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K-ASSAY® CRP (Ver.2) is intended to be used for the quantitative determination of C-reactive protein (CRP) in human serum and plasma (potassium-EDTA or lithium-heparin) by immunoturbidimetric assay. Measurement of CRP aids in the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases. FOR IN VITRO DIAGNOSTIC USE.

The K-ASSAY® CRP (Ver.2) assay quantifies C-reactive protein based on immunoturbidimetric assay. The reagent uses latex combined with goat polyclonal antibody specific to human CRP. By adsorbing CRP in the sample to the surface of the latex particles and reacting it with the anti-CRP antibody, specific aggregation corresponding to the CRP concentration occurs. Since the absorbance of the reaction changes in proportion to the amount of aggregation, the concentration of CRP in the sample is determined based on the calibration curve prepared using a standard of known CRP concentrations. The K-ASSAY® CRP (Ver.2) assay can be run using a chemistry analyzer. 6 levels of calibrators from the K-ASSAY® CRP Calibrator (Ver.2) calibrators are used for quantifying the levels of CRP present in the patient's sample.

This document describes the FDA 510(k) clearance for the K-ASSAY CRP (Ver.2) IVD device. This device is an in-vitro diagnostic test system, which means it analyzes biological samples in a lab setting rather than directly interacting with a patient.

Therefore, the concepts of "human readers," "AI assistance," "effect size," "multi reader multi case (MRMC) comparative effectiveness study," and "standalone (i.e. algorithm only without human-in-the loop performance)" are not applicable in this context. These terms are typically used for medical imaging AI/ML devices where human interpretation is involved.

For this in-vitro diagnostic device, the "acceptance criteria" and "study that proves the device meets the acceptance criteria" are related to its analytical performance characteristics when compared to a predicate device, and the reported device performance refers to the results of these analytical studies.

Here's the breakdown of the information provided within the scope of this IVD device:

1. Table of Acceptance Criteria and Reported Device Performance

For an IVD device like the K-ASSAY® CRP (Ver.2), the acceptance criteria are generally established by demonstrating equivalent or superior analytical performance compared to a legally marketed predicate device, and meeting established CLSI guidelines for accuracy, precision, linearity, and interference. The "reported device performance" refers to the actual study results for these characteristics.

• Within-Run CV: 0.8% to 2.2%
• Between-Run CV: 0.0% to 0.6%
• Within-Lot CV: 0.9% to 1.9%
• Between-Lot CV: 0.0% to 1.2%
• Total CV: 0.9% to 2.3%
  Multisite Precision (Combined Data From 3 Analyzers):
• Repeatability CV: 0.5% to 1.5%
• Between-Run CV: 0.0% to 1.1%
• Between-Day CV: 0.6% to 1.8%
• Between-Site CV: 0.9% to 1.8%
• Reproducibility CV: 1.1% to 2.5% |
  | Interference: No significant interference from common endogenous and exogenous substances (recovery within 10% of initial value). | Endogenous Substances (up to listed concentrations, no significant interference): Bilirubin C (40 mg/dL), Bilirubin F (40 mg/dL), Cholesterol (300 mg/dL), Hemoglobin (1,000 mg/dL), Intralipid (500 mg/dL), Rheumatoid Factor (1,000 IU/mL), Triglycerides (1,000 mg/dL).
  Exogenous Substances (up to listed concentrations, no significant interference): Acetaminophen (1.5 mM), Amoxicillin (400 µmol/L), Aspirin (3.6 mM), Cephalexin (360 µmol/L), Fluconazole (480 µmol/L), Ibuprofen (2.5 mg/dL), Methotrexate (1,400 µmol/L), Prednisolone (2 µmol/L), Vitamin C (500 mg/L). |
  | Method Comparison: Strong correlation and minimal bias against the predicate device. | Regression Equation: y = 1.005x - 0.002, r = 0.999 (n = 175 clinical native serum samples), where y = K-ASSAY® CRP (Ver.2), x = predicate device. |
  | Linearity: Demonstrates linearity across the claimed assay range. | Regression Equation: y = 0.9709x - 1.095, r = 0.999 (tested range: 4.6 - 441.2 mg/L). |
  | Limit of Quantitation (LoQ): Clinically acceptable LoQ (within-laboratory precision ≤ 20% CV). | Reported LoQ: 1.0 mg/L (highest observed across 3 reagent lots). Claimed LoQ: 5.0 mg/L. |
  | Matrix Comparison: No significant difference in results across different sample matrices (serum vs. plasma). | K2-EDTA Plasma vs Serum: y = 1.007x - 0.141, r = 0.999
  Li-Heparin Plasma vs Serum: y = 0.972x + 0.074, r = 0.999 |
  | Expected Values (Verification): Distribution in normal population consistent with clinical literature. | 168 normal U.S. serum samples tested; 4 out of 168 samples (>5.0 mg/L, 2.4%) consistent with literature (≤ 5 mg/L indicates apparently healthy). |

