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The Access anti-HAV assay is a paramagnetic particle, chemiluminescent immunoassay for the in vitro qualitative detection of total antibodies (anti-HAV IgG and IgM) to hepatitis A virus (HAV) in human pediatric (2 through 21 years) and adult serum and serum separator tubes or plasma [lithium heparin, lithium heparin separator tubes, sodium citrate, acid-citrate-dextrose (ACD), and citrate phosphate-dextrose (CPD)] using the Dxl 9000 Access Immunoassay Analyzer.

The Access anti-HAV assay is indicated as an aid in the diagnosis of current or past HAV infection in persons with risk factors and/or signs or symptoms of hepatitis A, when used in conjunction with other serological and clinical information. The assay may also be used in the identification of HAV susceptible individuals and to determine the presence of an antibody response to HAV in vaccine recipients.

This assay is not intended for use for screening donors of blood or blood products or human cells, tissues, or cellular or tissue-based products (HCT/Ps).

The Access anti-HAV assay requires Access anti-HAV (reagent packs), Access anti-HAV Calibrator (C1), and Access anti-HAV QC (QC1-QC2). The Access anti-HAV assay is a two-step competitive immunoassay. During incubation, the anti-HAV antibodies present in the patient sample bind to the coated antigen. After incubation in a reaction vessel, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. A monoclonal anti-HAV antibody alkaline phosphatase conjugate is added to the reaction vessel and the conjugate competes with the bound patient antibodies to affix the HAV antigen coated on the particles. After a second incubation and wash step, the chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is compared to the cutoff value defined during calibration. The Qualitative assessment is automatically determined from a stored calibration.

Quality control (QC) materials simulate the characteristics of patient samples and are essential for monitoring the system performance of the Access anti-HAV immunoassay. In addition, they are an integral part of good laboratory practices. When performing assays with Access reagents for anti-HAV, include quality control materials to validate the integrity of the assay. The assayed values should fall within the acceptable range if the test system is working properly.

The Access anti-HAV reagents are provided in liquid ready-to-use format designed for optimal performance on the Beckman Coulter DxI 9000 Access Immunoassay Analyzer only. Each reagent kit contains two reagent packs. The Access anti-HAV Calibrator kit contains one vial, and the Access anti-HAV QC kit contains three vials, each of anti-HAV positive control and anti-HAV negative control. Other items needed to run the assay include Lumi-Phos PRO (chemiluminescent substrate) and UniCel DxI Wash Buffer II.

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The HAVAb IgG II assay is a chemiluminescent microparticle immunoassay (CMA) used for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric (4 through 21 years) serum (collected in serum and serum separator tubes) and plasma (collected in sodium heparin, lithium heparin separator, dipotassium EDTA, and tripotassium EDTA tubes) from patients with signs and symptoms or at risk for hepatitis A on the Alinity i system.

The HAVAb IgG II assay is used to determine the immune status of individuals to hepatitis A virus (HAV) infection. Warning: This assay has not been cleared for use in screening blood, plasma, or tissue donors. This assay camot be used for the diagnosis of acute HAV infection.

Assay performance characteristics have not been established when the HAVAb IgG II assay is used in conjunction with other hepatitis assays.

The HAVAb IgG II assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric (4 through 21 years) serum (collected in serum and serum separator tubes) and plasma (collected in sodium heparin, lithium heparin separator, dipotassium EDTA, and tripotassium EDTA tubes) from patients with signs and symptoms or at risk for hepatitis A on the Alinity i system. The kit includes reagents (Microparticles, Conjugate, Assay Diluent), Calibrator, and Controls. The assay is an automated, two-step immunoassay.

Considering the provided document, the device described is an in vitro diagnostic (IVD) assay (HAVAb IgG II) for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV). The FDA 510(k) summary focuses on establishing substantial equivalence to a predicate device, not on meeting specific acceptance criteria in the context of an AI/ML medical device's performance evaluation against clinical ground truth.

Therefore, many of the requested criteria (like ground truth establishment by experts, adjudication methods, multi-reader multi-case studies, and separate training/test sets with their ground truth establishment) are generally not applicable to the performance claims made for this in vitro diagnostic device in this FDA submission. The document describes analytical and clinical performance studies typical for an IVD, focusing on agreement with a predicate device and reproducibility/precision, rather than predictive performance of an AI model against a complex clinical endpoint established by human experts.

Based on the provided text, here's a breakdown of the information that is applicable and a clear indication where the requested information is not present or relevant to this type of device submission:

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

The document doesn't explicitly state "acceptance criteria" in a table format that would typically be found for an AI/ML model for diagnostic imaging (e.g., target sensitivity/specificity values). Instead, it presents performance data for comparison to a predicate device and for reproducibility. The implicit "acceptance criterion" for a 510(k) is demonstrating "substantial equivalence" to a legally marketed predicate device.

However, we can infer some performance metrics presented as evidence of equivalence:

2. Sample sizes used for the test set and the data provenance

• Clinical Performance Test Set (Agreement with Predicate):

  • Individuals at Increased Risk of HAV Infection: n=250
  • Individuals with Signs and Symptoms of Hepatitis Infection: n=499
  • Pediatric Population: n=105
  • Total for Agreement Study: 250 + 499 + 105 = 854 specimens.
  • Data Provenance: Prospective multi-center study.
    • Increased Risk of HAV: collected in California, Colorado, Florida, Illinois, Massachusetts, North Carolina, and Texas.
    • Signs and Symptoms of Hepatitis: collected in California, Colorado, Florida, Illinois, Massachusetts, and Texas.
    • Pediatric Population: collected in the US (California and Massachusetts) and Belgium.

• Precision/Reproducibility Test Sets:

  • Within-Laboratory Precision: n=80 per sample/control for a representative combination (tested over 20 days, 2 replicates/day). Total tested for this study was 4 reagent/calibrator/instrument combinations.
  • System Reproducibility: n=360 per sample/control (tested at 3 sites, with 4 replicates/run, 2 runs/day, 5 days).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

• Not applicable / Not stated. For this IVD device, the "ground truth" for the clinical performance study was the result produced by the legally marketed predicate device (ARCHITECT HAVAB-G). This is a common practice for 510(k) submissions for IVDs. There were no human experts adjudicating results for the purpose of establishing a "ground truth" beyond what the predicate device determined.

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

• Not applicable. As the ground truth was the predicate device's result, no human adjudication method (like 2+1, 3+1) was used or described.

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

• Not applicable. This is an in vitro diagnostic assay, not an imaging AI device intended to assist human readers. Therefore, an MRMC study and evaluation of human reader improvement with AI assistance were not performed.

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

• Yes, in spirit. The device (HAVAb IgG II assay) functions as a standalone test; it's an automated immunoassay that generates a qualitative result (Reactive or Nonreactive) without human interpretation in the loop influencing the output beyond sample collection and instrument operation. Its performance was assessed directly against the predicate device's results.

