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The LIAISON® VZV IgG HT assay uses chemiluminescent immunoassay (CLIA) technology for the in vitro qualitative detection of specific IgG antibodies to varicella-zoster virus (VZV) in human serum (with gel and without gel-SST), dipotassium EDTA (K2- EDTA), lithium heparin and sodium heparin plasma samples. This assay is intended as an aid in the determination of previous infection of varicella- zoster virus. The test must be performed on the LIAISON® XL Analyzer. The assay performance in detecting antibodies to VZV in individuals vaccinated with the FDA-licensed VZV vaccine is unknown. The user of this assay is responsible for establishing the performance characteristics with VZV vaccinated individuals.

The LIAISON® VZV IgG HT is an indirect chemiluminescence immunoassay (CLIA) for qualitative detection of specific IgG antibodies to varicella-zoster virus in human serum and plasma.

The LIAISON® Control VZV IgG HT are liquid ready-to-use controls based in human serum and plasma. The negative control is intended to provide an assay response characteristic of negative patient specimens and the positive control is intended to provide an assay response characteristic of positive patient specimens.

The assay and controls are designed for use with DiaSorin LIAISON® analyzer family

Here's an analysis of the provided text regarding the DiaSorin LIAISON® VZV IgG HT device, focusing on acceptance criteria and supporting study details:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are primarily expressed as Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a predicate device, as well as satisfactory performance in interference, cross-reactivity, precision, and high-dose saturation studies.

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

• Test Set Sample Size:
  • Total Clinical Agreement Study: 1544 clinical human serum samples (1543 used in analysis due to one sample with insufficient volume).
  • Breakdown: 125 known positive, 200 known negative, 135 pregnant women, and 1084 routine lab specimens.
  • Specific sub-studies:
    • Interfering Substances: Not specified, but involved VZV IgG antibody negative, around the cut-off, low positive, and high positive samples.
    • Cross-Reactivity: 226 samples from various conditions.
    • Precision (Within-Lab): 7 samples (panel of coded samples) tested 240 times each.
    • Reproducibility (Multi-site): 7 samples tested 90 times each across sites.
    • High-dose saturation: 3 high-titer samples.
    • Analytical sensitivity: Not a sample size of patient specimens, but derived from serial dilutions of WHO International Standard on 3 assay lots.
• Data Provenance: The general clinical samples were collected within the United States. The study was prospective in execution as it involved testing these samples with the new device and comparing them to a predicate, conducted at three independent external laboratories.

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 and their qualifications for establishing the ground truth of the test set.

4. Adjudication Method for the Test Set

The document does not explicitly state an adjudication method (like 2+1, 3+1). The "ground truth" for the clinical agreement study appears to be defined by the results of the FDA cleared predicate device (LIAISON® VZV IgG, K150375), which is referred to as the "comparator." It notes that "Specimens which were repeatedly equivocal by the predicate device were graded against the performance of the LIAISON® VZV IgG HT assay which does not have an equivocal zone." This implies a direct comparison to the predicate's results rather than an independent expert adjudication process for the clinical samples. For cross-reactivity, samples were "pre-screened with another commercially available VZV IgG assay" and then confirmed for the presence of potential cross-reactants using "US-marked assays."

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an automated in vitro diagnostic assay (CLIA technology) for qualitative detection of antibodies, not an imaging device requiring human reader interpretation or AI assistance in the human-in-the-loop context.

6. Standalone (Algorithm Only) Performance Study

Yes, the entire clinical performance evaluation described (Clinical Agreement, Interfering Substances, Cross-Reactivity, Precision, Reproducibility, High-dose saturation, Analytical Sensitivity) is essentially a standalone algorithm-only performance study. The LIAISON® VZV IgG HT assay is an automated system run on the LIAISON® XL Analyzer, meaning its performance is evaluated without human interpretation of results beyond reading the automated output.

7. Type of Ground Truth Used

The primary ground truth for the clinical agreement study was established by the FDA cleared predicate device (LIAISON® VZV IgG, K150375). For the "known positive" and "known negative" specimens, their status was pre-determined, likely by previous clinical diagnosis or established VZV serology results (though the exact method for this is not detailed beyond being "known"). For cross-reactivity studies, ground truth was based on positive results from "US-marked assays" for the specific cross-reacting agent.

8. Sample Size for the Training Set

The document does not specify a training set sample size. This is typical for in vitro diagnostic (IVD) assays like this one. While there is an "algorithm" (the CLIA technology and interpretation logic), it's not a machine learning model that undergoes a separate training phase with a distinct dataset in the way a medical imaging AI would. The "development" and "optimization" of such assays usually happen using internal samples and established chemical/biological principles, not a formalized, reported training set size like in AI/ML submissions.

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

Since a formalized "training set" for a machine learning algorithm isn't explicitly mentioned or directly applicable in the typical sense for this type of IVD, the concept of establishing ground truth for it is also not directly addressed. The assay's performance characteristics are developed and validated based on its underlying chemical and biological reactions and internal testing, which ensures it correctly identifies VZV IgG 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.

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 DiaSorin LIAISON® Calprotectin assay is an in vitro diagnostic chemiluminescent immunoassay (CLIA) intended for the quantitative measurement, in human stool, of fecal calprotectin, a neutrophilic protein that is a marker of mucosal inflammation. The LIAISON® Calprotectin assay can be used as an aid in the diagnosis of inflammatory bowel diseases (IBD), specifically Crohn's disease and ulcerative colitis, and as an aid in differentiation of IBD from irritable bowel syndrome (IBS). Test results are to be used in conjunction with information obtained from the patients' clinical evaluation and other diagnostic procedures.

The test has to be performed on the LIAISON® Analyzer Family.

The DiaSorin LIAISON® Q.S.E.T. Device Plus (Quantitative Stool Extraction and Test) is intended for use in the preparation of human stool specimens for testing in the LIAISON® Calprotectin assay.

The LIAISON® Calprotectin assay is a sandwich assay that uses 2 monoclonal antibodies for capture and detection of calprotectin. The LIAISON® Calprotectin assay must be run on the LIAISON® Analyzer family, a fully automated system with continuous loading.

