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The Diagnostic Hybrids, Inc. D3 DFA Herpes Simplex Virus Identification and Typing Kit is intended for use in the qualitative detection and typing of human herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) in cell cultures by immunofluorescence using fluoresceinated monoclonal antibodies (MAbs). Negative results do not rule out an infection and should not be used as the sole basis for diagnosis, treatment or other management decisions. Performance using direct specimen testing has not been evaluated.

The Diagnostic Hybrids, Inc. D3 DFA Herpes Simplex Virus Identification and Typing Kit uses two separate blends of HSV Type-1 (HSV-1) and HSV Type-2 (HSV-2) antigen-specific murine MAbs that are directly labeled with fluorescein for the rapid detection and typing of HSV. The reagents can specifically detect and type either HSV-1 or HSV-2. The HSV-1 MAbs were developed using HSV-1(f) cell lysate as immunogen - one MAb has been determined to be directed against HSV-1 glycoprotein C1; the antigen to the other is undetermined. The HSV-2 MAbs were developed using a HSV-2 recombinant glycoprotein G as immunogen.
Kit Components:
• HSV-1 DFA Reagent - One dropper bottle containing a blend of two fluorescein labeled murine monoclonal antibodies directed against HSV-1 specific glycoproteins. The HSV-1 MAbs were developed using HSV-1(f) cell Ivsate as immunogen - one MAb has been determined to be directed against HSV-1 glycoprotein C1, the antigen to the other is undetermined. The buffered, stabilized, aqueous solution contains Evan's Blue as a counter-stain and 0.1% sodium azide as preservative.
• HSV-2 DFA Reagent - One dropper bottle containing a blend of two fluorescein labeled murine monoclonal antibodies directed against HSV-2 specific glycoproteins. The HSV-2 MAbs were developed using a HSV-2 recombinant glycoprotein G immunogen. The buffered, stabilized, aqueous solution contains Evan's Blue as a counter-stain and 0.1% sodium azide as preservative
• HSV-1/HSV-2 Antigen Control Slides - Individually packaged control slides containing wells with cell culture derived positive and negative control cells. Each slide consists of four wells containing acetone fixed cells; two wells of noninfected cells and one well each of HSV-1 infected cells and HSV-2 infected cells. Each slide is intended to be stained only one time.
• PBS Concentrate - A 40X concentrate consisting of 4% sodium azide in phosphate buffered saline (after dilution to 1X in water, the concentration of sodium azide in the solution is 0.1%).
• Mounting Fluid - an aqueous, buffered, stabilized solution of glycerol and 0.1% sodium azide.

The cells to be tested, on a slide prepared from a tube culture or on a monolayer of cells cultured in a multi-well plate or a coverslip in a shell vial, are fixed in acetone. The HSV-1 DFA Reagent or HSV-2 DFA Reagent is added to the cells to detect the presence of HSV specific viral antigens. After incubating for 15 to 30 minutes at 35° to 37°C, the stained cells are washed with the supplied Phosphate Buffered Saline (PBS). To prepare the slide for examination, a drop of the supplied Mounting Medium is added to the stained cells and a coverslip is placed on the slide. To prepare the centrifuge enhanced cell cultures for examination, a drop of Mounting Fluid is placed on a clean microscope slide. The coverslip is removed from the shell vial and placed on to the Mountina Fluid.

For multi-well plates, monolayers are fixed with an 80% aqueous acetone solution. The HSV DFA Reagent is added to the cells to detect the presence of any HSV specific viral antigens. After incubating for 15 to 30 minutes at 35° to 37°C, the stained cells are washed with the supplied Phosphate Buffered Saline (PBS). Mounting Fluid is added to each well to cover the monolayers.

The slides or wells are examined using a fluorescence microscope equipped with the correct filter combination for FITC at a magnification of 100-400X. Virus infected cells will be stained with bright apple-green fluorescence while uninfected cells will contain no apple-green fluorescence but will fluoresce red by the Evan's Blue counterstain which is included in the HSV DFA Reagent.

If no fluorescent cells are found, report result as, "No herpes simplex virus detected."