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

• Method Comparison: n = 175 clinical native serum samples.
• Linearity: The number of samples/dilutions used is not explicitly stated, but the tested range was 4.6 - 441.2 mg/L.
• Limit of Quantitation (LoQ): Not specified in terms of sample size for the LoQ determination itself (typically involves low-concentration samples measured multiple times).
• Matrix Comparison: 42 donor samples (each collected into 3 different tubes: serum, K2-EDTA plasma, Li-Heparin plasma).
• Precision (Single-site): For each of the 7 samples/controls, N=240 individual measurements (2 runs/day x 2 replicates/run x 20 days x 3 lots).
• Precision (Multisite): For each of the 7 samples/controls, N=75 individual measurements (1 run/day x 5 replicates/run x 5 days x 3 analyzers).
• Interference: The number of unique samples tested for interference is not explicitly stated. Typically, a few samples (e.g., low, medium, high concentration) are spiked with interferents and compared to unspiked controls.
• Expected Values: 168 normal serum samples.
• Data Provenance: The document states for "Expected Values" that 168 normal serum samples were "taken from healthy individuals in the U.S." This indicates a U.S. origin for at least this specific study. For other studies (Method Comparison, Precision, Linearity, Interference, Matrix Comparison), the specific country of origin is not mentioned. All studies are retrospectively analyzed in the sense that they were completed performance validation studies submitted to FDA.

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

For an in-vitro diagnostic device like this CRP assay, the "ground truth" is established through highly accurate and precise reference methods or established predicate devices, adhering to rigorous analytical chemistry best practices and guidelines (e.g., CLSI standards). There isn't a panel of human "experts" like radiologists interpreting images. The "ground truth" is quantitative and objective, derived from reference measurements.

In this case:

• Method Comparison: The predicate device (K-ASSAY® CRP (3), K023828) serves as the comparator for method comparison, which represents the established "ground truth" for clinical samples.
• Linearity, LoQ, Precision, Interference, Matrix Comparison: The "ground truth" for these analytical performance studies is established by rigorous laboratory protocols, highly calibrated equipment, reference materials, and adherence to CLSI guidelines. The performance is assessed against predefined statistical criteria rather than expert consensus on individual cases.
• Expected Values: The ground truth comes from established clinical literature and verified normal ranges based on studies of healthy populations.

4. Adjudication Method for the Test Set

Not applicable for an IVD device. Adjudication methods (e.g., 2+1, 3+1) are used in studies where subjective human interpretation (e.g., image reading) requires consensus building for ground truth establishment. For quantitative IVD assays, the results are numerical and objectively measured; therefore, there's no need for adjudication.

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

No. As explained above, this is an in-vitro diagnostic device, not an imaging AI/ML device involving human readers.

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

Yes, in essence, all the analytical performance studies (Method Comparison, Linearity, LoQ, Precision, Interference, Matrix Comparison) are "standalone" in nature for an IVD. The device's performance is evaluated based solely on its ability to accurately and precisely measure CRP concentrations in samples, without any human interpretation of the measurement itself or the involvement of an "algorithm" in the AI/ML sense. The device directly processes the sample and outputs a quantitative result.

7. The Type of Ground Truth Used

The ground truth for this IVD device's performance studies is primarily based on:

• Reference Method/Predicate Device Comparison: For the method comparison study, the predicate device serves as the reference against which the new device's measurements are compared.
• Reference Materials and Calibrators: For linearity, LoQ, and precision studies, the ground truth for concentration values is established using certified reference materials and meticulously prepared calibrators with known concentrations.
• Spiked Samples: For interference studies, known amounts of interfering substances are added to samples, and the true CRP concentration (before interference) serves as the baseline ground truth.
• Clinical Literature/Established Norms: For "Expected Values," the ground truth is derived from widely accepted clinical ranges and population studies cited in the literature.

8. The Sample Size for the Training Set

This document describes a 510(k) submission for a traditional IVD device, not an AI/ML-based device. Therefore, there is no "training set" in the context of machine learning. The device's performance is based on its chemical and physical principles (latex-enhanced immunoturbidimetric assay) and validated through the analytical studies detailed.