Calprotectin is first extracted from human stool samples with LIAISON® Q.S.E.T. Buffer using either the weigh method, the LIAISON® Q.S.E.T. Device or the LIAISON® Q.S.E.T. Device Plus. The assay incubates extracted sample, calibrator, control, or calibration verifiers with assay buffer and paramagnetic particles coated with a monoclonal antibody that specifically recognizes the calprotectin heterocomplex. Following incubation, a wash cycle is performed to remove any unbound material. An isoluminol conjuqated monoclonal antibody that recognizes calprotectin is then added to the reaction and incubated. The unbound conjugate is removed with a second wash step. Starter reagents are then added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of calprotectin present in the calibrators, controls or samples.

All assay steps and incubations are performed by the LIAISON® XL Analyzer. The analyzer software automatically calculates the concentration of calprotectin in the sample. This concentration is expressed in ug/g.

The Q.S.E.T. Device Plus differs from its predicate Q.S.E.T. Device in that it is provided ready to use, and comes prefilled with the same extract buffer as required for use with the Q.S.E.T. Device, eliminating the need for the user to prepare the buffer and add it to the device themselves. In addition, minor changes to the shape and design of the tube were made.

The provided text is related to the FDA 510(k) premarket notification for the DiaSorin LIAISON® Calprotectin assay and the LIAISON® Q.S.E.T. Device Plus. None of the information requested in your prompt (Acceptance criteria, Study proving device meets criteria, Sample size, data provenance, expert numbers, etc. for AI/clinical studies) is present in the document.

The document describes an in vitro diagnostic (IVD) chemiluminescent immunoassay (CLIA) for fecal calprotectin, intended as an aid in diagnosing Inflammatory Bowel Diseases (IBD) and differentiating it from Irritable Bowel Syndrome (IBS). It also details a device for stool sample preparation.

The performance data included in the document specifically refers to the analytical performance of the IVD device and its sample preparation component, such as:

• Precision/Reproducibility: This section details the reproducibility of the LIAISON® Q.S.E.T. Device Plus extraction using five (5) stool samples with 90 measurements per sample (6 replicates over 5 days by 3 operators). It also shows sampling reproducibility using 5 human stool specimens, sampled by 3 operators with 5 replicates per specimen per operator on 3 lots of devices, totaling 225 sampling events.
• Reagent Stability: Mentions stability of the LIAISON® Q.S.E.T. Device Plus at 2-8°C for 12 months.
• Specimen Stability: Provides stability data for stool specimens under various storage conditions (refrigerated, room temperature, frozen, freeze/thaw cycles) and for sample extracts.

Therefore, I cannot provide the requested information regarding acceptance criteria for an AI/clinical study, the study setup to prove meeting those criteria, sample sizes for test/training sets in an AI context, expert qualifications, adjudication methods, MRMC studies, or standalone algorithm performance, as these concepts are not applicable to the analytical validation described for this IVD device.

The document solely focuses on the analytical performance validation of an IVD immunoassay, not on clinical performance or AI/machine learning aspects.

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The DiaSorin LIAISON® MeMed BV® is an automated in vitro diagnostic semi-quantitative assay that uses chemiluminescent immunoassay (CLIA) technology to measure three non-microbial (host) proteins (TRAIL, IP-10, and CRP) in adult and pediatric serum samples and is intended for use in conjunction with clinical assessments and other laboratory findings as an aid to differentiate bacterial from viral infection. The LIAISON® MeMed BV® assay is indicated for use in patients presenting to the emergency department or urgent care center and with samples collected at hospital admission from patients with suspected acute bacterial or viral infection, who have had symptoms for seven days or less. The LIAISON® MeMed BV® assay generates a numeric score that falls within discrete interpretation ranges based on the increasing likelihood of bacterial infection. The assay has to be performed on the automated LIAISON® XL Analyzer.

The DiaSorin LIAISON® MeMed BV® Control Set is intended for use as assayed quality control to monitor the performance of the DiaSorin LIAISON® MeMed BV® assay. The performance characteristics of the LIAISON® controls have not been established for any other assays or instrument platforms different from the automated LIAISON® XL Analyzer. The control set is intended for in vitro diagnostic use in a professional laboratory only.

The LIAISON MeMed BV assay consists of three individual chemiluminescence immunoassay (CLIA) for quantitative determination of TRAIL, IP-10, and CRP. The LIAISON MeMed BV test result is a score between 0 and 100 derived from computational integration of the measurements of the three proteins TRAIL, IP-10, and CRP, where low scores are indicative of viral infection and high score of bacterial infection. All three reagent packs must be the same lot and present at the same time on the same instrument used for sample testing. All three reagent packs are individually calibrated and quality controlled. Specimens are to be assigned to the MMBV assay protocol where all three reagent packs will be utilized to provide combined results and a final score.

The TRAIL reagent pack uses a monoclonal antibody for capture of TRAIL and a polyclonal antibody for the detection of TRAIL. The assay incubates sample, calibrator or control with assay buffer and paramagnetic particles coated with a monoclonal antibody that specifically recognizes the TRAL. Following the incubation, an isoluminol conjugated polyconal antibody that recognizes TRAIL is then added to the reaction and incubated. The unbound conjugate is removed with a wash step. Starter reagents are then added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of TRAL present in the calibrators, controls or samples. The result of the TRAIL reagent pack is only used to calculate a final LIAISON MeMed BV Score and should not be used individually for diagnosis.

The IP-10 reagent pack uses a monoclonal antibody for the capture of IP-10 and a polyclonal antibody for the detection of IP-10. The assay incubates sample, calibrator or control with assay buffer and paramagnetic particles coated with a monoclonal antibody that specifically recognizes the IP-10. Following the incubation, an isoluminol conjugated polyclonal antibody that recognizes IP-10 is then added to the reaction and incubated. The unbound conjugate is removed with a wash step. Starter reagents are then added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of IP-10 present in the calibrators, controls or samples. The result of the IP-10 reagent pack is only used to calculate a final LIAISON MeMed BV Score and should not be used individually for diagnosis.

