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The cobas pro integrated solutions is an IVD device used for the quantitation of clinical chemistry and Ion Selective Electrolyte parameters from various biological fluids.

Glucose HK Gen.3 is an in vitro test for the quantitative determination of glucose in human serum, plasma, urine and CSF on Roche/Hitachi cobas c systems. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia and pancreatic islet cell tumors.

The ISE indirect Na for Gen. 2 is intended for the quantitative determination of sodium in serum, plasma or urine using ion-selective electrodes. Sodium measurements are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion 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.

Elecsys TSH immunoassay is intended for the in vitro quantitative determination of thyrotropin in human serum and plasma. Measurements of TSH are used in the diagnosis of thyroid and pituitary disorders. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

The cobas pro integrated solutions (cobas pro) is a fully automated, random-access, software controlled system intended for in vitro quantitative analysis of analytes in body fluids. It will typically be used in clinical laboratories with large workload. The system consolidates clinical chemistry, homogenous and heterogeneous immunoassays as well as electrolyte testing within one workplace. It consists of a high throughput sample distribution unit (core unit) and different analytical units for ISE (cobas pro ISE analytical unit), clinical chemistry (c 503 analytical unit) and immunoassay (e 801 analytical) testing. The system hardware is comprised of new or previously cleared members of the Roche/Hitachi cobas c or Elecsys families of analyzers. The instrument software is unique to the cobas pro and was developed from previous generations of Roche/Hitachi instrument systems.

Here's a breakdown of the acceptance criteria and study information for the cobas pro integrated solutions device, specifically focusing on the Glucose HK Gen.3, ISE indirect Na for Gen.2, and Elecsys TSH assays.

Preamble: This document describes a Traditional 510(k) Premarket Notification for the cobas pro integrated solutions. The core purpose is to show that previously cleared Glucose, Sodium, and TSH assays, when run on the new cobas pro integrated solutions system, are substantially equivalent to their predicate devices. Therefore, the acceptance criteria and studies presented are largely comparative or validation studies demonstrating consistent performance with previously cleared devices and established analytical standards.

1. Table of Acceptance Criteria and Reported Device Performance

Given that this is a 510(k) submission demonstrating substantial equivalence to pre-existing predicate devices for assays and a new integrated system, the acceptance criteria are generally focused on meeting established performance claims or showing equivalence within acceptable statistical limits. The summary provided focuses on the reported device performance which is then implicitly compared to internal acceptance criteria (often relative to the predicate device or CLSI guidelines).

Note on Acceptance Criteria: The document explicitly states "All samples met the predetermined acceptance criterion" for precision studies. For LoQ, it states "LoQ determined at maximum allowable %TE (total error) of no more than 20% (Glucose and TSH) and 30% (Sodium)." For endogenous interference, it was "recovery of 100±10%". For exogenous interference (common drugs for Elecsys TSH), it was "± 10% of the reference value". For method comparisons, the slope, intercept, and correlation coefficients approaching 1 or 0 respectively, indicate strong agreement, satisfying the intent of substantial equivalence. Specific numerical acceptance criteria are not always stated outright but are implied by the study design and conclusion of meeting criteria.

• Serum Repeatability CV: 0.4%-9.2%
• Serum Intermediate Precision CV: 0.5%-10.0%
• Urine Repeatability CV: 0.4%-8.3%
• Urine Intermediate Precision CV: 0.7%-8.5%
• CSF Repeatability CV: 0.4%-3.0%
• CSF Intermediate Precision CV: 0.5%-3.5%
  ISE indirect Na (N=84 per application):
• Plasma Repeatability CV: 0.3%-0.6%
• Plasma Intermediate Precision CV: 0.5%-1.5%
• Serum Repeatability CV: 0.3%-0.5%
• Serum Intermediate Precision CV: 0.5%-1.7%
• Urine Repeatability CV: 0.3%-0.5%
• Urine Intermediate Precision CV: 0.6%-4.8%
  Elecsys TSH (N=84):
• Repeatability CV: 1.6%-6.3%
• Intermediate Precision CV: 2.4%-11.7% |
  | Analytical Sensitivity | LoQ: Total error not more than 20% (Glucose, TSH), 30% (Na). | Glucose HK Gen.3: LoB: 0.2 mg/dL, LoD: 0.4 mg/dL, LoQ: 1.4 mg/dL.
  Claimed: LoB: 2 mg/dL, LoD: 2 mg/dL, LoQ: 2 mg/dL.
  ISE indirect Na: LoB: 3.50 mmol/L, LoD: 4.42-4.51 mmol/L, LoQ: 11.8-12.2 mmol/L.
  Claimed: LoB: 3.5 mmol/L, LoD: 4.5 mmol/L, LoQ: 12.2 mmol/L.
  Elecsys TSH: LoB: 0.0013-0.0015 µIU/mL, LoD: 0.00282-0.00348 µIU/mL, LoQ: 0.00386-0.00495 µIU/mL.
  Claimed: LoB: 0.0025 µIU/mL, LoD: 0.005 µIU/mL, LoQ: 0.005 µIU/mL. |
  | Linearity/Reportable Range | Deviations within predetermined acceptance criteria. | Glucose HK Gen.3: Serum (R2=0.9999), Urine (R2=0.9997), CSF (R2=0.9992) linear in claimed range (2.0-750 mg/dL).
  ISE indirect Na: Plasma (R2=0.9998), Serum (R2=0.9998), Urine (R2=0.9999) linear in claimed range (80-180 mmol/L for S/P, 20-250 mmol/L for U).
  Elecsys TSH: Serum (R2=0.9972) linear in range 0.004-118 uIU/mL. |
  | High Dose Hook Effect | No hook effect observed up to a specified concentration. | Elecsys TSH: No hook effect up to 1466 uIU/mL TSH. |
  | Endogenous Interference | Recovery of 100 ± 10%. | Glucose HK Gen.3: No interference from albumin, bilirubin, hemolysis, IgG, lipemia, etc. at specified high concentrations.
  ISE indirect Na: No interference from bilirubin, hemolysis, lipemia at specified high concentrations.
  Elecsys TSH: No interference from biotin, lipemia, hemoglobin, bilirubin, rheumatoid factor, immunoglobulins at specified high concentrations. |
  | Exogenous Interference (Drugs) | ± 10% of the reference value in comparison to unspiked samples. | ISE indirect Na: No interference from various common and special drugs at specified concentrations.
  Elecsys TSH: No interference from common and special drugs at specified concentrations. |
  | Analytical Specificity/Cross-Reactivity | % cross-reactivity near zero. | Elecsys TSH: hGH, hCG, LH, FSH showed 0.000% cross-reactivity at high tested concentrations. |
  | Method Comparison to Predicate | Strong correlation (slope ≈ 1, intercept ≈ 0, high R/tau values) indicating substantial equivalence to predicate device/reference method. | Glucose HK Gen.3: Slope close to 1.0, intercept close to 0, strong correlation (Pearson r/Kendall tau close to 1) comparing to cobas c 501.
  ISE indirect Na: Slope close to 1.0, intercept close to 0, strong correlation (Pearson r close to 1) comparing to cobas c 501 ISE and Flame Photometer.
  Elecsys TSH: Slope = 1.018 (LCL/UCL: 1.004/1.025), Intercept = -0.0018 µIU/mL (LCL/UCL: -0.0040/-0.0001), Pearson r = 0.999, Kendall tau = 0.977 when compared to predicate Elecsys TSH on cobas 8000. |
  | Sample Matrix Comparison | Acceptable recovery of analyte values and strong correlation between different sample types (e.g., serum vs. various plasma anticoagulants). | Glucose HK Gen.3: Strong correlation (slope near 1, intercept near 0, r near 1) comparing serum to serum tube with separation gel, and various plasma anticoagulants (K2EDTA, Li-Heparin, NaF/K-Oxalate, NaF/Na2-EDTA, NaF/Citrate/Na2-EDTA, KF/Na2-EDTA).
  ISE indirect Na: Strong correlation (Slope = 1.015, Intercept = -2.69, r = 0.998) between Serum and Li-Heparin Plasma.
  Elecsys TSH: Strong correlation (slope near 1, intercept near 0, r near 1) comparing serum to Li-Heparin, K2-EDTA, and K3-EDTA plasma. |
  | Stability | Stability data supports Roche Diagnostic's claims as reported in the package inserts. (Implied: device maintains performance over its claimed shelf life and in-use stability.) | Stability data for Glucose HK Gen.3, ISE indirect Na, and Elecsys TSH was provided in prior 510(k)s (K061048, K060373, and K190773 respectively) and supports the claims. |

