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The Atellica® CH Diazo Total Bilirubin (D TBil) assay is for in vitro diagnostic use in the quantitative determination of total bilirubin in adults and children (non-neonates) in human serum and plasma using the Atellica® CH Analyzer. Measurement of total bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.

Atellica CH Diazo Total Bilirubin is a photometric test using 2,4-dichloroaniline (DCA). Direct bilirubin in presence of diazotized 2,4-dichloroaniline forms a red colored azocompound in acidic solution. A specific mixture of detergents enables the determination of the total bilirubin.

The provided document describes the Siemens Atellica® CH Diazo Total Bilirubin (D_TBil) assay, an in vitro diagnostic device, and its performance characteristics to demonstrate substantial equivalence to a predicate device (Dimension TBI Flex reagent cartridge).

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

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this in-vitro diagnostic device are generally defined by demonstrating performance within established statistical limits or comparison to a predicate device, as per CLSI (Clinical and Laboratory Standards Institute) guidelines. The "acceptance criteria" themselves are not always explicitly stated as pass/fail thresholds for each performance characteristic in a simple numerical format, but rather as meeting the objectives of the study design (e.g., correlation coefficient of ≥ 0.950).

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The Total Bilirubin2 assay is used for the quantitation of total bilirubin in human serum or plasma, of adults and neonates, on the ARCHITECT c System.

Measurement of total bilirubin, an organic compound formed during the normal destruction of red blood cells, is used in the diagnosis and treatment of liver, hematological, and metabolic disorders, including hepatitis and disorders of the biliary tract. In newborn infants, the Total Bilirubin2 assay is intended to measure the levels of total bilirubin (conjugated and unconjugated) in serum or plasma to aid in the diagnosis and management of neonatal jaundice and hemolytic disease of the newborn.

The Total Bilirubin2 assay (subject device) is an automated clinical chemistry assay for the quantitation of total bilirubin in human serum or plasma, of adults and neonates, on the ARCHITECT c System. Total (conjugated and unconjugated) bilirubin couples with a diazo reagent in the presence of a surfactant to form azobilirubin. The diazo reaction is accelerated by the addition of surfactant as a solubilizing agent. The increase in absorbance at 548 nm due to azobilirubin is directly proportional to the total bilirubin concentration. The methodology is Diazonium salt.

The provided text describes a 510(k) premarket notification for a medical device called "Total Bilirubin2", an in vitro diagnostic assay. This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device, rather than proving clinical effectiveness through the extensive studies typically associated with AI/ML diagnostic tools. Therefore, the questions related to AI/ML specific criteria (like MRMC studies, number of experts for ground truth, sample size for training sets, etc.) are not applicable in this context.

The document primarily details the analytical performance of the Total Bilirubin2 assay.

Here's an analysis based on the information provided, adhering to the request:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for this in vitro diagnostic device are typically defined by ranges of acceptable analytical performance, following established CLSI (Clinical and Laboratory Standards Institute) guidelines. The reported device performance is compared against these internal acceptance criteria.

Study Details:

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

   • Precision (Within-Laboratory): 80 replicates for each control/panel (on a representative combination out of 3 multi-lot/instrument combinations).
   • Reproducibility (System): 84 replicates for each control/panel.
   • Lower Limits of Measurement: ≥ 60 replicates for LoB and LoD for each of 3 lots on 2 instruments.
   • Interfering Substances: Not explicitly stated, but "Each substance was tested at 2 levels of the analyte."
   • Method Comparison:
     • Serum: 167 samples
     • Neonatal serum: 163 samples
   • Tube Type: Samples collected from a minimum of 40 donors.
   • Dilution Verification: 5 samples prepared with varying concentrations.
   • Data Provenance: Not explicitly stated regarding country of origin or whether retrospective/prospective. However, given the nature of in vitro diagnostic analytical studies, samples are typically acquired prospectively or from biobanks for specific analytical testing purposes.

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

   • For in vitro diagnostic devices like this bilirubin assay, "ground truth" is established by reference methods or highly characterized calibrators/control materials, not by expert human readers. The accuracy study, for example, compares results to material standardized to the Doumas Total Bilirubin reference method, which represents the "ground truth" for bilirubin measurement. Therefore, expert readers/adjudicators as typically seen in imaging AI studies are not applicable here.

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

   • Not applicable. This is an in vitro diagnostic assay, and its performance is evaluated against analytical measurements, not human interpretations requiring 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 device is an in vitro diagnostic test, not an AI/ML-driven imaging or diagnostic algorithm designed to assist human readers.

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

   • Not applicable. This is an assay performed on an automated system, providing a quantitative result. Its "performance" is inherently "standalone" in generating the numerical value, but it's not an AI algorithm in the sense of image interpretation or complex diagnostic inference.

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

   • For analytical performance studies, the "ground truth" for bilirubin concentration is established by reference methods (e.g., the Doumas method for accuracy) or by using certified reference materials and calibrators with known concentrations. This is the gold standard for quantitative in vitro diagnostic measurements.

7. The sample size for the training set:

   • Not applicable. This is not an AI/ML device that requires a "training set" in the computational sense. The device's performance is a function of its reagents, instrument, and established methodology, not a learned algorithm.

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

   • Not applicable. See above.

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Medicon Hellas Albumin: Reagent for the quantitative measurement of albumin in serum. Albumin measurements are used in the diagnosis and treatment of numerous diseases involving primarily the liver or kidneys.