The CRP reagent pack uses monoclonal antibodies for capture and detection of CRP. First the patient serum sample is pre-diluted 1:196 with assay buffer. The assay incubates the pre-diluted sample, calibrator or control with assay buffer and paramagnetic particles coated with a monoclonal antibody that specifically recognizes the CRP. Following the incubation, an isoluminol conjugated monoclonal antibody that recognizes CRP is then added to the reaction and incubated. The unbound conjugate is removed with a wash step. Starter reagents are then added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of CRP present in the calibrators, controls or samples. The result of the CRP reagent pack is only used to calculate a final LIAISON MeMed BV Score and should not be used individually for diagnosis.

The provided document describes the FDA clearance (K213936) for the DiaSorin LIAISON® MeMed BV® assay, which aids in differentiating bacterial from viral infections. Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

The document primarily focuses on demonstrating substantial equivalence to a predicate device rather than explicitly listing predefined acceptance criteria with numerical targets. However, the performance data presented implies a set of internal acceptance criteria related to statistical significance, agreement with expert adjudication, and reproducibility.

Given the information provided, here's a table summarizing the reported device performance, with implicit acceptance criteria derived from the study's conclusions:

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

• Clinical Agreement Test Set: 285 serum samples.
  • Provenance: Collected at hospital admission, Emergency Department, and Urgent Care Centers. Patients ranged in age from 5 months to 92 years. The origin country is not explicitly stated, but the mention of "21 international experts" suggests a multi-national or at least internationally adjudicated dataset. The study is retrospective in the sense that samples were likely collected before the adjudication process and testing with the device.
• Method Correlation Test Set:
  • Primary Endpoint analysis: 285 clinical samples (the same as the clinical agreement test set).
  • Secondary Endpoint analysis: 257 clinical samples (28 of the 285 were excluded).
• Expected Values Test Set: 150 serum samples from apparently healthy asymptomatic adults.
  • Provenance: Collected in the Southwestern U.S.
• Reproducibility Study Test Set: 4 serum samples (1 normal, 1 viral, 1 bacterial, 1 equivocal) plus kit controls.
• Cross-Reactivity Study Test Set: Two (2) serum samples (one low, one high SCORE) for each cross-reactant being tested.
• Interfering Substances Study Test Set: Two (2) serum samples (one low, one high SCORE) for each interfering substance being tested.
• Matrix Equivalence Study Test Set: 43 fresh serum samples from individual patients, with 20 spiked for range coverage.
• Limit of Blank, Detection, Quantitation Test Set: Varied based on particular limit, ranging from 4-8 serum/spiked matrix samples for LoD/LoQ studies and 5 calibrator matrix samples for LoB.

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

• Number of Experts: A pool of 21 international experts.
• Qualifications of Experts: Clinicians with at least 7 years of relevant clinical experience. Each panel comprised at least three experts.

4. Adjudication Method for the Test Set

• Method: Expert adjudication.
  • Process: Panelists for each subject adjudication were drawn from the pool of 21 international experts. Each panel comprised at least three experts who independently adjudicated the etiologic label for each patient. The etiologic label was determined as bacterial, viral, or non-infectious. The adjudication was based on anonymized patient data. Critically, the adjudicators were blinded to the MeMed BV result (for the primary endpoint) and to CRT and PCT results (for the primary endpoint). For the secondary endpoint, adjudicators were un-blinded to PCT and CRP results.

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 document describes the analytical and clinical performance of an in vitro diagnostic assay (a laboratory test that measures protein levels and computes a score), not an AI-assisted diagnostic tool that human readers interpret. Therefore, an MRMC comparative effectiveness study involving human readers assisting with AI is not applicable and was not performed. The device itself is the "AI" (computational algorithm) that processes biomarker data.

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

• Yes, the performance presented for the "LIAISON MeMed BV" assay is a standalone performance of the device (assay and its integrated computational scoring). The "SCORE" is generated by the device's algorithm based on the measured protein levels (TRAIL, IP-10, and CRP), without a human in the loop for the scoring itself. The clinical utility is then evaluated by comparing this score to expert adjudication.

7. The Type of Ground Truth Used

• Type of Ground Truth: Expert consensus (physician expert adjudication). Specifically, physicians were forced to make a bacterial, viral, or non-infectious diagnosis.

8. The Sample Size for the Training Set

• The document does not specify the sample size used for training the algorithm (the "SCORE" computation). This document focuses on the validation of the device for FDA clearance. Typically, details of the training dataset are considered proprietary or part of the algorithm development process prior to clinical validation.

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

• Since the training set size and details are not provided, information on how its ground truth was established is also not available in this document. It is typical for such algorithms to be trained on large, well-characterized datasets, often with similar expert-adjudicated ground truth, but these details are not part of the premarket notification summary.

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The DiaSorin LIAISON® Ferritin assay is a quantitative automated chemiluminescent immunoassay (CLIA) for the in vitro detection of ferritin in human serum, serum separator tubes (SST), or lithium (Li) heparin plasma to aid in the diagnosis of iron deficiency anemia and iron overload.

This assay must be performed on the LIAISON® XL Analyzer.

The chemiluminescence immunoassay method for the quantitative determination of ferritin is a sandwich immunoassay.

A specific mouse monoclonal antibody is coated on the magnetic particles (solid phase); another monoclonal antibody (mouse) is linked to an isoluminol derivative (isoluminolantibody conjugate).

During the incubation, ferritin present in calibrators, samples or controls binds to the solid phase monoclonal antibody, and subsequently the antibody conjugate reacts with ferritin already bound to the solid phase.

After 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 coniugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of ferritin concentration present in calibrators, samples or controls.

The provided document is a 510(k) Summary for the DiaSorin LIAISON® Ferritin assay, a chemiluminescent immunoassay for the quantitative determination of ferritin in human serum, serum separator tubes (SST), or lithium (Li) heparin plasma. Its intended use is to aid in the diagnosis of iron deficiency anemia and iron overload.

This document details the performance characteristics required to demonstrate substantial equivalence to a legally marketed predicate device (Roche Elecsys® Ferritin assay), rather than defining and proving against acceptance criteria in the context of an AI/ML device or a complex diagnostic with multiple discrete outcomes. The data presented are for an in vitro diagnostic immunoassay, which relies on analytical performance metrics rather than clinical outcome studies of the type implied by the original request's questions about expert consensus, MRMC studies, human-in-the-loop performance, etc.

