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The OPTIGEN® Allergen-Specific IgE Assay 12 Allergen Bundle A is an in vitro test for use in the semi-quantitative determination of circulating allergen specific IgE concentrations in human serum. OPTIGEN® Allergen-Specific IgE assays are meant to be included in panel tests to be used with the AP3600™ instrument. Each assay is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergenic disorders in conjunction with other clinical findings and are to be used in clinical laboratories.

The OPTIGEN® 12 Allergen Bundle A includes Almond (f20), Bermuda Grass (g2), Cashew (f207), Crab (f23), Hazelnut (Food) (f17), Oak, White (f7), Salmon (f41), Sesame Seed (f10), Shrimp (f24), Tuna (f40), and Walnut (Food) (f256).

Not Found

This document is a marketing authorization letter for a device, not a study report. It does not contain information about acceptance criteria or a study proving the device meets those criteria.

Therefore, I cannot provide the requested information. The document focuses on the regulatory clearance of a device based on its substantial equivalence to previously marketed devices, not on the presentation of performance data from a specific study against predefined acceptance criteria.

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The AP 3600 Automated Instrument, in conjunction with the OPTIGEN Allergen-Specific IgE Assay, is for the semiquantitative measurement of circulating allergen-specific IgE antibodies in human serum. The OPTIGEN Allergen-Specific IgE Assay is intended to aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings. The AP 3600 Automated Instrument is a software-enabled instrument designed for use with the OPTIGEN Allergen-Specific IgE Assay in clinical laboratories for sample processing, measurement analyses, and reporting of OPTIGEN Allergen-Specific IgE Assay results.

The AP 3600 Automated Instrument is a software-enabled instrument designed for use with the OPTIGEN Allergen-Specific IgE Assay in clinical laboratories for sample processing, measurement analyses, and reporting of OPTIGEN Allergen-Specific IgE Assay results.

I am sorry, but the provided text is a 510(k) clearance letter for a medical device (AP3600 Automated Instrument). This type of document primarily confirms that the FDA has reviewed the device and determined it is substantially equivalent to legally marketed predicate devices.

The letter itself does not contain information about:

• Specific acceptance criteria for device performance.
• The details of a study (sample sizes, provenance, ground truth, expert qualifications, adjudication methods).
• Whether MRMC or standalone studies were performed.
• Training set details.

Therefore, I cannot fulfill your request for a table of acceptance criteria and device performance, or details about the studies, as this information is not present in the provided text. The document focuses on regulatory clearance, not detailed study results.

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The S TEST Reagent Cartridge Carbon Dioxide (CO2) is intended for the quantitative determination of carbon dioxide concentration in serum or lithium heparin plasma using the HITACHI Clinical Analyzer E40. Carbon dioxide measurements are used in the diagnosis and treament of numerous potentially serious disorders associated with changes in body acid-base balance. The S TEST Reagent Cartridge Carbon Dioxide (CO2) is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

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, e.g., expiration dating. The 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 serum or plasma and results are available in approximately 15 minutes per test. This submission is for Reagent Cartridge Carbon Dioxide.

The provided text describes the 510(k) summary for the Hitachi S TEST Reagent Cartridge Carbon Dioxide (CO2), a device for quantitative determination of carbon dioxide concentration in serum or lithium heparin plasma. The document focuses on demonstrating the substantial equivalence of this device to a legally marketed predicate device (Carbon Dioxide L.3K Assay, Sekisui Diagnostics, PEI, Inc., Canada- K042362) through nonclinical and clinical performance studies.

Here's an analysis of the acceptance criteria and the studies conducted:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of "acceptance criteria" but rather describes the performance characteristics tested and their results, often comparing them to the predicate device or established standards. I will infer acceptance criteria based on standard clinical chemistry performance requirements and the described study outcomes.

• Low (10.11 mmol/L): 1.3% (4.4%)
• Middle (19.41 mmol/L): 1.3% (3.7%)
• High (33.06 mmol/L): 1.2% (3.7%) |
  | Precision (External POL Study) | Similar to in-house, %CVs within acceptable clinical limits. | Total %CV (n=30 for each level at each site)
• Site 1: 4.1% (Low), 4.8% (Mid), 3.2% (High)
• Site 2: 6.0% (Low), 4.4% (Mid), 3.7% (High)
• Site 3: 3.1% (Low), 1.9% (Mid), 3.7% (High) |
  | Interference | Recoveries between 90% and 110% of the neat value in the presence of interferents. | No interference from Lipemia (up to 1,000 mg/dL Intralipid), Ascorbic acid (up to 50 mg/dL), Hemoglobin (up to 1,000 mg/dL), Unconjugated bilirubin (up to 19.1 mg/dL) |
  | Method Comparison (Accuracy) | Strong correlation (r > 0.95), slope close to 1, y-intercept close to 0, and agreement with predicate/reference method. | In-house (vs. standard lab system): n=96, r=0.981, Slope=1.03 (0.97-1.08), y-intercept=0.98 (-0.17-2.12)
  External POL Study (vs. comparative method):
• Site 1: n=47, r=0.984, y=0.91x+1.49 (Slope CI: 0.87-0.95, Intercept CI: 0.67-2.32)
• Site 2: n=45, r=0.970, y=0.92x+0.56 (Slope CI: 0.80-1.04, Intercept CI: -2.31-3.43)
• Site 3: n=47, r=0.982, y=0.92x+0.79 (Slope CI: 0.87-0.97, Intercept CI: -0.43-2.01) |
  | Matrix Comparison (Serum vs. Plasma) | Strong correlation between serum and plasma results (r > 0.95), slope close to 1, y-intercept close to 0. | n=50, r=0.980, Slope=1.00 (0.94-1.05), y-intercept=-0.34 (-1.97-1.30) |
  | Stability (Shelf Life) | Claimed shelf life supported by real-time stability data. | Supported shelf life of 6 months at 2-8°C (real-time testing ongoing). |
  | Reportable Range | Match clinical requirements; within demonstrated linearity. | 5.0 to 40.0 mmol/L (Predicate: 2.9 to 50.0 mmol/L) |
  | Detection Wavelength | Not an acceptance criterion for performance, but a technical specification. | 405/508 nm (Predicate: 405/415 nm) |

