(70 days)
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:
| Performance Characteristic | Implicit Acceptance Criteria (based on CLSI guidelines & stated outcomes) | Reported Device Performance (Results) | Device Meets Criteria? |
|---|---|---|---|
| Measuring Range | Limit of detection, quantitation, and linearity appropriate for intended use. | Serum: | Yes (Stated "appropriate") |
| LOD (Detection Capability) | 0.13 mg/L | Yes | |
| LOQ (Quantitation Capability) | 0.16 mg/L | Yes | |
| Linearity Range | 0.03 to 11.53 mg/L | Yes | |
| Measuring Range | 0.2 to 10 mg/L (For hsCRP with 1:5 dilution, EMI is 10-50 mg/L) | Yes | |
| Accuracy and Precision | Within-run and total precision (CV limits) within defined specifications. | Serum (Calibration every week): | Yes (Stated "within specifications") |
| Within-run (%CV) | Low: 1.5-4.7%, Mid: 1.6-2.8%, High: 0.6-0.8% (for samples 1-4); Stated CV limits (general): Low 9.0%, Mid 4.5%, High 3.8% | Yes | |
| Total Precision (%CV) | Low: 3.0-5.9%, Mid: 2.1-3.8%, High: 2.4-3.1% (for samples 1-4); Stated CV limits (general): Low 12.0%, Mid 6.0%, High 5.0% | Yes | |
| Heparin-Lithium (Within-run precision): | Sample 1 (0.35 mg/L): 2.17% CV; Sample 2 (0.51 mg/L): 2.11% CV; Sample 3 (1.25 mg/L): 1.00% CV; Sample 4 (4.75 mg/L): 2.27% CV; Sample 5 (7.77 mg/L): 1.31% CV; Sample 6 (9.31 mg/L): 0.69% CV. Stated CV limits: Low 9.0%, Mid 4.5%, High 3.8%. | Yes (Stated "within specifications") | |
| Interferences | Acceptable bias +/-10% of value without interfering substances. | Highest values with no >10% interference: Hemoglobin 290 µmol/L, Triglycerides 279 mg/dL (Note: specific observation of -11.2% at 395 mg/dL triglycerides for 4.15 mg/L CRP, and -10.5% at 517 mg/dL for 0.83 mg/L CRP), Total Bilirubin 27.61 mg/dL, Direct Bilirubin 30.41 mg/dL, Ascorbic Acid 5.98 mg/dL, Acetylsalicylic Acid 65.16 mg/dL, Ibuprofen 50.10 mg/dL, Acetaminophen 20 mg/dL, Rheumatoid Factor up to 400 IU/mL. | Yes (Interference data stated to be included in labeling) |
| Matrix Comparison | No significant difference between Serum and Heparin-Lithium specimens. | Passing Bablok: N=54, Intercept -0.003012, Slope 0.9787, Correlation 0.998. | Yes (Stated "no significant difference") |
| Method Comparison | Good correlation/agreement with comparator device. | Passing Bablok (with predicate): N=138, Intercept -0.06852, Slope 0.9987, Correlation r² 0.995. | Yes |
| Reagent Stability | Meeting specified shelf life and on-board stability. | Closed Stability: 24 months (stable until expiry date at 2-10°C). | Yes |
| Open Stability (On-board): 8 weeks. | Yes (Stated "correct") |
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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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food & Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the agency's name on the right. The symbol is a stylized representation of human services. To the right of the symbol is the text "FDA U.S. FOOD & DRUG ADMINISTRATION" in blue.
October 3, 2019
Horiba ABX SAS Caroline Ferrer Regulatory Affairs Manager Parc Euromédecine, Rue du Caducée - BP7290 34184 Montpellier Cedex 4 France
Re: K191993
Trade/Device Name: Yumizen C1200 CRP Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCK Dated: July 24, 2019 Received: July 25, 2019
Dear Caroline Ferrer:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you. however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal
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cies. You must comply with all the Act's
statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
For: Kellie B. Kelm, Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K191993
Device Name Yumizen C1200 CRP
Indications for Use (Describe)
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.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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SECTION 007: 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
510(k) Number : K191993
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- 1- Date of Summary Date submitted : 25th September, 2019
2- Company
HORIBA ABX SAS HORIBA MEDICAL Parc Euromédecine Rue du Caducée – BP 7290 34184 Montpellier cedex 4 France
3- Contact person
Contact Person: Caroline Ferrer (caroline.ferrer@horiba.com) Telephone: + (33) 4 67 14 1843 Fax: + (33) 4 67 14 1517
4- Product Name
Yumizen C1200 CRP
5- Device Name and Classification
. Intended use
The devices involved by the 510(k) submission file are the following:
. Classification and Description
| Device's names | Intended Use |
|---|---|
| Yumizen C1200CRP | Yumizen C1200 CRP reagent is intended for use as a high sensitive assayfor the quantitative in vitro diagnostic determination of the C-reactive proteinin human serum and plasma based on an immunoturbidimetric assay. CRP isused to evaluate conditions thought to be associated with inflammation inotherwise healthy individuals. |
| Trade/Proprietary Name: | Yumizen C1200 CRP |
|---|---|
| Device Class: | Class II / 510(k) required |
| Classification Name: | §866.5270: C-reactive protein immunological test system |
| Product Code: | DCK |
| Panel: | Immunology (82) |
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- In this submission, HORIBA Medical presents Yumizen C1200 CRP with the High sensitive ● application.