Therefore, many of the requested elements are not applicable to the type of device and study described in this document.

Below, I've addressed the applicable points from your request based on the provided text.

Device: DiaSorin LIAISON® Ferritin assay (K193650)

Type of Device: Quantitative automated chemiluminescent immunoassay (CLIA) for the in vitro detection of ferritin.

Purpose of the Study (as presented in the 510(k) Summary): To demonstrate substantial equivalence of the DiaSorin LIAISON® Ferritin assay to the predicate device, Roche Elecsys® Ferritin assay, based on analytical performance characteristics.

Acceptance Criteria and Reported Device Performance

For an in vitro diagnostic assay, acceptance criteria typically relate to analytical performance metrics to ensure accuracy, precision, linearity, and other factors. While the document does not explicitly list "acceptance criteria" against each performance metric in a table format, it reports the results of various studies (e.g., method comparison, precision) which would have been previously agreed upon with the FDA as sufficient to demonstrate substantial equivalence.

Here's a summary of the reported performance. The implied "acceptance criteria" are that these results fall within acceptable ranges for diagnostic assays of this type, often relative to a predicate device or industry standards (e.g., CLSI guidelines).

• Slope: 0.965 (95% CI: 0.95 - 0.98)
• Intercept: -1.12 (95% CI: -2.13 to -0.32)
• R²: 0.995 | Slope close to 1, Intercept close to 0, and R² close to 1, indicating strong agreement with the reference method (likely the predicate or another validated method), within pre-defined acceptable limits for analytical measurements. |
  | Sample Matrix Comparison | Serum vs. SST:
• Slope: 1.002 (0.9727 to 1.038)
• Intercept: 0.0179 (-0.7744 to 0.6374)
  Serum vs. Li Heparin:
• Slope: 0.984 (0.9413 to 0.9905)
• Intercept: -1.732 (-2.137 to -0.5159) | Slopes near 1 and intercepts near 0 for different matrix types compared to serum, demonstrating equivalence across specified sample types. |
  | Precision (Total %CV) | Kit Control 1 (32.81 ng/mL): 4.3%
  Kit Control 2 (300 ng/mL): 5.4%
  Panel 1 (5.84 ng/mL): 5.6%
  Panel 2 (18.26 ng/mL): 4.6%
  Panel 3 (178 ng/mL): 4.1%
  Panel 4 (1093 ng/mL): 5.6%
  Panel 5 (404.9 ng/mL): 4.6%
  Panel 6 (1883 ng/mL): 6.4% | Total CV (Coefficient of Variation) within acceptable limits for a quantitative immunoassay across its measuring range, demonstrating reproducibility and reliability of results. These limits are typically defined by regulatory bodies or industry standards (e.g., CLSI EP5-A3). |
  | Linearity | Equation for 2000 ng/mL sample:
  Observed Ferritin = -1.402 + 1.006 * Expected Ferritin
  R²=1.000 | R² close to 1, and slope near 1 with intercept near 0, demonstrating accurate measurement across the assay’s claimed analytical measuring range (0.46 – 2,200 ng/mL). |
  | Recovery | Average Recovery: 101% (Individual recoveries ranging from 98% to 104% for spiked samples) | Recovery values typically between 90-110% (or tighter, depending on the analyte and assay sensitivity) for spiked samples, indicating the assay accurately measures the target analyte when added to a sample. |
  | Limit of Blank (LoB) | 0.004 ng/mL | LoB consistent with the lower end of the claimed analytical measuring range and adequate for the intended clinical application. |
  | Limit of Detection (LoD) | 100.0%
  Human spleen ferritin: 78.8% | Specificity for the intended analyte (ferritin) without significant cross-reactivity with closely related substances or other components that could lead to false results. |

Applicable Information from the Request (Based on provided document):

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

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

   • Method Comparison: 173 samples. Provenance not specified (e.g., country of origin, retrospective/prospective), but it usually implies clinical samples collected for analytical validation purposes.
   • Sample Matrix Comparison: 37 matched patient sets (serum, Li Heparin plasma) and 6 contrived matched patient samples. Provenance not specified.
   • Expected Values/Reference Range: 78 human serum samples; 39 healthy female, 39 healthy male subjects (age 18+). Provenance not specified.
   • Precision: 2 kit controls and 6 samples assayed 320 times each (twice per day in duplicate, over 20 operating days on two LIAISON® XL Analyzers using two reagent lots). Provenance: DiaSorin GmbH, implying internal lab testing.
   • Linearity: Dilution series of 4 samples.
   • Recovery: 4 representative human serum samples. Provenance not specified.
   • Interference, Cross-Reactivity, LoB/LoD/LoQ studies also involved specific numbers of samples/replicates, but detailed sample sizes for each are not individually listed beyond the overall study design (e.g., "controlled studies... at Ferritin level of approximately 20 ng/mL and 2000 ng/mL").

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. This document describes an in vitro diagnostic device measuring a quantitative biomarker (Ferritin). Ground truth is established through reference methods, calibration materials traceable to international standards (e.g., NIBSC 94/572 for Ferritin), and gravimetric/dilution/spiking studies, not by expert interpretation of images or clinical outcomes that require human experts for ground truth.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set: Not applicable. Adjudication methods are relevant for studies involving human interpretation (e.g., radiology reads) where discrepancies need to be resolved. This is an automated analytical test.

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 AI/ML device that assists human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Not applicable in the context of an "algorithm" as typically referred to in AI/ML. The device itself is an automated analyzer that performs the "standalone" measurement of ferritin. No human interpretation is involved in the measurement process after sample loading.

7. The type of ground truth used:

   • For Method Comparison, the "Reference Method" was used as ground truth. This would typically be a highly accurate and precise method, often the predicate device itself or a laboratory developed test that is well-validated.
   • For Linearity and Recovery, ground truth was established by preparing samples with known concentrations through spiking and dilution from a characterized stock solution or pool.
   • For Precision, samples with known (or previously characterized) ferritin concentrations were used.
   • For Traceability, the calibrators are traceable to an internal reference standard "oriented at the 2nd reference standard NIBSC 94/572." This international standard serves as a form of ground truth for absolute concentration.

