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The Alkaline Phosphatase assay is used for the quantitation of alkaline phosphatase in human serum or plasma.

Measurements of alkaline phosphatase or its isoenzymes are to be used as an aid in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

The Alkaline Phosphatase assay is an automated clinical chemistry assay.

Alkaline phosphatase in the sample catalyzes the hydrolysis of colorless p-nitrophenyl phosphate (p-NPP) to give p-nitrophenol and inorganic phosphate. At the pH of the assay (alkaline), the p-nitrophenol is in the yellow phenoxide form. The rate of absorbance increase at 404 nm is directly proportional to the alkaline phosphatase activity in the sample. Optimized concentrations of zinc and magnesium ions are present to activate the alkaline phosphatase in the sample.

The FDA document provided is a 510(k) premarket notification for an in vitro diagnostic device, the Alkaline Phosphatase assay. This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device, rather than proving safety and effectiveness de novo. Therefore, the information provided relates to testing done to establish equivalence for a pre-existing device with modifications, not a new device.

The study proves that the modified device meets acceptance criteria, primarily by demonstrating that it performs equivalently to the predicate device and that incremental changes do not adversely affect its performance.

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

Acceptance Criteria and Reported Device Performance

The document provides a general statement that the device "met the pre-defined product requirements for all characteristics evaluated in the verification studies." It doesn't present a specific table of acceptance criteria vs. performance in the typical format of a clinical study, but rather a comparison of characteristics to a predicate device and a statement about the results of verification studies.

The key acceptance criterion discussed is substantial equivalence to the predicate device (K023807), particularly regarding:

• Intended Use and Indications for Use: The subject device is intended for the same use as the predicate: "quantitation of alkaline phosphatase in human serum or plasma," as an aid in diagnosis and treatment of various diseases.
• Methodology and Assay Principle: Both use para-nitrophenyl phosphate and a kinetic measurement method.
• Performance (specifically after IFCC calibration factor change): The 6.5% increase in reported results due to the optional IFCC calibration factor is deemed acceptable because it falls within the acceptable assay bias specifications (up to +/-10%) and the customer would be aware of this change.
• Risk Mitigation: The comprehensive risk-based assessment for all changes ensured that "the accumulated modifications did not impact the performance of the device."

Since this is an in vitro diagnostic device for measuring a specific analyte (Alkaline Phosphatase), the "performance" here refers to analytical performance characteristics rather than clinical diagnostic accuracy in the way a medical imaging AI would.

Here's a table summarizing the implicit acceptance criteria and the reported performance as derived from the document:

Study Details (based on the provided text, which is an FDA clearance letter for an IVD, not a detailed study report for AI/imaging device)

The document relates to modifications made to an existing in vitro diagnostic (IVD) device, not a new AI-powered diagnostic for imaging. Therefore, many of the typical questions for an AI/imaging device (e.g., sample size for test set, expert readers, MRMC study, ground truth for imaging) are not directly applicable or detailed in this type of FDA letter.

However, based on the information provided, we can infer some details relevant to an IVD device:

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

   • Sample Size: Not explicitly stated. The document refers to "verification studies" which typically involve testing samples across the measurement range, parallelism, interference, precision, etc. for an IVD. The exact number of samples (patients or analytical runs) isn't specified in this summary.
   • Data Provenance: Not specified regarding country of origin. The studies are described as "verification studies" and "comprehensive risk-based assessment." For IVDs, these are typically prospective laboratory studies conducted by the manufacturer to validate performance characteristics. It's safe to assume they were laboratory-controlled, likely prospective.

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

   • This question is not applicable in the context of this IVD device. "Ground truth" for an IVD like Alkaline Phosphatase is established by the analytical measurement itself, often compared to reference methods or known concentrations, or through internal validation against established performance claims. It does not involve human expert interpretation of an image or signal.

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

   • This question is not applicable for this IVD. Adjudication methods like 2+1 or 3+1 are used in AI/imaging studies where multiple human readers interpret data that then needs to be reconciled to establish a "ground truth" for comparison with AI. For an IVD, there isn't subjective interpretation of this kind. The measurement process itself generates the result.

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:

   • This type of study is not applicable to this IVD. MRMC studies are specific to AI-assisted imaging diagnostics, evaluating the impact of AI on human reader performance. This device provides a quantitative biochemical measurement, not an image for human interpretation.

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

   • In a sense, yes, the fundamental performance of the IVD is "standalone" in that the automated analyzer (ARCHITECT c System) quantitatively measures alkaline phosphatase activity. The "algorithm" here is the chemical reaction and photometric measurement, and its output is a numerical value (U/L). The verification studies would assess this standalone analytical performance (e.g., precision, accuracy, linearity, detection limits) against pre-defined specifications. The IFCC factor is a mathematical change to this standalone output.