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

• The "ground truth" for the clinical performance comparison was the results from a legally marketed predicate device (ARCHITECT HAVAB-G assay). In essence, the performance of the new device was compared to the established performance of the predicate. This is a common form of "truth" in demonstrating substantial equivalence for IVDs.

8. The sample size for the training set

• Not explicitly stated in terms of a "training set" for model development. This is an immunoassay, not an AI/ML model where a distinct training dataset size is typically reported. The document describes analytical verification and clinical performance studies, not model training.

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

• Not applicable. As this is not an AI/ML device in the sense of a machine learning model requiring a training set with a ground truth established by experts for supervised learning, this information is not provided. The development process for an immunoassay does not involve "training data" in the same way an AI/ML model does.

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The LIAISON® Anti-HAV assay is an in vitro chemiluminescent immunoassay intended for the qualitative detection of total antibodies to hepatitis A (anti-HAV) in human serum and sodium heparin plasma samples using the LIAISON® Analyzer family*. The assay is indicated as an aid in the laboratory diagnosis of current or previous HAV infections in conjunction with other serological and clinical information and to determine the presence of an antibody response to HAV in vaccine recipients.

This assay is not intended for screening blood or solid or soft tissue donors.

The DiaSorin LIAISON® XS Analyzer is a fully automated, closed, continuous loading of samples and reagents in vitro diagnostic immunoassay system utilizing chemiluminescent technology to provide rapid sample results. The analyzer uses DiaSorin proprietary reagents in which chemiluminescence of an analyte is measured in a sample by the reaction of a magnetic particle solid phase coated with antigen or antibody and a chemiluminescent tracer. The LIAISON® XS Analyzer is intended for use in professional clinical laboratories only.

The method for qualitative determination of anti-HAV is a competitive sandwich chemiluminescence immunoassay (CLIA) based on neutralization. The assay uses magnetic particles (solid phase) coated with IgG antibodies to HAV (mouse monoclonal), and a mouse monoclonal anti-HAV antibody conjugate linked to an isoluminol derivative (isoluminolantibody conjugate).

The provided text describes a 510(k) premarket notification for a modified medical device, the LIAISON® XS Analyzer, used with the LIAISON® Anti-HAV assay. However, the document does not contain specific details about acceptance criteria, reported device performance (in terms of sensitivity, specificity, etc.), sample sizes for test sets, data provenance, number of experts, adjudication methods, MRMC studies, standalone performance, or ground truth details for either test or training sets.

The submission is for a device modification (moving fluid canisters onboard) to an already cleared device (K210272). The focus of the provided text is on demonstrating that these modifications do not negatively impact the device's performance or safety/effectiveness, rather than a full de novo performance study of the Anti-HAV assay itself.

Therefore, most of the requested information cannot be extracted from this document. The "Summary of Performance Data" section states that "Non-clinical verification and validation activities conducted with the LIAISON® XS Analyzer demonstrate that the modified device met predetermined acceptance criteria," but it does not specify what those criteria were or quantitatively report the performance. It merely lists the types of studies conducted.

Here is what can be inferred or stated based on the provided text:

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

The document does not explicitly list the acceptance criteria or quantitative performance results (e.g., sensitivity, specificity, accuracy) for the LIAISON Anti-HAV assay after the modifications. It broadly states: "Non-clinical verification and validation activities conducted with the LIAISON® XS Analyzer demonstrate that the modified device met predetermined acceptance criteria, supporting equivalency of the modified device to the cleared device." And "Testing verified all acceptance criteria were met."

The primary goal of this 510(k) is to demonstrate that the modifications to the analyzer (moving fluid canisters onboard) do not alter the safety and effectiveness of the existing cleared device. The previous clearance (K210272) would have contained the detailed performance data for the LIAISON® Anti-HAV assay itself.

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

Not provided in this document. The document refers to "non-clinical verification and validation activities" which are typically internal testing, not necessarily clinical studies with patient test sets.

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)

Not applicable and not provided. This information would be relevant for a de novo clinical study with expert ground truth, which is not the focus of this modification submission.

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

Not applicable and not provided.

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

Not applicable. The LIAISON® XS Analyzer is an in vitro diagnostic immunoassay system, not an AI-assisted diagnostic tool that requires human reader interpretation.

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

The LIAISON® Anti-HAV assay on the LIAISON® XS Analyzer is a standalone diagnostic test. Its performance is evaluated based on its accuracy in detecting antibodies, as indicated by the chemiluminescence signal, and does not involve human interpretation of complex images or signals in the same way an AI algorithm might. The document does not provide the specific performance metrics (e.g., sensitivity, specificity, NPV, PPV) for this standalone device in the context of this specific 510(k) submission, as it refers to these having been established in the previous clearance (K210272).

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

Not explicitly stated in this specific document. For an immunoassay like this, the ground truth for clinical studies would typically be established through a combination of:

• Established reference methods: Usually another FDA-cleared or gold standard HAV antibody test.
• Clinical diagnosis: Based on patient symptoms, epidemiological information, and other laboratory markers.
• Seroconversion panels: Well-characterized samples from individuals demonstrating progression of infection or immune response.

Since this 510(k) is for a modification to an existing device, it relies on the ground truth established during the original clearance of the LIAISON® Anti-HAV assay.

8. The sample size for the training set

Not applicable and not provided. Immunoassays are not "trained" in the same way machine learning models are. Performance characteristics are established through various analytical and clinical studies.

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

Not applicable and not provided (see point 8).

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The LIAISON® Anti-HAV assay is an in vitro chemiluminescent immunoassay intended for the qualitative detection of total antibodies to hepatitis A (anti-HAV) in human serum and sodium heparin plasma samples using the LIAISON® Analyzer family. The assay is indicated as an aid in the laboratory diagnosis of current or previous HAV infections in conjunction with other serological and clinical information and to determine the presence of an antibody response to HAV in vaccine recipients.

This assay is not intended for screening blood or solid or soft tissue donors.

The DiaSorin LIAISON® XS Analyzer is a fully automated, closed, continuous loading of samples and reagents in vitro diagnostic immunoassay system utilizing chemiluminescent technology to provide rapid sample results. The analyzer uses DiaSorin proprietary reagents in which chemiluminescence of an analyte is measured in a sample by the reaction of a magnetic particle solid phase coated with antigen or antibody and a chemiluminescent tracer. The LIAISON® XS Analyzer is intended for use in professional clinical laboratories only.

The method for qualitative determination of anti-HAV is a competitive sandwich chemiluminescence immunoassay (CLIA) based on neutralization. The assay uses magnetic particles (solid phase) coated with IgG antibodies to HAV (mouse monoclonal), and a mouse monoclonal anti-HAV antibody conjugate linked to an isoluminol derivative (isoluminol-antibody conjugate).

