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The Yumizen H2500 is a quantitative multiparameter fully automated hematology analyzer intended for in-vitro diagnostic use in clinical laboratories by qualified healthcare professionals for the screening of patient populations.

The Yumizen H2500 is intended to perform tests on the following specimens:

• Anticoagulated whole blood specimens ●
• Body fluids (synovial fluids, serous fluids and cerebrospinal fluids). .

The Yumizen H2500 classifies and enumerates the following parameters:

• A complete blood count (CBC) consisting of TNC, WBC, RBC, HGB, calculated . HCT, MCV, calculated MCH, calculated MCHC, RDW-SD, RDW-CV, PLT, PLT-Ox, LPF, MPV.
• A leukocyte differential count consisting of LYM (%#), MON (%#), NEU (%/#), ● EOS (%/#), BAS (%/#), IMG (%/#)
• A nucleated red blood cell count consisting of NRBC (%/#). ●
• A reticulocyte analysis consisting of RET (%/#), calculated CRC, IRF, RHCC. ●
• Quantitative determination of blood cells in synovial fluids, serous fluids and . cerebrospinal fluids consisting of BFWBC, BFRBC, BFPN (%/#), BFMN (%/#).

Note: Venous and capillary whole blood should be collected in K2EDTA anticoagulant. Serous and synovial fluids should be collected without anticoagulant or in K2EDTA anticoagulant to prevent clotting of fluid. The use of anticoagulants with cerebrospinal fluid specimens is neither required nor recommended. Alternatively, Sodium Heparin or Lithium Heparin may be used for synovial fluid.

The HORIBA Medical analyzer modules Yumizen H2500 are multi-parameter hematology analyzers intended to perform tests on whole blood samples collected in K2EDTA and body fluids (synovial and serous) collected in K2EDTA anticoaqulant. The analyzers can also perform tests on cerebrospinal fluids which should not be collected in any anticoaqulant.

The Analyzer Units (Yumizen H2500) aspirate, dilute, mix, and analyze blood and body fluid samples.

The Yumizen H2500 model provides Complete Blood Count (CBC), Differential (DIFF), Reticulocyte counts (RET) and Optical Platelet counts as well as Body Fluid counts (BF).

The analyzer models may function with:

• · a Data Management Unit (Yumizen P8000) which is the interface with the laboratory connections (LIS) and the Analyzer Unit(s). Through its interface, the Yumizen P8000 enables the user to monitor the workflow of patient data, centralize result data, perform reflex testing, customize rules, centralize the validation operations, run quality control, manage quality assurance on results.

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

Since specific acceptance criteria values were not explicitly stated for all performance aspects, I will infer them as generally "met predefined acceptance criteria" or "demonstrated comparable performance" where stated in the document.

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

• Repeatability:
  • Whole Blood: 116 residual K2EDTA whole blood samples (mixed normal and contrived for extremes) used for within-run repeatability.
  • Body Fluid: 87 residual body fluid samples (Synovial, Serous and Cerebrospinal Fluids) (mixed normal and contrived for extremes) used for within-run repeatability.
  • Provenance: Retrospective, samples around medical decision levels or contrived to cover analytical measuring range. Collected from multiple sites (4 test sites for whole blood, 4 test sites for body fluid). Country of origin is not explicitly stated beyond "4 test sites" which include "2 US sites and 2 European sites" for some studies, implying data from both regions.
• Reproducibility:
  • Whole Blood: Three levels of control material (ABX Difftrol and ABX Minotrol Retic) run in duplicate twice a day for a minimum of 20 days (total 320 runs per level for each parameter if 4 sites and 2 runs/day * 20 days * 2 replicates * 2 instruments = 320 runs).
  • Body Fluids: Two levels of control material (BFTROL) run in duplicate twice a day for a minimum of 20 days (total 320 runs per level for each parameter).
  • Provenance: Control materials, conducted at 4 test sites (4 instruments, one per site).
• Linearity:
  • Whole Blood: Minimum of seven concentration levels (commercial or prepared from dilutions) for each parameter. Each level tested in a minimum of 4 replicates on 2 instruments using 2 reagent lots.
  • Body Fluids: Mimimum of seven concentration levels (prepared from dilutions) for each parameter. Each level tested in a minimum of 4 replicates on 2 instruments using 2 reagent lots.
  • Provenance: One test site (for both whole blood and body fluids).
• Interferences:
  • Whole Blood: Two concentration levels of interferent (Hemoglobin, Lipemia, Bilirubin, Glucose, Yeast) for direct interference. A subset of samples from the method comparison study (unique, native whole blood specimens identified with potential interference analysis, minimum of 17 specimens per interferent) for intrinsic interferences.
  • Body Fluids: Two concentration levels of interferent (Hemoglobin, Lipemia, Bilirubin, Total Protein, Yeast) for direct interference. A subset of samples from the method comparison study (unique, native body fluid specimens identified with potential interferents) for intrinsic interferences.
  • Provenance: 4 test sites (for both whole blood and body fluids).
• Stability:
  • Whole Blood: 14 whole venous blood specimens.
  • Body Fluid: 28 body fluid specimens (13 serous, 7 synovial, and 8 cerebrospinal fluids).
  • Provenance: 3 test sites for whole blood, 2 test sites for body fluid.
• Detection Limits (LoB, LoD, LoQ):
  • Six blank samples, six low concentration samples (for LoD), at least four low concentration samples (for LoQ). Each sample run 10 repeated times.
  • Provenance: Not specified beyond "different analyzers" and "two different reagent lots".
• Carry-over:
  • High and low target value samples run consecutively (3 high, 3 low) for each parameter. Three sets of carry-over sequences.
  • Provenance: One test site, three analyzers.
• Method Comparison:
  • Whole Blood: 969 venous and/or capillary specimens (pediatric (≤21 years) and adult). 143 with known medical conditions. Maximum 10% contrived.
  • Body Fluids: 427 residual body fluid specimens (pediatric (≤21 years) and adult) - 174 synovial, 138 serous, 115 CSF.
  • Provenance: 4 clinical sites (2 US sites and 2 European sites for whole blood); 3 clinical sites (2 US sites and 1 European site for body fluids). Mostly retrospective (leftover specimens).
• Matrix Comparison (Comparability between sampling types):
  • 84 normal and pathological paired capillary and venous whole blood specimens.
  • Provenance: One clinical site. Prospective collection.
• Matrix Comparison (Comparability between body fluid anticoagulants):
  • Synovial fluid: 9 without anticoagulant, 39 with K2EDTA, 92 with Lithium Heparin, 34 with Sodium Heparin.
  • Serous fluid: 82 without anticoagulant, 56 with K2EDTA.
  • Provenance: 3 clinical sites.
• Matrix Comparison (Comparability between analytical modes):
  • DIR vs DIF: 166 normal and pathological residual whole blood specimens.
  • RBC_PLTO vs DIF: 172 normal and pathological residual whole blood specimens.
  • DIF_LV vs DIF: 187 normal and pathological residual whole blood specimens.
  • Provenance: One clinical site for each comparison.
• Matrix Comparison (Comparability mode to mode):
  • 83 normal and pathological residual whole blood samples. (Automatic rack mode vs manual STAT mode).
  • Provenance: One clinical site.
• Clinical Sensitivity:
  • 456 residual normal and abnormal whole blood samples (from method comparison study).
  • Provenance: 4 clinical sites.
• Expected Values/Reference Range:
  • Adult Whole Blood: 240 apparently healthy adults (120 male, 120 female).
  • Pediatric Whole Blood: At least 80 apparently healthy neonates, infants, children, and adolescents (

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Yumizen C1200 Creatinine PAP reagent is intended for the quantitative in vitro diagnostic determination of Creatinine in human serum, plasma and urine based on an enzymatic method using a multi- step approach ending with a photometric end-point reaction. 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.