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

• Analytical Sensitivity (LoD/LoQ): 60 replicates of reagent blank and three low samples. Three low-level specimens in six runs with three instruments over three days for LoQ.
• Linearity: 10 serial dilutions plus zero standard (n=11), assayed in duplicate.
• Precision (In-house): Three levels of serum-based commercial controls, each tested in two runs, twice a day, for 20 days.
• Interference Testing: Two serum pools with approximately 17 and 30 mmol/L carbon dioxide.
• Method Comparison (In-house): 96 clinical specimens (including 3 spiked and 3 diluted samples).
• Matrix Comparison: 50 matched serum/plasma samples (including 2 spiked and 4 diluted samples).
• Precision (External POL Study): Three blinded serum samples (low, middle, high CO2 concentrations). Each sample assayed six times per day for five days, reporting 30 results per level per site.
• Method Comparison (External POL Study): 47 serum specimens (including three spiked and four diluted samples) per site (Site 2 used 45 samples due to 2 below dynamic range).

Data Provenance:

• The studies were performed by Hitachi Chemical Diagnostics, Inc. ("in-house") and at three external Physician Office Laboratory (POL)-type sites.
• Specific countries of origin for the clinical specimens are not explicitly stated, but the company address is Mountain View, CA, USA, and POL studies suggest U.S. clinical settings.
• The studies appear to be prospective for the purpose of validating the device's performance characteristics.

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

The document does not specify the number or qualifications of experts used to establish "ground truth" for the test set in the traditional sense of expert consensus for diagnostic interpretation. Instead, the ground truth is established through:

• Reference Methods/Comparative Methods: In the method comparison studies, a "standard laboratory system" or "comparative method as the reference method" was used. The qualifications of the operators of these reference methods are not provided.
• Known Concentrations: For studies like linearity, precision, and interference, known concentrations (e.g., commercial controls, spiked samples, diluted samples) are used.
• Industry Standards: Adherence to CLSI (Clinical and Laboratory Standards Institute) guidelines (e.g., CLSI EP17-A2, CLSI EP-6A, CLSI EP5-A2, CLSI EP7-A2) implies reliance on established laboratory best practices for determining analytical performance.

4. Adjudication Method for the Test Set

This type of in vitro diagnostic device (IVD) performance study (analytical and clinical chemistry accuracy/precision) typically does not involve adjudication by multiple human readers in the same way an imaging or pathology study might. Instead, the device's results are compared against:

• Reference measurements: From the predicate device or a "standard laboratory system."
• Known values: For controls, linearity standards, and spiked/diluted samples.
  The document states that method comparison samples were assayed "in singleton and in a blinded fashion" (in-house) and "assayed on the Hitachi E40 Clinical Analyzer... and a comparative method as the reference method" (external POL study), implying direct comparison without a formal adjudication panel.

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 design is typically used for diagnostic imaging or pathology devices where multiple human readers interpret cases, and the AI's impact on their performance is assessed. For an in vitro diagnostic (IVD) device like a CO2 reagent cartridge, the evaluation focuses on analytical performance characteristics (accuracy, precision, linearity, etc.) rather than human reader improvement with AI assistance.

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

Yes, the studies conducted are standalone performance studies. The Hitachi S TEST Reagent Cartridge Carbon Dioxide operates as an in vitro diagnostic device on an automated analyzer (Hitachi Clinical Analyzer E40). The performance results (accuracy, precision, linearity, etc.) described are the performance of the device and its associated system without direct "human-in-the-loop" interpretive input influencing the result generation. Human operators load samples and reagents and review results, but the device itself generates the quantitative CO2 concentration.

7. The Type of Ground Truth Used

The ground truth for the performance studies was established using a combination of:

• Reference Measurement/Comparative Method: For method comparison, results from a "standard laboratory system" or "comparative method" served as the reference.
• Known Values: For analytical studies like linearity, precision, LoD, and interference, commercial controls, calibrators, and spiked/diluted samples with known or traceable concentrations were used.
• Industry Standards: Adherence to CLSI guidelines ensures that the methods for establishing ground truth for these analytical parameters align with recognized best practices in laboratory medicine.

8. The Sample Size for the Training Set

The document does not describe a "training set" in the context of machine learning or AI development. This is an IVD device providing a quantitative measurement based on a chemical reaction and photometric detection. Its underlying "algorithm" is the chemistry reaction and calculation based on Beer-Lambert Law, not a learned AI model that requires a training set. Manufacturers establish internal specifications and calibration parameters based on extensive R&D and analytical validation, but this typically does not involve an external "training set" as understood in AI/ML.