The information provided pertains to the DiaSorin LIAISON® Anti-HAV assay running on the LIAISON® XS Analyzer. This premarket notification is a "Special 510(k)" for device modifications to the existing LIAISON® XS analyzer (K193532), primarily addressing improvements in reliability related to the reagent pipettor. The LIAISON® Anti-HAV assay component and procedures themselves remain unchanged.

Here's an analysis of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample size used for the test set and the data provenance

The document does not explicitly state the sample size used for the test set for the immunometrical performance assessment.

• Data Provenance: Not specified. It's unclear if the data is retrospective or prospective, or the country of origin.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not applicable for this type of in vitro diagnostic device (immunoassay). Ground truth for these assays is typically established by reference methods or clinical diagnosis, not by experts reviewing images or other data.

4. Adjudication method for the test set

Not applicable for this type of in vitro diagnostic device. Result determination is quantitative or qualitative based on the assay's output measurements against a defined cutoff, not through expert adjudication of individual cases.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done

No, an MRMC comparative effectiveness study was not done. This type of study is typically associated with imaging devices or AI-assisted diagnostic tools where human readers interpret results. The LIAISON® Anti-HAV assay is an automated chemiluminescent immunoassay.

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

Yes, the performance presented in Table 6-3 represents the standalone performance of the LIAISON® Anti-HAV assay on the modified LIAISON® XS Analyzer. This device is an automated immunoassay system, and its output is directly interpreted as a qualitative detection of antibodies.

7. The type of ground truth used

The ground truth for the immunometrical performance assessment:

• Analytical Sensitivity: Established against a "WHO standard preparation."
• Positive/Negative Agreement: Implied to be established against a reference method or clinical diagnosis for Hepatitis A infection, as is standard for serological assays. The document does not explicitly name the specific reference method used for establishing positive and negative agreement.

8. The sample size for the training set

The document does not provide information regarding a separate "training set" or its sample size. For an immunoassay like this, the development likely involves optimization and validation steps, but not a distinct "training set" in the machine learning sense. The performance data presented is for the evaluation of the validated device.

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 machine learning, there is no information on how its ground truth was established. The development of such an assay involves careful analytical and clinical validation, ensuring its performance aligns with established diagnostic standards.

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The LIAISON® Anti-HAV assay is an in vitro chemiluminescent immunoassay intended for the qualitative detection of total antibodies to hepatitis A (anti-HAV) in human serum and sodium heparin plasma samples using the LIAISON® Analyzer family. The assay is indicated as an aid in the laboratory diagnosis of current or previous HAV infections in conjunction with other serological and clinical information and to determine the presponse to HAV in vaccine recipients.

The assay is not intended for screening blood or solid or soft tissue donors.

The method for qualitative determination of anti-HAV is a competitive sandwich chemiluminescence immunoassay (CLIA) based on neutralization. The assay uses magnetic particles (solid phase) coated with IqG antibodies to HAV (mouse monoclonal), and a mouse monoclonal anti-HAV antibody conjugate linked to an isoluminol derivative (isoluminol-antibody conjuqate). The first incubation step consists of adding the HAV antigen to calibrators, samples or controls, during which anti-HAV present in calibrators, samples or controls binds to a fixed and limited amount of HAV. thus forming an HAV-anti-HAV immune complex. After this step the second incubation follows and it involves addition of magnetic microparticles and conjugate into the cuvette, during which the antibody conjugate and the solid-phase antibody compete with anti-HAV present in the specimen for HAV. This allows the conjugate to bind to the solid phase and to form a sandwich. If all HAV added is sequestered in an HAV-anti-HAV immune complex during the first incubation, no sandwich is formed during the second incubation. After the second incubation, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and hence the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is inversely indicative of anti-HAV present in calibrators, samples or controls.

Here's an analysis of the provided text regarding the DiaSorin Inc. LIAISON® Anti-HAV device, outlining acceptance criteria and study details:

Acceptance Criteria and Device Performance

The provided document describes two main performance studies: a Method Comparison study and a Reproducibility study. The "acceptance criteria" are implied by the reported agreement percentages and coefficient of variation (%CV) values, which are generally expected to be high for agreement and low for variation in diagnostic assays.

Table of Acceptance Criteria and Reported Device Performance

Study Details for LIAISON® Anti-HAV

Here's a breakdown of the specific information requested, based on the provided text:

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

• Method Comparison Test Set: 100 frozen serum samples.

• Data Provenance: Samples were "either selected or prepared by DiaSorin Inc." The text does not explicitly state the country of origin or if the samples were retrospective or prospective, but the selection/preparation by the manufacturer suggests a controlled, potentially retrospective or spiked sample set rather than a purely prospective real-world patient cohort. The testing was performed at "2 external sites and at DiaSorin Inc."

• Reproducibility Study Test Set: A coded precision panel consisting of seven (7) serum specimens manufactured by DiaSorin S.p.A. and two (2) kit controls (a positive and negative from a single control lot). Each sample was run with 4 replicates per day for 12 days at each of the 3 sites, totaling 144 replicates per sample (4 replicates/day * 12 days * 3 sites) for both samples and controls.

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

The studies described are for an in vitro diagnostic (IVD) immunoassay, not an imaging device or AI-driven diagnostic that typically involves human expert interpretation for ground truth. Therefore, no human experts were used to establish ground truth in the traditional sense for these performance studies.

• In the method comparison study, the ground truth for samples was based on the results from a predicate device (LIAISON® Anti-HAV, Reference K082049).
• In the reproducibility study, the "ground truth" for the precision panel samples would be their known or assigned concentration/status based on their manufacturing and characterization, against which the assay's consistency is measured. The text doesn't specify how these concentrations were established, but it would typically be through reference methods or rigorous characterization during manufacturing.

4. Adjudication Method for the Test Set

Given that these are performance studies for an in vitro diagnostic where comparison is primarily against a predicate device or known sample characteristics, no human adjudication method (e.g., 2+1, 3+1) was mentioned or would typically be applicable. The "adjudication" is effectively the direct comparison of results between the new device and the predicate device or the statistical analysis of quantitative measurements against expected values (for reproducibility).

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are typically performed for medical imaging or AI diagnostics where multiple human readers interpret cases and their performance is compared with and without AI assistance. This document describes an in vitro diagnostic assay that determines the presence of antibodies in serum/plasma, not a technology that human readers interpret.

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

The LIAISON® Anti-HAV assay itself is a standalone in vitro diagnostic device, meaning its performance is evaluated based on its own output (chemiluminescence signal leading to qualitative detection of antibodies) without direct human interpretation of complex patterns or images. The "algorithm" in this context refers to the assay's chemical and instrumental process, which produces results independently. The provided studies directly assess this standalone performance (e.g., agreement with a predicate, and reproducibility).