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

   • For an IVD like this, "ground truth" is typically established through:
     • Reference Methods: Comparison of results to established, highly accurate reference methods for alkaline phosphatase.
     • Known Concentrations: Testing samples with precisely known concentrations of alkaline phosphatase.
     • Clinical Correlation: Demonstrating that the assay measures the analyte in patient samples consistently and reliably across relevant patient populations, although the primary ground truth is analytical.
   • The document implies that the "pre-defined product requirements" and "acceptable assay bias specifications" served as the benchmarks for determining if the device performed acceptably. The 6.5% shift from the IFCC factor was evaluated against these analytical specifications.

7. The sample size for the training set:

   • This question is not directly applicable in the context of a traditional IVD chemical assay development, as there isn't an "AI model" that requires a training set in the typical sense. The "training" for such a system would be the chemical formulation and instrument calibration based on extensive R&D and optimization, not a data-driven machine learning process. The "validation" of the final product involves the verification studies mentioned.

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

   • As above, not directly applicable. The IVD operates on established biochemical principles. Its "ground truth" for development and optimization would be based on fundamental chemistry, enzyme kinetics, and metrological traceability to international standards (e.g., IFCC reference methods for calibrator values).

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The Alkaline Phosphatase2 assay is used for the quantitation of alkaline phosphatase in human serum or plasma on the ARCHITECT c System.

Measurements of alkaline phosphatase or its isoenzymes are to be used as an aid in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

The Alkaline Phosphatase2 assay is an automated clinical chemistry assay for the quantitation of alkaline phosphatase in human serum or plasma on the ARCHITECT c System. Alkaline Phosphatase in a sample catalyzes the hydrolysis of colorless para-nitrophenyl phosphate (p-NPP) to give para-nitrophenol (yellow phenoxide form at alkaline pH) and inorganic phosphate. The rate of absorbance increase at 404 nm is directly proportional to the alkaline phosphatase activity in the sample. Optimized concentrations of zinc and magnesium ions are present to activate the alkaline phosphatase in the sample.

The provided document is a 510(k) Premarket Notification for a clinical chemistry assay (Alkaline Phosphatase2) and does not describe an AI medical device. Therefore, the questions related to AI-specific acceptance criteria, ground truth establishment by experts, adjudication methods, multi-reader multi-case studies, and human-in-the-loop performance are not applicable.

The document focuses on the analytical performance of the Alkaline Phosphatase2 assay, demonstrating its substantial equivalence to a legally marketed predicate device. The information details various non-clinical performance studies to establish the device's reliability and accuracy for quantitating alkaline phosphatase in human serum or plasma.

Here's a breakdown of the relevant information from the document, tailored to the context of a diagnostic assay's performance evaluation, substituting the AI-specific questions with applicable details:

Acceptance Criteria and Device Performance for Alkaline Phosphatase2 Assay

This submission (K223317) is for a clinical chemistry assay, not an AI medical device. The acceptance criteria and performance studies are focused on the analytical performance of the assay to demonstrate its intended use for quantitative measurement of alkaline phosphatase.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a "table of acceptance criteria" for regulatory review, but it details various performance studies with implicit acceptance ranges. The reported device performance metrics are presented instead.

Performance Metrics of Alkaline Phosphatase2 Assay (Representative Values)

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BA400: The BA400 analyser is used to determine analyte concentrations by in vitro biochemical and turbidimetric measurements of human samples of serum, urine, plasma, cerebrospinal fluid or total blood. This device is intended to replace manual analytical procedures by performing automatically various steps such as pipetting, heating, and measuring color intensity.

ALBUMIN: Reagent for the measurement of albumin concentration in human serum or plasma. The obtained values are useful as an aid in the evaluation of protein synthesis of the liver in the chronic liver diseases and for the nutritional status. This reagent is for use in the BioSystems BA analyzers. Only for in vitro use in the clinical laboratory.

ALKALINE PHOSPHATASE (ALP) - AMP: Reagent for the measurement of alkaline phosphatase (ALP)-AMP concentration in human serum or plasma. The obtained values are useful as an aid in the diagnosis and treatment of hepatobiliary and bone diseases with impaired osteoblastic activity diseases. This reagent is for use in the BioSystems BA analyzers. Only for in vitro use in the clinical laboratory.

GLUCOSE-HEXOKINASE: Reagent for the measurement of glucose concentration in human serum, plasma, urine or cerebrospinal fluid. The obtained values are useful as an aid in the diagnosis and monitoring of the diabetes mellitus. This reagent is for use in the BioSystems BA analyzers. Only for in vitro use in the clinical laboratory.