Yumizen C1200 Creatinine PAP reagent is intended for the quantitative in vitro diagnostic determination of Creatinine in human serum, plasma and urine based on an enzymatic method using a multi- step approach ending with a photometric end-point reaction.

The Horiba ABX SAS Yumizen C1200 Creatinine PAP device is an in vitro diagnostic intended for the quantitative determination of Creatinine in human serum, plasma, and urine. Its performance was evaluated through various analytical studies to demonstrate substantial equivalence to its predicate device, the ABX Pentra Enzymatic Creatinine CP.

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

1. Table of Acceptance Criteria and Reported Device Performance

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

• Measuring Range:
  • Limit of detection and quantitation: Determined according to CLSI guideline EP17-A2. (Specific sample size not provided in the summary but typically involves multiple replicates of low-concentration samples).
  • Linearity: Determined according to CLSI guideline EP06-A. (Specific sample size not provided in the summary but involves multiple concentrations with replicates).
• Accuracy and Precision:
  • Instrument Variability (Serum/Plasma & Urine): 240 measurements (20x2x2 means 20 replicates for each of 3 samples, on 2 runs for 2 instruments over a certain period - or 20 days x 2 runs/day x 2 instruments). The samples were control materials and native samples.
  • Lot-to-Lot Variability (Serum/Plasma & Urine): 90 measurements (3x5x2x3 implies 3 lots, 5 days, 2 runs/day, 3 samples). The samples were control materials and native samples.
• Interferences: Not explicitly stated, but typically involves testing known concentrations of interferents in base samples.
• Matrix Comparison: 84 paired samples (serum and lithium heparin plasma) from single donors.
• Method Comparison:
  • Serum/Plasma: 103 native human serum samples. Data provenance: collected from CHU Nîmes (University Hospital Center). Retrospective (remnants).
  • Urine: 129 native human urine samples. Data provenance: collected from routine clinical laboratory. Retrospective (remnants).
• Reagent Stability: Determined according to CLSI guideline EP25-A. (Specific sample size not provided).
• Reference Range Verification:
  • Serum/Plasma - Men: 45 "normal samples" from a blood bank.
  • Serum/Plasma - Women: 41 "normal samples" from a blood bank.
  • Children & Urine: Verification could not be made due to lack of availability of samples from healthy pediatric patients/healthy people.

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

The document does not mention the use of experts to establish ground truth for this device, which is a quantitative in vitro diagnostic for creatinine levels. For such devices, ground truth is typically established by:

• A reference method (e.g., mass spectrometry) for accuracy studies.
• The established values of control materials.
• The results from a legally marketed predicate device (as seen in method comparison).
• Literature values for reference range verification.

4. Adjudication method for the test set

Not applicable. This is a quantitative diagnostic device, not one requiring expert 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

Not applicable. This is a quantitative diagnostic device, not an AI-assisted diagnostic imaging device requiring human reader interpretation. No MRMC study was performed.

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

This is a standalone in vitro diagnostic device (reagent and instrument system). Its performance described above (e.g., precision, accuracy, linearity, interference) represents the algorithm-only (device-only) performance, without human interpretation of the result influencing the quantitative output.

7. The type of ground truth used

• Measuring Range, Accuracy, Precision, Interferences, Reagent Stability: Internal specifications, established reference materials (controls), and recognized scientific methods (e.g., spiked samples for linearity and interference).
• Matrix Comparison: Paired samples from the same donor, with comparison between results from serum and plasma. The expectation is that the creatinine value should be the same across matrices for the same individual.
• Method Comparison: The predicate device's results (ABX Pentra Enzymatic Creatinine CP) served as the reference for comparison using method comparison studies (Passing Bablok regression).
• Reference Range Verification: Reference ranges cited in scientific literature (e.g., Mazzachi BC et al., Schlebusch Soldin SJ et al., Roberts WL et al.) were used for verification against measured values in "normal" samples.

8. The sample size for the training set

The document describes performance evaluation studies (validation) rather than a clear "training set" for an algorithm. For a device like this, the "training" usually refers to the development and optimization of the reagent formulation and instrument parameters. The specific sample sizes used for this developmental phase are not detailed in the summary. The provided sample sizes are for the analytical performance studies which are typically considered validation.

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

As there isn't a "training set" in the context of machine learning, this question isn't directly applicable. For the development of an IVD like this, ground truth would be established during the R&D phase through:

• Using purified creatinine standards.
• Comparison with established and highly accurate reference methods (e.g., isotope dilution mass spectrometry, IDMS).
• Clinical samples with results from well-characterized, clinically accepted methods.

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Yumizen C1200 Immunoglobulin A reagent is intended for the quantitative in vitro diagnostic determination of Immunoglobulin A (IgA) in serum and lithium heparin plasma by immunoturbidimetry on Yumizen analyzers.Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. This test should be used in conjunction with other findings,

Yumizen C1200 Immunoglobulin G reagent is intended for the quantitative in vitro diagnostic determination of Immunoglobulin G (IgG) in serum and lithium heparin plasma by immunoturbidimetry on Yumizen analyzers.Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. This test should be used in conjunction with other findings.

Yumizen C1200 Immunoglobulin M reagent is intended for the quantitative in vitro diagnostic determination of Immunoglobulin M (IgM) in serum and lithium heparin plasma by immunoturbidimetry on Yumizen analyzers. Measurement of this immunoglobulin aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

This test should be used in conjunction with other laboratory and clinical findings.

This submission consists in the Yumizen C1200 Immunoglobulin A (1300023881), Yumizen C1200 Immunoglobulin G (1300023883) and Yumizen C1200 Immunoglobulin M (1300023884) reagent for serum and plasma testing for Yumizen C1200 reagent.

The Yumizen C1200 Level 1 Protein Control (1300023944) and Yumizen C1200 Level 2 Protein Control (1300023945) for use on Yumizen C1200 Analyzer and the Yumizen C1200 Protein Cal (1300023893) for use on Yumizen C1200 Analyzer are sold separately.

This document describes the analytical performance characteristics of the Yumizen C1200 Immunoglobulin A, G, and M reagents, intended for quantitative in vitro diagnostic determination of immunoglobulins in serum and lithium heparin plasma. The study aims to demonstrate that the device meets acceptance criteria for various analytical parameters, ensuring its safety and effectiveness.

1. Table of Acceptance Criteria and Reported Device Performance

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

• Measuring Range (Linearity):
  • IgA, IgG, IgM: Samples were "spiked" to create different concentrations, then serially diluted. The exact number of initial samples for spiking is not specified, but dilutions were "assayed in quadruplicate within a single run."
• Precision (Total Precision: analyzer variability - 20x2x2 study):
  • IgA, IgG, IgM: 5 human sera samples and 2 levels of Yumizen C1200 Protein Control. Tested with "two replicates per run, two runs per day for 20 days on each of three analyzers" (n=240 per sample).
• Precision (Lot to Lot variability study: 3x5x2x3):
  • IgA, IgG, IgM: 5 human sera samples and 2 levels of Yumizen C1200 Protein Control. Tested in "triplicates per run, two runs per day for five days on each of three lots" (n=90 per sample).
• Interferences: The exact sample size is not stated, but the study implies testing samples with varying concentrations of interfering substances to determine acceptable bias.
• Matrix Comparison:
  • IgA: 62 paired samples (serum and heparinized plasma) from single donors.
  • IgG: 45 paired samples (serum and heparinized plasma) from single donors. Of these, 43 were used for correlation analysis.
  • IgM: 43 paired samples (serum and heparinized plasma) from single donors.
• Method Comparison:
  • IgA: 190 "native samples" from human serum.
  • IgG: 214 "native samples" from human serum.
  • IgM: 153 "native samples" from human serum.