7. The Type of Ground Truth Used

• Method Comparison Study: The ground truth for the test set was established by the predicate device (LIAISON® Anti-HAV, Reference K082049) results. This is a common practice for demonstrating substantial equivalence for IVDs.
• Reproducibility Study: The ground truth, in terms of expected values for precision, was based on the known characteristics of the manufactured serum specimens and kit controls. This is not "expert consensus" or "pathology" but rather scientifically characterized samples.

8. The Sample Size for the Training Set

The document does not specify a training set sample size. This is expected because the LIAISON® Anti-HAV assay is a chemiluminescent immunoassay, which is a traditional laboratory diagnostic method based on biochemical reactions, not a machine learning or AI algorithm that requires a "training set" in the context of model development. The development of such an assay involves extensive R&D, reagent optimization, and analytical validation but not a "training set" in the computational sense.

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

Since there is no "training set" in the AI/ML sense, this question is not applicable based on the provided information. The development of the assay would have relied on established scientific principles, method validation, and characterization of reagents and controls.

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Immunoassay for the in vitro qualitative detection of total antibodies (IgG and IgM) to hepatitis A virus (HAV) in human pediatric (ages 2 through 21 years) and adult serum and plasma (Li-heparin, potassium EDTA, Na-hebarin). The assay, in conjunction with other serological and clinical information, is indicated as an aid in the clinical laboratory diagnosis of acute or past hepatitis A virus infection in persons with signs or symptoms of hepatitis and in persons at increased risk for hepatitis A infection, or as an aid to identify HAV susceptible individuals and to determine the presence of an antibody response to HAV in vaccine recipients.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the cobas e immunoassay analyzers.

Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients. This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

Elecsys Anti-HAV II is a second generation assay by Roche Diagnostics for the in vitro qualitative detection of total antibodies (IgG and IgM) to the hepatitis A virus (HAV) in human pediatric (ages 2 through 21 years) and adult serum and plasma. It is intended for use on the cobas e 601 immunoassay analyzer. The cobas e family of analyzers employs the electrochemiluminescence "ECLIA" technology. The assay is an 18-minute assay utilizing a competition principle.

Results are determined automatically by the software by comparing the electrochemiluminescence signal obtained from the reaction product of the sample with the signal of the cutoff value previously obtained by calibration.

The reagent rackpack working solutions include:

• M: Streptavidin-coated microparticles .
• R1: HAV Ag (cell culture) .
• R2: Biotinylated monoclonal anti-HAV antibody, monoclonal Anti-HAV antibody . labeled with ruthenium complex
• AHAV 2 Cal1: Negative Calibrator 1 (human serum) .
• AHAV 2 Cal2: Positive Calibrator 2 (anti-HAV (human), approximately 60 IU/L in . human serum)

PreciControl Anti-HAV II is a ready-for-use control serum based on human serum both in the negative and positive concentration range. The controls are used for monitoring the performance of the Elecsys Anti-HAV II immunoassay. PreciControl Anti-HAV II is sold separately from the Elecsys Anti-HAV II immunoassay reagent.

The Elecsys Anti-HAV II is an immunoassay for the in vitro qualitative detection of total antibodies (IgG and IgM) to hepatitis A virus (HAV) in human pediatric (ages 2 through 21 years) and adult serum and plasma. Its purpose is to aid in the clinical laboratory diagnosis of acute or past hepatitis A virus infection in persons with signs or symptoms of hepatitis and in persons at increased risk for hepatitis A infection, or as an aid to identify HAV susceptible individuals and to determine the presence of an antibody response to HAV in vaccine recipients.

Here's an analysis of the acceptance criteria and the studies performed:

1. Table of Acceptance Criteria and Reported Device Performance:

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

• Precision (Repeatability and Within-Laboratory Precision): 5 human serum sample pools and 2 PreciControl materials, tested in 2 aliquots per run, 2 runs per day for 21 days (total 84 measurements per sample/control).
• Analytical Sensitivity (Cut-off): 10 serially diluted samples of the 2nd International Standard for Anti-Hepatitis A, Immunoglobulin, Human, NIBSC code: 97/646. Tested fourfold with three different reagent and calibrator lots.
• HAMA Interference: 11 human serum samples, double positive for HAMA and anti-HAV antibodies.
• Endogenous Interferences (Hemoglobin/Bilirubin/Lipemia, Rheumatoid Factor, Serum Albumin/IgG/IgA/IgM): Four human serum samples for each interfering substance, tested in accordance with CLSI EP07-A2.
• Biotin Interference: Five human serum samples.
• Analytical Specificity/Cross-Reactivity: 12 sample pools, each containing 10 samples (total 120 samples) with antibodies to various infectious agents.
• Exogenous Interferences (Drugs): Four human serum samples (native human serum pools) for each of 18 pharmaceutical compounds.
• Sample Matrix Comparison: At least 60 serum/plasma pairs for each anticoagulant type (K2-EDTA, K3-EDTA, Na-Heparin, Li-Heparin, Na-Citrate).
• Analytical Method Comparison to Predicate: A total of 215 modified serum samples (≥100 negative and ≥100 positive samples).
• Reagent Stability:
  • After First Opening: 2 control samples and 7 samples, tested in duplicate.
  • On-Board Reagent Stability: 2 control samples (singleton) and 7 samples (duplicate).
• Calibration Stability:
  • Lot Calibration Stability: 2 control samples (singleton) and 7 human serum samples (duplicate).
  • On-Board Calibration Stability: 2 control samples (singleton) and 7 human serum samples (duplicate).
• Sample Stability:
  • 2-8°C, Room Temperature, -15 to -25°C, Freeze/Thaw Cycles: 6 human serum, K2-EDTA, Li-Heparin, and Na-Citrate plasma samples, and 7 K3-EDTA and Na-Heparin plasma samples.
• Reproducibility (External Testing): Four human serum pools and two PreciControl materials. Tested in 3 replicates per run, 2 runs per day for 5 days (total 90 measurements per sample/control per site).
• Method Comparison Versus Predicate (Clinical): 961 specimens from various cohorts.
  • Routine HAV testing: 91 PPA, 109 NPA
  • Hospitalized: 56 PPA, 144 NPA
  • Increased risk for hepatitis: 119 PPA, 87 NPA
  • Symptomatic: 129 PPA, 91 NPA
  • Characterized acute HAV: 65 PPA, 10 NPA
  • Pediatric: 42 PPA, 18 NPA
• Pre- and Post-HAV Vaccination: Specimens from 49 subjects.
• Prevalence Study: 400 evaluable subjects from a "high prevalence" region (Western US) and 400 evaluable subjects from a "low prevalence" region (Eastern US).

Data Provenance for Clinical Studies:
The method comparison and prevalence studies were conducted using specimens that are likely from the United States, as they reference "US- and non-US-obtained specimens" and "Western United States" and "Eastern United States" for the prevalence study. These studies appear to be prospective in nature, as they involve specimen collection for specific study purposes (e.g., cohorts for method comparison, pre- and post-vaccination, and prevalence studies with subjects recruited from specific regions).