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

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

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The Procise CRP assay is a time-resolved fluorescence energy transfer immunoassay for the quantitative determination of C-Reactive Protein (CRP) levels in human serum. The test is carried out by means of the ProciseDx Analyzer.

Measurement of CRP aids in evaluation of injury to body tissues, inflammatory disorders. The instrument and assay are for use by trained professionals in the clinical laboratory. For in vitro diagnostic use only. Not for point of care use.

The Procise CRP assay is a homogeneous sandwich immunoassay assay that uses a fluorescence resonance energy transfer (FRET) signal to detect and quantify CRP. FRET is a process in which a donor molecule, in an excited state, transfers excitation energy to an acceptor fluorophore when the two are brought into close proximity. Upon excitation at a characteristic wavelength the energy absorbed by the donor is transferred to the acceptor, which in turn emits light energy. The level of light emitted from the acceptor fluorophore is directly proportional to the degree of donor/acceptor complex formation.

The Procise CRP assay format is designed as a competitive format. A monoclonal anti-CRP antibody and exogenous CRP antigen are labeled with donor and acceptor fluorophores, respectively. The monoclonal antibody specific for CRP is labelled with the donor fluorophores and the CRP antigen is labelled with the acceptor fluorophore. Similar to other competitive assay formats, as the concentration of CRP increases a proportional decrease in the signal is observed.

The Procise CRP Assay Kit, ProciseDx Instrument, and ProciseDx Calibration Cartridge (K201256) is a device for the quantitative determination of C-Reactive Protein (CRP) levels in human serum. It is intended to aid in the evaluation of injury to body tissues, infection, and inflammatory disorders.

Here's an analysis of the acceptance criteria and the study proving the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The FDA clearance document does not explicitly state "acceptance criteria" in a quantified table for all performance characteristics. Instead, it presents the results of individual studies and implicitly expects them to demonstrate substantial equivalence to the predicate device and meet typical analytical performance standards for in vitro diagnostic devices. Below is a summary of the performance characteristics obtained from the studies. For qualitative criteria like specificity, "No significant interference" serves as the reported performance, implying it met an internal acceptance threshold. For quantitative metrics like precision, the reported values are the performance.

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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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The CRP Vario assay [CRPVa] is for in vitro diagnostic use in the quantitative immunoturbidimetric determination of C-reactive protein in human serum and plasma (sodium and lithium heparin) using the ARCHITECT c Systems. Measurement of C-reactive protein is useful in the detection and evaluation of infection, tissue injury and inflammatory disorders.

CRP Calibrators (including CRP Calibrator Set, CRP Calibrator HS and CRP Calibrator WR) are intended to be used for the calibration of the CRP Vario for the quantitative determination of C-reactive protein in human serum or plasma samples.

The CRP Vario assay is intended for the quantitative immunoturbidimetric determination of C-reactive protein in human serum and plasma. It is supplied as a two-reagent kit. The kit contains Reagent 1 (Glycine buffer) and Reagent 2 (Anti-CRP polyclonal antibodies adsorbed on latex particles). Two different sizes of the product are available. The submission also describes CRP Calibrators (CRP Calibrator Set, CRP Calibrator HS, and CRP Calibrator WR) which are prepared by diluting CRP with human serum and stabilized by adding sodium azide.

Here's an analysis of the acceptance criteria and study as described in the provided document:

Acceptance Criteria and Device Performance for CRP Vario

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document explicitly refers to an "Acceptance Criteria" column for Method Comparison in Table 15-3. For other performance characteristics, the "acceptance criteria" can be inferred by comparing the candidate device's stated performance to that of the predicate device, or by general statements about meeting recommendations or consistency with original submissions.

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

• Method Comparison Test Set:

  • High Sensitivity Method: N = 111 human serum samples
  • Standard Method: N = 119 human serum samples
  • Wide Range Method: N = 119 human serum samples
  • Data Provenance: The document states "Human serum samples, spanning the measuring range, were tested." No information is provided regarding the country of origin or whether the data was retrospective or prospective.

• Limit of Quantitation (LoQ) Test Set:

  • The study used serum pools diluted with SeraSub (a synthetic serum) to create 8 low-level analyte samples (0.08, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01, and 0.005 mg/dL).
  • Each sample was tested in a minimum of 10 replicates per run, with 2 runs per day over 3 days, resulting in a total of 60 replicates per sample.

