Search Results

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.

Ask a specific question about this device

The Direct Bilirubin test system is a device intended for the quantitative in vitro determination of Direct Bilirubin in serum and plasma. Bilirubin measurements can be used in the diagnosis and treatment of liver, hematological and metabolic disorders including hepatitis and gall bladder block.

This device is for prescription use only.

The Randox Direct Bilirubin kit consists of ready to use reagent solutions.

CATALOGUE NUMBER: BR8308 COMPONENTS: R1. 4 x 20ml, R2. 4 x 8ml

REAGENT COMPOSITION

R1. Direct Bilirubin RI Tartrate buffer, pH2.9 Detergent Antimicrobials and Preservatives Inhibitors Initial Concentration of Solutions 0.1 mol/L
R2. Direct Bilirubin R2 Phosphate buffer, pH 7.0 Sodium Metavanadate Initial Concentration of Solutions 10 mmol/L 4 mmol/L

Here's a breakdown of the acceptance criteria and the study details for the Randox Direct Bilirubin device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document provides performance characteristics but does not explicitly state "acceptance criteria" in a tabulated format derived from a regulatory body or a specific standard with pass/fail thresholds. Instead, it presents the results of various analytical performance studies. However, some sections imply acceptance criteria through their phrasing (e.g., "deviation from linearity is less than 5%" for linearity, "no significant interference" for specificity, and "≤20% CV imprecision" for LoQ).

Here's an interpretation of implied acceptance criteria and reported performance:

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

• Precision/Reproducibility:
  • Sample Size: Not explicitly stated as a number of samples but rather as "control material and unaltered human serum samples" divided into pools (Pool 1, 2, 4) and tested over 20 non-consecutive days with 2 replicates per run. This implies a significant number of measurements for each pool.
  • Data Provenance: "unaltered human serum samples." The country of origin is not specified, but the submission is from the UK. The study is prospective in nature (testing conducted for the device).
• Linearity/Assay Reportable Range:
  • Sample Size: Samples prepared at 11 levels. Each level run in replicates of five.
  • Data Provenance: Not specified, but samples were prepared to cover a range of analyte concentrations. Prospective.
• Detection Limit:
  • Sample Size: 240 determinations (for LoD) with 4 low-level samples.
  • Data Provenance: Not specified. Prospective.
• Analytical Specificity/Interference:
  • Sample Size: Not explicitly stated as a number of samples, but "the analytes detailed below were tested up to the levels indicated at Bilirubin concentrations of 0.14mg/dl and 5.03mg/dl."
  • Data Provenance: Not specified. Prospective.
• Method Comparison with Predicate Device:
  • Sample Size: 103 serum patient samples.
  • Data Provenance: "patient samples." The country of origin is not specified. Likely retrospective, as existing patient samples were used, but the testing itself was prospective.
• Matrix Comparison:
  • Sample Size: A minimum of 40 matched patient sample pairs.
  • Data Provenance: "Patient samples." The country of origin is not specified. Likely retrospective, as existing patient samples were used, but the testing itself was prospective.

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

This device is an in vitro diagnostic (IVD) test for quantitative determination of Direct Bilirubin. The "ground truth" for such devices is typically established through reference methods or established predicate devices, not through expert consensus in the same way an imaging or pathology AI might.

• Precision, Linearity, Detection Limit, Specificity: Ground truth is inherent in the analytical methods themselves (e.g., gravimetric dilutions for linearity, spiked samples, controlled interferent concentrations). No external experts are mentioned.
• Method Comparison and Matrix Comparison: The ground truth for these studies is the measurement obtained by the predicate device (Wako Direct Bilirubin V, K053132) or the matched serum/plasma results themselves. No external experts are described as establishing this "ground truth."

4. Adjudication Method for the Test Set

Not applicable for this type of IVD device. Adjudication is typically used in studies involving human interpretation (e.g., radiology reads) to resolve discrepancies.

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

Not applicable. This is an automated in vitro diagnostic test, not an AI-assisted human reading device.