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

• Glucose HK Gen.3 (Precision):
  • Sample Size: 84 measurements for each control level (PreciControl ClinChem Multi 1 and 2) and 5 human serum samples per application (serum, urine, CSF). So, for repeatability and intermediate precision, 84 measurements for 2 controls + 5 samples, across serum, urine, and CSF applications.
  • Data Provenance: Human serum, plasma, urine, and CSF samples. These were "native, single donors as well as pools." The study was conducted in-house by Roche Diagnostics (implied by the submission).
• ISE indirect Na (Precision):
  • Sample Size: 84 measurements for each control level (PreciControl ClinChem Multi 1 and 2, Liquichek 1 and 2) and 5 human plasma, serum, and urine samples per application. So, for repeatability and intermediate precision, 84 measurements for controls + 5 samples, across Li-Heparin Plasma, Serum, and Urine.
  • Data Provenance: Human Li-Heparin plasma, serum, and urine samples. These were "native, single donors as well as pools." Conducted in-house by Roche Diagnostics.
• Elecsys TSH (Precision):
  • Sample Size: 84 measurements for each control level (PreciControl Universal, PC Thyro Sensitive) and 5 human serum samples.
  • Data Provenance: Human serum samples. These were "native, single donors as well as pools." Conducted in-house by Roche Diagnostics.
• Analytical Sensitivity (LoB, LoD, LoQ) for all assays:
  • Sample Size:
    • LoB: ≥ 60 measurements of analyte-free samples.
    • LoD: 60 measurements (5 low-analyte concentration samples, measured in duplicate over 6 runs, 3 days).
    • LoQ: ≥ 60 measurements per sample type (samples with low analyte concentration measured over 3 to 5 days).
  • Data Provenance: Not explicitly stated for specific blanks or low-concentration samples beyond "analyte-free" or "low-analyte concentration". Conducted in-house by Roche Diagnostics.
• Linearity/Assay Reportable Range:
  • Glucose HK Gen.3: Three high analyte human serum, urine, and CSF samples diluted to 12 levels.
  • ISE indirect Na: Three high analyte human serum, urine, and CSF samples diluted to multiple aliquot concentrations.
  • Elecsys TSH: Three high analyte human serum samples diluted to concentrations covering the measuring range.
  • Data Provenance: Human serum, urine, CSF samples. Conducted in-house by Roche Diagnostics.
• Endogenous Interference:
  • Glucose HK Gen.3: Plasma and urine samples, glucose levels ~79.5 mg/dL and ~116.3 mg/dL.
  • ISE indirect Na: Human plasma, serum, and urine samples. Low (~124 mmol/L) and high (~151 mmol/L) for S/P; low (26.3 mmol/L) and high (188 mmol/L) for urine.
  • Elecsys TSH: Human serum samples with TSH concentrations ~0.462 uIU/mL, ~3.95 µIU/mL, and ~7.54 µIU/mL.
  • Data Provenance: Human samples. Conducted in-house by Roche Diagnostics.
• Exogenous Interference (Drugs):
  • ISE indirect Na: Two sample pools (low and high concentration ISE indirect Na).
  • Elecsys TSH: Two human serum samples (~0.5 uIU/mL and ~8 uIU/mL TSH).
  • Data Provenance: Human samples. Conducted in-house by Roche Diagnostics.
• Analytical Specificity/Cross-Reactivity (Elecsys TSH):
  • Sample Size: Native human serum sample pool.
  • Data Provenance: Human serum samples. Conducted in-house by Roche Diagnostics.
• Method Comparison to Predicate:
  • Glucose HK Gen.3: 74 native human serum samples, 67 native human urine samples, 75 native CSF samples.
  • ISE indirect Na: 120 human Lithium heparin plasma samples (vs cobas c 501 ISE), 118 human Lithium heparin plasma (vs Flame Photometer), 120 human serum (vs cobas c 501 ISE), 120 human serum (vs Flame Photometer), 120 human urine (vs cobas c 501 ISE/Flame Photometer).
  • Elecsys TSH: 138 samples (129 native human serum, 9 diluted human serum samples; single donors and pools).
  • Data Provenance: Native human samples (serum, plasma, urine, CSF), some diluted. Conducted in-house by Roche Diagnostics.
• Sample Matrix Comparison:
  • Glucose HK Gen.3: At least 39 serum/plasma pairs for each anticoagulant type (K2-EDTA, Li-Heparin, NaF/K-Oxalate, NaF/Na2-EDTA, NaF/Citrate/Na2-EDTA, KF/Na2-EDTA plasma tubes) + serum vs. serum tube with separation gel.
  • ISE indirect Na: 50 serum/Li-Heparin plasma pairs.
  • Elecsys TSH: Minimum of 56 serum/plasma pairs for Li-Heparin, K2-EDTA, K3-EDTA plasma tubes. Serum separation tubes from 3 manufacturers, blood from five donors were used.
  • Data Provenance: Native human samples. Conducted in-house by Roche Diagnostics.