If fluorescent cells are found in the HSV-1 DFA Reagent stained monolayer, report result as "Herpes simplex virus type 1 isolated by cell culture". If fluorescent cells are found in the HSV-2 DFA Reagent stained monolaver, report result as "Herpes simplex virus type 2 isolated by cell culture." If fluorescent cells are found in both the HSV-1 and HSV-2 stained wells, the results should be reported as "Herpes simplex virus types 1 and 2 isolated by cell culture".

Included in the kit are HSV-1/HSV-2 Antigen Control Slides. A Control Slide is intended to function as an indicator that the kit reagents are working properly in the test. [The slides are prepared with wells of HSV-1 infected cells, HSV-2 infected cells, and uninfected cells.] Positive and negative controls must demonstrate appropriate staining characteristics for specimen results to be valid. Controls may also aid in the interpretation of test results.

It is recommended that cell culture positive (infected with known HSV isolate) and negative (uninfected cells) controls be run with each assay to provide a means to ensure adequate performance of the cell culture system used. If control cultures fail to perform correctly, results are considered invalid.

Here's a breakdown of the acceptance criteria and study details for the DIAGNOSTIC HYBRIDS, INC. D3 DFA HERPES SIMPLEX VIRUS IDENTIFICATION KIT, based on the provided 510(k) summary:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are implied by the reported performance metrics, specifically the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with comparison devices. While explicit thresholds for "acceptance" are not stated, the high agreement percentages achieved indicate sufficient performance for regulatory clearance.

Study Details

2. Sample Size and Data Provenance

• Test Set Sample Size: 398 specimens (out of 401 prospectively collected, 3 were excluded due to bacterial contamination).
• Data Provenance: Prospectively collected specimens at three different laboratories. The country of origin is not explicitly stated but implied to be the US given the submission to the FDA.

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number of experts used to establish the ground truth or their specific qualifications (e.g., radiologist with X years of experience). Instead, the "ground truth" for the clinical study was established by "currently marketed HSV identification kits ('Comparison Devices')". This implies that these comparison devices, which are already cleared and established in clinical practice, served as the reference standard.

4. Adjudication Method

The document does not describe an adjudication method for the test set. The comparison was directly between the D3 DFA HSV ID & Typing Kit and the "Comparison Devices." Discrepancies are simply reported as either the D3 DFA kit being positive and the comparison negative, or vice versa, contributing to the PPA and NPA calculations.

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

There is no mention of a Multi-Reader Multi-Case (MRMC) comparative effectiveness study being performed. The study focuses on comparing the new device's performance against existing, marketed identification kits, not on the improvement of human readers with AI assistance. The device is a diagnostic kit, not an AI-assisted interpretation tool for human readers.

6. Standalone Performance Study

Yes, a standalone performance study was done. The entire clinical performance section evaluates the algorithm (kit) only, without human-in-the-loop performance being a variable. The results are reported based on the kit's ability to detect and type HSV-1 and HSV-2 compared to predicate devices.

7. Type of Ground Truth Used

The ground truth used for the clinical performance study was based on diagnostic results from "currently marketed HSV identification kits ('Comparison Devices')". This can be considered a form of reference standard test result.

8. Sample Size for the Training Set

The document does not specify a separate training set or its sample size. The focus is on the performance evaluation of the final device against a clinical test set. The "development" of the monoclonal antibodies involved using HSV-1(f) cell lysate andHSV-2 recombinant glycoprotein G as immunogens, which would be part of the initial development and optimization phase, but not a distinct "training set" in the context of an AI/algorithm.

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

As no specific training set is mentioned in the context of machine learning, the concept of ground truth for a training set is not directly applicable here. The development of the reagents involved using specific antigens (HSV-1(f) cell lysate and HSV-2 recombinant glycoprotein G) to generate type-specific monoclonal antibodies. The analytical specificity (cross-reactivity) was evaluated using known ATCC reference strains, various other microorganisms, and cell types, which served to confirm the expected reactivity and non-reactivity of the reagents during development and validation.

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The Diagnostic Hybrids D3 DFA Herpes Simplex Virus Identification Kit is intended for use in the qualitative detection of human herpes simplex virus (HSV) in cell cultures by immunofluorescence using fluoresceinated monoclonal antibodies (MAbs). Negative results do not preclude an infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.