Medicon Hellas Calcium: Reagent for the quantitative measurement of calcium in serum or urine. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Medicon Hellas Creatinine: Reagent for the quantitative measurement of creatinine in serum and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases and in monitoring renal dialysis.

Medicon Hellas Glucose: Reagent for the quantitative measurement of glucose in serum and urine. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.

Medicon Hellas Direct Bilirubin; Reagent for the quantitative measurement of direct bilirubin (conjugated) in serum. Measurements of the level of direct bilirubin is used in the diagnosis and treatment of liver, hemolytic, hematological, and metabolic disorders, including hepatitis and gall blader block.

Medicon Hellas Total Bilirubin: Reagent for the quantitative measurements of total bilirubin in serum. Measurements of the levels of total bilirubin is used in the diagnosis and treatment of liver. hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.

Medicon Hellas Urea Nitrogen: Reagent is for the quantitative measurement of urea nitrogen in serum and urine. Measurements are used in the diagnosis and treatment of certain renal and metabolic diseases.

The Medicon Hellas Albumin, Medicon Hellas Calcium, Medicon Hellas Creatinine, Medicon Hellas Glucose, Medicon Hellas Direct Bilirubin, Medicon Hellas Total Bilirubin, and Medicon Hellas Urea Nitrogen are reagents for use with Diatron Pictus 500 Clinical Chemistry Analyzers. They are test systems for the quantitative measurement of albumin, calcium, creatinine, glucose, direct and total bilirubin, and urea nitrogen in human serum and urine where clinically applicable. The methods employed are photometric, utilizing reactions between the sample and reagents to produce a colored chromophore or a change in absorbance that is proportional to the concentration of the analyte. The analyzer photometer reads the absorbances at time intervals dictated by the method application stored in the analyzer memory, and the change in absorbance is calculated automatically.

The provided text describes the performance of several Medicon Hellas assays (Albumin, Calcium, Creatinine, Glucose, Direct Bilirubin, Total Bilirubin, and Urea Nitrogen) when run on the Diatron Pictus 500 Clinical Chemistry Analyzer, demonstrating their substantial equivalence to predicate devices (Beckman Coulter AU reagents on AU2700 analyzer, and Abbott Architect Direct Bilirubin on Architect c8000 analyzer).

Here's an analysis of the provided information, structured to address your specific points regarding acceptance criteria and study details:

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

The document doesn't explicitly state "acceptance criteria" in a single, overarching table with pass/fail remarks. Instead, it describes each performance characteristic and then presents the results. The "Summary" sections for each study type imply that the results met the pre-defined acceptance criteria for demonstrating substantial equivalence. For instance, for accuracy, it states "Accuracy studies completed on at least three lots of each candidate reagent confirm that Medicon albumin... are substantially equivalent to the related predicate devices." This implies that the statistical analyses (Deming regression, R2, slope, intercept) fell within acceptable ranges. Similarly, for precision, it states "All lots passed acceptance criteria for each applicable sample type at each level."

Since explicit acceptance criteria are not presented, they are inferred from the demonstrated performance and the statement that the devices "passed acceptance criteria" or "met statistical acceptance criteria." Below is a table summarizing the reported device performance for each analyte. The "Acceptance Criteria" column will reflect the general statements of success or the implied ranges from the results themselves, as explicit numerical targets for individual tests are not given.

Implied Acceptance Criteria and Reported Device Performance

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For in vitro diagnostic use in the quantitative determination of total bilirubin in serum and plasma of adults and neonates on the ADVIA® Chemistry systems. Measurement of total bilirubin, an organic compound formed and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block. A total bilirubin measurement in newborn infants is intended to aid in indicating the risk of bilirubin encephalopathy (kernicterus).

The ADVIA® Chemistry Total Bilirubin_2 (TBIL_2) reagents are liquid ready to use. They are packaged as a kit with two kit sizes available as follows.
Kit Size – 70 mL Wedge Reagent 1 and 70 mL Reagent 2 Wedge
Reagent 1: 4 wedges x 68 mL
Reagent 2: 4 wedges x 25 mL
Kit Size - 40 mL Reagent 1 and 20 mL Reagent 2 Wedge
Reagent 1: 4 wedges x 38 mL
Each reagent kit consists of reagents of components and concentrations summarized below.
Reagent 1: Citrate buffer, pH 2.9 (0.1 mol/L); Detergent
Reagent 2: Phosphate buffer, pH 7.0 (10mmol/L); Sodium metavanadate (4 mmol/L)

Here's a breakdown of the acceptance criteria and study information for the ADVIA® Chemistry Total Bilirubin 2 (TBIL 2) device, based on the provided document:

Acceptance Criteria and Device Performance

The document doesn't explicitly state "acceptance criteria" for each performance characteristic as a distinct set of pre-defined thresholds. Instead, it presents the results of validation studies for various parameters. However, we can infer the implicit "acceptance criteria" by looking at industry standards (like CLSI guidelines cited) and typical performance expectations for such devices. The "reported device performance" directly comes from the study results.

Note: For some parameters, the "acceptance criteria" are implied by the method and regulatory guidelines (e.g., CLSI EP09-A3 for method comparison, which focuses on demonstrating accuracy through strong correlation and acceptable bias at medical decision points).