3. Number of Experts and Qualifications for Ground Truth

This submission concerns in vitro diagnostic (IVD) devices for quantitative measurements of analytes. For such devices, "ground truth" is typically established by:

• Reference methods (e.g., flame photometry for Sodium reference),

• Previously cleared and validated predicate devices,

• Known concentrations in control materials or spiked samples, or

• The inherent chemical/physical measurement by the device itself (for analytical performance criteria like precision, linearity).

• No human "experts" (like radiologists interpreting images) were used to establish ground truth in the context of these analytical performance studies. The "ground truth" is analytical, derived from established chemical/instrumental methods and reference standards.

4. Adjudication Method for the Test Set

Since this is an IVD device for quantitative measurements and the studies are analytical performance evaluations based on instrumental precision, accuracy, and comparison to established methods or predicate devices, there is no adjudication method (e.g., 2+1, 3+1) involving human experts as would be seen in diagnostic imaging studies. The data points are quantitative measurements from the instruments themselves or reference methods. Statistical analysis (e.g., regression, CVs, SDs) is used to assess performance against pre-defined criteria.

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

No MRMC comparative effectiveness study was done. This type of study, involving multiple human readers interpreting cases with and without AI assistance, is relevant for diagnostic imaging AI algorithms where human interpretation is part of the clinical pathway. This submission is for an in vitro diagnostic (IVD) measurement system, not an AI-powered diagnostic imaging tool that assists human readers. The comparative studies involved comparing the new system's analytical performance against predicate IVD systems or reference methods, not human readers.

6. Standalone Performance Study (Algorithm Only)

The entire non-clinical performance evaluation could be considered analogous to a "standalone" performance study, as it describes the analytical performance of the device itself (the integrated system with its assays) without human intervention in the measurement process. The device provides quantitative results, and these results are directly evaluated for precision, linearity, sensitivity, interference, and agreement with predicate devices or reference methods. There is no "human-in-the-loop" aspect to the core measurement and output of these IVD assays.

7. Type of Ground Truth Used

The ground truth used for these analytical studies consists of:

• Known concentrations: For studies like linearity, analytical sensitivity (LoB, LoD, LoQ), and interference, samples prepared with known concentrations of analytes or interferents serve as the ground truth.
• Reference methods: For method comparison studies, well-established and often independently validated reference methods (e.g., flame photometry for sodium measurement) serve as the ground truth or gold standard for comparison.
• Predicate device results: For demonstrating substantial equivalence, the results obtained from a legally marketed predicate device (which itself has established ground truth capabilities) serve as the comparative ground truth.
• Internal statistical controls: For precision studies, consistent and stable control materials are used, where the expected range or value is the "ground truth" against which repeatability and intermediate precision are measured.

8. Sample Size for the Training Set

This document describes the non-clinical performance evaluation for a 510(k) submission, primarily for demonstrating analytical performance and substantial equivalence. It does not describe the development or training of an AI algorithm based on machine learning, so there is no specific "training set" in the context of AI/ML models. The data presented here are validation data for the analytical performance of the assay and integrated system.

For a traditional IVD device, method development involves internal studies and optimization, but this is distinct from "training data" for a machine learning model. The various studies (precision, linearity, etc.) use samples/replicates as described in point 2.

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

As noted in point 8, there isn't a "training set" in the machine learning sense described in this document. If this were to refer to the developmental studies for the underlying assays (Glucose HK Gen.3, ISE indirect Na, Elecsys TSH, which are previously cleared), their ground truth would have been established during their initial development and validation process using:

• Reference materials: Certified reference materials (CRMs) with known analyte concentrations.
• Clinical samples: Patients samples characterized by confirmed diagnoses or clinical outcomes for intended use populations.
• Comparison to established methods: Correlation with existing, approved methods, often considered the "gold standard."
• Spiking and dilution experiments: Preparing samples with known added amounts of analyte.

These are standard practices in IVD assay development, ensuring the analytical and clinical performance of the individual assays before they are integrated into a new system like the cobas pro integrated solutions.

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Immunoassay for the in vitro qualitative detection of IgM antibodies to CMV in human serum, lithium-heparin plasma, K2-EDTA plasma, and K3-EDTA plasma. The test is intended as an aid in the diagnosis of recent or current CMV infection in individuals for which a CMV IgM test was ordered, including pregnant women.

Performance characteristics have not been evaluated in immunocompromised or immunosuppressed individuals. This test is not intended for use in neonatal screening or for use at point of care facilities. This test is not intended for use in screening blood and plasma donors.

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

Elecsys CMV IgM is a qualitative assay for the detection of IgM antibodies to CMV in human serum and plasma for use on the cobas e 801 immunoassay analyzer. The cobas e 801 immunoassay analyzer is a fully automated, software controlled analyzer system for in vitro determination of analytes in human body fluids. It is part of the cobas 8000 modular analyzer series cleared under K100853. It uses electrochemiluminescent technology for signal generation and measurement.

The document describes the Elecsys CMV IgM assay on the cobas e 801 analyzer, which is a qualitative immunoassay for the detection of IgM antibodies to CMV. The submission (K163569) seeks to demonstrate substantial equivalence to a predicate device, the Elecsys CMV IgM on the cobas e 601 (K142133).

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

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly present a "table of acceptance criteria" with corresponding performance values in every section, but rather states "All results met predefined acceptance criteria" for various performance characteristics. I will compile the relevant performance data points that were provided.

