coordination of testing, results and patient management with public health authorities. The OraQuick Ebola Rapid Antigen Test is intended for use with specimens from:

• individuals with epidemiological risk factors with signs and symptoms of EVD or
• . recently deceased individuals with epidemiological risk factors who are suspected to have died of EVD.

EVD is a nationally notifiable condition and must be reported to public health authorities in accordance with local, state, and federal regulations.

The OraQuick Ebola Rapid Antigen Test is intended for use with venipuncture whole blood and fingerstick whole blood specimens as an aid in diagnosis of EVD in patients suspected of and with signs or symptoms consistent with EVD who have epidemiological risk factor(s) for Ebolavirus exposure (e.g., contact with a known or suspected case, travel to a geographic location at a time when Ebolavirus transmission was known or suspected to have occurred). Performance of the device with Ebolavirus positive fingerstick whole blood was established in a non-human primate model.

The OraQuick Ebola Rapid Antigen Test is intended for use with cadaveric oral fluid collected from recently deceased individuals with epidemiological risk factors who are suspected to have died of EVD. Cadaveric oral fluid should be collected directly with the device or collected with oral swabs in viral transport media. The OraQuick Ebola Rapid Antigen Test is intended as an aid in the determination of EVD as the cause of death to inform decisions on safe handling of cadavers to prevent disease transmission.

The OraQuick Ebola Rapid Antigen Test results are presumptive, definitive identification of EVD requires performing additional testing and confirmation procedures in consultation with public health and/or other authorities to whom reporting is required.

Negative results were observed in individuals with low levels of circulating virus, therefore negative results do not preclude infection with viruses within the Ebolavirus genus.

The level of Ebolavirus antigens that would be present in EVD clinical specimens from individuals with early systemic infection is unknown. Test performance of the OraQuick Ebola Rapid Antigen Test is associated with the level of Ebolavirus antigens in the patient; therefore, the test is not intended for use in an asymptomatic population for massscreening purposes (e.g., as the sole means of EVD control at airports or bordercrossings) or for testing of individuals at risk of exposure without observable signs of infection.

The OraQuick Ebola Rapid Antigen Test is intended for use by experienced personnel who have documented device specific training offered by OraSure Technologies Inc., training in the correct use of recommended personal protective equipment (PPE) and expertise in infectious disease diagnostic testing, including the safe handling of clinical specimens potentially containing Ebolavirus. The test is intended for use by laboratory professionals or healthcare workers who have demonstrated availability of biosafety equipment, access to patient containment facilities, and established procedures (e.g., SOP) for coordinating testing, results and patient management with public health authorities consistent with state, local and federal recommendations and guidelines.

The OraQuick Ebola Rapid Antigen Test is a manually performed, visually read immunoassay for the qualitative detection of Ebola virus in human venipuncture whole blood, fingerstick whole blood and cadaveric oral fluid. The OraQuick Ebola Rapid Antigen Test is comprised of both a single-use test device and a vial containing a pre-measured amount of a buffered developer solution. The single-use test devices consist of a plastic housing that protects the assay test strip with the reagents. The assay strip can be viewed through the test device result window. The test result window has indicated zones for the Ebolavirus specific Test Line and the Control Line of the test. The test consists of a sealed pouch with two separate compartments for each of the following two components:

• 1. OraQuick Ebola Rapid Antigen Test
• 2. Developer Vial

The OraQuick Ebola Rapid Antigen Test further contains the following materials for the sample processing:

• 1. Test Stand
• 2. Micropipettes capable of pipetting 20ul of sample

The OraQuick Ebola Rapid Antigen Test kit must be used with the OraQuick Ebola Rapid Antigen Test Kit Controls and a Visual Reference Panel (available separately). The OraQuick Ebola Rapid Antigen Test Kit Controls contain:

• 1. One Ebola positive control vial (orange capped)
• 2. One Ebola negative control vial (white capped)

The positive control contains 0.25mL of Ebola recombinant VP40 equivalent to a moderate positive result and is diluted in a defibrinated pool of normal human plasma negative for Ebolavirus. The negative control contains 0.25 mL of defibrinated pool of normal human plasma negative for Ebolavirus. The controls do not contain infectious Ebolavirus material.

