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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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cobas e 801 immunoassay analyzer is intended for the in-vitro determination of analytes in body fluids.

Elecsys TSH immunoasay 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 or pituitary disorders. The Elecsys TSH immunoassay is an electrochemiluminescence immunoasay 'ECLIA', which is intended for use on the cobas e immunoassay analyzers.

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.

Here's a breakdown of the acceptance criteria and study information for the Elecsys TSH assay on the Cobas e 801 immunoassay Analyzer, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" for each performance characteristic as pass/fail thresholds. Instead, it presents the results of various validation studies. I will present the reported performance, and where applicable, infer the implied acceptance based on the presentation of the results as successful.

2. Sample Size and Data Provenance for Test Set

• Repeatability and Intermediate Precision:
  • Sample Size:
    • 7 human serum samples (5 pooled, 5 pooled spiked) and 2 control samples (PC Universal, PreciControl TS).
    • Each sample tested in 2 replicates per run, 2 runs per day for 21 days (total of 84 replicate measurements per sample type).
• Linearity:
  • Sample Size: 3 high analyte serum samples diluted to 12 concentrations. Each concentration assayed in 3-fold determination within a single run.
• Analytical Sensitivity (LoB, LoD, LoQ):
  • LoB: Blank sample tested with 60 replicates (10 replicates per run, 6 days).
  • LoD: 5 low-level human serum samples tested with 60 replicates (2 replicates per sample per run, 6 days).
  • LoQ: 10 low-level TSH samples tested over 5 days, 5 replicates per sample per day.
• Endogenous Interferences:
  • Human serum samples. Specific number not provided, but the outcome is qualitative ("No interference observed").
• Exogenous Interferences (Anticoagulants):
  • A minimum of 40 serum/plasma pairs per sample material (presumably 40 serum, 40 Li-Heparin plasma, 40 K2-EDTA plasma, 40 K3-EDTA plasma). Tested in singleton for each type.
• Exogenous Interferences (Drugs):
  • 16 commonly used drugs and 13 special drugs. Specific number of samples not provided, but the outcome is qualitative ("No interference").
• Method Comparison:
  • Sample Size: 130 human serum samples (single donors and serum pools; native, spiked as well as diluted).
• Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, the use of "human serum samples" and "human serum/plasma pairs" indicates biological samples. The studies are prospective in nature, conducted specifically to validate the device.

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

This device is an immunoassay for quantitative determination of TSH. The "ground truth" for the test set is established by the reference measurement method or the quantitative value itself. No human experts are used to establish ground truth in the same way they would be for image interpretation. The accuracy of the quantitative measurements is assessed against known concentrations (e.g., in linearity, LoB/LoD studies) or against a predicate device (method comparison).

4. Adjudication Method

Not applicable for an immunoassay. Adjudication is typically used when human interpretation of results contributes to the ground truth, which is not the case here.

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

No. This type of study is relevant for diagnostic imaging or other interpretations where human readers are involved. This document describes the performance of an in-vitro diagnostic device (IVD) for quantitative measurement, which operates without direct human interpretive input being part of the core measurement.

6. Standalone Performance

Yes, these studies describe the standalone (algorithm only, in this context meaning the device's automated performance without human intervention after sample loading) performance of the Elecsys TSH assay on the cobas e 801 immunoassay analyzer. The results presented are directly from the instrument's measurements.

7. Type of Ground Truth Used

• Reference Materials/Known Concentrations: For precision, linearity, LoB, LoD, LoQ, endogenous and exogenous interference studies, ground truth implicitly refers to the expected concentration/value based on the preparation of known samples or the absence of an analyte (for blanks).
• Predicate Device Measurements: For the method comparison study, the "ground truth" for comparison is the measurement obtained from the predicate device (Elecsys TSH on Elecsys 2010 analyzer).
• Expected Values: The "Expected Values" section establishes a reference range (0.27-4.20 µIU/mL) based on healthy test subjects. This is a clinical reference range, not a direct ground truth for individual measurements, but rather a benchmark for interpretation.