Not Found

This document is a 510(k) premarket notification decision letter from the FDA for several in vitro diagnostic reagents and an analyzer. It only provides information about the intended use of the devices and their regulatory classification. It does not contain any data, studies, acceptance criteria, or performance results for the devices mentioned (ALBUMIN, ALKALINE PHOSPHATASE (ALP)-AMP, GLUCOSE-HEXOKINASE reagents, or the BA400 analyzer).

Therefore, I cannot provide the requested information in the requested format because the input document does not contain it.

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The Randox RX Daytona Plus Alkaline Phosphatase (ALP) test system is intended for the quantitative in vitro determination of Alkaline Phosphatase (ALP) activity in serum and lithium heparinized plasma. Measurements of alkaline phosphatase are used in the diagnosis, treatment and investigation of hepatobiliary disease and in bone disease.

The Randox RX Daytona Plus Alkaline Phosphatase (ALP) assay consists of ready to use reagent solutions.

Here's a breakdown of the acceptance criteria and study information for the Randox RX Daytona Plus Alkaline Phosphatase (ALP) device, based on the provided text:

Acceptance Criteria and Device Performance

Study Details

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

• Precision/Reproducibility: Not explicitly stated for specific test sets, but 80 determinations per sample (QC or serum) were performed for each of the two reagent lots. Human serum samples (altered and unaltered, some spiked or diluted) were used. Data provenance is not explicitly stated beyond "human serum samples."
• Linearity/Reportable Range: 11 levels of samples were prepared. Each level was run in replicates of five. Provenance of these samples is not specified.
• Detection Limit: Not explicitly stated for a separate "test set" size, but the LoD was based on 240 determinations using 4 low-level samples. Provenance not specified.
• Analytical Specificity: Not explicitly stated for a separate "test set" size for each interferent, but the study implies testing at ALP concentrations of 80 U/I and 240 U/I. Provenance not specified.
• Method Comparison with Predicate Device: 106 serum patient samples. Data provenance is not explicitly stated but implies patient samples from the UK, given the manufacturer's location. The study was retrospective, comparing the new device results against an existing predicate device using collected samples.
• Matrix Comparison: 46 matched patient sample pairs (serum and lithium heparin plasma). Provenance not explicitly stated.
• Expected Values/Reference Range Verification: Human serum from 30 normal donors. Provenance not explicitly stated.

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

• Not Applicable. This document describes the analytical performance of an in vitro diagnostic device (a laboratory test for Alkaline Phosphatase activity). The "ground truth" for such devices is typically established through reference methods, certified standards, or consensus values from established quality control materials, rather than expert interpretation of images or patient data. The document does not mention the use of experts to establish ground truth for the analytical performance studies.
  • For the precision study, control materials and altered/unaltered human serum samples were used.
  • For linearity, pooled samples with known concentrations were used.
  • For method comparison, the predicate device (Siemens Alkaline Phosphatase (ALPAMP) Assay, K991576) served as the reference for comparison.

4. Adjudication Method for the Test Set:

• Not Applicable. As noted above, this study evaluates the analytical performance of an in vitro diagnostic device, not interpretive performance requiring adjudication.

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

• Not Applicable. This is an evaluation of an in vitro diagnostic device for quantitative chemical analysis, not an AI-powered diagnostic imaging system requiring human reader studies.

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

• Yes, a standalone study was done. The entire submission details the performance of the Randox RX Daytona Plus Alkaline Phosphatase (ALP) system itself, comprising reagents and the RX Daytona Plus analyzer. This is the inherent nature of an in vitro diagnostic test; its performance is measured independently of human interpretation of the result, though human operators perform the test and interpret the clinical significance of the result. The performance metrics (precision, linearity, detection limits, accuracy/method comparison) are all measures of the device's standalone analytical capabilities.

7. The Type of Ground Truth Used:

• Reference Methods/Comparative Devices and Spiked/Diluted Samples:
  • Precision and Linearity: Values derived from known concentrations in quality control materials, spiked samples, or diluted samples where the true value is calculable.
  • Method Comparison: The predicate device (Siemens Alkaline Phosphatase (ALPAMP) Assay, K991576) served as the comparative "ground truth" to establish substantial equivalence.
  • Detection Limits: Determined statistically using defined protocols (CLSI guideline EP17-A2).
  • Analytical Specificity: Known concentrations of interferents added to known ALP concentrations.

8. The Sample Size for the Training Set:

• Not Applicable. The document describes a traditional analytical performance study for an in vitro diagnostic assay, not an AI/machine learning model that requires a training set. The device is a chemical reagent and analyzer system.

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

• Not Applicable. See point 8.

