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The BD Veritor™ System for SARS-CoV-2 is a chromatographic digital immunoassay for the rapid, qualitative detection of SARS-CoV-2 nucleocapsid protein antigens directly in anterior nasal swab specimens from individuals with signs and symptoms of upper respiratory infection (i.e., symptomatic). The test is intended for use as an aid in the diagnosis of SARS-CoV-2 infections (COVID-19) in symptomatic individuals when either: tested at least twice over three days with at least 48 hours between tests; or when tested once, and negative by the BD Veritor™ System for SARS-CoV-2 and followed up with a molecular test.

A negative test result is presumptive and does not preclude SARS-CoV-2 infection; it is recommended these results be confirmed by a molecular SARS-CoV-2 assay.

Positive results do not rule out co-infection with other bacteria or viruses and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

Performance characteristics for SARS-CoV-2 were established between April 2024 and August 2024 when SARS-CoV-2 Omicron was the predominant SARS-CoV-2 variant in circulation. Performance characteristics may vary with newly emerging SARS-CoV-2 virus variants.

The BD Veritor™ System for SARS-CoV-2 is a rapid (approximately 15 minutes) chromatographic digital immunoassay for the direct detection of the presence or absence of SARS-CoV-2 antigens in anterior nasal swab specimens taken from patients with signs and symptoms of upper respiratory infection (i.e., symptomatic) who are suspected of COVID-19 by their healthcare provider. The test is intended for use with an opto-electronic interpretation instrument, the BD Veritor™ Plus Analyzer Instrument and is not interpreted visually.

• When specimens are processed and added to the test device, SARS‑CoV‑2 antigens present in the specimen bind to biotinylated antibodies and antibodies conjugated to detector particles in the test strip.
• The biotinylated antibody‑antigen‑conjugate complexes migrate across the test strip to the reaction area and are captured by a line of streptavidin bound on the membrane.
• A positive result is determined by the BD Veritor™ Plus Analyzer when antigen‑conjugate is deposited at the Test "T" position and a control conjugate is deposited at the Control "C" position on the assay device.
• The instrument analyzes and corrects for non‑specific binding and detects positives not recognized by the unaided eye to provide an objective result.

Procedures to evaluate test devices depend on the BD Veritor™ Plus Analyzer workflow configuration chosen. In Analyze Now mode, the instrument evaluates assay devices after manual timing of their development. In Walk Away mode, devices are inserted immediately after application of the specimen, and timing of assay development and analysis is automated. Additionally, connection of a BD Veritor™ Plus Analyzer to a printer or IT system is possible if desired. Additional result documentation capabilities are possible with the integration of a BD Veritor™ barcode scanning enabled module.

The Analyzer uses a proprietary algorithm that subtracts the nonspecific signal at the negative control line from the signal present at the test line. If the resultant test line signal is above a preselected cutoff, the specimen is scored as positive. If the resultant test line signal is below or equal to the cutoff, the specimen is scored as negative. Use of the active negative control feature allows the BD Veritor™ Plus Analyzer to correctly interpret test results that cannot be scored visually because the human eye is unable to accurately perform the subtraction of the nonspecific signal. The Analyzer measures the amount of light reflected from various zones along the assay strip. The measurement of the assay background zone is an important factor during the test interpretation as the reflectance value is compared to that of the control and test zones.

The provided FDA 510(k) clearance letter and summary describe the BD Veritor System for SARS-CoV-2. Here's an analysis of the acceptance criteria and the study that proves the device meets those criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets in the document. However, based on the clinical study results and FDA clearance, the implicit acceptance criteria for clinical performance are related to the confidence intervals for Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA). The reported device performance is presented below:

Note: The document does not explicitly state numerical acceptance thresholds for PPA and NPA (e.g., "PPA must be > 80%"). Therefore, the "Implicit Acceptance Criteria" are inferred from the demonstrated performance and the fact that the device received clearance. The FDA typically evaluates these metrics within acceptable ranges for diagnostic tests.

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

• Sample Size for Test Set: 1,032 direct anterior nasal swabs.
• Data Provenance: The samples were prospectively collected from individual symptomatic patients across 15 geographically diverse areas across the United States between April and August 2024.

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

The document does not specify the number of experts used to establish the ground truth. The ground truth was established by an FDA-cleared SARS-CoV-2 RT-PCR test. For the false positive/negative re-testing, it broadly states "a second RT-PCR method," implying multiple tests might have been performed to confirm results without specifying expert involvement in interpreting these specific results beyond the RT-PCR outcome itself.

4. Adjudication Method for the Test Set

The primary ground truth for the clinical study was established by an FDA-cleared SARS-CoV-2 RT-PCR test without explicit mention of expert adjudication for every case. However, there was a form of adjudication for discordant results:

• False Positive Adjudication: The three BD Veritor System for SARS-CoV-2 false positive results were retested with a second RT-PCR method and were confirmed negative. This suggests a method where initial discrepancies against the reference method were independently verified.
• False Negative Adjudication: The 23 BD Veritor System for SARS-CoV-2 false negative results were retested with a second RT-PCR method in which 14 were confirmed positive and 9 were negative.

This indicates a process of re-testing or confirmation for discordant results, which serves as a form of adjudication.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a multi-reader multi-case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance (or similar comparative effectiveness of human readers with vs. without the device) was not explicitly mentioned or described in the provided document. The BD Veritor System for SARS-CoV-2 uses an instrument (BD Veritor™ Plus Analyzer) for interpretation, replacing visual interpretation with an automated read. The comparison is between the device's performance and a reference RT-PCR, not between human readers with and without assistance from the device.

