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The ARK Levetiracetam II Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of levetiracetam in human serum or plasma on automated clinical chemistry analyzers. Levetiracetam concentrations can be used as an aid in management of patients treated with levetiracetam.

The ARK Levetiracetam II Assay is a homogeneous immunoassay based on competition between drug in the specimen and levetiracetam labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly related to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenzyme NAD functions only with the bacterial enzyme used in the assay.

The ARK Levetiracetam II Assay consists of reagents R1 anti-levetiracetam monoclonal antibody with substrate and R2 levetiracetam labeled with bacterial G6PDH enzyme.

The provided text describes the performance of a diagnostic assay (ARK Levetiracetam II Assay), not an AI/ML-enabled medical device. Therefore, many of the requested criteria related to AI/ML evaluation (such as MRMC studies, training set details, expert ground truth establishment for AI) are not applicable.

However, I can extract the relevant acceptance criteria and performance data for this in-vitro diagnostic device:

Device Name: ARK Levetiracetam II Assay
Regulatory Class: Class II
Product Code: ORI
Intended Use: Quantitative determination of levetiracetam in human serum or plasma on automated clinical chemistry analyzers, as an aid in management of patients treated with levetiracetam.

Here's the information based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

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

• LoQ: 40 replicates (8 replicates x 5 runs) for each of 3 concentrations (pooled human serum supplemented with levetiracetam).
• Recovery: 6 replicates (3 replicates x 2 analytical runs) for each concentration (human serum negative for levetiracetam, spiked with drug).
• Linearity: 6 replicates (3 replicates x 2 analytical runs) for each dilution (human serum, spiked with drug and diluted).
• Method Comparison: 104 samples (levetiracetam concentrations 3.4 ug/mL to 98.3 ug/mL). No specific provenance (e.g., country of origin) is mentioned, but the samples are clinical human samples or quality control materials. The study is a prospective analytical study comparing two assays.
• Precision: 160 replicates per sample/control level (quadruplicate twice a day for 20 non-consecutive days) for tri-level controls and three human serum samples.
• Interfering Substances: 6 replicates (3 replicates x 2 analytical runs) for each interfering substance level in two known levetiracetam concentrations (human serum).
• Metabolites/Drug Interference: Not explicitly stated, but similar to interfering substances: "high concentration of each compound was spiked into normal human serum with known levels of levetiracetam."

The data provenance is from analytical studies conducted by the manufacturer, likely in a laboratory setting, using human serum/plasma samples/materials. The document does not specify country of origin for the samples/data, beyond "human serum/plasma". These are prospective analytical studies designed to characterize the device's performance.

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

This section is not applicable as the document describes an in-vitro diagnostic assay for quantitative determination of a drug. The "ground truth" for such an assay is established by the known concentrations of calibrators, controls, and spiked samples, and comparison to a legally marketed predicate device using analytical methods (e.g., spectrophotometry). There are no human "experts" establishing a "ground truth" in the sense of image interpretation or clinical diagnosis.

4. Adjudication Method for the Test Set

Not applicable. This is an in-vitro diagnostic device providing quantitative measurements. There is no qualitative assessment or interpretation by multiple readers that would require an adjudication method.

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

No. This is an in-vitro diagnostic assay, not an AI/ML medical device where human readers interact with AI.

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

Yes, in essence. The performance studies (LoQ, Recovery, Linearity, Precision, Interference) demonstrate the "standalone" performance of the assay itself, as an automated clinical chemistry analyzer performs the measurements. There is no human-in-the-loop variable in the measurement process of an immunoassay. The output is a quantitative value, not a diagnostic interpretation that a human would then use as "assistance."

7. The Type of Ground Truth Used

The ground truth used for performance evaluation is primarily:

• Known concentrations: For LoQ, Recovery, Linearity, Interfering Substances, Metabolites, and Drug Interference studies, concentrations of levetiracetam and potential interferents are precisely measured, prepared, or spiked into matrices.
• Reference Method/Predicate Device: For Method Comparison, the predicate ARK Levetiracetam Assay performed on the Roche/Hitachi 917 serves as the comparative "reference" for evaluating the substantial equivalence of the new assay. This is a common practice for IVD assays.

8. The Sample Size for the Training Set

Not applicable. This is a reagent-based immunoassay, not an AI/ML algorithm that requires a training set in the typical sense for machine learning. The "development" or "training" of such a diagnostic involves chemical formulation, antibody development, and optimization of reaction conditions, not data-driven model training.

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

Not applicable. As explained above, there is no AI/ML training set in this context.

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The ONLINE TDM Phenytoin - Free Phenytoin application is an in vitro test for the quantitative determination of free phenytoin in human serum and plasma on cobas c systems. The determination of free phenytoin is used in monitoring levels of free phenytoin to ensure appropriate therapy.

The ONLINE TDM Phenytoin - Free Phenytoin application is an in vitro test for the quantitative determination of free phenytoin in human serum and plasma on cobas c systems. The determination of free phenytoin is used in monitoring levels of free phenytoin to ensure appropriate therapy.

Prior to measurement using the ONLINE TDM Phenytoin - Free Phenytoin application, the sample is processed by ultrafiltration to remove the bound phenytoin generating a result for free phenytoin.