• Indican: 10 mg/dL
• Cyanokit: 40 ug/mL
• HbF: 1000 mg/dL
• HbA: 1000 mg/dL |
  | Expected Values (Reference Interval) | Reference intervals established or verified in accordance with CLSI guidelines and supported by literature. (Based on CLSI EP28-A3c and Wu AHB. Tietz Clinical Guide) | Verified expected values:
• 0-1 day: 5 days – 60 years: 0.3-1.2 mg/dL
• 60 - 90 years: 0.2-1.1 mg/dL

• 90 years: 0.2-0.9 mg/dL (Reference: Wu AHB. Tietz Clinical Guide to Laboratory Tests, 4th edition, 2006:172) |

Detailed Study Information:

The provided document describes analytical performance studies for the ADVIA® Chemistry Total Bilirubin 2 (TBIL 2) device. It is a standalone (algorithm only without human-in-the-loop performance) study, as it evaluates the analytical performance of a clinical chemistry assay, not a diagnostic imaging device with human interpretation.

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

   • Method Comparison: N = 119 patient samples.
   • Analytical Measuring Range/Linearity: The document states "9 levels" for linearity but does not specify the number of individual samples tested at each level or overall (implied to be an internally prepared linearity panel).
   • Limits of Detection and Quantitation: Not explicitly stated for specific test sets, usually involves multiple replicates of blank and low-concentration samples.
   • Interferences: Not explicitly stated for specific test sets; involved samples with low and high concentrations of bilirubin plus various interferents.
   • Data Provenance: Not explicitly stated. These are typically laboratory-generated samples or de-identified patient samples obtained for research purposes within the testing laboratory's region. The adult population data were previously cleared under K063845, implying this testing focused on neonatal-specific aspects or reaffirming general performance on the new instrument.

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

   • For this type of in vitro diagnostic device, "ground truth" is established through well-characterized reference methods or highly accurate comparator devices/methods. There are no "experts" in the human interpretation sense (like radiologists) involved in establishing the ground truth for these analytical measurements.
   • The "comparator method" for the method comparison study served as the reference for ground truth in that context. Its specifics (e.g., gold standard, reference material) are not detailed beyond being a "legally marketed comparator method."

3. Adjudication Method for the Test Set:

   • Not applicable. This is an analytical performance study of a quantitative assay, not a study involving human readers' interpretations of images or clinical reports requiring adjudication.

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

   • No, an MRMC study was not done. This document describes the analytical performance of an in vitro diagnostic assay, which traditionally does not involve human readers interpreting "cases" in the way an imaging device might.

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

   • Yes, a standalone study was done. The entire document details the analytical performance of the ADVIA® Chemistry Total Bilirubin 2 (TBIL 2) assay on an automated instrument (ADVIA® Chemistry 1800 System) without human interpretive input for the final result beyond loading samples and running the assay.

6. The Type of Ground Truth Used:

   • For the Method Comparison study, the ground truth was established by a legally marketed comparator method.
   • For Linearity, LoD/LoQ, and Interference studies, the ground truth involves carefully prepared samples (e.g., spiked samples, diluted samples, reference materials) with known concentrations or expected responses, tested against established analytical validation protocols.
   • For Expected Values (Reference Interval), the ground truth was established by literature reference (Wu AHB. Tietz Clinical Guide to Laboratory Tests, 4th edition, 2006:172) and verified according to CLSI guidelines.

7. Sample Size for the Training Set:

   • Not applicable. This document describes the validation of a finished assay and instrument system. Clinical chemistry assays are developed and optimized through iterative research and development, but there isn't a "training set" in the machine learning sense. The "reagent formulation and method parameters" (mentioned as remaining the same for adult claims from K063845) represent the output of prior development.

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

   • Not applicable. As a traditional in vitro diagnostic assay, the concept of a "training set" and associated ground truth is not relevant in the machine learning context. The assay's performance is governed by its chemical reaction principle and instrument calibration/characteristics.

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The GEM Premier 5000 is a portable critical care system for use by health care professionals to rapidly analyze heparinized whole blood samples at the point of health care delivery in a clinical setting and in a central laboratory. The instrument provides quantitative measurements of glucose, lactate and total bilirubin from venous, arterial and capillary heparinized whole blood. These parameters aid in the diagnosis of a patient's metabolite balance.

Glucose (Clu) measurement is used in the diagnosis, monitoring and treatment of carbohydrate metabolism disturbances including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and pancreatic islet cell carcinoma.

Lactate (Lac) measurement is used:

• to evaluate the acid-base status of patients suspected of having lactic acidosis;
• to monitor tissue hypoxia and strenuous physical exertion;
• in the diagnosis of hyperlactatemia.

Total bilirubin measurement is used to aid in assessing the risk of kernicterus and hyperbilirubinemia in neonates.

The GEM Premier 5000 system provides health care professionals in central laboratory or point-of-care clinical settings with fast, accurate, quantitative measurements of glucose, lactate and total bilirubin from venous, arterial and capillary heparinized whole blood.

Key Components:

• Analyzer: Employs a unique color touch screen and a simple set of menus and buttons for user interaction. The analyzer guides operators through the sampling process with simple, clear messages and prompts.
• GEM Premier 5000 PAK (disposable, multi-use GEM PAK): Houses all required components necessary to operate the instrument once the cartridge is validated. These components include the sensors, CO-Ox/tBili optical cell, Process Control (PC) Solutions, sampler, pump tubing, distribution valve and waste bag. The GEM PAK has flexible menus and test volume options to assist facilities in maximizing efficiency.
• Intelligent Quality Management 2 (iQM2): iQM2 is an active quality process control program designed to provide continuous monitoring of the analytical process before, during and after sample measurement with real-time, automatic error detection, automatic correction of the system and automatic documentation of all corrective actions. iQM2 is a statistical process control system that performs 5 types of continuous, quality checks to monitor the performance of the GEM PAK, sensors, CO-Ox, and reagents. These checks include System, Sensor, IntraSpect, Pattern Recognition and Stability Checks.