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

The document does not explicitly state the number or qualifications of "experts" used to establish the ground truth in the traditional sense of consensus reading or clinical adjudication by medical specialists.

• For the method comparison study, the "ground truth" was established by the predicate device, Elecsys Anti-HAV assay (FDA-cleared). This means the predicate device's results were accepted as the reference against which the new device's performance was measured.
• For the Pre- and Post-HAV Vaccination study, the "ground truth" was established by the predicate assay (Elecsys Anti-HAV).
• For the Analytical Specificity/Cross-Reactivity study, samples were defined as "Anti-HAV negative samples containing potential cross-reacting antibodies to other infectious diseases," implying these diagnoses were previously established, likely through standard diagnostic tests.
• For the Prevalence study, the "ground truth" for HAV antibody status was determined by the Elecsys Anti-HAV II assay itself, as the study evaluated its performance in determining prevalence in different populations rather than comparing it to an external gold standard for individual cases.

4. Adjudication Method for the Test Set:

• None explicitly mentioned in the typical sense of expert review for ambiguous cases.
• For the Method Comparison study, discordant results were counted against the Elecsys Anti-HAV II when calculating agreement. Specifically, specimens with results in the borderline range of the predicate device (18.0 ≤ IU/L < 22.0) were counted as discordant with the Elecsys Anti-HAV II assay. This indicates a pre-defined rule for handling discrepancies relative to the predicate, rather than an expert adjudication process.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

• No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) immunoassay, not an imaging device that would typically involve multiple human readers interpreting images. The studies performed compare the new device's performance to a predicate device or pre-defined analytical acceptance limits, not to human reader performance with or without AI assistance.

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

• Yes, the studies are inherently standalone. The Elecsys Anti-HAV II is an automated immunoassay designed for use on cobas e immunoassay analyzers. All performance evaluations described (precision, sensitivity, specificity, interference, stability, and method comparison) are based solely on the algorithm and analytical performance of the device itself, with no human interpretation of individual assay results affecting the determination of the final qualitative output (Reactive/Non-Reactive). The human role is limited to performing the test and reviewing the results generated by the analyzer.

7. The Type of Ground Truth Used:

• The primary ground truth for the comparative studies was the predicate device (Elecsys Anti-HAV assay), which is an FDA-cleared immunoassay. This indicates that the predicate device's results were considered the reference standard for classification of samples as Reactive, Borderline, or Non-Reactive for HAV antibodies.
• For other studies (e.g., cross-reactivity), samples were selected based on established diagnoses of other infectious agents.
• For precision and stability studies, the results are evaluated against internal consistency or expected recovery values rather than an external ground truth for individual samples.
• For the analytical sensitivity, the ground truth was the 2nd International Standard for Anti-Hepatitis A, Immunoglobulin, Human (NIBSC code: 97/646).

8. The Sample Size for the Training Set:

• The document does not provide information on a specific "training set" in the context of machine learning or AI algorithm development. This is an immunoassay (IVD), not an AI/ML-based device in the typical sense. Data described are for analytical and clinical validation.

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

• As a "training set" is not described for this immunoassay, this question is not applicable. The device's cut-off and performance characteristics are established through internal studies (e.g., "internal studies" for cut-off determination) and validated through the non-clinical and clinical performance evaluations described.

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ADVIA Centaur, ADVIA Centaur XP, and ADVIA Centaur XPT systems:

The ADVIA Centaur® HAV (gM (aHAVM) assay is an in vitro diagnostic immunoassay for the qualitative determination of IgM response to the hepatitis A virus (HAV) in human pediatric (2 through 21 years) and adult serum or plasma (potassium EDTA, lithium or sodium heparinized) using the ADVIA Centaur XP, and ADVIA Centaur XPT systems. This assay is intended for use as an aid in the diagnosis of acute or recent infection (usually 6 months or less) with hepatitis A virus.

Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, or patients less than 2 years of age.

ADVIA Centaur CP system:

The ADVIA Centaur® HAV IgM (aHAVM) assay is an in vitro diagnostic immunoassay for the qualitative determination of IgM response to the hepatitis A virus (HAV) in human pediatric (2 through 21 years) and adult serum or plasma (potassium EDTA, lithium or sodium heparinized) using the ADVIA Centaur CP system. This assay is intended for use as an aid in the diagnosis of acute or recent infection (usually 6 months or less) with hepatitis A virus.

Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, or patients less than 2 years of age.

The ADVIA Centaur HAV IgM reagent kit contains the following:

• ReadyPack® primary reagent pack containing ADVIA Centaur HAV IgM Lite Reagent, Solid Phase Reagent, and Ancillary Well Reagent
• ReadyPack ancillary pack containing ADVIA Centaur HAV IgM Ancillary Reagent
• ADVIA Centaur HAV IgM Low Calibrator
• ADVIA Centaur HAV IgM High Calibrator
• ADVIA Centaur systems HAV IgM Master Curve cards
• ADVIA Centaur systems HAV IgM Calibrator Assigned Value Card

The HAV IgM ReadyPack consists of the following:

Primary reagent pack

• The Lite Reagent is an anti-HAV mouse monoclonal antibody (F(ab) ¿ fragment: ~0.3 µg/mL) labeled with acridinium ester in buffer with bovine serum albumin, surfactant, sodium azide (<0.1%), and preservatives
• . The Solid Phase is streptavidin coated paramagnetic microparticles in buffer with bovine serum albumin, surfactant, sodium azide (< 0.1%), and preservatives
• The Ancillary Well Reagent is inactivated purified hepatitis A virus (<0.1 uq/mL) in ● buffer with bovine serum albumin, surfactant, sodium azide (<0.1%), and preservatives

Ancillary pack

• The Ancillary Reagent is biotinylated monoclonal mouse anti-human IgM (~0.500 . uq/mL) in buffer with bovine serum albumin, mouse IgG, surfactant, sodium azide (< 0.1%), and preservatives
  HAV IgM Calibrators

• Processed human plasma negative and positive for anti-HAV IgM antibodies with sodium azide (< 0.1%) and preservatives

The provided text describes the acceptance criteria and a study demonstrating the performance of the ADVIA® Centaur HAV IgM (aHAVM) assay when including pediatric populations (2-21 years).

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria for the pediatric population study in a table format. However, it presents the results of a comparative study with a "Comparative anti-HAV IgM Assay" and calculates agreement percentages. We can infer that the implicit acceptance criteria would be for these agreement percentages to be acceptably high.

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

• Sample Size for Test Set: 132 pediatric serum samples.
• Data Provenance: The origin of the data (e.g., country) is not specified. It is a retrospective study ("One hundred and thirty-two (132) pediatric serum samples (male and female, age range from 2 to 21 years) from suspected positive or high risk population were evaluated...").