The ONLINE TDM Phenytoin - Free Phenytoin application is based on the kinetic interaction of microparticles in a solution (KIMS). Phenytoin antibody is covalently coupled to microparticles and the drug derivative is linked to a macromolecule. The kinetic interaction of microparticles in solutions, photometrically detected by turbidity measurements is induced by binding of drugconjugate to the antibody on the microparticles and is inhibited by the presence of phenytoin in the sample. A competitive reaction takes place between the drug conjugate and phenytoin in the serum sample for binding to the phenytoin antibody on the microparticles. The resulting turbidity is indirectly proportional to the amount of drug present in the sample.

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

Device Name: ONLINE TDM Phenytoin - Free Phenytoin application

1. Table of Acceptance Criteria and Reported Device Performance

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

• Precision (Repeatability and Intermediate Precision):
  • Repeatability: n = 84 (implied total measurements, as 2 aliquots per run, 2 runs per day, 21 days = 84 measurements for intermediate precision, and repeatability likely collected within this structure).
  • Intermediate Precision: 2 aliquots per run, 2 runs per day, 21 days.
  • Data Provenance: Not explicitly stated, implied to be laboratory-prepared controls and human serum samples.
• Analytical Sensitivity (LoB, LoD, LoQ):
  • LoB: One analyte-free sample (ultrafiltrate of human phenytoin-free serum) measured with three reagent lots in 6 runs, each with 10-fold determination (total 180 measurements).
  • LoD: 5 serum samples with low analyte concentrations (spiked with phenytoin and ultrafiltrated) measured on three reagent lots with 2-fold determination per run, over 6 runs (total 180 measurements).
  • LoQ: 6 serum samples (spiked with phenytoin and ultrafiltrated) measured with three reagent lots, 5 replicates per run, over 5 days (total 450 measurements).
  • Data Provenance: Human phenytoin-free serum, spiked human serum samples (ultrafiltrated).
• Linearity/Assay Reportable Range:
  • Sample Size: A dilution series ( > 9 levels) prepared from a spiked human ultrafiltrated serum pool and a negative ultrafiltrated serum pool. Tested with 3 reagent lots and 4 replicates per sample. The process was repeated with K3-EDTA plasma.
  • Data Provenance: Spiked human ultrafiltrated serum pool and negative ultrafiltrated serum pool, K3-EDTA plasma.
• Dilution:
  • Sample Size: Three ultrafiltrates prepared with specific phenytoin concentrations (5.00, 6.00, 7.00 µg/mL).
  • Data Provenance: Laboratory-prepared ultrafiltrates with spiked phenytoin.
• Endogenous Interferences:
  • Sample Size: Not explicitly stated, but various endogenous substances were evaluated. The description suggests samples were prepared by adding interferents to ultrafiltrate or present in the sample before ultrafiltration.
  • Data Provenance: Laboratory-prepared samples with added endogenous substances or naturally occurring levels.
• Analytical Specificity/Cross-Reactivity:
  • Sample Size: Two ultrafiltrated human serum pools spiked with phenytoin (1.00 and 2.50 µg/mL) for each potential cross-reacting compound. Phenytoin concentration determined in at least 5-fold determination.
  • Data Provenance: Ultrafiltrated human serum pools spiked with phenytoin and cross-reactants.
• Exogenous Interferences - Drugs:
  • Sample Size: Not explicitly stated, but drugs were tested individually at specified concentrations. Some drugs were tested by spiking into serum, others into ultrafiltrate.
  • Data Provenance: Laboratory-prepared samples with added drugs.
• Sample Matrix Comparison:
  • Sample Size: ≥ 50 samples comparing serum, Li-Heparin, K2-EDTA, and K3-EDTA plasma.
  • Data Provenance: Native human samples collected in different tube types, spiked and ultrafiltrated.
• Method Comparison:
  • Sample Size: 138 native human ultrafiltrated serum samples (≤10% spiked).
  • Data Provenance: Native human ultrafiltrated serum samples.

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

This device is an in vitro diagnostic (IVD) test system for the quantitative determination of free phenytoin. The "ground truth" for such a device is typically established by reference methods or established analytical techniques, often involving highly skilled laboratory personnel operating calibrated equipment, rather than clinical experts (like radiologists).

The text does not mention the use of clinical experts (e.g., radiologists) or their qualifications to establish ground truth. The methodologies like CLSI guidelines (EP05-A3, EP17-A2, EP06-A-Ed2) imply adherence to established laboratory standards and practices for analytical validation, often performed by trained laboratory scientists or technicians.

4. Adjudication Method for the Test Set

This type of analytical device validation does not typically involve an "adjudication method" in the way it's understood for image-based diagnostics (e.g., 2+1, 3+1 consensus among radiologists). Results are quantitative and are compared directly to expected values, reference methods, or statistical acceptance criteria.

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

No, an MRMC comparative effectiveness study was not done. MRMC studies are relevant for AI-powered diagnostic devices where human readers interpret images or data, and the study assesses how AI assistance impacts their performance. This submission is for an in vitro diagnostic (IVD) laboratory test system, not an image-interpretation AI device.

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

This device is a standalone in vitro diagnostic test system. Its performance characteristics (precision, sensitivity, linearity, interference, etc.) are evaluated directly as the device itself operates. There isn't a separate "human-in-the-loop performance" concept for this type of quantitative assay, as the device provides a direct numerical result. The reported performance is the standalone performance of the ONLINE TDM Phenytoin - Free Phenytoin application on cobas c systems.

