(335 days)
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
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Measuring Range | Limit of Quantitation (LOQ): Not explicitly stated as an acceptance criterion, but determined according to CLSI EP17-A2. | LOQ: 5 mg/L (Serum) |
| Linearity: Not explicitly stated as an acceptance criterion, but evaluated according to CLSI EP06-A. Range should cover desirable range and extend to lowest and highest ends. | Linearity Range: 9.42 to 150.78 mg/L (Serum) | |
| Measuring Range: Not explicitly stated as an acceptance criterion, but based on LOQ and linearity studies. | Measuring Range: 5.0 to 160 mg/L (until 800 mg/L with post-dilution) | |
| Accuracy and Precision | Within-run CV limits: Low level: 9.0%, Middle level: 4.5%, High level: 3.8% | Within-run CV: All reported values for samples and controls are well below the limits (e.g., 0.8% - 1.8%) |
| Total precision CV limits: Low level: 12.0%, Middle level: 6.0%, High level: 5.0% | Total Precision CV: All reported values for samples and controls are well below the limits (e.g., 1.5% - 2.9%) | |
| Interferences | Acceptable bias is defined at +/-10% of the value without interfering substances. | Highest reported values for various interferents show no interference higher than 10%. |
| Matrix Comparison | Not explicitly stated as an acceptance criterion, but results should show no significant difference between serum and plasma with heparin specimens. | Correlation (R) of 0.996 and slope (0.8973 – 1.007) and intercept (-0.1611 – +0.6459) for 38 samples; concluded "no significative difference." |
| Method Comparison | Not explicitly stated as an acceptance criterion, but evaluated using NCCLS (CLSI) EP-9A3. | Correlation (R2) of 0.998 and slope (0.9680 – 0.9976) and intercept (-0.1357 – +0.6287) for 102 samples. |
| Reagent Stability | Closed stability: Stable up to the expiry date on the label if stored at 2-10°C. | Shelf Life: 24 months. |
| Open stability (on-board): Not explicitly stated as an acceptance criterion, but assessed. | On-board stability: 8 weeks. | |
| Reference Range | Verification studies should support established reference ranges in literature for adults: 20-60 years < 5 mg/L. | Verification studies support the reference range of < 5 mg/L for adults (20-60 years). |
2. Sample size used for the test set and the data provenance
- Limit of Quantitation (LOQ): Five samples were used, assayed over five days, with two runs of four replicates per sample per day (for each reagent lot). These samples came from diluting individual serum samples by commercial depleted serum.
- Linearity: Each level of a range of samples (covering 9.42 to 150.78 mg/L) was assayed 3 times. The highest concentration sample was pooled human sera spiked with CRP stock solution.
- Total Precision (20x2x2):
- Sample Size: 240 measurements per sample/control (20 days * 2 series/day * 2 replicates/series * 3 analyzers * 3 reagent lots, assuming pooling of data) for 5 specimens (pooled human sera) and 2 controls (Yumizen C1200 Level 1 and 2 Protein Control).
- Provenance: Pooled human sera were anonymous remnants of human sera specimens collected from routine clinical laboratory.
- Instrument Variability (3x5x2x3):
- Sample Size: 90 measurements per sample/control (3 instruments * 5 days * 2 series/day * 3 replicates/series) for 6 samples (pooled human sera) and 2 controls (Yumizen C1200 Level 1 and 2 Protein Control).
- Provenance: Pooled human sera were anonymous remnants of human sera specimens collected from routine clinical laboratory.
- Lot to Lot Variability (3x5x2x3):
- Sample Size: 90 measurements per sample/control (3 reagent lots * 5 days * 2 series/day * 3 replicates/series) for 6 samples (pooled human sera) and 2 controls (Yumizen C1200 Level 1 and 2 Protein Control).
- Provenance: Pooled human sera were anonymous remnants of human sera specimens collected from routine clinical laboratory.
- Interferences: Pooled Human sera were used. Substances were added to base sera at two different CRP concentrations (normal and high).
- Exogenous Interferences (Matrix Comparison): 38 paired samples (sera and heparinized plasma) from individual donors from a blood bank were evaluated. Only native samples were used.
- Method Comparison: 102 native samples were used, assayed in duplicate. These samples were anonymous remnants of human serum specimens collected from routine clinical laboratory.
- Reference Range: 80 "normal samples" from a blood bank were assayed in duplicates.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not provided in the given text. For an in vitro diagnostic device like the Yumizen C1200 CRP, the "ground truth" for quantitative measurements is typically established through reference methods or established calibrators, not through expert consensus in the same way an imaging AI algorithm's ground truth might be. The reference ranges are verified against literature, not established by experts for the study itself.