The provided text describes the performance of the GEM Premier 5000 device for measuring Glucose, Lactate, and Total Bilirubin. The document primarily focuses on analytical and clinical studies to demonstrate substantial equivalence to predicate devices, rather than establishing acceptance criteria against a specific benchmark.

However, we can infer acceptance criteria based on the "Total Error Observed" compared to "Total Error Specifications" in the "Whole Blood Performance at Medical Decision Levels" section. The document states, "Total Error was computed based on the following equation and the results were compared to the GEM Premier 5000 Total Error Specifications." This implies that the 'Total Error Specifications' are the acceptance criteria.

1. Table of acceptance criteria and the reported device performance:

Note: The document explicitly states "All results were within specification" for precision studies and "All parameter levels passed specification for all sample modes" for internal method comparison, and "The analytical and clinical study results demonstrate that the GEM Premier 5000 is safe and effective for its intended purpose and equivalent in performance to the predicate devices." While specific numerical acceptance criteria (Total Error Specifications) are not detailed in the provided excerpts, the text indicates that the observed total error for Glucose, Lactate, and tBili met these internal specifications. For the clinical testing section concerning capillary samples, a "TEa" (Total Error Allowable) is given, which serves as an acceptance criterion for those specific tests.

Capillary Samples Acceptance Criteria (TEa) and Performance:

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

• Internal Precision Study - Aqueous Controls: N=120 per analyte/level for each of the 3 controls (GEM System Evaluator and CVP 5 tBili). The study was internal to the manufacturer (Instrumentation Laboratory Co.).
• Internal Precision Study – GEM PAK (Cartridge) Process Control Solutions D and E: N=120 per analyte/level for each of the 2 solutions. The study was internal to the manufacturer.
• Internal Precision Study – Whole Blood: N=120 per analyte/level/sample mode (Normal and Micro) for five different concentrations of whole blood. The study was internal to the manufacturer.
• Reproducibility Study with Aqueous Controls – Point-of-Care (POC) Setting: N=90 pooled data (30 replicates per level) per analyte/level. This involved 3 external clinical POC sites, suggesting prospective data collection in a point-of-care setting.
• External Precision - Whole Blood: Patient samples were tested at 2 external central laboratories and 1 internal Customer Simulation Laboratory (CSL), and 3 external POC locations. At least two whole blood specimens were analyzed in triplicate daily for 5 days. Specific "N" values for each site and analyte are provided in the tables within the document (e.g., for Glu Normal Mode, POC1 N=51, POC2 N=39, POC3 N=27, CSL N=33, Lab1 N=30, Lab2 N=30). Data provenance is a mix of internal CSL (contrived and native specimens) and external clinical labs and POC sites (patient samples), implying prospective collection of patient samples.
• LoB, LoD, LoQ: Three (3) lots of GEM Premier 5000 PAKs (cartridges) were used.
• Linearity: Nine (9) levels per analyte, each analyzed in triplicate on three (3) GEM Premier 5000 test analyzers. Data provenance appears to be internal.
• Analytical Specificity: Interference study conducted on the GEM Premier 5000. Data provenance appears to be internal.
• Internal Method Comparison: N=373 for Glucose and Lactate, N=163 for tBili. Clinical samples were used, and samples were altered as needed to cover medical decision levels. Data provenance appears to be internal to the manufacturer, comparing to predicate devices.
• Clinical Testing (Method Comparison in POC):
  • Glucose and Lactate (Normal Mode): N=489 for Glucose, N=488 for Lactate. Pooled results from 3 external POC sites and 1 internal CSL. This included patient samples and spiked samples (at CSL).
  • Glucose and Lactate (Native Capillary Samples): N=171. Pooled results from an external POC site and the internal CSL using finger-stick samples.
  • Glucose and Lactate (Contrived Capillary Samples): N=197 for Glucose, N=201 for Lactate. Pooled native capillary samples with additional contrived capillary samples prepared internally.
  • Total Bilirubin (Normal, Capillary, and tBili/CO-Ox Modes): Against Roche Cobas 6000: N=53 (Normal), N=58 (Capillary), N=53 (tBili/CO-Ox). Against Ortho Clinical Diagnostics Vitros 5600: N=76 (Normal), N=77 (Capillary), N=77 (tBili/CO-Ox). Pooled results from external POC sites with neonate samples, adult samples, and spiked samples.

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

The document does not specify the number or qualifications of experts for establishing ground truth. The devices being compared are laboratory diagnostic instruments. Therefore, "ground truth" is likely established by reference methods or predicate devices, which are themselves high-accuracy laboratory instruments (e.g., GEM Premier 4000, ABL 837, Roche Cobas 6000, Ortho Clinical Diagnostics Vitros 5600). The "experts" in this context would be the technicians or clinical laboratory scientists operating these reference systems, though their specific qualifications are not stated.

4. Adjudication method for the test set:

Not applicable. This is a medical device performance study, not a clinical trial with human interpretation requiring adjudication. Performance is assessed by comparing results to established reference methods or predicate devices.

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 document pertains to an in vitro diagnostic device for quantitative measurements of analytes, not an AI-assisted diagnostic imaging or interpretation system involving human readers.

