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The Atellica IM Thyroglobulin (Tg) assay is for in vitro diagnostic use in the quantitative measurement of thyroglobulin in human serum and plasma (EDTA and lithium heparin) using the Atellica IM Analyzer.

Thyroglobulin measurements are used as an aid in monitoring differentiated thyroid cancer patients who have undergone thyroidectomy with or without radioiodine ablation.

The Atellica IM Thyroglobulin (Tg) assay includes:

• Tg ReadyPack primary reagent pack:
  • Lite Reagent: mouse monoclonal anti-human Tg antibody labeled with acridinium ester (~1.13 μg/mL); bovine serum albumin (BSA); mouse IgG; buffer; stabilizers; preservatives (7.5 mL/reagent pack).
  • Solid Phase: streptavidin-coated paramagnetic microparticles preformed with biotinylated mouse monoclonal antihuman Tg antibody (~267 μg/mL); BSA; mouse IgG; buffer; stabilizers; preservatives (15.0 mL/reagent pack).
• Ancillary Well Reagent: BSA; bovine gamma globulin; buffer; preservatives (6.0 mL/reagent pack).
• Tg CAL: After reconstitution, human thyroglobulin; BSA; buffer; stabilizers; preservatives (2.0 mL/vial).

The following devices are sold separately:

• Atellica IM Tg MCM:
  • MCM 1: After reconstitution, bovine serum albumin (BSA); buffer; stabilizers; preservatives (1.0 mL/vial).
  • MCM 2–5: After reconstitution, various levels of human thyroglobulin; BSA; buffer; stabilizers; preservatives (1.0 mL/vial).

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided FDA 510(k) summary for the Atellica IM Thyroglobulin (Tg) assay:

Device: Atellica IM Thyroglobulin (Tg) Assay
Purpose: Quantitative measurement of thyroglobulin in human serum and plasma as an aid in monitoring differentiated thyroid cancer patients who have undergone thyroidectomy with or without radioiodine ablation.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document describes various performance characteristics, which serve as acceptance criteria for the device. The reported performance is directly from the summary.

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The Atellica® CH Creatinine_3 (Crea3) assay is for in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma (lithium heparin, dipotassium EDTA, and sodium heparin), and urine using the Atellica® CH Analyzer. Such measurements are used in the diagnosis and treatment of renal diseases, and in monitoring renal dialysis.

The Atellica CH Crea3 assay is based on the reaction of picrate with creatinine in an alkaline medium to produce a red chromophore creatinine picrate complex. The rate of complex formation is measured at 505/571 nm and is proportional to the creatinine concentration. The Atellica CH Crea3 assay is a modification of the Jaffe method, using rate blanking and intercept correction. Rate blanking is used to minimize bilirubin interference. Also, because non-specific serum/plasma protein interactions with this reagent have been found to produce a positive bias of approximately 0.3 mg/dL (26.5 µmol/L), serum/plasma measurements are automatically corrected by subtracting 0.3 mg/dL (26.5 µmol/L) from each result.

The provided text describes the performance characteristics and studies for the Atellica® CH Creatinine_3 (Crea3) assay, a new in vitro diagnostic device for quantitative determination of creatinine. It compares this new device to a predicate device, the Atellica® CH Creatinine_2 (Crea_2) assay.

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

Important Note: The document focuses on establishing substantial equivalence for an in vitro diagnostic (IVD) test, which primarily relies on analytical performance characteristics rather than clinical outcome studies or multi-reader multi-case (MRMC) comparative effectiveness studies typically seen with imaging AI devices. Therefore, some of your requested information (like number of experts for ground truth, adjudication methods, MRMC studies, and training set details for an AI model) are not directly applicable or provided in this type of submission.

Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are established through various analytical performance studies, primarily comparing it to a legally marketed predicate device (Atellica® CH Creatinine_2). The acceptance criteria are implicitly defined by the successful demonstration of equivalence or meeting pre-defined performance goals for each characteristic.

Here's a table summarizing the acceptance criteria (inferred from the "designed to have" or "determined in accordance with" statements and the reported results meeting these) and the reported device performance:

• Serum 1 (0.38 mg/dL): Repeatability SD 0.006, CV 1.6%; Within-Lab SD 0.012, CV 3.2%
• Serum 2 (0.73 mg/dL): Repeatability SD 0.023, CV 3.2%; Within-Lab SD 0.029, CV 4.0%
• Serum 3 (0.73 mg/dL): Repeatability SD 0.006, CV 0.8%; Within-Lab SD 0.019, CV 2.6%
• Serum 4 (1.18 mg/dL): Repeatability SD 0.007, CV 0.6%; Within-Lab SD 0.019, CV 1.6%
• Serum QC 1 (1.85 mg/dL): Repeatability SD 0.007, CV 0.4%; Within-Lab SD 0.024, CV 1.3%
• Serum QC 2 (6.21 mg/dL): Repeatability SD 0.011, CV 0.2%; Within-Lab SD 0.067, CV 1.1%
• Serum 5 (17.39 mg/dL): Repeatability SD 0.035, CV 0.2%; Within-Lab SD 0.189, CV 1.1%
• Serum 6 (28.54 mg/dL): Repeatability SD 0.056, CV 0.2%; Within-Lab SD 0.317, CV 1.1%
  Urine Samples (n=80 each):
• Urine 1 (56.74 mg/dL): Repeatability SD 0.102, CV 0.2%; Within-Lab SD 0.746, CV 1.3%
• Urine 2 (135.80 mg/dL): Repeatability SD 0.206, CV 0.2%; Within-Lab SD 1.601, CV 1.2%
• Urine QC 1 (195.79 mg/dL): Repeatability SD 0.253, CV 0.1%; Within-Lab SD 2.376, CV 1.2%
  (All results demonstrate low CVs, indicating good precision). |
  | Reproducibility | Determined in accordance with CLSI Document EP05-A3 (implies meeting specific statistical targets for variability components across different days, lots, and instruments). | Serum Samples (n=225 each): Overall CV (%) for reproducibility ranges from 1.0% to 5.0%.
  Urine Samples (n=225 each): Overall CV (%) for reproducibility ranges from 1.4% to 1.6%.
  (All results demonstrate good reproducibility across conditions). |
  | Assay Comparison | Serum: Correlation coefficient $\ge$ 0.950 and slope of 1.00 ± 0.05, compared to predicate (Atellica CH Creatinine 2), using Weighted Deming regression.
  Urine: Correlation coefficient $\ge$ 0.950 and slope of 0.000 ± 3.00, compared to predicate (Atellica CH Creatinine 2), using Weighted Deming regression. | Serum (n=151): Regression equation y = 1.00x - 0.04 mg/dL, correlation coefficient (r) = 1.000. Sample range 0.44 to 28.64 mg/dL.
  Urine (n=113): Regression equation y = 1.00x + 0.14 mg/dL, correlation coefficient (r) = 1.000. Sample range 12.60 to 237.06 mg/dL.
  (Both serum and urine results meet the acceptance criteria for correlation and slope). |
  | Specimen Equivalence | Determined using Weighted Deming regression (implicitly, the regression line should demonstrate equivalence, i.e., close to y=x, with high correlation coefficient). | Sodium Heparin (n=50): y = 1.00x + 0.00 mg/dL, r=0.999.
  Lithium Heparin (n=50): y = 0.99x + 0.06 mg/dL, r=0.999.
  Dipotassium EDTA (n=50): y = 0.98x + 0.04 mg/dL, r=0.998.
  (All demonstrate strong equivalence to serum reference). |
  | Interferences (HIL) | $\le$ 10% interference from hemoglobin, bilirubin, and lipemia. Bias > 10% or 0.15 mg/dL (whichever is greater for serum/plasma) is considered interference. | Reported biases for Hemoglobin (1000 mg/dL), Conjugated Bilirubin (40-45 mg/dL), Unconjugated Bilirubin (45-60 mg/dL), and Lipemia (2250-3000 mg/dL) are all within the ±10% or ±0.15 mg/dL threshold for the tested analyte concentrations, demonstrating acceptable interference profiles. |
  | Interfering Substances | Bias $\le$ 10% or ±0.15 mg/dL for Serum/plasma samples. Bias $\le$ 10% for Urine samples (for listed substances). | Most tested substances (e.g., Acetaminophen, Ascorbic Acid, etc.) show negligible bias, meeting the criteria.

