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The Anti-Neutrophil Cytoplasmic Antibodies (Ethanol-fixed) test system is an indirect immunofluorescence assay (IFA) for the qualitative and semi-quantitative determination of anti-neutrophil cytoplasmic antibodies (ANCA) of the IgG isotype in human serum by manual fluorescence microscopy or with dIFine. The presence of ANCA in conjunction with other clinical and laboratory findings can be used to aid in the diagnosis of ANCA associated vasculitis (AAV). All suggested results obtained with dIFine must be confirmed by a trained operator.

The Anti-Neutrophil Cytoplasmic Antibodies (Formalin-fixed) test system is an indirect immunofluorescence assay (IFA) for the qualitative and semi-quantitative determination of anti-neutrophil cytoplasmic antibodies (ANCA) of the IgG isotype in human serum by manual fluorescence microscopy or with dIFine. The presence of ANCA in conjunction with other clinical and laboratory findings can be used to aid in the diagnosis of ANCA associated vasculitis (AAV). All suggested results obtained with dIFine must be confirmed by a trained operator.

Not Found

The provided FDA 510(k) clearance letter for "Anti-Neutrophil Cytoplasmic Antibodies (Ethanol-Fixed)" and "Anti-Neutrophil Cytoplasmic Antibodies (Formalin-Fixed)" from ZEUS Scientific does not contain the detailed information necessary to describe the acceptance criteria and the study that proves the device meets those criteria.

This document is primarily a clearance letter, confirming that the device is substantially equivalent to a predicate device and outlining regulatory guidelines and requirements. It mentions the "dIFine" system, which likely refers to an automated interpretation component, but it does not provide any specific performance data, study design, or methodology for demonstrating the device's accuracy or effectiveness.

Therefore, I cannot fulfill your request for the following information based solely on the provided text:

1. A table of acceptance criteria and the reported device performance: This information is not present.
2. Sample sized used for the test set and the data provenance: Not mentioned.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not mentioned.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set: Not mentioned.
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 mentioned. The letter states that "All suggested results obtained with dIFine must be confirmed by a trained operator," implying a human-in-the-loop, but no study details are provided.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Not mentioned, although the statement about human confirmation suggests the primary use case is not standalone.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.): Not mentioned.
8. The sample size for the training set: Not mentioned.
9. How the ground truth for the training set was established: Not mentioned.

To obtain this information, you would typically need to refer to the 510(k) Summary or the full 510(k) submission document, which often includes a detailed description of the validation studies conducted. The clearance letter itself is a summary of the FDA's decision, not the full technical dossier.

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The Aptiva APS IgG Reagent is an immunoassay utilizing particle-based multi-analyte technology for the semiquantitative determination of anti-cardiolipin (aCL) and anti-beta 2 glycoprotein 1 (all2GPI) IgG autoantibodies in human serum as an aid in the diagnosis of primary antiphospholipid syndrome (APS), when used in conjunction with other laboratory findings.

The Aptiva APS IgG Reagent is intended for use with the Aptiva System.

The Aptiva APS IgM Reagent is an immunoassay utilizing particle-based multi-analyte technology for the semiquantitative determination of anti-cardiolipin (aCL) and anti-beta 2 glycoprotein 1 (aß2GPI) IgM autoantibodies in human serum as an aid in the diagnosis of primary and secondary antiphospholipid syndrome (APS), when used in conjunction with other laboratory findings.

The Aptiva APS IgM Reagent is intended for use with the Aptiva System.

The Aptiva APS IgG and Aptiva APS IgM reagent utilize particle based multi-analyte technology (PMAT) in a cartridge format. Each analyte (anti-cardiolipin [aCL] and anti-B2-Glycoprotein I [aB2GPI]) in the Aptiva APS IgG and Aptiva APS IgM reagent is a solid phase immunoassay utilizing fluorescent microparticles. This technology allows each of the two analytes, along with a human IgG or human IgM capture antibody (IgG or IgM Control Microparticle), to be coated onto three uniquely recognizable paramagnetic microparticles, which are combined into one tube.

The Aptiva instrument is a fully automated, random-access analyzer. This platform is a closed system with continuous load and random-access capabilities that processes the samples, runs the reagent and reports results. It includes liquid handling hardware, optical module (OM), and integrated computer with proprietary software and touch screen user interface.

The two analyte microparticles, along with the control microparticle, are stored in the reagent cartridge under conditions that proteins in their reactive states. When the assay cartridge is ready to be used for the first time, the reagent tube seals are pierced using the cartridge lid. The reagent cartridge is then loaded onto the Aptiva instrument, where the microparticles are automatically rehydrated using a buffer located within the cartridge.

The Aptiva System dilutes the sample 1:8, then combines an aliquot of diluted sample, and reagent into a cuyette. The mixture is incubated at 37°C. After a wash cvcle, conjugated antihuman IgG or IdM antibodies are added to the particles and this mixture is incubated at 37°C. Excess conjugate is removed in another wash cycle, and the particles are re-suspended in system fluid.

Multiple images are generated by the system to identify and count the two (2) unique analyte particles, as well as determine the amount of coniugate on each particle. Coated with goat anti-human lgG or IdM antibodies, is present as a control to flaq low concentrations of IgG or IgM in the sample as an assay verification step. The median fluorescent intensity (MFI) for each analyte is proportional to the concentration of conjugate bound to human IgG or IgM, which is proportional to the concentration of IgG or IgM antibodies bound to the corresponding particle population. The system uses the MFI from at least 50 particles of each population. The identity of the particles is determined by the unique signature of the particles.

Each analyte in the Aptiva APS IgG Reagent and the Aptiva APS IgM Reagent is assigned a predefined lot specific master curve. The analyte specific master curve is stored on the reagent cartridge RFID label. Based on results obtained by running calibrators (supplied separately), the system creates individual working curves. Working curves are used by the software to calculate Fluorescent Light Units (FLU) for each analyte from the MFI values obtained for each sample.

Aptiva APS IgG and Aptiva APS IgM Calibrators and Aptiva APS IgG and Aptiva APS IgM Controls are sold separately.

The provided text describes the analytical and clinical performance characteristics of the Aptiva APS IgG and Aptiva APS IgM Reagents, which are immunoassays for the semi-quantitative determination of anti-cardiolipin (aCL) and anti-beta 2 glycoprotein 1 (aβ2GPI) IgG/IgM autoantibodies. This information is presented in the context of a 510(k) premarket notification for FDA clearance.

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

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

The document does not explicitly state "acceptance criteria" as a separate, quantified set of thresholds for each performance metric. Instead, it presents the results of various analytical and clinical studies, implying that these results met the internal criteria for substantial equivalence to predicate devices and overall performance claims for an in vitro diagnostic (IVD) device.

However, we can infer performance targets based on the presented data and the overall context of an FDA submission for an IVD. The primary performance metrics presented are related to precision, detection limits, linearity, interference, and clinical sensitivity/specificity.