8. Sample Size for the Training Set

The document describes validation studies for an in vitro diagnostic device (IVD), specifically an immunoassay analyzer and assay. IVDs like this do not typically have a "training set" in the machine learning sense. The device's operational parameters, calibration curves, and algorithms are developed during the product development phase by the manufacturer, which might involve internal data, but generally, the submission focuses on external validation. The document does not provide details on the development data used.

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

As there is no "training set" described in the context of machine learning, this question about establishing ground truth for it is not applicable here. The device output is a quantitative value based on chemical reactions and detection, not a learned prediction from a ground-truthed dataset in the AI sense.

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The cobas 8000 ISE module is a fully automated ion-specific analyzer intended for the in vitro potentionetric determination of chloride, potassium, and sodium in serum, plasma, and urine ion-selective electrodes. Measurements obtained by this device are used in the diagnosis and treatment of diseases or conditions involving electrolyte imbalance.

The cobas 8000 ISE module is an Ion-Selective Electrode (ISE) system for the determination of sodium, potassium, and chloride in serum, plasma, and urine. The cobas 8000 ISE module and the ISE Gen 2 reagents were previously cleared for serum and plasma sample types under K100853 and urine sample type on K123726. This premarket notification seeks to obtain FDA review and clearance for the urine sample type for the ISE Gen 2 reagents on the cobas 8000 ISE module using an expanded measuring range for sodium and chloride analytes at the low end of the measuring range and the new calibration method cleared in K132418. 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 jons 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). Please refer to K 100853 for detailed hardware and software information relating to the cobas 8000 modular analyzer series.

This document describes the performance of the cobas 8000 ISE Indirect Na, K, Cl for Gen. 2 device, specifically focusing on its use for urine samples with an expanded measuring range for sodium and chloride.

1. Acceptance Criteria and Reported Device Performance

The device performance is compared to a predicate device (cobas 8000 ISE Module using Low/High/Serum Compensator calibration cleared under K123726) and a reference method (flame photometry for Na and K, coulometry for Cl). The acceptance criteria are implicitly demonstrated by showing substantial equivalence to the predicate device and by meeting established performance metrics for analytical devices (repeatability, intermediate precision, linearity, detection limits).

Notes on Acceptance Criteria:

• The document implies that the device meets acceptance criteria if its performance is substantially equivalent to the predicate device and the reference methods, and if the within-run precision (repeatability), total precision (intermediate precision), and detection limits are within acceptable analytical limits for clinical chemistry devices.
• For the expanded measuring range for Sodium and Chloride (20-59.9 mmol/L), the acceptance criteria are demonstrated by the stated precision (repeatability and intermediate precision) within that new range.
• The high correlation coefficients (e.g., 0.9995 for Sodium to reference method) and slopes close to 1 with small intercepts indicate good agreement with the reference methods and predicate.

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

• Test Set Sample Sizes for Method Comparison Studies:
  • Sodium:
    • Method Comparison to Reference (flame photometer): N = 106
    • Method Comparison to Predicate: N = 92
  • Potassium:
    • Method Comparison to Reference (flame photometry): N = 99
    • Method Comparison to Predicate: N = 92
  • Chloride:
    • Method Comparison to Reference (coulometry): N = 100
    • Method Comparison to Predicate: N = 92
• Data Provenance: The document does not explicitly state the country of origin of the data. The "Date Prepared: May 8, 2014" and the submitter being Roche Diagnostics (Indianapolis, IN, USA) with manufacturing in Mannheim, Germany (K100853 reference), suggests an international context, but the specific location of sample collection for the studies is not specified. The studies appear to be prospective as they are conducted to demonstrate the performance of the candidate device for a 510(k) submission.

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

This type of analytical device (Ion-Selective Electrode system for chemical determination) relies on established reference methods (e.g., flame photometry, coulometry) rather than expert interpretation of images or clinical cases. Therefore, the concept of "experts establishing ground truth" in the way it applies to diagnostic imaging or clinical decision support systems is not directly applicable here. The "ground truth" is typically defined by the accurate results obtained from the reference methods, which are performed by trained laboratory personnel following standardized protocols. No specific number or qualification of "experts" for ground truth establishment is mentioned, as it's an analytical performance study.

