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For in vitro diagnostic and laboratory professional use.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator is a chemiluminescent immunoassay intended for the qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma (K2-EDTA and K3-EDTA) samples collected on or after 15 days post-symptom onset using the VITROS ECi/ECiO/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator

For use in the calibration of the VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems for the in vitro qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is a qualitative chemiluminescent immunoassay performed on the VITROS Systems (VITROS ECi/ECiO Immunodiagnostic System, VITROS 3600 Immunodiagnostic System, VITROS 5600 Integrated System and VITROS XT 7600 Integrated System) providing fully automated random-access testing.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is performed using the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls on the VITROS Systems.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack is supplied as ready to use and contains:

• 100 wells coated with 100ng/well of recombinant SARS-CoV-2 spike antigen derived from human cells.
• 18.0 mL assay reagent (buffer with bovine protein stabilizers and antimicrobial agent)
• 20.4 mL conjugate reagent [anti-human IgG (murine monoclonal) conjugated to horseradish peroxidase, 5ng/mL] in buffer with bovine protein stabilizers and antimicrobial agent.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator contains:

• 2 vials of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 1gG Calibrator 0 (anti-SARS-CoV-2 IgG in anti-SARS-CoV-2 IgG negative human serum with antimicrobial agent, 1 mL)
• Lot calibration card
• Protocol card
• 8 calibrator bar code labels

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls contain:

• 3 sets of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Controls 1 and 2 (defibrinated human plasma with anti-microbial agent, 2 mL). Control 1 is non-reactive and Control 2 is reactive

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG test is designed for use on the VITROS Systems. The VITROS Systems use the following ancillary reagents (general purpose reagents):

• VITROS Immunodiagnostic Products Signal Reagent
• VITROS Immunodiagnostic Products Universal Wash Reagent

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

Device: VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Reagent Pack, VITROS Immunodiagnostic Products Anti-SARS-CoV-2 IgG Calibrator (Chemiluminescent Immunoassay)

Purpose: Qualitative detection of IgG antibodies to SARS-CoV-2 in human serum and plasma, intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

1. Table of Acceptance Criteria and Reported Device Performance

The document describes the performance of the device rather than explicitly stating pre-defined acceptance criteria in a dedicated table. However, we can infer the implicit acceptance criteria from the observed results and the FDA's decision to grant the De Novo request.

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For in vitro diagnostic and laboratory professional use.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack when used in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator is a chemiluminescent immunoassay intended for the qualitative detection of total antibodies to SARS-CoV-2 in human serum and plasma (K-EDTA. K-EDTA and lithium heparin) samples collected on or after 15 days post-symptom onset using the VITROS ECi/ECiQ/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems. The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is intended for use as an aid in identifying individuals with an adaptive immune response to SARS-CoV-2, indicating recent or prior infection.

For use in the calibration of the VITROS ECi/ECiO/3600 Immunodiagnostic Systems and the VITROS 5600/XT 7600 Integrated Systems for the in vitro qualitative detection of total antibodies to SARS-CoV-2 in human serum and plasma.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is a qualitative chemiluminescent immunoassay performed on the VITROS Systems (VITROS ECi/ECiQ Immunodiagnostic System, VITROS 3600 Immunodiagnostic System, VITROS 5600 Integrated System and VITROS XT 7600 Integrated System) providing fully automated random-access testing.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is performed using the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack in combination with the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator and the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls on the VITROS Systems.

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack is supplied as ready to use and contains:

• . 100 coated wells (streptavidin, bacterial; binds ≥3 ng biotin per well; biotin recombinant SARS-CoV-2 antigen 0.1 ug/mL)
• 6.0 mL assay reagent (buffer with bovine protein stabilizers and antimicrobial agent) .
• . 16.2 mL conjugate reagent (HRP-recombinant SARS-CoV-2 antigen) in buffer with bovine protein stabilizers and antimicrobial agent

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator contains:

• . 2 vials of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator (anti-SARS-CoV-2 in anti-SARS-CoV-2 negative human plasma with antimicrobial agent, 1 mL)
• . Lot calibration card
• . Protocol card
• . 8 calibrator bar code labels

The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls contain:

• . 3 sets of VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Controls 1 and 2 (defibrinated human plasma with anti-microbial agent, 2 mL). Control 1 is non-reactive and Control 2 is reactive.
  The VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is designed for use on the VITROS Systems. The VITROS Systems use the following ancillary reagents (general purpose reagents):
• . VITROS Immunodiagnostic Products Signal Reagent
• VITROS Immunodiagnostic Products Universal Wash Reagent .

The document describes the evaluation of the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Calibrator, a chemiluminescent immunoassay intended for qualitative detection of total antibodies to SARS-CoV-2.

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

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

The document does not explicitly state "acceptance criteria" for the clinical performance in a single, clear table with pass/fail thresholds. However, the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) are the key clinical performance metrics presented. The FDA's decision to grant De Novo status implies that the reported performance met their internal criteria for safety and effectiveness for its intended use.

Here's a summary of the reported clinical performance:

Note: The PPA for samples collected early (0-7 days and 8-14 days post-symptom onset) is considerably lower (e.g., 36.00% to 44.00% for 0-7 days), reflecting the time required for antibody development. The indication for use specifies "samples collected on or after 15 days post-symptom onset," making the PPA for ≥15 days the most relevant for the primary intended use.

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

• Test Set Sample Size:

  • PPA (Clinical Sensitivity Equivalent): 296 samples from individuals with prior SARS-CoV-2 positive RT-PCR results were initially acquired. However, the "Number of Subjects Tested" varies slightly per analyzer, typically around 282-286 for individual system reporting, and 237-239 for the ≥15 days post-symptom onset group which is the most relevant for the device's claims.
  • NPA (Clinical Specificity Equivalent): 513 presumed SARS-CoV-2 negative samples collected prior to the COVID-19 pandemic. The "Presumed Negative" count also varies slightly per analyzer, typically around 505-511.

• Data Provenance:

  • Country of Origin: All samples were collected within the United States.
  • Retrospective or Prospective: The samples were collected retrospectively. Population 1 (positive samples) was collected between April 2020 and April 2021. Population 2 (negative samples) was collected prior to December 2019.

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 is an in vitro diagnostic device for antibody detection, not an imaging AI system. Therefore, the "ground truth" for the clinical study was established by RT-PCR test results for SARS-CoV-2 infection (for positive samples) and collection of samples prior to the COVID-19 pandemic (for negative samples). There is no mention of human experts (e.g., pathologists or radiologists) adjudicating the ground truth for this type of test.