• Linearity Test Set:

  • A high CRP serum pool was mixed with a low serum pool to generate 12 concentrations.
  • Each concentration level was tested in triplicate determinations.

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

This section is not applicable to this type of device and study. The CRP Vario is an in vitro diagnostic device that quantifies C-reactive protein. Its performance is evaluated against reference methods (e.g., predicate devices, established analytical protocols) and CLSI guidelines, not against expert human interpretations of images or clinical reports. There are no "experts" establishing a subjective ground truth in the way described for AI in image analysis.

4. Adjudication Method for the Test Set

This section is not applicable. As an in vitro diagnostic device, the performance is determined by quantitative measurements and statistical comparisons with reference methods, not by adjudication of interpretations by multiple human readers.

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 evaluates human reader performance often in the context of imaging diagnostics. The CRP Vario is an in vitro diagnostic for laboratory analysis, not a device requiring human interpretation in this manner.

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

Yes, the studies reported here (Method Comparison, Linearity, Limit of Quantitation) are standalone performance evaluations of the CRP Vario assay. The device itself is an automated immunoturbidimetric system (ARCHITECT c8000 system) for quantitative measurement, operating without human interpretation of the final result, beyond standard laboratory quality control and result reporting.

7. The Type of Ground Truth Used

The "ground truth" for the performance evaluation of the CRP Vario was established by:

• Reference Methods / Predicate Device: For the Method Comparison study, the candidate CRP Vario (traceable to ERM-DA472/IFCC) was compared against a Beckman Coulter CRP Latex REF. OSR6199 (traceable to CRM 470) on an AU5800 platform.
• CLSI Guidelines: Formal CLSI (Clinical and Laboratory Standards Institute) protocols (EP09-A3 for Method Comparison, EP06-A for Linearity, EP17-A2 for LoQ) were followed, indicating that the acceptable statistical and analytical measures defined by these standards served as the basis for evaluating performance.
• Dilution Series / Known Concentrations: For Linearity and LoQ, the "ground truth" was derived from precisely prepared serum pools and their serial dilutions to known or targeted concentrations.

8. The Sample Size for the Training Set

This section is not applicable. The CRP Vario is a re-submission for a modification of an existing in vitro diagnostic device, not an AI/ML device that requires a distinct "training set" in the computational sense. Its performance is characterized through analytical verification and validation studies.

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

This section is not applicable for the reasons stated in point 8.

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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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For in vitro diagnostic use only. Rx Only.

VITROS Chemistry Products hsCRP Reagent is used on the VITROS 5,1 FS Chemistry System, the VITROS 4600 Chemistry System and the VITROS 5600 Integrated System to quantitatively measure C-reactive protein (CRP) in human serum and plasma. CRP is used to evaluate conditions thought to be associated with inflammation in otherwise healthy individuals.

The quantitative measurement of C-reactive protein (CRP) is performed using the VITROS Chemistry Products hsCRP Reagent in conjunction with the VITROS Chemistry Products Calibrator Kit 17 and VITROS Chemistry Products FS Calibrator 1 on the VITROS 5,1 FS/4600 Chemistry System and the VITROS 5600 Integrated System. The VITROS Chemistry Products hsCRP Reagent is a dual chambered package containing ready-to-use liquid reagents. Samples, calibrators and controls are mixed with Reagent 1 containing a buffer. Addition of anti-CRP antibodies coupled to latex microparticles (Reagent 2) produces an immunochemical reaction yielding CRP antigen/antibody complexes. The turbidity is measured spectrophotometrically at 660 nm. Once a calibration has been performed for each reagent lot, the CRP concentration in each unknown sample can be determined using the stored calibration curve and the measured absorbance obtained in the assay of the sample.

The provided document describes the K160712 510(k) submission for the VITROS Chemistry Products hsCRP Reagent. This is an in vitro diagnostic (IVD) device, not an AI/ML medical device. Therefore, the information regarding acceptance criteria and study design (especially related to human readers, ground truth establishment, and test set/training set specifics) is described through the lens of an IVD device, focusing on analytical performance rather than diagnostic accuracy based on images or clinical data interpreted by AI.

Here's a breakdown of the information provided, tailored to the context of an IVD device:

1. Table of Acceptance Criteria and Reported Device Performance

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QuikRead go® CRP: The QuikRead go® CRP test is an immunoturbidimetric assay for the in vitro quantitative determination of C-reactive protein (CRP) in K2-EDTA and lithium heparin whole blood, K2-EDTA and lithium heparin plasma and in serum samples. The test is carried out by means of the QuikRead go® instrument. Measurement of C-reactive protein aids in the evaluation of injury to body tissues, and inflammatory disorders. The instrument and assay are for use by trained professionals in the clinical laboratory. For in vitro diagnostic use only. Not for point-of-care use.