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

Yes, the studies presented are all standalone performance evaluations of the Randox Direct Bilirubin assay system, an automated IVD device. The results reported are directly from the instrument measurements.

7. The Type of Ground Truth Used

• For analytical performance studies (Precision, Linearity, Detection Limit, Specificity): The 'ground truth' is established through controlled laboratory preparations (e.g., known concentrations of analytes, spiked samples, dilutions) and comparisons to established analytical methods as described in CLSI guidelines.
• For method comparison: The 'ground truth' is the predicate FDA-cleared device (Wako Direct Bilirubin V, K053132).
• For matrix comparison: The 'ground truth' is the serum sample measurement when comparing to lithium heparin plasma.

8. The Sample Size for the Training Set

Not applicable. This is a chemical assay, not a machine learning model that requires a training set. The "development" or "optimization" phase of such an assay would involve internal R&D, but it's not a "training set" in the context of AI/ML.

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

Not applicable. There is no training set for an IVD chemical assay as described here. Parameter settings and reagent formulations are determined through standard chemical and biochemical R&D processes, not through machine learning ground truth establishment.

Ask a specific question about this device

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.

Ask a specific question about this device

For in vitro diagnostic use in the quantitative determination of total billrubin in human serum and plasma on the ADVIA Chemistry Systems. Such measurements are used in the diagnosis and treatment of hemolytic, biliary, and liver disorders, including hepatitis and cirrhosis.

The ADVIA Chemistry Total Bilirubin_2 is used for the in vitro quantitative determination of total bilirubin in human serum and plasma on the ADVIA® Chemistry Systems. The proposed labeling indicates the ADVIA Chemistry Total Bilirubin_2 reagents can be used on the ADVIA Chemistry Systems 1650, 1800, 2400, and 1200. The Total Bilirubin_2 assay is based on a chemical oxidation method, utilizing vanadate as the oxidizing agent. Total bilirubin (conjugated and unconjugated) is oxidized by vanadate at about pH 2.9 to produce biliverdin. In the presence of detergent and vanadate, both conjugated and unconjugated bilirubin are oxidized. This oxidation causes a decrease in optical density of the yellow color, which is specific to bilirubin. The decrease in optical density at 451/545 nm is proportional to the total bilirubin concentration in the sample. The concentration is measured as an endpoint reaction.

Here's an analysis of the provided 510(k) summary regarding the ADVIA® Chemistry Total Bilirubin_2 device, focusing on acceptance criteria and supporting studies:

1. Table of Acceptance Criteria and Reported Device Performance

The 510(k) summary does not explicitly state formal "acceptance criteria" in terms of pre-defined thresholds for performance metrics. Instead, it demonstrates "substantial equivalence" to a predicate device (ADVIA® IMS Total Bilirubin) by comparing performance characteristics. The implied acceptance criterion is that the new device's performance is comparable to or better than the predicate device's performance, and within generally accepted analytical standards for clinical laboratory assays.

2. Sample Size and Data Provenance for the Test Set

• Imprecision Study (Test Set):

  • The sample size for the imprecision study is not explicitly stated as a single "test set" size. Instead, it reports CVs at multiple bilirubin levels. The common practice for imprecision studies involves running samples (controls or patient pools) multiple times over several days. The table shows 3-5 different bilirubin levels tested on each of the four ADVIA Chemistry Systems.
  • Data Provenance: Not specified in the summary (e.g., country of origin). The studies appear to be prospective as they were conducted specifically for this 510(k) submission to evaluate the performance of the new device.

• Correlation (Method Comparison) Study (Test Set):

  • Sample Size:
    • Serum, ADVIA 1650 vs ADVIA IMS: 118 samples (N=118)
    • Serum, ADVIA 2400 vs ADVIA 1650: 119 samples (N=119)
    • Serum, ADVIA 1200 vs ADVIA 1650: 119 samples (N=119)
  • Data Provenance: Not specified (e.g., country of origin). Appears to be prospective as these studies would have been designed to compare the new device against existing methods.