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

Not applicable for this type of in vitro diagnostic test where RT-PCR is the comparator and pre-pandemic samples define the negative group. Discrepancy resolution with expert radiologists would be relevant for imaging-based AI studies, not serology tests.

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

Not applicable. This is an in vitro diagnostic (IVD) device for laboratory use, not an AI-assisted diagnostic tool for human readers (e.g., radiologists interpreting images). Its performance is evaluated as a standalone laboratory test.

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

Yes, the clinical performance (PPA and NPA) presented for the VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total test is its standalone performance as an automated laboratory assay. There is no human-in-the-loop component for the interpretation or usage of the result beyond the laboratory professional's decision to report the qualitative positive/negative result.

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

• For Positive Samples (PPA): Ground truth was established by prior SARS-CoV-2 positive RT-PCR test results. The document states, "...using a comparator that FDA determined is appropriate (RT-PCR test)."
• For Negative Samples (NPA): Ground truth was established by collection date prior to the widespread outbreak of COVID-19 (i.e., prior to December 2019), deeming them "presumed SARS-CoV-2 negative samples."

8. The sample size for the training set

This document describes the validation of a commercial in vitro diagnostic (IVD) product, not an AI/machine learning model where a distinct 'training set' of patient data in the typical AI sense would be used to train the algorithm. The "training" of this device involves the development and optimization of the chemical reagents, assay parameters, and cutoff values performed internally by the manufacturer (Ortho-Clinical Diagnostics).

The closest equivalent to a "training" activity described in the context of setting the device's operational parameters is the Assay Cut-Off determination study (page 12-13). This study used:

• "a collection of negative samples collected prior to the COVID-19 pandemic"
• "samples collected from individuals with a prior SARS-CoV-2 RT-PCR positive result."

The specific numbers of these samples for the cutoff determination are not explicitly stated, but are implied to be part of the broader pool of samples available to the manufacturer during development. The ROC curve analysis was performed on these samples to optimize sensitivity and specificity at the S/C = 1.00 cutoff.

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

As noted in point 8, this isn't an AI model with a conventional training set. For the "samples" used in the Assay Cut-Off determination (analogous to internal optimization/training data):

• Negative Ground Truth: Established by "negative samples collected prior to the COVID-19 pandemic."
• Positive Ground Truth: Established by "samples collected from individuals with a prior SARS-CoV-2 RT-PCR positive result."

This implies a similar method to the clinical validation set for establishing true positive and true negative status, but performed during the device development phase to define the S/C cutoff.

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VITROS Immunodiagnostic Products 25-OH Vitamin D Total Reagent Pack:

For in vitro diagnostic use only

For the quantitative measurement of total 25-OH vitamin D in human serum using the VITROS ECi/ECiQ Immunodiagnostic Systems, the VITROS 3600 Immunodiagnostic System and the VITROS 5600 Integrated System.

The results of the VITROS 25-OH Vitamin D Total assay are used in the assessment of Vitamin D sufficiency. Assay results may be used in conjunction with other clinical or laboratory data to assist the clinician in patient management.

VITROS Immunodiagnostic Products 25-OH Vitamin D Total Calibrators:

For in vitro diagnostic use only.

For use in the calibration of the VITROS ECi/ECiQ Immunodiagnostic Systems, the VITROS 3600 Immunodiagnostic Systems and the VITROS 5600 Integrated System for the quantitative measurement of total 25-OH vitamin D in human serum.

The VITROS Immunodiagnostic Products Vitamin D test system comprises three main elements:

• 1. The VITROS Immunodiagnostic range of products. In this case the VITROS Immunodiagnostic Products 25-OH Vitamin D Total Reagent Pack and the VITROS Immunodiagnostic Products 25-OH Vitamin D Total Calibrators are required to perform a VITROS Vitamin D test.
• The VITROS Immunodiagnostic and Integrated Systems: Instrumentation, which 2. provides automated use of the immunoassay kits.

The VITROS ECi/ECiQ Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919). This product was updated to the VITROS ECiQ Immunodiagnostic System by addition of a flat panel monitor with an accompanying articulating arm, cosmetic changes to the instrument cabinetry, and with FDA notification in January of 2004.

The VITROS 3600 Immunodiagnostic System: Instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K083173).

The VITROS 5600 Integrated System: Instrumentation, which provides automated use of the immunoassay kits. The VITROS Integrated System was cleared for market by a separate 510(k) pre-market notification (K081543).

• 3. Common reagents used by the VITROS System in each assay: The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 Reagent Pack and VITROS Immunodiagnostic Products Total T3 Calibrators 510(k) premarket notification (K964310).
     The VITROS Immunodiagnostic and Integrated Systems and common reagents are dedicated specifically for use only with the VITROS Immunodiagnostic Products range of immunoassay products.

The provided 510(k) summary describes the acceptance criteria and performance data for the VITROS® Immunodiagnostic Products 25-OH Vitamin D Total Reagent Pack and Calibrators.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a single, consolidated table with pass/fail remarks. Instead, it presents performance study results. The implied acceptance criteria are the demonstrated performance characteristics (e.g., precision, linearity, limit of detection, specificity, and method comparison results meeting statistical thresholds).

Table: Implied Acceptance Criteria and Reported Device Performance

• ECI/ECIQ System 1 Lot 1: 5.5-15.3%
• ECI/ECIQ System 2 Lot 2: 5.4-16.4%
• 3600 System 1 Lot 1: 6.0-16.5%
• 3600 System 1 Lot 3: 4.8-15.8%
• 5600 System 1 Lot 2: 5.6-12.8% |
  | Linearity/Measuring Range | Assay should be linear across the claimed measuring range. | Linear from 12.8 to 126 ng/mL (32.0 to 315 nmol/L). |
  | Limit of Detection (LoD) | LoD should be adequately low for clinical utility. | 8.64 ng/mL (21.6 nmol/L) (with 10% bias at indicated concentrations in 25-OH Vitamin D concentrations of 30-80 ng/mL, with the exception of Paricalcitol (Zemplar). |
  | Specificity (Cross-Reactivity) | Cross-reactivity should be characterized and acceptable. | 25-OH Vitamin D2: 104.9%
  25-OH Vitamin D3: 98.9%
  (Other listed substances showed lower or context-dependent cross-reactivity/bias) |
  | Method Comparison (Correlation with Predicate) | Strong correlation (high 'r' value) and acceptable slopes/intercepts compared to predicate device. | VITROS 5600 vs IDS-iSYS: r = 0.92, Slope CI (0.86-1.12), Intercept CI (-10.2 to -0.53)
  VITROS 3600 vs IDS-iSYS: r = 0.93, Slope CI (0.96-1.22), Intercept CI (-12.4 to -2.95)
  VITROS ECi/ECiQ vs IDS-iSYS: r = 0.94, Slope CI (0.86-1.09), Intercept CI (-14.2 to -4.69) |