Substances showing bias beyond acceptance criteria for Serum:

• Cefoxitin: Significant interference (e.g., 243.6% and 947.9% bias at high concentrations).
• Cephalothin: Shows significant bias (e.g., 44.0% bias at 180 mg/dL).
• Glucose: Shows bias beyond 10% at higher concentrations (e.g., 11.5% at 500 mg/dL and 22.5% at 1000 mg/dL).
• Total Protein: Shows bias beyond 0.15 mg/dL at 15 g/dL (0.45 mg/dL).
• Acetohexamide: Shows bias beyond 10% at 2.0 mg/dL (10.4%).
• Hydroxocobalamin (Cyanokit): Shows significant bias (e.g., 14.5% and 49.3% at higher concentrations).

Substances showing bias beyond acceptance criteria for Urine:

• Cefoxitin: Shows bias beyond 10% at higher concentrations (e.g., 11.3% and 15.4%).
  (The document explicitly lists these substances under "Interference beyond ±10% for Serum" and "Interference beyond ±10% for Urine," indicating that they failed the non-interference criteria at the tested concentrations. This is typical for IVD submissions, where known interferences are identified for labeling purposes). |
  | Standardization | The assay shall be traceable to the reference material SRM967, from the National Institute of Standards and Technology (NIST). | Statement confirms the assay is traceable to NIST SRM967. |

Study Details:

1. Sample Size and Data Provenance:

   • Test Set Sample Sizes:
     • Detection Capability: Not explicitly stated as "sample size" but data points obtained according to CLSI EP17-A2.
     • Precision: 80 data points per serum/urine sample type (duplicate runs for 20 days, 2 runs/day).
     • Reproducibility: 225 data points per serum/urine sample type (n=5 in 1 run for 5 days using 3 instruments and 3 reagent lots).
     • Assay Comparison: 151 serum samples and 113 urine samples.
     • Specimen Equivalence: 50 samples for each plasma type (Sodium Heparin, Lithium Heparin, Dipotassium EDTA) compared to serum.
     • Interference (HIL & Non-Interfering Substances): Not explicitly stated as a total sample size, but experiments are designed to test specific analyte concentrations with and without interferents, following CLSI EP07-ED3.
   • Data Provenance: Not explicitly stated in terms of country of origin. Given the manufacturer (Siemens Healthcare Diagnostics Inc. in Tarrytown, New York, USA) and FDA submission, it's highly probable the studies were conducted in the US or in compliance with US regulatory standards. The studies described are retrospective in the sense that they use pre-collected or prepared samples to assess the analytical performance of the device under controlled conditions, not prospective in tracking patient outcomes in a clinical trial.

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

   • For an in vitro diagnostic (IVD) device measuring a quantitative analyte like creatinine, "ground truth" is typically established by reference methods or established laboratory standards and calibrators, not by human expert consensus or labeling of medical images.
   • The "ground truth" for creatinine concentration in this context is based on traceable reference materials (NIST SRM 967) and established laboratory measurement principles, and the performance is compared against a legally marketed predicate device.
   • Therefore, this question (relevant for AI/imaging devices) does not directly apply to this type of IVD submission.

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

   • Not applicable. Adjudication methods are typically used in clinical trials or image labeling pipelines where there's human interpretation involved and a need to resolve disagreements among multiple readers; this is an analytical performance study of an IVD assay.

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/imaging device. It's an in vitro diagnostic assay.

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

   • This is an automated IVD assay performed on the Atellica® CH Analyzer. Its intended use is quantitative determination of creatinine. Therefore, the performance described (precision, accuracy, interference, etc.) is its standalone performance without a human in the loop for the analytical measurement itself, though a human still interacts with the instrument and interprets the results in a clinical context.

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

   • The primary "ground truth" for the Atellica® CH Creatinine_3 assay's performance is traceability to NIST SRM 967 (a certified reference material for creatinine) and comparison to a legally marketed predicate device (Atellica® CH Creatinine_2) using method comparison validated against CLSI guidelines. This is a form of analytical reference standard and comparative performance to an established method.

7. The sample size for the training set:

   • This device is an analytical chemistry assay, not a machine learning/AI algorithm that requires a "training set" in the computational sense. The "development" or "optimization" of the assay would involve various experimental data, but it's not codified as a "training set" for an algorithm.

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

   • Not applicable, as there is no "training set" in the AI/ML context for this type of device. The assay development would rely on scientific principles of analytical chemistry, reagent formulation, and instrument calibration against known standards.

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The Atellica® IM High-Sensitivity Troponin I (TnIH) assay is for in vitro diagnostic use in the quantitative measurement of cardiac troponin I in human serum or plasma (lithium heparin) using the Atellica® IM Analyzer. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI).

The Atellica IM TnIH assay can be used as an aid in prognosis for 30-, 182-, and 365-day all-cause mortality (ACM) and major adverse cardiac events (MACE) in patients presenting with signs and symptoms suggestive of acute coronary syndrome (ACS). MACE consists of myocardial infarction, urgent revascularization, cardiac death, or heart failure hospitalization.

The Atellica® IM TnIH assay is a 3-site sandwich immunoassay using direct chemiluminescent technology. The Solid Phase reagent consists of magnetic particles conjugated with streptavidin with 2 bound biotinylated capture monoclonal antibodies, each recognizing a unique cTnl epitope.

The Lite Reagent comprises a conjugate with an architecture consisting of a proprietary acridinium ester and a recombinant anti-human cTnl sheep Fab covalently attached to bovine serum albumin (BSA) for chemiluminescent detection.