7. The Type of Ground Truth Used

The ground truth for the analytical performance studies primarily relied on:

• Reference Materials: Calibrators (Preciset TDM I), Controls (TDM Control Set), and laboratory-prepared samples with known concentrations of phenytoin and/or interferents (e.g., spiked serum, ultrafiltrates).
• Established Methods: Comparison to a predicate device (Phenytoin - Free Phenytoin Application on COBAS INTEGRA 400 plus) in the method comparison study.
• Theoretical Standards: Adherence to CLSI (Clinical and Laboratory Standards Institute) guidelines (EP05-A3, EP17-A2, EP06-A-Ed2) for defining analytical limits and linearity.

There is no mention of pathology, outcomes data, or expert consensus in the clinical sense for establishing ground truth for this analytical performance.

8. The Sample Size for the Training Set

The document does not describe a "training set" as would be relevant for a machine learning or AI-based device. This device is a chemical assay (Kinetic Interaction of Microparticles in a Solution - KIMS). The development of the assay itself would involve optimization and calibration phases, but these are not referred to as statistical "training sets" in the context of general device validation.

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

Since there is no "training set" described in the context of an AI/ML algorithm, this question is not applicable. The assay's performance is driven by its chemical and optical principles, not by learning from a labeled dataset. The "ground truth" during assay development would be established through careful analytical chemistry techniques to ensure the reagents and measurement system accurately quantify free phenytoin.

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The ARK Lacosamide Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lacosamide in human serum on automated clinical chemistry analyzers. The measurements obtained are used in monitoring levels of lacosamide to help ensure appropriate therapy.

The ARK Lacosamide Assay is a homogeneous enzyme immunoassay based on competition between drug in the specimen and lacosamide labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly related to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenzyme NAD functions only with the bacterial enzyme used in the assay.

The ARK Lacosamide Assay consists of reagents R1 anti-lacosamide polyclonal antibody with substrate and R2 lacosamide labeled with bacterial G6PDH enzyme.

The provided text describes the ARK Lacosamide Assay, a homogeneous enzyme immunoassay for quantitative determination of lacosamide in human serum. This device is intended for monitoring lacosamide levels to ensure appropriate therapy. The substantial equivalence is demonstrated through comparative testing against a predicate device (ARKTM Topiramate Assay, K083799) and various performance characteristic studies.

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

1. Table of Acceptance Criteria and Reported Device Performance:

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

• LoQ: 40 replicates (8 replicates x 5 runs) for each of 3 concentrations. Data provenance is implied to be laboratory-generated (pooled human serum supplemented with lacosamide).
• Measurement Range: Not a directly tested "test set" in terms of patient samples; rather, it refers to the range characterized by other studies like recovery and linearity.
• Recovery: Not explicitly stated as a separate "test set" size for recovery studies, but involved adding concentrated lacosamide to pooled human serum. "Two analytical runs of three replicates of each sample were assayed."
• Linearity: Dilutions of a 30.00 µg/mL lacosamide serum sample. "Two analytical runs of three replicates of each sample were assayed."
• Method Comparison: 150 unaltered, human serum specimens. The data provenance is described as "human serum specimens" which implies retrospective clinical samples, but the country of origin is not specified. They are "not individually identifiable."
• Precision: 160 replicates for each of 6 samples/controls (quadruplicate twice a day for 20 days). Implied laboratory-generated (tri-level controls and pooled human serum with lacosamide).
• Interfering Substances: For each interfering substance, lacosamide was present at 2 concentrations (2.0 and 15.0 µg/mL). "Two analytical runs of three replicates of each sample (6 replicates total) were assayed." Implied laboratory-generated.
• Specificity (O-Desmethyl Metabolite): Assayed lacosamide at 2 concentrations (2.00 and 15.00 µg/mL) in the absence and presence of the metabolite at 2 concentrations (5.0 and 30.0 µg/mL). Implied laboratory-generated.
• Crossreactivity (Other Drugs): For each of 77 compounds, lacosamide was present at 2 concentrations (2.00 and 15.00 µg/mL). Implied laboratory-generated.
• Sample Stability: Not a statistical "test set" but based on supporting data; implies samples stored under different conditions.

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

• This device is an in vitro diagnostic assay that measures a chemical compound (lacosamide concentration). The "ground truth" for method comparison studies is established by a reference method, not by expert interpretation.
• In the method comparison study, the ARK Lacosamide Assay results were compared against LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry). LC-MS/MS is a highly accurate and sensitive analytical chemistry technique, often considered a "gold standard" for quantifying small molecules like drugs in biological matrices.
• Therefore, no human experts were used to establish the ground truth; instead, an established analytical method served as the reference.

4. Adjudication method for the test set:

• Not applicable as the ground truth is established by a quantitative analytical method (LC-MS/MS), not by human interpretation or consensus.

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

• Not applicable. This device is an in vitro diagnostic assay, not an AI-powered diagnostic imaging or interpretation tool that assists human readers.

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

• Yes, the performance characteristics described (LoQ, Measurement Range, Recovery, Linearity, Precision, Interfering Substances, Specificity, Crossreactivity, Stability) are all standalone algorithm (assay) performance studies. The method comparison study also evaluated the standalone performance of the ARK Lacosamide Assay against LC-MS/MS.
• The device explicitly states it is "intended for the quantitative determination of lacosamide in human serum on automated clinical chemistry analyzers," indicating standalone operation with human oversight rather than human-in-the-loop interpretation of complex data.