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

• Precision: 3 patient samples and 1 commercial control sample per system/lot condition. Each sample tested as 2 replicates per day, on at least 20 different days (total 80 observations per sample per system/lot combination).
• Linearity: Two pools of patient samples (low and high) were used to create 7 intermediate pools.
• Limit of Detection: 1 blank and 6 low-level samples, with 700 determinations in total.
• Specificity (Interference/Cross-reactivity): Patient samples near 30 ng/mL and 80 ng/mL Vitamin D. The exact number of individual samples for interference testing is not specified, but the cross-reactivity table shows results for specific compounds.
• Method Comparison: A minimum of 117 human serum samples were used.
• Reference Range: 399 apparently healthy adults.
• Data Provenance:
  • For the reference range study, samples came from individuals in the North, South, and Central regions of the United States, collected in both summer and winter. This indicates prospective collection of samples specifically for this study.
  • For other studies (precision, linearity, method comparison), the document mentions "patient samples" and "human serum samples." The specific country of origin or whether these were purely retrospective or prospectively collected is not explicitly stated, but they are clearly human-derived samples.

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

Not applicable. For in vitro diagnostic (IVD) assays like this one, "ground truth" is typically established by reference methods or comparison to a legally marketed predicate device, rather than expert consensus on images or interpretations. The product measures a specific analyte concentration.

4. Adjudication method for the test set

Not applicable. This is an IVD device for quantitative measurement of a biomarker, not a diagnostic imaging device requiring expert adjudication of interpretations.

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

Not applicable. This is an in vitro diagnostic (IVD) device, not an AI-assisted diagnostic imaging or interpretation device that would involve human readers.

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

Yes, the device is a standalone in vitro diagnostic (IVD) system. Its performance (e.g., precision, linearity, limit of detection, and quantitative measurements in method comparison studies) represents the "algorithm only" performance, as it directly quantifies 25-OH Vitamin D in human serum samples on automated immunodiagnostic systems without human interpretation of results influencing the measurement itself.

7. The type of ground truth used

The "ground truth" for this quantitative assay is established by:

• Reference measurements/Predicate Device Comparison: The method comparison study uses a legally marketed predicate device, the IDS-iSYS® 25-Hydroxy Vitamin D Assay, as the reference for comparison, and demonstrates substantial equivalence.
• Internal analytical validation: Performance claims (precision, linearity, LoD/LoQ, specificity) are established through rigorous analytical testing against recognized CLSI guidelines, implying accepted analytical standards for correctness.

8. The sample size for the training set

The document does not explicitly mention "training set" or "validation set" in the context of an algorithm. For IVD devices, a "training set" in the machine learning sense is not typically used. Instead, the analytical performance (precision, linearity, etc.) is established using various samples, and calibration is performed using specific calibrators.

• The linearity study used two pools of patient samples.
• The precision study used patient samples and commercial controls.
• The specificity studies used patient samples.

These samples are used to characterize the device's performance, not to "train" an algorithm.

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

Not applicable, as a "training set" in the machine learning sense for an algorithm is not described. For the types of samples used in analytical studies:

• Patient samples: Their ground truth would be their actual 25-OH Vitamin D concentration, as measured by a highly accurate or reference method at the time of study or by the predicate device (as in the method comparison).
• Commercial control samples: These have assigned target values for specific analytes, often established through an internal reference method or inter-laboratory consensus.

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VITROS Immunodiagnostic Products TSH Reagent Pack
For the in vitro quantitative measurement of thyroid stimulating hormone (TSH) in human serum and plasma (EDTA or Heparin) using the VITROS ECi/ECIQ Immunodiagnostic Systems, VITROS 3600 Immunodiagnostic System and VITROS 5600 Integrated System to aid in the differential diagnosis of thyroid disease.

VITROS Immunodiagnostic Products TSH Calibrators
For in vitro use in the calibration of the VITROS ECi/ECIQ Immunodiagnostic Systems, VITROS 3600 Immunodiagnostic System and VITROS 5600 Integrated System for the quantitative measurement of thyroid stimulating hormone (TSH) in human serum and plasma (EDTA or Heparin).

VITROS 3600 Immunodiagnostic System
For use in the in vitro quantitative, semi-quantitative, and qualitative measurement of a variety of analytes of clinical interest, using VITROS Immunodiagnostic Products Reagents.

The VITROS Immunodiagnostic Product TSH Reagent and Calibrators is intended for use on the VITROS 3600 Immunodiagnostic System.

The VITROS 3600 Immunodiagnostic System utilizes the existing VITROS ECi/ECIQ Immunodiagnostic System technology (K962919) and adds increased operating efficiency and throughput by utilizing the same immunoassay hardware and software subsystem design as the VITROS 5600 Integrated System (K081543). All VITROS Immunodiagnostic Product technology, methodologies and analytical methods currently available on the existing two systems (VITROS ECi/ECIQ Immunodiagnostic System and VITROS 5600 Integrated System) are available on the new VITROS 3600 Immunodiagnostic System.

This document describes a Special 510(k) submission for the VITROS Immunodiagnostic Products TSH Reagent Pack, TSH Calibrators, and VITROS 3600 Immunodiagnostic System. The primary purpose of this submission is to notify FDA of the modification to allow the existing TSH Reagent Pack and Calibrators to be used with the new VITROS 3600 Immunodiagnostic System.

The information provided focuses on the substantial equivalence of the modified device to a previously cleared predicate device (K081543) and does not contain detailed primary study data or acceptance criteria typically found in initial device clearance submissions. Therefore, a comprehensive table of acceptance criteria and reported device performance directly from a new study is not available in the provided text. Instead, the document asserts substantial equivalence based on shared technology and performance characteristics with established systems.

Here's an analysis of the available information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state specific acceptance criteria or report new device performance metrics from a dedicated study for this particular Special 510(k) submission. This is because the submission's core argument is substantial equivalence to a previously cleared device (K081543, for the VITROS TSH assay on the VITROS 5600 Integrated System) and prior cleared technology (K962919, for the VITROS ECi/ECiQ Immunodiagnostic System).

The submission states: "The modified device has the same intended use, fundamental scientific technology and operating principle as the predicate device. The modified VITROS Immunodiagnostic Products TSH assay is substantially equivalent to the product previously cleared with Premarket Notification number K081543."