6. Standalone (Algorithm Only) Performance Study

Yes, a standalone study was done. The entire clinical performance study (Table 9 and 11) is a standalone study, as it evaluates the performance of the BD Veritor System for SARS-CoV-2 (algorithm/device only) compared to a reference RT-PCR without human interpretation of the lateral flow assay itself. The BD Veritor™ Plus Analyzer instrument is explicitly stated to read and interpret the results, and the device "is not interpreted visually."

7. Type of Ground Truth Used

The ground truth used for the clinical study was an FDA-cleared SARS-CoV-2 RT-PCR test (molecular test results).

8. Sample Size for the Training Set

The document does not specify a sample size for a training set. This submission is for a device, and the analytical and clinical studies described are for validation of the device's performance, not for developing or training an AI/ML algorithm in the context of a typical AI/ML development pipeline. The device uses a "proprietary algorithm" for signal subtraction and interpretation, but it's not presented as a machine learning model that requires a distinct training set in the typical sense.

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

Since no specific training set and its ground truth establishment are discussed in the context of AI/ML model training, this information is not applicable/provided based on the document. The "proprietary algorithm" for the instrument is described in terms of processing reflectance data and applying a preselected cutoff, and its development process (including any data used for internal calibration or parameter setting) is not detailed here.

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The BinaxNOW COVID-19 Ag Card is a lateral flow immunochromatographic assay for the rapid, qualitative detection of the SARS-CoV-2 nucleocapsid protein antigen directly in anterior nasal swab specimens from individuals with signs and symptoms of upper respiratory tract infection (i.e., symptomatic). The test is intended for use as an aid in the diagnosis of SARS-CoV-2 infections (COVID-19) in symptomatic individuals when either: tested at least twice over three days with at least 48 hours between tests; or when tested once, and negative by the BinaxNOW COVID-19 Ag Card and followed up with a molecular test.

A negative test is presumptive and does not preclude SARS-CoV-2 infection; it is recommended these results be confirmed by a molecular SARS-CoV-2 assay.

Positive results do not rule out co-infection with other bacteria or viruses and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

The BinaxNOW COVID-19 Ag Card is an immunochromatographic membrane assay that uses antibodies to detect SARS-CoV-2 nucleocapsid protein from anterior nasal swab specimens. SARS-CoV-2 specific antibodies and a control antibody are immobilized onto a membrane support as two distinct lines and combined with other reagents/pads to construct a test strip. This test strip and a well to hold the swab specimen are mounted on opposite sides of a cardboard, book-shaped hinged test card.

To perform the test, an anterior nasal swab specimen is collected from the patient, 6 drops of extraction reagent from a dropper bottle are added to the top hole of the swab well. The patient sample is inserted into the test card through the bottom hole of the swab well, and firmly pushed upwards until the swab tip is visible through the top hole. The swab is rotated 3 times clockwise and the card is closed, bringing the extracted sample into contact with the test strip. Test results are interpreted visually at 15 minutes based on the presence or absence of visually detectable pink/purple colored lines. Results should not be read after 30 minutes.

The provided document is a 510(k) summary for the BinaxNOW COVID-19 Ag Card. It does not describe a study proving a device meets acceptance criteria in the manner typically associated with AI/ML-driven medical devices, which would involve measures like sensitivity, specificity, or AUC against a ground truth, often with human readers involved (MRMC studies).

Instead, this document describes the validation of an immunochromatographic assay (a rapid antigen test) for COVID-19. The "acceptance criteria" here are typically performance targets for analytical and clinical characteristics (e.g., Limit of Detection, cross-reactivity, Positive Percent Agreement, Negative Percent Agreement). The "study" refers to the analytical and clinical studies conducted to demonstrate these performance characteristics.

Therefore, the following response will interpret "acceptance criteria" as the performance benchmarks for a diagnostic assay and describe the validation studies for the BinaxNOW COVID-19 Ag Card based on the provided text.

Here's a breakdown of the information requested, interpreted in the context of a rapid antigen test (not an AI/ML device):

Acceptance Criteria and Device Performance for BinaxNOW COVID-19 Ag Card

The BinaxNOW COVID-19 Ag Card is a lateral flow immunochromatographic assay, not an AI/ML diagnostic device. Therefore, the "acceptance criteria" are based on the analytical and clinical performance characteristics typical for such an in-vitro diagnostic (IVD) device, rather than metrics like AUC, sensitivity/specificity of an AI algorithm, or human reader improvement with AI assistance.

1. Table of Acceptance Criteria and Reported Device Performance

• Day 0: 69.23% (Omicron Study)
• Day 1: 94.12% (Original), 88.24% (Omicron)
• Day 2: 73.33% (Original), 97.22% (Omicron)
• Day 3: 76.00% (Original), 100.00% (Omicron)
• Day 4: 88.89% (Original), 66.67% (Omicron)
• Day 5: 100.00% (Original), 100.00% (Omicron) |
  | | Invalid Rate | Low invalid rate. | 0.68% overall (5/730). |
  | User/Environmental Factors | Flex Studies (Robustness) | Device performs accurately under various usage and environmental conditions. | Demonstrated robustness to usage variation and environmental factors. Identified that direct exposure of test strip to wet cleaning solutions or excessive glove powder may cause erroneous results, leading to specific instructions for use. |

2. Sample Sizes and Data Provenance (Clinical Studies)

• Clinical Test Set Sample Size:
  • Study 1 (Original): 295 evaluable subjects.
  • Study 2 (Omicron): 309 evaluable subjects.
  • Combined Clinical Data: 604 evaluable nasal swabs from symptomatic patients (within 5 days of symptom onset).
• Data Provenance: Clinical studies were conducted within the United States.
  • Study 1: November 2020 through March 2021 (when Delta and Omicron were dominant).
  • Study 2: February 2022 to July 2022 (when Omicron and its variants were prevalent).
• Retrospective/Prospective: Both clinical studies were prospective.