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

• For the method comparison study, the ground truth was "results from LC-MS/MS," which is a reference analytical method.
• For other performance studies (LoQ, recovery, linearity, precision, interference, specificity, cross-reactivity), the ground truth was based on the known concentrations of lacosamide and interfering substances added to human serum samples.

8. The sample size for the training set:

• This is an in vitro diagnostic assay, not a machine learning or AI model that requires a "training set" in the conventional sense. The development of the assay's reagents and methodologies involves analytical chemistry and biochemical principles rather than statistical training on data.

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

• Not applicable for the reasons stated in point 8. The "ground truth" for the development of this assay would be the accurate chemical characterization of lacosamide and its antibodies, and the optimization of the enzymatic reaction to accurately reflect lacosamide concentration.

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The ARK™ Gabapentin Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of gabapentin in human serum or plasma on automated clinical chemistry analyzers. Gabapentin concentrations can be used as an aid in management of patients treated with gabapentin.

The ARKTM Gabapentin Calibrator is intended for use in calibration of the ARK Gabapentin Assay.

The ARKTM Gabapentin Control is intended for use in quality control of the ARK Gabapentin Assay.

The ARK Gabapentin Assay is a homogeneous immunoassay based on competition between drug in the specimen and gabapentin labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay.

The ARK Gabapentin Assay consists of reagents R1 anti-gabapentin polyclonal antibody with substrate and R2 gabapentin labeled with bacterial G6PDH enzyme. The ARK Gabapentin Calibrator consists of a six-level set to calibrate the assay, and the ARK Gabapentin Control consists of a three-level set used for quality control of the assay.

ARK Gabapentin products contain ≤0.09% sodium azide. As a precaution, affected plumbing should be flushed adequately with water to mitigate the potential accumulation of explosive metal azides. No special handling is required regarding other assay components.

Here's a summary of the acceptance criteria and study findings for the ARK™ Gabapentin Assay, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Recovery: Not explicitly stated how many unique samples were tested, but "Six replicates of each sample were assayed." The samples were "human serum negative for gabapentin" spiked with pure gabapentin. Provenance: Not specified (retrospective/prospective, country of origin).
• Linearity: Not explicitly stated how many unique samples, but dilutions were made from a 48.0 µg/mL serum sample. Provenance: Not specified.
• Method Comparison:
  • Study 1: 183 samples. Provenance: Not specified.
  • Study 2: 64 samples. Provenance: Not specified.
  • Study 3: 49 samples. Provenance: Not specified.
• Precision: 160 measurements were taken for each of the three control levels and three human serum pooled specimens (quadruplicate, twice a day for 20 days). Provenance: Not specified.
• Interfering Substances: For each interfering substance, samples were prepared with gabapentin at approximately 2 µg/mL and 20 µg/mL, and assayed against a serum control. The number of individual samples (beyond the spiked ones) isn't specified. Provenance: Not specified.
• Drug Interference: Similar to interfering substances, samples were prepared with gabapentin at approximately 2 µg/mL and 20 µg/mL, spiked with high concentrations of various drugs, and assayed against a serum control. Provenance: Not specified.
• Anticoagulants: "Studies were conducted to determine the performance characteristics of the assay for both serum and plasma samples." Specific sample sizes not provided. Provenance: Not specified.
• Sample Stability: Specific sample sizes not provided, but studies addressed various storage conditions and freeze-thaw cycles. Provenance: Not specified.

It is common for these types of in vitro diagnostic device submissions for a new assay to describe the preparation of test materials and not necessarily the specific provenance of every human sample component (e.g., general "human serum").

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

This type of in vitro diagnostic device (quantitative immunoassay) does not typically involve human experts for establishing "ground truth" in the way an imaging AI device would. Instead, the "ground truth" for the performance studies described is established by:

• Reference methods: For method comparison, reference standards like LC-MS/MS and HPLC are used to define the true concentration of gabapentin in samples. These are highly accurate analytical techniques, not human expert consensus.
• Spiking studies: For recovery, linearity, interference, and drug interference, known quantities of high-purity gabapentin or interfering substances are added to negative serum/plasma, establishing a precise theoretical "ground truth" concentration.

Therefore, the concept of "number of experts" and their "qualifications" for ground truth determination is not applicable in this context.

4. Adjudication Method for the Test Set

Not applicable. As explained above, the ground truth is established by analytical reference methods or known spiked concentrations, not by human interpretation or 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

Not applicable. This device is a quantitative immunoassay for measuring drug concentration in blood, not an imaging device or a diagnostic aid that would involve human "readers" or AI assistance in interpretation.

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

Yes, the studies described are all "standalone" in nature, as they assess the performance of the assay itself (the "algorithm only" in a broader sense of an analytical method) to accurately measure gabapentin concentrations. The output of the device is a quantitative value (gabapentin concentration in µg/mL), which is then used by clinicians. There is no "human-in-the-loop performance" component for how the assay itself functions.

7. The Type of Ground Truth Used

The ground truth for the performance studies was established using:

• Reference analytical methods: High Performance Liquid Chromatography - Mass Spectrometry (LC-MS/MS) and High Performance Liquid Chromatography (HPLC) were used as reference methods for the method comparison studies.
• Spiked samples: For recovery, linearity, interference, and drug interference studies, known, precise amounts of pure gabapentin or interfering substances were added to gabapentin-negative human serum/plasma to create samples with known theoretical concentrations.