This implies that the performance of the VITROS TSH assay on the VITROS 3600 system is expected to meet the same performance criteria that were established and accepted for the K081543 submission. Without access to K081543, specific quantitative acceptance criteria cannot be listed here.

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

The provided text does not include information about a specific test set sample size or data provenance (country of origin, retrospective/prospective) for this Special 510(k) submission. Given that this is a Special 510(k) focused on system modification and substantial equivalence, new clinical performance studies with dedicated test sets are often not required if the changes do not significantly impact safety or effectiveness. The claim is that the VITROS 3600 uses the existing VITROS ECi/ECiQ technology and the same immunoassay hardware and software subsystem design as the VITROS 5600.

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

This information is not provided in the document. As this is a laboratory diagnostic device, ground truth for TSH measurements would typically be based on established reference methods, external quality assurance programs, or certified reference materials, rather than expert consensus on individual cases.

4. Adjudication method for the test set

This information is not provided in the document. It is unlikely to be relevant for a submission of this nature, focused on an in vitro diagnostic device measuring a specific analyte.

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 device is an in vitro diagnostic immunodiagnostic system for measuring Thyroid Stimulating Hormone (TSH). It is not an AI-assisted diagnostic imaging device or a device involving human "readers" in the context of interpretation that would necessitate an MRMC study.

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

Not applicable in the context of "algorithm only." The device is an automated in vitro diagnostic instrument. Its performance is evaluated as a standalone system (instrument, reagent, calibrators) in measuring TSH concentration. The "algorithm" here would refer to the instrument's internal measurement and calculation processes, and its "standalone performance" is what the overall system performance studies (implicitly referenced by substantial equivalence to K081543) would evaluate. The results are quantitative measurements, not interpretations requiring human review in the same way an imaging algorithm might.

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

The document does not explicitly state the ground truth type used for the original validation of the TSH assay (K081543). However, for quantitative in vitro diagnostic assays like TSH, ground truth is typically established through:

• Reference Intervals: Established by analyzing samples from a healthy population using a highly accurate and precise reference method.
• Assigned Values of Certified Reference Materials: Using internationally recognized standards and calibrators.
• Correlation with Established Methods: Comparing results to a legally marketed predicate device or gold standard method for TSH measurement.

8. The sample size for the training set

This information is not provided as the submission is not focused on developing a new algorithm but adapting an existing assay to a new instrument platform. The concept of a "training set" is generally more relevant for machine learning algorithms or new assay development, neither of which is the primary focus of this Special 510(k). All "technology, methodologies and analytical methods" are stated to be "currently available on the existing two systems."

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

This information is not provided and is likely not applicable for the reasons stated in point 8.

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VITROS Immunodiagnostic Products TSH Reagent Pack: For the in vitro quantitative measurement of thyroid stimulating hormone (TSH) in human serum and plasma (EDTA or Heparin) using the VITROS ECi/ECiQ Immunodiagnostic Systems and VITROS 5600 Integrated System to aid in the differential diagnosis of thyroid disease.
VITROS Immunodiagnostic Products TSH Calibrators: For in vitro use in the calibration of the VITROS ECI/ECIQ Immunodiagnostic Systems and VITROS 5600 Integrated System for the quantitative measurement of thyroid stimulating hormone (TSH) in human serum and plasma (EDTA or Heparin).
VITROS Chemistry Products PHYT Slides: For in vitro diagnostic use only. VITROS Chemistry Products PHYT Slides quantitatively measure phenytoin (PHYT) concentration in serum and plasma using VITROS 250/350/950 and 5,1 FS Chemistry Systems and the VITROS 5600 Integrated System.
VITROS Chemistry Products Calibrator Kit 9: For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 9 is used to calibrate VITROS 250/350/950 and 5.1 FS Chemistry Systems and the VITROS 5600 Integrated System for the quantitative measurement of ACET, CRBM, DGXN, PHBR, and PHYT.
VITROS 5600 Integrated System: For use in the in vitro quantitative, semi-quantitative measurement of a variety of analytes of clinical interest, using VITROS Chemistry Products Slides, VITROS Chemistry Products MicroTip Reagents and VITROS Immunodiagnostic Products Reagents.

The VITROS Immunodiagnostic Products TSH assay and VITROS Chemistry Products PHYT assay are intended for use on the VITROS 5600 Integrated System. The VITROS 5600 Integrated System combines the existing VITROS 5,1 FS Chemistry System (K031924) and the VITROS ECi/ECiQ Immunodiagnostic System (K962919) into a single system. All technology, methodologies and analytical methods currently available on the existing two systems are available on the new integrated system.

This is a 510(k) premarket notification for modifications to existing assays (VITROS Immunodiagnostic Products TSH and VITROS Chemistry Products PHYT) to be used with a new integrated system (VITROS 5600 Integrated System). The submission focuses on demonstrating substantial equivalence to previously cleared devices.

Therefore, the typical "acceptance criteria" and "study that proves the device meets the acceptance criteria" in the context of a new diagnostic algorithm's performance are not explicitly detailed in the provided text. This is because the submission is for a system modification rather than a new algorithmic diagnostic device with performance metrics like sensitivity, specificity, etc.

However, based on the context of a 510(k) for a laboratory diagnostic system, we can infer the types of performance criteria that would be relevant for demonstrating substantial equivalence for the modified use of the assays on the new system. These would typically include:

• Method Comparison: Showing that results obtained on the new integrated system are comparable to those obtained on the predicate systems.
• Precision: Demonstrating acceptable within-run and between-run variability on the new system.
• Linearity/Analytical Measurement Range: Confirming the ability to accurately measure analytes across a defined range on the new system.
• Interference: Ensuring common interfering substances do not significantly impact results on the new system.
• Stability: Verifying the stability of reagents and calibrators when used with the new system.
• Reference Range: Confirming the appropriate reference intervals for the assays on the new system.

Since the provided text does not contain detailed study results for these specific performance characteristics (as it's a summary document), I cannot fill out all sections. I will address what can be inferred or is explicitly stated:

1. Table of Acceptance Criteria and the Reported Device Performance:

The document doesn't explicitly state numerical acceptance criteria for performance metrics (e.g., "TSH bias must be within X%") or report detailed performance data. Instead, the submission relies on the concept of "substantial equivalence" of the modified device to the predicate devices. This implies that the performance on the new combined system is expected to be equivalent to the already cleared separate systems.

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

• Sample Size: Not explicitly stated in the summary document. For method comparison studies in IVDs, hundreds of clinical samples are typically used across the analytical range.
• Data Provenance: Not explicitly stated. Assumed to be clinical samples relevant to the intended use.