4. Adjudication method for the test set
This information is not applicable for this type of in vitro diagnostic device study. Adjudication methods like 2+1 or 3+1 are typically used for establishing ground truth in studies involving human interpretation (e.g., radiology reads for an AI algorithm), not for quantitative analytical performance studies of a laboratory instrument and reagent.
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 as this is an in vitro diagnostic device for C-reactive protein (CRP) measurement, not an AI-assisted diagnostic tool that involves human readers/interpreters.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is a standalone diagnostic system (instrument + reagent) for measuring CRP. Its performance is entirely "algorithm only" in the sense that the instrument provides a quantitative result without human-in-the-loop interpretation of raw data, beyond operating the instrument and interpreting the numerical output. The studies detailed (linearity, precision, interference, method comparison) are all evaluating this standalone performance.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The "ground truth" for the performance characteristic studies of the Yumizen C1200 CRP reagent is established through:
- Reference methods and calibrators: For accuracy and linearity, performance is assessed against known concentrations or calibrated materials (e.g., using ERM-DA 474 or IRMM/ERM-DA472/IFCC for traceability).
- Statistical analysis: Precision measurements rely on statistical reproducibility.
- Comparative methods: Method comparison studies compare the device's results to a legally marketed comparator device (BECKMAN COULTER CRP reagent model: CRP LATEX REAGENT OSR6199 on Olympus AU400).
- Reference literature: The reference range for CRP is verified against established scientific literature.
8. The sample size for the training set
This information is not applicable as this is an in vitro diagnostic device, not a machine learning or AI model that requires a "training set." The development of the reagent and instrument might involve internal optimization, but it's not described in terms of a formal "training set" like an AI model.
9. How the ground truth for the training set was established
This information is not applicable for the reasons stated in point 8.
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June 25, 2020
Horiba ABX SAS Caroline Ferrer Regulatory Affairs Manager Parc Euromedecine, Rue du Caducee BP7290 Montpellier Cedex 4, 34184France
Re: K192028
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 25, 2019 Received: July 26, 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 statutes and regulations administered by other Federal agencies. You must comply with all the Act's
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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 (OS) 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 mediation-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,
Ying (Katelin) Mao, Ph.D. Acting Chief Division of Immunology and Hematology 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) K 192028
Device Name Yumizen C1200 CRP
Indications for Use (Describe)
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.
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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K192028 Yumizen C1200 Reagents
SECTION 007 : 510(k) Summary of K192028
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.
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K192028 Yumizen C1200 Reagents
- 1- Date of Summary Date submitted :25th June, 2020
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 (1300023877)
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 the quantitative in vitrodiagnostic determination of the C-reactive protein in human serum andlithium heparin plasma based on an immunoturbidimetric assay.Measurement of C-reactive protein aids in evaluation of the amount ofinjury to body tissues and for evaluation of infections, tissue injury andinflammatory disorders. This test should be used in conjunction with otherlaboratory and clinical findings. |
| 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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K192028 Yumizen C1200 Reagents
- In this submission, HORIBA Medical presents Yumizen C1200 CRP with the Conventional application.
- Predicate: K142993 : QuickRead go CRP on QuickRead go CRP Analyzer / Orion Diagnostica, Oy
Comparator : K051564 : CRP reagent model : CRP LATEX REAGENT OSR6199 ● on Olympus AU400 Clinical Chemistry Analyzer / BECKMAN COULTER
- This submission allows to evaluate the functionality of the Yumizen C1200 analyzer for immunology analytes (ie.immunoturbidimetry).