A direct relationship exists between the amount of cTnl present in the patient sample and the amount of relative light units (RLUs) detected by the system.

The provided document is a 510(k) summary for the Atellica® IM High-Sensitivity Troponin I (TnIH) assay, detailing its substantial equivalence to a predicate device and supporting the addition of a prognostic indication for use. However, it does not explicitly define acceptance criteria as a separate, quantitative table with pass/fail metrics. Instead, the "Performance Characteristics – Clinical Study" section presents the study objective and results that demonstrate the device's performance for the new prognostic indication, implicitly serving as the validation for meeting the FDA's requirements for substantial equivalence.

Based on the information provided, here's a breakdown of the requested elements:

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

The document does not provide a formal table of acceptance criteria with quantitative thresholds for "pass/fail". The study's objective was to demonstrate the ability of the device to predict future mortality or adverse cardiac events. The reported performance focuses on:

• Hazard Ratios (Unadjusted and Adjusted): Showing the increased risk of ACM/MACE for patients with cTnI levels >99th percentile compared to those ≤99th percentile.
• Post-test risk: The cumulative incidence of ACM/MACE for the two troponin level groups.
• Kaplan-Meier Curves: Visually representing the absolute risk of events over time for the two groups.

The implicit acceptance criteria for this prognostic indication would be that the device's measurements (specifically, cTnI levels > 99th percentile) demonstrate a statistically significant association with increased future risk of all-cause mortality (ACM) and major adverse cardiac events (MACE) across the specified follow-up periods (30, 90, 182, and 365 days) in the relevant patient populations.

Reported Device Performance (Excerpted from the document, focusing on statistically significant findings):

Note: Bolded Hazard Ratios indicate statistically significant findings (95% CI does not cross 1.0). Italicized Hazard Ratios (e.g., serum at 30, 90, 365 days for Population 2) are explicitly marked as "Not Statistically Significant" in the document.

The overall conclusion states: "The results of the clinical study provided in this submission support the addition of an indication for use as an aid in prognosis for all-cause mortality (ACM) and major adverse cardiac events (MACE) in patients presenting with signs and symptoms suggestive of acute coronary syndrome (ACS)." This implies that the observed effects (higher risk for cTnI > 99th percentile) were deemed sufficient, particularly for the statistically significant findings.

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:
  • Population 1: 2064 patients
  • Population 2:
    • Lithium Heparin Plasma: 1190 patients
    • Serum: 1214 patients
  • Population 3: 874 patients
• Data Provenance: The document states, "This prognostic risk analysis utilized the same emergency department cohort previously described in K171566." It does not explicitly state the country of origin. The study was prospective in terms of follow-up for outcomes after initial presentation, as patients were "followed up for 30-, 90-, 182-, and 365-day progression to ACM and MACE."

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 ground truth for Adjudicated AMI was mentioned ("Entire Population Excluding Subjects with Adjudicated AMI"). The document does not specify the number or qualifications of experts used for establishing this adjudication or for the MACE/ACM outcomes. It says "a detailed symptom history was obtained for each subject" and "the following information was collected from each subject's medical chart." This suggests medical record review, but the specific adjudicators are not detailed.

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

The document mentions "adjudicated AMI" and the collection of outcome data (ACM/MACE events). However, it does not describe the specific adjudication method (e.g., how many reviewers, conflict resolution) for AMI or the MACE/ACM outcomes. It implies that MACE consisted of clearly defined clinical events (myocardial infarction, urgent revascularization, cardiac death, or heart failure hospitalization) which are typically obtained from medical records.

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 (IVD) assay for measuring a biomarker (Troponin I). It is not an AI-assisted imaging device or a device involving "human readers" in the typical sense of an MRMC study. The study assesses the prognostic performance of the cTnI assay result itself, not human interpretation enhanced by AI.

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

Yes, in a sense. The performance evaluated is that of the assay (the Atellica® IM High-Sensitivity Troponin I (TnIH) measurement) as a standalone prognostic indicator, reported as a quantitative value. It's the "algorithm" of the assay (producing the cTnI value) that is assessed for its ability to predict outcomes in patient populations, without direct human cognitive input being part of the primary performance metric. Clinical decision-making would then incorporate this result.

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

The ground truth for the prognostic indication was outcomes data, specifically:

• All-Cause Mortality (ACM)
• Major Adverse Cardiac Events (MACE): Consisting of myocardial infarction, urgent revascularization, cardiac death, or heart failure hospitalization.
  This long-term outcome data was collected from patient follow-up over 30, 90, 182, and 365 days.

8. The sample size for the training set

The document describes a clinical performance study for the new prognostic indication. It does not mention a separate "training set" for model development, implying that this was a single-cohort validation study using the full collected dataset (the test set described above). The purpose of the submission is to expand the intended use of an already existing device (cleared under K171566), suggesting the core assay technology was already established.

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

As no separate "training set" is explicitly mentioned for the prognostic model development (if one occurred), this question is not fully answerable from the provided text. The ground truth for the clinical validation (the "test set") was established through prospective follow-up for clinical outcomes (ACM/MACE) as described in point 7.

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The ADVIA Centaur® TSH3-Ultra II (TSH3ULII) assay is for in vitro diagnostic use in the quantitative determination of thyroid-stimulating hormone (TSH, thyrotropin) in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur® XP system. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

This assay is a third-generation assay that employs anti-FITC monoclonal antibody covalently bound to paramagnetic particles, an FITC-labeled anti-TSH capture mouse monoclonal antibody, and a tracer consisting of a proprietary acridinium ester and an anti-TSH mouse monoclonal antibody conjugated to bovine serum albumin (BSA) for chemiluminescent detection.

The provided text describes the ADVIA Centaur® TSH3-Ultra II (TSH3ULII) assay, a device for in vitro diagnostic quantitative determination of thyroid-stimulating hormone (TSH). The document covers the device's indications for use, comparison with a predicate device, and performance characteristics data.