3. Number of Experts and Qualifications for Ground Truth for Test Set

This type of diagnostic device (lateral flow immunoassay) does not typically utilize human experts in the same way an AI/ML device would for image interpretation or clinical diagnosis. For the BinaxNOW COVID-19 Ag Card, the ground truth for the clinical studies was established by a comparator molecular test (RT-PCR). The experts involved would be the laboratory personnel performing and interpreting the RT-PCR assays. Their specific qualifications are not detailed in this summary but are implicitly assumed to be standard for clinical laboratory professionals performing EUA-authorized RT-PCR tests.

4. Adjudication Method for the Test Set

Not applicable in the typical sense for an AI/ML study involving human interpretation. The comparator method (RT-PCR) serves as the reference standard. The document mentions for the serial testing study's composite comparator method that in cases of discordant RT-PCR results, a third RT-PCR test was performed, and the final result based on majority rule.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. This is a rapid antigen test, not an AI/ML system where human readers would interpret results "with vs. without AI assistance." The test is visually read by the user, and its performance is assessed against a molecular gold standard.

6. Standalone Performance (Algorithm Only without Human-in-the-Loop Performance)

This question is not applicable in the context of this device. The BinaxNOW COVID-19 Ag Card is a manually read, qualitative visual assay. There is no AI algorithm to evaluate for standalone performance. The "performance" tables provided in the document (PPA and NPA) essentially represent the "standalone" performance of the rapid antigen test itself when interpreted visually.

7. Type of Ground Truth Used

• For Clinical Studies: The primary ground truth for clinical performance (PPA, NPA) was an FDA Emergency Use Authorized real-time Polymerase Chain Reaction (RT-PCR) assay for the detection of SARS-CoV-2.
• For Serial Testing Study: A composite comparator method was used, involving at least two highly sensitive EUA RT-PCRs. If discordant, a third RT-PCR was performed, and the final result was based on majority rule.
• For Analytical Studies: Ground truth was established by known concentrations of heat-inactivated SARS-CoV-2 virus or WHO International Standard for SARS-CoV-2 Antigen (NIBSC 21/368) for LoD and inclusivity studies, and known presence/absence of specific microorganisms for cross-reactivity.

8. Sample Size for the Training Set

This information is not applicable for this type of IVD device. The BinaxNOW COVID-19 Ag Card is a laboratory-developed lateral flow assay, not an AI/ML model that is 'trained' on data. Its 'training' is the fundamental assay development and optimization process, not a computational training set.

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

Not applicable for this device type. The manufacturing process and quality control of the reagents and test strip govern its 'performance' characteristics, which are then analytically and clinically validated.

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The SCOV-2 Ag Detect Rapid Test is a lateral flow immunochromatographic assay for the rapid, qualitative detection of the SARS CoV-2 nucleocapsid protein antigen directly in anterior nasal swab specimens from individuals with signs and symptoms of upper respiratory tract infection (i.e., symptomatic). This test is intended for use as an aid in the diagnosis of SARS-CoV-2 infections (COVID-19) in symptomatic individuals when either: tested at least twice over three days with at least 48 hours between tests; or when tested once, and negative by the SCoV-2 Ag Detect Rapid Test and followed up with a molecular test.

A negative test result is presumptive, and does not preclude SARS-CoV-2 infection; it is recommended these results be confirmed by a molecular SARS-CoV-2 assay.

Positive results do not rule out co-infection with other bacteria or viruses and should not be used as tor diagnosis, treatment, or other patient management decisions.

Performance characteristics for SARS-CoV-2 were established during the SARS-CoV-2 pandemic from April 2021- April 2024. The dominant variant in circulation varied throughout this period. Performance characteristics may vary with newly emerging SARS-CoV-2 virus variants.

The SCOV-2 Ag Detect Rapid Test is a lateral flow immunochromatographic assay for the rapid, qualitative detection of the SARS CoV-2 nucleocapsid protein antigen directly in anterior nasal swab specimens.

The provided text is a 510(k) clearance letter from the FDA for the "SCoV-2 Ag Detect Rapid Test." It primarily focuses on the regulatory aspects of the device's clearance and does not contain detailed information about the acceptance criteria, specific study design, or performance metrics from the validation study.

Therefore, I cannot extract the requested information (table of acceptance criteria, sample size, expert qualifications, etc.) from this document. The letter itself confirms the device's substantial equivalence to legally marketed predicates but does not include the performance data that supported this determination.

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The Healgen Rapid COVID-19 Antigen Test is a lateral flow immunochromatographic assay intended for the rapid, qualitative detection of SARS-CoV-2 nucleocapsid protein antigens directly in anterior nasal swabs specimens from individuals with signs and symptoms of upper respiratory infection within the first six (6) days of symptom onset. The test is intended for use as an aid in the diagnosis of SARS-CoV-2 infections (COVID-19) in symptomatic individuals when either: tested at least twice over three days with at least 48 hours between tests; or when tested once, and negative by the Healgen Rapid COVID-19 Antigen Test and followed with a molecular test
The test does not differentiate between SARS-CoV and SARS-CoV-2.
A negative test result is presumptive and it is recommended these results be confirmed by a molecular SARS-CoV-2 assay. Negative results do not preclude SARS-CoV-2 infections and should not be used as the sole basis for treatment or other patient management decisions.
Positive results do not rule out co-infection with other respiratory pathogens
Performance characteristics for SARS-CoV-2 were established from May 2022 to July 2022 when SARS-CoV-2 Omicron was the predominant SARS-CoV-2 variant in circulation. When other SARS-CoV-2 virus variants are emerging, performance characteristics may vary.