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 is not applicable in the context of this 510(k) for an in vitro diagnostic (IVD) system. For IVDs, "ground truth" is typically established by reference methods, comparison to predicate devices, or spiking studies, not by expert interpretation of images or clinical data.

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

Not applicable. Diagnostic assays like TSH and PHYT use quantitative measurements, and "adjudication" in the sense of resolving discrepancies between human readers is not relevant. The comparison would be between the numerical results of the new system and the predicate system.

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 IVD system for quantitative measurement, not an AI-assisted diagnostic imaging device that involves human reader interpretation.

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

The device (VITROS 5600 Integrated System running the TSH and PHYT assays) is a standalone automated system for quantitative measurement. Its performance is evaluated intrinsically through analytical studies (precision, accuracy, method comparison, etc.) as described under point 1.

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

For this type of IVD device, ground truth would typically be established by:

• Reference Methods: Comparison against established, highly accurate analytical methods.
• Predicate Device Comparison: Demonstrating statistical equivalence of results when compared to the existing cleared devices (VITROS ECi/ECiQ and VITROS 5,1 FS Chemistry System) on the same samples.
• Spiked Samples: Using samples with known concentrations of the analyte.

The submission heavily relies on the "substantial equivalence" to predicate devices, indicating that the predicate device's performance effectively serves as the "ground truth" for comparison.

8. The sample size for the training set:

Not applicable in the AI/machine learning sense. For IVD systems, "training" refers to calibration and quality control. The training of the system for measuring TSH and PHYT would involve:

• Calibration: Using the specific calibrators (VITROS Immunodiagnostic Products TSH Calibrators and VITROS Chemistry Products Calibrator Kit 9). The sample sizes for calibration materials are determined by statistical design to ensure accurate curve fitting.
• Quality Control: Regular testing of quality control materials to ensure the system is performing within specifications.

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

• Calibrators: The ground truth (assigned value) for the calibrators is established through a rigorous process by the manufacturer, typically involving reference methods, traceability to international standards (if available for TSH), and extensive internal validation studies.
• Quality Control Materials: Similar to calibrators, assigned values for quality control materials are established by the manufacturer through reference methods and internal validation.

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For quantitative measurement of human chorionic gonadotropin (hCG) and its ß-subunit in human serum and plasma (EDTA or heparin) to aid in the early detection of pregnancy.

For use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of human chorionic gonadotropin (hCG) and its ß-subunit in human serum and plasma (EDTA or heparin).

For in vitro use in verifying the calibration range of the VITROS Immunodiagnostic System when used for the measurement of human chorionic gonadotropin (hCG) and its ß-subunit.

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum and plasma. Coated microwells are used as the solid phase separation system.

The assay is comprised of three main elements:

1. The VITROS Immunodiagnostic Products range of immunoassay products in this case the VITROS Immunodiagnostic Products Total B-hCG II Reagent Pack, the VITROS Immunodiagnostic Products Total B-hCG II Calibrators, and the VITROS Immunodiagnostic Products Total B-hCG II Range Verifiers (which are combined by the VITROS Immunodiagnostic system to perform the VITROS Total B-hCG II assay).

2. The VITROS Immunodiagnostic System - instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).

3. Common reagents - used by the VITROS Immunodiagnostic System in each assay include the VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 Reagent Pack and VITROS Immunodiagnostic Products Total T3 Calibrators 510(k) premarket notification (K964310).

Note: High Sample Diluent B was cleared as part of the VITROS Immunodiagnostic Products Total B-hCG Reagent Pack and VITROS Immunodiagnostic Products Total β-hCG Calibrators 510(k) premarket notification (K970894).

The VITROS Immunodiagnostic System and common reagents are dedicated specifically for use only with the VITROS Immunodiagnostic Products range of immunoassay products.

Here's an analysis of the provided 510(k) summary regarding the acceptance criteria and study details for the VITROS Immunodiagnostic Products Total β-hCG II assay.

Please note: This document is a 510(k) summary for an in-vitro diagnostic device, not an AI/ML-based medical device. Therefore, many of the requested categories (e.g., sample size for test set/training set, number of experts for ground truth, adjudication method, MRMC study, human reader improvement) are not applicable or available in this type of submission. This summary focuses on demonstrating substantial equivalence to a predicate device, primarily through performance characteristics of the assay itself.

Acceptance Criteria and Reported Device Performance

The acceptance criteria for the new device are implicitly established by demonstrating substantial equivalence to the predicate device. This is primarily done by comparing performance characteristics such as analytical sensitivity, specificity, precision, and measuring range, and showing that the new device performs comparably or better.

Here's a table summarizing the reported device performance compared to the predicate, which serves as the de-facto acceptance criteria. The new device must meet or exceed the performance of the predicate to demonstrate substantial equivalence.

Note: The "Expected Values" table is also presented for comparison, but these are typically reference ranges derived from clinical populations rather than strict acceptance criteria for the device's technical performance.

Study Details

Given this is a 510(k) for an in-vitro diagnostic assay (laboratory test), the study design differs significantly from that of an AI/ML device.

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

   • The document does not explicitly state a "test set" sample size in the context of a diagnostic test for comparing against ground truth. Instead, performance characteristics (precision, sensitivity, specificity, measuring range) are evaluated using various types of samples.
   • Specificity and Analytical Sensitivity: The document states 0.70 mIU/mL analytical sensitivity and ≤ 10% cross-reactivity for FSH, LH, and TSH without providing specific sample counts for these tests.
   • Precision: Precision studies involved measuring samples multiple times to calculate Coefficients of Variation (CV). The specific number of samples for these studies is not detailed in the summary, but typical studies involve multiple replicates over several days with different operators and instrument runs.
   • Expected Values: The table for "Expected Values" in Table 1 shows sample sizes (n) for different gestational age groups: 1-10 weeks (n=112 for new device, n=50 for predicate), 11-15 weeks (n=43 for new device, n=50 for predicate), 16-20 weeks (n=50 for new device, n=50 for predicate), and 23-40 weeks (n=45 for new device, n=50 for predicate). This data provenance is generally from clinical populations.
   • Data Provenance: Not explicitly stated as retrospective or prospective, nor country of origin for all performance data, though the manufacturer site is in the United Kingdom. The "Expected Values" imply clinical samples.

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

   • Not applicable / Not explicitly stated. For an immunoassay, the "ground truth" for analytical performance tests (sensitivity, specificity, precision) is established through reference methods, certified reference materials, and standardized laboratory practices, not typically by expert consensus of human readers. For clinical reference ranges ("Expected Values"), the ground truth is derived from the measured hGC levels in a healthy population or population with known pregnancy status, often confirmed by clinical means (e.g., last menstrual period, ultrasound), but not requiring human expert adjudication of visual data.