Inferred Acceptance Criteria and Reported Device Performance (Summary)

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

• Clinical Performance Test Set Sample Sizes:

  • Aptiva APS IgG (aCL IgG & aβ2GPI IgG): N=526 (122 APS combined, 404 controls/non-APS)
  • Aptiva APS IgM (aCL IgM & aβ2GPI IgM): N=689 (291 APS combined, 398 controls/non-APS)
  • Normal Population for Expected Values: N=200 apparently healthy blood donors.

• Method Comparison Test Set Sample Sizes:

  • Aptiva APS IgG (aCL IgG vs. QUANTA Flash aCL IgG): N=202
  • Aptiva APS IgG (aβ2GPI IgG vs. QUANTA Lite Beta 2GP1 IgG ELISA): N=108
  • Aptiva APS IgM (aCL IgM vs. QUANTA Flash aCL IgM): N=422
  • Aptiva APS IgM (aβ2GPI IgM vs. QUANTA Flash β2GPI IgM): N=244

• Analytical Performance Test Set Sample Sizes:

  • Precision: 7 samples for IgG, 7 samples for IgM (80 replicates each for within-lab; 75 replicates each for between-site/lot reproducibility from multiple sites/lots).
  • LoB/LoD/LoQ: Blanks (LoB: 4 samples, 60 data points/lot); Low-level samples (LoD/LoQ: 4 samples, 120 data points/assay/lot).
  • Interference: 6 human specimens (negative, cutoff, positive) for each analyte, spiked with various interferents and tested in 5 replicates.
  • Sample Stability: 5 serum samples (IgG), 5 serum samples (IgM) tested in duplicates over time/cycles.
  • In-use Stability: 11 samples (IgG), 7 samples (IgM) tested periodically.

• Data Provenance: The document states that a "cohort of characterized samples, none of which were used for establishing the reference range, was used to validate the clinical performance." It does not explicitly state the country of origin of the data or whether the studies were retrospective or prospective. However, for a 510(k) submission, clinical validation studies typically involve retrospective or prospectively collected clinical samples, but the exact nature (e.g., specific clinical sites, patient populations beyond disease groups) and geographic origin are not detailed here. The studies were likely conducted within a controlled laboratory setting by the manufacturer (Inova Diagnostics, Inc. in San Diego, CA) or its affiliates, using sourced human serum 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 establishment of "ground truth" for IVD devices like these typically relies on well-characterized clinical samples and established diagnostic criteria for the disease (Antiphospholipid Syndrome - APS).

• The document states that the clinical performance validation was performed using "a cohort of characterized samples." The characterization of these samples (i.e., whether they definitively represent APS or control) would serve as the ground truth.
• However, the document does not specify the number of experts or their qualifications (e.g., rheumatologists, clinical immunologists/pathologists) who established the diagnostic status (ground truth) of the clinical samples (APS vs. control) used in the clinical sensitivity and specificity studies. It is implied that these were "characterized samples," meaning their disease status was determined by established clinical and laboratory criteria, likely involving clinical consensus or previous diagnoses.
• For cut-off establishment, the reference population included "apparently healthy subjects," and the "internal APS samples (data not provided)" and "distribution of result values of healthy controls" were used. This suggests clinical characterization of these samples.

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

The concept of "adjudication method" (like 2+1 or 3+1) is typically relevant for interpretative tasks, such as reading medical images, where multiple human readers interpret the same data and their interpretations need to be reconciled to establish a ground truth.

For these types of IVD assays, ground truth for clinical performance is established based on the clinical diagnosis of the patient from whom the sample was collected. This diagnosis is usually a culmination of clinical findings, established criteria (e.g., the revised Sapporo criteria for APS), and other laboratory tests, rather than an "adjudication" of multiple independent interpretations of the test results themselves.

Therefore, the document does not mention any adjudication method in the context of establishing ground truth for the test samples, as it's not applicable in the same way it would be for an AI-medical imaging device. The "ground truth" for the samples (APS vs. non-APS) is assumed to be pre-established clinical diagnosis.

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

No MRMC study was conducted or is applicable here.

This device is an in vitro diagnostic (IVD) immunoassay, not an AI-powered image analysis or diagnostic aid that assists human readers (e.g., radiologists interpreting images). The device directly measures biomarker levels in a sample, and its output is a quantitative value (FLU) which then determines a semi-quantitative result (Positive/Negative/Indeterminate based on cut-offs). Human "readers" (laboratory personnel) operate the instrument and interpret the final quantitative results based on predefined cut-offs, but they are not subjectively interpreting complex data that AI would assist with, in the sense of an MRMC study.

Therefore, an MRMC comparative effectiveness study, and an effect size related to human reader improvement with AI assistance, are not relevant for this type of device and are not mentioned in the document.

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

This is a "standalone" device in terms of its core functionality, but the term "algorithm only" or "human-in-the-loop" isn't directly analogous.

• The Aptiva System is a fully automated, random-access analyzer (page 6). This means the instrument itself, with its integrated software and optical module, processes the samples, runs the reagents, and reports results independently after the sample is loaded and the assay initiated.
• The "performance" described here (sensitivity, specificity, precision, linearity, etc.) is the device's performance (including its internal algorithms and mechanics) in generating quantitative results. There isn't a separate "algorithm only" performance that needs to be differentiated from a "human-in-the-loop" performance, because the device is the automated system determining the FLU values. The human interaction is primarily in sample loading, reagent handling, and result review/reporting, not in interpreting raw data that the device itself would also interpret in an unassisted mode.

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

The ground truth for the clinical performance studies (sensitivity and specificity) was established based on "characterized samples" representing patients with Antiphospholipid Syndrome (APS) and various control groups (patients with other autoimmune/infectious diseases, apparently healthy subjects).

While the document doesn't explicitly state "expert consensus," it's highly implied that the "characterization" of these samples as APS or control would be based on:

• Clinical findings: Presenting symptoms, medical history.
• Other laboratory findings: Beyond the novel antibodies, other relevant diagnostic tests.
• Established diagnostic criteria: For APS, this would typically be the revised Sapporo classification criteria, which combine clinical and laboratory criteria.

So, it's a combination of established clinical diagnoses and potentially other laboratory data, which implicitly would involve the consensus or findings of medical experts involved in patient diagnosis. It is not based on pathology (e.g., tissue biopsy) or outcomes data (e.g., long-term disease progression as the sole ground truth).

8. The sample size for the training set

The document describes the submission of a "new device" and its performance characteristics. It does not explicitly mention or quantify a "training set" in the context of machine learning.

For IVD devices, a "training set" isn't a standard concept unless the device incorporates adaptive algorithms or AI that learns from data. In this case, the device is an immunoassay with predefined master curves and calibrated reagents. The master curves are generated "at Inova for each reagent lot, where in-house Master Curve Standards with assigned FLU values are run multiple times." These "in-house Master Curve Standards" could be considered analogous to a "training" or calibration process, but it's not a dataset for training a generalized AI model but rather for calibrating each reagent lot of a classical assay.

The sample sizes provided in the document are for:

• Analytical performance (precision, LoB/LoD/LoQ, linearity, interference, stability).
• Clinical validation (sensitivity/specificity studies).
• Method comparison studies.
• Reference range establishment.