• HSP 1: 1.2%
• HSP 2: 1.3%
• HSP 3: 1.6%
• HSP 4: 1.0%
• HSP 5: 1.0%
• PC CMV IgM 1: 0.9%
• PC CMV IgM 2: 1.9% |
  | | | Intermediate Precision (CV)
• HSP 1: 2.8%
• HSP 2: 1.8%
• HSP 3: 1.8%
• HSP 4: 1.4%
• HSP 5: 1.8%
• PC CMV IgM 1: 2.6%
• PC CMV IgM 2: 2.2% |
  | Analytical Sensitivity | Implicit: LoD below cut-off. | Limit of Blank (LoB): 0.243 COI
  Limit of Detection (LoD): 0.276 COI (well below cut-off of 0.7 COI) |
  | High Dose Hook Effect | Implicit: No high-dose hook effect observed. | "All results met the predefined acceptance criteria demonstrating no high dose hook effect for the Elecsys CMV IgM assay." |
  | Endogenous Interferences | Implicit: No significant interference from tested substances. | No interference from:
• Hemoglobin up to 500 mg/dL
• Intralipid up to 1500 mg/dL
• Bilirubin up to 20 mg/dL
• Biotin up to 100 ng/mL
• Rheumatoid factor up to 899 IU/mL |
  | Exogenous Interferences (Anticoagulants) | Implicit: Acceptable sample types. | Serum, serum with separating gel, Li-heparin plasma, K2EDTA plasma, K3EDTA plasma are acceptable. |
  | Exogenous Interferences (Drugs) | Implicit: No significant interference from tested drugs. | No interference from 18 common drugs, Ganciclovir, and Valganciclovir. |
  | Method Comparison (Platform Equivalence) | Implicit: High positive and negative agreement. | Negative Percent Agreement (NPA): 100% (142/142)
  Positive Percent Agreement (PPA): 100% (73/73)
  Agreement rate for Indeterminate: 75% (6/8) |

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

The document focuses on the technical performance of the device and its equivalence to a predicate. It does not clearly define a "test set" in the context of clinical cohorts but rather describes samples used for various analytical performance studies.

• Precision Study: 84 runs for repeatability and intermediate precision for each of the 7 samples (HSP 1-5, PC CMV IgM 1-2). The samples are referred to as "serum samples." Provenance is not specified (e.g., country of origin, retrospective/prospective).
• Method Comparison (Between Analyzer Platforms): 142 negative plasma samples, 73 positive plasma samples, and 8 indeterminate plasma samples. This totals 223 plasma samples. Provenance (e.g., country, retrospective/prospective) is not specified.
• Interference Studies: Number of samples not explicitly stated; typically involves spiking substances into a limited number of samples.
• Analytical Sensitivity (LoB/LoD): Number of runs/replicates used for determination is not specified, but the methodology (CLSI EP17-A2) implies a structured approach.

Data Provenance: The document generally lacks explicit details on the country of origin for the samples used in these performance studies or whether they were retrospective or prospective. It refers to "in-house studies" and "external clinical studies" for cutoff validation, but specifics are missing from this summary.

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

This device is an in vitro diagnostic immunoassay, not an imaging device. Therefore, the concept of "experts" (like radiologists) establishing ground truth for a "test set" in the traditional sense of image interpretation is not directly applicable.

For this type of device:

• The "ground truth" for the test samples (e.g., positive, negative, indeterminate) would typically be established by known clinical status (e.g., confirmed CMV infection or absence of infection based on various clinical and laboratory parameters, potentially using a "gold standard" or reference assay).
• The document implies that the "cutoff was established with in-house studies by characterizing samples using several commercially available CMV IgG and CMV IgM assays" and "validation of the assay cutoff was performed by external clinical studies." This suggests the ground truth (or referent status) for the samples was determined by established laboratory methods, not expert consensus on qualitative interpretation.

No specific number or qualification of "experts" is mentioned for establishing the ground truth of the performance study samples.

4. Adjudication Method for the Test Set

Since this is an immunoassay and "ground truth" is established by laboratory methods rather than subjective expert interpretation, the concept of an "adjudication method" (like 2+1 or 3+1) is not applicable here. The results are quantitative (COI values) and then categorized based on predefined cut-offs.

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 specifically designed for evaluating diagnostic aids (like AI algorithms in imaging) that assist human readers. The Elecsys CMV IgM assay is a standalone laboratory diagnostic test.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) was Done

Yes, the performance data presented (precision, sensitivity, interference, method comparison) represents the standalone performance of the Elecsys CMV IgM assay on the cobas e 801 analyzer. This device does not have a human-in-the-loop component for its primary diagnostic function.

7. The Type of Ground Truth Used

The ground truth used for establishing performance characteristics and assay cut-offs appears to be:

• For Method Comparison: The results from the predicate device (Elecsys CMV IgM on cobas e 601) and potentially other established/commercial CMV IgM assays. The document states "Positive and negative agreement of the results between the two platforms were calculated."
• For Assay Cut-off: "in-house studies by characterizing samples using several commercially available CMV IgG and CMV IgM assays." Additionally, "Validation of the assay cutoff was performed by external clinical studies on the Elecsys 2010." This implies a combination of reference assay results and potentially clinical outcomes/established disease status for the samples used in those studies.

It's not explicitly stated as "pathology" or "outcomes data" in this summary, but rather defined by comparison to other commercial assays and clinical studies.

8. The Sample Size for the Training Set

This document describes the validation of a commercial in vitro diagnostic assay, not an AI/machine learning algorithm that requires a "training set" in the same way. The principles for developing diagnostic assays involve extensive research and development phases where reagents, protocols, and cutoffs are refined. The "training" in this context refers to the development and optimization studies that led to the final assay characteristics.

The specific sample sizes for these development/optimization phases are not provided in this 510(k) summary, as the summary focuses on the final analytical and comparative performance data for the substantial equivalence determination.

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

Again, applying the term "training set" directly to a traditional immunoassay is not precise. However, for the establishment of the assay cut-off (which is analogous to setting decision boundaries in an algorithm), the summary states:

• "The cutoff was established with in-house studies by characterizing samples using several commercially available CMV IgG and CMV IgM assays."
• "Validation of the assay cutoff was performed by external clinical studies on the Elecsys 2010."

This indicates that the "ground truth" for determining the assay cut-offs was established through a combination of results from other established commercial CMV assays and samples from clinical studies, which would have had their CMV status determined by other means (e.g., patient history, other diagnostic tests, or clinical follow-up). The exact "how" for these broader clinical studies is referenced as being included in the predicate device's K-submission (K142133).

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In vitro test for the quantitative determination of vancomycin in serum and plasma on Roche/Hitachi cobas c systems.

A vancomycin test system is a device intended to measure vancomycin, an antibiotic drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of vancomycin overdose and in monitoring the level of vancomycin to ensure appropriate therapy.

The ONLINE TDM Vancomycin Gen.3 is a two reagent assay for the in vitro quantitative determination of vancomycin in human serum or plasma on automated clinical chemistry analyzers. It is a homogeneous microparticle agglutination immunoassay based on the kinetic interaction of microparticles in solution (KIMS). A competitive reaction takes place between the drug conjugate and vancomycin in the serum sample for binding to the vancomycin antibody on the microparticles. The resulting kinetic interaction of microparticles is indirectly proportional to the amount of drug present in the sample.

The provided text details the performance evaluation of the "ONLINE TDM Vancomycin Gen.3" device. Here's a breakdown of the requested information:

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

The document doesn't explicitly state "acceptance criteria" as separate rows but presents performance study results, implying these results are considered acceptable for substantial equivalence. The table below compiles the reported performance data.