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

As explained above, there is no "training set" for this type of IVD device in the AI sense. The "ground truth" for manufacturing and calibration would be established through:

• Primary Reference Materials: Traceability to primary reference standards (e.g., American Chemical Society (ACS) reagent grade sodium carbonate alkalimetric standard for CO2).
• Internal Validation: Rigorous internal testing and validation during the device's development to ensure the chemical reaction and photometric measurements yield accurate and precise results across the dynamic range.
• Quality Control: Ongoing use of quality control materials with known values to monitor performance.
  The document states, "Each lot of S TEST Reagent Cartridge Carbon Dioxide (CO2) is calibrated by the manufacturer prior to shipment using material referenced to a standard which is traceable to American Chemical Society (ACS) reagent grade sodium carbonate alkalimetric standard." This describes the process for establishing and maintaining calibration, which is akin to "ground truth" for the device's quantitative output.

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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 S TEST Reagent Cartridge Lactate Dehydrogenase (LD) is intended for the quantitative determination of LD in serum and plasma using the HITACHI Clinical Analyzer E40. The S TEST Reagent Cartridge Lactate Dehydrogenase (LD) is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. Measurements of LD are used in the diagnosis and treatment of liver and cardiac diseases.

The S TEST Reagent Cartridge Amylase (AMY) is intended for the quantitative determination of AMY in serum and plasma using the HITACHI Clinical Analyzer E40. The S TEST Reagent Cartridge Amylase (AMY) is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only. Measurements of AMY are mainly used in the diagnosis and treatment of pancreatic diseases.

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, e.g., expiration dating. The 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 serum or plasma and results are available in approximately 15 minutes per test. This submission is for Reagent Cartridge ALP.

Chemistry reactions: (LD) Lactate dehydrogenase in samples catalyzes the reaction of converting lactic acid to pyruvic acid. During this reaction, NAD is converted into NADH with an increase in absorbance at 340 nm. The LD activity can be determined by measuring the production rate of the resulting NADH.

(AMY) Amylase in blood samples reacts with the substrate alfa-2-chloro-4-nitropheny]galactopyranosylmaltoside (Gal-G2-CNP), and the substrate is cleaved into 4galactopyranosylmaltose (Gal-G2) and 2-chloro-4-nitrophenol (CNP). Amylase activity is determined by measuring the production rate of CNP (yellow).

Here's a breakdown of the acceptance criteria and the study details for the Hitachi Chemical Diagnostics S TEST Reagent Cartridges for Lactate Dehydrogenase (LD) and Amylase (AMY):

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are implied by the reported performance and comparison to predicate devices, rather than explicitly stated as discrete pass/fail thresholds in a formal table from the provided text. However, we can infer the expected performance based on the studies conducted.

S TEST Reagent Cartridge Lactate Dehydrogenase (LD)

S TEST Reagent Cartridge Amylase (AMY)

2. Sample Size and Data Provenance for the Test Set

• 10-day In-house Precision (LD, AMY):
  • Sample Size: Three levels of samples were tested. Each level was tested in two runs, twice a day, for 20 days. This implies a significant number of replicates (e.g., 3 levels * 2 runs/day * 2 times/day * 20 days = 240 measurements per analyte, though typically results are grouped for analysis). The text explicitly states 30 replicates per sample per site for the external precision studies.
  • Data Provenance: Not explicitly stated, but "in-house" implies from the manufacturer's laboratory. "Clinical specimens" for method comparison suggest human samples.
• Method Comparison (LD):
  • Sample Size (Test Set): 106 clinical specimens.
  • Data Provenance: Not explicitly stated, but "clinical specimens" implies human samples, presumably retrospective or prospectively collected for the study. No country of origin is mentioned.
• Method Comparison (AMY):
  • Sample Size (Test Set): 105 clinical specimens.
  • Data Provenance: Not explicitly stated, but "clinical specimens" implies human samples, presumably retrospective or prospectively collected for the study. No country of origin is mentioned.
• Matrices Comparisons (LD):
  • Sample Size (Test Set): 39 matched serum/plasma samples.
  • Data Provenance: Not explicitly stated; "clinical samples" implies human.
• Matrices Comparisons (AMY):
  • Sample Size (Test Set): Approximately 43 matched serum/plasma samples.
  • Data Provenance: Not explicitly stated; "clinical samples" implies human.
• External Site Precision (LD, AMY):
  • Sample Size (Test Set): Three blinded serum samples (low, middle, high concentrations for each analyte). Each sample was assayed six times per day for five days, yielding 30 replicates per sample per site. This was done at three external sites.
  • Data Provenance: "three external POL-type sites" (Physician Office Laboratory-type sites). Implies human serum samples.
• External Site Method Comparison (LD):
  • Sample Size (Test Set): Approximately 70-80 serum specimens (specifically, 87 for Site 1, 78 for Site 2, 86 for Site 3).
  • Data Provenance: "three external POL-type sites" using "serum specimens with LD values". Implies human serum samples.
• External Site Method Comparison (AMY):
  • Sample Size (Test Set): Approximately 70-80 serum specimens (specifically, 76 for Site 1, 69 for Site 2, 71 for Site 3).
  • Data Provenance: "three external POL-type sites" using "serum specimens with AMY values". Implies human serum samples.

3. Number of Experts and Qualifications for Ground Truth

This device is a quantitative diagnostic test for measuring enzyme levels (LD and AMY) in blood samples, typically analyzed by laboratory equipment. The "ground truth" for such devices is established by validated reference methods or predicate devices, not typically by expert review of images or clinical assessments in the same way an AI diagnostic imaging device would use radiologists.