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The ACE Alkaline Phosphatase Reagent is intended for the quantitative determination of alkaline phosphatase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Measurements of alkaline phosphatase are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

The ACE Amylase Reagent is intended for the quantitative determination of α-amylase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Amylase measurements are used primarily for the diagnosis and treatment of pancreatitis (inflammation of the pancreas). This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

The ACE ALT Reagent is intended for the quantitative determination of alanine aminotransferase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Alanine aminotransferase measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart diseases. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

The ACE AST Reagent is intended for the quantitative determination of aspartate aminotransferase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Measurements of aspartate aminotransferase are used in the diagnosis and treatment of certain types of liver and heart disease. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.

In the ACE Alkaline Phosphatase Reagent assay, alkaline phosphatase catalyzes the hydrolysis of colorless p-nitrophenyl phosphate to p-nitrophenol and inorganic phosphate. In an alkaline solution (pH 10.5), p-nitrophenol is in the phenoxide form and has a strong absorbance at 408 nm. The rate of increase in absorbance, monitored bichromatically at 408 nm/486 nm, is directly proportional to the alkaline phosphatase activity in the sample.

In the ACE Amylase Reagent assay, α-amylase hydrolyzes the 2-chloro-p-nitrophenyl-α-D-maltotrioside substrate to release 2-chloro-p-nitrophenol and form 2-chloro-p-nitrophenyl-α-D-maltoside, maltotriose and glucose. The rate of increase in absorbance, monitored bichromatically at 408 nm/ 647 nm, is directly proportional to the α-amylase activity in the sample.

In the ACE ALT Reagent assay, alanine aminotransferase converts the L-alanine and α-ketoglutarate substrates in the reagent to L-glutamate and pyruvate, respectively. Lactate dehydrogenase (LDH) catalyzes the oxidation of the reduced cofactor to the cofactor. The rate of conversion of the reduced cofactor to the cofactor can be determined by monitoring the decrease in absorbance bichromatically at 340 nm/647 nm. This rate of conversion from the reduced cofactor to the cofactor is a function of the activity of ALT in the sample.

In the ACE AST Reagent assay, aspartate aminotransferase converts the L-aspartate and α-ketoglutarate in the reagent to oxaloacetate and L-glutamate, respectively. The oxaloacetate undergoes reduction, with concurrent oxidation of NADH to NAD+ in the malate dehydrogenase-catalyzed indicator reaction. NADH absorbs strongly at 340 nm, whereas NAD+ does not. Therefore, the rate of conversion of NADH to NAD+ can be determined by monitoring the decrease in absorbance bichromatically at 340 nm/647 nm. This rate of conversion from NADH to NAD+ is a function of the activity of AST in the sample. Lactate dehydrogenase is added to prevent interference from endogenous pyruvate, which is normally present in blood.

Here's an analysis of the provided information regarding the acceptance criteria and study for the ACE reagents:

Summary of Acceptance Criteria and Reported Device Performance

The acceptance criteria for these in vitro diagnostic reagents (ALP, Amylase, ALT, AST) appear to be primarily demonstrated through comparisons with predicate devices and comprehensive performance characteristics like precision, linearity, and interference. The documentation focuses on demonstrating that the new devices perform equivalently to the existing predicate devices and meet established performance expectations for clinical chemistry assays.

1. Table of Acceptance Criteria and Reported Device Performance

Since this document describes multiple reagents and doesn't explicitly state pass/fail acceptance values for each performance metric, I will summarize the demonstrated performance and what can be inferred as the "acceptance criteria" (i.e., that the results are comparable to established predicate device performance and within acceptable clinical ranges).

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

• Precision (Serum vs. Plasma):
  • In-House: Each dataset (low, mid, high for serum and plasma) involved "n=20" (number of replicates, likely over multiple days, contributing to within-run and total precision calculations).
  • POL Precision (ACE & Alera): For each analyte (ALP, AMY, ALT, AST) and each POL site (POL 1, POL 2, POL 3), there were 2 to 3 sample levels (Low, Mid, High), with a reported "n" for each (e.g., n=24 for ALT/AST in initial in-house, but the POL tables don't explicitly state the 'n' for each specific mean/SD/CV, implying a standard number of replicates as per precision studies).
• Matrix Comparison (Serum vs. Plasma):
  • ALP: ACE (108 pairs), ACE Alera (108 pairs), ACE Axcel (62 pairs).
  • Amylase: ACE (104 pairs), ACE Alera (101 pairs), ACE Axcel (52 pairs).
  • ALT: ACE (54 pairs), ACE Alera (52 pairs), ACE Axcel (56 pairs).
  • AST: The number of pairs for AST in the serum vs. plasma matrix comparison is not explicitly stated in the provided snippet. However, based on the pattern of other analytes, it would likely be similar (e.g., 50+ pairs).
• Method Comparison (In-House vs. POL Sites):
  • ALP: 49-50 samples per site.
  • Amylase: 51 samples per site.
  • ALT: 44-49 samples per site.
  • AST: 50 samples per site.
• Linearity: Not explicitly stated as an "n" for samples, but rather as "low level tested," "upper level tested," and "linear to" values, which typically involve preparing a dilution series from a high concentration sample.
• Data Provenance: The studies are labeled "In-House" and "POL" (Point of Care). This suggests:
  • Country of Origin: Likely the USA, given the FDA 510(k) submission.
  • Retrospective or Prospective: These types of performance studies for IVDs are typically prospective, with samples analyzed specifically for the study. The method comparison data often uses a mix of native patient samples and spiked samples to cover the measuring range.