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

The document does not mention the use of experts to establish a "ground truth" for the test set. Instead, it uses a "commercially available assay" as a comparator to assess agreement. This suggests the "ground truth" for the comparison was established by the results of this comparator assay, rather than a panel of human experts.

4. Adjudication Method for the Test Set

Not applicable. There was no mention of expert adjudication for the test set, as the comparison was made against another commercial assay.

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

Not applicable. This is an in vitro diagnostic immunoassay, not an imaging device or AI-assisted diagnostic tool typically evaluated with MRMC studies involving human readers.

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

Yes, the study described is a standalone performance evaluation of the ADVIA Centaur HAV IgM assay. It compares the device's results directly against another commercial assay without human intervention in the interpretation or decision-making process for the device itself.

7. The Type of Ground Truth Used

The "ground truth" in this context is established by the results of a "commercially available assay" which served as the comparative method. The samples were collected from a "suspected positive or high-risk population," implying clinical presentation also factored into their selection, but the definitive comparison was against the other assay.

8. The Sample Size for the Training Set

The document does not mention a distinct "training set" as it refers to a comparative study for adding pediatric populations. The assay itself was previously cleared or approved (K081716, P040018), and this submission is for an expanded indication. It's likely that a training set would have been used for the initial development and validation of the original assay, but that information is not provided here. The focus of this submission's study is limited to the pediatric population expansion.

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

Not applicable, as no training set is explicitly discussed in this document for the purpose of the reported study. For the original assay development, the ground truth would have been established through clinical diagnosis, potentially using PCR, viral culture, or other definitive methods, but this is outside the scope of the provided text.

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The LIAISON® HAV IgM assay is an in vitro chemiluminescent immunoassay intended for the qualitative detection of IgM antibodies to hepatitis A virus (IgM anti-HAV) in human serum and plasma (sodium citrate, potassium EDTA, lithium and sodium heparin, and citrate dextrose (ACD)) using the LIAISON® Analyzer. Assay results, in conjunction with other serological and clinical information, may be used for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis as an aid in the laboratory diagnosis of acute or recent HAV infection. This assay is not intended for screening blood or soft tissue donors. Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients. The user is responsible for establishing their own assay performance characteristics in these populations.

The LIAISON® Control HAV IgM (negative and positive) are intended for use as assayed quality control samples to monitor the performance of the LIAISON® HAV IgM assay.

The method for qualitative determination of HAV IgM is an antibody capture chemiluminescence immunoassay (CLIA).

IgG to human IgM (mouse monoclonal) is used for coating magnetic particles (solid phase) and a mouse monoclonal antibody to HAV is linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, IgM antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with HAV antigen just added and the immune complex thus formed reacts with IgM already bound to the solid phase. After each incubation, the unbound material is removed with a wash cycle.

Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and hence the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of anti-HAV IgM present in calibrators, samples or controls.

The provided text describes the LIAISON® HAV IgM assay, an in vitro chemiluminescent immunoassay for the qualitative detection of IgM antibodies to hepatitis A virus (IgM anti-HAV). The submission is a 510(k) for proposed modifications to the original device (K082050), not for a new device requiring extensive de novo studies. Therefore, the information provided focuses on demonstrating that the modifications do not raise new questions of safety and effectiveness and maintain substantial equivalence to the predicate device.

Here's an analysis based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a quantitative table for accuracy or clinical performance metrics (like sensitivity and specificity) of the modified device. Instead, it demonstrates equivalence to a comparator assay for sensitivity and elaborates on reproducibility and stability. The primary "acceptance criteria" for the modifications appear to be about maintaining the performance established by the original device and ensuring that the changes do not negatively impact its intended use, which is demonstrated through comparative studies and reproducibility.

However, based on the comparative studies, the implicit acceptance criterion for sensitivity was equivalence to the comparator assay in seroconversion panels.

Note: For HAVM Negative and HAVM-P01, RLU (Relative Light Units) were used for calculations as they were below the detectable limit of the curve.

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

• Seroconversion Panels (Sensitivity): 5 commercially available HAV seroconversion panels. The provenance (country of origin, retrospective/prospective) is not specified for these panels, but they are commercial and commonly used for such evaluations.
• Reproducibility/Precision Study: A coded panel comprised of 6 frozen serum samples (negative, low positive, mid positive) and 2 controls (negative and positive). The provenance is not specified other than being prepared by DiaSorin S.p.A.
• Sample Equivalency and Stability Studies: 40 matched sets of samples (serum, serum in SST, and plasma in Sodium Citrate, Potassium EDTA, Lithium and Sodium heparin, and Citrate Dextrose (ACD)). The provenance is not specified.
• Overall: The studies appear to be retrospective as they use pre-existing seroconversion panels, frozen serum samples, and matched sample sets to evaluate the modifications.

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

The document does not mention the use of experts to establish ground truth for the test set beyond the inherent nature of the seroconversion panels and the classification of samples (negative, low positive, mid positive) in the reproducibility study.

• For the seroconversion panels, the "ground truth" for the timing of seroconversion is established by the commercial panel provider, typically based on comprehensive characterization.
• For other studies, the "ground truth" for the samples is based on their preparation (e.g., spiking or diluting) or their known status prior to testing.

4. Adjudication Method for the Test Set

No explicit adjudication method (e.g., 2+1, 3+1) is mentioned for establishing the ground truth or resolving discrepancies for the test set performance. Results are compared directly to the comparator assay or the expected values based on sample preparation.

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 device is an in vitro diagnostic (IVD) immunoassay, not an AI-powered imaging or interpretation device that would involve human "readers" in the sense of a MRMC study. Therefore, this section is not applicable. The device provides a quantitative result (RLU) that is converted into an Index value and then interpreted qualitatively (Negative, Equivocal, Reactive) by the healthcare professional using the provided cut-off values.

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

Yes, the studies presented evaluate the standalone performance of the LIAISON® HAV IgM assay. The assay itself provides a quantitative result and then an interpreted qualitative result based on predefined cut-off values. There is no "human-in-the-loop" interaction with the algorithm itself for interpretation; the human uses the algorithm's output (qualitative result) in conjunction with other clinical information.

7. The Type of Ground Truth Used

The ground truth used depends on the study:

• Seroconversion Panels: The ground truth for seroconversion timing is established by the commercial panel manufacturer, likely based on multiple reference assays and characterization of the samples.
• Reproducibility/Precision: The "expected" result for each sample (negative, low positive, mid positive) is based on how the panel was prepared (spiking or diluting) by DiaSorin S.p.A.
• Sample Equivalency and Stability: The ground truth for comparison is largely the serum specimen from the matched set, assumed as the reference for other matrix types. The stability ground truth is based on the initial characterization of the samples.
• Cut-off Verification: This implicitly relies on the original clinical validity studies for the un-modified device to ensure the continued appropriateness of the existing cut-offs.