• For Method Comparison studies, the "ground truth" or reference method was "a standard laboratory system" (in-house studies) or "a comparative method as the reference method" (external POL studies). These are assumed to be legally marketed and validated laboratory instruments. No human experts are described as establishing "ground truth" in this context.

4. Adjudication Method for the Test Set

Not applicable for this type of quantitative diagnostic device. Adjudication methods like 2+1 or 3+1 are used in interpretation tasks (e.g., radiology for AI devices) where human judgment is pooled to establish a consensus ground truth. Here, the "ground truth" is determined by the output of a reference laboratory instrument or method.

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

No. An MRMC study is not relevant for this type of device, which is an automated quantitative assay. This device does not involve human readers interpreting images or clinical data with or without AI assistance. The studies performed compare the device's quantitative output to established reference methods or predicate devices.

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

Yes, the studies described are standalone performance assessments of the device (Hitachi E40 Clinical Analyzer with S TEST Reagent Cartridges). The performance characteristics (analytical sensitivity, linearity, precision, interference, method comparison, matrices comparison) evaluate the instrument and reagent system's ability to accurately and precisely measure the target analytes entirely autonomously. There is no human interaction in producing the raw quantitative result from the device.

7. Type of Ground Truth Used

The ground truth used for performance evaluation was:

• Validated Reference Methods / Predicate Devices: For linearity, analytical sensitivity, and method comparison studies, the Hitachi E40 system results were compared against established reference methods or legally marketed predicate devices (Roche cobas c systems LDHI2 and AMYL2). The specific details of these reference methods are not provided but are generally understood to be highly accurate and precise laboratory assays.
• Known Concentrations: For precision studies, samples with "low, middle, and high concentrations" were used, implying that the approximate target concentrations were known or characterized.
• Spiked Samples: For interference studies, substances were added to samples at known concentrations to assess their impact on the assay (e.g., "50 mg/dL bilirubin").

8. Sample Size for the Training Set

This information is not provided in the summary. For a medical device like this (a reagent cartridge and analyzer), there isn't typically a "training set" in the sense of machine learning. The device's operational parameters, algorithms (for calculation), and calibration are established during its design and development, likely using extensive internal testing and optimization. Manufacturers establish operating procedures and calibration protocols based on R&D, not a discrete "training set" in the AI sense.

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

Given that this is a traditional in-vitro diagnostic device and not a machine learning algorithm, the concept of a "training set" and establishing "ground truth" for it, as typically understood in AI/ML, does not directly apply. The "ground truth" for developing the device itself would stem from fundamental principles of analytical chemistry, enzyme kinetics, and rigorous laboratory validation processes using primary calibrators and reference materials. The device's calibration curves and internal calculations are based on well-established scientific principles and extensive validation during its development phase.

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The S TEST Reagent Cartridge Alanine Amino Transferase (ALT) is intended for the quantitative measurement of the activity of the enzyme alanine amino transferase (ALT) 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. ALT measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart diseases.

The S TEST Reagent Cartridge Aspartate Amino Transferase (AST) is intended for the quantitative measurement of the activity of the enzyme aspartate amino transferase (AST) 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. AST measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart diseases.

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, e.g., expiration dating. The 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 serum or plasma and results are available in approximately 15 minutes per test. This submission is for reagent cartridge test systems for glucose.

The Hitachi Chemical Diagnostics S TEST Reagent Cartridges for Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST) underwent nonclinical and clinical testing to demonstrate their safety and effectiveness.

Here’s a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance:

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

• Nonclinical Studies (Internal):
  • Analytical Sensitivity (LoD): Sample sizes not explicitly stated for individual calculations beyond "followed CLSI EP17."
  • Linearity: Sample sizes not explicitly stated beyond "followed CLSI EP-6A."
  • 20-day In-house Precision: 80 replicates per level for AST (ALT not clearly defined due to formatting issues in the document but likely similar).
  • Interference Testing: Sample sizes not explicitly stated.
  • Method Comparisons: 103 serum samples for ALT, 169 serum samples for AST.
  • Matrices Comparisons: Approximately 35 matched serum/plasma samples (28-31 for ALT, 38-39 for AST) per plasma type.
• Clinical Studies (External POL-type sites):
  • External Precision Study: 30 replicates per sample per site (6 times a day for 5 days) for 3 sample levels (A, B, C or D, E, F) at each of 3 sites.
  • External Method Comparisons: 49-50 blinded serum samples for ALT per site; 62-64 blinded serum samples for AST per site tested at 3 POL sites.
• Data Provenance: The document does not explicitly state the country of origin for the data. The studies were conducted internally ("in-house") and at "three external POL-type sites," suggesting the data is retrospective as it was collected before submission.

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

• For the nonclinical and clinical method comparison studies, the "ground truth" was established by "routine laboratory methods" or "traditional methods at the central laboratory."
• The document does not specify the number or qualifications of experts involved in performing these reference methods. It relies on the established accuracy and widely accepted nature of these "traditional" or "routine" methods.

4. Adjudication Method for the Test Set:

• No explicit adjudication method is described. The "ground truth" was derived from measurements by established laboratory methods, and the Hitachi device's results were compared to these.