QuikRead go® CRP Control Set: The QuikRead go® CRP Control Set is intended for use as assayed quality-control material for monitoring the performance of the quantitative QuikRead go® CRP assay with the QuikRead go® Instrument. For in vitro diagnostic use.

QuikRead go® CRP Verification Set: The QuikRead go® CRP Verification Set is designed to be used for calibration verification and for method validation of the QuikRead go® CRP system. This assayed verification material is intended for use with the QuikRead go® CRP test and the QuikRead go® instrument. For in vitro diagnostic use.

QuikRead go® Instrument: The Orion Diagnostica QuikRead go® is an in vitro diagnostic test system. The QuikRead go® instrument has been designed to measure quantitative test results from patient samples using QuikRead go® reagent kits. Not for point-of-care use.

Not Found

This document is a 510(k) premarket notification for the QuikRead go® CRP system, which includes the QuikRead go® CRP assay, Control Set, Verification Set, and Instrument. It confirms that the device is substantially equivalent to legally marketed predicate devices. However, this document does not contain the acceptance criteria or the study details to prove the device meets those criteria.

The provided text only outlines the indications for use of the various components of the QuikRead go® CRP system and regulatory information from the FDA. It does not include:

1. A table of acceptance criteria and reported device performance.
2. Sample sizes used for test sets or data provenance.
3. Number of experts, their qualifications, or adjudication methods for ground truth establishment.
4. Information about Multi-Reader Multi-Case (MRMC) comparative effectiveness studies or standalone algorithm performance.
5. Details on the type of ground truth used (e.g., pathology, outcomes data).
6. Sample size for the training set or how its ground truth was established.

To obtain this information, one would typically need to refer to the full 510(k) submission, specifically the sections detailing analytical and clinical performance studies, which are not included in this FDA clearance letter.

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VITROS Chemistry Products CRP Slides:
For in vitro diagnostic use only.
VITROS Chemistry Products CRP Slides quantitatively measure C-reactive protein (CRP) concentration in serum and plasma using VITROS 250/350/5.1 FS and 4600 Chemistry Systems and the VITROS 5600 Integrated System.
C-reactive protein is synthesized by the liver and is one of the acute phase response, increased concentrations of a number of plasma proteins, including CRP, are observed. CRP concentration measurements are useful in the detection and evaluation of inflammatory disorders, tissue injury, and infections.

VITROS Chemistry Products Calibrator Kit 7:
For in vitro diagnostic use only.
VITROS Chemistry Products Calibrator Kit 7 is used to calibrate VITROS 250/350/5,1 FS and 4600 Chemistry Systems and the VITROS 5600 Integrated System for the quantitative measurement of CRP.

The VITROS CRP Slide method is performed using the VITROS CRP Slides and the VITROS Chemistry Products Calibrator Kit 7 on VITROS Chemistry and Integrated Systems.
The VITROS CRP Slide is a multilayered, analytical element coated on a polyester support. The immuno-rate format for CRP is based on an enzymatic heterogeneous, sandwich immunoassay format. In this format a derivative of phosphorylcholine (PC) is covalently bound to polystyrene polymer beads and in the presence of calcium serves as a capture agent. Monoclonal anti-CRP antibody conjugated to horseradish peroxidase (HRP) serves as a signal generator.
A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. CRP in the sample binds to PC-linked capture beads and anti-CRP antibody labeled with horseradish peroxidase to form an insoluble sandwich complex in Incubation 1. The subsequent addition of 12 microliters of VITROS Immuno-Wash Fluid to the slide removes unbound materials from the read area, while also providing the hydrogen peroxide required for the enzyme-mediated oxidation of leuco dye.
The reflection density of the dye is measured after the addition of VITROS Immuno-Wash Fluid at the end of Incubation 2. This reflection density is directly proportional to the concentration of CRP in the sample. To determine if an adequate wash has occurred, the wash detection dye is read at 540 nm immediately after Incubation 2.

The VITROS Calibrator Kit 7 is prepared from processed human serum to which purified human C-reactive protein, inorganic salts, and preservatives have been added.
The human blood products provided as components of VITROS Calibrator Kit 7 have been tested at the individual donor level and found nonreactive for hepatitis B surface antigen (HBsAg), antibody to HCV, and antibody to HIV using FDA approved methods.