• Interfering Substances Study (Test Set):

  • The sample size for the interfering substances experiment is not explicitly stated. Typically, a small number of samples (e.g., one or two per interference level) are spiked with the interfering substance and tested.
  • Data Provenance: Not specified. Appears to be prospective.

• Analytical Range Study (Test Set):

  • The sample size used to establish the analytical range (linearity) is not explicitly stated. These studies typically use a series of diluted/spiked samples to cover the claimed range.
  • Data Provenance: Not specified. Appears to be prospective.

3. Number of Experts and Qualifications for Ground Truth

• No external "experts" (e.g., radiologists) were explicitly used to establish ground truth for these analytical performance studies.
• For an in vitro diagnostic (IVD) device like a bilirubin assay, "ground truth" is typically established by:
  • Reference Methods: The "AACC Reference Method" is stated as the standardization method for both the new device and the predicate. This is a highly standardized and validated analytical method.
  • Predicate Device: The predicate device itself (ADVIA IMS Total Bilirubin) serves as a gold standard or "truth" for comparison in the method correlation studies. Its results are assumed to be accurate.
  • Known Concentrations: For studies like imprecision, interfering substances, and analytical range, commercial controls or spiked samples with known, verified concentrations are used.

4. Adjudication Method for the Test Set

• Not applicable. This product is an in vitro diagnostic (IVD) lab assay. Adjudication, particularly multi-reader methods (e.g., 2+1, 3+1), is typically relevant for interpretative devices like imaging diagnostics where human readers make a judgment, and their discrepancies need to be resolved. For a quantitative chemical assay, the measurement itself is the output, and any discrepancies would be resolved through re-testing, calibration checks, or investigation into analytical errors, rather than expert adjudication of a qualitative result.

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

• No MRMC study was done. This type of study is for interpretative devices involving human perception (e.g., radiology AI). The ADVIA Chemistry Total Bilirubin_2 is a quantitative analytical device that produces numerical results, not images or qualitative interpretations that a human reads. Therefore, the concept of "how much human readers improve with AI vs without AI assistance" does not apply here.

6. Standalone (Algorithm Only) Performance Study

• Yes, this entire submission is a standalone performance study in the context of an IVD. The device is the algorithm/reagent system that performs the measurement without human interpretation of the primary data (other than reading the final numerical output). The performance data (imprecision, correlation, etc.) reflects the algorithm/reagent system's capabilities without human-in-the-loop directly influencing the outputted bilirubin concentration. Human interaction is limited to operating the instrument, loading samples, and interpreting the final numerical result in a clinical context.

7. Type of Ground Truth Used

• Reference Methods and Predicate Device:
  • For standardization, the AACC Reference Method is explicitly stated as the ground truth.
  • For method comparison/correlation, the ADVIA IMS Total Bilirubin assay (predicate device) served as the comparison method, implicitly representing the accepted "truth" for validating the new device's accuracy.
  • For imprecision, analytical range, and interfering substances, the ground truth would have been established using calibrated materials, known-concentration controls, and carefully prepared spiked samples.

8. Sample Size for the Training Set

• Not applicable / Not explicitly stated for algorithm training. This device is a traditional chemical assay, not an AI/ML-based device that undergoes a distinct "training" phase with a large dataset in the sense of machine learning algorithms. The development of such an assay involves chemical formulation, optimization, and extensive analytical validation in a laboratory setting, but not typically "training data" as would be used for neural networks or similar AI.

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

• Not applicable. As explained above, this is not an AI/ML device with a training set in the conventional sense. The "ground truth" for the device's development and optimization would have been established through standard chemical and laboratory practices, utilizing reference methods, standards, and control materials to ensure the reagents and measurement principles were accurate and robust.

Ask a specific question about this device

Determination of serum and plasma bilirubin is useful in the screening of liver function disorders or in the diagnosis of jaundice.