8. The Sample Size for the Training Set

Not applicable. This is an immunoassay, not a machine learning or AI algorithm in the contemporary sense that would involve a "training set" for model development. The development of the assay (e.g., antibody selection, reagent formulation) is a traditional chemical and biological process, not a computational learning process with distinct training and test sets.

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

Not applicable, as there is no "training set" in the context of this immunoassay.

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The ARK™ Lamotrigine Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lamotrigine in human serum or plasma on automated clinical chemistry analyzers. Lamotrigine concentrations can be used as an aid in management of patients treated with lamotrigine.

The ARKTM Lamotrigine Calibrator is intended for use in calibration of the ARK Lamotrigine Assay.

The ARKTM Lamotrigine Control is intended for use in quality control of the ARK Lamotrigine Assay.

The ARK Lamotrigine Assay is a homogeneous immunoassay based on competition between drug in the specimen and lamotrigine labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay.

The ARK Lamotrigine Assay consists of reagents R1 anti-lamotrigine polyclonal antibody with substrate and R2 lamotrigine labeled with bacterial G6PDH enzyme. The ARK Lamotrigine Calibrator consists of a six-level set to calibrate the assay, and the ARK Lamotrigine Control consists of a three-level set used for quality control of the assay.

The ARK™ Lamotrigine Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lamotrigine in human serum or plasma. The device performance was evaluated through various studies, including limit of quantitation (LOQ), assay range, recovery, linearity, method comparison, precision, interfering substances, specificity, and anticoagulant studies.

1. Acceptance Criteria and Reported Device Performance:

2. Sample Size and Data Provenance for Test Set:

• Recovery: Not explicitly stated, but "six replicates of each sample" were assayed across various concentrations, implying a total of 48 individual assays. Data provenance is human serum negative for lamotrigine, spiked with concentrated drug.
• Linearity: Not explicitly stated, but dilutions from a 48.00 µg/mL serum sample were made. Data provenance is human serum negative for lamotrigine, spiked with drug.
• Method Comparison (Study 1 - HPLC): 193 samples. Provenance not explicitly stated (e.g., country of origin, retrospective/prospective), but implied to be clinical samples or samples prepared to simulate clinical range.
• Method Comparison (Study 2 - Turbidimetric Immunoassay): 77 samples. Provenance not explicitly stated.
• Precision: Tri-level controls and three human serum pooled specimens. Each level assayed in quadruplicate twice a day for 20 days (160 measurements per control/pool level).
• Interfering Substances: Clinically high concentrations of substances in human serum with known lamotrigine levels (approximately 3 and 15 µg/mL).
• Specificity (Metabolites): Metabolites spiked into two separate samples each containing low (3 µg/mL) and high (15 µg/mL) therapeutic levels of lamotrigine.
• Specificity (Drug Interference): High concentration of each compound spiked into normal human serum with known lamotrigine levels (approximately 3 and 15 µg/mL).
• Anticoagulants: Not explicitly stated but implies a set of serum and plasma samples were tested.
• Sample Stability: Not explicitly stated, but samples were subject to various conditions (frozen, room temp, refrigerated, freeze/thaw cycles).

3. Number of Experts and their Qualifications for Ground Truth:
This type of device (quantitative immunoassay) relies on analytical performance against established reference methods or known concentrations, rather than expert interpretation of images or clinical data. Therefore, the concept of "experts establishing ground truth" as it applies to subjective assessments is not directly applicable here. The ground truth for analytical studies like recovery and linearity are based on gravimetric dilutions/known concentrations, and for method comparisons, the reference methods themselves (HPLC, predicate immunoassay) serve as the comparative standard.

4. Adjudication Method for the Test Set:
Not applicable for this type of analytical device validation. The studies involve quantitative measurements and comparisons to reference methods or known values, not subjective interpretations requiring adjudication.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for diagnostic devices requiring human interpretation of results, such as imaging studies, where the AI's effect on human reader performance is evaluated. This device is an automated immunoassay for quantitative measurement.

6. Standalone (Algorithm Only) Performance:
Yes, the entire submission describes the standalone performance of the ARK™ Lamotrigine Assay. The studies (LOQ, assay range, recovery, linearity, method comparison, precision, interference, specificity, stability) evaluate the device's analytical performance independently. The device operates on automated clinical chemistry analyzers without human intervention for result generation.

7. Type of Ground Truth Used:

• Known Concentrations/Gravimetric Dilutions: For studies such as Limit of Quantitation, Recovery, Linearity, Precision, Interfering Substances, Specificity (Metabolites, Drug Interference), and Anticoagulants, the ground truth is established by preparing samples with known, precise concentrations of lamotrigine or interfering substances through gravimetric dilutions.
• Reference Methods: For method comparison studies, the reference methods are High Performance Liquid Chromatography (HPLC) and a predicate turbidimetric immunoassay (QMS® Lamotrigine, K062966).

8. Sample Size for the Training Set:
Not applicable. This device is a quantitative immunoassay with "wet lab" validation, not an AI/ML algorithm that typically requires a large clinical "training set" to learn patterns. The validation process involves demonstrating analytical performance against known standards and comparative methods.