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 | QuickRead go CRP | Orion Diagnostica, Oy | K142993 |
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
Conventional method
i. Comparison with predicate Device : Similarities
| Device & Predicate Device(s) : | Predicate K142993 | Candidate K192028 |
|---|---|---|
| Device Trade Name | QuikRead Go CRP | Yumizen C1200 CRP (1300023877) |
| Intended Use | The QuikRead go CRP test is animmunoturbidimetric assay for the in vitroquantitative determination of C-reactiveprotein (CRP) in K2-EDTA and lithiumheparin whole blood, K2-EDTA andlithium heparin plasma and in serumsamples.The test is carried out by means of theQuikRead go instrument. Measurement ofC-reactive protein aids in the evaluation ofinjury to body tissues, and infection andinflammatory disorders. The instrumentand assay are for use by trainedprofessionals in the clinical laboratory. Forin vitro diagnostic use only.Not for point-of-care use. | Yumizen C1200 CRP reagent isintended for the quantitative in vitrodiagnostic determination of the C-reactive protein in human serum andlithium heparin plasma based on animmunoturbidimetric assay.Measurement of C-reactive protein aidsin evaluation of the amount of injury tobody tissues and for evaluation ofinfections, tissue injury andinflammatory disorders. This test shouldbe used in conjunction with otherlaboratory and clinical findings. |
| Technology | Immunoturbidimetry | Same |
| Assay Type | Quantitative | Same |
| Analyte | C-reactive protein | Same |
| Product Code | DCK | Same |
| Reference Range | < 5 mg/L* | Same |
*20 to 60 years
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ii. Comparison with predicate Device: Differences
| Device & PredicateDevice(s) : | Predicate K142993 | Candidate K192028 |
|---|---|---|
| Device TradeName | QuikRead Go CRP | Yumizen C1200 CRP (1300023877) |
| Instrument | QuikRead go Analyzer | Yumizen C1200 Clinical chemistryAnalyzer |
| Test | Microparticles | Latex particles |
| Antibody | Anti-human CRP F(ab)2 fragment | Rabbit anti-CRP antibodies |
| Sample Type | serum,plasma (Li-Heparin,K2-EDTA),whole blood (Li-heparin, K2-EDTA) | Serum,lithium heparin plasma |
| AnalyticalMeasuring Range | 5 to 200 mg/L: serum and plasma5 to150 mg/L: whole blood | 5 to 160 mg/L |
| Traceability | ERM-DA 474 | IRMM/ERM-DA472/IFCC |
| Control | Control 1: ~30 mg/LControl 2: ~70 mg/L | Control 1: ~15 mg/LControl 2: ~80 mg/L |
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
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- CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures - Second Edition - June 2012
- 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 : 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. References Cited
- Valtec guideline (Vassault et al., Ann. Biol. Clin., 1986, (44), 686-745
8- Device Description
- Method
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.
- Reagent : composition and Description
Reagents Yumizen C1200 CRP is ready-to-use.
Reagent 1: Buffer solution: Glycine buffer solution Reagent 2:
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K192028 Yumizen C1200 Reagents
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.
9- Analytical Performance Characteristics
9.1 Measuring Range
● LOQ
The limit of detection and quantitation was determined according to the CLSI guideline EP17-A2.
Description of Test Procedure/Method
A range of low concentrations samples has been assayed following this conditions:
- Two reagents lots -
- One instrument system -
- -Five days
- -Five samples
- Two run, four replicates per run per sample (for each reagent lot, each day) -
- -1 technician
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Sample selection: Samples come from dilution of individual serum samples by commercial depleted serum.
● Linearity
The reagent linearity was determined according to CLSI guideline EP06-A.
Description:
The linearity is evaluated using a range of samples, at different concentrations covering the desirable range, extended in the lowest and the highest ends.
Each level has been assayed 3 times.
The highest concentration sample used for this study is a pooled human sera sample spike with CRP stock solution.
The limit of quantitation and the linearity studies showed that claimed measuring range is appropriate.
-
Results :
| Limit ofdetection | Limit ofquantitation | Linearity Evaluated | Measuring range | |
|---|---|---|---|---|
| Serum | 0.23 mg/L | 5 mg/L | 9.42 to 150.78 mg/L. | 5.0 to 160 mg/L, |
| SerumPost-dilution | NA | NA | up to 737.40 mg/L | until 800 mg/L |
With Linearity – range 9.42 – 150.78 mg/L
| Range (mg/L) | Slope(95%CI) | Intercept(95% CI) | R2 |
|---|---|---|---|
| 9.42 - 150.78 | 1.026(1.005 – 1.047) | -1.33(-3.23 – +0.58) | 0.9972 |
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9.2 Accuracy and Precision
Standards Followed CLSI document, EP5-A3
-
. Total Precision : 20x2x2
Study materials : -
Yumizen C1200 Level 1 Protein Control ı
-
i Yumizen C1200 Level 2 Protein Control
-
i Pooled human sera, anonymous remnants of human sera specimens collected from routine clinical laboratory.
Description of Test Procedure/Method
This evaluation was performed using 3 analyzers using 3 reagent lot.
The dedicated controls and 5 specimens covering the measuring range (low, medium and high) were tested in duplicate for 20 days, two series per day.