When a sample is mixed with the reagent containing the detergent and the vanadate, at around pH3, direct bilirubin in the sample is oxidized to biliverdin. This causes the absorbance of yellow, specific to bilirubin, to decrease. Therefore, the direct bilirubin concentration in the sample can be obtained by measuring the adsorbances before and after the vanadate oxidation.

This document is a 510(k) Summary of Safety and Effectiveness for the Wako Direct Bilirubin V assay. It highlights that the device is based on a chemical oxidation method and can determine direct bilirubin concentration in serum and plasma samples. The primary goal of the submission is to add plasma as an approved sample type to an already existing and approved device (Wako's previous Direct Bilirubin assay, 510(k) #970986).

1. Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state specific performance acceptance criteria in numerical terms (e.g., sensitivity, specificity, accuracy thresholds). Instead, the crucial acceptance criterion for this 510(k) submission is "substantial equivalency" to the previously marketed device (Wako's Direct Bilirubin assay, 510(k) #970986).

The reported device performance is:

• "shows good correlation with conventional methods"
• "practically no interference by coexistent serum and plasma substances"
• "convenient ready-to-use liquid type reagent"

Table of Acceptance Criteria and Reported Device Performance:

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

The document does not provide details on the sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective). It only states that the submission adds the use of plasma as a sample to the previously cleared device. Therefore, any testing related to substantial equivalence for plasma samples would have been conducted, but the specific details are not included in this summary.

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

This submission describes an in vitro diagnostic (IVD) assay for measuring bilirubin, not an imaging device or one requiring expert interpretation of results for ground truth establishment. Therefore, the concept of "experts used to establish ground truth" as it applies to, for example, radiologists interpreting images, is not applicable here. The "ground truth" for chemical assays typically relies on established reference methods, calibrated standards, and a comparison to a predicate device.

4. Adjudication Method for the Test Set

Given that this is an IVD assay and not an imaging or interpretative device, an "adjudication method" in the sense of multiple experts resolving discrepancies is not applicable. Assay results are quantitative measurements, and accuracy is typically assessed against reference methods or the performance of a predicate device.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study is not applicable for this type of in vitro diagnostic assay. MRMC studies are typically used to evaluate the diagnostic performance of human readers, often with and without AI assistance, in interpreting medical images or other complex data. This device is an automated chemical assay.

6. Standalone Performance Study

The information provided within this summary does not explicitly describe a separate "standalone" study in the way it might be for an AI algorithm. However, the 510(k) submission itself implicitly represents a standalone performance evaluation by comparing its performance to predicate devices (the previous Wako Direct Bilirubin assay) and conventional methods. The core of a 510(k) relies on demonstrating that the new device is "substantially equivalent" in performance to a legally marketed predicate device. This inherently means its performance was evaluated independently to make that claim.

7. Type of Ground Truth Used

The ground truth for chemical assays like this is typically established through:

• Comparison to established, validated reference methods: The summary mentions "good correlation with conventional methods," indicating such comparisons were likely part of the underlying studies.
• Calibrated standards: Assays are typically validated against precisely known concentrations of the analyte (bilirubin in this case).
• Performance of the predicate device: The primary ground truth for this specific submission is the performance of the legally marketed predicate device (Wako's previous Direct Bilirubin assay, 510(k) #970986), against which "substantial equivalency" is claimed.

8. Sample Size for the Training Set

The concept of a "training set" with a specified sample size is primarily relevant to machine learning or AI algorithms. This device is a chemical reagent-based assay. Therefore, a "training set" in the machine learning sense is not applicable. The development of such assays involves extensive R&D, formulation optimization, and analytical validation.

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

As noted above, a "training set" in the context of AI is not applicable for this chemical assay. The validation of the assay's chemical principles and performance would have involved laboratory studies using known bilirubin concentrations, spiked samples, and clinical samples analyzed by reference methods and the predicate device to ensure accuracy, precision, and linearity.

Ask a specific question about this device

Indication of serum and plasma bilirubin is useful in the screening of liver function disorders or in the diagnosis of jaundice.