The Healgen Rapid COVID-19 Antigen Test is a lateral flow immunochromatographic assay that uses highly sensitive monoclonal antibodies to detect nucleocapsid protein from SARS-CoV-2 virus in nasal swab collected specimens. The test strip is composed of the following components: sample pad, reagent pad, reaction membrane, and absorbing pad housed within a test cassette. The reagent pad contains colloidal-gold-conjugated monoclonal antibody that recognizes and binds to the nucleocapsid protein of SARS-CoV-2; the reaction membrane in the test line (T) contains the second antibody that recognizes another epitope of the nucleocapsid protein of SARS-CoV-2.
External quality controls are required but not included with the test kit and are sold separately as the COVID-19 Antigen Control Kit. The control swabs should be processed according to the Instructions for Use (IFU) and are intended to be used as quality control samples to demonstrate that the test is performing and is being performed correctly.

The provided text describes the performance characteristics and acceptance criteria for the Healgen Rapid COVID-19 Antigen Test.

Here's an analysis to extract the requested information:

1. A table of acceptance criteria and the reported device performance:

The document doesn't explicitly state "acceptance criteria" as a separate, pre-defined set of thresholds in a table. Instead, it presents the results of various performance studies. The implicit acceptance criteria are that the device performance should be clinically acceptable and comparable to existing devices for substantial equivalence.

Here's a table summarizing the reported device performance, which can be interpreted as having met the (implicit) acceptance criteria:

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Test Set Sample Size: 806 evaluable subjects.
• Data Provenance:
  • Country of Origin: Not explicitly stated, but the submission is to the U.S. FDA, and the virus strain mentioned is "USA-WA1/2020," suggesting a U.S. context.
  • Retrospective/Prospective: Prospective. The clinical performance study collected samples "prospectively collected from symptomatic subjects between May 2022 and July 2022 at six clinical point of care sites."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

The ground truth for the clinical test set was established using RT-PCR assays, not expert human readers. Therefore, the concept of "number of experts" for ground truth establishment isn't applicable in the context of this device. The RT-PCR assays are considered the gold standard for detecting SARS-CoV-2 viral nucleic acid.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

The adjudication method used for the comparator (RT-PCR) was a "2 out of 3 rules." This means that if the first two FDA-cleared, highly sensitive RT-PCR assays had discordant results, a third FDA-cleared RT-PCR comparator assay was performed, and the final result was determined by the majority.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No MRMC comparative effectiveness study was done. This device is a rapid antigen test read visually by users (healthcare professionals), not an AI-powered diagnostic imaging device that assists human readers. The study focuses on the diagnostic accuracy of the device itself compared to a molecular gold standard.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

The device itself is a standalone "algorithm" in the sense of a chemical diagnostic assay that produces a visual result. There is no separate "algorithm" being evaluated without human-in-the-loop, as the human (healthcare professional) is part of reading the visually interpreted result. The "performance characteristics" section details the standalone performance of the device (the antigen test) against the RT-PCR comparator, which represents the device's accuracy without a separate human interpretation study impacting the core result.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The type of ground truth used for the clinical performance test set was molecular SARS-CoV-2 assay results, specifically composite RT-PCR assays. This is a highly sensitive and specific laboratory-based "diagnostic truth" for the presence of the virus.

8. The sample size for the training set

The document does not mention a training set in the context of machine learning or AI models. This device is a lateral flow immunochromatographic assay, a chemical test, not a software or AI-based diagnostic tool that would typically involve a separate training phase with a distinct dataset. The "development" of such a test involves chemical formulation and design, not typically data training in the AI sense.

9. How the ground truth for the training set was established

As there is no mention of a training set for an AI/ML model, this question is not applicable to the Healgen Rapid COVID-19 Antigen Test.

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The Nano-Check™ COVID-19 Antigen Test is a lateral flow immunochromatographic assay for the rapid, qualitative detection of SARS-CoV-2 nucleoprotein antigens directly in anterior nasal swab specimens from individuals with signs and symptoms of upper respiratory infection (i.e., symptomatic) when testing is started within 4 days of symptom onset. The test is intended for use as an aid in the diagnosis of SARS-CoV-2 infections (COVID-19) in symptomatic individuals when either: tested at least twice over three days with at least 48 hours between tests; or when tested once, and negative by the Nano-Check™ COVID-19 Antigen Test and followed up with a molecular test.

The test does not differentiate between SARS-CoV or SARS-CoV-2.

A negative test result is presumptive, and it is recommended these results be confirmed by a molecular SARS-CoV-2 assay. Positive results do not rule out co-infection with other bacteria or viruses and should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

Performance characteristics for SARS-CoV-2 were established during the 2022-2023 SARS-CoV-2 pandemic when SARS-CoV-2 Omicron was the predominant SARS-CoV-2 variant in circulation. When other SARS-CoV-2 virus variants are emerging, performance characteristics may vary.

The Nano-Check™ COVID-19 Antigen Test is an immunochromatographic assay for detection of extracted SARS-CoV-2 nucleoprotein antigens in human anterior nasal swab specimens.

The assay kit consists of 20 test cassette devices, 20 reagent tubes containing extraction buffer for Set A or 20 empty reagent tubes and 20 ampules containing extraction buffer for Set B, 20 anterior nasal specimen collection swabs, one positive control swab, one negative control swab and an Instructions for Use/Quick Reference Instruction. An external positive control swab is used with recombinant SARS-CoV-2 nucleocapsid dried onto the swab and an external negative control swab contains blank universal viral transport media dried on the swab. The kit should be stored at 2°C - 30°C.

Here's an analysis of the acceptance criteria and the study that proves the Nano-Check COVID-19 Antigen Test meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for clinical performance are implicitly derived from the reported Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA). While explicit numerical acceptance targets are not stated, the device's performance is presented in comparison to a molecular RT-PCR test.

For analytical performance, acceptance criteria are generally "no interference" for cross-reactivity and endogenous/exogenous interference, and "100% agreement" for precision and reproducibility at moderate to high concentrations.

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

• Sample Size (Clinical Study Test Set): 670 subjects
• Data Provenance: Multi-center, prospective clinical study in the U.S. in 2022-2023. At the time of the study, the SARS-CoV-2 Omicron variant was the predominant strain.

