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The Atellica® CH Diazo Direct Bilirubin (D DBil) assay is for in vitro diagnostic use in the quantitative determination of direct bilirubin in human serum and plasma using the Atellica® CH Analyzer. Measurement of direct 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 Direct 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. Absorbance is measured at 545/658 nm.

The provided text describes the performance characteristics and acceptance criteria for the Atellica® CH Diazo Direct Bilirubin (D DBil) assay. Here's a breakdown of the requested information:

Acceptance Criteria and Device Performance

1. Table of Acceptance Criteria and Reported Device Performance:

Note: Specific acceptance criteria for precision and reproducibility are not explicitly listed as single values but are implied by the comprehensive presentation of the data, demonstrating acceptable variability for a diagnostic assay. The document states that the results "support that the Candidate Device... is substantially equivalent."

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

• Assay Comparison: N = 100 samples
• Specimen Equivalency (Plasma vs. Serum): N = 53 samples for each plasma type (Lithium heparin, Sodium heparin, K2(EDTA)).
• Precision: N = 80 for each serum level (4 serum levels tested, total 320 measurements).
• Reproducibility: N = 225 for each serum level (4 serum levels tested, total 900 measurements).
• Interferences (HIL and Non-interfering Substances): The number of samples for interference testing is not explicitly stated as a single 'N' for the test set. However, the tables indicate specific analyte concentrations tested (e.g., for Hemoglobin, Lipemia, Acetaminophen, etc.), implying multiple measurements were performed for each interference level.

Data Provenance: The document does not explicitly state the country of origin or if the data was retrospective or prospective.

3. 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 device is an in vitro diagnostic assay for quantitative determination of direct bilirubin. The "ground truth" in this context refers to the measured concentration of direct bilirubin, which is established by established laboratory methods, standard reference materials, and comparison to a predicate device, rather than expert interpretation of images or clinical cases.

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

This information is not applicable. Adjudication methods like 2+1 or 3+1 are typically used in studies involving subjective interpretation (e.g., medical imaging interpretation) where multiple readers assess cases and discrepancies are resolved by a super-reader. For a quantitative diagnostic assay, the "ground truth" is determined by objective measurement rather than expert consensus on subjective findings.

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

This information is not applicable. The device is an in vitro diagnostic assay, not an AI-assisted diagnostic tool that would involve human readers interpreting cases. Therefore, an MRMC study or evaluation of human reader improvement with AI assistance is not relevant to this submission.

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

The device is a standalone in vitro diagnostic assay. Its performance is measured independently of human interpretation in the clinical setting, although laboratory personnel operate the analyzer and interpret the numerical results in the context of a patient's overall clinical picture. The studies described (Precision, Reproducibility, Assay Comparison, Specimen Equivalency, Interferences) all reflect the standalone performance of the assay on the Atellica CH Analyzer.

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

The "ground truth" for this device's performance studies is established by:

• Reference Methods/Predicate Device: The "Assay Comparison" section uses the Wako Direct Bilirubin V assay as the comparative method.
• Internal Reference Standards: The assay's traceability is to internal reference standards manufactured by gravimetric methods.
• Control Samples/Spiking: For precision, reproducibility, and interference studies, samples are prepared with known concentrations of analyte or interferents.

8. The sample size for the training set:

This information is not provided in the document. This type of detail is typically associated with machine learning or AI algorithm development, which is not the primary focus of this in vitro diagnostic device submission. The device involves a chemical reaction and photometric measurement, not a "training set" in the machine learning sense.

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

This information is not provided and is not applicable as the device does not involve a "training set" in the context of machine learning. The assay mechanism is based on a defined chemical reaction (diazo colorimetry) rather than a trained algorithm.

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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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Rx Only For in vitro diagnostic use only

The TBIL test within the VITROS XT Chemistry Products TBIL-ALKP Slides quantitatively measure total bilirubin (TBIL) concentration in serum and plasma using VITROS XT 7600 Integrated Systems. Measurements of the levels of bilirubin, an organic compound formed during the normal destruction of red blood cells, are used in the diagnosis and treatment of liver, hematological and metabolic disorders, including hepatitis and gall bladder block.

The ALKP test within the VITROS XT Chemistry Products TBIL-ALKP Slides quantitatively measure alkaline phosphatase (ALKP) activity in serum and plasma using VITROS XT 7600 Integrated Systems. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Not Found

This is an FDA 510(k) clearance letter for an in vitro diagnostic (IVD) device, specifically for VITROS XT Chemistry Products TBIL-ALKP Slides. The provided text is a regulatory communication and does not contain the acceptance criteria or study details for the device's performance.