6- Substantial Equivalence Information
The following tables show the similarities and differences and demonstrates substantial equivalence between the candidate device and its predicate device identified below.
a. Predicate Device Name and 510(k) number
| Candidate device | Predicate device | Predicate Manufacturer | Predicate510(k)number |
|---|---|---|---|
| Yumizen C1200 CRP | VITROS Chemistry ProductshsCRP Reagent | Ortho-Clinical Diagnostics,Inc. | K160712 |
The following tables show the similarities and differences and demonstrates substantial equivalence between the candidate device and its predicate device identified below.
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b. Yumizen C1200 CRP
i. Comparison with predicate Device : Similarities
| Item | Predicate K160712 | Candidate |
|---|---|---|
| Device Name | VITROS Chemistry Products hsCRPReagent | Yumizen C1200 CRP |
| Intended Use | 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. | 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. |
| Reagent format | Liquid | Same |
| Method | Immunoturbidimetry | Same |
| Measurement | Quantitative | Same |
| Product code | DCK | DCK |
| Sample type | Serum,and Lithium heparin plasma | Serum,and Lithium heparin plasma |
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| Item | Predicate K160712 | Candidate |
|---|---|---|
| Device Name | VITROS Chemistry Products hsCRPReagent | Yumizen C1200 CRP |
| Instrument | VITROS 4,1 FS/4600 Chemistry | Yumizen C1200 Clinical chemistryAnalyzer |
| Manufactured by | Ortho-Clinical Diagnostics, Inc. | HORIBA ABX SAS |
| Calibrators | VITROS Chemistry Products CalibratorKit 17VITROS Chemistry Products FSCalibrator 1VITROS Chemistry Products FS DiluentPack 2 (BSA/Saline) (for calibration only) | Yumizen C1200 CRPhs Cal(1300071246) |
| Controls | VITROS Chemistry Products hsCRPPerformance Verifier I, II and III | Yumizen C1200 Level 1 CRPhs Control(1300071247)Yumizen C1200 Level 2 CRPhs Control(1300071248) |
| Analytical Range | 0.10 to 15.00 mg/L | 0.2 to 10 mg/L |
| ReagentOn board Stability | ≤ 4 weeks | 8 weeks |
| Shelf-life | Stable until the expiration date printed onthe label when stored at 2-8°C | Stable up to expiry date on the label ifstored at 2-10°C |
ii. Comparison with predicate Device: Differences
- Calibrators&Controls : Yumizen C1200 CRP uses Yumizen C1200 CRPhs Cal and 2 Levels of controls : Yumizen C1200 Level 1 CRPhs Control and Yumizen C1200 Level 2 CRPhs Control.
on Yumizen C1200 whereas the predicate uses VITROS Chemistry Products calibrator Kit 17.
- Analytical range: The measuring range for Yumizen C1200 CRP is different.
Concerning low value, it is similar but slightly lower than the predicate value.
Concerning high value, it is lower than the predicate value.
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| Item | Predicate K160712 | Candidate |
|---|---|---|
| 4.On board stability: | The on board stability of Yumizen C1200CRP is longer.Stability depends on the reagent composition and cassette capacity. | |
| 5.Shelf-life | Yumizen C1200 CRP has a reagent stability up to the expiration date when unopened and stored in 2-10°C. |
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7- Special Control/Guidance Document Referenced
a. Standards Followed
The following standards & FDA guidance documents have been used to support this submission:
CLSI Guidelines:
- CLSI EP05-A3:Evaluation of Precision of Quantitative Measurement Procedures- Third Edition - October 2014
- CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement ● Procedures - Second Edition - June 2012
- CLSI EP09-A3: Measurement Procedure Comparison and Biais Estimation Using Patient ● Samples- Third Edition - August 2013
- . CLSI EP06-A: Evaluation of the Linearity of Quantitative measurement Procedures A Statistical Approach - First Edition - April 2003
- CLSI C28-A3: Defining, Establishing, and Verifying Reference Intervals in the Clinical ● laboratory- Third Edition - November 2008
- CLSI EP25-A : Evaluation of Stability of In Vitro Diagnostic reagents- First Edition-September 2009
b. FDA Guidances Followed
- Guidance for Industry and FDA Staff : Format for Traditional and Abbreviated 510(k)s - 2005
- Refuse To Accept (RTA) Policy for 510(k) - Guidance for Industry and Food and Drug Administration Staff - Document issued on: February 21, 2019.