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

The document does not specify the number or qualifications of experts used to establish the ground truth for the clinical study. The ground truth was established using an "FDA Cleared SARS-CoV-2 RT-PCR Test as comparator." RT-PCR tests are molecular diagnostic methods and are considered the gold standard for SARS-CoV-2 detection, generally not requiring expert interpretation for generating positive/negative results.

4. Adjudication Method for the Test Set

The document does not explicitly state an adjudication method (like 2+1, 3+1, none) for discordant results between the Nano-Check COVID-19 Antigen Test and the RT-PCR comparator. The results are presented directly from this comparison.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

There was no MRMC comparative effectiveness study and no mention of AI or human readers being assisted by AI in this context. This device is a visually-read, lateral flow immunochromatographic assay, meaning results are interpreted directly by the user looking at control and test lines.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

This is not applicable as the device is a visually-read assay. There is no algorithm for standalone performance. The interpretation is directly by the user.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

The ground truth used for the clinical study was an FDA Cleared SARS-CoV-2 RT-PCR Test. This is considered the molecular "gold standard" for detecting the presence of SARS-CoV-2 viral RNA.

8. The Sample Size for the Training Set

The document does not report a sample size for a training set. This is expected as the Nano-Check COVID-19 Antigen Test is a traditional immunoassay, not an AI/machine learning-based device that typically requires a training set. The "training" of such a device is in its biochemical formulation and physical design, not in data-driven algorithm optimization.

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

As no training set is mentioned or applicable for this type of device, this information is not provided.

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The Sofia 2 SARS Antigen+ FlA is a lateral flow immunofluorescent sandwich assay that is used with the Sofia 2 instrument for the rapid, qualitative detection of SARS-CoV-2 nucleocapsid protein antigens directly in anterior nasal swab specimens from individuals with signs and symptoms of upper respiratory infection (i.e., symptomatic) when testing is started within 6 days of symptom onset. The test is intended for use as an aid in the diagnosis of SARS-CoV-2 infections (COVID-19) in symptomatic individuals when either: tested at least twice over three days with at least 48 hours between tests; or when tested once, and negative by the Sofia 2 SARS Antigen+ FIA and followed up with a molecular test.

The test does not differentiate between SARS-CoV and SARS-CoV-2.

A neqative test result is presumptive, and it is recommended these results be confirmed by a molecular SARS-CoV-2 assay.

Positive results do not rule out co-infection with bacteria or other viruses and should not be used as the sole basis for treatment or other patient management decisions.

Performanc characteristics for SARS-CoV-2 were established during the 2021-2022 SARS-CoV-2 pandemic when SARS CoV 2 Omicron was the predominant SARS-CoV-2 variant in circulation. When other SARS-CoV-2 virus variant are emerging, performance characteristics may vary.

This test is intended for prescription use only and can be used in Point-of-Care settings.

Sofia 2 SARS Antigen+ FIA Control Swab Set:

The Sofia 2 SARS Antigen+FIA Control Swabs are intended to be used as quality control samples with the Sofia 2 SARS Antigen+ FIA and are representative of positive and negative test samples. These Controls may be used to demonstrate that the reagents and assay procedure perform properly.

The Sofia 2 SARS Antigen+FIA is based upon a lateral flow technology that employs immunofluorescence technology in a sandwich design that is used with Sofia 2 to detect nucleocapsid protein from the SARS-CoV-2 virus in human anterior nasal swab specimens.

The patient sample is placed in the Reagent Tube, during which time the virus particles in the sample are disrupted, exposing internal viral nucleoproteins. After disruption, the sample is dispensed into the Test Cassette sample well. The Test Strip is composed of the following biochemical components dried and immobilized onto the nitrocellulose membrane: 1) sample pad that receives the specimen: 2) a label pad that contains detection fluorescent micro-particles, coated with monoclonal antibodies that are specific for SARS-CoV-2 nucleocapsid antigen; 3) embedded monoclonal antibodies specific for SARS-CoV-2 nucleocapsid antigen to capture the antigen-microparticle complex at the tocation. The sample pad facilitates migration of the sample fluid across the nitrocellulose strip into the absorbent pad (See Figure 4-1 in attachment). The test strip also contains a desiccant that does not participate in the assay but serves as a stabilizing agent during storage.

Sample is applied to in the sample well and migrates through a test strip, then passes through the test and control lines. If SARS-CoV-2 viral antigen is present, they will be bound by the fluorescent microparticles io the label pad reqion, forming an antigen-microparticle complex.

The test line is coated with monoclonal antibodies that are specific to SARS-CoV-2 nucleocapsid antigen and is intended to capture the antigen-microparticle complex. If SARS-CoV-2 viral antigen is not present, the fluorescent microparticles will not be trapped by the capture antibodies nor detected by Sofia 2.

The Sofia 2 SARS Antigen+ FIA employs antibody tagged microparticles dyed with a fluorescent compound, to be detected and read by the Sofia 2 reader instrument. The Sofia 2 analyzers automatically scan/image the test strip, collect and analyze the fluorescence data, and report the result as either positive, negative, or invalid.

Additionally, the Sofia 2 Antigen+ FIA utilizes a reference line for the Sofia 2 reader (to locate the test line and negative control line) and a procedural control (to assess for sample presence and adequate sample flow). No colored lines will be visible in the test window of the fluorescent assay cassette, thereby preventing visual interpretation of the test results. The operator must use the Sofia 2 analyzer to obtain a test result.

The Sofia 2 SARS Antigen+ FIA Control Swabs are intended to be used as quality control samples representative of positive and neqative test samples, to demonstrate that the reagents are that the assay procedure is correctly perform.