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

• No, an MRMC comparative effectiveness study was not done. This submission focuses on the analytical performance of an in vitro diagnostic (IVD) device (reagent cartridges for an analyzer), not a diagnostic imaging or AI-driven decision-support system that typically involves human reader performance. Therefore, there is no mention of human readers, AI assistance, or effect sizes related to human improvement.

6. If a Standalone Study (algorithm only without human-in-the-loop performance) was done:

• Yes, this entire submission is effectively a standalone performance study. The device itself is an automated chemical analyzer with reagent cartridges. The studies evaluate the analytical performance of this automated system directly (e.g., sensitivity, linearity, precision, method comparison to reference methods). There is no "human-in-the-loop" component in the operational use or performance evaluation of the ALT/AST test results themselves, beyond the initial sample loading and result interpretation by laboratory personnel.

7. The Type of Ground Truth Used:

• The ground truth used for method comparison and accuracy studies was established by measurements from "routine laboratory methods" or "traditional methods at the central laboratory." This implies a highly accurate and well-established chemical assay, which serves as the reference standard for the analyte concentration or activity.

8. The Sample Size for the Training Set:

• This submission describes a premarket notification (510(k)) for an IVD device (reagent cartridges). It does not involve a machine learning or AI algorithm that typically requires a distinct "training set." Therefore, no training set sample size is reported or relevant in this context. The "training" of the device is inherent in its chemical design and calibration, not in data-driven machine learning.

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

• As stated above, this is an IVD device, not an AI/ML-driven device. Thus, the concept of a "training set" and associated ground truth establishment for such a set does not apply. The device's performance is validated against established laboratory standards and reference methods as described in point 7.

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The S TEST Reagent Cartridge Total Protein (TP) is intended for the quantitative determination of TP in serum, lithium heparinized plasma, K3 EDTA plasma and sodium citrate plasma using the HITACHI Clinical Analyzer E40. The S TEST Reagent Cartridge TP is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

Total protein measurements are used in the diagnosis and treatment of a variety of diseases involving the liver, kidney, or bone marrow as well as other metabolic or nutritional disorders.

The S TEST Reagent Cartridge Albumin (ALB) is intended for the quantitative determination of ALB in serum, lithium heparinized plasma, K3 EDTA plasma and sodium citrate plasma using the HITACHI Clinical Analyzer E40. The S TEST Reagent Cartridge ALB is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

Albumin measurements are used in the diagnosis and treatment of numerous diseases involving primarily the liver or kidneys.

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, e.g., expiration dating. The 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 serum or plasma and results are available in approximately 15 minutes per test. This submission is for Reagent Cartridges TP and ALB.

Chemistry reactions: (TP) Proteins in samples react with the biuret reagent to form a purplered complex. The concentration of total protein can be determined by measuring the absorbance of the purple-red substance.

(ALB) Albumin in the sample combines with bromcresol green to form a blue-green dye conjugate. The albumin concentration is directly proportional to the color intensity and can be determined photometrically by measuring the absorbance of this resulting blue-green color.

The provided document is a 510(k) summary for the Hitachi S TEST Reagent Cartridge Total Protein (TP) and Albumin (ALB). It details the nonclinical and clinical studies performed to demonstrate the safety and effectiveness of these in-vitro diagnostic devices.

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

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a singular, formal table. Instead, performance characteristics are presented as results from various studies, often implicitly comparing them to the predicate device or general industry standards (e.g., CLSI guidelines). The performance characteristics are reported as the outcome of the tests performed.

Below is a table summarizing the reported device performance for both TP and ALB, drawing from the "Technological Similarities and Differences to the Predicate" section and the "Brief Description of Nonclinical Data" and "Brief Description of Clinical Data" sections. Implicit acceptance is typically shown by these results being deemed "safe and effective for their intended uses."

Hitachi S TEST Reagent Cartridge: Reported Device Performance

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

The document describes test sets for various studies:

• Method Comparison (Internal):
  • TP: 115 clinical specimens
  • ALB: 118 clinical specimens
  • Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). Described as "clinical specimens."
• Matrices Comparison:
  • TP: 45 matched serum/plasma samples
  • ALB: 41 matched serum/plasma samples
  • Provenance: Not explicitly stated.
• External Site Precision Study:
  • TP: 3 "blinded serum samples" (low, middle, high) at each of 3 sites. Each sample assayed 30 times (6 times/day for 5 days). So, 3 samples * 30 replicates * 3 sites = 270 measurements per analyte for total precision.
  • ALB: 3 "blinded serum samples" (low, middle, high) at each of 3 sites. Each sample assayed 30 times (6 times/day for 5 days). So, 3 samples * 30 replicates * 3 sites = 270 measurements per analyte for total precision.
  • Provenance: "three external POL-type sites," implying clinical settings, likely within the US given the submission to the FDA. Retrospective/prospective not specified for the samples, but the testing itself was prospective within the study timeframe.
• External Method Comparison Studies (POL Accuracy Data Summary):
  • TP: Approximately 50-80 serum specimens per site (n=52, 52, 53). Total around 157.
  • ALB: Approximately 50-80 serum specimens per site (n=87, 81, 81). Total around 249.
  • Provenance: "three external POL-type sites," implying clinical settings, likely within the US. Retrospective/prospective not specified for samples but the comparative testing was prospective.

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

This document describes a diagnostic device for quantitative determination of Total Protein and Albumin. For such devices, "ground truth" is typically established by recognized reference methods, not by expert consensus (e.g., radiologists).