To answer your request, I would need access to the actual 510(k) summary, often referred to as a "510(k) Premarket Notification." This document typically includes the performance data, acceptance criteria, and study designs to demonstrate substantial equivalence to a predicate device.

The information you've provided only states:

• Device Name: VITROS XT Chemistry Products TBIL-ALKP Slides
• Intended Use: Quantitative measurement of total bilirubin (TBIL) and alkaline phosphatase (ALKP) in serum and plasma using VITROS XT 7600 Integrated Systems.
• Regulatory Class: Class II
• Product Code: CIG (Bilirubin (total or direct) test system), CJE (Alkaline phosphatase test system)
• Date of Clearance: April 26, 2019

Without the 510(k) summary or a similar technical document, I cannot extract the specific acceptance criteria, study details, sample sizes, or ground truth information you've requested.

Therefore, I cannot provide the requested table and study details based solely on the provided text.

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1. VITROS Chemistry Products CRBM Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products CRBM Slides quantitatively measure carbamazepine (CRBM) concentration in serum and plasma using VITROS 250/350/950/5.1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Measurements obtained are used in monitoring levels of carbamazepine to help ensure appropriate therapy.
2. VITROS Chemistry Products CREA Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Product CREA Slides quantitatively measure creatinine (CREA) concentration in serum, plasma, and urine using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
3. VITROS Chemistry Products TBIL Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products TBIL Slides quantitatively measure total bilirubin (TBIL) concentration in serum and plasma using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Measurements of the levels of bilirubin are used in the diagnosis and treatment of liver, hematological and metabolic disorders, including hepatitis and gall bladder block.
4. VITROS XT 7600 Integrated System: Rx Only. For in vitro diagnostic use only. The VITROS XT 7600 Integrated System is intended for use in the measurement of a variety of analytes of clinical interest.

The VITROS XT 7600 Integrated System is a fully automated, computer controlled, clinical chemistry and immunodiagnostic analyzer intended for the in vitro determination of a variety of general chemistries, therapeutic drugs, drugs of abuse, proteins, infectious diseases, as well as cardiac, metabolic, thyroid, anemia, and oncology markers in biological fluids such as serum, plasma, urine and cerebral spinal fluid. The System operates in conjunction with reagents, calibrators and controls designed for use with the System in the MicroSlide, MicroTip or MicroWell format.

The VITROS Chemistry MicroSlide range of products (in this case VITROS Chemistry Products CRBM Slides, VITROS Chemistry Products CREA Slides, and VITROS Chemistry Products TBIL Slides), are combined with the VITROS XT 7600 Integrated System to perform the VITROS CRBM, CREA, and TBIL assays.

The document describes the performance of the VITROS Chemistry Products CRBM Slides, VITROS Chemistry Products CREA Slides, VITROS Chemistry Products TBIL Slides, and the VITROS XT 7600 Integrated System. The main purpose of the study is to demonstrate substantial equivalence to legally marketed predicate devices.

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

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state acceptance criteria in a dedicated table format for each performance metric, but rather describes how results were evaluated in the "Specificity" section and implies acceptance based on the comparison to predicate devices and established guidelines. For the method comparison, precision, linearity, and detection limits, the "reported device performance" is the direct result of the testing.

Given the nature of the submission (510(k) for substantial equivalence in an in-vitro diagnostic device), the acceptance criteria would typically revolve around demonstrating comparable performance to the predicate devices and adherence to established clinical laboratory standards (CLSI guidelines).

Below is a table summarizing the reported performance, with implied acceptance criteria based on standard practices for demonstrating substantial equivalence for in-vitro diagnostic devices.

Table of Acceptance Criteria and Reported Device Performance

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

• Method Comparison Test Set:

  • CRBM: 118 human serum samples.
  • CREA: 116 human serum samples and 122 human urine samples.
  • TBIL: 125 human serum samples.
  • Data Provenance: The document states "human serum samples" and "human urine samples," implying these are clinical samples. The country of origin and whether the data is retrospective or prospective is not specified.

• Precision Test Set: For each assay (CRBM, CREA serum, CREA urine, TBIL), the study involved:

  • 80 replicates (N=80) for each of the multiple fluid levels (e.g., 6 for CRBM, 6 for CREA serum, 6 for CREA urine, 5 for TBIL). The total number of analyses is much higher (e.g., 80 replicates x 6 levels = 480 for CRBM).
  • The samples used were Quality Control fluids and human-based precision fluids.
  • Data Provenance: Not specified.

• Linearity Test Set: A series of eleven proportionally related admixtures of low and high test fluids. Each sample was tested in triplicate.

  • Data Provenance: Not specified.