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

1. Table of Acceptance Criteria and Reported Device Performance

• Limit of Detection (LoD): 0.008 µIU/mL (mIU/L)
• Limit of Quantitation (LoQ): 0.010 µIU/mL (mIU/L) (Lower than predicate device's LoQ of 0.008 µIU/mL, but within acceptable range for the new device as specified in assay range) |
  | Precision | - Repeatability (Within-Run):
  • ≤ 12% CV for 0.020–0.299 µIU/mL (mIU/L)
  • ≤ 6% CV for ≥ 0.300–90.000 µIU/mL (mIU/L)
  • ≤ 7% CV for > 90.000 µIU/mL (mIU/L)
• Within-Laboratory (Total Precision):
  • ≤ 16% CV for 0.020–0.299 µIU/mL (mIU/L)
  • ≤ 8% CV for ≥ 0.300–90.000 µIU/mL (mIU/L)
  • ≤ 10% CV for > 90.000 µIU/mL (mIU/L) | Reported values (all calculated Repeatability CV and Within-Laboratory CV values are within the specified limits):
• Serum A (0.088 µIU/mL): Repeatability CV 2.5%, Within-Lab CV 3.6%
• Serum B (0.196 µIU/mL): Repeatability CV 1.8%, Within-Lab CV 3.1%
• Serum C (0.507 µIU/mL): Repeatability CV 1.7%, Within-Lab CV 2.6%
• Serum D (4.752 µIU/mL): Repeatability CV 2.3%, Within-Lab CV 2.7%
• Serum E (46.749 µIU/mL): Repeatability CV 2.4%, Within-Lab CV 4.0%
• Serum F (97.929 µIU/mL): Repeatability CV 2.2%, Within-Lab CV 3.5%
  Similar acceptable results for Plasma and Controls. |
  | Reproducibility | - Reproducibility (Total):
  • ≤ 18.5% CV for 0.020-0.299 µIU/mL (mIU/L)
  • ≤ 10.5% CV for ≥ 0.300-90.000 µIU/mL (mIU/L)
  • ≤ 12.5% CV for > 90.000 µIU/mL (mIU/L) | Reported values (all calculated Reproducibility CV values are within the specified limits):
• Serum A (0.090 µIU/mL): Reproducibility CV 3.11%
• Serum B (0.178 µIU/mL): Reproducibility CV 4.87%
• Serum C (0.474 µIU/mL): Reproducibility CV 2.21%
• Serum D (4.684 µIU/mL): Reproducibility CV 2.47%
• Serum E (56.562 µIU/mL): Reproducibility CV 2.33%
• Serum F (99.522 µIU/mL): Reproducibility CV 4.12%
  Similar acceptable results for Plasma and Controls. |
  | Assay Comparison | - Correlation coefficient (r) ≥ 0.95
• Slope of 1.0 ± 0.1 | - Correlation coefficient (r): 0.999
• Regression Equation (Slope): 0.97 (within 1.0 ± 0.1) |
  | Specimen Equivalency | - Correlation coefficient (r) ≥ 0.95
• Slope of 0.95-1.05 | - Plasma, EDTA vs. Serum: r = 0.999, Slope = 0.99 (within 0.95-1.05)
• Plasma, lithium heparin vs. Serum: r = 0.990, Slope = 1.01 (within 0.95-1.05) |
  | Interferences (HIL) | Bias due to hemoglobin, bilirubin (conjugated/unconjugated), and Intralipid does not exceed 10% | Hemoglobin (500mg/dL), Bilirubin (40mg/dL), Intralipid (1000mg/dL) do not exceed 10% bias at TSH concentrations of ~0.900 µIU/mL and ~8.000 µIU/mL. |
  | Interferences (Other Substances) | Bias due to various common substances does not exceed 10% | Various substances (e.g., Acetaminophen, Aspirin, Biotin, Heparin, Ibuprofen, Levothyroxine) at specified concentrations do not exceed 10% bias at TSH concentrations of ~0.900 µIU/mL and ~8.000 µIU/mL. |
  | Cross-Reactivity | Cross-reactivity of hCG, FSH, and LH does not exceed 5% | hCG (200000 mIU/mL), FSH (1500 mIU/mL), LH (600 mIU/mL) at specified concentrations do not exceed 5% cross-reactivity at TSH concentrations of ~0.400, 5.00, 17.00, and 90.00 µIU/mL. |
  | Linearity | Device is linear throughout its measuring interval (0.010–150.000 µIU/mL) | "The assay is linear for the measuring interval of 0.010–150.000 µIU/mL (mIU/L)." |
  | High-Dose Hook Effect | Results for TSH concentrations above the measuring interval and up to 3000 µIU/mL should report > 150 µIU/mL (not a paradoxical decrease) | "Patient samples with TSH concentrations above the measuring interval and as high as 3000 µIU/mL will report > 150 µIU/mL (mIU/L)." (This confirms the absence of a significant high-dose hook effect within this specified range, meaning the device displays the result as above the measurable range.) |

The study that proves the device meets the acceptance criteria is detailed across the "Performance Characteristics Data" section (Section 8) of the 510(k) Summary.

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

• Detection Capability (LoQ): Not specified (CLSI Document EP17-A2 was followed).
• Precision: 80 measurements (replicates of 2, 2 runs/day, 20-day protocol) for each of the 6 serum samples, 5 plasma samples, and 5 control samples. Total N for Precision study is 80 x (6+5+5) = 1280 measurements.
• Reproducibility: 225 measurements (replicates of 5, 1 run/day, 5-day protocol) for each of the 6 serum samples, 5 plasma samples, and 5 control samples. Total N for Reproducibility study is 225 x (6+5+5) = 3600 measurements.
• Assay Comparison: 973 samples.
• Specimen Equivalency:
  • Plasma, EDTA vs. Serum: 52 samples.
  • Plasma, lithium heparin vs. Serum: 57 samples.
• Interferences (HIL and Other Substances): Samples at two TSH concentrations (~0.900 µIU/mL and ~8.000 µIU/mL) were tested for each interfering substance. The exact number of individual samples tested is not given, but multiple samples would be required for the two TSH levels per substance.
• Cross-Reactivity: Samples at four TSH concentrations (~0.400, 5.00, 17.00, and 90.00 µIU/mL) were spiked with hCG, FSH, or LH. The exact number of individual samples is not given.
• Linearity: Not explicitly stated, but performed in accordance with CLSI Document EP06-ed2, which involves testing multiple diluted samples.
• High-Dose Hook Effect: Samples with TSH concentrations up to 3000 µIU/mL were evaluated. The number of samples tested is not explicitly stated.

Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given it's an in vitro diagnostic device, the samples would generally be human biological specimens, likely collected from a clinical laboratory setting. The use of CLSI documents (Clinical and Laboratory Standards Institute) suggests standard laboratory practices.

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

This information is not provided in the document. For an in vitro diagnostic assay like TSH, "ground truth" is typically established by:

• The reference method against which the new assay is compared (for accuracy/assay comparison). In this case, "ADVIA Centaur TSH3-UL assay" is used as the comparative assay (the predicate device).
• Traceability to an international standard (WHO 3rd International Reference Preparation for human TSH (IRP 81/565)), which implies that the TSH values are calibrated against a universally accepted standard, rather than expert consensus on individual patient cases.

4. Adjudication Method for the Test Set

This refers to the process of resolving discrepancies in expert opinions, which is not applicable here as it is an analytical performance study for an IVD, not an interpretative AI device requiring human expert label agreement.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for AI-assisted diagnostic imaging devices where human readers interpret medical images with and without AI assistance. This document pertains to an in vitro diagnostic assay, which involves automated quantitative measurement of a biomarker.

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

Yes, implicitly. The entire performance characterization (Detection Capability, Precision, Reproducibility, Assay Comparison, Specimen Equivalency, Interferences, Cross-Reactivity, Linearity, High-Dose Hook Effect) is describing the standalone performance of the TSH3-Ultra II assay as an automated laboratory test. There is no mention of "human-in-the-loop" for this device's intended diagnostic function.