1. Table of Acceptance Criteria and Reported Device Performance:

The document describes performance characteristics rather than explicit "acceptance criteria" with pass/fail thresholds in a formal table. However, we can infer the criteria from the studies conducted.

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

• Sample Size: 98 to 103 human serum samples were used for the method comparison study.
• Data Provenance: The document states "Human serum samples were tested." The country of origin is not specified, but the context implies it was likely from a clinical setting. It is a retrospective dataset as it involves testing existing samples.

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

This information is not explicitly provided. The "ground truth" for the test set is established by comparing the new device's readings against a "predicate method" (VITROS Chemistry Products CRP assay traceable to ERM-DA472). The document describes this predicate as generating the reference measurements, not a panel of experts.

4. Adjudication Method for the Test Set:

Not applicable. The study compares the new device's measurements to a predicate device's measurements, not to expert consensus.

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

Not applicable. This device is an in vitro diagnostic (IVD) assay for quantitative measurement, not an AI or imaging device requiring human reader interpretation or assistance.

6. Standalone Performance:

Yes, the studies described (Method Comparison, Limits of Blank, Detection, and Quantitation, Linearity, Analytical Range) directly assess the standalone performance of the VITROS Chemistry Products CRP Slides without human-in-the-loop performance. The results are generated solely by the device and its associated systems.

7. Type of Ground Truth Used:

The ground truth used for performance evaluation is comparative measurement against a legally marketed predicate device (VITROS Chemistry Products CRP assay traceable to ERM-DA472), which itself has established performance characteristics and traceability to a recognized international reference material (ERM-DA472). In essence, it's a reference measurement from an established method.

8. Sample Size for the Training Set:

The document does not mention a "training set." This type of in vitro diagnostic device typically undergoes analytical validation studies (as described) rather than machine learning model training.

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

Not applicable, as there is no training set for this device as described. Its performance is evaluated through direct analytical studies.

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FastPack® High Sensitivity C-Reactive Protein Immunoassay is to be used for evaluation of conditions thought to be associated with inflammation, in otherwise healthy individuals. The FastPack® High Sensitivity C-Reactive Protein Immunoassay is intended for use with the FastPack® Analyzer. Not intended for Point-of-Care use.

FastPack® High Sensitivity C-Reactive Protein Calibrators are used for calibrating the quantitative FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.

FastPack® High Sensitivity C-Reactive Protein Controls are used for quality control of the FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.

FastPack® High Sensitivity C-Reactive Protein Verifiers are used in the quantitative verification of calibration and assay range of the quantitative FastPack® High Sensitivity C-Reactive Protein Immunoassay on the FastPack® Analyzer.

The FastPack® High Sensitivity C-Reactive Protein Immunoassay employs a Sandwich immunoassay principle. Endogenous CRP in a patient sample, calibrator, control, or verifier is dispensed into a FastPack® reagent pack. In the reagent pack, the sample binds with a monoclonal anti-CRP antibody covalently linked to alkaline phosphatase (ALP) and a different monoclonal anti-CRP antibody linked to biotin. After incubation, immunoreacted complex (Monoclonal anti-CRP antibody-ALP conjugate and anti-CRP antibody linked to biotin reacted with CRP in the sample) is mixed with streptavidin coated paramagnetic particles. After washing steps (using a Tris buffer containing detergents) to separate bound from unbound anti-CRP monoclonal antibody-ALP, a chemiluminogenic substrate mixture is added to the system. This mixture contains indoxyl-3-phosphate, a substrate for ALP, and lucigenin (N,N'-dimethyl-9,9'-biacridinium dinitrate). ALP dephosphorylates indoxyl-3-phosphate to indol-3-ol, which subsequently undergoes oxidation. As a result, lucigenin is reduced to form a dioxetane structure that is cleaved to yield Nmethylacridone. This compound produces a sustained luminescent glow following excitation. The raw relative luminescence units (RLUs) generated are measured by a photomultiplier tube in the FastPack® Analyzer and are directly proportional to the concentration of CRP in the sample. The entire reaction sequence takes place at 37 ± 0.5 ℃ and is protected from external light.

The provided document describes the FastPack® High Sensitivity C-Reactive Protein Immunoassay (device) and its performance to demonstrate substantial equivalence to a predicate device.