The OraQuick Ebola Visual Reference Panel (VRP) is intended to assist new operators in becoming proficient at reading specimens with antigen levels near the limit of detection of the device. The devices in the VRP do not contain any infectious material. The VRP contains three Quick Ebola Rapid Antigen Test devices that have been designed to represent reading intensities representative of

• 1. A test result near the limit of detection (LoD)
• 2. A low positive test result
• 3. A negative test result

Additional materials required but not provided include

1. Timer

Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for the OraQuick Ebola Rapid Antigen Test are primarily demonstrated through various analytical and clinical performance studies. While explicit pass/fail criteria are not always stated quantitatively (e.g., "must achieve X% PPA"), the reported performance in tables is presented as meeting the expectations for De Novo classification.

Here is a table summarizing the reported device performance, which implies the acceptance criteria established for this device:

Study Details Proving Acceptance Criteria

1. Sample Size and Data Provenance:

• Test Set Sample Sizes:
  • Clinical Sensitivity (Natural Samples):
    • Venous Whole Blood: 25 Ebola positive, 50 Ebola negative samples (retrospective).
    • Cadaveric Oral Fluid (West Africa): 35 comparator PCR positive, 193 comparator PCR negative samples (prospective & retrospective).
    • NHP Study (Fingerstick/Venous): 5 non-human primates, samples collected at multiple time points (pre- and post-exposure, up to day 8).
  • Clinical Sensitivity (Contrived Samples):
    • Venous Whole Blood: 25 individual samples (12 at 1.5x LoD, 13 at 5x LoD), additional negative samples for blinding.
    • Cadaveric Oral Fluid: 20 positive (9 at 1.5x LoD, 10 at 5x LoD), 5 negative samples.
  • Clinical Specificity (Natural Samples):
    • Venous Whole Blood (Non-endemic): 226 samples.
    • Fingerstick Whole Blood (Non-endemic): 249 samples (224 from main cohort, 25 from previous EUA study).
    • Direct Cadaveric Oral Fluid (Endemic): 147 samples (50 from Sierra Leone, 97 from Liberia).
    • VTM Cadaveric Oral Fluid (Non-endemic): 63 matched sets (BD Universal VTM and Σ-Virocult).
  • Reproducibility: Three panel members (negative, 2x LoD, 5x LoD) tested twice daily with each of three lots over 5 days by 3 operators per site (3 sites). Exact N/n values are redacted for specific numbers but overall concordance is provided.
  • Detection Limit (LoD) Confirmation: 20 replicates each for tentative LoD, negative, and moderate positive samples.
  • Analytical Specificity (Reactivity/Cross-Reactivity): 3 replicates for each concentration tested.
  • Interference: 6 or 12 replicates for negative and positive (2x or 4x LoD) samples depending on the interferent.
• Data Provenance:
  • Retrospective/Prospective: A mix of retrospective and prospective studies.
    • Retrospective: Clinical sensitivity studies for venous whole blood and cadaveric oral fluid from West Africa (2014/15 Ebola Zaire outbreak).
    • Prospective: Clinical specificity studies for venous and fingerstick whole blood from a non-endemic U.S. population. NHP study was also prospective.
  • Country of Origin:
    • West Africa (Sierra Leone, Liberia, Guinea) for actual outbreak samples.
    • United States for non-endemic population studies and contrived samples.
    • NHP study performed at a BSL-4 laboratory at (b) (4).
  • Sample Types: Venipuncture whole blood, fingerstick whole blood, cadaveric oral fluid. Contrived samples used both living human matrix and NHP models.