None of these are explicitly labeled as a "training set."

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

As there is no explicitly defined "training set" for a machine learning model, the concept of establishing ground truth for such a set is not applicable here.

However, if we consider the "Master Curve Standards" as analogous to calibration/training data for the assay, their "ground truth" (assigned FLU values) would be established through a rigorous internal process by the manufacturer (Inova Diagnostics) based on:

• Carefully prepared and characterized aliquots (standards) with known or assigned concentrations of the target antibodies.
• Repeat measurements and statistical analysis for consistent and accurate assignment of FLU values.
• This is a standard practice for calibrating quantitative IVD assays, ensuring the device outputs accurate and traceable results.

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ACL TOP 970 CL: The ACL TOP 970 CL is a bench top, fully automated, random access analyzer designed specifically for in vitro diagnostic use by health care professionals in a clinical laboratory. The system provides results for both direct measurements and calculated parameters.
HemosIL CL Anti-Cardiolipin IgM: HemosIL CL Anti-Cardiolipin IgM is a fully automated chemiluminescent immunoassay for the semi-quantitative measurement of anti-cardiolipin (aCL) IgM antibodies in human 3.2% or 3.8% citrated plasma on the ACL TOP 970 CL in the laboratory setting by a healthcare professional, as an aid in the diagnosis of Antiphospholipid Syndrome (APS) when used in conjunction with other laboratory and clinical findings. For use with adult population. For prescription use only.
HemosIL CL Anti-ß2 Glycoprotein-I IgM: HemosIL CL Anti-B2 Glycoprotein-I IgM is a fully automated chemiluminescent immunoassay for the semi-quantitative measurement of anti-B2 Glycoprotein-I (anti-B2GPI) IgM antibodies in human 3.2% or 3.8% citrated plasma on the ACL TOP 970 CL in the laboratory setting by a healthcare professional, as an aid in the diagnosis of Antiphospholipid Syndrome (APS) when used in conjunction with other laboratory and clinical findings. For use with adult population. For prescription use only.

ACL TOP 970 CL Instrument: The ACL TOP 970 CL is an instrument that integrates new chemiluminescent test capability similar to the ACL AcuStar, K083518.
HemosIL CL Anti-Cardiolipin IgM: HemosIL CL Anti-Cardiolipin IgM is a chemiluminescent two-step immunoassay consisting of magnetic particles coated with cardiolipin and human purified ß2GPI, which capture, if present, the aCL antibodies from the sample. After incubation, magnetic separation, and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgM antibody is added and may bind with the captured aCL IgM on the particles. After a second incubation, magnetic separation, and wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLU) by the ACL TOP 970 CL optical system. RLUs are directly proportional to the aCL IgM concentration in the sample.
HemosIL CL Anti-ß2 Glycoprotein-I IgM: HemosIL CL Anti-ß2 Glycoprotein-I IgM is a chemiluminescent two-step immunoassay consisting of magnetic particles coated with human purified ß2GPI, which capture, if present, the aß2GPI antibodies from the sample. After incubation, magnetic separation, and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgM antibody is added and may bind with the captured aß2GPI IgM on the particles. After a second incubation, magnetic separation, and wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLUs) by the ACL TOP 970 CL optical system. RLUs are directly proportional to the aß2GPI IgM concentration in the sample.

The provided text describes the 510(k) summary for the ACL TOP 970 CL instrument and two associated immunoassays, HemosIL CL Anti-Cardiolipin IgM and HemosIL CL Anti-β2 Glycoprotein-I IgM. The studies presented focus on analytical performance and comparability to predicate devices, rather than AI model performance or human-in-the-loop studies. Therefore, many of the requested elements pertaining to AI-driven diagnostic devices (such as expert adjudication, MRMC studies, or training set details for AI) are not applicable or cannot be extracted from this document.

However, I can extract information related to the acceptance criteria for the analytical performance of the assays and how that performance was demonstrated.

Here's a breakdown of the available information:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for these in vitro diagnostic devices are demonstrated through various analytical performance studies, focusing on precision, linearity, analytical sensitivity (LoD/LoQ), analytical specificity, and method comparison to predicate devices. The document does not explicitly state pre-defined acceptance thresholds for each parameter (e.g., minimum CV for precision, minimum slope for linearity). Instead, it presents the results of these studies, implying that the observed performance met internal or regulatory acceptance.

HemosIL CL Anti-Cardiolipin IgM

HemosIL CL Anti-β2 Glycoprotein-I IgM

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

• Precision Study (Test Set):
  • HemosIL CL Anti-Cardiolipin IgM & Anti-β2 Glycoprotein-I IgM: 5 plasma samples (3 positive, 2 negative) and 2 levels of controls. Each material was run in duplicate, twice per day over 20 days.
• Reproducibility Study (Test Set):
  • HemosIL CL Anti-Cardiolipin IgM & Anti-β2 Glycoprotein-I IgM: 4 plasma samples (3 positive, 1 negative for Anti-Cardiolipin IgM; 3 positive for Anti-β2 Glycoprotein-I IgM) and 2 levels of controls. Each material tested in triplicate, twice a day for 5 days, totaling 30 replicates per level.
• Analytical Sensitivity (LoD/LoQ):
  • Specific sample numbers for LoD/LoQ for new reagent lots are not detailed, but samples prepared by combining Ab-positive and normal donor plasma were used.
• Linearity:
  • For each assay, samples were prepared by diluting a high antibody plasma sample with a negative antibody plasma sample to create required concentrations. Each level was measured in seven replicates.
• Normal Reference Range:
  • 100 citrated plasma normal donor samples.
• Method Comparison:
  • HemosIL CL Anti-Cardiolipin IgM: N = 131 samples.
  • HemosIL CL Anti-β2 Glycoprotein-I IgM: N = 123 samples.
• APS Outcome Study (Diagnostic Performance):
  • HemosIL CL Anti-Cardiolipin IgM: N = 500 samples.
  • HemosIL CL Anti-β2 Glycoprotein-I IgM: N = 503 samples (indicated by the sum of Positive/Negative categories: 63+17+128+295=503).

Data Provenance: The document does not specify the country of origin for the data or whether the studies were retrospective or prospective, though typical clinical performance studies for diagnostic devices are usually prospective or utilize carefully curated samples. Reproducibility studies were conducted at "3 external sites."

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

This information is not provided. For these in vitro diagnostic immunoassays, the "ground truth" for the analytical performance studies (precision, linearity, etc.) is the quantitative measurement itself, validated against established laboratory methods or reference materials. For the "APS Outcome Study," the ground truth is "APS disease classification per 2006 International Consensus Statement from Miyakis et al." This classification is typically based on a combination of clinical and laboratory findings, interpreted by clinicians, but the specific number and qualifications of experts involved in this classification for the study samples are not detailed.

4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set

Not applicable, as this is an in vitro diagnostic device measuring analyte concentrations, not an imaging AI relying on expert interpretations or adjudications. The diagnostic performance (sensitivity/specificity) is compared against pre-defined clinical classification criteria (Miyakis et al. 2006).