4. Adjudication Method for the Test Set

Not applicable. As noted above, this is an analytical performance study of a laboratory device measuring chemical analytes, not a diagnostic interpretation task requiring adjudication of results from multiple observers.

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

No. An MRMC study is relevant for diagnostic devices that involve human interpretation (e.g., radiologists reading images). This device is an automated in vitro diagnostic instrument; its performance is evaluated through analytical studies, not human reader performance.

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

Yes, the studies presented are standalone performance evaluations. The data provided (repeatability, intermediate precision, method comparison, detection limits) are direct measurements of the instrument's analytical capabilities without human intervention in the measurement process itself, beyond standard laboratory operation and quality control.

7. The Type of Ground Truth Used

The ground truth for the method comparison studies was established using reference methods:

• Sodium: Flame photometer
• Potassium: Flame photometry
• Chloride: Coulometry

For repeatability, intermediate precision, and detection limit studies, the "ground truth" is intrinsic to the statistical analysis of the measurements themselves, often against a known concentration of controls or calibrators.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning. This device is an automated analytical instrument based on established electrochemical principles (Ion-Selective Electrodes) and conventional calibration methods, not an AI/ML-based device that learns from a training dataset in the same way. The instrument is "trained" or calibrated using "ISE Standard Low, High, High" (LHH) calibrators, which are commercially available standards with known concentrations. The exact number of calibrator measurements for system calibration or "training" (in the sense of instrument calibration) is not provided but is typically specified by the manufacturer's protocol.

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

Not applicable as an AI/ML training set. The "ground truth" for the device's calibration refers to the assigned values of the calibrator materials (ISE Standard Low, High, High). These values are established by the manufacturer, typically through highly accurate and traceable reference methods, and are verified for consistency and accuracy. The document mentions that "Aqueous ISE standards Low and High were cleared under K053165. The LHH calibration scheme was cleared under K132418," indicating that the standards themselves and the calibration methodology have been previously reviewed and deemed acceptable.

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The S TEST Reagent Cartridge Blood Urea Nitrogen (BUN) is intended for the quantitative measurement of BUN in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma on the Hitachi Clinical Analyzer E40. The test system is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. BUN measurements are used in the diagnosis and treatment of certain renal and metabolic diseases.

The S TEST Reagent Cartridge Creatinine (CRE) is intended for the quantitative measurement of creatinine in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma on the Hitachi Clinical Analyzer E40. The test system is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.

The Hitachi Clinical Analyzer is an automatic, bench-top, wet chemistry system intended for use in clinical laboratories or physician office laboratories. The instrument consists of a desktop analyzer unit, an operations screen that prompts the user for operation input and displays data, a printer, and a unit cover. The analyzer unit includes a single probe, an incubation rotor, carousels for sample cups and reagent cartridges, and a multi-wavelength photometer. The single-use reagent cartridges may be placed in any configuration on the carousel, allowing the user to develop any test panel where the reagent cartridges are available.

The S TEST reagent cartridges are made of plastic and include two small reservoirs capable of holding two separate reagents (R1 and R2), separated by a reaction cell/photometric cuvette. The cartridges also include a dot code label that contains all chemistry parameters, calibration factors, and other production-related information, c.g., expiration dating, dimensions of the reagent cartridges are: 13.5 mm (W) × 28 mm (D) × 20.2 mm (H).

System operation: After the sample cup is placed into the carousel, the analyzer pipettes the sample, pipettes the reagent, and mixes (stirs) the sample and reagent together. After the sample and reagent react in the incubator bath, the analyzer measures the absorbance of the sample, and based on the absorbance of the reactions. it calculates the concentration of analyte in the sample. The test system can measure analytes in scrum or plasma and results are available in approximately 15 minutes per test. This submission is for reagent cartridge test systems for glucose.