Performance using direct specimen testing has not been evaluated.

The Diagnostic Hybrids D3 DFA Herpes Simplex Virus Identification Kit includes a DFA Reagent that contains a blend of four fluorescein-labeled murine monoclonal antibodies (MAbs), two directed against HSV type 1 (HSV-1) and two against HSV type 2 (HSV-2). The HSV-1 MAbs were developed using HSV-1(f) cell lysate as immunogen -- one has been determined to be directed against HSV-1 glycoprotein C1, the antigen to the other is undetermined. The HSV-2 MAbs were developed using a HSV-2 recombinant glycoprotein G immunogen.

The kit includes the following components:
• HSV DFA Reagent - A blend of fluorescein labeled murine monoclonal antibodies directed against antigens produced in HSV-infected cell culture. The buffered, stabilized, aqueous solution contains Evan's Blue as a counter-stain and 0.1% sodium azide as preservative.
• HSV Antigen Control Slides - Individually packaged control slides containing wells with cell culture derived positive and negative control cells. Each HSV positive well is identified. The negative wells contain uninfected cells. Each slide is intended to be stained only one time.
• PBS Concentrate - A 40X concentrate consisting of 4% sodium azide in phosphate buffered saline (after dilution to 1X in water, the concentration of sodium azide in the solution is 0.1%).
• Mounting Fluid - an aqueous, buffered, stabilized solution of glycerol and 0.1% sodium azide.

The cells to be tested, on a slide prepared from a tube culture or on a monolayer of cells cultured in a multi-well plate or a coverslip in a shell vial, are fixed in acetone. The HSV DFA Reagent is added to the cells to detect the presence of HSV specific viral antigens. After incubating for 15 to 30 minutes at 35° to 37°C, the stained cells are washed with the supplied Phosphate Buffered Saline (PBS). To prepare the slide for examination, a drop of the supplied Mounting Medium is added to the stained cells and a coverslip is placed on the slide. To prepare the centrifuge enhanced cell cultures for examination, a drop of Mounting Fluid is placed on a clean microscope slide. The coverslip is removed from the shell vial and placed on to the Mounting Fluid.

For multi-well plates, monolayers are fixed with an 80% aqueous acetone solution. The HSV DFA Reagent is added to the cells to detect the presence of any HSV specific viral antigens. After incubating for 15 to 30 minutes at 35° to 37°C, the stained cells are washed with the supplied Phosphate Buffered Saline (PBS). Mounting Fluid is added to each well to cover the monolayers.

The slides or wells are examined using a fluorescence microscope equipped with the correct filter combination for FITC at a magnification of 100-400X. Virus infected cells will be stained with bright apple-green fluorescence while uninfected cells will contain no apple-green fluorescence but will fluoresce red by the Evan's Blue counterstain' which is included in the HSV DFA Reagent.

If no fluorescent cells are found, report result as, "No herpes simplex virus detected". If fluorescent cells are found, report result as, "Herpes simplex virus isolated by cell culture."

Included in the kit are HSV Antigen Control Slides. A Control Slide is intended to function as an indicator that the kit reagents are working properly in the test. [The slides are prepared with wells of HSV infected cells and uninfected cells.] Positive and negative controls must demonstrate appropriate staining characteristics for specimen results to be valid. Controls may also aid in the interpretation of test results.

It is recommended that cell culture positive (infected with known HSV isolate) and negative (uninfected cells) controls be run with each assay to provide a means to ensure adequate performance of the cell culture system used. If control cultures fail to perform correctly, results are considered invalid.

Here's a breakdown of the acceptance criteria and the study details for the D3 HERPES SIMPLEX VIRUS IDENTIFICATION KIT, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance:

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

• Sample Size: 530 specimens were initially collected. After excluding 3 specimens due to bacterial contamination, 527 specimens were used for analysis.
• Data Provenance: The data was collected from four different laboratories as part of a clinical study. The information does not specify the country of origin, but the company address is in Athens, Ohio, USA, suggesting the study likely took place in the US. The study appears to be prospective as it involved comparing the D3 DFA HSV Kit performance to comparison tests using these specimens. The specimens were a combination of fresh (250) and frozen (280).