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

Yes, the studies presented are essentially "standalone" evaluations of the device's analytical performance, without direct human interpretation being part of the measurement process itself. The device (GEM Premier 5000) provides quantitative measurements, and its accuracy and precision are assessed against reference methods. While human operators are involved in running the device and collecting samples, the device's output is a direct quantitative result, not an interpretation that is then refined or improved by a human.

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

The "ground truth" for the performance studies is established through comparative analysis with predicate devices (GEM Premier 4000 for glucose and lactate, ABL 837 for total bilirubin) and commercially available laboratory reference analyzers (e.g., Roche Cobas 6000, Ortho Clinical Diagnostics Vitros 5600) for total bilirubin. These predicate and reference devices represent highly accurate and established measurement methods in clinical chemistry.

8. The sample size for the training set:

Not applicable. This document describes the validation of a laboratory instrument, not a machine learning model that requires a "training set." The device's performance is based on its internal design, sensors, and chemical reactions, which are validated through empirical studies rather than algorithm training.

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

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

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For the quantitative in vitro determination of Total Bilirubin for serum and plasma. Total Bilirubin measurements are used in the diagnosis and treatment of hemolytic, biliary and liver disorders, including hepatitis and cirrhosis.

This in vitro diagnostic device is intended for prescription use only.

The Total Bilirubin kit assay consists of ready to use reagent solutions.

CATALOGUE NUMBER: BR8307

R1. Total Bilirubin R1 4 x 20 mL
R2. Total Bilirubin R2 4 x 8 mL

REAGENT COMPOSITION

Contents Initial Concentration of Solutions
R1. Total Bilirubin R1
Citrate buffer, pH2.9 0.1 mol/L
Detergent 0.9%
Antimicrobial
R2. Total Bilirubin R2
Phosphate buffer, pH 7.0 10 mmol/L
Sodium Metavanadate 4 mmol/L

MATERIALS REQUIRED BUT NOT PROVIDED

Randox Assayed Multisera Level 2 (Cat. No. HN 1530) and Level 3 (Cat. No. HE 1532); 510(k) # K942458 Randox Calibration Serum Level 3 (Cat. No. CAL 2351); 510(k) # K053153 RX series Saline (Cat. No. SA 8396)

Here's an analysis of the provided text, focusing on the acceptance criteria and the studies conducted to meet them for the Total Bilirubin (T BIL) device.

Acceptance Criteria and Reported Device Performance

Study Details

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

   • Precision/Reproducibility: 80 determinations per sample type (LIN Pool, LOQ Pool, QC 1, QC 2, Serum Pool 1-4) across two lots, two RX Daytona plus systems, over 20 non-consecutive days with 2 replicates per run. Data provenance is not specified, but the study design suggests prospective testing of control materials and human serum samples (spiked or diluted).
   • Linearity/Assay Reportable Range: 11 levels, each run in replicates of five across two lots of reagent on one RX Daytona plus system. Data provenance is not specified.
   • Detection Limit: 240 determinations (for LoD) using 4 low-level samples. Data provenance is not specified.
   • Analytical Specificity (Interference): Not explicitly stated how many samples or replicates per interferent. Samples were spiked with interferents and compared to control samples. Data provenance is not specified.
   • Method Comparison: 106 serum patient samples spanning 0.21 to 26.9 mg/dL. Data provenance is not specified, but these are "patient samples," suggesting retrospective or prospective clinical samples.
   • Matrix Comparison: A minimum of 40 matched patient sample pairs (serum and lithium heparin plasma). Data provenance is not specified, but these are "patient samples," suggesting retrospective or prospective clinical samples.
   • Expected values/Reference range: Human serum from 30 normal donors. Data provenance is not specified. The study was prospective in nature, testing new samples.

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

   • This is an in vitro diagnostic device for quantitative chemical analysis. The "ground truth" is established by the analytical reference methods or established values of control materials, or comparison to a predicate device. There is no mention of human experts defining ground truth through consensus in the way a radiological study might. For the method comparison, the predicate device (Siemens Healthcare Diagnostic Inc, Total Bilirubin 2 reagent, K063845) serves as the reference, which itself would have undergone rigorous analytical validation.

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

   • Not applicable. This is an analytical chemistry device, not an imaging device requiring human adjudicated interpretations. The performance is assessed by quantitative analytical metrics.

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 analytical chemistry device, not an AI-assisted diagnostic tool involving human readers.

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

   • This is an in vitro diagnostic assay, which by nature operates "standalone" in terms of measurement. The results are then interpreted by a clinician, but the device itself generates a quantitative result without human-in-the-loop performance influencing the measurement. Performance studies like precision, linearity, and analytical specificity are inherently "standalone" evaluations of the device's analytical function.

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

   • Reference Methods/Materials: For linearity and precision, the ground truth is based on gravimetrically prepared samples, known concentrations of control materials, or dilutions with expected values.
   • Predicate Device: For method comparison, the results from the legally marketed predicate device (Siemens Healthcare Diagnostic Inc, Total Bilirubin 2 reagent, K063845) serve as the comparative ground truth.
   • Literature/Guidelines: For reference range verification, established normal ranges from scientific literature (e.g., "Tietz Clinical Guide to laboratory Tests") and guidelines (NCCLS C28-A3) are used.

7. The sample size for the training set

   • Not applicable. This is an analytical chemistry device, not a machine learning model that requires a training set.