Data Provenance: The human serum samples used for precision, matrix comparison, and method comparison studies were "anonymous remnants of human serum specimens collected from blood bank." "Spiked" samples were used for linearity studies, and "normal samples" from a blood bank were used for reference range verification. The document does not explicitly state the country of origin, but the manufacturer is based in France. The studies appear to be prospective analytical performance evaluations.

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

No external experts are mentioned for establishing ground truth in these analytical performance studies. The studies rely on established CLSI guidelines for evaluation and comparison with a legally marketed predicate device. The ground truth for quantitative measurements is the direct measurement by the devices themselves and comparison against predicate devices or known spiked concentrations.

4. Adjudication Method for the Test Set

Not applicable. These are analytical performance studies for an in vitro diagnostic device, not studies involving human interpretation or adjudication.

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

No. This document describes the analytical performance of an in vitro diagnostic reagent and analyzer system, not a device requiring human interpretation for diagnostic purposes where MRMC studies would typically be conducted.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, this can be considered a standalone performance study. The Yumizen C1200 system (reagents and analyzer) performs the quantitative determination of immunoglobulins. The studies evaluate the analytical capabilities of the system itself, such as accuracy (via method comparison, linearity), precision, interference, and stability, without direct human intervention in the result generation or diagnostic interpretation loop. The intent is to demonstrate the device's ability to accurately measure predefined analytes.

7. Type of Ground Truth Used

The ground truth for these analytical performance studies is established through:

• Known concentrations: For linearity studies, spiked samples with known concentrations were used.
• Predicate device measurements: For method comparison, results from the candidate device were compared against measurements obtained from legally marketed predicate devices (Beckman Coulter's Olympus IgA, IgG, IgM reagents on AU analyzers).
• CLSI guidelines and established methodologies: The studies adhere to CLSI guidelines (e.g., EP05-A3 for precision, EP17-A2 for detection capability, EP06-A for linearity, EP25-A for stability, C28-A3 for reference intervals, EP-9A3 for method comparison) which define accepted methods for evaluating analytical performance and establishing performance characteristics.
• Literature-established reference ranges: For reference range verification, the device's measurements on "normal" samples were compared against ranges cited in scientific literature (e.g., Dati et al., 1996).

8. Sample Size for the Training Set

The document does not explicitly delineate a "training set" in the context of machine learning or AI models. This device is an in vitro diagnostic reagent and analyzer system, not an AI/ML-based diagnostic algorithm that typically undergoes a distinct training phase with a dedicated dataset. The performance studies described here are for analytical validation rather than algorithm training.

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

Not applicable, as there is no mention of a "training set" in the context of an AI/ML model for this in vitro diagnostic device. The analytical evaluations described involve testing the reagent and instrument system, not training a learning algorithm.

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Yumizen C1200 CRP reagent is intended for the quantitative in vitro diagnostic determination of the C-reactive protein in human serum and lithium heparin plased on an immunoturbidimetric assay. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues and for evaluation of infections, tissue injury and inflammatory disorders. This test should be used in conjunction with other laboratory and clinical findings.

Yumizen C1200 CRP (Licensed for USP6, 248, 597/ USP6, 828, 158 and equivalent patents in other countries) is a latex-enhanced immunoturbidimetric assay developed to accurately measure CRP levels in serum and plasma samples for conventional CRP ranges.

When an antigen-antibody reaction occurs between CRP in a sample and anti-CRP antibody which has been sensitized to latex particles, agglutination results. This agglutination is detected as an absorbance change, with the magnitude of the change being proportional to the quantity of CRP in the sample. The actual concentration is then determined by interpolation from a calibration curve prepared from calibrators of known concentration.

Reagents Yumizen C1200 CRP is ready-to-use.

Reagent 1: Buffer solution: Glycine buffer solution Reagent 2: Latex suspension: 0.20% w/v suspension of latex particles sensitized with anti-CRP antibodies (rabbit)

After measurements are taken, reagent cassettes should remain in the refrigerated tray.

Care should be taken not to interchange the caps with others cassettes.

Reagents with different lot numbers should not be interchanged or mixed.

This submission consists of the Yumizen C1200 CRP (1300023877) reagent for serum and plasma testing for Yumizen C1200 reagent CRP, the submission includes the controls Yumizen C1200 Level 1 Protein Control (1300023944) and Yumizen C1200 Level 2 Protein Control (1300023945) for use on Yumizen C1200 Analyzer. The submission for Yumizen C1200 reagent CRP also includes the corresponding calibrator Yumizen C1200 CRP Cal (1300023899) for use on Yumizen C1200 Analyzer.

The acceptance criteria and study proving the device meets them are detailed below for the Yumizen C1200 CRP reagent.

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

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Yumizen C1200 Ferritin reagent is intended for the quantitative in vitro diagnostic determination of Ferritin in human serum by latex-enhanced immunoturbidimetric assay. Measurements of ferritin aid in the diagnosis of diseases affecting iron metabolism, hemochromatosis (iron overload) and iron deficiency anemia.

Yumizen C1200 Transferrin reagent is intended for the quantitative in vitro diagnostic determination of transferrin in human serum and lithium heparin plasma by turbidimetry.

Measurement of transferrin levels ads in the diagnosis of malnutrition, acute inflammation, infection, and iron deficiency anemia.

Yumizen C1200 Rheumatoid Factor reagent is intended for the quantitative in vitro diagnostic determination of rheumatoid factor in human serum by latex-enhanced immunoturbidimetric assay. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis.

Not Found

The document describes the analytical performance characteristics of three devices: Yumizen C1200 Ferritin, Yumizen C1200 Transferrin, and Yumizen C1200 Rheumatoid Factor. Each device is intended for the quantitative in vitro diagnostic determination of specific substances in human serum, and sometimes plasma, using immunoturbidimetric or turbidimetric assays.

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

Yumizen C1200 Ferritin

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Size and Data Provenance (for test set)

• Measuring Range, Precision, Interferences, Prozone/Antigen Excess: Not explicitly stated as "test set" in the context of supervised learning, but these are analytical performance studies. Samples used for precision studies include 240 replicates for analyzer variability and 90 replicates for lot-to-lot variability (for each sample/control). The samples are clinical samples or controls, but the origin (country, retrospective/prospective) is not specified beyond "human serum specimens".
• Method Comparison: 103 native sera samples. Origin: "Anonymous remnants of human serum specimens collected from blood bank." Retrospective.
• Reference Range: Women: 50 "normal samples". Men: 95 "normal samples". Origin: "blood bank." Retrospective.

3. Number of experts and qualifications (for ground truth)

• Not applicable as this is an in vitro diagnostic device for quantitative measurement, not an AI evaluation requiring expert adjudication. Ground truth is instrument-derived or defined by reference methods/literature.

4. Adjudication method (for test set)

• Not applicable.

5. Multi Reader Multi Case (MRMC) comparative effectiveness study

• No, not applicable for this type of IVD device.