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

• Detection Limit (LoB, LoD):
  • LoB: 60 measurements (5-fold determinations per run, 6 runs over 3 days, across one or two instruments) per lot.
  • LoD: 30 samples/measurements (5 serum samples, 6 runs over 3 days, 1-fold or 2-fold determination per run, across one or two instruments) per lot.
  • LoQ: 15 serum samples, tested in two aliquots over 6 runs for 4 days.
• Precision: Not explicitly stated, but "two runs per day for $\geq$ 21 days" were performed. The number of samples for controls (3) and human serum (5) are listed, with replicates per run not specified but implied to be sufficient for precision calculations.
• Linearity: Sixteen levels (dilution series from a human serum sample pool and diluent) were prepared. The process was repeated for plasma samples.
• Matrix Comparison: 67 full tubes and 9 half-filled tubes of serum and plasma from a single donor. (K2-EDTA plasma had 10 half-filled tubes).
• Interferences (H, L, I Indices): Two human serum sample pools spiked with Vancomycin. An 11-step dilution series prepared for each interferent, with 3 aliquots per level tested.
• Interferences (Drugs): Two human serum sample pools spiked with Vancomycin. Tested with 3 replicates.
• Method Comparison to Predicate: 125 single native human serum samples from patients taking Vancomycin. 8 additional native Vancomycin samples were spiked, and 1 sample diluted to cover the range.

The data provenance regarding the country of origin is not specified. All studies appear to be prospective experimental studies conducted in a controlled lab setting, rather than retrospective patient data analysis.

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 device is an in-vitro diagnostic (IVD) assay for quantitative determination of vancomycin concentration. The "ground truth" for these types of devices is based on established analytical reference methods or assigned values.

• For LoQ, the expected value was determined with Vancomycin LCMS/MS, which is a highly accurate reference method, not expert consensus.
• For Method Comparison to Predicate, the predicate device (ONLINE TDM Vancomycin, K060586) served as the reference standard for comparison, not human experts.
• No human experts were involved in establishing the ground truth for any of these analytical performance studies. These are laboratory-based measurements.

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

Not applicable. This is an IVD device for quantitative measurement, not an imaging or qualitative diagnostic device requiring expert adjudication. The "truth" is determined by analytical reference methods or comparison to a predicate device.

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 device for quantitative measurement, not an AI-assisted diagnostic tool for human readers.

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

This entire submission describes the standalone performance of the ONLINE TDM Vancomycin Gen.3 assay. The device itself is an automated chemical analyzer system (Roche/Hitachi cobas c systems) that performs the assay, not an AI algorithm. The performance metrics listed (detection limit, precision, linearity, interference, method comparison) are all standalone analytical performance characteristics of the device.

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

The ground truth or reference methods used for evaluation include:

• LCMS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry): Used for determining expected values for the Limit of Quantitation (LoQ).
• Predicate Device (ONLINE TDM Vancomycin, K060586): Used as the comparative reference for the method comparison study.
• Standard Analytical Protocols: Studies like precision, linearity, and interference follow established CLSI guidelines, where the "truth" is defined by the experimental setup (e.g., known concentrations of analytes, spiked interferents).

8. The sample size for the training set

Not applicable. This device is an IVD assay, not a machine learning or AI-based system that requires a "training set" in the conventional sense. The development of such assays involves reagent formulation, optimization, and extensive analytical verification and validation, but not typically "training data" for an algorithm.

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

Not applicable, as there is no "training set" for an AI algorithm here.

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The LDL-Cholesterol Gen. 3 assay is an in-vitro test for the quantitative determination of LDL-cholesterol in human serum and plasma on Roche/Hitachi cobas c systems. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.

The LDL-Cholesterol Gen. 3 assay is a homogeneous enzyme colorimetric assay which provides the quantitative measurement of LDL-cholesterol in human serum and plasma. Reagents are packaged in a cassette labeled with their instrument positioning R1 (Reagent 1) and R2 (Reagent 2).

R1 contains Bis-trisb) buffer: 20.1 mmol/L, pH 7.0; 4-aminoantipyrine:0.98 mmol/L; ascorbic oxidase (AOD, Acremonium spec.): ≥ 66.7 µkat/L; peroxidase (recombinant from Basidiomycetes): ≥ 166.7 µkat/L; BSA: 4.0 g/L; preservative R2 contains MOPSC) buffer: 20.1 mmol/L, pH 7.0; EMSE: 2.16 mmol/L, cholesterol esterase (Pseudomonas spec.): ≥ 33.3 µkat/L; cholesterol oxidase (recombinant from E.coli)): ≥ 31.7 µkat/L; peroxidase (recombinant from Basidiomycetes): ≥ 333.3 µkat/L; BSA: 4.0 g/L; detergents; preservative

Here's a breakdown of the acceptance criteria and study information for the LDLC3 LDL-Cholesterol Gen.3 device, organized as requested:

Acceptance Criteria and Device Performance Summary

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The ISE module of the Roche / Hitachi systems is intended for the quantitative determination of sodium, potassium, and chloride in serum, plasma, or urine using ion-selective electrodes.

Sodium measurements are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large 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.

Potassium measurements 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 cobas 6000 analyzer series with an ISE module is an Ion-Selective Electrode (ISE) system for the determination of sodium, potassium, and chloride in serum, plasma, and urine. The cobas 6000 analyzer series, including the cobas c 501 with ISE for Serum, Plasma and Urine sample types was previously cleared in K060373. This premarket notification seeks to obtain FDA review and clearance for the cobas c 501 ISE, Modified Calibration for Serum, Plasma and Urine sample types.

An ISE makes use of the unique properties of certain membrane materials to develop an electrical potential (electromotive force, EMF) for the measurements of ions in solution. The electrode has a selective membrane in contact with both the test solution and an internal filling solution. The internal filling solution contains the test ion at a fixed concentration. Because of the particular nature of the membrane; the test ions will closely associate with the membrane on each side. The membrane EMF is determined by the difference in concentration of the test ion in the test solution and the internal filling solution. The EMF develops according to the Nernst equation for a specific ion in solution (see package insert for further explanation).

Aqueous ISE Standards Low and High were cleared in K053165. The modified calibration in this submission included the use of ISE Standards Low (S1) and High (S2) for 2-point calibration and the Standard High for compensation (S3). Previously, a serum-based ISE compensator was used for S3 compensation. The modification is switching from serum-based ISE compensator for S3 to ISE Standard High. In the new calibration scheme, the ISE Standard High will be used for both S2 and S3.