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

This document describes the performance of IVD reagents on clinical chemistry systems. The "ground truth" here is not subjective, human interpretation (like in imaging AI), but rather the quantitative measurement of analytes.

• Number of Experts: Not applicable in the context of IVD reagent performance. The "ground truth" is established by the analytical method itself, or by comparison to a recognized reference method or a legally marketed predicate device.
• Qualifications of Experts: Not applicable. The "experts" would be qualified laboratory professionals operating the instruments and performing the biochemical assays according to established protocols.

4. Adjudication Method for the Test Set

Not applicable. As described above, the "truth" for these quantitative measurements is derived directly from the biochemical reactions and instrument readings, not subjective human judgment requiring adjudication. The predicate device's established performance serves as a comparative benchmark.

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

No. This is a submission for in vitro diagnostic reagents, not an AI-assisted diagnostic device that involves human readers interpreting images or complex data. Therefore, an MRMC study is not relevant.

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

Yes, in essence, the performance data presented is "standalone" in the context of the device's function. The ACE reagents, when used on the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems, operate as an automated system to quantify the target analytes. The performance metrics (precision, linearity, method comparison, interferences) reflect the intrinsic analytical performance of the regent-analyzer combination without human intervention influencing the measurement itself. Human operators are involved in sample loading, quality control, and result review, but not in directly influencing the quantitative output in a way that would require a human-in-the-loop comparison for algorithm performance.

7. The Type of Ground Truth Used

The "ground truth" in this context is established by:

• Comparison to Predicate Devices: The primary method is demonstrating substantial equivalence to previously cleared devices (K113253, K931786, K930104, K113436, K113382). This means the new reagents provide results that are analytically comparable to those already accepted by the FDA.
• Expected Analytical Performance: Meeting industry-standard requirements for precision (low CV%), accuracy (linearity, inter-instrument/site agreement via regression analysis), and specificity (minimal interference).
• Expected Values/Ranges: The devices are expected to produce results that align with established "expected values" for healthy individuals.

8. The Sample Size for the Training Set

Not applicable. These are chemical reagents for quantitative diagnostic tests, not machine learning algorithms that require a "training set" in the conventional sense. The "training" for such systems involves analytical validation experiments to define reagent stability, reaction kinetics, and instrument parameters.

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

Not applicable for the same reason as point 8. The "ground truth" for developing and validating these reagents is based on fundamental principles of analytical chemistry, biochemical reactions, and extensive internal testing to ensure the reagents perform as intended within the specified analytical parameters.

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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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The ALPI method is an in vitro diagnostic test for the quantitative measurement of alkaline phosphatase in human serum and plasma on the Dimension Vista® System. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

ALPI CAL is an in vitro diagnostic product for the calibration of alkaline phosphatase (ALPI) method on the Dimension Vista® System.

The ALPI method employs alkaline phosphatase that catalyzes the transphosphorylation of pnitrophenylphosphate (p-NPP) to p-nitrophenol (p-NP) in the presence of the transphosphorylating buffer, 2 amino-2-methyl-1-propanol (AMP). The reaction is enhanced through the use of magnesium and zinc ions. The change in absorbance at 405 nm due to the formation of p-NP is directly proportional to the ALP activity, since other reactants are present in non-rate limiting quantities and is measured using a bichromatic (405, 510 nm) rate technique.

p-NPP + AMP -> p-NP + AMP + PO4 (reaction conditions: pH 10.25, Mg/Zn)

The ALPI CAL is a one (1) level, liquid calibrator. It is packaged as a kit of three vials of Calibrator A (Level 2) with 1.0 mL per vial. The product matrix is a human serum albumin based product containing alkaline phosphatase from porcine kidney. Level 1 is a zero level (system water). Level 2 contains alkaline phosphatase at 1000 U/L.