7. Type of Ground Truth Used

The ground truth for the performance studies is established by:

• Reference materials/standards: For accuracy, the assay is traceable to the World Health Organization (WHO) 3rd International Reference Preparation for human TSH (IRP 81/565).
• Comparative method: For assay comparison, the predicate device (ADVIA Centaur TSH3-UL assay) results serve as the comparative standard.
• Defined concentrations: For precision, linearity, interferences, and cross-reactivity, samples with known or spiked concentrations of TSH or interfering substances are used.

8. Sample Size for the Training Set

The document does not report a training set sample size. This is because the ADVIA Centaur TSH3-Ultra II is a chemical immunoassay, not a machine learning or AI-based device that would typically involve a "training set" in the computational sense. The "development" process for such an assay involves reagent formulation, assay optimization, and calibration curve development, which are distinct from training an AI model.

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

As there is no "training set" in the context of an AI/ML model, this question is not applicable. The assay's analytical characteristics are established through various studies (precision, accuracy, linearity, etc.) using calibrated materials and established reference methods, as detailed in the performance characteristics.

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The Atellica® CH High Sensitivity C-Reactive Protein 2 (hCRP2) assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein (CRP) in human serum and plasma (lithium heparin, sodium heparin or K2 EDTA) on the Atellica® CH Analyzer.

Measurements from Atellica® CH High Sensitivity C -Reactive Protein 2 (hCRP2) may be used as an aid in identification of individuals at risk for future cardiovascular disease. Measurement of hCRP2, when used in coniunction with traditional clinical laboratory evaluation of acute coronary syndromes, may be useful as an independent marker of prognosis for recurrent events in patients with stable coronary disease or acute coronary syndromes.

The Atellica CH High Sensitivity C-Reactive Protein 2 (hCRP2) assay is used for the quantitative determination of C-Reactive protein in human serum and plasma using the Atellica CH analyzer. This device is two ready-to-use reagent packs consisting of 23.1mL Phosphate buffer, polidocanol (1.9g/L), and sodium azide (0.1%) in Pack 1 and 12.3mL Mouse anti-CRP monoclonal antibodies (13mg/L), polystyrene particles (1g/L), human albumin (0.05%) and sodium azide (

Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided FDA 510(k) summary:

Device: Atellica® CH High Sensitivity C-Reactive Protein 2 (hCRP2) assay

1. Table of Acceptance Criteria and Reported Device Performance:

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

• Detection Capability:
  • LoB: 3 reagent lots, 6 blank samples, 5 replicates per sample = 90 determinations.
  • LoD: 495 determinations (270 blank, 225 low-level replicates) using 3 reagent lots.
  • LoQ: 5 native low analyte serum samples, 5 replicates each = 25 determinations.
• Precision (Repeatability/Within-Lab): 80 replicates per specimen (5 serum samples + 1 QC, total 6 specimens).
• Reproducibility (Multi-site/Multi-lot): 225 replicates per specimen (5 serum samples + 3 QCs, total 8 specimens).
• Assay Comparison (Method Comparison): 100 patient samples.
• Specimen Equivalency: 55 patient samples for each specimen type (Sodium Heparin, Potassium EDTA, Lithium Heparin).
• Interferences (HIL & Non-interfering Substances): Not explicitly stated, but typically involves a smaller number of samples spiked with interferents at multiple analyte concentrations.

Data Provenance: Not explicitly stated, but the sample types are human serum and plasma, diluted with Atellica CH diluent (saline) or enriched as needed. This usually implies a mix of commercially sourced and/or in-house collected human samples. There is no information regarding the country of origin or whether the studies were retrospective or prospective.

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

This device is an in vitro diagnostic test for C-Reactive Protein (CRP) concentration. The "ground truth" for a quantitative assay like this is typically established by:

• Reference methods/standards (e.g., ERM-DA474/IFCC for CRP, as mentioned).
• Comparative analysis against a legally marketed predicate device (BN ProSpec CardioPhase hsCRP).
• Standard preparation and gravimetric/volumetric assurance for spiked samples or known concentrations.

Therefore, "experts" in the sense of clinical reviewers or pathologists establishing a diagnostic ground truth is not applicable here. The accuracy of the measurements is compared against established analytical criteria and methodologies.

4. Adjudication Method for the Test Set:

Not applicable in the context of this type of IVD performance study, as there is no subjective interpretation requiring adjudication of results from different observers. The output is a quantitative value (mg/L).

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

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for imaging or diagnostic tests where human interpretation plays a significant role and AI assistance might influence reader performance. For a quantitative in vitro diagnostic assay like high-sensitivity CRP, the measurement is automated and objective.

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

Yes, the studies described (Detection Capability, Precision, Reproducibility, Assay Comparison, Specimen Equivalency, Interferences, High-Dose Hook Effect) are all standalone performance evaluations of the Atellica CH High Sensitivity C-Reactive Protein 2 (hCRP2) assay as an automated laboratory test on the Atellica CH Analyzer. The device is intended for in vitro diagnostic use, meaning it operates without direct human interpretive input beyond running the test and reading the numerical result.

7. The Type of Ground Truth Used:

The ground truth for this device is established through:

• Analytical Standards: The assay is traceable to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference material ERM-DA474/IFCC, which serves as a primary ground truth for CRP concentration.
• Predicate Device Comparison: The performance is compared against a legally marketed predicate device (BN ProSpec CardioPhase hsCRP assay), where the predicate's measurements serve as a comparative standard.
• Reference Intervals: Expected values for cardiovascular risk prediction are based on established clinical guidelines (Pearson TA et al., 2003).
• Spiked Samples: For interference studies, known concentrations of interfering substances are added to samples, and the known concentration of the analyte is the ground truth.

8. The Sample Size for the Training Set:

Not explicitly stated in the 510(k) summary. For a device like this, the "training set" would refer to the samples used during the development and optimization phase of the assay (e.g., reagent formulation, calibration curve development), rather than a machine learning training set. The approval document focuses on the validation or test sets.

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

Similar to point 7, the ground truth for potential "training" (development/optimization) would involve analytical standards (like ERM-DA474/IFCC), purified CRP, and well-characterized human serum/plasma samples, often with known CRP concentrations determined by reference methods or gravimetric/volumetric preparation. The goal would be to develop a robust assay that accurately measures CRP across its analytical range.

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The ADVIA Centaur® NT-proBNPII (PBNPII) assay is for in vitro diagnostic use in the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur® XP system.

In the Emergency Department (ED) and Outpatient (OP) populations, measurements of NT-proBNP are used as an aid in the diagnosis of heart failure (HF) in patients with clinical suspicion of new onset or worsening HF.

The ADVIA Centaur® NT-proBNPII (PBNPII) assay kit includes the Primary Reagent ReadyPack and the Calibrator. The Primary Reagent ReadyPack contains Lite Reagent, Solid Phase Reagent, and Ancillary Well Reagent. The Calibrator includes Low and High Calibrators which are lyophilized.