• Detection Limits (LoB, LoD, LoQ) Test Set:

  • LoB: 4 blank samples, tested in replicates of 6 over 3 days, using 3 lots of reagents, 4 samples every day, for a total of 216 observations (72 results per reagent lot).
  • LoD: 4 pools of human samples with analyte concentrations close to the expected detection limit, tested in replicates of 6 over 3 days, using 3 lots of reagents, with the 4 human sample pools every day, for a total of 216 observations (72 results per reagent lot).
  • LoQ: 4 pools of low level samples, tested in replicates of 4 over 3 days, using 3 lots of reagents, 4 samples every day, for a total of 144 observations (48 results per reagent lot).
  • Data Provenance: The LoD and LoQ studies used "human samples." The country of origin and whether the data is retrospective or prospective is not specified.

• Specificity (Interference) Test Set: Chemical interferents, common chemical substances, and claimed non-interferents, including hemoglobin, bilirubin, and intralipid. Testing employed "paired-difference" assessment at a minimum of two analyte levels.

  • Data Provenance: Not specified.

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

This device measures quantitative concentrations of specific analytes (Carbamazepine, Creatinine, Total Bilirubin). Ground truth for these types of in vitro diagnostic devices usually refers to the reference method (predicate device in this case) or a highly accurate reference standard rather than expert interpretation in the way it applies to image analysis or clinical diagnosis. The document does not mention human experts establishing ground truth in the context of radiologists or similar clinical diagnosticians. The ground truth for the method comparison study was established by the predicate device, VITROS 5600 Integrated System.

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

None mentioned. Adjudication methods are typically used when there's a subjective element to ground truth establishment, often involving multiple human readers for diagnostic image interpretation. For quantitative measurements in clinical chemistry, the "truth" is established by reference methods, precision, and linearity studies, not by human adjudication of results.

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

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that involve human interpretation, particularly in radiology or pathology, and often involves AI assistance. This document describes an automated in-vitro diagnostic device for quantitative chemical measurements, where human interpretation of results is direct measurement rather than subjective assessment. Therefore, the concept of "human readers improving with AI assistance" is not applicable here.

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

Yes, the studies described are, in essence, standalone performance evaluations of the VITROS XT 7600 Integrated System itself, with the VITROS Chemistry Products slides, operating automatically without continuous human intervention during the measurement process. The system performs the tests, generates results, and its performance (method comparison, precision, linearity, detection limits, specificity) is evaluated. The comparison is against a predicate device, which is also an automated system.

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

The ground truth for the test set, especially for the method comparison, was established by comparison to the legally marketed predicate device (VITROS 5600 Integrated System), which itself would have been previously cleared based on demonstrating accuracy against established reference methods or accepted gold standards for each analyte. For precision, linearity, and detection limits, the ground truth is established by the known characteristics of reference materials and statistical analysis.

8. The sample size for the training set

The document does not mention a training set. This is because the device described is not an AI/ML-based diagnostic algorithm that learns from data. It is a traditional in-vitro diagnostic instrument with chemical reagent slides. The studies are validation studies for the performance of the integrated system, not for training an algorithm.

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

Since there is no training set mentioned or used for this type of device, this question is not applicable.

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ELITech Clinical Systems BILIRUBIN TOTAL 4+1 is intended for the quantitative in vitro diagnostic determination of total bilirubin in human serum and plasma on ELITech Clinical Systems Selectra Pro Series Analyzers.

ELITech Clinical Systems BILIRUBIN DIRECT 4+1 is intended for the quantitative in vitro diagnostic determination of direct bilirubin in human serum and plasma on ELITech Clinical Systems Selectra Pro Series Analyzers.

It is not intended for use in Point of Care settings.

Measurements of the levels of bilirubin (direct or total), an organic compound formed during the normal and abnormal distruction of red blood cells, are used in the diagnosis and treatment of liver, hematological, and metabolic disorders, including hepatitis and gall bladder block.

ELITech Clinical Systems BILIRUBIN TOTAL 4+1 and ELITech Clinical Systems BILIRUBIN DIRECT 4+1 are available as a kit only. Each kit consists of a bi-reagent R1 & R2.

ELITech Clinical Systems BILIRUBIN TOTAL 4+1:
Reagent 1: R1 Sulphanilic acid 29 mmol/L, Cetrimide 29 mmol/L.
Reagent 2: R2 Sodium nitrite 11 mmol/L.

ELITech Clinical Systems BILIRUBIN DIRECT 4+1:
Reagent 1: R1 Sulphanilic acid 29 mmol/L,
Reagent 2: R2 Sodium nitrite 11 mmol/L.