8. The Sample Size for the Training Set

This document describes studies for modifications to an already approved device (K082050). IVD assays typically do not have "training sets" in the machine learning sense. The assay parameters (like detection antibodies, conjugate, and cut-offs) are established during the original device development. The studies here are for verification and validation of the modifications, not for training a new algorithm. Therefore, the concept of a "training set" as it applies to AI/ML is not applicable here. The original device development would have involved extensive sample testing to establish initial assay parameters and cut-offs.

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

As explained above, the concept of a "training set" in the AI/ML sense is not applicable for this IVD immunoassay. The ground truth for establishing the original assay's performance and cut-offs (which these modification studies confirm are still valid) would have been established through extensive testing of clinical samples with known HAV infection status (confirmed by reference methods, clinical diagnosis, and potentially follow-up outcomes).

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ADVIA Centaur and ADVIA Centaur XP systems:

The ADVIA Centaur HAV Total (HAVT) assay is an in vitro diagnostic immunoassay for the qualitative deternination of total antibodies to hepatitis A virus (anti-HAV) in human neonatal, pediatric, and adult serum or plasma (potassium EDTA, lithium or sodium heparinized) using the ADVIA Centaur XP systems. This anti-HAV assay is indicated as an aid in the diagnosis of previous or ongoing hepatitis A viral infection or HAVsusceptible individuals for vaccination.

Assay performance characteristics have not been established for immunosompromised or immunosuppressed patients.

WARNING: This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

United States federal law restricts this device to sale by or on the order of a physician.

ADVIA Centaur CP system:

The ADVIA Centaur HAV Total (HAVT) assay is an in vitro diagnostic immunoassay for the qualitative deternination of total antibodies to hepatitis A virus (anti-HAV) in human neonatal, pediatric, and adult serum or plasma (potassium EDTA, lithium or sodium heparinized) using the ADVIA Centaur CP system. This anti-HAV assay is indicated as an aid in the diagnosis of previous or ongoing hepatitis A viral infection of HAV-susceptible individuals for vaccination.

Assay performance characteristics have not been established for immunosuppressed patients.

WARNING: This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

United States federal law restricts this device to sale by or on the order of a physician.

The ADVIA Centaur HAVT reagent kit contains the following:

• ReadyPack primary reagent pack containing ADVIA Centaur HAVT Lite Reagent, Solid Phase Reagent, and Antigen Reagent
• ReadyPack ancillary pack containing ADVIA Centaur HAVT Ancillary Reagent
• ADVIA Centaur HAVT Low Calibrator
• ADVIA Centaur HAVT High Calibrator
• ADVIA Centaur systems HAVT Master Curve card
• ADVIA Centaur systems HAVT Calibrator Assigned Value Card

The HAVT ReadyPack consists of the following:

Primary reagent pack

• The Lite Reagent is an anti-human HAV monoclonal antibody (~1.0 ug/mL) labeled with acridinium ester and biotinylated monoclonal mouse anti-HAV Fab fragment (~0.08 µg/mL) in phosphate buffer with bovine serum albumin, sodium azide (< 0.1%) and preservatives
• The Solid Phase is a streptavidin coated paramagnetic microparticles in phosphate buffer with bovine serum albumin, sodium azide (< 0.1%) and preservatives
• The Antigen Reagent is HAV antigen (~0.06 µg/mL) in tricine buffer with bovine serum albumin, stabilizers, sodium azide (< 0.1%) and preservatives

Ancillary pack

• The Ancillary Reagent is cysteine in citrate buffer with EDTA and preservatives

HAVT Calibrators

• Processed human plasma positive for anti-HAV antibodies with sodium azide (< 0.1%)

This document describes the request to add neonate and pediatric populations to the intended use statement of the ADVIA® Centaur HAV Total Assay. The submission focuses on demonstrating that the assay's performance remains acceptable for these new populations without requiring a full re-evaluation of all analytical performance characteristics.

Here's the breakdown of the acceptance criteria and study information provided:

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

The document does not explicitly state formal acceptance criteria with numerical targets. Instead, it presents study results and implies that "substantially equivalent in principle and performance" to the predicate device (VITROS Immunodiagnostic Products Anti-HAV Total Reagent Pack) for these new populations is the underlying acceptance criterion. The performance data focuses on demonstrating comparable results between adult, neonate, and pediatric samples, and concordance with an existing cleared assay.

Here's a table summarizing the reported device performance for the introduced data:

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

• Spike/Recovery studies (Neonatal and Pediatric):
  • Test Set Sample Size: 30 neonatal cord blood samples and 30 pediatric serum samples. In both studies, these were compared against 30 adult serum samples.
  • Data Provenance: Not specified (e.g., country of origin). The data appears to be prospective in nature, as samples were "spiked with anti-HAV positive stock to yield samples at different analyte levels."
• Concordance Study (Pediatric):
  • Test Set Sample Size: 55 pediatric serum samples (male and female, age range from 2 to 21 years), including samples from a high-risk population.
  • Data Provenance: Not specified (e.g., country of origin). The study "evaluated...samples with the ADVIA Centaur HAVT assay and another commercially available assay," suggesting a retrospective evaluation of collected samples.

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 studies described in the document do not rely on expert-established ground truth in the traditional sense.

• For the spike/recovery studies, the "ground truth" is based on the known spiking concentrations of anti-HAV antibodies and comparison to adult serum samples.
• For the concordance study, the "ground truth" is established by a "commercially available assay" which serves as the comparator. No information is provided about experts involved in establishing the results of this comparative assay.

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

Not applicable. The studies are based on quantitative (spike/recovery) or comparative (concordance with another assay) measurements, rather than subjective expert interpretations requiring adjudication.

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

Not applicable. This is an in-vitro diagnostic (IVD) immunoassay, not an AI-assisted diagnostic device that involves human readers interpreting cases.

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

Yes, the studies presented represent the standalone performance of the ADVIA Centaur HAV Total Assay. It's an automated immunoassay, and its output is a direct measurement (index value) or a qualitative result (Reactive/Nonreactive). There is no human interpretation integrated into the assay's performance evaluation as described.

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

• Spike/Recovery studies: The ground truth is effectively the known concentration of spiked analyte and the comparison against a referencable population (adult serum).
• Concordance study: The ground truth is established by a comparative commercially available assay.

8. The sample size for the training set

The document does not detail specific "training set" information for the submitted studies. The original ADVIA Centaur HAVT assay was approved under PMA P040017, and the current submission is an amendment. The original PMA would have involved extensive studies using a large number of samples for assay development, optimization, and establishment of performance characteristics (which could be considered analogous to a training phase in machine learning, though it's not explicitly called that here). The current submission leverages that prior approval and focuses on bridging data for new populations.