This product is sold separately from the Flex® reagent cartridge. Values are assigned to new lots from a Masterpool that is from an International Federation of Clinical Chemistry (IFCC) reference.

Here's a breakdown of the acceptance criteria and study information for the Dimension Vista® Alkaline Phosphatase Flex® reagent cartridge (ALPI) and Calibrator (ALPI CAL), based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

• Level 1: 1.0 U/L (2.9% CV)
• Level 2: 1.9 U/L (1.2% CV)
• Level 3: 4.0 U/L (1.3% CV)
• Serum Pool 1: 1.3 U/L (1.7% CV)
• Serum Pool 2: 13.6 U/L (1.6% CV)
  Within-Lab:
• Level 1: 1.4 U/L (4.1% CV)
• Level 2: 3.1 U/L (2.0% CV)
• Level 3: 4.6 U/L (Not legible in original doc)
• Serum Pool 1: 1.5 U/L (1.9% CV)
• Serum Pool 2: 15.0 U/L (1.8% CV) |
  | Linearity/Measuring Range | Established linear range according to CLSI EP-6A, ensuring accurate measurements within the stated range. The curve fit (R-squared) should show high linearity. | 10 - 1000 U/L
  Linearity Assessment: y = 1.010x + 3.461, R-squared = 0.999 |
  | Analytical Specificity/Interferences | Bias due to interferents (hemoglobin, bilirubin, lipemia) should be less than 10%. | Bias

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The ALPI method is an in vitro diagnostic test for the quantitative measurement of alkaline phosphatase in human serum and plasma on the Dimension® clinical chemistry system. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

ALPI CAL is an in vitro diagnostic product for the calibration of alkaline phosphatase (ALPI) method on the Dimension® clinical chemistry system.

The ALPI method employs alkaline phosphatase that catalyzes the transphosphorylation of pnitropheny | phosphate (p-NPP) to p-nitrophenol (p-NP) in the presence of the transphosphorylating buffer, 2 amino-2-methyl-1-propanol (AMP). The reaction is enhanced through the use of magnesium and zinc ions. The change in absorbance at 405 nm due to the formation of p-NP is directly proportional to the ALP activity, since other reactants are present in non-rate limiting quantities and is measured using a bichromatic (405, 510 nm) rate technique.

The ALPI CAL is a three (3) level, liquid calibrator. It is packaged as a kit of six vials, two vials per level (1, 2 and 3) with 1.0 mL per vial. The product matrix is a human serum albumin based product containing alkaline phosphatase from porcine kidney. Levels 2 and 3 contain alkaline phosphatase at the following concentrations.

Level 1: 0 U/L
Level 2: 500 U/L
Level 3: 1000 U/L

This product is sold separately from the Flex® reagent cartridge. Values are assigned to new lots from a Masterpool that is from an International Federation of Clinical Chemistry (IFCC) reference.

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

Acceptance Criteria and Device Performance

• BioRad QC Level 1: Mean 37 U/L, SD 0.6 U/L, %CV 1.5
• BioRad QC Level 2: Mean 157 U/L, SD 1.0 U/L, %CV 0.6
• BioRad QC Level 3: Mean 303 U/L, SD 3.3 U/L, %CV 1.1
• Serum Pool 1: Mean 81 U/L, SD 1.1 U/L, %CV 1.4
• Serum Pool 2: Mean 842 U/L, SD 5.7 U/L, %CV 0.7
  Within-Lab:
• BioRad QC Level 1: SD 1.6 U/L, %CV 4.2
• BioRad QC Level 2: SD 3.7 U/L, %CV 2.3
• BioRad QC Level 3: SD 7.1 U/L, %CV 2.4
• Serum Pool 1: SD 1.8 U/L, %CV 2.2
• Serum Pool 2: SD 13.3 U/L, %CV 1.6 |
  | Linearity | Analytical measurement range demonstrates linear response. | Analytical measurement range: 10 - 1000 U/L. Scatter plot showed y = 0.9868x + 9.7726 with R-squared = 0.9992. |
  | Analytical Specificity/Interferences | Bias due to common interferents (hemoglobin, bilirubin, lipemia)

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The ACE Axcel Clinical Chemistry System is an automated, discrete, bench-top, random access analyzer that is intended for in vitro diagnostic use in the quantitative determination of constituents in blood and other fluids.