The provided document discusses the ADVIA Centaur® NT-proBNPII (PBNPII) assay, an in vitro diagnostic device for measuring N-terminal pro-brain natriuretic peptide (NT-proBNP) to aid in the diagnosis of heart failure in Emergency Department (ED) and Outpatient (OP) populations. The submission aims to demonstrate substantial equivalence to the predicate device, the Roche Elecsys proBNP II assay (K072437).

Here's an analysis of the acceptance criteria and the studies that support them:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as a single, consolidated table with pass/fail values for all performance characteristics. Instead, it presents various performance studies with their results. Based on the "Comparison of Technological Characteristics with the Predicate Device" and the "Performance Characteristics" sections, we can infer some criteria and compare the device's performance.

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The Atellica® CH Phencyclidine (Pcp) assay is for in the qualitative or semiguantitative analyses of phencyclidine in human urine using the Atellica® CI Analyzer, using a cutoff of 25 ng/mL. The Pop assay provides only a preliminary analytical test result. A more specific alternative chemical must be used to obtain a confirmed analytical result. Gas chromatography-mass spectrometry (GCMS) is the preferred confirmatory method. The semiquantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas chromatography/mass spectrometry (GC-MS) or liquid chromatography/tandem mass spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.

Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.

The Atellica® CH Vancomycin (Vanc) assay is for in vitro diagnostic use in the quantitative measurement of vancomycin in human serum and plasma (lithium heparin) using the Atellica® CI Analyzer. Vanc test results may be used in the diagnosis and treatment of vancomycin overdose and in monitoring levels of vancomycin to ensure appropriate therapy.

The Atellica CH Pcp assay is a homogenous enzyme immunoassay based on competition between drug in the specimen and drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites. G6PDH activity decreases upon binding to the antibody, so the drug concentration in the specimen can be measured in terms of enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD+) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically at 340/410 nm. Endogenous G6PDH does not interfere because the coenzyme NAD+ functions only with the bacterial (Leuconostoc mesenteroides) enzyme employed in the assay.

The Atellica CH Vanc assay is based on a homogeneous particle enhanced turbidimetric inhibition immunoassay (PETINIA) technique which uses a synthetic particle-vancomycin conjugate (PR) and monoclonal vancomycin specific antibody (Ab). Vancomycin present in the sample competes with vancomycin on the particles for available antibody, thereby decreasing the rate of aggregation. Hence, the rate of aggregation is inversely proportional to the concentration of vancomycin in the sample. The rate of aggregation is measured using bichromatic turbidimetric readings at 545 and 694 nm.

This document describes the analytical performance of two in vitro diagnostic (IVD) assays, the Atellica® CH Phencyclidine (Pcp) assay and the Atellica® CH Vancomycin (Vanc) assay, and does not contain information related to AI/ML clinical studies or multi-reader multi-case (MRMC) comparative effectiveness studies. Therefore, it is not possible to address acceptance criteria and study designs typically found in AI/ML performance evaluations (e.g., sample size for training/test sets, data provenance, expert ground truth, adjudication methods, MRMC studies, standalone performance, etc.).

However, I can extract and present the analytical performance criteria and reported device performance based on the provided text, which are relevant for IVD devices.

Analytical Acceptance Criteria and Reported Device Performance

Atellica® CH Phencyclidine (Pcp) Assay

This assay is for qualitative or semi-quantitative analysis of phencyclidine in human urine. The primary "acceptance" is demonstrated through agreement with a confirmatory method (GC/MS) and robust precision and recovery.

Table 1: Atellica® CH Phencyclidine (Pcp) Assay - Analytical Performance

• Overall POS agreement: 95% (19 true positives + 81 high positives / 108 total positives by Atellica CH)
• Overall NEG agreement: 94% (42 low negatives + 7 negatives / 54 total negatives by Atellica CH)
  Discordant Results (Atellica CI Pcp vs GC/MS cut-off 25 ng/mL):
• Atellica POS, GC/MS NEG: Samples 47 (27 ng/mL vs 18.0 ng/mL), 51 (30 ng/mL vs 24.2 ng/mL), 52 (26 ng/mL vs 24.8 ng/mL) - 3 false positives relative to GC/MS cut-off
• Atellica NEG, GC/MS POS: Samples 53 (21 ng/mL vs 25.8 ng/mL), 54 (20 ng/mL vs 26.7 ng/mL), 56 (22 ng/mL vs 27.6 ng/mL), 57 (24 ng/mL vs 27.8 ng/mL), 58 (24 ng/mL vs 28.5 ng/mL) - 5 false negatives relative to GC/MS cut-off |
  | Precision (Repeatability) | Overall Low CV% (e.g., 2.2% at 18.75 ng/mL, 2.4% at 25 ng/mL, 2.8% at 31.25 ng/mL)
• 0 ng/mL: SD 0.1, N/A CV
• 6.25 ng/mL: SD 0.4, 6.7% CV
• 12.5 ng/mL: SD 0.4, 3.3% CV
• 18.75 ng/mL: SD 0.4, 2.2% CV
• 25 ng/mL (Cutoff): SD 0.6, 2.4% CV
• 31.25 ng/mL: SD 0.9, 2.8% CV
• 37.5 ng/mL: SD 0.9, 2.3% CV
• 43.75 ng/mL: SD 1.1, 2.6% CV
• 50 ng/mL: SD 1.7, 3.3% CV |
  | Precision (Within-Lab) | Overall Low CV% (e.g., 4.4% at 18.75 ng/mL and 25 ng/mL, 5.3% at 31.25 ng/mL)
• 0 ng/mL: SD 0.20, N/A CV
• 6.25 ng/mL: SD 0.6, 10.0% CV
• 12.5 ng/mL: SD 0.6, 5.0% CV
• 18.75 ng/mL: SD 0.8, 4.4% CV
• 25 ng/mL (Cutoff): SD 1.1, 4.4% CV
• 31.25 ng/mL: SD 1.7, 5.3% CV
• 37.5 ng/mL: SD 2.3, 5.9% CV
• 43.75 ng/mL: SD 2.5, 5.8% CV
• 50 ng/mL: SD 3.7, 7.1% CV |
  | Reproducibility (Total) | Overall Low CV% (e.g., 6.1% for Urine QC 1, 5.8% for Urine QC 2, 6.5% for Urine QC 3)
• Urine QC 1 (18 ng/mL): SD 1.1, 6.1% CV
• Urine QC 2 (24 ng/mL): SD 1.4, 5.8% CV
• Urine QC 3 (34 ng/mL): SD 2.2, 6.5% CV |
  | Recovery | Mean Recovery ranging from 90% to 107% across various concentrations.
• 0 ng/mL: 0 ng/mL (N/A %)
• 4 ng/mL: 4 ng/mL (101 %)
• 5 ng/mL: 5 ng/mL (100 %)
• 10 ng/mL: 9 ng/mL (90 %)
• 15 ng/mL: 15 ng/mL (100 %)
• 20 ng/mL: 19 ng/mL (95 %)
• 25 ng/mL: 24 ng/mL (96 %)
• 30 ng/mL: 30 ng/mL (100 %)
• 40 ng/mL: 43 ng/mL (107 %)
• 60 ng/mL: 64 ng/mL (107 %)
• 80 ng/mL: 82 ng/mL (103 %) |
  | Endogenous Substances Interference | No false response relative to the 25 ng/mL cutoff for tested substances (Acetone, Ascorbic Acid, Conjugated bilirubin, Creatinine, Ethanol, Gamma Globulin, Galactose, Glucose, Hemoglobin, Human Serum Albumin, Oxalic Acid, Riboflavin, Sodium Azide, Sodium Chloride, Sodium Fluoride, Urea) at specified concentrations when spiked into control pools (19 ng/mL and 31 ng/mL). |
  | Specificity (Structurally Unrelated Compounds) | No false response relative to the 25 ng/mL cutoff for listed structurally unrelated compounds (e.g., Acetaminophen, Amitriptyline, Caffeine, Ibuprofen, etc.) at specified concentrations when spiked into control pools (19 ng/mL and 31 ng/mL). |
  | Specificity (Structurally Related Compounds - Cross-Reactivity) | Values range from 0.0% to 184.4% for structurally related compounds, indicating varying levels of cross-reactivity. Notably, 1-(1-Phenylcyclohexyl)pyrrolidine (PCPy) showed 154.4% and trans-4-phenyl-4-Piperidinocyclohexanol showed 184.4% cross-reactivity. This typically means these compounds may cause a positive result even if PCP itself is not present, emphasizing the need for confirmatory testing. |
  | Specific Gravity and pH Interference | No interference observed for negative urine pools with specific gravity 1.000–1.030 and pH 3–10, when tested at ±25% of the cutoff concentration. |
  | Standardization Traceability | Traceable to Emit Calibrators/Controls, which are referenced to gravimetrically prepared standards qualified by GC/MS from an independent laboratory (within ±10% of nominal). |