6. Standalone performance (algorithm only)

• Yes, the performance data presented is for the device operating in standalone mode (algorithm only) as a quantitative measurement system.

7. Type of ground truth used

• Analytical Performance (LOD, LOQ, Linearity, Precision, Interferences, Prozone/Antigen Excess): The "ground truth" is established through well-defined laboratory analytical methods and standards (CLSI guidelines EP17-A2, EP06-A, EP05-A3, EP07-A2). It relies on the accuracy of the reference materials and methods used in these studies.
• Method Comparison: Comparison against a legally marketed predicate device (Beckman Coulter Ferritin (OSR61203) [K092505]) is used as the reference, with correlation analysis.
• Reference Range: Verification against established literature references (e.g., TIETZ Textbook of Clinical Chemistry and Molecular Diagnostics).

8. Sample size for the training set

• Not applicable. This is not a machine learning model that requires a "training set" in that sense. The device's calibration curve establishment and internal parameters would be set by the manufacturer using validated reference materials and methodologies.

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

• Not applicable.

Yumizen C1200 Transferrin

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Size and Data Provenance (for test set)

• Measuring Range, Precision, Interferences, Prozone/Antigen Excess: Not explicitly stated as "test set" in the context of supervised learning, but these are analytical performance studies. Samples used for precision studies include 240 replicates for analyzer variability and 90 replicates for lot-to-lot variability (for each sample/control). The samples are clinical samples or controls, but the origin (country, retrospective/prospective) is not specified beyond "human serum/plasma".
• Method Comparison: 115 native samples. Origin: "Anonymous remnants of human serum specimens collected from CHU Nîmes (University Hospital Center)." Retrospective.
• Anticoagulant Study: 59 paired serum/plasma samples. Origin: "single donors." Not specified if retrospective or prospective.
• Reference Range: 85 "normal samples" (28 women + 57 men). Origin: "blood bank." Retrospective.

3. Number of experts and qualifications (for ground truth)

• Not applicable.

4. Adjudication method (for test set)

• Not applicable.

5. Multi Reader Multi Case (MRMC) comparative effectiveness study

• No, not applicable.

6. Standalone performance (algorithm only)

• Yes, the performance data presented is for the device operating in standalone mode (algorithm only).

7. Type of ground truth used

• Analytical Performance: Established through CLSI guidelines (EP17-A2, EP06-A, EP05-A3, EP07-A2).
• Method Comparison: Comparison against a legally marketed predicate device (Roche Diagnostics Transferrin Model :TRSF2 [K012393]).
• Reference Range: Verification against established literature references (e.g., Dati et al., Eur. J Clin Chem. Cli Biochem. 1996).

8. Sample size for the training set

• Not applicable.

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

• Not applicable.

Yumizen C1200 Rheumatoid Factor

1. Table of Acceptance Criteria and Reported Device Performance

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Yumizen C1200 CRP reagent is intended for use as a high sensitive assay for the quantitative in vitro diagnostic determination of the C-reactive protein in human serum and plasma based on an immunoturbidimetric assay. CRP is used to evaluate conditions thought to be associated with inflammation in otherwise healthy individuals.

Yumizen C1200 CRP reagent is intended for use as a high sensitive assay for the quantitative in vitro diagnostic determination of the C-reactive protein in human serum and plasma based on an immunoturbidimetric assay.

The provided text describes the analytical performance characteristics of the Yumizen C1200 CRP device, supporting its substantial equivalence claim for FDA 510(k) clearance.

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

1. Table of Acceptance Criteria and Reported Device Performance:

The document outlines various analytical performance characteristics (measuring range, accuracy, precision, interferences, matrix comparison, method comparison, and reagent stability) but does not explicitly state acceptance criteria in a single, dedicated table with pass/fail results. Instead, it presents the study methods and the results obtained, often followed by a statement indicating whether the results are "within specifications" or "appropriate." The acceptance criteria are implicitly defined by the chosen CLSI guidelines and the internal specifications of HORIBA Medical.

Based on the information provided, here's a table summarizing the reported device performance and the implicit acceptance as demonstrated by the study results:

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

• Measuring Range (Linearity): Not explicitly stated how many samples were used, but the method refers to CLSI EP06-A.

• Accuracy and Precision:

  • Serum: 240 measurements for each of 5 samples/controls (internal control, Sample 1-4) in both "calibration every week" and "calibration only at beginning" studies.
  • Heparin-Lithium: 20 measurements for each of 6 specimens.

• Interferences: Not explicitly stated how many samples were tested for each interfering substance, but the study method refers to CLSI EP07-A2.

• Matrix Comparison (Serum vs. Heparin-Lithium): 54 samples.

• Method Comparison (with comparator device): 138 native samples.

• Data Provenance:

  • The document states "Anonymous remnants of human serum specimens collected from routine clinical laboratory" for some studies (precision for lithium-heparin, method comparison). For the matrix comparison, it mentions "individual donors from blood bank (in serum and plasma for each donor)".
  • The studies appear to be retrospective as they use "remnants" and "collected" samples.
  • The country of origin is not explicitly stated, but the manufacturer (HORIBA ABX SAS) is based in Montpellier, France, suggesting the studies were likely conducted in France or a European context.

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

This device (Yumizen C1200 CRP) is an in vitro diagnostic device for quantitative measurement of C-reactive protein (CRP) in human serum and plasma. For such devices, ground truth is typically established by:

• Reference Methods: Highly accurate and precise laboratory methods (e.g., mass spectrometry, or comparison to a cleared predicate device).
• Certified Reference Materials: Samples with a known and certified concentration of the analyte.

The document does not mention the use of human experts (like radiologists for image analysis) to establish ground truth for the test set of this type of device. The accuracy and precision are determined by comparing results to expected values or reference materials, and the method comparison is done against a predicate device.

4. Adjudication Method for the Test Set:

Not applicable. As described above, for IVD devices like this, ground truth is established through analytical precision and accuracy, reference methods, and comparison against a predicate device, not through human reader adjudication like in imaging studies.

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

No. An MRMC study is relevant for diagnostic imaging AI systems where human readers interpret images. This device is a laboratory assay; therefore, MRMC studies are not applicable.

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

Yes, the entire analytical performance evaluation (measuring range, precision, interference, matrix comparison, method comparison, stability) describes the standalone performance of the Yumizen C1200 CRP device. This is typical for IVD devices where the result is generated solely by the analyzer and reagent system, without human interpretive input altering the result itself.

7. The Type of Ground Truth Used:

• Certified Reference Materials/Control Materials: Used for precision and accuracy studies (e.g., "Low CRP Control (internal control)").
• Native Patient Samples: Used for matrix comparison and method comparison studies (comparison against a predicate device).
• Spiked Samples: Used for interference studies (adding known interferents to samples).
• Reference Methods/Predicate Device: The predicate device (VITROS Chemistry Products hsCRP Reagent K160712) served as the comparative "ground truth" for method comparison and demonstrating substantial equivalence. The document explicitly states the method comparison was carried out using recommendations from CLSI EP-9A3 ("Measurement Procedure Comparison and Bias Estimation Using Patient Samples").

8. The Sample Size for the Training Set:

The document describes pre-market validation studies for a medical device submitted for 510(k) clearance. For traditional IVD devices (non-AI/ML based), there isn't typically a "training set" in the machine learning sense. The "training" of the device is inherent in its design, calibration, and manufacturing process. The studies described are validation and verification studies to demonstrate performance.