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 document describes an in vitro diagnostic device (immunoassay and analyzer), not an AI-driven imaging diagnostic device. There is no mention of human readers or AI assistance in diagnostic interpretation.

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

The performance data provided (precision, linearity, sensitivity, specificity, method comparison) is the standalone performance of the device (instrument + assay). The device provides a semi-quantitative measurement of antibodies, which then aids in diagnosis when used "in conjunction with other laboratory and clinical findings." There is no "human-in-the-loop" component in the assay's direct operation or result generation as described beyond the healthcare professional performing the test.

7. The Type of Ground Truth Used

• Analytical Studies (Precision, Linearity, LoD/LoQ, Specificity): The ground truth is inherent to the nature of these highly controlled analytical tests. For example, for linearity, serially diluted samples with known concentrations are used. For interference, samples spiked with known interferents are used.
• Method Comparison: The ground truth is established by the measurements obtained from the predicate (reference) devices: HemosIL AcuStar Anti-Cardiolipin IgM (K092181) and HemosIL AcuStar Anti-β2 Glycoprotein-I IgM (K091556) on the ACL AcuStar (K083518).
• Normal Reference Range: Established by testing 100 samples from "normal donors."
• APS Outcome Study: "APS disease classification per 2006 International Consensus Statement from Miyakis et al." This is a consensus-based clinical classification criteria.

8. The Sample Size for the Training Set

Not applicable, as this is not an AI/machine learning device that requires a distinct training set. The "development" of the assays would involve internal R&D, but not a "training set" in the context of AI.

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

Not applicable, as there is no training set mentioned for an AI model. For the development/validation of the immunoassay itself, the "ground truth" for calibrators and controls would be established through careful analytical procedures, often traceable to international standards or reference materials, under strict quality control.

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The KRONUS IA-2 Autoantibody (IA-2Ab) ELISA Kit is for the qualitative determination of antibodies to Islet Antigen-2 (IA-2) in human serum. The KRONUS IA-2 Autoantibody (IA-2Ab) ELISA Kit may be useful as an aid in the diagnosis of Type 1 diabetes mellitus (autoimmune mediated diabetes). The KRONUS IA-2 Autoantibody (IA-2Ab) ELISA Kit is not to be used alone and is to be used in conjunction with other clinical and laboratory findings.

Not Found

This document is an FDA clearance letter for an in vitro diagnostic (IVD) device, specifically an ELISA kit. It does not contain information about an AI/ML-driven medical device study or its performance characteristics. Thus, most of the requested information regarding acceptance criteria, study design, ground truth establishment, and expert involvement for an AI medical device cannot be extracted from this document.

The document discusses the clearance of the KRONUS IA-2 Autoantibody (IA-2Ab) ELISA Kit (K220085) for the qualitative determination of antibodies to Islet Antigen-2 (IA-2) in human serum, to be used as an aid in the diagnosis of Type 1 diabetes mellitus.

Therefore, I cannot provide the requested information based on the provided text. The questions are specifically tailored for an AI/ML device study, not for an ELISA kit's regulatory clearance.

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The Aptiva Celiac Disease IgG Reagent is an immunoassay utilizing particle-based multi-analyte technology for the semiquantitative determination of anti-tissue transglutaminase IgG autoantibodies and anti-deamidated gliadin peptide IgG autoantibodies in human serum. The presence of these antibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of celiac disease and dermatitis herpetiformis, particularly in patients with selective IgA deficiency.

The Aptiva Celiac Disease IgG Reagent is intended for use with the Inova Diagnostics Aptiva System.

The Aptiva Celiac Disease IgG reagent utilizes particle based multi-analyte technology (PMAT) in a cartridge format. Each analyte (tissue transglutaminase [tTG] and deamidated gliadin peptide [DGP]) in the Aptiva Celiac Disease IgG reagent is a solid phase immunoassay utilizing fluorescent microparticles. This technology allows each of the two analytes, along with a human IgG capture antibody (IgG Control Microparticle), to be coated onto three uniquely recognizable paramagnetic microparticles, which are combined into one tube.

The Aptiva instrument is a fully automated, random access analyzer. This platform is a closed system with continuous load and random-access capabilities that processes the samples, runs the reagent and reports results. It includes liquid handling hardware, optical module (OM), and integrated computer with proprietary software and touch screen user interface.

The two analyte microparticles, along with the control microparticle, are stored in the reagent cartridge under conditions that preserve the proteins in their reactive states. When the assay cartridge is ready to be used for the first time, the reagent tube seals are pierced using the cartridge lid. The reagent cartridge is then loaded onto the Aptiva instrument, where the microparticles are automatically rehydrated using buffer located within the cartridge.

A patient's serum is diluted 1:23 with Aptiva system rinse by the instrument in a disposable cuvette. A small amount of the diluted sample is combined with assay buffer and the microparticle suspension in a second cuvette, and mixed (final serum dilution: 1:230). This reaction cuvette is incubated for 9 ½ minutes at 37°C. The cuvette is then exposed to a small magnet that holds the microparticles in place. The liquid is aspirated, and the microparticles are resuspended as system rinse is added to the cuvette and the magnet is removed. This wash cycle is repeated one more time. During the third wash, no system rinse is added after the aspiration step. After the third wash, phycoerythrin conjugated polyclonal anti-human lgG (known as PE Tracer IgG) is added to the microparticles in the cuvette, and mixed. Again, the cuvette is incubated for 9 ½ minutes at 37℃. Three wash steps, as described above, are performed on the microparticles. Following the wash steps, the microparticles are transferred to the of the instrument, where a charge coupled device (CCD) camera takes multiple images in order to identify and count the three unique microparticle regions, as well as determine the amount of conjugate on the microparticles. The control microparticle, a third particle, coated with goat anti-human IgG, is included in the reagent in as a control to flag low concentrations of IgG the patient serum sample as an assay verification step. The median fluorescent intensity (MFI) is proportional to the amount of PE Tracer that is bound to the human IgG, which is proportional to the amount of IgG antibodies bound to the corresponding microparticle regions.

For quantitation, the DGP IgG and tTG IgG assays (together as part of the Aptiva Celiac Disease IgG Reagent) each utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge RFID tag. Every new lot of reagent cartridge must be calibrated before first use with the reagent specific calibrators. Based on the results obtained with the calibrators included in the Aptiva Celiac Disease IgG Calibrator kit (sold separately), an instrument specific Working Curve is created for each assay, which is used to calculate reported fluorescent light units (FLU) from the median fluorescent intensity (MFI) instrument signal obtained for each sample, on each of the two assays within the reagent.

Aptiva Celiac Disease IgG Calibrators and Aptiva Celiac Disease IgG Controls are sold separately.

The Aptiva Celiac Disease IgG Reagent kit contains the following materials:

One (1) Aptiva Celiac Disease IgG Reagent Cartridge, containing the following reagents for 200 determinations:

• a. Aptiva Celiac Disease IgG microparticle containing 3 unique microparticle regions coated with recombinant tissue transglutaminase, deamidated gliadin peptide, or goat antihuman IgG antibody.
• b. Assay buffer - colored pink, containing protein stabilizers and preservatives.
• C. PE Tracer IgG - phycoerythrin (PE) labeled anti-human IgG antibody, containing buffer, protein stabilizers and preservative.
• ð. Rehydration Buffer - containing protein stabilizers and preservatives.