The document describes the analytical performance and comparison studies for the ELITech Clinical Systems BILIRUBIN TOTAL 4+1 and ELITech Clinical Systems BILIRUBIN DIRECT 4+1 devices. These devices are intended for the quantitative in vitro diagnostic determination of total and direct bilirubin, respectively, in human serum and plasma. The studies aim to demonstrate substantial equivalence to predicate devices (ABX Pentra Bilirubin, Total CP & ABX Pentra Bilirubin, Direct CP).

Here's the breakdown of the information based on your request:

1. Table of Acceptance Criteria and Reported Device Performance

For ELITech Clinical Systems BILIRUBIN TOTAL 4+1:

For ELITech Clinical Systems BILIRUBIN DIRECT 4+1:

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

• Precision (Test Set):

  • Sample Size: 80 measurements for each of 3 levels of samples (total 240 measurements per device) per instrument (2 instruments used).
  • Data Provenance: Not explicitly stated (e.g., country of origin). The samples are referred to as "samples" or "patient samples." The study was prospective in the sense that controlled experiments were performed to gather data for precision.

• Linearity (Test Set):

  • ELITech Clinical Systems BILIRUBIN TOTAL 4+1: 11 levels of mixed samples.
  • ELITech Clinical Systems BILIRUBIN DIRECT 4+1: 11 levels of mixed samples.
  • Data Provenance: Not explicitly stated. Likely prepared in a laboratory setting.

• Detection Limit (Test Set):

  • Sample Size: 15 measurements of 4 samples for each device.
  • Data Provenance: Prepared from patient samples and diluted with Albumin 6 g/dL - NaCl 0.9 %.

• Interference (Test Set):

  • Sample Size: For each potential interferent, 2 serum sample pools (low and high concentration), with aliquots spiked at various interferent concentrations (9 or 7 or 8 different concentrations). Each point was measured in triplicate per run. Two levels of control were also tested. A control sample was prepared from the sample pool diluted in appropriate diluent.
  • Data Provenance: "Serum sample pools." Not explicitly stated.

• Method Comparison (Test Set):

  • Sample Size: 100 serum patient samples for each device.
  • Data Provenance: "Serum patient samples." Not explicitly stated, but likely from a clinical laboratory or hospital in the country where the studies were conducted (France or USA, as these are locations given for the submitter and contact person). The study was likely prospective in nature for collecting these samples for comparison against the predicate.

• Matrix Comparison (Test Set):

  • Sample Size: 40 plasma patients (lithium heparin samples) for each device.
  • Data Provenance: "Plasma patients." Not explicitly stated. Likely from a clinical laboratory or hospital.

3. 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 (quantitative measurement of bilirubin), the "ground truth" is typically established by reference methods or comparison to legally marketed predicate devices, not by expert interpretation. The predicate devices are considered the "ground truth" for the method comparison studies. The document implicitly uses the performance of the legally marketed predicate device (ABX Pentra Bilirubin, Total CP & ABX Pentra Bilirubin, Direct CP) as the standard against which the new device's performance is compared for substantial equivalence.

There is no mention of experts establishing ground truth in the traditional sense of medical imaging or clinical diagnosis.

4. Adjudication Method for the Test Set

Not applicable. This is an in vitro diagnostic device performing quantitative measurements, not an AI or imaging device requiring human adjudication of results. The performance is assessed by comparing quantitative results against reference or predicate methods.

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

No, an MRMC comparative effectiveness study was not done. This type of study is typically for imaging devices where human readers interpret medical images with and without AI assistance. The described device is an in vitro diagnostic assay.

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

Yes, the studies described are standalone performance evaluations of the device (reagents on an analyzer). The device itself (the reagent system) functions as an "algorithm only" in the sense that it performs the chemical reaction and measurement without human interpretive input for each test result. Clinical laboratory technologists would operate the analyzer and interpret the numerical results, but the analytical performance described is the device's intrinsic capability.

7. The Type of Ground Truth Used

The primary ground truth for demonstrating substantial equivalence is the performance of the legally marketed predicate devices (ABX Pentra Bilirubin, Total CP & ABX Pentra Bilirubin, Direct CP). In the method comparison studies, the results from the new devices are compared against the results from the predicate devices using patient samples.

Additionally, for analytical performance like linearity, detection limit, and interference, the "ground truth" for evaluating the performance of the device is based on prepared samples with known concentrations or expected behaviors (e.g., spiked samples with interferents, serially diluted samples).

8. The Sample Size for the Training Set

Not applicable. This device is an in vitro diagnostic reagent system, not an AI/ML-based device that requires a "training set" in the computational sense. Its performance is based on chemical reactions and instrumental measurements, which are validated through analytical studies.

9. 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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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 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.

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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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