The provided text describes the performance of the Hitachi S TEST Reagent Cartridge Blood Urea Nitrogen (BUN) and S TEST Reagent Cartridge Creatinine (CRE) for use with the Hitachi Clinical Analyzer E40. These are in vitro diagnostic devices, not AI/ML-driven as commonly understood in medical imaging or other AI applications. Therefore, many of the requested categories (e.g., number of experts, adjudication method, MRMC study, training set ground truth) are not applicable to this type of device.

Below is a summary of the acceptance criteria and reported device performance based on the provided document, adapted for an in vitro diagnostic device regulatory submission.

1. Table of Acceptance Criteria and Reported Device Performance

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

• Analytical Sensitivity (LoD): No specific sample size for a test set is provided, as this is typically determined by testing multiple replicates of low-concentration samples.
• Linearity/Reportable Range: Not specified as a distinct "test set" sample size beyond the creation of concentration series.
• 20-day In-house Precision:
  • BUN: n=80 per level (3 levels), so 240 measurements in total.
  • CRE: n=80 per level (4 levels), so 320 measurements in total.
• Interference Testing: Two serum pools per analyte, spiked with various concentrations of interfering substances. Specific number of total samples not explicitly stated but implies multiple measurements for each.
• Method Comparison (Internal):
  • BUN: 162 clinical specimens.
  • CRE: 100 clinical specimens.
• Matrices Comparisons:
  • BUN: 36 matched serum/plasma samples.
  • CRE: 39 matched serum/plasma samples.
• External Site Precision: Each of 3 sites tested 3 blinded serum samples (low, middle, high levels) 6 times a day for 5 days. For each level, n=30 replicates per site.
• External Site Method Comparison:
  • BUN: Approximately 75 serum specimens at each of 3 sites (total ~225).
  • CRE: Approximately 45 serum specimens at each of 3 sites (total ~135).

Data Provenance: The studies were performed "in-house" (Hitachi Chemical Diagnostics, Inc.) and at "three external POL-type sites" (Physician Office Laboratory). The clinical specimens are implied to be human serum or plasma. No country of origin is explicitly stated for the clinical data, but the company is in the USA. The studies are prospective in the sense that they were designed and executed to evaluate the device performance for this 510(k) submission.

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

This is not applicable to this type of in vitro diagnostic device. The "ground truth" for chemical analyzers is established through reference methods and calibrated samples, not expert consensus in the way a radiologist would interpret an image. The comparative methods used in the method comparison studies serve as the reference.

4. Adjudication Method for the Test Set

Not applicable. This is a quantitative chemical assay. Discrepancies are resolved through re-testing or investigation of analytical issues, not by expert adjudication of interpretations.

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

Not applicable. This device is an automated chemical analyzer, not an AI-assisted diagnostic imaging tool that involves human readers interpreting cases.

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

Yes, the device operates in a standalone (algorithm only) manner. It is an automated instrument that performs the assay and calculates results based on the detected absorbance. Humans are involved in operating the instrument, loading samples, and interpreting the numerical output, but the measurement and calculation itself is automated. The performance metrics listed (precision, linearity, method comparison, etc.) reflect this standalone analytical performance.

7. The Type of Ground Truth Used

The ground truth for evaluating the device's performance is established by:

• Reference materials/calibrators: Used for linearity, detection limits, and precision studies.
• Comparative methods/Standard laboratory systems: The results from the Hitachi system are compared against established, legally marketed systems (e.g., Roche Cobas c systems) which serve as the reference or "ground truth" for method comparison and accuracy studies. These are not "expert consensus, pathology, or outcomes data" in the traditional sense, but rather established analytical methods.

8. The Sample Size for the Training Set

Not applicable. This device is a wet chemistry system, not an AI/ML model that requires a training set in that context. The "training" of such a system involves chemical reagent formulation and instrument calibration, not data-driven model training.

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

Not applicable. As noted above, this is not an AI/ML model with a data-driven training set.

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

The cobas 8000 ISE module is a fully automated ion-specific analyzer intended for the in vitro potentiometric determination of chloride, potassium, and sodium in serum, plasma, and urine using ion-selective electrodes. Measurements obtained by this device are used in the diagnosis and treatment of diseases or conditions involving electrolyte imbalance.