Atellica® CH Vancomycin (Vanc) Assay

This assay is for quantitative measurement of vancomycin in human serum and plasma.

Table 2: Atellica® CH Vancomycin (Vanc) Assay - Analytical Performance

• Serum QC 1 (6.1 µg/mL): SD 0.14, 2.3% CV
• Serum 1 (13.4 µg/mL): SD 0.13, 1.0% CV
• Serum QC 2 (19.5 µg/mL): SD 0.15, 0.8% CV
• Serum QC 3 (32.6 µg/mL): SD 0.34, 1.0% CV
• Serum 2 (46.1 µg/mL): SD 0.54, 1.2% CV |
  | Precision (Within-Laboratory) | Overall Low CV% (e.g., 1.5% - 2.8%).
• Serum QC 1 (6.1 µg/mL): SD 0.17, 2.8% CV
• Serum 1 (13.4 µg/mL): SD 0.20, 1.5% CV
• Serum QC 2 (19.5 µg/mL): SD 0.33, 1.7% CV
• Serum QC 3 (32.6 µg/mL): SD 0.61, 1.9% CV
• Serum 2 (46.1 µg/mL): SD 0.89, 1.9% CV |
  | Reproducibility (Total) | Overall Low CV% (e.g., 1.8% - 4.0%).
• Serum QC 1 (6.0 µg/mL): SD 0.24, 4.0% CV
• Serum 1 (13.4 µg/mL): SD 0.27, 2.0% CV
• Serum QC 2 (19.7 µg/mL): SD 0.38, 1.9% CV
• Serum QC 3 (32.9 µg/mL): SD 0.62, 1.9% CV
• Serum 2 (45.9 µg/mL): SD 0.81, 1.8% CV |
  | Assay Comparison (Correlation vs. Predicate) | Correlation coefficient ≥ 0.980 and slope 1.00 ± 0.10.
• Regression Equation: y = 0.97x + 0.3 µg/mL (y = 0.97x + 0.2 µmol/L)
• Correlation coefficient (r): 0.999 (for 107 serum samples in range 4.1–45.9 µg/mL). Meets criteria. |
  | Specimen Equivalency (Serum vs. Plasma (Lithium Heparin)) | Demonstrated equivalency between plasma and serum.
• Regression Equation: y = 1.00x - 0.1 µg/mL (y = 1.00x - 0.7 µmol/L)
• Correlation coefficient (r): 0.996 (for 50 samples in range 4.5–43.9 µg/mL). |
  | Interferences (Hemolysis, Icterus, Lipemia - HIL) | ≤ 10% bias.
• Hemoglobin (1000 mg/dL): 2% and 6% bias at two analyte levels.
• Bilirubin, conjugated (30 mg/dL): 0% and 1% bias.
• Bilirubin, unconjugated (30 mg/dL): -2% and -1% bias.
• Lipemia (Intralipid® 2000 mg/dL): 8% and 6% bias.
• Lipemia (from trig fraction 2000 mg/dL): 6% and 8% bias. *All results meet the

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The A-LYTE® Integrated Multisensor (IMT Na K Cl) is for in vitro diagnostic use in the quantitative determination of sodium, potassium, and chloride (Na, K, Cl) in human serum, plasma (lithium heparin) and urine using the Atellica® Cl Analyzer. Measurements of sodium obtained by this device are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of arge amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance. Measurements of potassium obtained by this device are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.

The A-LYTE Na, K, and Cl assays use indirect Integrated Multisensor Technology (IMT). There are four electrodes used to measure electrolytes. Three of these electrodes are ionselective for sodium, potassium and chloride. A reference is also incorporated in the multisensor.

A diluted sample (1:10 with A-LYTE IMT Diluent)) is positioned in the sensor and Na+. K+ or Cl- ions establish equilibrium with the electrode surface. A potential is generated proportional to the logarithm of the analyte activity in the sample. The electrical potential generated on a sample is compared to the electrical potential generated on a standard solution, and the concentration of the desired ions is calculated by use of the Nernst equation.

This document describes the performance characteristics of the A-LYTE® Integrated Multisensor (IMT Na K Cl) device, which is used for the quantitative determination of sodium, potassium, and chloride in human serum, plasma, and urine. The information provided outlines the acceptance criteria for various performance metrics and the study results demonstrating that the device meets these criteria.

Here's a breakdown of the requested information:

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

The document doesn't explicitly list "acceptance criteria" in a separate table, but rather describes the design goals or target performance for each characteristic, followed by the obtained results. I will present these as acceptance criteria and reported performance.