• Method Comparison (Internal and External): The comparison was made against a "standard laboratory system" or "comparative method as the reference method (x)." The specific details of this reference method are not given beyond its use for comparison. No information is provided about human expert involvement in establishing this ground truth.

4. Adjudication Method for the Test Set

Not applicable. Diagnostic devices like this establish their accuracy against a reference method, not through human adjudication of results.

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

No. This is an in-vitro diagnostic device that provides quantitative measurements. MRMC studies are relevant for imaging devices or those requiring human interpretation.

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

Yes, all studies described (analytical sensitivity, linearity, precision, interference, method comparisons, matrices comparisons) represent the standalone performance of the device (Hitachi Clinical Analyzer E40 with S TEST Reagent Cartridges) in measuring TP and ALB concentrations in samples. These are automated processes without direct human interpretation of results for the purpose of the measurement itself. Human operators are involved in running the analyzer, but the "performance" here refers to the device's analytical capability.

7. The Type of Ground Truth Used

The ground truth for the performance studies was established using:

• Reference Methods/Standard Laboratory Systems: For method comparison studies, the device's results (Y) were compared to a "standard laboratory system" or "comparative method" (X). This is a common approach for establishing accuracy of new in-vitro diagnostic devices.
• CLSI Guidelines: Studies like Analytical Sensitivity, Linearity, and Precision followed CLSI (Clinical and Laboratory Standards Institute) guidelines (e.g., EP17-A, EP-6A, EP5-A2). These guidelines define how to determine these performance characteristics, often involving reference materials or established statistical methods for calculation rather than external ground truth.
• Defined Concentrations: For precision and interference studies, samples were used that represented specific (low, middle, high) or known concentrations of the analytes.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI. This is a traditional in-vitro diagnostic device based on chemical reactions and photometric measurements. Its "development" would involve optimizing reagents and calibration, not "training" an algorithm in the AI sense. Therefore, the concept of a training set as understood in AI/ML is not applicable here.

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

As noted in #8, there is no "training set" in the context of AI/ML for this device. The ground truth for developing and calibrating such devices typically relies on:

• Primary Reference Materials: Highly characterized materials with known concentrations of analytes.
• Secondary Reference Materials: Materials traceable to primary reference materials.
• Validated Reference Methods: Established and highly accurate methods, often more complex or expensive, used to assign values to control or calibration materials.

The document implicitly refers to these as part of "assay performance claims were established on the HITACHI Clinical Analyzer."

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The S TEST Reagent Cartridge Total Bilirubin (T-BIL) is intended for the quantitative determination of total bilirubin in serum, lithium heparin plasma, K3 EDTA plasma, and sodium citrate plasma using the Hitachi Clinical Analyzer E40. The S TEST Reagent Cartridge Total Bilirubin is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

Total Billirubin measurements are used in the diagnosis and treatment of disorders of the liver.

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, e.g., expiration dating. The 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 serum or plasma and results are available in approximately 15 minutes per test. This submission is for Reagent Cartridge Total Bilirubin.

Chemistry reaction: Nitrous acid method: Total bilirubin in samples is oxidized to biliverdin by the action of nitrous acid at pH 3.7. The concentration of total bilirubin can be determined by measuring the decrease of absorbance at a wavelength of 450nm .

Here's a breakdown of the acceptance criteria and the study details for the Hitachi S TEST Reagent Cartridge Total Bilirubin (T-BIL), based on the provided document:

1. Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria for all performance characteristics in a single table. Instead, it presents various test results and implicitly suggests that these results are considered acceptable for demonstrating substantial equivalence to the predicate device.

However, based on the intended use and common analytical performance benchmarks for in vitro diagnostics, we can infer some criteria and list the reported performance:

2. Sample Sizes and Data Provenance

• Analytical Sensitivity (LoQ): Not specified for LoB and LoD. For LoQ, "three low level specimens in six runs over three [days] with three instruments."
• Linearity: 15 serial dilutions, plus the zero standard.
• 20-day In-house Precision: Four levels of samples, "each tested in two runs, twice a day, for 20 days." (Total of 80 measurements per level).
• Interference Testing:
  • Ascorbic acid and Hemoglobin: Two pools (approx. 1 and 4 mg/dL total bilirubin), spiked samples tested in triplicate.
  • Lipids: Three sets of serum samples with differing natural triglyceride levels and similar T-BIL, plus three sets of serum with low TG and similar T-BIL. Tested in triplicate.
• Method Comparison (Internal): 92 clinical specimens.
• Matrices Comparisons: 39 matched serum/plasma samples (sodium citrate, EDTA, lithium heparin).
• External Site Precision Study: Three blinded serum samples (A, B, C). Each sample assayed six times per day for five days, resulting in 30 replicates per level per site. (Total 90 replicates per sample level across 3 sites).
• External Method Comparison Studies: Approximately 50 serum specimens with total bilirubin values ranging from 0.4 to 38.1 mg/dL per site. (Total ~150 specimens across 3 sites).

Data Provenance: The document does not explicitly state the country of origin for the data. Given the address of the applicant (Mountain View, CA, USA) and the context of a 510(k) submission to the FDA, it is highly probable that the studies were conducted in the USA. All studies appear to be prospective as they were specifically designed and executed for this submission to evaluate the device's performance characteristics.

3. Number of Experts and Qualifications for Ground Truth

The document describes performance studies for an in vitro diagnostic device (reagent cartridge for total bilirubin). The "ground truth" in this context is typically established by a reference method or a standard laboratory system, not by human experts interpreting results.