This document describes the analytical and clinical performance of the Aptiva Celiac Disease IgG Reagent, an immunoassay for the semi-quantitative determination of anti-tissue transglutaminase IgG autoantibodies (tTG IgG) and anti-deamidated gliadin peptide IgG autoantibodies (DGP IgG) in human serum. This device is intended as an aid in the diagnosis of celiac disease and dermatitis herpetiformis.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Acceptance Criteria and Reported Device Performance

The document presents several analytical performance characteristics and their corresponding acceptance criteria, along with the reported performance values. The primary clinical acceptance criteria are related to sensitivity and specificity, and the agreement with a predicate device.

2. Sample Sizes and Data Provenance

• Test Set (Clinical Validation Set): A total of 515 characterized samples.
  • 171 samples from celiac disease patients.
  • 20 samples from patients with IgA deficient celiac disease.
  • 34 dermatitis herpetiformis patients.
  • 290 control samples from patients with various types of autoimmune and infectious diseases.
• Data Provenance: The document does not explicitly state the country of origin. Given it's an FDA submission, it's typically a mix of US and possibly international data, but this is not specified. The studies are retrospective as they use "characterized samples" from a "cohort."
• Precision and Reproducibility Studies: Between 75 to 80 replicates per sample for repeatability/precision and reproducibility studies. These numbers are for analytical performance, not clinical.
• LoB, LoD, LoQ: 120 data points were generated for each assay on each reagent lot for LoB and LoD studies. For LoQ, 120 data points per assay per reagent lot.
• Linearity: The number of dilutions and duplicates used is stated (e.g., 4 human serum samples for DGP IgG and 3 for tTG IgG serially diluted, assayed in duplicates).
• Interference: 3 human serum specimens (one positive, one near cut-off, one negative) were tested for each assay.
• Sample Stability: 6 samples for DGP IgG, 7 for tTG IgG (tested in duplicates).
• Reagent Stability: 3 lots of microparticle beads and 3 lots of PE Tracer IgG for accelerated stability. Real-time stability data from 2 different lots.
• Reference Range/Cut-off Establishment:
  • Reference Population: 192 subjects from various autoimmune/infectious disease groups (e.g., Crohn's Disease, Autoimmune Thyroid Disease, Rheumatoid Arthritis).
  • Celiac Disease Patients: 11 diagnosed celiac disease (CD) patient specimens were assayed to aid in cut-off determination.
  • Apparently Healthy Donors (Expected Values): 120 blood donors.

3. Number of Experts and Qualifications

• The document does not mention the number of experts used to establish the ground truth for the test set, nor their specific qualifications. It refers to "characterized samples" and "diagnosed celiac disease (CD) patient specimens," implying a pre-existing clinical diagnosis, but the process of how these characterizations were definitively made (e.g., biopsy confirmation, clinical consensus, expert review) is not detailed for the test set.

4. Adjudication Method

• The document does not describe any specific adjudication method for the test set. The samples are described as "characterized," suggesting that their disease status was already established prior to their use in the study, likely through standard clinical diagnostic procedures, but no expert review or consensus process for this specific study's set is detailed.

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

• Not Applicable. This is an in-vitro diagnostic (IVD) device, specifically an immunoassay for determining autoantibodies in serum. MRMC studies are typically performed for imaging diagnostic devices (e.g., AI for radiology) where human readers (e.g., radiologists) interpret images with and without AI assistance. This document describes the performance of a lab test that outputs a quantitative result (FLU) and a qualitative interpretation (positive/negative) and does not involve human interpretation of complex data in the same way an imaging AI device would.

6. Standalone Performance

• Yes, standalone performance was done. The entire study report describes the standalone performance of the Aptiva Celiac Disease IgG Reagent without human intervention beyond performing the test and interpreting the quantitative results per the device's defined cut-offs. The sensitivity, specificity, and agreement with predicate devices are measures of its standalone performance.

7. Type of Ground Truth Used

• The ground truth for the clinical validation was based on clinical diagnosis/characterization of the patient samples.
  • For celiac disease and dermatitis herpetiformis patients, they were "diagnosed" or "characterized." While not explicitly stated, the gold standard for celiac disease diagnosis usually involves intestinal biopsy with characteristic changes, alongside clinical symptoms and serology.
  • For the control group, patients were characterized with "various types of autoimmune and infectious diseases," implying a clinical diagnosis for these conditions to confirm they are not celiac disease.
  • For the cut-off determination, "diagnosed celiac disease (CD) patient specimens" were used in conjunction with a reference population.

8. Sample Size for the Training Set

• The document does not specify a separate "training set" in the context of an AI/machine learning model. This device is an immunoassay, which relies on chemical reactions and optical detection, not on a machine learning algorithm trained on large datasets in the conventional sense. The "training" in this context refers to the development and optimization of the assay's reagents and parameters, and the establishment of master curves and cut-offs. The data used for calibration and master curve generation (e.g., "in-house Master Curve Standards with assigned FLU values run multiple times," "Calibrators included in the Aptiva Celiac Disease IgG Calibrator kit") effectively serve a similar purpose to training/calibration data in general analytical chemistry.

9. How Ground Truth for Training Set was Established

• Given this is an immunoassay, the concept of "ground truth" for a training set (as defined for AI/ML) is not directly applicable. Instead, the assay's performance and "ground truth" are established through:
  • Calibration: Using Master Curve Standards with "assigned FLU values" (likely determined through extensive in-house characterization and reference methods).
  • Controls: Using Aptiva Celiac Disease IgG Controls with "lot specific values assigned."
  • Reference Materials: The development of the assay's antigens (recombinant tTG and deamidated gliadin peptide) and antibodies would have involved rigorous characterization against known reference materials and clinical samples during the assay development stages to ensure they correctly bind to their target autoantibodies.
  • Cut-off determination: As mentioned in point 7, this involved a reference population of 192 subjects and 11 diagnosed celiac disease patients to establish the 5.00 FLU cut-off.

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The Aptiva Celiac Disease IgA Reagent is an immunoassay utilizing particle-based multi-analyte technology for the semiquantitative determination of anti-tissue transglutaminase IgA autoantibodies and anti-deamidated gliadin peptide IgA autoantibodies in human serum. The presence of these autoantibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of celiac disease and dermatitis herpetiformis. The Aptiva Celiac Disease IgA Reagent is intended for use with the Inova Diagnostics Aptiva System.

The Aptiva Celiac Disease IgA reagent utilizes particle based multi-analyte technology (PMAT) in a cartridge format. Each analyte (tissue transglutaminase [tTG] and deamidated gliadin peptide [DGP]) in the Aptiva Celiac Disease IgA reagent is a solid phase immunoassay utilizing fluorescent microparticles. This technology allows each of the two analytes, along with a human IgA capture antibody (IgA Control Microparticle), to be coated onto three uniquely recognizable paramagnetic microparticles, which are combined into one tube.