8. The sample size for the training set: Not applicable. This is a traditional immunoassay, not an AI/ML device that requires a "training set" in the computational sense. The "training" of such a system involves calibrating it with known standards, which were traceable to an international reference standard (NIBSC 94/572).

9. How the ground truth for the training set was established: Not applicable, as there is no "training set" in the AI/ML sense. Calibration is performed using materials traceable to an international reference standard.

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The LIAISON® Lyme IgM assay uses chemiluminescent immunoassay (CLIA) technology for the qualitative detection of IgM antibodies to Borrelia burgdorferi in human serum and plasma samples (K2-EDTA, Li-heparin). This assay is intended for use on samples from patients with signs and symptoms consistent with or patients suspected of having Lyme disease to assess the presence of antibodies and exposure to Borrelia burgdorferi. In addition, the LIAISON® Lyme IgM assay may be used as a confirmatory test in the modified two-tier test (MTTT) in combination with the DiaSorin LIAISON® Lyme Total Antibody Plus assay.

If used as a first stage test, positive or equivocal results with the LIAISON® Lyme IgM assay should be confirmed through additional testing with a Standard two-tier test (STTT) methodology using an IgM Borrelia burgdorferi Western blot test following current guidelines.

Positive supplemental results are supportive evidence of the presence of antibodies and exposure to Borrelia burgdorferi and may be used along with patient history, symptoms and other laboratory data to support a clinical diagnosis of Lyme disease.

Negative results by the LIAISON® Lyme IgM assay should not be used to exclude Lyme disease.

The test must be performed on the LIAISON® XL Analyzer.

The DiaSorin LIAISON® Lyme IgM Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Lyme IgM assay. The performance characteristics of LIAISON® Lyme IgM controls have not been established for any other assays or instrument platforms different from the LIAISON® XL.

The LIAISON® Lyme IgM assay is an indirect chemiluminescence immunoassay (CLIA) for the qualitative detection of IgM antibodies to Borrelia burgdorferi in human serum and plasma samples. All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the Analyzer. The principal components of the test are magnetic particles (solid phase) coated with recombinant Borrelia antigens and a conjugate reagent containing an anti-human IgM mouse monoclonal antibody linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, anti-Borrelia burgdorferi antibodies present in calibrators, samples or controls bind to the solid phase. Unbound material is then removed with a wash cycle. During the second incubation, the antibody conjugate reacts with anti-Borrelia burgdorferi IgM antibodies that have bound to the solid phase. Excess antibody conjugate is then removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is 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 the presence of Borrelia burgdorferi IgM antibodies present in calibrators, samples or controls.

The provided document describes the LIAISON® Lyme IgM assay, which is a chemiluminescent immunoassay (CLIA) for the qualitative detection of IgM antibodies to Borrelia burgdorferi in human serum and plasma samples. The device performance was evaluated through various studies, including a method comparison with a predicate device, an evaluation using Standard Two-Tier Testing (STTT) and Modified Two-Tier Testing (MTTT) methodologies, testing of a characterized Lyme panel from the CDC, precision and reproducibility studies, a cross-reactivity study, and an interfering substances study.

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 values for agreement percentages (PPA, NPA) or specificity/sensitivity for the method comparison, STTT, or MTTT studies. Instead, it presents the calculated agreement results, implying these are the performance metrics. For precision and reproducibility, specific %CV ranges are not explicitly stated as acceptance criteria, but the calculated %CV values are reported.

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

• Method Comparison and Prospective MTTT Studies:
  • Sample Size: 2621 human serum specimens.
  • Data Provenance: Collected in 14 states across five (5) distinct U.S. geographical regions. This indicates prospective data.
• Characterized Lyme Panel and Retrospective MTTT Study:
  • Sample Size: 280 samples for the characterized Lyme Panel. For the retrospective MTTT, 279 samples were evaluated after one lacked sufficient volume.
  • Data Provenance: Acquired from the CDC. This indicates retrospective (or banked) data.
• Cross-Reactivity Study:
  • Sample Size: 191 specimens.
  • Data Provenance: From various disease states, implying samples from patients with known conditions, likely retrospective or banked.
• Interfering Substances Study:
  • Sample Size: Not explicitly stated, described as "serum specimens containing B. burgdorferi IgM antibodies."
  • Data Provenance: Not specified, likely laboratory-prepared samples.
• Matrix Equivalence Study:
  • Sample Size: 32 matched patient sets.
  • Data Provenance: Not specified, likely laboratory-prepared or procured patient samples, potentially retrospective.

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

The document does not specify the number or qualifications of experts used to establish the ground truth for the test sets.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method for the test sets. For the STTT and MTTT, Western blot (WB IgM) is used as a confirmatory test, which acts as a gold standard in the two-tier testing methodology, but it's not described as an "adjudication" in the sense of multiple expert readers resolving discrepancies.

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 document describes an in vitro diagnostic (IVD) device (an immunoassay), not an AI-powered diagnostic imaging or a reader-assisted device. Therefore, a multi-reader multi-case (MRMC) comparative effectiveness study focusing on human reader improvement with or without AI assistance is not applicable and was not performed.

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

Yes, the studies detailed (Method Comparison, STTT, MTTT, Characterized Lyme Panel, Precision, Reproducibility, Cross-Reactivity, Interfering Substances, Matrix Equivalence) represent the standalone performance of the LIAISON® Lyme IgM assay, which operates as an automated chemiluminescent immunoassay on the LIAISON® XL Analyzer without human interpretation of the primary result (the index value is generated by the machine and then converted to qualitative results). Humans perform the test, but the device provides the result.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The type of ground truth used varies:

• Method Comparison: The predicate device, ZEUS ELISA Borrelia burgdorferi IgM Test System, served as a reference for comparison. While not a "ground truth" in terms of pathology, it's a legally marketed device used for establishing substantial equivalence.
• Standard Two-Tier Testing (STTT): IgM Borrelia burgdorferi Western blot (following current guidelines) was used as the second-tier confirmatory test, representing the established serological "gold standard" for Lyme disease diagnosis, especially when combined with a positive first-tier test and clinical context. This is akin to a reference method ground truth.
• Modified Two-Tier Testing (MTTT): For the prospective study, the STTT protocol (LIAISON® Lyme Total Antibody Plus followed by B. burgdorferi IgM Western Blot) was considered the reference to which the MTTT (LIAISON® Lyme Total Antibody Plus followed by LIAISON® Lyme IgM assay) was compared. For the retrospective study using CDC samples, the STTT WB IgM results associated with the characterized panel served as the comparator.
• Characterized Lyme Panel (CDC): The classification of these samples (Acute, Convalescent, Late Lyme disease, Look-alike Diseases, Healthy controls) implies that these samples have a pre-established clinical and/or laboratory diagnosis/classification, representing a form of clinical ground truth.