Wako Total Bilirubin V is based on a chemical oxidation method, utilizing vanadate as an oxidating agent, shows good correlation with conventional methods, practically no interference by coexistent serum and plasma substances, and is convenient ready-to-use liquid type reagent. When a sample is mixed with the reagent containing the detergent and the vanadate, at around pH3, total bilirubin in the sample is oxidized to biliverdin. This causes the absorbance of yellow, specific to bilirubin, to decrease. Therefore, the total bilirubin concentration in the sample can be obtained by measuring the adsorbances before and after the vanadate oxidation.

This submission is for a reagent, the Wako Total Bilirubin V assay, and thus the acceptance criteria and study design are related to the analytical performance of the assay rather than a diagnostic device that requires expert consensus or advanced imaging.

Here's an analysis of the provided text in relation to your request:

Acceptance Criteria and Device Performance

The provided text does not explicitly state specific numerical acceptance criteria for the Wako Total Bilirubin V assay. Instead, it relies on demonstrating "substantial equivalency" to a previously marketed device (510(K) # 970985).

The reported device performance, in terms of meeting implicit acceptance criteria, is based on the following:

• Substantial Equivalency: The key claim is that "The safety and effectiveness of the Wako Total Bilirubin V assay is demonstrated by its substantial equivalency to our previous Total Bilirubin assay (510(K) # 970985)."
• Correlation with Conventional Methods: The device "[Wako Total Bilirubin V] shows good correlation with conventional methods."
• Interference by Coexistent Serum and Plasma Substances: It demonstrates "practically no interference by coexistent serum and plasma substances."
• Convenience and Stability: It is also "convenient ready-to-use liquid type reagent."

Table of Acceptance Criteria and Reported Device Performance (Inferred):

Study Details

Given the nature of the submission (510(k) for an in vitro diagnostic reagent, primarily adding a sample type), the study described is an analytical validation comparing the new device to a predicate and conventional methods. It is not a clinical study involving human readers or extensive ground truth establishment in the way a diagnostic imaging device would be studied.

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

   • Sample Size: Not explicitly stated in the provided text.
   • Data Provenance: Not explicitly stated, but typical for such submissions would be laboratory-based analytical studies using human serum and plasma samples. It does not specify country of origin or whether it's retrospective or prospective, but these are generally prospective analytical studies for IVD reagents.

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

   • Not applicable in the sense of expert human interpretation of images/data. The "ground truth" (or reference values) would be established by the "conventional methods" mentioned (diazo coupling, bilirubin oxidase enzymatic method) which are laboratory-based chemical analyses, often performed by trained medical technologists or clinical chemists. No specific number or qualifications of individual "experts" are provided as this is a chemical assay validation.

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

   • Not applicable. This is an analytical performance study of a chemical reagent, not a diagnostic interpretation study requiring adjudication of expert opinions.

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 not an AI-assisted diagnostic device, nor is it a study involving human readers.

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

   • This is inherently a "standalone" device in the sense that it is a chemical reagent that performs its function without a human-in-the-loop interpretative step once the sample is added. However, the term "standalone" usually refers to AI algorithms. In the context of IVDs, this refers to the assay's analytical performance on its own. The description implies such a standalone analytical validation was performed.

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

   • The "ground truth" for bilirubin measurement is established through reference laboratory methods, specifically the "conventional methods" like the diazo coupling method and the bilirubin oxidase enzymatic method, which are well-established chemical assays for bilirubin quantification.

7. The sample size for the training set:

   • Not applicable. This is a chemical reagent, not a machine learning algorithm that requires a "training set."

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

   • Not applicable. (See #7).

Ask a specific question about this device

Dri-STAT® Enzymatic Bilirubin Reagent, in conjunction with the SYNCHRON® Systems Bilirubin Calibrator, is intended for use in the in vitro diagnostic determination of total bilirubin in human serum and plasma as a User Defined Reagent (UDR) application on SYNCHRON® Systems. Measurements of total bilirubin in serum and plasma are used in the diagnosis and treatment of liver, hemolytic, hematologic, and metabolic disorders, such as jaundice, biliary obstruction, hepatitis and cirrhosis.