The Aptiva instrument is a fully automated, random access analyzer. This platform is a closed system with continuous load and random-access capabilities that processes the samples, runs the reagent and reports results. It includes liquid handling hardware, optical module (OM), and integrated computer with proprietary software and touch screen user interface.

The two analyte microparticles, along with the control microparticle, are stored in the reagent cartridge under conditions that preserve the proteins in their reactive states. When the assay cartridge is ready to be used for the first time, the reagent tube seals are pierced using the cartridge lid. The reagent cartridge is then loaded onto the Aptiva instrument, where the microparticles are automatically rehydrated using buffer located within the cartridge.

A patient's serum is diluted 1:46 with Aptiva system rinse by the instrument in a disposable cuvette. A small amount of the diluted sample is combined with assay buffer and the microparticle suspension in a second cuvette, and mixed (final serum dilution: 1:230). This reaction cuvette is incubated for 9 ½ minutes at 37°C. The cuvette is then exposed to a small magnet that holds the microparticles in place. The liquid is aspirated, and the microparticles are resuspended as system rinse is added to the cuvette and the magnet is removed. This wash cycle is repeated one more time. During the third wash, no system rinse is added after the aspiration step. After the third wash, phycoerythrin conjugated polyclonal anti-human IgA (known as PE Tracer IgA) is added to the microparticles in the cuvette, and mixed. Again, the cuvette is incubated for 9 ½ minutes at 37℃. Three wash steps, as described above, are performed on the microparticles. Following the wash steps, the microparticles are transferred to the of the instrument, where a charge coupled device (CCD) camera takes multiple images in order to identify and count the three unique microparticle regions, as well as determine the amount of conjugate on the microparticles. A third particle, coated with goat antibodies, is present in the reagent as a control to flag low concentrations of IgA in the sample as an assay verification step. The median fluorescent intensity (MFI) is proportional to the amount of PE Tracer that is bound to the human IgA, which is proportional to the amount of IgA antibodies bound to the corresponding microparticle regions.

For quantitation, the DGP IgA and tTG IgA assays (together as part of the Aptiva Celiac Disease IgA Reagent) each utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge RFID tag. Every new lot of reagent cartridge must be calibrated before first use with the reagent specific calibrators. Based on the results obtained with the calibrators included in the Aptiva Celiac Disease IgA Calibrator kit (sold separately), an instrument specific Working Curve is created for each assay, which is used to calculate reported fluorescent light units (FLU) from the median fluorescent intensity (MFI) instrument signal obtained for each sample, on each of the two assays within the reagent.

Aptiva Celiac Disease IgA Calibrators and Aptiva Celiac Disease IgA Controls are sold separately.

The Aptiva Celiac Disease IgA Reagent kit contains the following materials:

One (1) Aptiva Celiac Disease IgA Reagent Cartridge, containing the following reagents for 250 determinations:

• a. Aptiva Celiac IgA microparticle containing 3 unique microparticle regions coated with recombinant tissue transglutaminase, deamidated gliadin peptide, or goat anti-human IgA antibody.
• b. Assay buffer - colored pink, containing protein stabilizers and preservatives.
• PE Tracer IgA phycoerythrin (PE) labeled anti-human IgA antibody, containing buffer, C. protein stabilizers and preservative.
• d. Rehydration Buffer - containing protein stabilizers and preservatives.

The provided text is a 510(k) Summary for the Aptiva Celiac Disease IgA Reagent, an in vitro diagnostic device. It describes the analytical and clinical performance of the device to demonstrate its substantial equivalence to predicate devices. It does not describe an AI/ML-based device, a comparative effectiveness study with human readers, or the establishment of ground truth by expert consensus. Therefore, most of the requested information cannot be extracted from this document as it pertains to AI/ML device studies.

However, I can extract the acceptance criteria and reported performance for analytical aspects of this specific in vitro diagnostic device, as well as details regarding sample size, data provenance, and the type of ground truth used for performance evaluation.

Acceptance Criteria and Reported Device Performance

The device under review is an in vitro diagnostic (IVD) test, not an AI/ML-based medical imaging device. As such, the acceptance criteria and performance evaluation are based on typical analytical validation parameters for immunological assays, such as precision, limit of detection, linearity, interference, and clinical sensitivity/specificity against established reference methods or patient diagnoses.

Table of Acceptance Criteria and Reported Device Performance:

Study Details:

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

   • Precision: 9 samples for DGP IgA, 10 samples for tTG IgA (run in duplicates, twice a day, for 20 days).
   • Reproducibility (Between Sites): 7 samples for DGP IgA and 6 samples for tTG IgA.
   • Reproducibility (Between Lots): 6 samples for DGP IgA and 6 samples for tTG IgA.
   • LoB, LoD, LoQ:
     • LoB: 8 blank samples. For each assay (DGP IgA & tTG IgA), on two reagent lots, run in replicates of 5, once per day for 3 days (120 data points per lot).
     • LoD & LoQ: 4 low-level samples for each assay (DGP IgA & tTG IgA). For each assay, on two reagent lots, run in replicates of 5, twice per day for 3 days (120 data points per assay per lot).
   • Linearity: 4 human serum samples for each assay, serially diluted and assayed in duplicates.
   • Interference: 3 human serum specimens (one positive, one near cutoff, one negative).
   • Sample Stability: 8 test samples for DGP IgA, 6 test samples for tTG IgA.
   • Clinical Performance (Validation Set): A total of 495 characterized samples.
     • 171 samples from celiac disease patients.
     • 34 dermatitis herpetiformis patients.
     • 290 control samples from patients with various types of autoimmune and infectious diseases (e.g., Rheumatoid Arthritis, Ulcerative Colitis, Crohn's Disease, Hepatitis C/B, Syphilis, Sjögren's Syndrome, Systemic Sclerosis, Autoimmune Gastritis, HIV, Systemic Lupus Erythematosus, Epstein-Barr Virus).
     • The document does not explicitly state the country of origin but implies data collection from clinical settings. It describes the use of "characterized samples" and "diagnosed celiac disease (CD) patient specimens," indicating that this was likely a retrospective collection of samples with established diagnoses.
   • Expected Values (Normal Population): 120 apparently healthy blood donors.
   • Method Comparison: All 495 samples from the clinical validation study were also used for method comparison against the predicate devices.

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

   • This is an IVD device, not an AI/ML imaging device. The "ground truth" for the test set (clinical validation cohort) was based on patient diagnoses (e.g., "celiac disease patients," "dermatitis herpetiformis," "control samples from patients with various types of autoimmune and infectious diseases"). Therefore, the ground truth was established by clinical diagnosis, which would typically be made by medical doctors/specialists based on relevant clinical findings and other laboratory tests, rather than by a specific number of experts reviewing image data. The document does not specify the number or qualifications of clinicians involved in establishing these diagnoses.

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

   • Not applicable, as this is an IVD test assessing biochemical markers, not an imaging device requiring expert adjudication of interpretations. The "ground truth" is the established clinical diagnosis of the patient.