This document is a 510(k) Premarket Notification from the FDA regarding the Sofia 2 SARS Antigen+ FIA. It primarily details the device's indications for use, its description, and a comparison to a legally marketed predicate device.

Here's an analysis of the provided information to address your request:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in terms of performance metrics (e.g., sensitivity, specificity thresholds) for the currently reviewed device (K233688). This submission (K233688) is for a modification to the labeling of an already cleared device (DEN220039). The core performance characteristics were established during the clearance of the predicate device (DEN220039).

The "510(k) Summary" section explicitly states under "Non-Clinical and/or Clinical Tests Summary & Conclusions": "Not applicable." This indicates that no new performance studies were conducted or provided with this specific submission because the design, material, chemical composition, and principle of operation are unchanged from the predicate device. The changes are limited to a minor revision of the intended use statement on labeling.

Therefore, performance data to directly prove acceptance criteria for this specific submission is not provided in this document. The document refers to the established performance characteristics from the predicate device, stating: "Performanc characteristics for SARS-CoV-2 were established during the 2021-2022 SARS-CoV-2 pandemic when SARS CoV 2 Omicron was the predominant SARS-CoV-2 variant in circulation."

If we were to infer the implied acceptance criteria from the predicate device's clearance, it would be that the device performs "as safe, as effective, and performs as well as the predicate device." However, no specific numerical performance metrics are listed in this document.

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

As stated above, no new performance studies were conducted for this specific submission (K233688). The document explicitly states "Not applicable" for clinical tests. Therefore, there is no sample size for an additional test set, nor new data provenance provided here. Performance characteristics were established during the 2021-2022 SARS-CoV-2 pandemic for the predicate device.

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

Since no new studies were conducted, this information is not provided in the document.

4. Adjudication Method for the Test Set

Since no new studies were conducted, this information is not provided in the document.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

No MRMC study is mentioned or implied for this submission. The device is an in vitro diagnostic (IVD) rapid antigen test read by an instrument (Sofia 2 analyzer), not typically involving multiple human readers for interpretation in the same way an imaging AI would. The Sofia 2 analyzer automatically scans, collects, analyzes fluorescence data, and reports results as positive, negative, or invalid, preventing visual interpretation.

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

Yes, this device inherently operates in a "standalone" fashion as an algorithm-only device in terms of result interpretation. The Sofia 2 analyzer processes the test strip by detecting and reading fluorescent microparticles, analyzing the fluorescence data, and automatically reporting the result without human interpretation of the signal on the test strip. The human interaction is limited to collecting the sample, performing the assay steps, and reading the final result from the instrument.

7. The Type of Ground Truth Used

The document indicates the test is intended as an aid in diagnosis, and negative test results are presumptive and "recommended these results be confirmed by a molecular SARS-CoV-2 assay." This strongly implies that the ground truth for establishing the device's performance characteristics (for the predicate device) would have been molecular SARS-CoV-2 assays (e.g., RT-PCR), which are considered the gold standard for SARS-CoV-2 detection.

8. The Sample Size for the Training Set

No information about a training set or its sample size is provided in this document, as no new performance studies were conducted for this submission. The initial development and training (if applicable, for the Sofia 2 analyzer's signal processing algorithm) would have occurred prior to the predicate device's clearance.

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 mentioned. It is likely that for the predicate device, if machine learning was involved in interpreting the fluorescent signal, the training data's ground truth would have been established against molecular SARS-CoV-2 assays, similar to the test set ground truth.

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The Sofia 2 SARS Antigen+ FIA is a lateral flow immunofluorescent sandwich assay that is used with the Sofia 2 instrument for the rapid, qualitative detection of SARS-CoV-2 nucleocapsid protein antigens directly in anterior nasal swab specimens from individuals with signs and symptoms of upper respiratory infection (i.e., symptomatic) when testing is started within 6 days of symptom onset. The test is intended for use as an aid in the diagnosis of SARS-CoV-2 infections (COVID-19) in symptomatic individuals when tested at least twice over three days with at least 48 hours between tests.

The test does not differentiate between SARS-CoV and SARS-CoV-2.

A negative test result is presumptive, and it is recommended these results be confirmed by a molecular SARS-CoV-2 assay. Negative results do not preclude SARS-CoV-2 infections and should not be used as the sole basis for treatment or other patient management decisions.

Positive results do not rule out co-infection with other respiratory pathogens.

Performance characteristics for SARS-CoV-2 were established during the 2021-2022 SARS-CoV-2 pandemic when SARS-CoV-2 Omicron was the predominant SARS-CoV-2 variant in circulation. When other SARS-CoV-2 virus variant are emerging, performance characteristics mav vary.

This test is intended for prescription use only and can be used in Point-of-Care settings.

The Sofia 2 SARS Antigen+FIA is based upon a lateral flow technology that employs immunofluorescence technology in a sandwich design that is used with Sofia 2 to detect nucleocapsid protein from the SARS-CoV-2 virus in human anterior nasal swab specimens.

The patient sample is placed in the Reagent Tube, during which time the virus particles in the sample are disrupted, exposing internal viral nucleoproteins. After disruption, the sample is dispensed into the Test Cassette sample well. The Test strip is composed of the following biochemical components dried and immobilized onto the nitrocellulose membrane: 1) sample pad that receives the specimen; 2) a label pad that contains detection fluorescent micro-particles, coated with monoclonal antibodies that are specific for SARS-CoV-2 nucleocapsid antigen: 3) embedded monoclonal antibodies specific for SARS-CoV-2 nucleocapsid antigen to capture the antigen-microparticle complex at the test line location. The sample pad facilitates migration of the sample fluid across the nitrocellulose strip into the absorbent pad. The test strip also contains a desiccant that does not participate in the assay but serves as a stabilizing agent during storage.