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

   • Not applicable, as there is no training set for this type of device.

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The Total Bilirubin assay is used for the quantitation of total bilirubin in human serum or plasma of adults and neonates on the ARCHITECT c8000 System.

Measurement of total bilirubin, an organic compound formed during the normal destruction of red blood cells, is used in the diagnosis and treatment of liver, hematological and metabolic disorders, including hepatitis and gall bladder block. A bilirubin (total and unbound) in the neonate test system is a device intended to measure the levels of bilirubin (total and unbound) in the blood (serum) of newborn infants to aid in indicating the risk of bilirubin encephalopathy (kernicterus).

The Total Bilirubin reagent kit contains Reagent 1 and Reagent 2. Reagent 1 contains Surfactants and HCl. Reagent 2 contains 2, 4-dichloroaniline, HCl, Sodium nitrite, and Surfactant. The principles of the procedure involve total (conjugated and unconjugated) bilirubin coupling with a diazo reagent in the presence of a surfactant to form azobilirubin. The increase in absorbance at 548 nm due to azobilirubin is directly proportional to the total bilirubin concentration. The detection of the analyte is end-point colorimetric.

Here's an analysis of the provided text regarding the acceptance criteria and study for the Total Bilirubin device:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" for each test in a formal table, but rather describes the methodology and then reports the results. I will infer the acceptance criteria from the statements provided about what is considered acceptable or how performance supports the claims.

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

• Limit of Quantitation (LOQ), Limit of Detection (LOD), Limit of Blank (LOB):
  • Zero-analyte samples: 4 samples. Tested in a minimum of 5 replicates on 5 separate runs.
  • Low-analyte samples: Minimum of 2 samples gravimetrically prepared at 8 target concentrations. Tested in a minimum of 10 replicates on 5 separate runs.
  • Data Provenance: Not explicitly stated (e.g., country of origin) but "human serum albumin" and "unconjugated bilirubin" are used. The study is prospective in nature, as samples are prepared for the purpose of the test.
• Linearity: 12 levels per pool in each of three combined bilirubin pools. Tested in a minimum of 4 replicates.
  • Data Provenance: "combined bilirubin pools" from "conjugated bilirubin stock" and "unconjugated bilirubin stock", "serum". Prospective.
• Within-Laboratory Precision: 4 control materials (Bio-Rad serum based). Tested in a minimum of 2 replicates, 2 times per day for 20 days.
  • Data Provenance: Commercial control materials (Bio-Rad Lyphochek Unassayed Chemistry Control, Bio-Rad Liquichek Pediatric Control). Prospective.
• Interference: Not specified.
  • Data Provenance: Not specified, but uses "bilirubin concnetrations". Prospective.
• Method Comparison:
  • Adult patient specimens: 124. 4 spiked.
  • Neonatal patient specimens: 64. 4 spiked.
  • Data Provenance: Patient specimens. Not specified if retrospective or prospective or country of origin, but generally method comparison studies use collected patient samples.
• Reference Range: 40 adult patient serum samples.
  • Data Provenance: Fresh, adult patient serum samples from a clinically healthy population. Stored at 2-8°C, protected from light. Assumed to be prospective as samples were collected for the study.
• Automated Dilution Protocol versus Manual Dilution Procedure: Not specified (samples were pooled to create desired concentrations).
  • Data Provenance: "Fresh serum specimens" obtained and pooled. Prospective.
• Specimen Tube Type (Matrix Equivalence): Minimum of 40 samples from adult subjects for each tube type. (Serum glass N=41, SST N=40, EDTA N=39, Lithium Heparin N=40, PST N=40, Sodium Heparin N=39).
  • Data Provenance: "Fresh or frozen sample sets" from subjects. Assumed to be prospective as these are explicitly collected to test tube types.

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 (IVD) for quantitative measurement. The "ground truth" for such devices is typically established through analytical methods, reference materials, gravimetric preparation, or comparison to a gold standard reference method/device, rather than expert human interpretation.
• Therefore, the concept of "experts used to establish the ground truth" as it applies to image-based AI or clinical diagnostic interpretation by physicians is not applicable here. The ground truth is the chemical concentration of bilirubin.

4. Adjudication Method for the Test Set:

• Again, as this is a quantitative chemical measurement, adjudication methods for expert interpretation (like 2+1, 3+1) are not applicable. The "adjudication" is inherent in the analytical process (e.g., repeating measurements, using certified reference materials, performing statistical analysis of replicates).

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 is an in vitro diagnostic (IVD) device. MRMC studies, which assess human reader performance with and without AI assistance, are typically conducted for AI-powered medical image analysis or clinical decision support systems.
• Therefore, an MRMC comparative effectiveness study is not applicable to this type of device. There are no "human readers" interpreting an output in the same way a radiologist reads an image.

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

• Yes, this entire submission is a standalone performance evaluation of the assay (the "algorithm only" in a broader sense of the measurement procedure). The device is designed to quantitatively measure bilirubin, and the tests (LOQ, linearity, precision, interference, method comparison) evaluate its analytical performance without direct human interpretive intervention beyond running the instrument and analyzing the data.

7. The Type of Ground Truth Used:

• For LOQ, LOD, LOB: Gravimetrically prepared samples (human serum albumin and unconjugated bilirubin) provide the known "ground truth" concentrations.
• For Linearity: Combined bilirubin pools with known proportional compositions.
• For Precision: Commercial control materials with established (though perhaps unassayed) target ranges, tested repeatedly.
• For Method Comparison: The predicate device's measurements are used as the comparative "ground truth" or reference, as the goal is to show substantial equivalence.
• For Reference Range: Clinical health status of the adult population samples.
• For Automated Dilution: Known target concentrations and manual dilution results.
• For Specimen Tube Type: The control tube type (serum plastic tube) serves as the reference for comparison.