Therefore, the concept of "number of experts used to establish the ground truth" and their "qualifications" as it applies to image analysis or diagnostic interpretation by humans is not applicable to this type of device and study. The comparison is against established chemical measurement techniques.

4. Adjudication Method

As the "ground truth" is established by chemical reference methods rather than human interpretation, an adjudication method (like 2+1 or 3+1 often used in imaging studies) is not applicable. The results are quantitative measurements compared against other quantitative measurements.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed, nor would it be appropriate for this type of in vitro diagnostic device. MRMC studies are typically used to evaluate diagnostic accuracy and reader performance (e.g., radiologists, pathologists) for devices that involve human interpretation of images or other diagnostic data, often comparing AI-assisted vs. unassisted human performance.

This device, the "S TEST Reagent Cartridge Total Bilirubin (T-BIL)," is an automated chemistry assay that provides a quantitative measurement. There is no human "reader" in the loop whose performance would be improved by AI assistance.

6. Standalone (Algorithm Only) Performance Study

Yes, a standalone performance study was done. All the studies described (analytical sensitivity, linearity, precision, interference, and method comparisons) evaluate the performance of the S TEST Reagent Cartridge Total Bilirubin when used with the Hitachi Clinical Analyzer E40, without human intervention in the result generation beyond operating the analyzer and collecting the samples.

The method comparison studies specifically compare the algorithm-generated result (from the S TEST T-BIL system) against results from a "standard laboratory system" or "comparative method," demonstrating its standalone performance.

7. Type of Ground Truth Used

The ground truth used for the performance studies was comparison against a standard laboratory system (or comparative method). For example:

• Linearity, Precision, Interference: These studies used prepared samples with known concentrations or manipulated matrices where the expected result provides the ground truth benchmark.
• Method Comparison (Internal & External): The results from the S TEST T-BIL system were compared against a "standard laboratory system" or a "comparative method" (implicitly, another cleared and accepted total bilirubin assay).
• Matrices Comparisons: Comparison was made between the T-BIL results in plasma types against serum using the same or an established method.

There is no mention of pathology, outcome data, or expert consensus in the setting of diagnostic interpretation, as this is a quantitative chemical measurement.

8. Sample Size for the Training Set

The document does not provide information on a training set sample size. This is common for traditional in vitro diagnostic devices like reagent cartridges. These devices are developed based on established chemical principles (Nitrous acid method in this case) and tested for performance, rather than being "trained" using a dataset in the way an AI algorithm for image recognition would be.

Thus, the concept of a "training set" in the context of machine learning or AI is not applicable here. The development and validation process focuses on analytical performance characteristics.

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

Since there is no "training set" as understood in AI/ML, the question of how its ground truth was established is not applicable. The device's performance is validated against established laboratory standards and reference methods as detailed in section 7.

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The S TEST Reagent Cartridge Calcium (CA) is intended for the quantitative determination of calcium in serum, lithium heparinized plasma, and sodium citrate plasma using the HITACHI Clinical Analyzer E40. The S TEST Reagent Cartridge Calcium is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

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, e.g., expiration dating. The 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 serum or plasma and results are available in approximately 15 minutes per test. This submission is for Reagent Cartridge Calcium.

Chemistry reactions: Calcium in the sample combines with o-cresolphthalein complexone to form a purple-red complex. The concentration of calcium can be determined by measuring the absorbance of the resulting purple-red color. (With this method, the influence of magnesium is excluded by the addition of 8-hydroxyquinoline.)

Here's a breakdown of the acceptance criteria and study information for the Hitachi S TEST Reagent Cartridge Calcium, based on the provided text:

Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" for each performance characteristic. Instead, it presents the results of various studies (precision, linearity, method comparison, interference, matrix comparison) and implies that these results meet regulatory and performance expectations for substantial equivalence. For the purpose of this analysis, I will infer the implied acceptance by comparing the device performance to the predicate device where applicable, or noting the performance demonstrated without a direct comparative statement if no specific target is given.

Study Details

This device is an in vitro diagnostic (IVD) chemistry analyzer for calcium, not an AI/ML device. Therefore, several of the requested sections regarding AI-specific studies (experts, adjudication, MRMC, training set) are not applicable.

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

   • Analytical Sensitivity (LOD): Not explicitly stated, but the study followed CLSI EP17-A.
   • Linearity: Not explicitly stated, but the study followed CLSI EP-6A.
   • 20-day In-house Precision: Three levels of samples, each tested in two runs, twice a day, for 20 days. (Total of 120 measurements per level).
   • Interference Testing: Two serum pools.
   • In-house Method Comparison: 97 clinical specimens (spanning 1.2 to 14.8 mg/dL).
   • Matrices Comparisons: 44 matched serum/plasma samples (spanning 0.9 to 14.7 mg/dL).
   • External Site Precision (Clinical Data): Three blinded serum samples (low, middle, high calcium concentrations) tested at each of three external POL sites. Each sample was assayed 6 times per day for 5 days, resulting in 30 results per level per site.
   • External Method Comparison (Clinical Data): Approximately 55 serum specimens (ranging from 1.3 to 14.6 mg/dL) at each of three external POL sites.
   • Data Provenance: Not explicitly stated for specific samples, but the studies were conducted by "Hitachi Chemical Diagnostics, Inc." (in-house) and at "three external POL-type sites." The specimens are clinical specimens (serum and plasma). The country of origin is not specified but implicitly the US given the FDA submission. All data appears to be prospective collection for the validation of this device.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):

   • Not applicable. This is an IVD device for quantitative chemical analysis; ground truth is established by the analytical reference methods or comparative methods used.