Sample is applied to in the sample well and migrates through a test strip, then passes through the test and control lines. If SARS-CoV-2 viral antigen is present, they will be bound by the fluorescent microparticles in the label pad region, forming an antigen-microparticle complex. The test line is coated with monoclonal antibodies that are specific to SARS-CoV-2 nucleocapsid antigen and is intended to capture the antigen-microparticle complex. If SARS-CoV-2 viral antigen is not present, the fluorescent microparticles will not be trapped by the capture antibodies nor detected by Sofia 2.

The Sofia 2 SARS Antigen+FIA employs antibody-tagged microparticles dyed with a fluorescent compound, to be detected and read by the Sofia 2 reader instrument. The Sofia 2 analyzers automatically scan/image the test strip, collect and analyze the fluorescence data, and then calculate and report the result as either positive, negative, or invalid.

Additionally, the Sofia 2 Antigen+ FIA utilizes a reference line for the Sofia 2 reader (to locate the test line and negative control line) and a procedural control (to assess for sample presence and adequate sample flow). No colored lines will be visible in the test window of the fluorescent assay cassette, thereby preventing visual interpretation of the test results. The operator must use the Sofia 2 analyzer to obtain a test result.

The Sofia SARS Antigen FIA Control Swabs are intended to be used as quality control samples representative of positive and negative test samples, to demonstrate that the reagents are functional and that the assay procedure is correctly perform.

Acceptance Criteria and Device Performance for Sofia 2 SARS Antigen+ FIA

The Sofia 2 SARS Antigen+ FIA is a qualitative lateral flow immunoassay designed for rapid detection of SARS-CoV-2 nucleocapsid protein antigens in anterior nasal swab specimens. The following details outline the acceptance criteria and the studies conducted to prove the device meets these criteria.

1. Acceptance Criteria and Reported Device Performance

• Low Positive samples (1 x LoD) should demonstrate an expected positive agreement (e.g., >95%).
• Moderate Positive samples (3 x LoD) should demonstrate high expected positive agreement (e.g., >95%).
• Zero invalid test results throughout the study (or very low %). | - Negative samples: 99.4% expected negative agreement (159/160)
• High Negative samples (0.04 x LoD): 95.0% expected negative agreement (152/160)
• Low Positive samples (1 x LoD): 98.1% expected positive agreement (157/160)
• Moderate Positive samples (3 x LoD): 99.4% expected positive agreement (159/160)
• 0 invalid test results (out of 640 replicates) |
  | Reproducibility (Inter-site)| - High Negative samples (0.04 x LoD) should demonstrate reasonable negative agreement across sites and operators.
• Low Positive samples (1 x LoD) should demonstrate high positive agreement across sites and operators.
• Moderate Positive samples (3 x LoD) should demonstrate high positive agreement across sites and operators.
• Zero invalid test results throughout the study (or very low %). | - Negative samples: 100.0% expected negative agreement (120/120)
• High Negative samples (0.04 x LoD): 55.0% expected negative agreement (66/120) - Note: This is lower than typical ideal scenarios, but likely deemed acceptable given the nature of a "high negative" near the detection limit.
• Low Positive samples (1 x LoD): 99.2% expected positive agreement (119/120)
• Moderate Positive samples (3 x LoD): 99.2% expected positive agreement (119/120)
• 0 invalid test results (out of 480 samples) |
  | Analytical Specificity (Cross-reactivity & Interference) | - No cross-reactivity with a defined panel of common respiratory pathogens (bacteria, viruses, fungus) at specified concentrations.
• No interference from common endogenous and exogenous substances found in nasal specimens at specified concentrations.
• 100% negative agreement in the absence of SARS-CoV-2.
• 100% positive agreement in the presence of SARS-CoV-2. | - All 28 organisms/viruses tested showed 100.0% negative agreement (5/5 replicates) for cross-reactivity and 100.0% positive agreement (5/5 replicates) for interference.
• All 13 endogenous/exogenous substances tested showed 100.0% positive agreement (5/5 replicates) and 100.0% negative agreement (5/5 replicates). |
  | Limit of Detection (LoD) | - The device should consistently detect SARS-CoV-2 at a specific low concentration (LoD) with high positivity (e.g., 95% or 100%) in confirmatory studies.
• Negative clinical matrix should consistently result in negative readings. | - Confirmed LoD: 1.44 x 10^4 TCID50/mL.
• At confirmed LoD: 100% positivity (20/20 replicates) across both tested lots.
• NCM (Negative Clinical Matrix): 0% positivity (0/5 replicates). |
  | High-dose Hook Effect | - No false negative results should be observed at very high concentrations of SARS-CoV-2. | - All spiked samples from 10X LoD up to a maximum virus concentration (unspecified highest concentration) were 100% positive (5/5 replicates each). No hook effect observed. |
  | Inclusivity | - The device should detect various clinically relevant SARS-CoV-2 strains/variants (e.g., Delta, Omicron BA.1, BA.2) with high positivity. | - Heat-inactivated SARS-CoV-2 (isolate Italy-INMI1): 100.0% positivity (5/5 replicates) at 2.43E+05 TCID50/mL.
• Heat-inactivated SARS-CoV-2 (Delta B.1.617.2): 100.0% positivity (5/5 replicates) at 1.00E+04 TCID50/mL.
• Heat-inactivated SARS-CoV-2 (Omicron BA.1): 100.0% positivity (5/5 replicates) at 2.36E+04 TCID50/mL.
• Heat-inactivated SARS-CoV-2 (Omicron BA.2): 100.0% positivity (5/5 replicates) at 8.22E+03 TCID50/mL. |
  | Clinical Performance | - Demonstrate acceptable Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a highly sensitive RT-PCR comparator, within defined confidence intervals. The specific thresholds would be pre-defined by regulatory guidelines (e.g., FDA's EUA templates or De Novo requirements for diagnostics). While not explicitly stated as a numerical criterion, the presented results suggest approval, implying the performance met the agency's expectations for a Class II device. | - PPA (Clinical Sensitivity): 89.0% (97/109; 95% CI: 81.7% - 93.6%)
• NPA (Clinical Specificity): 99.6% (470/472; 95% CI: 98.5% - 99.9%) |