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly list "acceptance criteria" as a separate section with pass/fail values. Instead, it presents performance characteristics and compares them to the predicate device or established guidelines (e.g., CLSI). Based on the provided sections, a table can be constructed as follows:

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

• Precision Study: 6 serum patient samples were used, each with 320 replicate determinations.
• Limits of blank, detection, and quantitation: Information not provided about the specific "samples" used for these determinations.
• Linearity Study: A high patient sample was intermixed with a low sample to generate 8 concentration levels, each tested in triplicate.
• Interferences: Specific concentrations of various substances were tested. The number of samples/replicates isn't explicitly stated, but implies a controlled study.
• Cross-reactivity: Specific concentrations of substances like Rheumatoid factor, human anti-mouse IgG, and heterophile samples were tested.
• Serum and Plasma Equivalence: Blood collections from 41 volunteers.
• Expected Values/Reference Intervals: Serum samples from 211 subjects.
• Method Comparison: 131 samples.

Data Provenance:
The document states that the reference interval study employed serum samples from "211 subjects representing 4 different geographic regions of the United States." This indicates a prospective or retrospective collection of patient samples within the US for this specific study. For other studies (precision, linearity, interferences, serum/plasma equivalence, method comparison), specific provenance details like country of origin or retrospective/prospective nature are not explicitly stated, but are generally assumed to be carried out under controlled laboratory conditions often using commercially available or anonymized clinical samples.

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 to this type of device (in-vitro diagnostic immunoassay). The "ground truth" for a C-reactive protein immunoassay is typically the actual concentration of CRP in the sample, which is determined by established reference methods or by the device's own calibrated measurement. There are no human "experts" establishing ground truth in the sense of image interpretation or clinical diagnosis for this kind of analytical device. The "ground truth" for method comparison is the result obtained from the predicate device or a reference method.

4. Adjudication Method for the Test Set:

This information is not applicable for this type of device. Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies where multiple human readers interpret data (e.g., medical images) and their interpretations need to be resolved for ground truth. For an immunoassay, the results are quantitative measurements, not subjective interpretations requiring adjudication.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

This information is not applicable to this device. An MRMC study is relevant for AI-assisted diagnostic tools where human readers are part of the diagnostic workflow. The FastPack® Immunoassay is an automated analytical device that directly measures CRP concentration, not an AI system assisting human interpretation.

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

The device described, the FastPack® High Sensitivity C-Reactive Protein Immunoassay, is an automated immunoassay system. Its performance is inherently "standalone" in the sense that the analyzer performs the measurement without human intervention influencing the quantitative result. The performance data presented (precision, linearity, limits, interference, method comparison) is the standalone performance of the algorithm/system. There is no "human-in-the-loop" component in terms of result generation for this type of device.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.):

The "ground truth" for the performance studies of this immunoassay primarily relies on:

• Reference Methods/Predicate Device Results: For method comparison, the results obtained from a legally marketed predicate device (Olympus AU2700 for the method comparison) served as the reference for comparison.
• Known Concentrations: For studies like linearity, limits of detection/quantitation, and precision, samples with known, spiked, or characterized CRP concentrations are used.
• Clinical Samples: For serum and plasma equivalence and reference interval studies, collected human serum and plasma samples are used. The CRP concentrations in these samples, as measured by the device itself or a reference method, serve as the "true" or observed values for evaluating performance parameters.

8. The Sample Size for the Training Set:

This information is not applicable in the context of this document. This device is an immunoassay, not an AI/machine learning system that requires a "training set" in the computational sense. The device's operational parameters, calibration curves, and analytical procedures are established through manufacturing and analytical validation processes, not through machine learning training on a dataset.

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

This information is not applicable as there is no "training set" for this type of immunoassay device in the context of an AI/machine learning system. The "ground truth" for calibrating immunoassays is established using reference materials with assigned values traceable to international standards (e.g., ERM-DA474/IFCC for CRP, as mentioned in the device's traceability). These reference materials are meticulously characterized using highly accurate and precise analytical methods.

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The Diazyme high sensitivity C-reactive protein (hsCRP) POC Test Kit is for the in vitro quantitative determination of C-reactive protein (CRP) in human venous whole blood on SMART analyzers. Measurement of CRP is of use for the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. For in vitro diagnostic use only.

The Diazyme hsCRP POC control set is intended for use as quality controls for the Diazyme hsCRP POC Test Kit. For in vitro diagnostic use only.