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

The document does not explicitly state the number of experts used to establish the ground truth or their specific qualifications. However, it indicates that the comparison was made against "comparison tests" which are legally marketed devices (predicates: Bartels® Herpes Simplex Virus Fluorescent Monoclonal Antibody Test, Pathodx® Herpes Typing Kit, MicroTrak® HSV 1/HSV 2 Culture Identification and Typing Test). The "comparison device" results were used as the reference against which the subject device was evaluated. It is implied that these comparison tests' results, and their interpretation, constitute the ground truth.

4. Adjudication Method for the Test Set:

The document does not explicitly describe an adjudication method for discrepancies between the subject device and the comparison device. The agreement percentages are calculated directly based on the reported positive and negative results from both the subject and comparison devices.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was NOT done in the context of human readers improving with AI vs. without AI assistance. This device is a diagnostic kit (reagent and controls) for laboratory use, specifically for immunofluorescence detection of HSV in cell cultures, not an AI-powered diagnostic tool for human interpretation.

6. Standalone (Algorithm Only) Performance:

Not applicable as this is a laboratory diagnostic kit, not an algorithm. The kit relies on a trained laboratory professional to perform the staining and interpret the results under a fluorescence microscope.

7. Type of Ground Truth Used:

The ground truth was established by comparison to legally marketed predicate devices (comparison tests). The "comparison device" results from cell cultures are considered the reference standard for the clinical performance evaluation. The clinical performance section states, "Clinical studies have been conducted at four different laboratories where they compared the D3 DFA HSV Kit performance to that of comparison tests..."

8. Sample Size for the Training Set:

The document does not mention a training set in the context of machine learning or AI. This is a traditional laboratory diagnostic kit, not an AI-driven product. The "training" for such a kit would involve laboratory personnel learning to use the kit according to its instructions.

However, if we interpret "training set" as the data used for internal development and optimization of the reagent, the analytical specificity and reactivity tests provide some insight into the range of organisms and conditions tested during development. The cross-reactivity panel included 59 viral strains, 17 host cell types, 27 bacterial cultures, 1 yeast, and 1 protozoan culture. The analytical specificity included ATCC reference HSV-1 and HSV-2 strains.

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

As mentioned, there isn't a "training set" in the AI sense. For the analytical studies (specificity, cross-reactivity), the ground truth was established by:

• Known (ATCC reference) HSV-1 and HSV-2 strains: These were confirmed positive for HSV.
• Known uninfected cell cultures: Used as negative controls and for testing specificity against various cell lines.
• Known cultures of other microorganisms (viruses, bacteria, yeast, protozoans): These were confirmed non-HSV organisms to test for cross-reactivity. The concentration of these organisms was also tested at high titers to challenge the specificity.
• Commercially available slides: Some cross-reactivity testing used commercially prepared slides for certain organisms, implying the manufacturer of those slides established their content.

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Light Diagnostics SimulFluor® HSV1/2 Immunofluorescence Assay is a direct immunofluorescence test intended for the detection and identification of herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2) following amplification in cell culture or by direct examination of clinical specimens prepared by cytocentrifugation. Specimens found to be negative on direct specimen examination should be tested by cell culture.

For in vitro diagnostic use.

Light Diagnostics SimulFluor® HSV 1/2 Immunofluorescence Assay utilizes a single reagent for the simultaneous detection and identification of HSV-1 and HSV-2. The SimulFluor® HSV 1/2 Reagent consists of two components; the primary component specific for HSV-1 will bind to the glycoprotein C and a capsid-associated protein in HSV-1 infected cells, while the secondary component, specific for HSV-2, will bind to the glycoprotein G in HSV-2 infected cells. Unbound reagent is removed by rinsing with phosphate-buffered saline (PBS). Illumination with ultraviolet light allows visualization of the antigenantibody complexes by fluorescence microscopy. When an FITC filter set is used, HSV-1- infected cells will exhibit apple-green fluorescence and HSV-2infected cells will exhibit yellow-gold fluorescence. The uninfected cells will stain a dull red due to the presence of Evans blue in the SimulFluor® HSV 1/2 reagent.