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

   • Not applicable. Adjudication methods like 2+1 are used for human interpretation of images or complex data where consensus is needed to establish ground truth. For an automated immunoassay, the result is quantitative or qualitative based on the assay's chemical reaction and signal detection.

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. An immunoassay is an automated diagnostic test; it does not involve human "readers" interpreting results in the way an AI medical device for image analysis would. Therefore, no MRMC study or assessment of human reader improvement with AI assistance was performed or is relevant.

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

   • Yes, in essence. Immunoassays are inherently "standalone" in that once the sample is loaded and the test is run, the instrument produces the result without further human interpretation beyond reporting the quantitative value. The performance metrics discussed (sensitivity, specificity, precision, measuring range) are all measures of the device's standalone analytical performance.

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

   • The "ground truth" for demonstrating the performance of this in-vitro diagnostic device would typically involve:
     • Reference standards/materials: For analytical sensitivity and linearity, using known concentrations of hCG.
     • Clinical samples: For establishing expected values and potentially for cross-reactivity studies, samples from healthy individuals or individuals with confirmed conditions (e.g., pregnant patients, patients with elevated FSH/LH/TSH) might be used.
     • Comparative methods: Often, performance is validated by comparing results to a gold standard or well-established reference method.
   • The document does not explicitly detail the exact nature of the "ground truth" for all studies, but it is inferable from the types of performance claims made.

7. The sample size for the training set:

   • Not applicable. This device is an immunoassay, not an AI/ML algorithm that requires a "training set" in the computational sense. The assay's chemistry and detection principles are pre-determined during development, not "trained" on data.

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

   • Not applicable. As there is no training set for an immunoassay, there is no ground truth established for it in this context.

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VITROS® Troponin I ES Reagent Pack:
For in vitro diagnostic use only.
For the quantitative measurement of cardiac Troponin I (cTnI) in human serum and plasma (heparin and EDTA) using the VITROS Immunodiagnostic System, to aid in the assessment of myocardial damage and risk stratification.
Cardiac Troponin I measurement aids in the diagnosis of acute myocardial infarction and in the risk stratification of patients with non-ST-segment elevation acute coronary syndromes with respect to relative risk of mortality, myocardial infarction (MI) or increased probability of ischemic events requiring urgent revascularization procedures.

VITROS® Troponin I ES Calibrators:
For in vitro diagnostic use only.
For use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of cardiac Troponin I (cTnI) in human serum and plasma (heparin and EDTA).

VITROS® Troponin I ES Range Verifiers:
For in vitro diagnostic use only.
For in vitro use in verifying the calibration range of the VITROS Immunodiagnostic System when used for the quantitative measurement of cardiac Troponin I (cTnI).

1. The VITROS Immunodiagnostic Products range of immunoassav products: VITROS Immunodiagnostic Products Troponin I ES Reagent Pack, the VITROS Immunodiagnostic Products Troponin I ES Calibrators and the VITROS Immunodiagnostic Products Troponin I ES Range Verifiers, (which are combined by the VITROS Immunodiagnostic System to perform the VITROS Troponin I ES assay), and VITROS Immunodiagnostic Products High Sample Diluent B.
2. The VITROS Immunodiagnostic System: Instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).
3. Common reagents used by the VITROS System in each assay: The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 Reagent Pack and VITROS Immunodiagnostic Products Total T3 Calibrators 510(k) premarket notification (K964310).
   Note: High Sample Diluent B was cleared as part of the VITROS Immunodiagnostic Products Total ß-hCG Reagent Pack and VITROS Immunodiagnostic Products Total ß-hCG Calibrators 510(k) premarket notification (K970894).
   The VITROS Immunodiagnostic System and common reagents are dedicated specifically for use only with the VITROS Immunodiagnostic Products range of immunoassay products.

This 510(k) summary describes the VITROS® Immunodiagnostic Products Troponin I ES Reagent Pack, Calibrators, and Range Verifiers, designed for the quantitative measurement of cardiac Troponin I (cTnI). The submission aims to demonstrate substantial equivalence to predicate devices.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the new device are implied by a comparison to a predicate device (BECKMAN Access® AccuTnI Troponin I assay) and various clinical and analytical standards. The document primarily focuses on establishing "substantial equivalence" rather than specific numerical acceptance criteria for each performance characteristic. However, the listed "Differences" section in Table 1 can be interpreted as the reported device performance compared to specific characteristics of the predicate.

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VITROS Anti-HAV IgM Reagent Pack: For the in vitro qualitative determination of IgM antibody to hepatitis A virus (anti-HAV IgM) in human adult and pediatric serum or plasma (EDTA, heparin or citrate) using the VITROS ECi/ECiQ Immunodiagnostic System. The assay is indicated for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis. Assay results in conjunction with other clinical information, may be used for the laboratory diagnosis of individuals with acute or recent hepatitis A.

VITROS Anti-HAV IgM Calibrator: For in vitro use in the calibration of the VITROS Immunodiagnostic System for the qualitative determination of IgM antibody to hepatitis A viral antigen (HAV) in human serum and plasma (EDTA, heparin or citrate.

VITROS Anti-HAV IgM Controls: For in vitro use in monitoring the performance of the VITROS Immunodiagnostic System when used for the detection of anti-HAV IgM.

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum and plasma. Coated microwells are used as the solid phase separation system. The system is comprised of three main elements: The VITROS Immunodiagnostic Products range of immunoassay products (in this case the VITROS Immunodiagnostic Products Anti-HAV IgM Reagent Pack and the VITROS Immunodiagnostic Products Anti-HAV IgM Calibrators) and VITROS Immunodiagnostic Products High Sample Diluent B which are combined by the VITROS Immunodiagnostics System to perform the VITROS Anti-HAV IgM assay. The VITROS Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits. Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent.

The VITROS Anti-HAV IgM assay utilizes an antibody class capture assay design, for the measurement of IgM antibodies to hepatitis A antigen, in human serum or plasma. The assay involves dilution of the sample and the simultaneous reaction of IgM in the diluted sample with biotinylated mouse monoclonal anti-human IgM antibody. The immune complex is captured by streptavidin on the wells, unbound materials are removed by washing. Horseradish peroxidase (HRP)-labeled mouse monoclonal anti-HAV antibody that has been complexed with inactivated HAV antigen (conjugate) is then captured by anti-HAV specific IgM bound to the wells. Unbound material is removed by washing. Enzyme substrate is then added and bound HRP conjugate is measured by a luminescent reaction. He binding of HRP conjugate is indicative of the presence of anti-HAV IgM.