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

Not applicable, as there is no "training set" in the context of an AI/ML device for this traditional IVD product. The calibration curves for the device are established during the development phase using calibrator materials, which would have their values traceable to a higher-order reference method or standard. The document mentions "Yumizen C1200 CRPhs Cal" as the calibrator used, and its properties would be traceable to ensure accurate measurements.

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Yumizen C1200 ALP reagent is intended for the quantitative in vitro diagnostic determination of alkaline phosphatase in human serum and plasma based on a kinetic photometric test using p-Nitropherylphosphate. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Yumizen C1200 Albumin reagent is intended for the quantitative in vitro diagnostic determination of albumin in human serum and plasma by colorimetry. Albumin measurements are used in the diagnosis and treatment of numerous diseases involving primarily the liver or kidneys.

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The provided text describes analytical performance characteristics and comparison studies for two in vitro diagnostic reagents, Yumizen C1200 ALP and Yumizen C1200 Albumin, intended for use on the Yumizen C1200 clinical chemistry analyzer. The document is a 510(k) summary, demonstrating substantial equivalence to predicate devices.

Here's an analysis of the acceptance criteria and the studies performed, structured according to your request:

Acceptance Criteria and Reported Device Performance

For both assays, the acceptance criteria are implicitly defined by the successful demonstration of performance characteristics within established guidelines (CLSI) and comparison to their respective predicate devices. The "Results are within predefined acceptance criteria" statements affirm that the tested parameters met the company's internal benchmarks, which are aligned with industry standards for analytical performance.

Here's a table summarizing the reported device performance for key analytical characteristics:

Study Details:

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

   • Yumizen C1200 ALP:
     • Measuring Range/Linearity: Data not explicitly stated for individual samples, but the study showed linearity from 0 to 1620 U/L.
     • Precision: "Single site: 20x2x2" and "Multi site: 3x5x2x3". This notation often refers to runs x replicates x instrument/lots, but the exact number of unique "samples" (control and general) for precision is stated as N=240 for single site, and N=90 for multi-site across various levels (control and patient samples). The provenance of these samples is not specified (e.g., country of origin) but they are "control" or "patient" samples. It's an analytical performance study, not a clinical study on specific patient populations.
     • Interferences: Specific sample numbers for this study are not provided, but the tested interferent concentrations are listed.
     • Method Comparison: 165 native serum samples.
     • Matrix Comparison: 40 lithium-heparin plasma samples (individual donors).
   • Yumizen C1200 Albumin:
     • Measuring Range/Linearity: Data not explicitly stated for individual samples, but the study showed linearity from 0 to 60.2 g/L.
     • Precision: "Single site: 20x2x2" and "Multi site: 3x5x2x3". Again, N=240 for single site and N=90 for multi-site across various levels.
     • Interferences: Specific sample numbers for this study are not provided.
     • Method Comparison: 111 native serum samples.
     • Matrix Comparison: 70 lithium-heparin plasma samples (individual donors).
   • Data Provenance: The document does not specify the country of origin for the samples. The studies are described as analytical performance validations, which are typically retrospective using banked/collected samples. The term "native serum samples" and "individual donors" implies real patient samples.

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

   • This is an in vitro diagnostic device (measurement of lab analytes), not an imaging AI or diagnostic AI device where human experts establish "ground truth" in the typical sense of clinical interpretation.
   • The ground truth for the test set is established by the predicate devices (Roche Diagnostics ALP IFCC Gen2 on COBAS INTEGRA systems, and HORIBA ABX SAS ABX Pentra Albumin CP on ABX Pentra 400/Pentra C400) or by established analytical methods for measuring concentrations (e.g., gravimetric for linearity, standard additions for LoD/LoQ).
   • The "experts" involved are likely laboratory professionals, biochemists, and statisticians who design and execute these analytical validation studies according to CLSI (Clinical and Laboratory Standards Institute) guidelines. Their specific qualifications (e.g., MD, PhD) or number are not explicitly stated in this document but are assumed to be standard for medical device development.

3. Adjudication Method for the Test Set:

   • Not applicable in the context of analytical performance studies of laboratory reagents. Adjudication (e.g., 2+1, 3+1 consensus) is typical for clinical studies involving subjective interpretations (e.g., radiology reads). For a quantitative IVD, the "truth" is the measured value from a reference method or known concentration.

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

   • No, an MRMC study was not done. This type of study is relevant for diagnostic imaging interpretation or other scenarios where human readers make subjective judgments, and AI provides assistance. This document is for quantitative lab reagents, where the assessment is about the accuracy and precision of the measurement itself.

5. If a Standalone Performance Study Was Done:

   • Yes, the entire document describes standalone performance of the Yumizen C1200 ALP and Albumin reagents on the Yumizen C1200 analyzer. This is not an "algorithm only without human-in-the-loop" performance as the device itself is an integrated system of reagent, instrument, and software. "Standalone" in this context means the performance of the new device/reagent system as a complete unit, not in comparison to human interpretation.

6. The Type of Ground Truth Used:

   • External Reference Measurement: For method comparison studies, the "ground truth" is the result obtained from the legally marketed predicate device (Roche Diagnostics ALP IFCC Gen2 for ALP, and HORIBA ABX SAS ABX Pentra Albumin CP for Albumin).
   • Known Concentrations/Standards: For linearity, limit of detection/quantitation, and interference studies, the ground truth is established by preparing samples with known concentrations of analytes and/or interferents.
   • Consensus/Literature: For reference ranges, the ground truth is based on established bibliographic references and a verification study using "normal samples" from a blood bank.

7. The Sample Size for the Training Set:

   • This document describes the validation/test phase for regulatory submission (510(k)). It does not detail the training set used for the development of the reagents or the analyzer's measurement algorithms. For IVDs, the "training" analogous to machine learning often involves extensive R&D, chemical optimization, and instrument calibration development using a variety of samples, but these are not explicitly quantified in terms of a "training set" size in this regulatory summary.

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

   • As above, details about the "training set" are not provided. However, for the development of quantitative IVD assays, ground truth for initial development/training would typically be established through:
     • Primary Reference Methods: Highly accurate and precise methods (e.g., isotope-dilution mass spectrometry) for specific analytes, often used for calibrator assignment.
     • Certified Reference Materials: Materials with an assigned value and uncertainty for an analyte, traceable to recognized metrological standards.
     • Large Sample Cohorts: A diverse range of clinical samples (with values determined by established methods) to ensure robustness across different patient populations and disease states.
     • Experimental Design: Controlled experiments to characterize reagent stability, reaction kinetics, and potential interferents.

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Yumizen C1200 Calcium AS reagent is a diagnostic reagent for quantitative in vitro determination of calcium in human serum, plasma and urine based on colorimetric method, using the clinical chemistry analyzer. Measurement of calcium is used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).

Yumizen C1200 Creatinine Jaffé reagent is a diagnostic reagent for quantitative in vitro determination of Creatinine in human serum, plasma and urine based on a kinetic method using alkaline picrate (Jaffé method). 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.

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The provided FDA 510(k) summary describes the analytical performance characteristics of the Yumizen C1200 Calcium AS and Yumizen C1200 Creatinine Jaffé reagents when used with the Yumizen C1200 clinical chemistry analyzer. The document focuses on demonstrating substantial equivalence to predicate devices.

Here's an analysis of the acceptance criteria and study designs based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document presents performance data across several analytical characteristics. For some categories, explicit "acceptance criteria" are mentioned (e.g., CV limits for precision), while for others, the results are presented as factual measurements from the studies conducted.