The provided text describes a 510(k) summary for the cobas c 501 ISE, Modified Calibration for Sodium, Potassium, and Chloride assays. It focuses on demonstrating substantial equivalence to a predicate device rather than presenting a study for meeting acceptance criteria in the typical AI/ML context. However, I can extract and structure the information into the requested format by interpreting "acceptance criteria" as the performance parameters considered for substantial equivalence and "reported device performance" as the data provided for the modified device.

Here's the breakdown:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly derived from the performance of the predicate device and the new device showing comparable or improved performance for various metrics. The study aims to demonstrate that the modified calibration maintains or improves performance.

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

The "test set" here refers to the samples used for method comparison studies.

• Sodium (Serum/Plasma): N = 52 (Plasma, Modified), N = 51 (Serum, Modified). N = 51 (Plasma, Predicate).
• Sodium (Urine): N = 100 (Modified). N = 51 (Predicate).
• Potassium (Serum/Plasma): N = 52 (Plasma, Modified), N = 54 (Serum, Modified). N = 51 (Plasma, Predicate).
• Potassium (Urine): N = 105 (Modified). N = 51 (Predicate).
• Chloride (Serum/Plasma): N = 52 (Plasma, Modified), N = 53 (Serum, Modified). N = 51 (Plasma, Predicate).
• Chloride (Urine): N = 105 (Modified). N = 51 (Predicate).

Data Provenance: The document does not specify the country of origin of the data. The studies appear to be prospective, laboratory-based analytical studies designed to test the performance of the modified device against a reference method and the predicate device. They are not clinical studies necessarily involving patient outcomes.

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

This type of information is not applicable to this submission. This is a submission for an in vitro diagnostic (IVD) device (a measurement instrument and reagents) used to quantify specific analytes (sodium, potassium, chloride) in biological samples. The "ground truth" for the test set is established by recognized reference methods (e.g., Flame Photometry, Coulometry) which are laboratory instruments, not human experts making diagnostic decisions. There were no experts involved in establishing ground truth for these analytical performance studies.

4. Adjudication Method for the Test Set

This is not applicable. As stated above, this is an analytical performance study using objective reference standard measurements, not human interpretation requiring adjudication.

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

This is not applicable. MRMC studies are typically performed for AI/ML diagnostic interpretation algorithms where human readers' performance is evaluated and compared with and without AI assistance. This submission is for an IVD device where measurements are performed by an automated analyzer, not human "readers" interpreting cases.

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

The study described is inherently a "standalone" or "algorithm only" performance evaluation relative to the context of AI/ML. The device (cobas c 501 ISE with modified calibration) performs the measurement and produces results without human interpretation of raw data in the same way an AI algorithm would. The study directly evaluates the analytical performance of this automated system.

7. The Type of Ground Truth Used

The ground truth for the analytical performance studies was established using:

• Reference Methods:
  • Flame Photometry for Sodium (Plasma, Urine) and Potassium (Plasma, Urine).
  • Coulometry for Chloride (Plasma, Urine).
• Predicate Device Performance: The original cobas c 501 ISE Gen. 2 with serum-based ISE Compensator (K053165) served as a benchmark for comparison to demonstrate substantial equivalence, rather than a "ground truth" per se.

8. The Sample Size for the Training Set

This is not applicable in the context of AI/ML. This device is a chemistry analyzer with a modified calibration process, not a machine learning algorithm that requires a "training set" in the conventional sense. The "training" of the device involves the 2-point calibration and compensation using ISE Standards Low (S1) and High (S2, S3), as described in the submission.

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

This is not applicable in the context of AI/ML. The "ground truth" for the calibration process is established by the known concentrations of the ISE Standards Low (S1) and High (S2, S3). These are manufactured with highly controlled, known concentrations, serving as the basis for the instrument's calibration.

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cobas c Bilirubin Total Gen.3 is an in vitro test for the quantitative determination of total bilirubin in serum and plasma of adults and neonates on Roche/Hitachi cobas c systems. Measurement of the levels of bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall bladder block.

cobas c Bilirubin Total Gen.3 reagent provides quantitative measurement of the total bilirubin that is present in serum and plasma of adults and neonates. Reagents are packaged in a cassette with two bottles labeled with their instrument positioning, R1 (Reagent 1) and R2 (Reagent 2). R1 contains detergent, buffer, and stabilizers at pH 1.0. R2 is a 3,5-dichlorophenyl diazonium salt: ≥ 1.35 mmol/L.

The provided text describes the 510(k) summary for the cobas c Bilirubin Total Gen.3 device, a quantitative colorimetric method for determining total bilirubin in serum and plasma. The acceptance criteria and supporting studies are detailed for various performance characteristics.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