The Dri-STAT® Enzymatic Bilirubin Reagent may be used in conjunction with the SYNCHRON® Systems Bilirubin Calibrator on the family of SYNCHRON® Systems. The reagent kit contains two reagent bottles that are transferred into a Beckman Coulter User-Defined Cartridge.

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 for this device are implied by the performance characteristics demonstrated to be substantially equivalent to the predicate device. The document states: "The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to chemistry test systems already in commercial distribution. A finding of substantial equivalence is demonstrated through method comparison, linearity, and imprecision experiments."

Therefore, the performance data presented from these experiments serve as the basis for demonstrating that the device meets the "acceptance criteria" of being substantially equivalent.

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

• Sample Size for Test Set:
  • For the method comparison studies, the sample size was 70 for both the Synchron LX System and the Synchron CX System.
  • For the imprecision studies, the sample size was 80 for each of the four samples (Serum Control 1, Serum Control 2, Serum Control 3, Human Pool) in both within-run and total imprecision measurements.
• Data Provenance: The document does not explicitly state the country of origin of the data or whether it was retrospective or prospective. It refers to "Human Pool" samples, implying clinical samples were used, but further details are not provided.

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

This information is not provided in the document. For in vitro diagnostic devices like the Dri-STAT® Enzymatic Bilirubin Reagent, ground truth is typically established through reference methods or highly accurate comparative assays, not through expert consensus on qualitative interpretation.

4. Adjudication Method for the Test Set

This information is not applicable and therefore not provided in the document. Adjudication methods are typically used when subjective interpretations are involved, such as in image analysis or clinical diagnosis. For a quantitative chemical assay, the comparison is to a reference method or a predicate device.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for devices that involve human interpretation of results, especially in fields like radiology or pathology. The Dri-STAT® Enzymatic Bilirubin Reagent is a fully automated in vitro diagnostic assay, where human intervention is minimal in the measurement process itself.

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

Yes, the performance data presented (method comparison, linearity, imprecision) represents the standalone performance of the Dri-STAT® Enzymatic Bilirubin Reagent on the SYNCHRON® Systems. As an automated in vitro diagnostic test, the "algorithm only" performance is the core functionality being evaluated without human interpretation of the measurement output (beyond reading the numerical result).

7. The Type of Ground Truth Used

The "ground truth" for the performance evaluation in this context is established by the predicate device (Dri-STAT® Enzymatic Bilirubin Reagent on Cobas Fara) for the method comparison study. For imprecision, it's about the consistency of the assay itself. The comparison to the predicate device demonstrates that the new device measures bilirubin in a substantially equivalent manner, implying its results are "true" in relation to a well-established method.

8. The Sample Size for the Training Set

This document does not mention a training set. For classical in vitro diagnostic reagents like this one, there isn't typically a "training set" in the machine learning sense. The assay is developed and validated, and then its performance is characterized using test samples.

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

As no training set is mentioned or applicable in the provided context, this information is not available.

Ask a specific question about this device

The Stanbio Direct Bilirubin LiquiColor® and Total Bilirubin LiquiColor® test systems are devices intended to measure the levels of bilirubin (direct and total) in serum and plasma. Measurements of the levels of bilirubin, and 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.

The Direct Bilirubin LiquiColor® test kit is comprised of two reagents, Reagent 1 (R1) and Reagent 2. The Total Bilirubin LiquiColor® test kit is comprised of two reagents, Reagent 1 (R1) and Reagent 2.

Here's a breakdown of the acceptance criteria and study information for the Stanbio Direct Bilirubin LiquiColor® and Total Bilirubin LiquiColor® devices, based on the provided 510(k) summary:

Acceptance Criteria and Reported Device Performance

Note: The document does not explicitly state numerical acceptance thresholds for each criterion but presents the results of the performance studies. It is implied that these reported performance metrics were considered acceptable for demonstrating substantial equivalence. For instance, the high correlation coefficients (r) suggest strong agreement with the predicate devices, which is a common acceptance criterion for equivalence in such tests.