8. The Sample Size for the Training Set

The document describes studies for substantial equivalence based on performance evaluation. It does not mention a "training set" in the context of machine learning model development. This is an IVD device, not an AI/ML device that requires explicit training data. The "performance data" presented is for evaluation (test sets).

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

As stated above, this is an IVD device and the document does not refer to a "training set" or "training data" in the typical AI/ML context. The various reference methods (predicate device, Western blot, CDC characterized panels) serve as the comparators or benchmarks for establishing the performance characteristics.

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The LIAISON® Lyme IgG assay uses chemiluminescent immunoassay (CLIA) technology for the qualitative detection of IgG antibodies to Borrelia burgdorferi in human serum and plasma specimens (K2-EDTA, Li-heparin). This assay is intended for use on samples from patients with signs and symptoms consistent with or patients suspected of having Lyme disease to assess the presence of IgG antibodies and exposure to Borrelia burgdorferi. In addition, the LIAISON® Lyme Ig G assay may be used as a confirmatory test in the modified two-tier test (MTTT) in combination with the DiaSorin LIAISON® Lyme Total Antibody Plus assay.

If used as a first stage test, positive or equivocal results with the LIAISON® Lyme IgG assay should be confirmed through additional testing with a Standard two-tier test (STT) methodology using an IgG Borrelia burgdorferi Western blot test following current guidelines.

Positive supplemental results are supportive evidence of the presence of antibodies and exposure to Borrelia burgdorferi and may be used along with patient history, symptoms and other laboratory data to support a clinical diagnosis of Lyme disease.

Negative results by the LIAISON® Lyme IgG assay should not be used to exclude Lyme disease.

The test must be performed on the LIAISON® XL Analyzer.

The DiaSorin LIAISON® Lyme IgG Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Lyme IgG assay. The performance characteristics of LIAISON® Lyme IgG controls have not been established for any other assays or instrument platforms different from the LIAISON® XL.

The LIAISON® Lyme IgG assay is an indirect chemilyminescence immunoassay (CLIA) for the qualitative detection of IgG antibodies to Borrelia burgdorferi in human serum and plasma samples. All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the Analyzer. The principal components of the test are magnetic particles (solid phase) coated with recombinant Borrelia antigens and a conjugate reagent containing an anti-human IgG mouse monoclonal antibody linked to an isoluminol derivative (isoluminol-antibody coniugate). During the first incubation, anti-Borrelia burgdorferi antibodies present in calibrators, samples or controls bind to the solid phase. Unbound material is then removed with a wash cycle. During the second incubation, the antibody conjugate reacts with anti-Borrelia burgdorferi IgG antibodies that have bound to the solid phase. Excess antibody conjugate is then removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is 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 the presence of Borrelia burgdorferi IgG antibodies present in calibrators, samples or controls.

Here's a breakdown of the acceptance criteria and study details for the LIAISON® Lyme IgG assay, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance:

The document implicitly defines acceptance criteria through its performance study results, specifically for percentage agreement (sensitivity and specificity) when compared to a predicate device and STTT/MTTT protocols.

Acceptance Criteria (Implicitly defined by performance targets in studies)

Note on Acceptance Criteria: The document does not explicitly state numerical acceptance criteria for each metric (e.g., "PPA must be >X%"). Instead, it presents the device's performance results and concludes substantial equivalence, implying that these results met the FDA's expectations for equivalence to legally marketed predicate devices.

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

• Method Comparison (First Tier and STTT):
  • Sample Size: 2621 human serum specimens.
  • Data Provenance: Collected in 14 states across five (5) distinct U.S. geographical regions. This was a prospective study ("All 2621 prospective (all comer) specimens").
• Modified Two Tier Testing Methodology (Prospective Population):
  • Sample Size: 225 specimens (from the initial 2621 that were positive or equivocal by the first-tier assay).
  • Data Provenance: U.S. geographical regions, prospective.
• Characterized Lyme Panel (CDC Panel):
  • Sample Size: 280 samples.
  • Data Provenance: Acquired from the CDC (Centers for Disease Control), making it a retrospective panel.
• Modified Two Tier Testing Methodology (Retrospective Population from CDC Panel):
  • Sample Size: 279 samples (1 sample from the 280 CDC panel lacked sufficient volume). 82 of these were further tested with STTT WB IgG or MTTT.
  • Data Provenance: CDC, retrospective.
• Cross-reactivity Study:
  • Sample Size: 222 specimens (from 22 different disease states).
  • Data Provenance: Not specified, but likely obtained from various sources or commercial vendors for specific disease states. Retrospective by nature of obtaining specific disease samples.
• Matrix Equivalence Study:
  • Sample Size: 32 matched patient sets.
  • Data Provenance: Not specified.

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

The document does not explicitly state the "number of experts" or their specific "qualifications" for establishing ground truth. However, the ground truth for some studies is based on established laboratory methods:

• For the Method Comparison and STTT/MTTT studies: The ground truth for confirming Borrelia burgdorferi infection or exposure is primarily established by Western blot testing (IgG Borrelia burgdorferi Western blot test) following current guidelines. This is a recognized laboratory "gold standard" or highly accepted confirmatory method for Lyme disease. While experts interpret WBs, the document doesn't detail the number or qualifications of individuals performing or interpreting these specific Western blots.
• For the Characterized Lyme Panel (CDC Panel): The samples were "characterized" by the CDC. This implies that the CDC itself, a leading public health agency with extensive expertise in infectious diseases, established the reference classification for these samples. The ground truth here is the CDC's reference classification, which would involve robust testing and expert consensus within the CDC, though specific expert numbers or qualifications are not provided in this submission summary.