Table 1: Acceptance Criteria and Reported Device Performance

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

• Test Set Sample Sizes:

  • Detection Capability (LoQ): 180 determinations for each analyte (Na, K, Cl) in both serum/plasma and urine.
  • Linearity: 5 replicates per level for at least nine levels, implying a minimum of 45 measurements per analyte and sample type.
  • Precision: N ≥ 80 for each sample type (serum and urine) for each analyte (Na, K, Cl).
  • Assay Comparison:
    • Na (Serum): 123 samples
    • Na (Urine): 117 samples
    • K (Serum): 119 samples
    • K (Urine): 117 samples
    • Cl (Serum): 123 samples
    • Cl (Urine): 127 samples
  • Reproducibility: N=225 results for each sample type (serum QC, human serum, human urine) per analyte (Na, K, Cl), with n=5 assays in 1 run for 5 days using 3 instruments and 3 sensor lots.
  • Specimen Equivalency:
    • Na (Lithium heparin plasma vs Serum): 138 samples
    • K (Lithium heparin plasma vs Serum): 56 samples
    • Cl (Lithium heparin plasma vs Serum): 136 samples
  • Interferences: Not explicitly stated as a single "sample size," but implied from the number of test concentrations and conditions evaluated (e.g., specific concentrations of hemoglobin, bilirubin, lipemia).
  • Non-Interfering Substances: Not explicitly stated as a single "sample size," but implied from the number of test concentrations and conditions evaluated.

• Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. Given it's a 510(k) submission for an in vitro diagnostic device, these studies are typically prospective validation studies conducted at the manufacturer's R&D facilities or contracted labs, adhering to CLSI guidelines.

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

This device is an in vitro diagnostic (IVD) for quantitative determination of electrolytes. The "ground truth" (or reference values) for these types of devices is established through:

• Reference Methods: Comparison against established, well-characterized reference methods or instruments (e.g., the predicate device in the assay comparison, or other highly accurate laboratory methods). In this case, "Atellica CH Na/K/Cl on Atellica CH Analyzer" served as the comparative assay, which itself would have been validated against reference standards.
• Certified Reference Materials: Use of calibrated standards and controls with known analyte concentrations derived from definitive methods.

Therefore, the concept of "experts" (like radiologists interpreting images) establishing ground truth does not directly apply here. Instead, ground truth is based on physical/chemical measurements and their traceability to metrological standards. There are no human experts involved in adjudicating the "truth" of an electrolyte concentration in a sample as there would be in image interpretation.

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

Not applicable. As explained in point 3, the ground truth for this type of quantitative IVD assay is established through comparison to reference methods, not human adjudication of a qualitative or semi-quantitative outcome.

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 automated laboratory analyzer, specifically an Integrated Multisensor for electrolyte measurement. It is not an imaging AI device that assists human readers.

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

Yes, the performance data presented (Detection Capability, Linearity, Precision, Reproducibility, Interferences) represent the standalone performance of the A-LYTE® Integrated Multisensor (IMT Na K Cl) on the Atellica® CI Analyzer. These are direct measurements of the device's analytical precision, accuracy, and interference profiles under controlled laboratory conditions, without human interpretation influencing the quantitative results. The Assay Comparison also represents the device's performance against another automated laboratory system (the predicate device).

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

The ground truth for this device's performance studies is based on:

• Reference Standards/Methods: Calibrated reference materials and comparison to a legally marketed predicate device (TD-LYTE Integrated Multisensor on Trinidad CH System, now Atellica CH System). This ensures that the measured concentrations are accurately determined against established analytical benchmarks.
• Known Concentrations: For linearity, precision, and interference studies, samples are often spiked or diluted to known concentrations, or quality control materials with certified values are used.

8. The sample size for the training set:

Not applicable. This device is a measurement instrument based on established potentiometric technology (Ion-Selective Electrodes). It does not employ machine learning or AI models that require a separate "training set" in the conventional sense. The development and calibration of such devices rely on comprehensive analytical chemistry and engineering principles, using calibration standards, quality control materials, and extensive internal testing during the development phase. The data presented here are for the validation of the finalized device, not for its iterative training.

9. How the ground truth for the training set was established:
Not applicable, as there is no "training set" for an AI model. For the development and calibration of the IMT, the ground truth would be established through a combination of:

• Primary Reference Materials: Use of highly pure chemical standards with accurately known concentrations.
• Secondary Reference Standards: Calibrated solutions traceable to primary standards.
• Reference Measurement Procedures: Highly accurate and precise analytical methods (e.g., flame photometry, coulometry, or isotope dilution mass spectrometry for elemental analysis) used to assign values to control materials and calibrators.
• Internal R&D and Optimization: Extensive testing and refinement of the sensor and instrument performance using these traceable standards during the development process.

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The Emit® II Plus Buprenorphine Assay is a homogeneous enzyme immunoassay with a 5 ng/mL cutoff. The assay is intended for use in laboratories for the qualitative and/or semiquantitative analyses of buprenorphine in human urine. Emit® II Plus assays are designed for use with a number of chemistry analyzers.

The semiquantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/Mass Spectrometry (LC/MS) or permitting laboratories to establish quality control procedures.

The Emit® II Plus Burrenorphine Assay provides only a preliminary analytical test result. A more specific alternative chemical method(s) must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/ MS) or LC/MS are the preferred confirmatory methods. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.

For Professional Use.

Caution: Federal (USA) law restricts this device to sale by or on the order of a licensed healthcare professional.

For in vitro diagnostic use.

The Emit® II Plus Buprenorphine Assay is a homogeneous enzyme immunoassay technique used for the analysis of specific compounds in human urine. The assay is based on competition between drug in the specimen and drug labeled with the recombinant glucose-6-phosphate dehydrogenase (rG6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen can be measured in terms of enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically. Endogenous serum G6PDH does not interfere because the coenzyme NAD functions only with the bacterial (Leuconostoc mesenteroides) enzyme employed in the assay.

The Emit® II Plus Buprenorphine Assay reagents are provided liquid, ready to use and may be used directly from the refrigerator. The product is sold in three (3) kit sizes: 28 mL, 115 mL, and 1000 mL. Reagents 1 and 2 are provided as a matched set. They should not be interchanged with components of kits with different lot numbers.

Antibody/Substrate Reagent 1: Mouse monoclonal antibodies to buprenorphine (0.53 µg/mL)*.NAD (6.9 mM), G6P (10.9 mM), bovine serum albumin, preservatives, and stabilizers. *The antibody titer and enzyme conjugate activity may vary from lot to lot.

Enzyme Reagent 2: Norbuprenorphine labeled with bacterial rG6PDH (0.50 µg/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers, where the antibody titer and enzyme conjugate activity may vary from lot to lot.

The marketing submission for the Siemens Healthineers Emit® II Plus Buprenorphine Assay (K221605) demonstrates that the device meets its acceptance criteria through various performance studies. Below is a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as strict numerical thresholds in the provided document, but rather demonstrated through the qualitative agreement and recovery percentages, as well as precision and specificity profiles. Based on the "Method Comparison" results, the implicit acceptance criterion for qualitative agreement against LC/MS/MS is a high percentage, and for recovery, it's generally close to 100%. For specificity, it's low or negligible cross-reactivity with other substances (ideally less than the cutoff concentration when tested at high concentrations). For precision, it's low coefficient of variation (CV).

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