Here's a summary of the acceptance criteria and study details for the VITROS Immunodiagnostic Products Anti-HAV IgM assay, based on the provided document:

Acceptance Criteria and Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity/specificity thresholds. Instead, it presents the "Summary of Performance" as the demonstration that the device is "safe and effective for the stated intended uses and is substantially equivalent to the cleared predicate devices."

The performance data presented serve as the evidence that the device meets an implied standard of effectiveness in line with its predicate.

Study Details

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

   • Prospectively Collected Samples (High-Risk/Symptomatic):
     • Positive: 32 samples
     • Negative: 1159 samples
     • Total: 1191 samples
     • Provenance: Samples obtained in the U.S. and India. The study was multi-center.
   • Known Anti-HAV IgM Reactive Samples: 77 samples. (Provenance not explicitly stated, but likely from clinical settings.)
   • Low-Risk Pediatric Subjects: 110 samples. (Provenance not explicitly stated, but implies healthy pediatric population.)

2. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications: Not explicitly stated in the provided document. The ground truth for hepatitis A IgM status would typically be established through a combination of clinical diagnosis, other reference laboratory tests (e.g., PCR, serology), and patient history. The document refers to "samples from subjects known to be anti-HAV IgM reactive," implying an established ground truth.

3. Adjudication Method for the Test Set: Not explicitly stated. Given that it's an in vitro diagnostic assay, adjudication typically refers to the process of resolving discrepancies between the new device's results and the established ground truth. This is generally handled by the study design and statistical analysis method rather than a reader adjudication process.

4. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study: No, this type of study was not conducted. MRMC studies are typically for imaging or interpretive devices where human readers evaluate cases. This document describes an in vitro diagnostic assay, which does not involve human readers interpreting results in the same way. The comparative effectiveness assessment is against a predicate device and established ground truth.

5. Standalone Performance: Yes, the described study assesses the standalone performance of the VITROS Anti-HAV IgM assay. The performance metrics (positive percent agreement, negative percent agreement) are purely based on the algorithm's output compared to the ground truth, without human intervention in the result determination process.

6. Type of Ground Truth Used: The ground truth appears to be based on:

   • Clinical Diagnosis/Known Status: For the prospectively collected samples, they were from "individuals at high risk for hepatitis and/or with signs or symptoms of hepatitis." For validation, "samples from subjects known to be anti-HAV IgM reactive" and "pediatric subjects at low risk for hepatitis" were used. This implies reliance on established clinical diagnoses, reference laboratory tests, and patient histories to classify samples as positive or negative for anti-HAV IgM.

7. Sample Size for the Training Set: Not explicitly stated. The document focuses on the performance study (test set). For in vitro diagnostic devices, the "training set" might refer to samples used during the assay development and optimization phases, which are rarely detailed in 510(k) summaries unless they contribute directly to a specific algorithm's performance claim within the submission.

8. How the Ground Truth for the Training Set Was Established: Not explicitly stated. As with point 7, details about development/training phases are not typically provided in this level of summary for IVD assays. It's presumed that standard methods for establishing HAV IgM status (e.g., reference assays, clinical correlation) would have been used during development.

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VITROS Anti-HAV Total Reagent Pack: For the in vitro qualitative detection of total antibody (IgG and IgM) to hepatitis A virus (anti-HAV) in human adult and pediatric serum and plasma (EDTA, heparin or citrate) using the VITROS ECi/ECiQ Immunodiagnostic System. The assay is indicated, in conjunction with other serological and clinical information, as an aid in the clinical laboratory diagnosis of individuals with acute or past hepatitis A virus infection, or as an aid in the identification of HAV-susceptible individuals prior to HAV vaccination. The detection of HAV-specific antibodies in human serum or plasma is laboratory evidence of acute or recent HAV infection.

VITROS Anti-HAV Total Calibrator: For in vitro use in the calibration of the VITROS Immunodiagnostic System for the qualitative detection of antibodies to hepatitis A virus (anti-HAV) in human serum and plasma (EDTA, heparin or citrate).

VITROS Anti-HAV Total Controls: For in vitro use in monitoring the performance of the VITROS Immunodiagnostic System when used for the detection of antibodies to Hepatitis A virus (anti-HAV).

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum and plasma. Coated microwells are used as the solid phase separation system. The system is comprised of three main elements: The VITROS Immunodiagnostic Products range of immunoassay products (in this case the VITROS Immunodiagnostic Products Anti-HAV Total Reagent Pack and the VITROS Immunodiagnostic Products Anti-HAV Total Calibrators) and VITROS Immunodiagnostic Products High Sample Diluent B which are combined by the VITROS Immunodiagnostics System to perform the VITROS Anti-HAV Total assay. The VITROS Immunodiagnostic System - instrumentation, which provides automated use of the immunoassay kits. Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent. The VITROS System and common reagents are dedicated specifically for use only with the VITROS Immunodiagnostic Products range of immunoassay products. The VITROS Anti-HAV Total assay utilizes a competitive assay design for the measurement of antibody to HAV Total (IgG and IgM). The competitive assay technique is used which involves pre-incubation of anti-HAV in the sample with HAV antigen in the Assay Reagent followed by incubation with a Conjugate Reagent that contains biotinylated mouse monoclonal anti-HAV antibody and horseradish peroxidase (HRP)-labeled mouse monoclonal anti-HAV antibody. The immune complex is captured by streptavidin on the wells, unbound materials are removed by washing. The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent, is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the VITROS System. The binding of HRP is indicative of the absence anti-HAV antibody. The VITROS Immunodiagnostic Products Anti-HAV Total Controls is comprised of two levels of human plasma that have been targeted to produce negative or positive results when used with the VITROS Immunodiagnostic Products Anti-HAV Total assay.

Here's a breakdown of the acceptance criteria and study information for the VITROS Immunodiagnostic Products Anti-HAV Total assay, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The 510(k) summary does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for positive percent agreement (PPA) and negative percent agreement (NPA). However, it reports performance metrics from a multi-center study. The implication is that these reported numbers met the internal standards for substantial equivalence.

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

• Overall Multi-center Study: The specific total sample size for this study is not explicitly stated, but it involved "samples obtained in the U.S. and India from individuals at high risk for hepatitis and/or with signs or symptoms of hepatitis."
• Anti-HAV IgM Reactive Samples: 77 samples were tested against a reference assay.
• Pediatric Samples: The sample size for the pediatric study is not explicitly stated beyond the percentages reported.
• Provenance: Data was collected from the U.S. and India. The section states the study was "multi-center" and involved "combined prospective samples," indicating a prospective data collection. Additionally, plasma from healthy individuals from "US population residing in areas of high (Western, US) and low (Eastern US) HAV disease prevalence" was used to determine expected results.