A blend of monoclonal antibodies directed against HSV-1 and HSV-2 is used in the Light Diagnostics SimulFluor® HSV 1/2 reagent. The use of monoclonal antibodies ensures increased specificity of reagent and reduces the risk of nonspecific background or interference.

This document describes the acceptance criteria and study details for the Light Diagnostics SimulFluor® HSV1/2 Immunofluorescence Assay.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the comparison to predicate devices and the confidence intervals reported for sensitivity, specificity, and percent agreement, indicating that the device's performance should be comparable to or ideally exceed these established methods. The "Clinical Study: Site 1" and "Clinical Study: Site 2" sections provide the reported device performance. Given the type of device (an immunofluorescence assay comparing to similar assays), the primary performance metrics are sensitivity, specificity, and percent agreement.

Note on Acceptance Criteria: The document does not explicitly state numerical acceptance criteria in a dedicated section. Instead, the "Conclusions drawn from evaluations" section states that the device's performance characteristics "were shown to be substantially equivalent to those of Bartels HSV Typing Test and the DPC PathoDx® Herpes Typing kit." Therefore, the reported performance metrics (sensitivity, specificity, and percent agreement with tight confidence intervals) meeting or exceeding those of the predicate devices are the implicit acceptance criteria.

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

• Clinical Study: Site 1

  • Test Set Sample Size: 191 specimens were submitted. After exclusions (40 insufficient cells, 1 contaminated culture, 3 VZV positive), the evaluable sample size for direct specimen testing was 147 (19+128 for HSV-1, 27+120 for HSV-2). For comparison against a comparative device, 33 HSV-1 and 29 HSV-2 isolates were identified by both reagents.
  • Data Provenance: North-central United States, retrospective (specimens "were submitted" indicating existing samples).

• Clinical Study: Site 2

  • Test Set Sample Size:
    • Shell vials: 214 specimens. 24 HSV-1 and 37 HSV-2 isolates were detected.
    • Culture plates: 227 specimens. 32 HSV-1 and 46 HSV-2 isolates were detected.
  • Data Provenance: Southwestern United States, retrospective (specimens "were submitted" indicating existing samples).

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. It refers to "clinical virology laboratory" and "reference laboratory" and implies standard laboratory procedures for culture confirmation.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for reconciling disagreements. For Site 1, the "culture confirmation" was used as the reference against which the direct specimen testing was compared. For the comparison against predicate devices, it appears a straightforward comparison of results was performed.

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

This section is not applicable as the described device is an immunofluorescence assay for detecting viruses, not an AI-assisted diagnostic tool interpreted by human readers. It's a laboratory test where a technician observes fluorescence, not a system that improves human diagnostic performance via AI.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This section is not applicable. The device is an immunofluorescence assay that requires manual preparation, staining, and microscopic observation by a trained laboratory technician. It is not an automated algorithm.

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

The ground truth used was cell culture (viral culture), which is a gold standard for detecting and identifying HSV-1 and HSV-2. In Site 1, "culture confirmation" was used. In Site 2, "standard cultures" and "spin-amplified shell vials" were used as reference methods.

8. The Sample Size for the Training Set

The document does not explicitly describe a separate "training set" for the clinical evaluation. The non-clinical evaluation section mentions that antibodies were "characterized for their ability to detect HSV types 1 and 2" using "reference viral strains and clinical isolates," but this is more akin to initial assay development and validation rather than a distinct training set for an algorithm.

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

Given the absence of an explicit "training set" as understood for machine learning algorithms, this question is not applicable in the context of this immunofluorescence assay submission. The "characterization" of the antibodies relied on testing with "reference viral strains and clinical isolates" whose identities would have been established through standard virological methods.

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The ELVIS® HSV ID/Typing Test System is a qualitative test indicated for use in the isolation and identification of HSV from lesions and body fluids suspected of containing viable HSV-1 and/or HSV-2. Both serotypes have been isolated from various parts of the body, particularly when HSV-associated disease is indicated. Performance of this assay has not been established for use with antiviral therapy or prenatal monitoring.