Yumizen C1200 Calcium AS

• Limit of detection: 0.12 mmol/L (0.48 mg/dL)
• Limit of quantitation: 0.14 mmol/L (0.57 mg/dL)
• Linearity: 0.00 to 4.84 mmol/L (0.00 to 19.40 mg/dL)
• Measuring range: 1.00 - 4.50 mmol/L (4.0 - 18.05 mg/dL)
• Post-dilution: Up to 13.5 mmol/L (54.15 mg/dL)
  Urine:
• Limit of detection: 0.06 mmol/L (0.24 mg/dL)
• Limit of quantitation: 0.16 mmol/L (0.64 mg/dL)
• Linearity: 0.00 to 4.84 mmol/L (0.00 - 18.60 mg/dL)
• Measuring range: 0.16 to 4.5 mmol/L (0.64 - 18.05 mg/dL)
• Post-dilution: Up to 13.5 mmol/L (54.15 mg/dL) |
  | Precision (Serum/Plasma) | Within run (CV limits): 1.2% for low (1.8 mmol/L), middle (2.4 mmol/L), high (3.4 mmol/L) levels.
  Total precision (CV limits): 1.6% for low (1.8 mmol/L), middle (2.4 mmol/L), high (3.4 mmol/L) levels. | Within-Run (%CV):
• Control N: 0.6%
• Control P: 0.5%
• Sample 1: 0.8%
• Sample 2: 0.6%
• Sample 3: 0.5%
  Total (%CV):
• Control N: 1.5%
• Control P: 1.4%
• Sample 1: 1.7%
• Sample 2: 1.6%
• Sample 3: 1.8%
  (Note: "Although the %CV of Total Precision is superior to the Acceptance criteria for some samples, the p-value with 5% acceptable remains acceptable for all the samples tested.") |
  | Precision (Urine) | Within run (CV limits): 3.0% for low (1.0mM), middle (2.5mM), high (4.0mM) levels.
  Total precision (CV limits): 4.0% for low (1.0mM), middle (2.5mM), high (4.0mM) levels. | Within-Run (%CV):
• Control L1: 0.7%
• Control L2: 0.5%
• Sample 1: 1.6%
• Sample 2: 0.8%
• Sample 3: 0.7%
• Sample 4: 0.6%
• Sample 5: 0.6%
  Total (%CV):
• Control L1: 3.8%
• Control L2: 3.9%
• Sample 1: 2.6%
• Sample 2: 2.1%
• Sample 3: 2.0%
• Sample 4: 1.7%
• Sample 5: 1.6%
  (Note: "The results are within the specifications.") |
  | Interferences | Acceptable bias is +/-10% of the value without interfering substances. | Highest values for which no interferences > 10% were observed provided for Hemoglobin, Triglycerides, Total Bilirubin, Direct Bilirubin, Acetylsalicylic Acid, Ascorbic Acid, Ibuprofen, Acetaminophen (for serum/plasma) and additionally Glucose for urine. |
  | Matrix Comparison | Not explicitly stated, but high correlation values (e.g., 0.997) suggest equivalence to predicate. | Calcium (mmol/L): Intercept 0.1159, Slope 0.9423, Correlation 0.997. (Plasma vs. Predicate) |
  | Method Comparison (Serum/Plasma) | Not explicitly stated, but high correlation values (e.g., 0.976) suggest equivalence to predicate. | Calcium (mmol/L): Intercept 0.06, Slope 1, Correlation (r2) 0.976. (Native serum vs. Predicate) |
  | Method Comparison (Urine) | Not explicitly stated, but high correlation values (e.g., 0.995) suggest equivalence to predicate. | Calcium (mmol/L): Intercept +0.1381, Slope 0.9436, Correlation (r2) 0.995. (Native urine vs. Predicate) |
  | Closed Reagent Stability | Stable up to the expiry date on the label if stored at 2-8°C. Shelf life claim: 24 months. | Claim supported by CLSI EP25-A. |
  | Open Reagent Stability | Supported by CLSI EP25-A. | Reagent stability claim: 6 weeks (on board). |
  | Reference Range | Verification studies support established ranges from literature. | Serum/Plasma (Adults): 2.15 - 2.55 mmol/L (8.6 - 10.2 mg/dL)
  Urine (24h): Women 10% were observed provided for Hemoglobin, Triglycerides, Total Bilirubin, Direct Bilirubin, Acetylsalicylic Acid, Ascorbic Acid, Ibuprofen, Acetaminophen, Glucose, Total Proteins (for serum/plasma) and additionally Glucose for urine (not listed, but implied from calcium's urine list). Note: Glucose for Creatinine urine interference is not listed in the table, but was for Calcium urine. Acetaminophen listed for Creatinine serum/plasma but not urine, similar to Calcium. |
  | Matrix Comparison | Not explicitly stated, but high correlation values (e.g., 0.999) suggest equivalence to predicate. | Creatinine (µmol): Intercept -7.102, Slope 1.087, Correlation 0.999. (Plasma vs. Predicate) |
  | Method Comparison (Serum/Plasma) | Not explicitly stated, but high correlation values (e.g., 0.995) suggest equivalence to predicate. | Creatinine (µmol/L): Intercept 9.158, Slope 0.9633, Correlation (r2) 0.995. (Native serum vs. Predicate) |
  | Method Comparison (Urine) | Not explicitly stated, but high correlation values (e.g., 0.997) suggest equivalence to predicate. | Creatinine (mmol/L): Intercept -41.4, Slope 0.9483, Correlation (r2) 0.997. (Native urine vs. Predicate) |
  | Closed Reagent Stability | Stable up to the expiry date on the label if stored at 2-8°C. Store protected from light. Shelf life claim: 24 months. | Claim supported by CLSI EP25-A. |
  | Open Reagent Stability | Supported by CLSI EP25-A. | Reagent stability claim: 7 days (on board). |
  | Calibration Stability | At least 3 days (Predicate). | 24 hours (Candidate). (Note: Candidate's calibration stability is shorter than predicate.) |
  | Reference Range | Verification studies support established ranges from literature. | Serum/Plasma: Mens: 62-106 µmol/L (7-12 mg/dL), Womens: 44-80 µmol/L (5-9 mg/dL)
  Urine (24h): Men: 14-26 mg/kg/day (124-230 µmol/kg/day), Women: 11-20 mg/kg/day (97-177 µmol/kg/day) |

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

• Yumizen C1200 Calcium AS:

  • Matrix Comparison (Plasma): 108 individual plasma samples. Data provenance: Not specified (but likely from within France, given the manufacturer's location).
  • Method Comparison (Serum/Plasma): 166 native serum samples. Data provenance: Not specified.
  • Method Comparison (Urine): 105 native urine samples. Data provenance: Not specified.
  • Precision (Serum/Plasma & Urine): "N" is 240 for each sample type/control tested. This is for multiple runs/days/instruments. Samples are controls (Yumizen C1200 N/P Multi Control, Urine Level 1/2 Control) and individual "Samples" (1-5).
  • Reference Range Verification (Serum/Plasma): 40 "normal samples" from blood bank.
  • Reference Range Verification (Urine): Not explicitly stated, but inferred to be derived from literature and verified through internal testing.
  • Limit of Quantitation/Linearity/Interferences: Sample sizes for these studies are not explicitly stated, but are implied to be sufficient for CLSI guidelines EP17-A2 and EP06-A.