9. How Ground Truth for the Training Set Was Established:
Not applicable, as there isn't a "training set" in the context of an AI/ML algorithm. The device's analytical characteristics are determined through laboratory experiments using carefully prepared samples with known concentrations or by comparison to reference methods.

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The ARK™ Zonisamide Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of zonisamide in human serum or plasma samples on automated clinical chemistry analyzers. Zonisamide concentrations can be used as an aid in management of patients treated with zonisamide.

The ARK™ Zonisamide Calibrator is intended for use in calibration of the ARK Zonisamide Assay.

The ARK™ Zonisamide Control is intended for use in quality control of the ARK Zonisamide Assav.

The ARK Zonisamide Assay is a homogeneous immunoassay based on competition between drug in the specimen and zonisamide labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay.

The ARK Zonisamide Assay consists of reagents R1 anti-zonisamide polyclonal antibody with substrate and R2 zonisamide labeled with bacterial G6PDH enzyme. The ARK Zonisamide Calibrator consists of a six-level set to calibrate the assay, and the ARK Zonisamide Control consists of a three-level set used for quality control of the assay.

Here's a breakdown of the acceptance criteria and the study details for the ARK Zonisamide Assay, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

Study Details

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

   • LOQ: 20 replicates for each sample. Data provenance not specified (likely laboratory-prepared samples).
   • Recovery: 20 replicates for each sample. Data provenance not specified (likely laboratory-prepared samples with added drug).
   • Linearity: Zonisamide concentrations ranged from 0.8 to 80.0 ug/mL, with dilutions made proportionally. Data provenance not specified (likely laboratory-prepared samples).
   • Method Comparison: 176 samples. Data provenance not specified.
   • Precision: 160 replicates per control level and human serum level (quadruplicate twice a day for 20 days). Data provenance not specified (likely laboratory-prepared controls and pooled human serum specimens).
   • Interfering Substances: Zonisamide levels of approximately 15 and 45 µg/mL, spiked with various interferents. Specific number of samples per interferent not specified, but each was "evaluated." Data provenance not specified (likely laboratory-prepared samples).
   • Metabolites: Zonisamide levels of 15 µg/mL and 45 µg/mL, spiked with NAZ (50.0, 10.0 µg/mL) and SMAP (50.0, 10.0 µg/mL). Data provenance not specified (likely laboratory-prepared samples).
   • Drug Interference: Zonisamide levels of approximately 15 and 45 µg/mL, spiked with various drug compounds. Specific number of samples per drug not specified, but each was "assayed." Data provenance not specified (likely laboratory-prepared samples).
   • Anticoagulants: Not explicitly stated, but "studies were conducted" on serum and plasma. Data provenance not specified.
   • Sample Stability: Not explicitly stated, but "serum specimens were shown to be stable" under various conditions. Data provenance not specified.
   • On-Board Stability: "Supporting data" cited, but specific sample sizes and provenance not detailed.

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

   • No expert ground truth was described for the test set. The ground truth for analytical performance studies (LOQ, recovery, linearity, precision) is typically established by precisely preparing samples with known concentrations. For method comparison, the predicate device serves as the comparative "truth."

3. Adjudication method for the test set:

   • Not applicable, as this is an in vitro diagnostic assay and not an image-based or qualitative diagnostic device requiring expert adjudication.

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 in vitro diagnostic assay, not an AI-assisted diagnostic tool for human readers.

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

   • Yes, the entire submission describes the standalone performance of the ARK Zonisamide Assay. Its function is to quantitatively determine zonisamide concentrations in samples, which is an algorithm-only (analytical assay) performance.

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

   • Analytical Ground Truth: For most studies (LOQ, recovery, linearity, interfering substances, drug interference, metabolites), the ground truth was established through gravimetrical or volumetric preparation of samples with known, spiked concentrations of zonisamide or interfering substances.
   • Comparative Ground Truth: For the method comparison study, the predicate device (QMS® Zonisamide Assay) served as the reference for comparison.

7. The sample size for the training set:

   • The document does not describe a "training set" in the context of machine learning or AI. This assay is a chemical immunoassay, not a learning algorithm. The studies described are analytical validation studies to characterize the performance of the chemical reaction and measurement system.

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

   • As there is no described training set, this question is not applicable.

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The ARK™ Levetiracetam Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of levetiracetam in human serum or plasma on automated clinical chemistry analyzers. Levetiracetam concentrations can be used as an aid in management of patients treated with levetiracetam. The ARKTM Levetiracetam Calibrator is intended for use in calibration of the ARK Levetiracetam Assay. The ARK™ Levetiracetam Control is intended for use in quality control of the ARK Levetiracetam Assay.

The ARK Levetiracetam Assay is a homogeneous immunoassay based on competition between drug in the specimen and levetiracetam labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay. The ARK Levetiracetam Assay consists of reagents RI anti-levetiracetam polyclonal antibody with substrate and R2 levetiracetam labeled with bacterial G6PDH enzyme. The ARK Levetiracetam Calibrator consists of a six-level set to calibrate the assay, and the ARK Levetiracetam Control consists of a three-level set used for quality control of the assay.

Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Device Performance for ARK™ Levetiracetam Assay

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Size and Data Provenance

• Accuracy: Not explicitly stated, but "highly pure levetiracetam was added volumetrically to human serum negative for levetiracetam, representing drug concentrations across the assay range." Six replicates of each sample were assayed. Data provenance not specified (retrospective/prospective, country of origin).
• Linearity: Not explicitly stated, but a 100.0 µg/mL serum sample was prepared and dilutions were made proportionally with human serum negative for levetiracetam. Data provenance not specified.
• Method Comparison: Number of samples = 305. Data provenance not specified.
• Precision: 160 measurements for each of the 6 levels (3 control levels, 3 human serum pools). This equates to 8 measurements per level per day (quadruplicate twice a day) over 20 days. Data provenance not specified.
• Interfering Substances: For each interfering substance, serum with known levels of levetiracetam (approx. 15 and 50 µg/mL) was evaluated. A serum control was also used. Amount of samples for each interfering substance is not explicitly stated. Data provenance not specified.
• Metabolites: Not explicitly stated for metabolite cross-reactivity. Data provenance not specified.
• Drug Interference: For each compound, normal human serum with known levels of levetiracetam (approx. 15 and 50 µg/mL) was spiked and assayed along with a serum control. Total number of samples is not explicitly stated. Data provenance not specified.
• Anticoagulants: Not explicitly stated. Data provenance not specified.

3. Number of Experts and Qualifications for Ground Truth

Not applicable. This is an in-vitro diagnostic device (immunoassay) for quantitative determination of a drug. Ground truth is established by spiked concentrations, a reference method (LC/MS/MS), or intrinsic characteristics of known substances. No human expert interpretation of images or other subjective data is involved.

4. Adjudication Method

Not applicable. For an immunoassay, the "ground truth" is typically verifiable concentrations of the analyte or comparison to a gold standard analytical method. There is no subjective assessment that would require expert adjudication.

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

No. This is an in-vitro diagnostic device for quantitative chemical analysis, not an imaging device or a device involving human interpretation where MRMC studies would be relevant.

6. Standalone Performance

Yes, the studies described are solely for the performance of the ARK™ Levetiracetam Assay system (algorithm/device only). There is no "human-in-the-loop" component to its stated intended use or the performance studies presented.

7. Type of Ground Truth Used

• Limit of Quantitation, Accuracy, Linearity, Interfering Substances, Metabolites, Drug Interference: Ground truth was established by known, spiked concentrations of levetiracetam and/or interfering substances into human serum, or by using highly pure reference materials.
• Method Comparison: Ground truth for comparison was established by a reference LC/MS/MS method.
• Precision: Ground truth was established by known concentrations in control materials and pooled human serum samples.

8. Sample Size for the Training Set

Not applicable. This is an immunoassay, which does not typically involve training a machine learning model in the same way as, for example, an AI for image analysis. The "training" in this context would be the development and optimization of the chemical reagents and assay parameters during the R&D phase, for which specific sample sizes and datasets for "training" are not usually reported in this manner.

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

Not applicable. As noted above, this is not a machine learning device that uses a "training set" in the conventional sense. The "ground truth" for the development of the assay would involve fundamental chemical and biological principles to ensure proper antibody-antigen binding specificity and enzyme activity, calibrated against known standards.

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The ARK™ Topiramate Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of topiramate in human serum or plasma on automated clinical chemistry analyzers. The results obtained are used in the diagnosis and treatment of topiramate overdose and in monitoring levels of topiramate to help ensure appropriate therapy.

The ARK™ Topiramate Calibrator is intended for use in calibration of the ARK Topiramate Assav.

The ARKTM Topiramate Control is intended for use in quality control of the ARK Topiramate Assay.

The ARK Topiramate Assay is a homogeneous immunoassay based on competition between drug in the specimen and topiramate epitope labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay.

The ARK Topiramate Assay consists of reagents R1 anti-topiramate polyclonal antibody with substrate and R2 topiramate epitope labeled with bacterial G6PDH enzyme. The ARK Topiramate Calibrator consists of a six-level set to calibrate the assay, and the ARK Topiramate Control consists of a three-level set used for quality control of the assay.

Here's a breakdown of the acceptance criteria and the studies that prove the device meets them, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Accuracy: Not explicitly stated as a "test set" in the traditional sense. Samples were human serum negative for topiramate, spiked with known topiramate concentrations. Six replicates were performed for each concentration. Data provenance is implied to be laboratory-generated through spiking.
• Linearity: A 60.0 µg/mL serum sample was prepared and proportionally diluted with human serum negative for topiramate. Topiramate concentrations ranged from 0.6 to 60.0 µg/mL. Data provenance is laboratory-generated.
• Method Comparison: 113 samples.
  • Data Provenance: Not explicitly stated for this particular study (e.g., country of origin, retrospective/prospective). However, given the context of a 510(k) for an in vitro diagnostic, these samples would typically come from patients, likely collected retrospectively or prospectively for method validation purposes.
• Precision: Tri-level controls were used. Each level was assayed in quadruplicate, twice a day for 20 days (N=160 for each level). Data provenance is laboratory-generated.
• Interfering Substances: Samples were human serum with known levels of topiramate (approximately 5 and 20 µg/mL) spiked with high concentrations of various interfering substances. Data provenance is laboratory-generated.
• Metabolites: Samples were human serum with known levels of topiramate spiked with 9-hydroxy-topiramate. Data provenance is laboratory-generated.
• Drug Interference: Samples were normal human serum with known levels of topiramate (approximately 5 and 20 µg/mL) spiked with high concentrations of various drug compounds. Data provenance is laboratory-generated.
• Anticoagulants: Not explicitly detailed, but implied to involve testing serum and plasma samples containing topiramate. Data provenance is laboratory-generated.