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

   • Not applicable. This is an IVD device for quantitative chemical analysis.

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

   • Not applicable. This is an IVD device for quantitative chemical analysis, not an AI-assisted diagnostic imaging device involving human readers.

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

   • Yes, implicitly. All studies (precision, linearity, method comparisons, interference, matrix comparisons) evaluate the performance of the device itself (Hitachi E40 Clinical Analyzer with S TEST Reagent Cartridge Calcium) in an automated or semi-automated standalone fashion, generating quantitative results. Human intervention is limited to sample loading, programming, and result interpretation, not in the analytical process itself.

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

   • For Method Comparison studies, "ground truth" is established by a "standard laboratory system" or "comparative method" (predicate or other established analyzer), generating quantitative calcium values.
   • For Analytical Sensitivity, Linearity, Precision, Interference, and Matrix Comparison studies, "ground truth" refers to the expected or known concentrations of calcium in control samples, calibrators, or spiked samples, verified through established analytical methods.

7. The sample size for the training set:

   • Not applicable. This is an IVD device for quantitative chemical analysis, not an AI/ML device requiring a training set in the typical sense. The "training" of the device is its calibration and quality control procedures, which are part of standard IVD practices.

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

   • Not applicable. (See above.)

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The S TEST Reagent Cartridge Alkaline Phosphatase (ALP) is intended for the quantitative measurement of alkaline phosphatase activity in serum, lithium heparinized plasma, or sodium citrate plasma using the HITACHI Clinical Analyzer. The S TEST Reagent Cartridge Alkaline Phosphatase (ALP) is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

Measurements of alkaline phosphatase are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

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, e.g., expiration dating. The 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 serum or plasma and results are available in approximately 15 minutes per test. This submission is for Reagent Cartridge ALP.

Chemistry reactions: Alkaline phosphatase (ALP) in the sample reacts with its substrate, pnitrophenyl phosphate (p-NPP), in ethylaminoethanol (EAE) buffer, to release p-nitrophenol (yellow). The ALP activity is determined by measuring the rate of p-nitrophenol production.

The provided text describes the performance characteristics and acceptance criteria for the Hitachi S TEST Reagent Cartridge Alkaline Phosphatase (ALP).

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" as a separate column for all metrics. However, the performance data provided implies that the reported results met the internal development criteria for each study. Where a specific acceptance range or threshold is mentioned (e.g., for interference testing), it is included.

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

• Analytical Sensitivity (Limits of Detection): Not specified, but likely involved multiple replicates for statistical analysis as per CLSI EP17-A.
• Linearity: Not specified, but involved samples spanning 5 U/L to 1,000 U/L as per CLSI EP-6A.
• 20-day In-house Precision: Three levels of samples, each tested in two runs, twice a day, for 20 days. This means 80 data points per level (2 runs/day * 2 times/run * 20 days). Total around 240 data points across 3 levels.
• Interference Testing: Two serum pools tested.
• Method Comparison (in-house): 97 clinical specimens. Data provenance: Not explicitly stated, but implied to be in-house or from a domestic source. Retrospective.
• Matrices Comparisons: 38 matched serum/plasma samples. Data provenance: Not explicitly stated, but implied to be in-house or from a domestic source. Retrospective.
• External Site Precision: Each site tested three blinded serum samples, six times per day for five days. This means 30 replicates per sample per site. With 3 sites and 3 samples, approximately 270 data points (30 * 3 * 3).
• External Site Method Comparison: Approximately 70 serum specimens per site, for a total of around 210 specimens (3 sites * ~70 samples/site). Data provenance: Not explicitly stated, but typically from within the country where the study is conducted (likely USA, given the FDA submission). Retrospective.

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

This information is not applicable as the device is a quantitative chemical analyzer. The "ground truth" for the test sets (samples used in the studies) is established by the reference methods or known concentrations, not by expert interpretation.

4. Adjudication Method for the Test Set:

This information is not applicable as the device is a quantitative chemical analyzer. Ground truth is determined objectively through reference methods or known concentrations, not through expert adjudication.

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

This information is not applicable. The device is a diagnostic instrument (chemistry analyzer) and not an AI-based imaging or diagnostic aid that involves human readers.

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

The studies described (precision, linearity, method comparison, interference, matrices comparison) represent the standalone performance of the Hitachi Clinical Analyzer with the S TEST Reagent Cartridge ALP. This is the direct measurement by the instrument, without a human interpretation step.

7. The Type of Ground Truth Used:

The ground truth for the performance studies was established using:

• Reference Methods: For method comparison studies, the Hitachi system was compared against a "standard laboratory system" (predicate device or another established method).
• Known Concentrations/Values: For linearity, precision, and interference studies, samples with known or carefully characterized concentrations of ALP and potential interferents were used.
• CLSI Guidelines: Studies followed established Clinical and Laboratory Standards Institute (CLSI) guidelines (e.g., EP17-A for detection limit, EP-6A for linearity, EP5-A2 for precision, EP7-A2 for interference).

8. The Sample Size for the Training Set:

This information is not applicable. This device is a traditional chemical analyzer, not an AI/machine learning system that requires a "training set" in the computational sense. The device's parameters are set during its manufacturing and calibration process, not through a data-driven training phase.

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

This information is not applicable for the reason stated in point 8.

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