- . Guidance for Industry and FDA Staff : eCopy Program for Medical Device Submissions -2015
- Guidance for Industry and FDA Staff : Review Criteria for Assessment of C-Reactive Protein ● (CRP), High Sensitivity C-Reactive Protein (hsCRP) and Cardiac C-Reactive Protein (cCRP Assays) - Document issued on : September 22, 2005
c. Others Guidances followed
- Valtec guideline (Vassault et al., Ann. Biol. Clin., 1986, (44), 686-745)
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8- Analytical Performance Characteristics
8.1 Measuring Range
The limit of detection and quantitation was determined according to the CLSI guideline EP17-A2. The reagent linearity was determined according to CLSI guideline EP06-A. The limit of quantitation and the linearity studies showed measuring range is appropriate.
≫ Results :
| Limit ofdetection | Limit ofquantitation | Linearity | Measuring range | |
|---|---|---|---|---|
| Serum | 0.13 mg/L | 0.16 mg/L | 0.03 to 11.53 mg/L. | 0.2 to 10 mg/L |
For hsCRP with 1:5 dilution, the EMI is 10-50 mg/L.
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8.2 Accuracy and Precision
- Repeatability (within-run precision) and Reproducibility (total precision) Serum samples .
Within run : CV limits, for the low, middle and high level are respectively 9.0 %, 4.5 % and 3.8 %. Total precision: CV limits, for the low, middle and high level are respectively 12.0 %, 6.0 % and 5.0 %.
Results with calibration every week (previous study):
| Sample | N | Mean(mg/L) | Within-Run(%CV) | Between-Run(%CV) | Between-Day(%CV) | Between-Instrument(%CV) | Total(%CV) |
|---|---|---|---|---|---|---|---|
| Low CRP Control(internal control) | 240 | 1.50 | 1.5 | 1.8 | 1.9 | 0.0 | 3.0 |
| Sample 1 | 240 | 0.34 | 4.7 | 2.8 | 2.3 | 0.1 | 5.9 |
| Sample 2 | 240 | 0.83 | 1.6 | 2.6 | 0.9 | 2.1 | 3.8 |
| Sample 3 | 240 | 4.13 | 0.6 | 1.7 | 1.7 | 1.9 | 3.1 |
| Sample 4 | 240 | 8.73 | 0.8 | 2.5 | 1.2 | 1.0 | 3.1 |
Results with calibration only at the beginning of the study (new study):
| Sample | N | Mean(mg/L) | Within-Run(%CV) | Between-Run(%CV) | Between-Day(%CV) | Between-Instrument(%CV) | Total(%CV) |
|---|---|---|---|---|---|---|---|
| Low CRP Control(internal control) | 240 | 1.50 | 1.3 | 0.4 | 1.0 | 1.1 | 2.0 |
| Sample 1 | 240 | 0.39 | 4.8 | 0.0 | 1.6 | 3.7 | 6.2 |
| Sample 2 | 240 | 1.27 | 3.3 | 1.7 | 1.7 | 2.1 | 4.6 |
| Sample 3 | 240 | 3.00 | 1.3 | 1.4 | 0.7 | 0.6 | 2.1 |
| Sample 4 | 240 | 8.81 | 0.8 | 0.4 | 1.6 | 1.5 | 2.4 |
The results are within the specifications.
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- Repeatability (within-run precision) for Heparin-Lithium sample
Study materials:
Anonymous remnants of human Heparin-Lithium specimens collected from routine clinical laboratory.The within-run precision is performed using one lot of reagent, one instrument in a single run.
Description:
6 specimens (sample low, mid, high) were tested 20 times in a single run for each sample.
Within run : CV limits, for the low (1 mg/L), middle (5 mg/L) and high level (9 mg/L) are respectively 9.0 %, 4.5 % and 3.8 %.
| Sample | N | Mean(mg/L) | Within-Run(%CV) | SD(mg/L) |
|---|---|---|---|---|
| Sample 1 | 20 | 0.35 | 2.17 | 0.01 |
| Sample 2 | 20 | 0.51 | 2.11 | 0.01 |
| Sample 3 | 20 | 1.25 | 1.00 | 0.01 |
| Sample 4 | 20 | 4.75 | 2.27 | 0.11 |
| Sample 5 | 20 | 7.77 | 1.31 | 0.10 |
| Sample 6 | 20 | 9.31 | 0.69 | 0.06 |
The results are within the specifications.