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

Not applicable. This is an in vitro diagnostic device for quantitative determination of a drug in serum/plasma. The "ground truth" for the test set (e.g., known concentrations for accuracy, reference method results for method comparison) is established through analytical techniques, not expert adjudication of images or clinical cases.

4. Adjudication Method for the Test Set

Not applicable. As noted above, this device performance is assessed through analytical measurements against known concentrations or a reference method, not through expert adjudication in the context of diagnostic interpretation.

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 typically conducted for diagnostic imaging devices where human readers interpret cases, and the AI's impact on their performance is evaluated. This device is an automated in vitro diagnostic assay.

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

Yes, the studies presented are all standalone validations of the analytical performance of the ARK Topiramate Assay. The device is intended for quantitative determination on automated clinical chemistry analyzers, meaning it operates without direct human-in-the-loop interpretation of its primary output.

7. The Type of Ground Truth Used

The ground truth used for these studies includes:

• Known Reference Concentrations: For accuracy and linearity studies, serum samples were spiked with precisely measured, highly pure topiramate to create samples with known theoretical concentrations.
• Reference Method Results: For the method comparison study, results from the ARK Topiramate Assay were compared against a "commercially available FPIA Immunoassay." The results from this predicate method served as the reference or ground truth for comparison.
• Known Spiked Levels: For interference, metabolite, and drug interference studies, known quantities of the interfering substance, metabolite, or drug were added to samples with known topiramate concentrations.

8. The Sample Size for the Training Set

Not applicable. This document describes the validation of a predefined assay, not the development or training of a machine learning algorithm. Therefore, there is no "training set" in the context of an AI/ML device. The reagents are pre-formulated for the immunoassay.

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

Not applicable for the same reason as point 8.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

8. The sample size for the training set:

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

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

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

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

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The ARCHITECT iPhenytoin assay is an in vitro chemiluminescent microparticle immunoassay (CMIA) for the quantitative measurement of phenytoin, an anticonvulsant drug, in human serum or plasma on the ARCHITECT i System with STAT protocol capability. The measurements obtained are used in monitoring levels of phenytoin to help ensure appropriate therapy.

The ARCHITECT iPhenytoin Calibrators are for the calibration of the ARCHITECT i System with STAT protocol capability when used for the quantitative determination of phenytoin in human serum or plasma.

The ARCHITECT iPhenytoin assay is a one-step STAT immunoassay for the quantitative measurement of phenytoin in human serum or plasma using CMIA technology, with flexible assay protocols, referred to as Chemiflex.

Sample, anti-phenytoin coated paramagnetic microparticles, and phenytoin acridinium-labeled conjugate are combined to create a reaction mixture. The antiphenytoin coated microparticles bind to phenytoin present in the sample and to the phenytoin acridinium-labeled conjugate. After washing, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). An indirect relationship exists between the amount of phenytoin in the sample and the RLUs detected by the ARCHITECT i System optics.

The acceptance criteria and study proving device performance are described below based on the provided text.

1. Table of Acceptance Criteria and Reported Device Performance

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

The document does not explicitly state the sample size used for the test set or the data provenance (e.g., country of origin, retrospective or prospective) for the clinical performance study. It only mentions "non-clinical performance data" and "clinical performance data."

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

This information is not provided in the document. The study compares the ARCHITECT iPhenytoin assay to a legally marketed predicate device (AxSYM Phenytoin assay), implying the predicate's results are used as the reference, rather than independent expert ground truth establishment for a test set in the traditional sense of image analysis or diagnostic interpretation.

4. Adjudication Method

This information is not applicable and not provided in the document. Adjudication methods are typically used in studies involving human interpretation where discrepancies need to be resolved; this study is an analytical performance comparison of an immunoassay.

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

No MRMC comparative effectiveness study was mentioned. The ARCHITECT iPhenytoin assay is an in vitro diagnostic device for quantitative measurement of a drug, not a diagnostic imaging or interpretive device that would typically involve human readers.

6. Standalone Performance Study

The entire study described is a standalone performance study in the context of an in vitro diagnostic device. The ARCHITECT iPhenytoin assay's performance (precision, linearity, interferences, and correlation) was evaluated independently and then compared to a predicate device. There is no human-in-the-loop component in the functionality of this immunoassay.

7. Type of Ground Truth Used

The "ground truth" for the clinical performance evaluation was the results obtained from the legally marketed predicate device, the AxSYM Phenytoin assay. The study aimed to demonstrate substantial equivalence by correlating the results of the new device with the predicate.

8. Sample Size for the Training Set

This information is not provided in the document. As an immunoassay, the device relies on chemical and biological reactions rather than machine learning algorithms that typically require dedicated training sets in the computational sense. The "training" for such devices involves assay development and optimization rather than data-driven machine learning training.

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

Not applicable in the context of an immunoassay. The development and optimization of the ARCHITECT iPhenytoin assay would involve standard laboratory practices to establish parameters (e.g., reagent concentrations, incubation times) that yield accurate and reproducible results, rather than a "ground truth" derived from a training dataset in the machine learning sense. The performance characteristics (precision, linearity, etc.) are established through validation studies.

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