2. Number of Experts and Qualifications:

• Ground Truth for Clinical Samples: Primarily established by RT-PCR assays, which are considered the highly sensitive and specific comparator method for Ebolavirus detection. These PCR tests were validated/EUA-authorized. The document refers to "experienced personnel" for test performance and interpretation, but specific numbers and qualifications of experts establishing the ground truth are not detailed for the natural clinical samples beyond the use of validated PCR methods.
• For Analytical Studies (e.g., LoD, Reproducibility): Operators were "blinded," and studies performed at "three (3) testing sites, two external and one internal." No specific "expert" roles are defined for establishing ground truth in these highly controlled analytical settings where ground truth is pre-defined by the spiked concentrations.

3. Adjudication Method for the Test Set:

• The primary ground truth for clinical samples was RT-PCR results.
• For reproducibility studies, "Sample testing was performed blinded." For LoD confirmation, samples were "randomized and tested by three blinded operators."
• "No replicate testing was performed" for the West African venous whole blood clinical sensitivity study.
• The text does not explicitly mention a multi-expert adjudication method (e.g., 2+1, 3+1) for discordant samples or for establishing a consensus "ground truth" through visual interpretation by multiple human readers. Decisions regarding inclusion/exclusion of samples (e.g., invalid PCR results, low volume samples) were based on specified criteria.

4. MRMC Comparative Effectiveness Study:

• No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was explicitly performed or reported in the sense of comparing human reader performance with AI assistance vs. without AI assistance. This device is a lateral flow immunoassay, a manually performed and visually read test, with "no software or instrument components." Therefore, the concept of "AI assistance" in reading or interpreting results does not apply to this device. Human readers are the sole interpreters of the visual lines on the test strip.

5. Standalone Performance:

• This device is a standalone diagnostic test in the context of its operation. Its "performance" refers to the accuracy of the device itself (the visual readout by a human operator) compared to a reference method (RT-PCR). There is no "human-in-the-loop" performance beyond the human visually interpreting the device's result. The robust human factors and usability studies assess the human's ability to correctly operate and read the device.

6. Type of Ground Truth Used:

• Expert Consensus: Not explicitly stated as the primary ground truth method, though trained personnel perform the visual interpretations.
• Pathology: Not used.
• Outcomes Data: Not directly stated as the ground truth. The primary ground truth for validation of clinical performance (sensitivity and specificity) is RT-PCR results, typically from samples collected from patients with signs, symptoms, and epidemiological risk factors. For cadaveric studies, PCR results from cadaveric oral fluid samples served as the comparator.
• Contrived Samples: A significant portion of the analytical and some clinical sensitivity studies utilized contrived samples with pre-defined concentrations of Ebolavirus or recombinant antigens. These concentrations represent the "ground truth" for those specific studies.
• NHP Infected Status: For the NHP study, "infected status" (based on viral challenge) was also used as a comparator for PPA.

7. Sample Size for the Training Set:

• The document describes a De Novo submission for a diagnostic device, which typically means it is the device, not a component developed using machine learning that requires a separate training set.
• As a manually read, lateral flow immunoassay without AI/machine learning components, the concept of a "training set" for an algorithm is not applicable. The "training" described relates to operator training (e.g., "device specific training offered by OraSure Technologies Inc.") and the use of a Visual Reference Panel to help operators become proficient in reading results, especially low-intensity lines. This refers to training human operators, not a machine learning model.

8. How Ground Truth for Training Set was Established:

• Given it's a visually read immunoassay with no AI/ML, there isn't an algorithm "training set" in the modern ML sense.
• For the Visual Reference Panel (VRP), which aids in human operator training, the VRP contains devices designed to represent specific reading intensities (LoD, low positive, negative). The "ground truth" for these VRP devices is their pre-designed antigen concentration levels during manufacturing to achieve those target visual intensities. The stability section for the VRP mentions "Target Reading Level 1+" and "Target Reading Level 3+", implying these were established by the manufacturer to calibrate visual interpretation.

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