4. 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 not an AI/ML imaging device, and no MRMC study was performed or is relevant to this type of IVD test.

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

   • The "standalone performance" of this device is represented by its analytical performance characteristics (precision, linearity, LoD, etc.) and its clinical sensitivity and specificity, where the device provides a quantitative result (FLU) to aid in diagnosis. There is no "human-in-the-loop" aspect to the performance of the device itself (it's an automated analyzer), though clinicians interpret its results in conjunction with other clinical findings.

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

   • The primary ground truth for the clinical performance evaluation was established clinical diagnoses of patients ("celiac disease patients," "dermatitis herpetiformis patients," and "control samples from patients with various types of autoimmune and infectious diseases"). This implicitly relies on a combination of clinical findings, potentially other laboratory tests, and possibly biopsy results (pathology) for definitive diagnoses like celiac disease. The document states, "The presence of these autoantibodies, in conjunction with clinical findings and other laboratory tests, is an aid in the diagnosis of celiac disease and dermatitis herpetiformis."

7. The sample size for the training set:

   • This device is an immunoassay (particle-based multi-analyte technology) operating on predefined Master Curves and calibrations. It does not use a "training set" in the sense of machine learning algorithms. The Master Curves and calibrations are established by the manufacturer through runs of precisely quantified standards (e.g., "in-house Master Curve Standards," "reagent specific calibrators"). The section "Quantitation and units of measure" describes how these curves are generated. For example, "Aptiva Celiac Disease IgA Master Curve Standards - DGP IgA" lists 6 standards with assigned FLU values. While these could be seen as "training data" for the device's internal quantitation function, it's not a machine learning model.

8. How the ground truth for the training set was established:

   • Not applicable in an AI/ML context. For this IVD device, the "ground truth" for its internal calibration (analogous to a training set for an AI model) is based on manufacturer-defined standards with assigned known values ("in-house Master Curve Standards with assigned FLU values"). These standards are run multiple times to generate the 4-parameter logistic (4PL) curve that quantifies the analyte concentration.

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The EUROIMMUN Anti-BP230-CF ELISA (IgG) test kit is intended for the qualitative or semi-quantitative determination of immunoglobulin class IgG antibodies against BP230 in human serum and plasma (K3-EDTA, Li+heparin, Na+-citrate). It is used as an aid in the diagnosis of bullous pemphigoid, in conjunction with other laboratory and clinical findings.

Not Found

This FDA 510(k) clearance letter pertains to an In Vitro Diagnostic (IVD) device, specifically an ELISA test for autoantibodies. The provided text does not contain the kind of information typically associated with the development and validation of an AI/ML-based medical device, which would usually include details about:

• Algorithms and machine learning models
• Training and test datasets (sizes, provenance, ground truth establishment)
• Expert review processes (number of experts, qualifications, adjudication)
• MRMC studies or standalone AI performance metrics

Therefore, I cannot provide a table of acceptance criteria and reported device performance, nor can I answer questions related to sample sizes, expert ground truth establishment, adjudication methods, MRMC studies, standalone performance, or training set details based on the provided text.

The document describes the regulatory clearance for the EUROIMMUN Anti-BP230-CF ELISA (IgG) test kit, which is a laboratory assay.

Here's what can be extracted from the document:

• Device Name: EUROIMMUN Anti-BP230-CF ELISA (IgG)
• Regulation Number: 21 CFR 866.5660
• Regulation Name: Multiple autoantibodies immunological test system
• Regulatory Class: Class II
• Product Code: OEG
• Indications for Use: The test kit is intended for the qualitative or semi-quantitative determination of immunoglobulin class IgG antibodies against BP230 in human serum and plasma. It is used as an aid in the diagnosis of bullous pemphigoid, in conjunction with other laboratory and clinical findings.

To answer the detailed questions about acceptance criteria and study data for an AI/ML device, a different type of regulatory submission document (e.g., a summary of safety and effectiveness data or a clinical study report) would be required.

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EliA Celikey IgG is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to tissue transglutaminase (tTG) in human serum and EDTA-plasma. EliA Celikey IgG is based on recombinant human tissue transglutaminase as antigen and is useful as an aid in the clinical diagnosis of patients with celiac disease in conjunction with other laboratory and clinical findings. EliA Celikey IgG uses the EliA IgG method on the instrument Phadia 2500/5000.

EliA GliadinDP IgA is intended for the in vitro semi-quantitative measurement of IgA antibodies directed to gliadin in human serum or plasma (Li-heparin, EDTA) to aid in the diagnosis of celiac disease in conjunction with other laboratory and clinical findings. EliA GliadinDP IgA uses the EliA IgA method on the instrument Phadia 2500/5000.

EliA GliadinDP IgG is intended for the in vitro semi-quantitative measurement of IgG antibodies directed to gliadin in human serum or plasma (Li-heparin, EDTA) to aid in the diagnosis of celiac disease in conjunction with other laboratory and clinical findings. EliA GliadinDP IgG uses the EliA IgG method on the instrument Phadia 2500/5000.

The method-specific reagents are identical with K062583 (EliA Celikey IgG) and K093459 (EliA Gliadin® IgA and EliA Gliadin® IgG), but are filled in containers specific for the Phadia 2500/5000 instrument. Each device consists of: Test Wells (EliA Celikey IgG Wells, EliA GliadinDP IgA Wells, EliA GliadinDP IgG Wells), EliA Sample Diluent, EliA IgG reagents (EliA IgG Conjugate, EliA IgG Calibrator Strips, EliA IgG Curve Control Strips, EliA IgG Calibrator Well), and EliA IgA reagents (EliA IgA Conjugate, EliA IgA Calibrator Strips, EliA IgA Curve Control Strips, EliA IgA Calibrator Well). The Phadia EliA Immunodiagnostic System is an automated system for immunodiagnostic testing. The EliA reagents are available as modular packages, each purchased separately. All packages are required to carry out EliA Celikey IgG and EliA GliadinDP IgA and EliA GliadinDP IgG tests.

The provided document is a 510(k) Premarket Notification from the FDA, detailing the substantial equivalence determination for the Phadia AB EliA Immunoassays (Celikey IgG, GliadinDP IgA, GliadinDP IgG) for use on the Phadia 2500/5000 instrument. The document primarily focuses on demonstrating that the performance of these assays on the new instrument platform is substantially equivalent to their performance on a previously cleared instrument (Phadia 250).

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

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

The document does not explicitly present a single table outlining "acceptance criteria" alongside "reported device performance" for the overall substantial equivalence determination. Instead, it details performance characteristics for various analytical aspects, and the acceptance criteria are implied by the ranges and thresholds specified for these studies. The primary "acceptance criteria" for the overall submission appear to be demonstrating equivalence to the predicate device and meeting specific statistical thresholds for precision and linearity.