• PCCC1: 0.02 mg/dL (2.1% CV)
• PCCC2: 0.02 mg/dL (0.6% CV)
• Human Serum 1 (0.51 mg/dL): 0.01 mg/dL (2.9% CV)
• Human Serum 2 (17.7 mg/dL): 0.10 mg/dL (0.6% CV)
• Human Serum 3 (31.8 mg/dL): 0.14 mg/dL (0.4% CV)
  Intermediate Precision (Total Imprecision):
• PCCC1: 0.02 mg/dL (2.1% CV)
• PCCC2: 0.03 mg/dL (0.8% CV)
• Human Serum 1 (0.51 mg/dL): 0.02 mg/dL (3.3% CV)
• Human Serum 2 (17.7 mg/dL): 0.14 mg/dL (0.8% CV)
• Human Serum 3 (31.8 mg/dL): 0.18 mg/dL (0.6% CV) |
  | Linearity/Measuring Range | For both serum and plasma, the first-order (linear) regression must be significant. | Serum: Range tested and found: 0.12-38.9 mg/dL. Recommended measuring range: 0.15-35.1 mg/dL. Linear Regression: y=1.0021x-0.0317, r² = 0.999881 (Significant).
  Plasma: Range tested and found: 0.12-39.0 mg/dL. Recommended measuring range: 0.15-35.1 mg/dL. Linear Regression: y = 1.0014x - 0.0232, r² = 0.999954 (Significant). |
  | Detection Limit (LoB, LoD, LoQ) | Not explicitly stated in terms of acceptance criteria values, but the reported claims represent the specifications. The LoQ is determined based on precision at 20% CV. | LoB claim: 0.10 mg/dL
  LoD claim: 0.15 mg/dL
  LoQ claim: 0.15 mg/dL |
  | Analytical Specificity (Endogenous Substances) | Lipemia: ≤± 0.10 mg/dL for samples ≤ 1 mg/dL or ≤± 10% for samples > 1 mg/dL
  Hemolysis HbA: ≤±0.20 mg/dL for samples ≤ 2 mg/dL or ≤± 10% for samples > 2 mg/dL
  Hemolysis HbF: ≤± 0.10 mg/dL for samples ≤ 1 mg/dL or ≤ ± 10% for samples > 1 mg/dL
  Indican: ≤± 0.10 mg/dL for samples ≤ 1 mg/dL or ≤± 10% for samples > 1 mg/dL | Lipemia: No significant interference up to an L index of 1000. (Tested up to 1196-1217 L index)
  Hemolysis HbA: No significant interference up to an H index of 800. (Tested up to 946-951 H index)
  Hemolysis HbF: No significant interference up to an H index of 1000. (Tested up to 1047-1053 H index)
  Indican: No significant interference from indican up to 3 mg/dL. (Tested up to 3.75 mg/dL) |
  | Analytical Specificity (Common Drugs) | Difference in recovery to the reference sample: ≤± 10% | All tested drugs (Acetylcystein, Ampicillin - Na, Ascorbic acid, Phenylbutazone, Cyclosporine A, Cefoxitin, Levodopa, Methyldopa + 1.5, Metronidazole, Doxycyclin, Acetylsalycilic acid, Rifampicin, Acetaminophen, Ibubrofen, Theophylline) passed the acceptance criteria at their respective highest concentrations. |
  | Matrix Comparison (Anticoagulants) | For sample concentrations ≤ 0.99 mg/dL, the deviation must be ≤ ± 0.10 mg/dL. For sample concentrations > 0.99 mg/dL, the deviation must be ≤± 10%. | All data passed the criteria.
• Li-Heparin (full & half), K2-EDTA (full & half), and Gel Separation Tube showed acceptable recovery within the tested ranges (e.g., Li-Heparin full: 0.35 - 34.52 mg/dL).
• Serum vs. Li-heparin: y = 1.000x + 0.000, r = 0.9998 |
  | Adult Method Comparison with Predicate Device | Not explicitly stated with a numerical criterion, but the strong correlation (r=0.9997) and the regression equation (y = 0.959x + 0.091 mg/dL) demonstrate substantial agreement. | Equation: y = 0.959x + 0.091 mg/dL
  Correlation coefficient: r = 0.9997 |

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

• Precision:
  • Human Sera Samples: 3 samples (0.51, 17.7, and 31.8 mg/dL)
  • Control Samples: 2 serum-based control samples (PCCC1, PCCC2)
  • Each sample/control run in two aliquots per run, two runs per day for 21 days.
  • Data Provenance: Not explicitly stated, but implied to be laboratory-generated (not from real patient populations with specific countries of origin). Retrospective or prospective is not specified, but the study design suggests prospective lab testing.
• Linearity/Assay Reportable Range:
  • Serum dilution series: 14 levels
  • Plasma dilution series: 13 levels
  • Data Provenance: Laboratory-generated, with human serum/plasma pool spiked with unconjugated bilirubin. Not specified for country of origin or retrospective/prospective.
• Detection Limits (LoB, LoD, LoQ):
  • LoB: One blank sample
  • LoD: Five low-analyte samples
  • LoQ: A low-level sample set of nine
  • Data Provenance: Laboratory-generated.
• Analytical Specificity (Endogenous Substances):
  • Interferents: Hemoglobin, lipids, indican.
  • Two pools of human serum used (one spiked, one unspiked) to create dilution series.
  • Interference tested at two levels of bilirubin.
  • Data Provenance: Laboratory-generated using human serum.
• Analytical Specificity (Common Drugs):
  • 15 commonly used drugs.
  • Serum sample pools at two target concentrations of total bilirubin (~1.0 mg/dL and ~14.0 mg/dL).
  • Data Provenance: Laboratory-generated using serum.
• Adult Method Comparison with Predicate Device:
  • Sample Size: n=131 human sera adult samples.
  • Data Provenance: Not explicitly stated for country of origin or retrospective/prospective, but implies de-identified human serum samples.
• Matrix Comparison (Anticoagulants):
  • Sample Size: 35 tubes collected per anticoagulant type (Li-heparin, K2-EDTA, Gel Separation Tube).
  • Data Provenance: Not explicitly stated for country of origin or retrospective/prospective, but implies human plasma/serum samples.

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 (IVD) for quantitative measurement of total bilirubin. Expert consensus is not typically used to establish ground truth for this type of quantitative biochemical assay. The ground truth is generally established by:

• Reference Methods: For this device, the "ground truth" or reference method for traceability is explicitly stated as "Standardized against the Doumas manual reference method."
• Predicate Device: For method comparison, the predicate device (Total Bilirubin reagent on the cobas c 501) serves as the comparator.

Therefore, the concept of "experts" in the context of clinical interpretation for ground truth is not applicable here.

4. Adjudication Method for the Test Set

Adjudication methods (e.g., 2+1, 3+1) are typically used in studies where human readers provide subjective assessments (e.g., image interpretation). This is a quantitative chemical assay, where measurements are objective. Therefore, no adjudication method was used or is relevant.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs without AI Assistance

No MRMC comparative effectiveness study was done. This device is a fully automated in vitro diagnostic test for measuring bilirubin levels. It does not involve human readers for interpretation, nor does it incorporate AI (Artificial Intelligence) in a way that would assist human readers.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, a standalone study was done. The entire performance evaluation (precision, linearity, detection limits, interference, method comparison) described in the document is for the device operating as a standalone quantitative assay without human intervention in the measurement process. The "algorithm" here refers to the chemical reaction principles and photometric measurement methodology.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, Etc.)

The ground truth for the quantitative measurement of total bilirubin is generally established by:

• Reference Methods: The device is standardized against the Doumas manual reference method (as stated under "Traceability"). This is the gold standard for bilirubin measurement.
• Comparator Methods: In the adult method comparison study, the predicate device (Total Bilirubin reagent) values served as the comparator for assessing agreement.

8. The Sample Size for the Training Set

The provided document describes a 510(k) submission for a diagnostic test. Unlike AI/ML-based diagnostic devices, this type of device does not typically involve "training sets" in the machine learning sense. The "training" in developing such a device involves refining chemical reagents and optimizing instrument parameters, which is a different process than training an algorithm on a dataset. The studies described are performance validation studies.

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

As explained above, there isn't a "training set" in the context of an AI/ML algorithm for this type of IVD device. The development process would involve optimizing the reagent formulation and assay conditions against an established reference method (like the Doumas method) to ensure accurate and precise measurements.

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The cobas b 123 POC system is a fully automated POC system for whole blood in vitro measurement of pH, blood gases (BG), electrolytes Na+, K+, iCa2+ (ISE), hematocrit (Hct), metabolites (Glu, Lac), total hemoglobin (tHb), hemoglobin derivatives (O2Hb, HHb, COHb, MetHb), and oxygen saturation (SO2). In addition, the cobas b 123 POC system calculates derived parameters. It is dedicated for use in a Point-of-Care environment and laboratory. The integrated AutoQC module and the oximeter module are available as an option.