The ACE Alkaline Phosphatase Reagent is intended for the quantitative determination of alkaline phosphatase activity in serum using the ACE Axcel Clinical Chemistry System. Measurements of alkaline phosphatase are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

The ACE Amylase Reagent is intended for the quantitative determination of a-amylase activity in serum using the ACE Axcel Clinical Chemistry System. Amylase measurements are used primarily for the diagnosis and treatment of pancreatitis (inflammation of the pancreas). This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

The ACE LDH-L Reagent is intended for the quantitative determination of lactate dehydrogenase activity in serum using the ACE Axcel Clinical Chemistry System. Lactate dehydrogenase measurements are used in the diagnosis and treatment of liver diseases such as acute viral hepatitis, cirrhosis, and metastatic carcinoma of the liver, cardiac diseases such as myocardial infarction and tumors of the lung or kidneys. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

The ACE Axcel Clinical Chemistry System consists of two major components, the chemistry instrument and an integrated Panel PC. The instrument accepts the physical patient samples, performs the appropriate optical or potentiometric measurements on those samples and communicates that data to an integral Panel PC. The Panel PC uses keyboard or touch screen input to manually enter a variety of data, control and accept data from the instrument, manage and maintain system information and generate reports relative to patient status and instrument performance. The Panel PC also allows remote download of patient requisitions and upload of patient results via a standard interface.

In the ACE Alkaline Phosphatase Reagent assay, alkaline phosphatase in serum catalyzes the hydrolysis of colorless p-nitrophenyl phosphate to p-nitrophenol and inorganic phosphate. In an alkaline solution (pH 10.5), p-nitrophenol is in the phenoxide form and has a strong absorbance at 408 nm. The rate of increase in absorbance, monitored bichromatically at 408 nm/486 nm, is directly proportional to the alkaline phosphatase activity in the sample.

In the ACE AST Reagent assay, a-amylase hydrolyzes the 2-chloro-p- nitrophenyl-a-D-maltotrioside substrate to release 2-chloro-p- nitrophenol and form 2-chloro-p- nitrophenyl-a-D-maltoside, maltotriose and glucose. The rate of increase in absorbance, monitored bichromatically at 408 nm/ 647 nm, is directly proportional to the a- amylase activity in the sample.

In the ACE LDH-L Reagent assay, lactate dehydrogenase catalyzes the conversion of L-lactate to pyruvate. Nicotinamide adenine dinucleotide (NAD+) acts as an acceptor for the hydrogen ions released from the L- lactate and is converted to reduced nicotinamide adenine dinucleotide (NADH). NADH absorbs strongly at 340 nm whereas NAD+ does not. Therefore, the rate of conversion of NAD+ to NADH can be determined by monitoring the increase in absorbance bichromatically at 340 nm/647 nm. This rate of conversion from NAD+ to NADH is directly proportional to the lactate dehydrogenase activity in the sample.

Here's an analysis of the provided text regarding the acceptance criteria and the study that proves the device meets those criteria:

Acceptance Criteria and Device Performance for ACE Alkaline Phosphatase, Amylase, and LDH-L Reagents on the ACE Axcel Clinical Chemistry System

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as numerical targets in the provided text. Instead, the study aims to demonstrate substantial equivalence to a predicate device (Alfa Wassermann ACE Clinical Chemistry System and ACE Reagents, K931786) by showing a high degree of correlation and acceptable precision. The reported device performance is compared to the predicate device.

ACE Alkaline Phosphatase Reagent

ACE Amylase Reagent

ACE LDH-L Reagent

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

• ACE Alkaline Phosphatase Reagent:

  • Accuracy (Correlation Study): 112 samples.
  • Accuracy (POL Patient Correlation): Not specified (implied to be numerous patient samples tested at 3 POL sites).
  • Precision (Central Lab): Data collected over 22 days, with 4 alkaline phosphatase levels tested. The exact number of individual samples run per level/day is not specified but is typical for precision studies (e.g., n=2 or n=3 replicates).
  • Precision (POL Sites): Data collected over 5 days at 3 separate Physician Office Laboratories (POLs), with 4 alkaline phosphatase levels tested. The exact number of individual samples run per level/day is not specified.
  • Data Provenance: Not explicitly stated, but the mention of "Central Lab" and "Physician Office Laboratory (POL) sites" suggests clinical laboratory settings. It does not specify country of origin or if retrospective/prospective, but stability studies and clinical accuracy studies usually involve prospective collection or use of banked clinical samples. Given it is a 510(k) submission, it is likely representing real-world clinical samples.

• ACE Amylase Reagent:

  • Accuracy (Correlation Study): 111 samples.
  • Accuracy (POL Patient Correlation): Not specified (implied to be numerous patient samples tested at 3 POL sites).
  • Precision (Central Lab): Data collected over 22 days, with 4 amylase levels tested.
  • Precision (POL Sites): Data collected over 5 days at 3 separate POL sites, with 4 amylase levels tested.
  • Data Provenance: Similar to Alkaline Phosphatase, suggesting clinical laboratory settings in the US, likely using prospective or banked clinical samples.