4. Adjudication Method for the Test Set:

Not explicitly described in the document. The studies primarily compare the LIAISON® Lyme IgG assay results against either a predicate ELISA assay or Western Blot results (STTT/MTTT). There isn't mention of a separate adjudication process beyond the defined "ground truth" method (e.g., WB results).

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study, as typically understood for AI-assisted image analysis where human readers improve with AI vs without AI assistance, was not explicitly mentioned or performed. This device is an in-vitro diagnostic (IVD) assay designed to detect antibodies, not an AI-powered diagnostic imaging system requiring human interpretation with AI assistance. Its performance is measured directly against other laboratory tests or characterized panels.

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

Yes, the performance studies described are essentially standalone evaluations of the LIAISON® Lyme IgG assay. The assay is an automated chemiluminescent immunoassay (CLIA) performed on the LIAISON® XL Analyzer. The results (Index values) lead to a qualitative positive, negative, or equivocal determination by the instrument's algorithm based on a predefined cutoff. There is no human-in-the-loop performance described in the context of interpreting the assay's primary output. Human involvement is in running the test and interpreting the final qualitative result provided by the system within a clinical context.

7. The Type of Ground Truth Used:

• Expert Consensus / Established Gold Standard:
  • For the prospective and retrospective studies that compare the LIAISON® assay to STTT (Standard Two-Tier Test) or MTTT (Modified Two-Tier Test), the ground truth is primarily based on IgG Borrelia burgdorferi Western Blot testing following current guidelines. Western blot is generally considered the confirmatory "gold standard" for Lyme disease serology.
  • For the "Characterized Lyme Panel" (from CDC), the ground truth is the CDC Reference Classification, which would be based on comprehensive testing and expert knowledge.
• Predicate Device Comparison: In the initial method comparison, the ground truth for calculating agreement percentages is the ZEUS ELISA B. burgdorferi IgG Test System (predicate device).

8. The Sample Size for the Training Set:

The document describes performance studies (method comparison, STTT, MTTT, cross-reactivity, precision, reproducibility, etc.) of the LIAISON® Lyme IgG assay. It does not explicitly mention a "training set" or "validation set" in the context of an algorithm or AI model development. The reported studies represent the testing and validation of the already developed assay.

• However, for the assay development process itself (not detailed in this summary), a training phase would typically occur during the R&D of the assay to establish optimal reagent concentrations, cut-offs, and assay parameters. This information is generally proprietary to the manufacturer and not typically included in a 510(k) summary unless the device is a novel AI/ML product.
• The calibration described ("Two-point verification (in triplicate) of stored 10 point master curve") indicates a specific calibration approach for the instrument, which would have been established during initial assay development using a set of characterized samples. The number of samples for developing this master curve is not provided.

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

As noted above, a distinct "training set" for an AI/ML algorithm is not described here, as this is an immunoassay. For the development of the assay itself (e.g., establishing optimal cut-offs), the ground truth would have been established using well-characterized samples from known Lyme disease patients and healthy controls, likely confirmed by established methods like Western blot and/or clinical diagnosis, similar to the methods used to establish the ground truth for the test sets presented. The specifics of this internal R&D process are not detailed in the FDA summary.

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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® Testosterone xt is a direct, competitive, chemiluminescence immunoassay (CLIA) intended for the quantitative determination of testosterone in human serum and EDTA plasma on the LIAISON® XL Analyzer. The assay is intended for in vitro diagnostic use.

Measurement of testosterone is used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.

The test has to be performed on the LIAISON® XL Analyzer.

The LIAISON® Testosterone xt assay's method for quantitative determination of testosterone is a direct, competitive, chemiluminescence immunoassay (CLIA). Specific antibody to testosterone is bound to magnetic particles (solid phase) and testosterone is linked to an isoluminol derivative. During the incubation, testosterone is dissociated from its binding protein and competes with labeled testosterone for binding sites on the antibody. After the incubation, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is inversely proportional to the concentration of testosterone present in calibrators, controls, or samples.

The LIAISON® Testosterone xt is an in vitro diagnostic device consisting of reagents provided in individual compartments within a plastic container called the Reagent Integral. The components provided in the unitized Reagent Integral include: PMP (paramagnetic particles), conjugate and assay buffer. All reagents in the integral are supplied ready to use. The assay configuration for the LIAISON® Testosterone xt allows for the performance of 100 tests.

The two-point calibrators are provided in the same kit box, but separate from the Reagent Integral. The two-point calibrators are supplied ready to use.

The LIAISON® Testosterone xt assay is performed on the LIAISON® XL Analyzer (Model 10050; originally FDA cleared under K103529), a fully automated system with continuous loading combining the chemiluminescence technology with magnetic microparticles as the solid phase.

Here's a breakdown of the acceptance criteria and study information for the LIAISON® Testosterone xt device, extracted from the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Size for the Test Set and Data Provenance

The provided document does not explicitly state the sample sizes used for each specific test (e.g., method comparison, precision, linearity, recovery). It only summarizes the results in "Table 6-2: Comparison to Predicate Device" and refers to "verification and validation activities" without detailing the exact number of samples for each.

The data provenance is not specified in terms of country of origin. The studies appear to be retrospective analyses of device performance characteristics, as they involve testing the LIAISON® Testosterone xt against existing methods or conditions to demonstrate equivalence and improved performance over the predicate device.

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

This information is not explicitly provided in the document. For the "Method Comparison," it refers to "commercially available immunoassay" and "CDC HoSt Testosterone RMP ID-LC-MS/MS values." The latter, CDC HoSt Testosterone RMP ID-LC-MS/MS, likely represents a highly accurate and standardized reference method, which serves as a widely accepted ground truth in laboratory medicine, rather than relying on individual expert consensus for each measurement. No human experts are mentioned for ground truth establishment.

4. Adjudication Method for the Test Set

No explicit adjudication method is mentioned. The studies focus on direct quantitative analytical performance comparisons rather than subjective human interpretation.

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 is not applicable. The LIAISON® Testosterone xt is an in vitro diagnostic device, specifically a chemiluminescence immunoassay (CLIA), for the quantitative determination of testosterone. It is an automated laboratory test, not an AI-assisted diagnostic imaging or interpretation tool that involves human readers. Therefore, an MRMC comparative effectiveness study involving human readers and AI is not relevant to this device.