• Yumizen C1200 Creatinine Jaffé:

  • Matrix Comparison (Plasma): 69 individual plasma samples. Data provenance: "individual donors from blood bank." Not explicitly stated country of origin.
  • Method Comparison (Serum/Plasma): 131 native samples. Data provenance: Not specified.
  • Method Comparison (Urine): 148 native samples. Data provenance: Not specified.
  • Precision (Serum/Plasma & Urine): "N" is 240 for each sample type/control tested. Samples are controls (Yumizen C1200 N/P Multi Control, Urine Level 1/2 Control) and individual "Samples" (1-5).
  • Reference Range Verification (Serum/Plasma): 35 "normal samples" from blood bank (Men), 25 "normal samples" from blood bank (Women).
  • Reference Range Verification (Urine): Not explicitly stated, but inferred to be derived from literature and verified through internal testing.
  • Limit of Quantitation/Linearity/Interferences: Sample sizes for these studies are not explicitly stated, but are implied to be sufficient for CLSI guidelines EP17-A2 and EP06-A.

Data Provenance (General): The general provenance of the "individual donors from blood bank" for Matrix Comparisons (plasma) is not specified geographically. The studies are described as analytical performance evaluations, suggesting they are prospective studies conducted in a controlled laboratory setting.

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

This document describes the performance of in-vitro diagnostic (IVD) reagents, which measure specific analytes in biological samples. The concept of "ground truth" here is tied to the accurate and precise measurement of these analytes by established laboratory methods, often against a reference method or predetermined values for controls/calibrators.

• Ground Truth Establishment: For IVD devices, "ground truth" is typically established by:
  • Certified Reference Materials/Control Materials: These have assigned values determined by highly accurate reference methods or extensive inter-laboratory studies.
  • Reference Methods: Highly accurate and precise analytical methods used to determine true values (e.g., isotope dilution mass spectrometry for some analytes).
  • Predicate Devices: Comparison against an already cleared and widely accepted device.
  • Expert Consensus/Pathology/Outcomes Data: These are generally relevant for diagnostic imaging or clinical decision support AI, not typically for quantitative chemical assays like Calcium and Creatinine.

The document does not mention the use of "experts" in the traditional sense (e.g., radiologists, pathologists) to establish ground truth for this type of IVD testing. The focus is on analytical performance metrics (linearity, precision, interference, method comparison to a predicate).

4. Adjudication method for the test set:

Not applicable. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies where subjective interpretation (e.g., reading medical images) is involved and multiple experts are used to reach a consensus for ground truth. This document describes the analytical performance of quantitative chemical assays, where measurements are objective.

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. MRMC studies are used for evaluating diagnostic imaging or AI systems that assist human readers in interpretation. This document pertains to the analytical performance of reagents for quantitative chemical measurements, which do not involve human "readers" in the context of interpretation.

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

Yes, in a sense. The studies described (e.g., measuring range, precision, interference, method comparison) evaluate the performance of the reagent and instrument system in generating a quantitative value for Calcium and Creatinine. This is akin to a "standalone" performance evaluation of the reagent system itself, without human interpretation of the final result, beyond standard laboratory quality control and result review. The device output is a numerical value, not an interpretation requiring human assistance.

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

The ground truth for these studies is established through:

• Reference Methods/Assigned Values: For precision studies, control materials with known target values are used. For linearity, serially diluted samples or spiked samples with known concentrations are employed.
• Comparison to a Predicate Device: For method comparison, patient samples are tested on both the candidate device and a legally marketed predicate device, with the predicate serving as the reference for equivalence.
• Literature Reference Intervals: For reference range verification, the device's measurements on "normal samples" are compared against established reference intervals from scientific literature.

8. The sample size for the training set:

Not applicable. This is an IVD reagent and instrument system, not an AI/Machine Learning model that undergoes a distinct "training" phase with a large dataset in the way a medical image analysis algorithm would. The development of reagents involves chemical formulation and optimization, and instrument calibration relies on calibrator materials, not necessarily "training datasets" in the AI sense.

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

Not applicable for the same reasons as point 8. The "ground truth" for calibrators (used for instrument calibration, which is analogous to "training" in the sense of setting up the system for accurate measurement) is typically established by the calibrator manufacturer using highly accurate reference methods and/or extensive certification processes. The document mentions "Yumizen C1200 Multical" as the calibrator for the candidate device.

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The ABX MICROS ES 60 (OT and CT models) is a quantitative multi-parameter, automated hematology analyzer for in vitro diagnostic use in clinical laboratories to identify and enumerate the following parameters: WBC, RBC, HGB, HCT, MCV, MCH, MCHC, RDW, PLT, MPV, LYM%, LYM#, MON%, MON#, GRA%, GRA#, in K2EDTA and K3EDTA anticoagulated venous whole blood samples of adult patients and pediatric patients ≥ 1 month of age.

The ABX MICROS ES 60 is an automated hematology analyzer developed by HORIBA Medical and cleared under K141161. No modification (hardware or software) to the ABX MICROS ES 60 cleared device (K141161) was made to support the pediatric claim addition. Performance verification has been done to support the pediatric claim addition. The corresponding User Instructions for Use was updated to include this additional claim to the intended use.

The document describes the ABX MICROS ES 60, an automated hematology analyzer, and the studies conducted to support its expanded use for pediatric patients (≥ 1 month of age).

Here's the breakdown of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The document primarily focuses on comparability with a predicate device and reference interval validation for the pediatric claim. Specific quantitative acceptance criteria are indirectly implied by the "Bias was estimated at various data points, particularly around medical decision points, for each parameter. Bias was estimated for one replicate. Acceptance criteria were met for all measurands at all levels, except for RDW" statement. While the exact numerical acceptance limits for bias are not explicitly listed in a table, the document states they were met for all measured parameters except RDW.

For the Reference Interval, the acceptance criteria were that the results obtained from normal pediatric samples on the ABX MICROS ES 60 should fall within established pediatric reference ranges.

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

• Comparability Study (Bias Estimation):

  • Sample Size: 137 venous whole blood specimens.
  • Age Range: Pediatric patients between 1 month and 21 years of age.
  • Data Provenance: The study was conducted at two test sites in the US and one test site in France. This indicates a prospective study design, collecting samples specifically for the evaluation.

• Reference Interval Study:

  • Sample Size: 69 normal pediatric samples (37 female and 32 male).
  • Age Range: Not explicitly stated for all, but categorized into 1m-2y, >2y-12y, and >12y-21y.
  • Data Provenance: Performed at one test site in the US. This also suggests a prospective collection of samples from normal pediatric patients.

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

The document does not mention the use of experts to establish ground truth for the test set.

• In the comparability study, the predicate device (Sysmex XN Series, XN-10) served as the reference standard for comparison. The performance of the predicate device is assumed to be the "ground truth" or accepted standard for those measurements.
• In the reference interval study, previously published pediatric reference ranges from several US hospitals were used as the "ground truth" for expected normal values.

Since this is an automated hematology analyzer measuring quantitative parameters, ground truth is typically established by comparison to other validated methods or established reference intervals, rather than by expert interpretation of images or data.

4. Adjudication Method for the Test Set

Not applicable, as expert adjudication (e.g., 2+1, 3+1) is specific to studies where human interpretation is involved in establishing ground truth, such as in image analysis or differential cell counts performed manually. For automated quantitative measurements, the comparison is typically against a reference method or validated ranges.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. These studies are typically performed to assess the impact of AI on human reader performance, usually in diagnostic imaging. This document describes the validation of an automated hematology analyzer, which does not involve human readers interpreting AI output.