The subject device provides Cells, Replacement Medium and Test Reagents for the culture, identification and typing of HSV isolated from patient specimens. It consists of ELVIS™ HSV Cells in a tube configuration [ELVIS™ HSV Gold Test, 510(k) No. K960578] and in shell vial and multiwell plate configurations [ELVIS™ HSV Test, 510(k) No. K941924],and reagents to which have been added HSV-typing monoclonal antibodies to permit the user to directly type the HSV-positive specimens. ELVIS™ HSV Cells are genetically engineered Baby Hamster Kidney cells, which, when infected with either HSV-1 or HSV-2 are induced to generate and accumulate an endogenous, intracellular bacterial enzyme, β-galactosidase. Other related viruses are not capable of inducing this enzyme. In addition to the induction of this specific enzyme, HSV infection of cells results in the formation of HSV, type-specific proteins. The presence of these proteins can be detected microscopically by their fluorescence when HSV-type-specific, fluorescent labeled antibodies are used. Thus, when HSV-infected monolayers are fixed using Solution 1 and treated with Solution 2T, which contains the chromogenic substrate for the ß-galactosidase enzyme, those cells infected with HSV are stained an indigo blue while uninfected cells remain colorless. Both type-2-specific, fluorescein labeled monoclonal antibodies and type-1-specific, non-labeled monoclonal antibodies are also incorporated in Solution 2T. This allows for the monoclonal antibodies to react with their specific antigens in the HSV-infected ELVIS™ Cells at the same time as the enzyme is causing the deposition of blue stain. After a 1 hour incubation period, which allows for these reactions to proceed in monolayers whose specimens contained viable HSV, the monolayers are examined for blue cells using standard light microscopy: those which do not contain blue cells are negative for HSV; those which contain blue cells are positive for HSV and can now be examined with a fluorescence microscope to determine the HSV type. I E fluorescent cells are seen, the HSV in the specimen is type 2; if no fluorescent cells are seen, the HSV in the specimen is type 1. This can be confirmed by treating the monolayer with Solution 3 which contains fluorescein-labeled goat-antimouse antibodies which will react with the type 1-specific monoclonal antibodies in the HSV-1 infected cells. Thus, the major change in the composition of the above legally marketed devices is the incorporation of the monoclonal antibodies into the Solution 2 which contains the chromogenic substrate for the ß-galactosidase enzyme (which has been re-named Solution 2T. Additionally, two other reagents are included with the subject device, i.e., Solution 3, the fluorescein-labeled goat-antimouse antibody, and a Buffered Glycerol Mounting Medium used on the fixed and stained monolayers, to prevent them from drying before microscopic examination for fluorescence.

Here's an analysis of the acceptance criteria and study details for the ELVIS™ HSV ID/Typing Test System, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" through numerical thresholds or specific benchmarks that the new device needed to meet. Instead, the primary focus of the study was to demonstrate substantial equivalence to a predicate device (Syva's HSV1/HSV2 Culture Identification/Typing Test). The key performance metrics reported are clinical sensitivity and specificity for the ID portion of the test, and complete agreement in typing results.

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

• Test Set Sample Size: Over 650 different clinical specimens were used across 4 different laboratories. Specifically, 218 HSV-positive specimens were tested concurrently with the laboratory's standard test (the predicate device).
• Data Provenance: Clinical specimens obtained from typical laboratory submissions for HSV testing. The document does not explicitly state the country of origin, but given the context of a US regulatory submission, it is highly likely to be from the United States. The data is prospective in nature for the concurrent testing, as sufficient residual samples were used from specimens normally submitted to the laboratories for HSV testing. For the antibody specificity testing, frozen positive clinical specimens and clinical isolates were used, implying a retrospective component for that specific part of the study.

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

The document does not explicitly state the number of experts used to establish ground truth or their specific qualifications (e.g., number of years of experience).

• Implicit Ground Truth: The "ground truth" for the comparative study was primarily established by the results of the predicate device (Syva's HSV1/HSV2 Culture Identification/Typing Test), which was the "laboratory's standard test."

4. Adjudication Method for the Test Set:

The document does not describe a formal adjudication method (e.g., 2+1, 3+1). Instead, it states that for the 218 HSV-positive specimens, there was "complete agreement in the typing results between the two tests" (the subject device and the predicate device). This implies that a consensus or arbitration mechanism was not necessary for these specific cases within the typing comparison, as there was full concordance. For the overall clinical sensitivity and specificity, the predicate device served as the reference.