2. Sample Size and Data Provenance

Test Set Sample Sizes:

• Precision/Repeatability: 640 replicates (160 replicates per analyte level/kit lot for 4 levels x 2 lots).
• Reproducibility: 480 replicates (120 replicates per analyte level x 4 levels).
• Analytical Specificity (Cross-reactivity & Interference):
  • Cross-reactivity: 5 replicates per organism/virus (28 tested) = 140 replicates for negative agreement. 5 replicates per organism/virus + 2xLoD SARS-CoV-2 (25 tested, some "Not Tested" for interference) = 125 positive replicates for interference.
  • Interfering Substances: 5 replicates per substance (13 tested) for both positive and negative agreement = 130 replicates.
• Limit of Detection (LoD):
  • Preliminary LoD: 5 replicates per dilution (6 dilutions) x 2 lots = 60 replicates.
  • Confirmatory LoD: 20 replicates at preliminary LoD concentration for each of 2 lots = 40 replicates.
• High-dose Hook Effect: 5 replicates per concentration (4 concentrations) = 20 replicates.
• Inclusivity: 5 replicates per strain/variant (4 tested) = 20 replicates.
• Clinical Study (Accuracy): 581 evaluable subjects.

Data Provenance:

• Country of Origin: Not explicitly stated for analytical studies, but given the FDA review, it is implicitly expected to be a regulated environment. For the clinical study, it was a multi-center study in a "CLIA-waived" setting, which refers to US clinical laboratories.
• Retrospective or Prospective:
  • Analytical Performance Studies (Precision, Reproducibility, Analytical Specificity, LoD, Hook Effect, Inclusivity): These are typically prospective, lab-controlled experiments with contrived samples designed specifically for the study.
  • Clinical Studies: "multi-center, prospective study conducted from August 2021 to November 2022."

3. Number of Experts and Qualifications for Ground Truth

• Analytical Studies: For analytical studies (Precision, Reproducibility, LoD, Cross-reactivity, Interference, Hook Effect, Inclusivity), the ground truth is established by the known concentrations of spiked analytes (e.g., heat-inactivated SARS-CoV-2, other microbes, interfering substances). This does not involve human experts establishing ground truth beyond standard laboratory technician expertise in preparing and measuring these concentrations.
• Clinical Study: The ground truth for the clinical study was established by an "highly sensitive Emergency Use Authorization (EUA) authorized RT-PCR comparator assay." This is a laboratory-based molecular test, often considered the gold standard for SARS-CoV-2 detection, and does not involve human experts in the conventional sense of image adjudication or clinical consensus. The RT-PCR results themselves serve as the ground truth.

4. Adjudication Method for the Test Set

• Analytical Studies: Not applicable. Ground truth is determined by precise laboratory methods and known concentrations.
• Clinical Study: Not applicable. The comparator RT-PCR assay is a definitive laboratory test; there is no mention of a human-based adjudication process for the RT-PCR results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No, a MRMC comparative effectiveness study was not done.
• This device is an automated, instrument-read diagnostic assay (Sofia 2 SARS Antigen+ FIA). The results are generated by the instrument (Sofia 2 Analyzer) based on fluorescent signals and programmed algorithms, not by human interpretation of images or signals. Therefore, a human-in-the-loop study to assess how human readers improve with AI assistance is not relevant to this type of device. The study evaluates the standalone performance of the device compared to a reference method (RT-PCR).

6. Standalone Performance (Algorithm Only without Human-in-the-Loop)

• Yes, the performance data presented for the Sofia 2 SARS Antigen+ FIA are standalone performance, i.e., algorithm only without human-in-the-loop performance.
• The "Sofia 2 analyzers automatically scan/image the test strip, collect and analyze the fluorescence data, and then calculate and report the result as either positive, negative, or invalid." The operator only uses the analyzer to obtain the result; they do not visually interpret the test or make diagnostic decisions based on human observation of the test strip.

7. Type of Ground Truth Used

• Analytical Studies: The ground truth was based on known concentrations of heat-inactivated SARS-CoV-2 or other microorganisms/substances in controlled laboratory settings. This is a form of "spiked sample" ground truth.
• Clinical Study: The ground truth was established using an "highly sensitive Emergency Use Authorization (EUA) authorized RT-PCR comparator assay." This is a laboratory-based molecular diagnostic method, considered the gold standard for detecting SARS-CoV-2 RNA.

8. Sample Size for the Training Set

• No information is provided about a specific "training set" related to an AI/algorithm development in the context of machine learning. The algorithms referenced ("method-specific algorithms," "software specific cutoff," "specific algorithms") for the Sofia 2 analyzer relate to processing fluorescent signals and determining thresholds for positive/negative results, which are typically derived from extensive analytical characterization and optimization using laboratory-controlled samples, rather than a distinct "training set" in the machine learning sense often seen with image-based AI. The document implies these algorithms are developed and refined through the analytical performance studies (such as LoD, linearity, etc.) using various known concentrations.

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

• As mentioned above, a traditional "training set" as understood in a machine learning context is not explicitly described. The "ground truth" for establishing the device's operational algorithms and cut-offs would have been determined through laboratory experiments with precisely known concentrations of analytes. This process involves:
  • Identifying the Limit of Detection (LoD).
  • Evaluating signal response across a range of concentrations.
  • Using reference lots and known values during development to establish parameters for calculations and cut-offs.
  • "Final cut-off values were further validated as part of the analytical and clinical studies." This suggests an iterative process of development, testing, and validation against a known ground truth (spiked samples for analytical studies, RT-PCR for clinical).

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