Study Details

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

   • Direct Bilirubin Test Set:
     • Correlation: 85 samples.
     • Comparison (Plasma vs. Serum): 22 samples.
     • Precision (Intra-assay & Inter-assay): n=20 for each sample level tested.
   • Total Bilirubin Test Set:
     • Correlation: 247 samples.
     • Comparison (Plasma vs. Serum): 19 samples.
     • Precision (Intra-assay & Inter-assay): n=20 for each sample level tested.
   • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, given that these are in vitro diagnostic devices for measuring analytes in human samples, the samples would typically be human serum or plasma.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. These are quantitative assays for chemical analytes, not image-based or clinical diagnostic tests requiring expert interpretation to establish ground truth in the traditional sense. The "ground truth" for the correlation and comparison studies is established by the results from a "commercially available test" (Roche Direct Bilirubin/Total Bilirubin tests).

3. Adjudication method for the test set: Not applicable. No human interpretation or adjudication process is involved in determining the "ground truth" for these types of quantitative assays.

4. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance: Not applicable. This is an in vitro diagnostic device, not an AI-assisted diagnostic tool that involves human readers.

5. If a standalone (i.e. algorithm only without human-in-the loop performance) was done: The device's performance data (precision, sensitivity, linearity) represents standalone performance, as it is a fully automated/instrument-based chemical assay. The "correlation" and "comparison" studies are essentially comparisons of the new device's standalone performance against another commercially available standalone device.

6. The type of ground truth used:

   • For Correlation studies, the ground truth was established by the measurements obtained from the predicate devices: Roche Direct Bilirubin (K910593) and Roche Total Bilirubin (K910591).
   • For Precision, Sensitivity, and Linearity, the ground truth is effectively the expected chemical value of the calibrators and samples used in the study, and the assessment is of the device's ability to consistently and accurately measure those values.

7. The sample size for the training set: Not applicable. This is a chemical assay, not an machine learning/AI model that requires training data.

8. How the ground truth for the training set was established: Not applicable, as there is no training set for this type of device.

Ask a specific question about this device

Not Found

When a sample is mixed with the reagent containing the detergent and the vanadate, at around pH 3, total bilirubin in the sample is oxidized to biliverdin. This causes the absorbance of yellow, specific to bilirubin, to decrease. Therefore, the total bilirubin concentration in the sample can be obtained by measuring the absorbance before and after the vanadate oxidation.

Here's a breakdown of the acceptance criteria and the study details for the Wako Total Bilirubin V assay, based on the provided text:

Acceptance Criteria and Reported Device Performance

Study Details

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

   • The document states that "serum samples" were used for comparison studies against the predicate assay. The exact number of samples is not specified.
   • The data provenance (country of origin, retrospective or prospective) is not specified.

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

   • This information is not applicable as the study compares a new device to a predicate device, not against a clinical expert's interpretation. The "ground truth" for the test set is established by the results from the predicate device (Wako's previous Total Bilirubin assay, K912024/A).

3. Adjudication method for the test set:

   • Not applicable. This is a comparison of quantitative measurements between two devices, not a qualitative assessment requiring adjudication of human interpretations.

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:

   • No. This is a study comparing two laboratory diagnostic devices for bilirubin measurement, not a study involving human readers or AI assistance.

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

   • Yes. This study describes the performance of a standalone laboratory assay (Wako Total Bilirubin V) in comparison to another standalone laboratory assay (the predicate device). There is no "human-in-the-loop" component in the direct measurement process being evaluated.

6. The type of ground truth used:

   • The "ground truth" for the comparative study was the results obtained from the predicate device (Wako's previous Total Bilirubin assay, 510(k)#K912024/A).

7. The sample size for the training set:

   • This concept is not applicable to this type of device and study. The Wako Total Bilirubin V assay is a chemical measurement method; it does not involve machine learning algorithms that require a "training set."

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

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

Ask a specific question about this device