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

No, an MRMC comparative effectiveness study was not done. This study focused on the standalone performance of the device compared to a predicate device, not on how human readers' performance improved with AI assistance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:

Yes, a standalone study was done. The ELVIS™ HSV ID/Typing Test System is a diagnostic assay (a laboratory test kit) and its performance metrics (clinical sensitivity, clinical specificity, and typing agreement) are reported as the performance of the device itself, not in conjunction with human interpretation improvement. The examination of blue cells using standard light microscopy and fluorescent cells using a fluorescence microscope are part of the device's operational protocol, not a separate human interpretation task being augmented.

7. Type of Ground Truth Used:

The primary ground truth used for the clinical performance assessment was the predicate device's results (Syva's HSV1/HSV2 Culture Identification/Typing Test), which was considered the "laboratory's standard test." For defining analytical sensitivity and antibody specificity, the "specificity of the antibodies used in the subject device yield results identical to those results using the predicate device" was the benchmark. This points to a reference standard method (the predicate device) as the ground truth.

8. Sample Size for the Training Set:

The document does not report a specific sample size for a training set. This device is a diagnostic test kit based on genetically engineered cells and reagents, not a machine learning or AI algorithm that typically requires a distinct training set. The development efforts likely involved iterative testing and refinement of the reagents and protocols, but not in the sense of a machine learning "training set."

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

As there is no explicit mention of a "training set" in the context of an algorithm, the method for establishing ground truth for such a set is not described. The product development involved demonstrating that selected antibodies "yielded the same typing result as a predicate device," which would have guided the selection and formulation of reagents. This is more akin to traditional assay development and validation rather than ground truth establishment for a machine learning model.

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HSV-1 Antigen Control Slides are quality control materials used to confirm the accuracy of staining reagents used in cell culture confirmatory assays for the detection of HSV-1. Each individual slide contains two wells of fixed cells, one HSV-1 infected well and one uninfected well. The two wells of cells on the HSV-1 Antigen Control Slide are stained concomitantly with the cells inoculated with patient sample providing both a positive and negative control for the staining reagents and procedure. Lack of staining of the positive well indicates a failure of one or more components of the staining reagent.

Each individual slide contains two wells of fixed cells, one HSV-1 infected well and one uninfected well.

This document, a 510(k) Pre-Market Notification for the "HSV-1 Antigen Control Slides," primarily provides regulatory information and outlines the intended use and potential problems associated with the device. It does not contain information about a study proving the device meets acceptance criteria.

The document details:

• Device Name: HSV-1 Antigen Control Slides
• Regulatory Class: III
• Product Code: GQN
• Intended Use: To confirm the accuracy of staining reagents used in cell culture confirmatory assays for the detection of HSV-1. Each slide contains one HSV-1 infected well and one uninfected well to act as positive and negative controls for staining reagents and procedure.
• Potential Problems (Type of Problems):
  1. Loss of biological activity caused by antigenic deterioration.
  2. Loss (Removal) of the fixed cells in either the infected or uninfected slide wells.
• Impact of Problems: If these problems occur, the slides would indicate staining reagents are not working properly, leading to the test being discarded, but not a false positive or false negative clinical test result.

Therefore, I cannot provide the requested information about acceptance criteria or a study proving the device meets acceptance criteria based on the provided text. The document focuses on the regulatory approval and a certification regarding known safety/effectiveness problems, not on performance data from a specific study.

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HSV-2 Antigen Control Slides are quality control materials used to confirm the accuracy of staining reagents used in cell culture confirmatory assays for the detection of HSV-2. Each individual slide contains two wells of fixed cells, one HSV-2 infected well and one uninfected well. The two wells of cells on the HSV-2 Antigen Control Slide are stained concomitantly with the cells inoculated with patient sample providing both a positive and negative control for the staining reagents and procedure. Lack of staining of the positive well indicates a failure of one or more components of the staining reagent.

Each individual slide contains two wells of fixed cells, one HSV-2 infected well and one uninfected well.