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

As above, explicit "training set" and its ground truth establishment are not detailed in this specific document. For an IVD assay like this, the "ground truth" for the original PMA approval would typically involve:

• Reference materials: Use of well-characterized positive and negative samples, often with known HAV infection status confirmed by other methods (e.g., PCR for viral load, clinical diagnosis, seroconversion panels).
• Clinical correlation: Samples from patients with confirmed HAV infections (acute, past) and uninfected individuals.
• Comparison to established gold standards: Benchmarking against widely recognized and validated assays.

The goal is to ensure the assay accurately detects the presence or absence of anti-HAV antibodies.

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The LIAISON® Anti-HAV assay is an in vitro chemiluminescent immunoassay intended for the qualitative detection of total antibodies to hepatitis A (anti-HAV) in human serum and sodium heparin plasma samples using the LIAISON® Analyzer family. The assay is indicated as an aid in the laboratory diagnosis of current or previous HAV infections in conjunction with other serological and clinical information and to determine the presence of an antibody response to HAV in vaccine recipients.

This assay is not intended for screening blood or solid or soft tissue donors. Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients. The user is responsible for establishing assay performance characteristics in these populations. Caution: U.S. Federal Law restricts this device to sale by or on the order of a physician.

The LIAISON® XL Analyzer is an automated discrete continuous loading chemiluminescent immunoassay (CLIA) analyzer for in vitro diagnostic analysis of CLIAs on human specimens cleared for use on the analyzer. It is only to be used with FDA cleared chemiluminescent immunoassays that are marketed by DiaSorin for the LIAISON® XL Analyzer. The analyzer can be connected to a third party Laboratory Automation System (LAS) which has been previously cleared for use with FDA cleared assays.

The LIAISON® Control Anti-HAV (negative and positive) is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Anti-HAV assay.

The performance characteristics of LIAISON® controls have not been established for any other assays or instrument platforms different from LIAISON® XL and LIAISON® XL with LIAISON® XL Workcell Upgrade Kit.

The LIAISON® XL Analyzer is an in vitro diagnostic device consisting of loading areas (for samples, Reagent Integrals, ancillary reagents, Starter Reagents, Cuvettes, Disposable Tips, water, Wash Buffer, maintenance liquid); incubator, wash station, reader, and a barcode reader for reagents and samples. Installation of the LIAISON® XL Workcell Upgrade Kit allows the LIAISON® XL Analyzer to be used with a compatible LAS and extends the sample pipetting capabilities to a point-in-space located external to the analyzer.

This submission (K141116) describes the LIAISON® XL Workcell Upgrade Kit, which allows the LIAISON® XL Analyzer (predicate device K103529) to connect to a Laboratory Automation System (LAS) and extends its sample pipetting capabilities. The device itself (the Workcell Upgrade Kit) is essentially a modification to the LIAISON® XL Analyzer, enabling new functionality rather than being a diagnostic assay with specific performance metrics like sensitivity or specificity for a disease.

Therefore, the acceptance criteria and study proving its efficacy are focused on demonstrating that the modified LIAISON® XL Analyzer (with the Workcell Upgrade Kit) performs equivalently to the predicate LIAISON® XL Analyzer for its intended use (running the LIAISON® Anti-HAV assay).

Here's an analysis based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't provide a typical table of acceptance criteria and performance for a diagnostic assay (e.g., sensitivity, specificity, accuracy). Instead, the acceptance criteria for this device modification are implicitly about maintaining the performance and functional equivalence of the predicate device when the upgrade kit is installed and used, especially when connected to a Laboratory Automation System.

The "device performance" reported is that the new device (LIAISON® XL with Workcell Upgrade Kit) is "substantially equivalent" to the predicate device (LIAISON® XL Analyzer) for its existing intended use with the LIAISON® Anti-HAV assay.

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

The document does not specify a sample size for a "test set" in the traditional sense of a diagnostic assay evaluation (e.g., number of patient samples for sensitivity/specificity). This submission is for a device modification (an upgrade kit for an existing analyzer) rather than a novel diagnostic assay.

The evaluation would likely involve:

• Functional testing: Verifying that the Workcell Upgrade Kit integrates correctly with the LIAISON® XL Analyzer and a Laboratory Automation System.
• Performance verification: Ensuring that the LIAISON® Anti-HAV assay, when run on the LIAISON® XL Analyzer with the Workcell Upgrade Kit (especially through LAS integration), yields results consistent with those obtained on the predicate device without the upgrade. This would involve running a series of samples (controls, patient samples) to confirm precision, accuracy, and overall analytical performance are maintained.

Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the nature of a 510(k) submission for a device modification, the studies would typically be prospective functional and performance verification studies conducted in a controlled laboratory environment.

3. Number of Experts Used to Establish Ground Truth and Qualifications:

Not applicable. This is not a study assessing diagnostic accuracy against a clinical ground truth established by experts. It is a technical submission for a device modification.

4. Adjudication Method:

Not applicable for a device modification study focused on functional and performance equivalence.

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

Not applicable. This is not a study evaluating human reader performance, with or without AI assistance.

6. Standalone Performance:

Yes, a standalone performance was done in the sense that the studies demonstrated that the LIAISON® XL Analyzer with the Workcell Upgrade Kit still functions as a standalone analyzer (where samples are placed directly into the sample bay, as in the predicate device). The capabilities are maintained ("Same (in the stand alone mode)"). Additionally, the primary purpose of the upgrade is to enable the "LAS mode" functionality. The non-clinical studies would have verified the performance of the analyzer both in standalone mode and with the LAS integration.

7. Type of Ground Truth Used:

The "ground truth" for this type of submission would be the established and cleared performance characteristics (e.g., precision, linearity, analytical sensitivity, cut-off values) of the LIAISON® Anti-HAV assay when run on the predicate LIAISON® XL Analyzer. The studies would have demonstrated that the modified analyzer's performance for this assay does not deviate significantly from these established values.

8. Sample Size for the Training Set:

Not applicable. This is not a machine learning or AI device that requires a distinct training set for algorithm development. The "training" in this context would refer to the development and internal testing of the hardware and software modifications of the Workcell Upgrade Kit to ensure it performs as intended.

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

Not applicable, as there's no machine learning "training set" in the context of this device modification. The "ground truth" for verifying the functional and performance aspects of the Workcell Upgrade Kit would be derived from:

• Engineering specifications and design requirements for the Workcell itself and its integration with LAS.
• The established performance specifications of the LIAISON® Anti-HAV assay on the predicate LIAISON® XL Analyzer.
• Industry standards and regulatory guidelines for laboratory automation and immunoassay systems.

In summary, this 510(k) is about demonstrating substantial equivalence for a modification to an existing device rather than establishing novel diagnostic performance for an assay. The studies focus on ensuring that the new functionalities (LAS connectivity, extended pipetting) correctly integrate without negatively impacting the already cleared performance of the LIAISON® XL Analyzer when running the LIAISON® Anti-HAV assay.

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