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

Yes, this is effectively a standalone device performance study. The LIAISON® Testosterone xt is an automated system where the measurement of testosterone is performed by the analyzer (LIAISON® XL Analyzer) without human intervention in the analytical process itself. The performance metrics (LoB, LoD, LoQ, precision, linearity, recovery) are all measures of the algorithm's and instrument's direct analytical capability.

7. The Type of Ground Truth Used

The ground truth used for method comparison was:

• For the predicate device: A "commercially available immunoassay."
• For the LIAISON® Testosterone xt: "CDC HoSt Testosterone RMP ID-LC-MS/MS values." This is a highly accurate, reference method-based measurement, representing the gold standard for testosterone quantification. Other ground truths were established by controlled experiments for limits (e.g., dilution series for LoB, LoD, LoQ), spiked samples for recovery, and replicated measurements for precision.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI. This device is an immunoassay, not an AI model that requires a distinct training phase with a labeled dataset in the typical sense. Its development would involve analytical validation using various samples to optimize reagent formulation, assay parameters, and calibration, but not as a machine learning training set.

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

As explained above, there is no "training set" in the machine learning sense for this immunoassay. The development and validation of an immunoassay involve:

• Reference materials: Use of certified reference materials or reference methods (like ID-LC-MS/MS) to establish accurate values for calibrators and controls.
• Spiked samples: Samples with known concentrations of testosterone added.
• Clinical samples: Testing a range of patient samples representing the intended use population, comparing results to established methods.
• Statistical analysis: Extensive statistical methods are used during development and validation to ensure accuracy, precision, linearity, and other performance characteristics.

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The DiaSorin LIAISON® Folate assay uses chemiluminescent immunoassay (CLIA) technology for the quantitative determination of Folic acid in human serum. Folic acid measurements are used in the diagnosis and treatment of anemias. Assay results should be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions.

The assay must be performed on the LIAISON® XL Analyzer.

The LIAISON® Folate assay is a competitive chemiluminescence immunoassay (CLIA) for quantitative determination of Folic acid in serum. During the first incubation, Folic acid is dissociated from its binding protein. After five (5) minutes, a high pH buffer is added to prevent re-association to the binding protein. After five (5) minutes, Folic acid binds to a Folate Binding Protein on the solid phase, which competes with a Folic acid linked to an isoluminol derivative. After a third incubation, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added to initiate a flash chemiluminescent reaction. The light signal is measured by a photomultiplier as relative light units (RLU) and is inversely proportional to the concentration of Folic acid present in calibrators, controls, or samples.

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

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" for each performance characteristic in a pass/fail format. Instead, it presents study results which implicitly demonstrate the device's acceptable performance. For clarity, I've inferred common acceptance standards for such in vitro diagnostic assays where explicit criteria aren't given and formatted the reported performance against these.

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

• Test Set (Method Comparison): 157 human serum samples, spanning the assay range.
• Test Set (Expected Values/Reference Range): 166 prospectively collected serum samples from apparently healthy U.S. adults (21-59 years old) of mixed ethnic backgrounds (30% Caucasian, 32% African American, 38% Hispanic).
• Data Provenance: The method comparison study and the expected value study used human serum samples. The expected values study explicitly mentions "United States" for its population, implying the data is from the US and prospectively collected. The nature of the other analytical performance studies (precision, linearity, recovery, etc.) generally involves contrived or spiked samples and do not typically draw from specific patient populations or geographical locations.

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

• General Context: For an in vitro diagnostic (IVD) device like the LIAISON® Folate assay, the "ground truth" for the test set is established by the predicate device (Abbott Laboratories, ARCHITECT Folate, K092740) for method comparison, or by the inherent concentration of the analyte in the samples for analytical performance characteristics (like precision, linearity, etc.).
• No human "experts" established ground truth for the test set in the way radiologists might agree on an image diagnosis. Instead, the predicate device (an established, cleared medical device) serves as the reference standard for comparative effectiveness.

4. Adjudication Method for the Test Set:

• This is not applicable to the analytical performance studies of an in vitro diagnostic assay. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies, particularly for diagnostic imaging or pathology, where human interpretation of results is involved and consensus among experts is needed to define the "true" diagnosis or finding for a given sample/case. Here, the comparison is against an instrument's measurement (predicate device) or against known concentrations.

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 question is not applicable to this type of device. The LIAISON® Folate assay is an automated in vitro diagnostic device, not an AI-assisted diagnostic tool that humans interpret. There are no "human readers" involved in interpreting the results from this specific device.

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

• Yes, this entire submission describes the standalone performance of the LIAISON® Folate assay. It is an automated chemiluminescent immunoassay (CLIA) system (LIAISON® XL Analyzer) that quantitatively determines Folic acid in human serum. Its performance characteristics (precision, linearity, accuracy, etc.) are evaluated intrinsically as a standalone device, without human intervention in the result determination process once the sample is loaded.

7. The Type of Ground Truth Used:

• Method Comparison: The "ground truth" was established by measurements from the predicate device, the Abbott Laboratories, ARCHITECT Folate (K092740).
• Other Analytical Performance (e.g., Precision, Linearity, Recovery, Specificity): The "ground truth" was established internally through various experimental designs:
  • Precision: By repeated measurements of samples with known or target concentrations.
  • Linearity: By testing serial dilutions from a high-concentration sample, where the "expected" concentration is mathematically derived from the initial concentration and dilution factor.
  • Recovery: By comparing measured concentrations of diluted samples to their calculated expected concentrations.
  • Analytical Specificity: By comparing results of samples spiked with potential interferents/cross-reactants to unspiked samples.
  • Limits (LoB, LoD, LoQ): Through statistical analysis of repeated measurements of blank and low-level samples.

8. The Sample Size for the Training Set:

• For an IVD like the LIAISON® Folate assay, there isn't a "training set" in the context of machine learning. The technology is based on established biochemical principles (chemiluminescence immunoassay) and reagents, rather than an AI/ML algorithm that learns from data. Therefore, this question is not applicable.

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

• As mentioned above, there is no "training set" for this type of device. The design and validation are based on chemical and biological principles and rigorous experimental testing, not machine learning model training.

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