• ACE LDH-L Reagent:

  • Accuracy (Correlation Study): 121 samples.
  • Accuracy (POL Patient Correlation): Not specified (implied to be numerous patient samples tested at 3 POL sites).
  • Precision (Central Lab): Data collected over 22 days, with 4 LDH levels tested.
  • Precision (POL Sites): Data collected over 5 days at 3 separate POL sites, with 4 LDH levels tested.
  • Data Provenance: Similar to the previous reagents, suggesting clinical laboratory settings in the US, likely using prospective or banked clinical samples.

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

This device is a clinical chemistry analyzer, not an imaging or diagnostic AI device that requires expert adjudication for "ground truth." The "ground truth" for the accuracy studies is established by the performance of the predicate device (Alfa Wassermann ACE Clinical Chemistry System). The predicate device itself would have been validated against established reference methods or clinical outcomes when it was initially cleared/approved. Therefore, no human experts directly establish "ground truth" in the way it might for image interpretation.

4. Adjudication Method for the Test Set

Not applicable for this type of device (clinical chemistry analyzer). Adjudication methods like 2+1 or 3+1 are used for subjective interpretations or classifications (e.g., by radiologists or pathologists) to reach a consensus "ground truth." For quantitative measurements, the "truth" is typically a measurement from a reference method or a well-established, previously validated method (in this case, the predicate device).

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

No. This type of study is typically for evaluating the performance of AI algorithms in conjunction with human readers, often in image interpretation tasks. This submission is for a clinical chemistry analyzer and reagents.

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

Yes, the studies presented are essentially "standalone" performance evaluations of the new ACE Axcel Clinical Chemistry System with the specific reagents. The system measures analyte concentrations automatically, and its performance (precision, accuracy, detection limit) is assessed without direct human intervention in the measurement process itself, although human operators load samples and maintain the system. The "comparison" is to the predicate device, which is also a standalone automated system.

7. The Type of Ground Truth Used

The "ground truth" used for accuracy (correlation) studies is the measurement result from the legally marketed predicate device: the Alfa Wassermann ACE Clinical Chemistry System and its corresponding ACE Reagents (K931786). This is a common approach for demonstrating substantial equivalence for in vitro diagnostic devices when a recognized gold standard method might not be readily available for routine testing or if the goal is to show equivalence to an existing market performer.

8. The Sample Size for the Training Set

Not applicable. This is not an AI/machine learning device that requires a training set in the conventional sense. The device is a traditional clinical chemistry analyzer based on established photometric and enzymatic reaction principles. The "training" for such a system would involve instrument calibration (which uses control materials, not a "training set" of patient data) and reagent manufacturing/quality control.

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

Not applicable, as there is no "training set" for an AI algorithm. For instrument calibration, the "ground truth" for calibrators would be established by the manufacturer using reference methods or certified reference materials, and then verified through quality control materials.

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The EasyRA Alkaline phosphatase (ALP) reagent is intended for the quantitative determination of alkaline phosphatase in human serum and plasma, using the MEDICA "EasyRA Chemistry Analyzer" in clinical laboratories. Measurement of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid and intestinal diseases. For in vitro diagnostic use only.

The EasyRA Aspartate Aminotranferase (AST) reagent is intended for the quantitative determination of the enzyme Aspartate Aminotranferase in human serum and plasma, using the MEDICA "EasyRA Chemistry Analyzer" in clinical laboratories. Measurement of alkaline phosphatase measurements are used in the diagnosis and treatment of certain types of liver and heart diseases. For in vitro diagnostic use only.

The EasyRA Amylase (AMY) reagent is intended for the quantitative determination of amylase in human serum and plasma, using the MEDICA "EasyRA Chemistry Analyzer" in clinical laboratories. a-Amylase in serum/plasma is used for the diagnosis and treatment of pancreatitis (inflammation of the pancreas) and other pancreatic disorders. For in vitro diagnostic use only.

Not Found

I am sorry, but the provided text does not contain the detailed information necessary to describe the acceptance criteria and the study that proves the device meets them in the format you requested. The document is a 510(k) clearance letter from the FDA for several "EasyRA" reagents. It focuses on the substantial equivalence determination and the indications for use of these diagnostic reagents.

Specifically, the document does not include:

• A table of acceptance criteria and reported device performance.
• Details about sample sizes for test sets, data provenance, training sets, or how ground truth was established for these.
• Information on the number or qualifications of experts used for ground truth, or adjudication methods.
• Any mention of multi-reader multi-case (MRMC) comparative effectiveness studies or standalone algorithm performance.
• The type of ground truth used (e.g., pathology, outcomes data).

The document is a regulatory approval, not a scientific study report. Therefore, I cannot fulfill your request based on the provided input.

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