The cobas b 123 POC system consists of a modular analyzer incorporating a Linux-based graphical user interface with a large color touch screen interfacing the analyzer electronic, sensor, fluidic and AutoQC modules. The user interface module contains the analyzer CPU and all required electronic interfaces for external communication, data storage and data transfer. A single electrochemical sensor system independent of the reagent delivery system that utilizes Roche thick film technology consolidates the following analytes: pCO2, pH, calcium, potassium and sodium (potentiometric measurement); pO2 (amperometric measurement); Hct (conductivity measurement); Glucose and Lactate enzyme reaction (amperometric measurement). An optionally integrated oximeter module consisting of a spectrometer, measurement and calibration light source, respectively, an ultrasonic hemolyzer and thermostatic components measure SO2, tHb, O2Hb, HHb, COHb, and MetHb. A disposable, self-contained sample and reagent delivery system contains: Liquid reagents, calibrators and waste container, stable for 42 days on-board; Built-in safety shielded sample port; Built-in oximeter cuvette; Two peristaltic pump fluidics system; Built-in air filter. The system also includes an optional integrated AutoQC module which utilizes a disposable cassette containing three levels of quality control material. A smart memory chip is incorporated into each biosensor, reagent pack (sample and reagent delivery system) and AutoQC cassette providing the lot number, expiration date and value assignments (for QC and CVC materials). The chip also tracks and monitors sensor, reagent pack, AutoQC and AutoCVC cassette usage.

This is a 510(k) Summary for a medical device and therefore does not contain details about acceptance criteria, study methodologies, or performance against specific metrics as these are typically found in the full 510(k) submission. Acceptance criteria and detailed study information are usually proprietary data submitted to the FDA and are not part of the publicly available 510(k) Summary.

This document focuses on establishing substantial equivalence by comparing the cobas b 123 POC System and its associated control packs to previously cleared predicate devices. It lists the intended use, device descriptions, and similarities and differences between the new device and the predicate devices for various analytes.

Therefore, the requested information (table of acceptance criteria and reported device performance, sample sizes, data provenance, number of experts, adjudication method, MRMC study details, standalone performance, training set sample size, and ground truth establishment) cannot be extracted from the provided text.

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The Roche Acetaminophen assay is an in vitro test for the quantitative determination of toxic levels of acetaminophen in serum and plasma on Roche COBAS Integra, Roche/ Hitachi and cobas c system analyzers.

The Roche Diagnostics Acetaminophen assays under consideration in this submission are the same assays as were cleared on the COBAS Integra in K991598, Hitachi 917 in K013757 and cobas c501 in K060373 for the quantitative determination of toxic levels of Acetaminophen in human serum and plasma on automated clinical chemistry analyzers. The same reagents are used on all three systems. Acetaminophen is hydrolyzed by an arylacylamidase to yield p-aminophenol and acetate. Subsequently, the p-aminophenol is converted to an indophenol in the presence of o-cresol and a periodate catalyst. The production of indophenol is followed colorimetrically. The change in absorbance is directly proportional to the quantitative drug concentration in the sample.

The acceptance criteria for the Roche Acetaminophen assay are based on demonstrating substantial equivalence to previously cleared predicate devices: Roche COBAS Integra Acetaminophen assay (K991598), Roche/Hitachi Acetaminophen assay (K013757), and cobas c501 Acetaminophen assay (K060373). The study performed by Roche Diagnostics focused on validating the performance of the new Roche Acetaminophen assays on the cobas 8000 Modular Analyzer Series, specifically on the cobas c501 and Hitachi 917 platforms, and confirming similar performance on the COBAS Integra platform.

The study did not explicitly state "acceptance criteria" in terms of numerical thresholds for performance metrics. Instead, it demonstrated equivalence by comparing the analytical characteristics of the new assays with those of the predicate devices. The key performance aspects compared include:

1. Table of Acceptance Criteria (Implied) and Reported Device Performance:

Important Note on Measuring Range and Sensitivity: While the new device's LoB is 1.2 µg/ml for all platforms, the "Measuring range" starts at 15 µg/ml. This is a key difference from the predicate devices which had measuring ranges starting at their respective LDLs (1.2 µg/ml or 0.7 µg/ml). The LoQ (Limit of Quantitation) of 15 µg/ml seems to define the lower end of the measuring range for the new device. Additionally, the new assays performed more extensive bilirubin interference testing (at 15, 30, and 50 µg/ml) compared to the predicates (only at 50 µg/ml).

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

• The document does not explicitly state the sample sizes used for the analytical performance studies (e.g., for LoB, LoD, LoQ, measuring range, specificity, or interference testing).
• The document does not specify the data provenance (e.g., country of origin, retrospective or prospective).

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

• This information is not applicable to this type of submission. This is a 510(k) for an in vitro diagnostic (IVD) assay based on chemical/enzymatic reactions. The "ground truth" for an IVD assay's analytical performance (e.g., concentration of acetaminophen) is established through reference methods, certified reference materials, and robust analytical chemistry techniques, not through expert consensus on images or clinical outcomes.

4. Adjudication method for the test set:

• This information is not applicable as it pertains to expert reviews of data, which is not how analytical performance of IVD assays is typically established.

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, an MRMC comparative effectiveness study was not done. This is an IVD device, not an AI-powered diagnostic system that assists human readers.

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

• Yes, the performance described is the standalone performance of the analytical assay (the "algorithm" here is the chemical reaction and measurement system). There is no "human-in-the-loop" performance being evaluated in the context of this device's function.

7. The type of ground truth used:

• The "ground truth" for the analytical performance of this assay would be established using reference methods (e.g., gas chromatography-mass spectrometry (GC-MS) or high-performance liquid chromatography (HPLC) for acetaminophen quantification) and certified reference materials with known concentrations of acetaminophen. The document doesn't explicitly detail the reference methods used but implies the use of quantitative standards for calibration and evaluation.

8. The sample size for the training set:

• This information is not explicitly stated as it's an analytical assay and not a machine learning algorithm that typically requires a distinct "training set." The development of such assays involves extensive R&D, method optimization, and analytical validation which uses various samples and experiments, but these are not typically referred to as a "training set" in the context of AI/ML.

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

• As above, the concept of a "training set" with established ground truth in the AI/ML sense is not applicable here. The analytical accuracy and precision are established through internal validation studies using known concentrations of analytes and comparison to reference methods, not through human-adjudicated ground truth.

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