Diazyme's hsCRP POC Test Kit is based on a latex enhanced immunoturbidimetric assay on Diazyme's SMART analyzer. Agglutination occurs when an antigen-antibody reaction occurs between CRP in a sample and anti-CRP which has been sensitized to latex particles. This agglutination is detected as an absorbance change (700 nm), with the magnitude of the change being proportional to the quantity of CRP in the sample. The instrument calculates the CRP concentration of patient specimen by use of a lot specific calibration curve that is stored in an RFID card provided with each hsCRP POC kit. The RFID card is inserted in the SMART analyzer and is needed for every single run.

Diazyme hsCRP POC Control Kit is intended for use as quality controls for the Diazyme hsCRP POC Test Kit and is packaged separately. The quality controls assist laboratory users in verification steps ensuring that the assay reagents are functioning correctly. OC materials are run exactly as samples. Users are instructed to verify the calibration curve with the controls and run controls each time a new lot of reagents are received. If OC materials fall outside laboratory acceptable range, users are instructed to re-test and call manufacturer customer service if problem persists.

SMART Analyzer (K092911) is a compact cuvette based spectrophotometer (10 inches x 5.5 inches x 5.5 inches) machine for point-of-care testing designed to analyze readings from single use reagent cuvette. The instrument only uses the Diazyme Reagent System (DRS) cuvette and caps and performs assay with a preprogrammed Radio Frequency ID (RFID) card. The DRS cuvette is supplied prefilled with Reagent 1 (R1) and the DRS cap is supplied prefilled with Reagent 2 (R2). The DRS cuvette and caps are kept separate until use. Users are instructed (see proposed labeling) to add 20ul of sample to the DRS cuvette prefilled with R1 containing proper amount of detergent for whole blood lysis. Users are then instructed to snap in place DRS cap and insert into analyzer. The instrument warms the cuvette to 37°C and after a predefined period adds the reagent R2 found in the DRS cap. The reagents and samples are mixed magnetically and absorbance readings are taken at 700nm. The lot specific RFID card contains reagent addition time, mixing time, reading time and calibration curve.

The Diazyme hsCRP POC Test Kit system thus consists of the following:

• hsCRP POC Test Kit. Reagents are provided in prefilled tubes, cuvettes and . cuvette caps. The DRS cuvette and cuvette caps can only work with the SMART analyzer.
• hsCRP POC Control Kit. Controls are provided for quality control of the . hsCRP POC Assay.

Equipment needed for Diazyme hsCRP POC Test Kit:

• SMART Analyzer (K092911).

Kit components

(Candidate device)

Reagent 1

40 DRS cuvette (prefilled)

• · 100 mM TrisCl buffer
  Reagent 2

40 DRS caps (prefilled)

• Suspension of anti-human CRP polyclonal antibody coated latex particles . (

The document describes the Diazyme hsCRP POC Test Kit, an in vitro diagnostic device for quantitative determination of C-reactive protein (CRP) in human venous whole blood. The device is intended for the detection and evaluation of inflammatory disorders, associated diseases, infection, and tissue injury.

Here's an analysis of the acceptance criteria and supporting studies:

1. Table of Acceptance Criteria and Reported Device Performance:

The document outlines several performance tests with specific acceptance criteria and the observed results.

• 0.813 mg/L: 9.62%
• 3.186 mg/L: 2.83%
• 12.560 mg/L: 1.79%
  Total Precision CV%:
• 0.813 mg/L: 8.17%
• 3.186 mg/L: 3.09%
• 12.560 mg/L: 2.12% |
  | Precision (External) | Within-run and total CV% (specific values not explicitly stated, but generally low for diagnostic devices) | Within Run CV% (POL sites):
• 0.798 mg/L: 4.67%
• 4.796 mg/L: 7.02%
• 0.758 mg/L: 9.04%
• 17.796 mg/L: 4.18%
• 7.780 mg/L: 5.43%
• 18.725 mg/L: 5.02%
  Total CV% (POL sites):
• 0.798 mg/L: 8.58%
• 4.796 mg/L: 7.37%
• 0.758 mg/L: 8.13%
• 17.796 mg/L: 4.02%
• 7.780 mg/L: 5.24%
• 18.752 mg/L: 4.78% |
  | Linearity | (Implicitly to support AMR) | Linearity data and LOQ data support Analytical Measuring Range (AMR) of 0.47 mg/L to 23.0 mg/L. |
  | Limit of Detection (LOD) | (Implicitly to determine lower detection limit) | LOD is 0.15 mg/L |
  | Limit of Quantitation (LOQ) | (Implicitly to determine lower quantitation limit) | LOQ is 0.47 mg/L |
  | Analytical Specificity (Interference) |

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