This document is a 510(k) clearance letter from the FDA for HSV-2 Antigen Control Slides. It does not contain information about the acceptance criteria and study proving device performance in the way requested for an AI/ML device. The device described is a quality control material for laboratory use, not an AI/ML diagnostic tool.

Therefore, I cannot extract the requested information like sample sizes, expert qualifications, or MRMC studies, as these concepts do not apply to this type of device or the content of this specific document.

The document discusses:

• The device being cleared for marketing (HSV-2 Antigen Control Slides).
• Its intended use as quality control for staining reagents in cell culture confirmatory assays for HSV-2.
• The FDA's determination of substantial equivalence to a predicate device.

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The Test Kit provides the cells and reagents necessary for detection and identification of HSV in patient specimens.

The subject device consists of a mixed cell monolayer comprised of MRC-5 (Human Fetal Lung) and genetically modified Baby Hamster Kidney Cells (ELVIS™ HSV cells) which, when infected with HSV-1 or -2, are activated to produce and accumulate intracellularly the bacterial enzyme, beta-galactosidase. As in standard tube culture procedures, inoculated monolayers are examined daily for CPE. When CPE is observed, the monolayers are fixed and stained for the presence of beta-galactosidase. If blue cells are detected, indicating the presence of the enzyme which was induced by HSV, then the specimen is confirmed as being positive for HSV. If CPE is not detected by day 7 after inoculation, the monolayers are stained for the presence of pre-CPE, blue, HSV-infected cells. If none are found, the specimens are negative for HSV.

Acceptance Criteria and Study Details for ELVIS™ HSV GOLD

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the ELVIS™ HSV GOLD device were implicitly established through a non-inferiority comparison to existing "Gold Standard" tube culture methods. While explicit numerical thresholds for acceptance were not stated, the study aimed to demonstrate "substantial equivalence" in terms of clinical sensitivity and specificity.

2. Sample Size and Data Provenance

• Sample Size (Test Set): Over 670 specimens.
• Data Provenance: The specimens were "normally submitted to the respective institution for HSV testing," implying they were clinical samples from human patients. The study was conducted in 4 different laboratories, suggesting a multi-center study. The information does not explicitly state the country of origin but given the 510(k) submission to the FDA, it is highly likely the data originated from the United States. The statement "ELVIS™ HSV GOLD testing was performed on those specimens for which there was sufficient residual sample" suggests a prospective collection of data for the ELVIS™ HSV GOLD testing, using samples that were also tested with the predicate methods.

3. Number of Experts and Qualifications for Ground Truth

The provided text does not specify the number of experts used or their qualifications for establishing the ground truth for the test set.

4. Adjudication Method for the Test Set

The provided text does not specify an adjudication method. The ground truth was established by "predicate tests" which are "Classical 'Gold' standard tube culture methods... Confirmation, where used, is by fluorescent antibodies directed against HSV antigens." This implies the results of these predicate methods served as the ground truth.

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

A multi-reader multi-case (MRMC) comparative effectiveness study was not conducted as the device is a diagnostic test kit and not an AI-based system assisting human readers. Therefore, there is no effect size reported for human readers in conjunction with AI.

6. Standalone Performance

Yes, a standalone study was performed. The reported clinical sensitivity of 98.1% and clinical specificity of 98.7% for the ELVIS™ HSV GOLD test are measures of its performance as a standalone diagnostic device.

7. Type of Ground Truth Used

The ground truth used was expert consensus / predicate method. Specifically, the "Classical 'Gold' standard tube culture methods commonly used by many clinical laboratories for isolation and identification of HSV." This includes confirmation by fluorescent antibodies where necessary.

8. Sample Size for the Training Set

The provided text does not specify a training set size. This is a diagnostic test kit based on biological assays, not a machine learning algorithm, so a "training set" in the computational sense is not applicable. The development of the device likely involved internal optimization and validation, but this is distinct from a machine learning training set.

9. How Ground Truth for the Training Set was Established

As there is no "training set" in the context of a machine learning algorithm, the concept of establishing ground truth for a training set is not applicable here. The inherent biological mechanisms of the ELVIS™ HSV GOLD system (genetically modified cells, beta-galactosidase induction) were developed and optimized based on known characteristics of HSV infection and cellular responses, rather than being "trained" on a dataset in the AI sense.

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