However, based on the sections "M. Performance Characteristics (if/when applicable)" and "2. Comparison studies: - Instrument comparison C.", we can construct a table for the analytical performance and comparative study results:

Table: Acceptance Criteria (Implied) and Reported Device Performance

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

• Precision Test Set: The study used "a total of 21 runs (3 instruments x 7 runs)". Each sample was tested in "four replicates/run giving in total 84 replicates per sample." The number of distinct samples for precision is not explicitly stated, but multiple samples covering various concentrations are typically used (e.g., 5 samples in the EliA Celikey IgG table).
• Linearity Test Set: "Four patient serum samples (five for Celikey IgG)" were diluted and tested.
• Detection Limit Test Set: "One blank sample and three low level samples were measured in thirty-three and eleven replicates, respectively, in each of two runs." For Celikey IgG LoD, "6 low level samples and a total of 132 determinations" were used. For LoQ, "66 determinations of 3 low level samples."
• Method Comparison Test Set: "More than 100 samples (≥20% of the samples within ±25% of the medical decision point)" were run for each of the three EliA tests.
• Expected Values/Reference Range: 400 "apparently healthy subjects ... from a Caucasian population obtained from a blood bank."

Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. It is a 510(k) submission for a device, and the focus is on analytical performance and comparison to a predicate device, not primary clinical trial data of patient outcomes. The "Expected Values/Reference Range" suggests the use of existing blood bank samples, which typically implies retrospective use 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)

This information is not applicable to this type of device and study. The EliA Immunoassays measure specific antibodies (tTG IgG, Gliadin IgA, Gliadin IgG) in patient samples. The "ground truth" for the analytical studies (precision, linearity, detection limits, method comparison) is based on the quantitative concentration of these analytes as measured by the predicate device or a reference method, rather than subjective expert interpretation (like in imaging studies). For the reference range, the "ground truth" is simply the measured values in a defined healthy population.

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

This information is not applicable. Adjudication methods (like 2+1 or 3+1 for resolving discrepancies) are typically used in clinical studies where expert readers independently interpret data (e.g., medical images) and their interpretations need to be reconciled to establish a "ground truth" or reference standard. This document describes analytical and comparative studies for an in vitro diagnostic immunoassay, where quantitative measurements are the primary data.

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 information is not applicable. MRMC studies are primarily relevant for AI-powered diagnostic devices, particularly in medical imaging, where multiple human readers interpret cases, and the AI's impact on their diagnostic performance is assessed. This document pertains to an in vitro diagnostic immunoassay, not an AI-assisted diagnostic tool that aids human "readers."

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

Yes, this can be considered a standalone performance evaluation in the context of an immunoassay. The device (EliA Immunoassays on Phadia 2500/5000) operates as an automated system to semi-quantitatively measure antibody levels. The analytical performance studies (precision, linearity, LoD/LoQ) and the instrument comparison are essentially the "standalone" performance of the assay on the new platform. It's not an "algorithm only" in the sense of a software-only device, but the analytical steps are automated, and the reported values are direct outputs of the system. Human intervention relates to sample loading and equipment maintenance, not interpretation of raw data for diagnosis.

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

The "ground truth" for the performance studies described is primarily:

• Quantitative Analytical Values: For precision, linearity, LoD/LoQ, the ground truth is derived from the inherent nature of the samples at known or measured concentrations, often established by reference methods or highly characterized materials.
• Predicate Device Measurements: For the "Instrument Comparison," the results obtained from the previously cleared Phadia 250 instrument serve as the reference or "ground truth" against which the new Phadia 2500/5000 is compared to demonstrate substantial equivalence.
• Clinically Defined Healthy Population: For "Expected Values/Reference Range," the ground truth is simply the distribution of the analyte in a healthy population.

It's important to note that this 510(k) is for "adding previously cleared assays on a new instrument platform." This means the clinical utility and diagnostic performance (e.g., clinical sensitivity/specificity for celiac disease) of the assays themselves were already established and reviewed in the original 510(k) clearances (K062583 and K093459). The current submission leverages that prior clinical validation by demonstrating that the new instrument maintains equivalent analytical performance. Thus, the "clinical ground truth" for celiac disease diagnosis (e.g., biopsy confirmation, clinical outcomes) was established in those prior studies, not detailed here. The current submission's focus is on bridging the analytical performance to the new instrument.

8. The sample size for the training set

This document describes a 510(k) submission for an IVD immunoassay, not a machine learning or AI model. Therefore, there is no "training set" in the context of artificial intelligence/machine learning. The assays are based on established biochemical principles (antigen-antibody reactions, fluorescence detection), not on training data to learn patterns or parameters.

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

As there is no "training set" for an AI/ML model, this question is not applicable. The methods for establishing the performance characteristics are described in point 7 above.

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The Anti-tissue Transglutaminase ELISA (IgA) test kit is intended for the qualitative determination of IgA class antibodies against tissue transglutaminase in human serum and EDTA plasma (K3-EDTA, Lit-heparin, Na+citrate). It is used as an aid in the diagnosis of gluten-sensitive enteropathy (celiac disease) and dermatitis herpetiformis Duhring, in conjunction with other laboratory and clinical findings.

The Anti-tissue Transglutaminase ELISA (IgG) test kit is intended for the qualitative determination of IgC class antibodies against tissue transglutaminase in human serum and EDTA plasma (K3-EDTA, Li+-citrate). It is used as an aid in the diagnosis of gluten-sensitive enteropathy (celiac disease), in conjunction with other laboratory and clinical findings.

Not Found

This document is a 510(k) clearance letter from the FDA for an In Vitro Diagnostic (IVD) device, specifically an ELISA test for anti-tissue transglutaminase antibodies. These types of regulatory documents typically do not contain the detailed study information (acceptance criteria, specific performance metrics, sample sizes, expert qualifications, etc.) that would be found in a clinical trial report or a submission summary.

The letter explicitly states: "We have reviewed your Section 510(k) premarket notification... and have determined the device is substantially equivalent...". This determination of substantial equivalence relies on the manufacturer providing adequate data, but the letter itself does not present that data in a public-facing way.

Therefore, I cannot extract the requested information from the provided text. The document is an FDA clearance letter and not a detailed clinical study report.

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The KRONUS Steroid 21-Hydroxylase Autoantibody (21-OHAb) ELISA Kit is for the qualitative determination of antibodies to steroid 21-hydroxylase (21-OH) in human serum. The Steroid 21-Hydroxylase Autoantibody (21-OHAb) ELISA Kit is useful as an aid in the diagnosis of autoimmune adrenal disease, whether expressed as autoimmune Addison's disease (isolated) or Addison's disease as part of the more complex autoimmune polyglandular syndrome (APS), type I or II. The assay result is to be used in conjunction with other clinical and laboratory findings and is not a substitute for functional testing required to diagnose adrenal insufficiency.

Not Found

I am sorry, but the provided text only contains an FDA approval letter and an "Indications for Use" statement for the KRONUS Steroid 21-Hydroxylase Autoantibody (21-OHAb) ELISA Kit. It does not contain any information regarding acceptance criteria, study details, sample sizes, ground truth establishment, or expert qualifications for a device performance study.

Therefore, I cannot fulfill your request to describe the acceptance criteria and the study that proves the device meets them based on the given text.

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