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

Yes, the studies described are standalone performance evaluations. The ABX MICROS ES 60 is an automated hematology analyzer, meaning it operates without direct human intervention in the measurement and parameter calculation process. The studies assessed the device's performance directly against a predicate device and established reference ranges.

7. The Type of Ground Truth Used

• For the comparability study (bias estimation): The Sysmex XN Series, XN-10 (K112605) predicate device served as the reference for comparison. The measurements from this established device were considered the "ground truth" for assessing bias.
• For the reference interval study: Published pediatric reference ranges obtained from several US hospitals were used as the ground truth.

8. The Sample Size for the Training Set

The document does not describe a "training set" in the context of machine learning, as the ABX MICROS ES 60 is an automated analyzer based on physical principles (impedance, spectrophotometry) rather than a machine learning algorithm that is "trained" on data. The device was previously cleared under K141161, and this submission is for an additional pediatric claim without hardware or software modification to the cleared device. Therefore, no new training set or training process for the algorithm is described for this specific submission.

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

Not applicable, as there is no mention of a "training set" for a machine learning algorithm in this 510(k) submission. The device operates based on established physical principles and its original validation (K141161) would have involved standard analytical validation studies.

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The PENTRA XLR is a quantitative multi-parameter automated hematology analyzer for in vitro diagnostic use in clinical laboratories to identify and enumerate the following parameters: WBC, RBC, HCT, MCV, MCH, MCHC, RDW, PLT, MPV, LYM (#, %), MON (#, %), NEU (#, %), EOS (#, %), BAS (#, %), as well as the Reticulocyte parameters RET (#, %), CRC, and IRF in K2EDTA and K3EDTA anticoagulated venous whole blood samples from patients ≥ 18 years of age.

The PENTRA XLR is a device modification to the ABX PENTRA 80 (K024002), which consists in the addition of the measurement of Reticulocytes (RET) parameters to the existing Complete Blood Count (CBC) and Differential (DIFF) counts already performed by the analyzer. The additional RET mode, based on the use of Thiazol orange reagent and fluorescence detection by optical bench, is independent from the modes already existing on the ABX PENTRA 80: the CBC and the CBC+DIFF modes, as there have been no modifications to the existing mechanical and analytical portions of the original device.

Here's an analysis of the acceptance criteria and study details for the HORIBA ABX SAS PENTRA XLR device, based on the provided text:

Important Note: The provided text is a 510(k) Summary, which typically focuses on demonstrating substantial equivalence to a predicate device rather than presenting a full, independent validation study in the format one might expect for a research paper. Therefore, some details like specific expert qualifications or adjudication methods for ground truth might not be explicitly stated for all aspects if they were part of the predicate device's original validation or are assumed by industry standards for this type of device.

1. Table of Acceptance Criteria and Reported Device Performance (Reticulocyte Parameters)

The document focuses on the newly added Reticulocyte (RET) parameters for the PENTRA XLR. Performance for existing CBC and DIFF parameters is stated to be unchanged from the predicate device (ABX PENTRA 80, K024002).

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

• Precision (Repeatability): Minimum of 10 normal and 5 abnormal fresh whole blood samples collected into K2EDTA. Data Provenance: Fresh whole blood samples, collected at 3 different clinical sites (implicitly prospective).
• Precision (Reproducibility): One single lot of control material (Minotrol Retic).
• Linearity / AMR: Commercial Linearity kits.
• Carryover: Alternating high and low concentration samples.
• Interfering Substances:
  • Addition Method: Samples with potential interfering substances added vs. control portions.
  • Comparison Method: 10 to 20 patient specimens per group with known or potential reticulocyte interferents, and control samples.
• Sample Stability: 10 whole venous blood specimens collected in K2EDTA. Data Provenance: US, implicitly prospective.
• Comparability with Predicate Device: Total of 376 whole blood specimens collected in K2EDTA from adult patients. Data Provenance: US, from three test sites, collected prospectively or not (retrospective/prospective mix).
• Comparability between Anticoagulant types: Total of 90 normal and pathological blood specimens. Data Provenance: US, from two sites, specifically prospectively collected for this study.
• Comparability between CBC and RET modes for RBC: Total of 107 normal and pathological blood specimens collected in K2EDTA. Data Provenance: France, from one site.
• Reference Interval: 242 normal adult samples (122 female and 120 male) collected in K2EDTA. Data Provenance: US, from two test sites.

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

The document does not explicitly mention the use of experts to establish ground truth in the traditional sense (e.g., for image interpretation or diagnosis). For an automated hematology analyzer measuring quantitative parameters, the "ground truth" for method comparison and accuracy studies is typically a reference measurement procedure, sometimes a manual count (e.g., manual reticulocyte count) or a highly accurate predicate device or method.

In this case:

• Comparability with Predicate Device: The ABX PENTRA DX 120 (K991839) served as the reference method for evaluating the new RET parameters. This is an existing FDA-cleared automated hematology analyzer.
• Interfering Substances (Comparison Method): ABX PENTRA DX 120 (K991839) was also used as the comparative measurement procedure.

Since the device evaluates quantitative hematological parameters, human expert visual review (e.g., microscopic differentiation) or adjudication is typically not the primary "ground truth" for the measured values themselves, which are generated parametrically. Ground truth for diagnosis based on these values might involve experts, but that's beyond the scope of device performance.

4. Adjudication Method for the Test Set

No explicit adjudication method (like 2+1 or 3+1 consensus) is described or would typically be applicable for the direct measurement of quantitative hematology parameters by an automated analyzer, as outlined above. The evaluation relies on statistical comparison against a reference method or against established internal specifications.

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

No MRMC comparative effectiveness study was done. This type of study is more common for diagnostic devices where human readers interpret outputs (e.g., radiographs, pathology slides). The PENTRA XLR is an automated analyzer producing quantitative values, not interpretations requiring human reading.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)

Yes, the studies described are essentially standalone performance studies for the algorithm (the automated analyzer). There is no "human-in-the-loop" component described for the measurement of the parameters. The output is a direct quantitative reading from the instrument.

7. Type of Ground Truth Used

The ground truth used depends on the specific study:

• Analytical Sensitivity, Precision, Linearity, Carryover: Internal specifications, commercial linearity kits with "expected values" considered "true values," and statistical analysis against these benchmarks.
• Interfering Substances: Comparison against a predicate device (ABX PENTRA DX 120) and acceptable bias limits.
• Sample Stability: Comparison against an initial measurement (T0) of the same sample.
• Comparability with Predicate Device: Measurements from the legally marketed predicate device, ABX PENTRA DX 120 (K991839).
• Comparability between Anticoagulant types & RBC Mode Comparability: Statistical comparison between measurements obtained from different conditions on the PENTRA XLR itself.
• Reference Interval: Statistical analysis of normal adult samples according to CLSI EP28-A3 guidelines.

8. The Sample Size for the Training Set

The document does not provide a specific sample size for a "training set." This is an automated diagnostic device, not a machine learning model in the contemporary sense that would undergo explicit "training" with a labeled dataset in the way a deep learning algorithm might. The device's "training" and calibration would be part of its engineering development, using internal standards and optimization, rather than a publicly reported "training set." The focus of this 510(k) is on the validation and verification of its analytical performance.

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

As noted above, a distinct "training set" with established ground truth as understood in machine learning contexts is not directly applicable or described here. The instrument's operational principles are based on established impedance and fluorescence cytochemistry, not a learned model from a large, expert-labeled dataset for classification/detection. Therefore, the concept of "ground truth for the training set" isn't explicitly addressed in this type of submission for this kind of device.

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