8. The Sample Size for the Training Set:

• This document describes the analytical validation of a re-agent kit for an existing instrument (ARCHITECT c8000 System). It's not an AI model that undergoes "training" in the conventional sense.
• Therefore, the concept of a "training set" for an AI algorithm is not applicable. The development of the reagent and its underlying chemical principles involved R&D and optimization, but not machine learning training on a dataset.

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

• As explained above, there is no "training set" in the context of an AI algorithm described here. The "ground truth" used during the development of the assay would have been based on established clinical chemistry principles, reference methods, and gravimetric preparations to ensure accurate concentration measurements during formulation and optimization.

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

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

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

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

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

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

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

1. Acceptance Criteria and Reported Device Performance

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

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

2. Sample Sizes and Data Provenance

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

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

3. Number of Experts and Qualifications for Ground Truth

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

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

4. Adjudication Method

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

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

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

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

6. Standalone (Algorithm Only) Performance Study

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

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

7. Type of Ground Truth Used

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

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

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

8. Sample Size for the Training Set

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

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

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

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

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The ACE Carbon Dioxide (CO2-LC) Reagent is intended for the quantitative determination of carbon dioxide concentration in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

The ACE Direct Bilirubin Reagent is intended for the quantitative determination of direct bilirubin concentration in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic, hematological and metabolic disorders, including hepatitis and gall bladder block. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

The ACE Total Bilirubin Reagent is intended for the quantitative determination of total bilirubin concentration in serum and lithium heparin plasma using the ACE, ACE Alera and ACE Axcel Clinical Chemistry System. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic, hematological and metabolic disorders, including hepatitis and gall bladder block. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

The ACE Magnesium Reagent is intended for the quantitative determination of magnesium in serum and lithium heparin plasma using the ACE, ACE Alera and ACE Axcel Clinical Chemistry Systems. Magnesium measurements are used in the diagnosis and treatment of hypomagnesemia (abnormally low plasma levels of magnesium) and hypermagnesemia (abnormally high plasma levels of magnesium). This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.

In the ACE Carbon Dioxide (CO2-LC) Reagent assay, serum carbon dioxide (in the form of bicarbonate) reacts with phosphoenolpyruvate in the presence of phosphoenolpyruvate carboxylase and magnesium to yield oxaloacetic acid and phosphate. In the presence of malate dehydrogenase, the reduced cofactor is oxidized by oxaloacetic acid. The reduced cofactor absorbs strongly at 408 nm whereas its oxidized form does not. The rate of decrease in absorbance, monitored bichromatically at 408 nm/692 nm, is proportional to the carbon dioxide content of the sample.

In the ACE Direct Bilirubin Reagent assay, sodium nitrite added to sulfanilic acid forms diazotized sulfanilic acid. Bilirubin glucuronide in serum reacts with diazotized sulfanilic acid to form azobilirubin, which absorbs strongly at 554 nm. The increase in absorbance, measured bichromatically at 554 nm/692 nm, one minute after sample addition, is directly proportional to the direct bilirubin concentration.

In the ACE Total Bilirubin Reagent assay, sodium nitrite, when added to sulfanilic acid, forms diazotized sulfanilic acid. Bilirubin in serum reacts with diazotized sulfanilic acid to form azobilirubin, which absorbs strongly at 554 nm. The inclusion of dimethyl sulfoxide (DMSO) in the reagent as an accelerator causes both direct and indirect bilirubin to react rapidly. The increase in absorbance, measured bichromatically at 554 nm/692 nm, is directly proportional to the total bilirubin concentration in the sample.

Magnesium ions in serum react with Xylidyl blue-1 in an alkaline medium to produce a red complex which is measured bichromatically at 525 nm/692 nm. The intensity of color produced is directly proportional to the magnesium concentration in the sample. EGTA prevents calcium interference by preferential chelation of calcium present in the sample. A surfactant system is included to remove protein interference.

The provided text describes several in vitro diagnostic reagents (ACE Carbon Dioxide (CO2-LC) Reagent, ACE Direct Bilirubin Reagent, ACE Total Bilirubin Reagent, and ACE Magnesium Reagent) and their associated performance data. There isn't information about an AI-powered device or software. Therefore, questions related to AI aspects like multi-reader multi-case studies, effect size of AI assistance, or standalone algorithm performance are not applicable.

The acceptance criteria are not explicitly stated as clear thresholds in the provided document; rather, the document presents detailed performance data (precision, linearity, interference, and method comparison) that demonstrates the device's capability to perform as intended and to be substantially equivalent to its predicate devices. The "reported device performance" is presented directly through tables and statistical analyses for each reagent.

Here's an attempt to structure the available information based on the request, interpreting "acceptance criteria" as the performance demonstrated to support substantial equivalence:

1. Table of Acceptance Criteria and Reported Device Performance

Since explicit "acceptance criteria" (i.e., predefined thresholds for performance metrics) are not provided in the document, the "Reported Device Performance" below represents the data presented that presumably met the internal criteria for demonstrating substantial equivalence. The document primarily focuses on precision, linearity, interference, and method comparison with predicate devices and between different systems (ACE, ACE Alera, ACE Axcel).