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

The 510(k) summary does not provide information on the number of experts used or their qualifications for establishing ground truth for the test set. It mentions comparison to a "reference anti-HAV assay" and "subjects known to be anti-HAV IgM reactive" for some parts of the study, implying established diagnostic methods and clinical status were used as ground truth.

4. Adjudication Method for the Test Set

The 510(k) summary does not describe an adjudication method (like 2+1 or 3+1 consensus) for the test set. Ground truth appears to be based on "reference anti-HAV assay" results or known clinical status ("subjects known to be anti-HAV IgM reactive").

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 as this device is an in vitro diagnostic (IVD) assay designed to detect antibodies, not an imaging or AI-assisted diagnostic tool for human readers. Therefore, an MRMC study and effect size for human reader improvement with AI are not relevant to this submission.

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

Yes, this was a standalone performance study of the VITROS Immunodiagnostic Products Anti-HAV Total assay. The device itself is an automated system for detecting antibodies, and its performance reported is its output, not an output requiring human interpretation of assisted results. The results (positive/negative) are directly generated by the device.

7. The Type of Ground Truth Used

The ground truth used in the studies appears to be a combination of:

• Reference Anti-HAV Assay: Explicitly mentioned for comparison where "the percent agreement was 96.1% (74/77) as three subjects were negative for HAV in the reference assay."
• Known Clinical Status: "samples from subjects known to be anti-HAV IgM reactive" and "pediatric subjects at low risk for hepatitis."
• Serological/Clinical Information: The intended use statement also refers to the assay as an "aid in the clinical laboratory diagnosis of individuals with acute or past hepatitis A virus infection," implying the results would be interpreted in conjunction with other patient data.

8. The Sample Size for the Training Set

The 510(k) summary does not mention a training set for this device. This is typical for an IVD assay where the "training" (development and optimization) would occur during the assay's design and formulation, rather than through a machine learning training set as seen with AI/ML devices. The studies described are performance validation studies.

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

Since no training set is mentioned in the context of machine learning, there is no information provided on how ground truth for a training set was established.

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The measurement of cortisol in human serum, plasma (heparin or EDTA) or urine aids in the assessment of adrenal status.

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum and plasma. Coated microwells are used as the solid phase separation system. The system is comprised of there main elements: The VITROS Immunodiagnostic Products range of immunoassay products in this case VITROS Immunodiagnostic Products Cortisol Reagent Pack, VITROS Immunodiagnostic Products Cortisol Calibrators (cleared under K983990) and VITROS Immunodiagnostic Products Metabolism Controls (cleared under K983990), which are combined by the VITROS Immunodiagnostic System to perform the VITROS Cortisol assay. The VITROS Immunodiagnostic System - instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919). Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 Reagent Pack and VITROS Immunodiagnostic Products Total T3 Calibrators 510(k) premarket notification (K964310).

The provided text describes a 510(k) premarket notification for a medical device, the VITROS Immunodiagnostic Products Cortisol Assay. It focuses on demonstrating substantial equivalence to a previously cleared predicate device, rather than proving that the device meets specific acceptance criteria through a clinical study with detailed performance metrics.

Therefore, the following information cannot be fully extracted or is not explicitly stated in the document:

• A table of acceptance criteria and the reported device performance: The document only provides a comparison of device characteristics between the new and predicate devices (Table 1) and a general statement of "equivalent performance." It does not list specific quantitative acceptance criteria (e.g., sensitivity, specificity, accuracy targets) or detailed performance data against those criteria.
• Sample sized used for the test set and the data provenance: The document states that "testing human samples throughout the assay range" was done, but does not provide specific sample sizes for test sets, data provenance (e.g., country of origin), or whether the study was retrospective or prospective.
• Number of experts used to establish the ground truth for the test set and the qualifications of those experts: This information is not provided.
• Adjudication method for the test set: Not provided.
• If a multi-reader multi-case (MRMC) comparative effectiveness study was done, and the effect size of how much human readers improve with AI vs without AI assistance: This is an in vitro diagnostic device, not an image-based AI system that would involve human readers. Therefore, an MRMC study is not applicable or mentioned.
• If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: The device is an immunoassay system, not an algorithm in the context of AI. Its performance is inherent in its design and operation.
• The type of ground truth used: The document mentions "manufactured reagents, positive and negative controls and testing human samples." For an immunoassay, the 'ground truth' would typically be established by reference methods or validated clinical diagnoses/outcomes, but this is not explicitly detailed.
• The sample size for the training set: Not applicable in the context of an immunoassay for which no separate "training set" is described for an algorithm.
• How the ground truth for the training set was established: Not applicable.

Here's what can be extracted based on the provided text, focusing on the comparison to the predicate device and the general statement of performance:

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

The document does not explicitly define acceptance criteria in terms of quantitative performance metrics (e.g., accuracy, precision, bias thresholds). Instead, "equivalent performance" to the predicate device is the overarching acceptance criterion for the 510(k) submission.

Study Proving Acceptance Criteria:

The study described is a comparison study demonstrating substantial equivalence of the modified VITROS Immunodiagnostic Products Cortisol Assay to the previously cleared predicate device (K983990). The conclusion states: "Equivalent performance was demonstrated using manufactured reagents, positive and negative controls and testing human samples throughout the assay range."

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

• Sample Size: Not explicitly stated. The document only mentions "testing human samples throughout the assay range."
• Data Provenance: Not specified (e.g., country of origin not mentioned).
• Retrospective or Prospective: Not specified.

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 as this is not an image-based diagnostic or expert interpretation study. The 'ground truth' for an immunoassay's performance would typically refer to the true concentration of cortisol in samples, usually determined by reference methods or clinical gold standards. The document does not detail how this ground truth was established for the "human samples."

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

• Not applicable for this type of immunoassay study.

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. This is an in vitro diagnostic device, not an AI system.

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

• The device itself is a standalone immunoassay system. The performance evaluated is the direct output of the system. There is no concept of an "algorithm only" in the context of human-in-the-loop for this device.

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

• The document implies that performance was assessed against "manufactured reagents, positive and negative controls and testing human samples." For human samples, the ground truth for cortisol levels would typically come from a well-established reference assay or a clinically validated method, but this is not explicitly detailed.

8. The sample size for the training set

• Not applicable. This is an immunoassay, not a machine learning algorithm requiring a distinct "training set."

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

• Not applicable.

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