The cobas 8000 ISE module is an Ion-Selective Electrode (ISE) system for the determination of sodium, potassium, and chloride in serum, plasma, and urine. The cobas 8000 ISE module and the ISE Gen 2 reagents were previously cleared for serum and plasma sample types under K100853. This premarket notification seeks to obtain FDA review and clearance for the urine sample type for the ISE Gen 2 reagents on the cobas 8000 ISE module.

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). Please refer to K100853 for detailed hardware and software information relating to the cobas 8000 modular analyzer series.

Commercially available controls are recommended for the urine sample type. Aqueous ISE standard calibrators (S1, S2, and S3) were cleared under K053165 and ISE Compensator under K052193.

The cobas 8000 ISE Indirect Na, K, Cl for Gen. 2 device is intended for the in vitro potentiometric determination of chloride, potassium, and sodium in serum, plasma, and urine using ion-selective electrodes. This summary outlines the acceptance criteria and the study results demonstrating the device's performance.

1. Acceptance Criteria and Reported Device Performance

The device's performance was evaluated against a predicate device (COBAS INTEGRA ISE cleared under K963627) and, for method comparison, against reference methods (flame photometer for Sodium and Potassium, coulometry for Chloride). While explicit acceptance criteria (e.g., target CV% or correlation coefficients) are not directly stated as numerical thresholds for substantial equivalence, the reported performance metrics are compared to the predicate device and reference methods to demonstrate analytical validity. The tables below summarize the reported performance for the cobas 8000 Urine ISE.

Sodium Performance

Potassium Performance

Chloride Performance

2. Sample Size and Data Provenance for the Test Set

• Sample Size for Test Set:
  • Method Comparison (to reference method and predicate): N = 59 unique samples were used for the method comparison studies for Sodium, Potassium, and Chloride. These samples were tested over 2 days.
  • Repeatability and Intermediate Precision: The number of unique samples for these studies is not explicitly stated as 'test set' but rather multiple levels of controls/samples were run, e.g., "Low", "Med", "High", "Liq 1", "Liq 2" for the cobas 8000 Urine ISE. The data presented are statistical summaries (mean, SD, CV%) derived from these runs.
• Data Provenance: The document does not explicitly state the country of origin for the data. However, the submitter is Roche Diagnostics (Indianapolis, IN, USA) with establishment registration in Mannheim, Germany, suggesting the studies could have been conducted in either or both locations. The studies appear to be prospective as they detail the evaluation of the new device for urine sample types.

3. Number of Experts and Qualifications for Ground Truth

Not applicable. This is a submission for an in vitro diagnostic device (analyzing electrolytes) where the 'ground truth' is established by established reference methods (e.g., flame photometry, coulometry) or by comparison to a legally marketed predicate device, not by expert human interpretation of medical images or other subjective data.

4. Adjudication Method for the Test Set

Not applicable. As described above, the ground truth is established by objective laboratory methods, not by human interpretation requiring adjudication.

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

Not applicable. This is an IVD device and does not involve human readers for interpretation, thus an MRMC study is not relevant.

6. Standalone Performance Study

Yes, a standalone performance study was done. The entire submission details the performance of the cobas 8000 ISE module as an algorithm-only (device-only) without human-in-the-loop performance measurement. The repeatability, intermediate precision, method comparison, detection limits (LOB, LOD, LOQ), and reportable range data reflect the standalone performance of the device.

7. Type of Ground Truth Used

The ground truth used for performance evaluation includes:

• Reference Methods:
  • For Sodium and Potassium: Flame Photometer
  • For Chloride: Coulometry
• Comparison to a Predicate Device: COBAS INTEGRA ISE (K963627)

8. Sample Size for the Training Set

Not applicable. This device is a diagnostic instrument using ion-selective electrodes, not a machine learning or AI algorithm that requires a "training set" in the context of supervised learning. The device's calibration and controls would be analogous to continuous internal checks, but there isn't a "training set" in the traditional AI sense.

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

Not applicable, as there is no training set in the context of an AI algorithm. The device's operational parameters and calibration are established through physical and chemical principles of ion-selective electrodes, and validated through the performance studies described.

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