ACE Carbon Dioxide (CO2-LC) Reagent

ACE Direct Bilirubin Reagent

ACE Total Bilirubin Reagent

ACE Magnesium Reagent

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

The document describes several types of studies:

• In-House Precision:

  • CO2-LC: Low, Mid, High serum and plasma samples were tested (number of replicates per sample and runs is implicitly part of SD/CV calculation, but not explicitly stated).
  • Direct Bilirubin: Low, Mid, High serum and plasma samples.
  • Total Bilirubin: Low, Mid, High serum and plasma samples.
  • Magnesium: Low, Mid, High serum and plasma samples.
  • Data Provenance: In-house (Alfa Wassermann Diagnostic Technologies, LLC, West Caldwell, NJ), prospective testing.

• POL (Physician Office Laboratory) Precision: Studies conducted at 3 POL sites.

  • CO2-LC: 3 samples at each of 3 POL sites and in-house.
  • Direct Bilirubin: 3 samples at each of 3 POL sites and in-house.
  • Total Bilirubin: 3 samples at each of 3 POL sites and in-house.
  • Magnesium: 3 samples at each of 3 POL sites and in-house.
  • Data Provenance: Not explicitly stated but inferred to be from POLs in the USA (prospective testing under typical POL conditions).

• In-House Matrix Comparison (Serum vs. Plasma):

  • CO2-LC: 53-54 pairs (serum/plasma) on ACE and ACE Alera; 51 pairs on ACE Axcel.
  • Direct Bilirubin: 102 pairs on ACE; 101 pairs on ACE Alera; 56 pairs on ACE Axcel.
  • Total Bilirubin: 102 pairs on ACE and ACE Alera; 56 pairs on ACE Axcel.
  • Magnesium: 101 pairs on ACE and ACE Alera; 55 pairs on ACE Axcel.
  • Data Provenance: In-house, retrospective (presumably collected for a range of values).

• POL Method Comparison (In-House ACE vs. POL ACE/Alera):

  • CO2-LC: 45-46 samples per POL site comparison.
  • Direct Bilirubin: 49-51 samples per POL site comparison.
  • Total Bilirubin: 48-50 samples per POL site comparison.
  • Magnesium: 50-52 samples per POL site comparison.
  • Data Provenance: Not explicitly stated but inferred to be from POLs in the USA (prospective testing under typical POL conditions) compared against in-house data.

• Detection Limits (LoB, LoD, LoQ), Linearity, Interferences (ACE Alera):

  • Sample sizes for detection limits and linearity: Not explicitly stated, typically involves multiple replicates at various concentrations.
  • Sample sizes for interferences: Not explicitly stated, typically involves samples spiked with various concentrations of interferents.
  • Data Provenance: In-house.

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

This information is not provided in the document. For in vitro diagnostic assays, the "ground truth" is typically the reference method or established clinical laboratory results obtained from a highly accurate and calibrated instrument or laboratory using validated methods, rather than human expert consensus for image or clinical interpretation. The document compares performance against other (presumably established) methods and predicate devices.

4. Adjudication Method for the Test Set

This concept (e.g., 2+1, 3+1 for resolving discrepancies) is not applicable to these types of in vitro diagnostic device studies. Performance is measured numerically and objectively.

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

No. This is an in vitro diagnostic assay, not an AI-powered diagnostic imaging device.

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

Not applicable. This is not an AI algorithm. The performance data presented are for the reagent and instrument system.

7. The Type of Ground Truth Used

For precision studies, the "ground truth" is the true concentration of the analyte in the control material or patient sample, which is established by reference methods or manufacturing specifications of the control materials. For method comparison studies, the predicate device's results or an established in-house method are used as the comparative reference. The document states the intended use is for "quantitative determination" of analytes, implying comparison to a quantitative gold standard.

8. The Sample Size for the Training Set

Not applicable. This is not a machine learning device and therefore does not have a "training set" in that context. The development of reagents and the establishment of their performance characteristics do not involve machine learning training sets.

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

Not applicable, as there is no "training set" for these reagents in the context of AI/ML.

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The ARCHITECT Total Bilirubin assay is used for the quantitation of total bilirubin in human serum or plasma on the ARCHITECT c8000 system. Measurement of total bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.

A bilirubin (total and unbound) in the neonate test system is a device intended to measure the levels of bilirubin (total and unbound) in the blood (serum) of newborn infants to aid in indicating the risk of bilirubin encephalopathy (kernicterus).

ARCHITECT Total Bilirubin is an in vitro diagnostic assay for the quantitative analysis of total bilirubin in human serum or plasma of adults and neonates. Total (conjugated and unconjugated) bilirubin couples with the diazo reagent in the presence of a surfactant to form azobilirubin. The increase in absorbance at 548 nm due to azobilirubin is directly proportional to the total bilirubin concentration.

This document is a 510(k) summary for the ARCHITECT Total Bilirubin assay. This device is an in vitro diagnostic assay, and therefore the acceptance criteria and study details are focused on analytical performance, not clinical performance based on human reader interpretations.

Here's a breakdown of the requested information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated in a quantitative manner (e.g., "correlation coefficient must be > 0.99"). Instead, the document states generally that the method comparison "yielded acceptable correlation" and that the data "demonstrate the performance of the modified ARCHITECT Total Bilirubin assay is substantially equivalent to the performance of Abbott Total Bilirubin assay." The reported device performance metrics are provided.

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