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8.3 Interferences
The Interferences were determined according to the CLSI guideline EP07-A2. The acceptable bias is defined at +/-10% of the value without interfering substances. These data in the following table represent the highest values for which no interferences higher than 10% have been observed.
| Serum | ||
|---|---|---|
| Hemoglobin | 290 µmol/L | 500 mg/dL |
| Triglycerides | 3.19 mmol/L | 279 mg/dL |
| Total Bilirubin | 472 µmol/ | 27.61 mg/dL |
| Direct Bilirubin | 520 µmol/L | 30.41 mg/dL |
| Ascorbic Acid | 340 µmol/L | 5.98 mg/dL |
| AcetylsalicylicAcid | 3.62 mmol/L | 65.16 mg/dL |
| Ibuprofen | 2.43 mmol/L | 50.10 mg/dL |
| Acetaminophen | 1324 µmol/L | 20 mg/dL |
| RheumatoidFactor | Up to 400 IU/mL |
Concerning Triglycerides Interferences :
At 395 mg/dL triglycerides, there was a deviation of -11.2% per sample with a concentration of 4.15 mg/L CRP, and at 517 mg/dL triglycerides, there was a deviation of -10.5% per sample with a concentration of 0.83 mg/L CRP.
Concerning Rheumatoid Factor Interferences :
"No significant influence is observed up to 400 IU/mL when tested at ~5 mg/L and ~9 mg/L CRP."
This information is included in the reagent Instruction for use.
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8.4 Matrix comparison
● Matrix comparison serum vs heparin-lithium on Yumizen C1200
Study materials :
Anticoagulant : heparin-lithium
Samples: individual donors from blood bank (in serum and plasma for each donor)
Description of Test Procedure/Method
54 samples were evaluated on Yumizen C1200 analyzer using Yumizen C1200 CRP reagent. For this study, each sample came from single donor. Samples was collected both in serum and heparin-lithium tube.
| Passing Bablok | N | Min | Max | Intercept | Slope | Correlation |
|---|---|---|---|---|---|---|
| CRP(mg/L) | 54 | 0.210 | 9.180 | -0.003012 | 0.9787 | 0.998 |
Conclusion :
The results show there is no significant difference between Serum and Heparin-Lithium specimens for the method in evaluation.
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8.5 _ Method comparison with a comparator device
Comparator :
This study has been carried out using recommendations found in the NCCLS (CLSI) EP-9A3guidance. Samples: Anonymous remnants of human serum specimens collected from routine clinical laboratory. These samples are in the candidate measuring range and comparator measuring range.
138 native samples have been assayed in duplicate, in ascendant order and descendant order on 6 working days.
The equation for the regression line using Passing Bablok was obtained.
| Passing Bablok | N | Min | Max | Intercept | Slope | Correlation - r² |
|---|---|---|---|---|---|---|
| CRP (mg/L) | 138 | 0.200 | 9.570 | -0.06852 | 0.9987 | 0.995 |
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8.6 Reagent Stability
Closed stability 8.2.1
The closed stability was determined according to the CLSI guideline EP25-A.
Stability before opening: Stable up to the expiry date on the label if stored at 2-10°C.
. CRP
The Shelf Life of Yumizen C1200 CRP is correct at 24 months.
8.6.2 Open stability
The open stability was determined according to the CLSI guideline EP25-A.
On board reagent Stability:
The stability claim after opening, on-Board, is 8 weeks.
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Traditional 510(k): Original Submission Yumizen C1200 Reagents
8.7 Reference range
Serum / Plasma
<1mg/L
Reference :
Raifai N, Ridker PM. Population Distributions of C- reactive Protein in Aparently Healthy Men and Women in the United States: Implication for Clinical Interpretation. Clin Chem (2003) 49: 666-669.
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8.8 Proposed Labeling
The labeling is written as per the recommendations given in standard EN18113-2. It takes into account the requirements of 21 CFR Part 809.10.
8.9 Conclusions for Performance Testing
The performance testing data conclude that the safety and effectiveness of the devices are not compromised, and that they met all acceptance criteria, demonstrating that this device is substantially equivalent to its predicate device.
§ 866.5270 C-reactive protein immunological test system.
(a)
Identification. A C-reactive protein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.(b)
Classification. Class II (performance standards).