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 %.
| Sample | N | Mean(mg/L) | Within-run | Between-run | Between-day | Between-instrument | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| 1 | 240 | 5.06 | 0.042 | 0.8 | 0.053 | 1.0 | 0.125 | 2.5 | 0.037 | 0.7 | 0.147 | 2.9 |
| 2 | 240 | 9.79 | 0.075 | 0.8 | 0.075 | 0.8 | 0.083 | 0.8 | 0.052 | 0.5 | 0.144 | 1.5 |
| 3 | 240 | 27.61 | 0.208 | 0.8 | 0.388 | 1.4 | 0.629 | 2.3 | 0.000 | 0.0 | 0.768 | 2.8 |
| 4 | 240 | 65.33 | 0.597 | 0.9 | 0.582 | 0.9 | 0.921 | 1.4 | 0.303 | 0.5 | 1.279 | 2.0 |
| 5 | 240 | 141.27 | 2.546 | 1.8 | 0.000 | 0.0 | 2.372 | 1.7 | 0.976 | 0.7 | 3.614 | 2.6 |
| Control 1 | 240 | 16.57 | 0.130 | 0.8 | 0.235 | 1.4 | 0.338 | 2.0 | 0.000 | 0.0 | 0.432 | 2.6 |
| Control 2 | 240 | 74.88 | 0.637 | 0.9 | 0.888 | 1.2 | 0.847 | 1.1 | 0.567 | 0.8 | 1.494 | 2.0 |
The results are within the specifications.
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- Instrument variability : 3x5x2x3 ●
- Yumizen C1200 Level 1 Protein Control Study materials: - Yumizen C1200 Level 2 Protein Control - Pooled human sera, anonymous remnants of human sera specimens collected
from routine clinical laboratory
Description of Test Procedure/Method
The experimental is:
- One reagent lot -
- -Three instruments systems
- -2 controls and 6 samples tested in triplicate for 5 days, two series per day.
- -Calibrations are done at the beginning of the study.
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 %.
| Sample | N | Mean(mg/L) | Within-day | Between-day | Within-instrument | Between-instrument | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| 1 | 90 | 5.16 | 0.055 | 1.1 | 0.066 | 1.3 | 0.086 | 1.7 | 0.104 | 2.0 | 0.135 | 2.6 |
| 2 | 90 | 9.80 | 0.085 | 0.9 | 0.049 | 0.5 | 0.098 | 1.0 | 0.094 | 1.0 | 0.136 | 1.4 |
| 3 | 90 | 25.44 | 0.268 | 1.1 | 0.174 | 0.7 | 0.319 | 1.3 | 0.653 | 2.6 | 0.727 | 2.9 |
| 4 | 90 | 71.28 | 0.944 | 1.3 | 1.078 | 1.5 | 1.433 | 2.0 | 0.884 | 1.2 | 1.683 | 2.4 |
| 5 | 90 | 94.77 | 1.227 | 1.3 | 0.714 | 0.8 | 1.420 | 1.5 | 1.052 | 1.1 | 1.767 | 1.9 |
| 6 | 90 | 139.02 | 2.080 | 1.5 | 0.815 | 0.6 | 2.234 | 1.6 | 1.839 | 1.3 | 2.893 | 2.1 |
| Control 1 | 90 | 14.32 | 0.162 | 1.1 | 0.196 | 1.4 | 0.254 | 1.8 | 0.320 | 2.2 | 0.409 | 2.9 |
| Control 2 | 90 | 71.50 | 1.024 | 1.4 | 1.244 | 1.7 | 1.611 | 2.3 | 1.232 | 1.7 | 2.028 | 2.8 |
The results are within the specifications.
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- Lot to Lot variability : 3x5x2x3 .
Study materials: - Yumizen C1200 Level 1 Protein Control
-
Yumizen C1200 Level 2 Protein Control
-
Pooled human sera, anonymous remnants of human sera specimens collected from routine clinical laboratory
Description of Test Procedure/Method The experimental is:
- -Three reagent lot
- -One instrument system
- -2 controls and 6 samples tested in triplicate for 5 days, two series per day.
- -Calibrations are done at the beginning of the study.
Within Run : CV limits, for the low, middle and high level are respectively 9.0 %, 4.5 % and 3.8 % for serum
Total Precision : CV limits, for the low, middle and high level are respectively 12.0 %, 6.0 % and 5.0 % for serum.
| Sample | N | Mean(mg/L) | Within-run | Between-day | Within-lot | Between-lot | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| 1 | 90 | 5.21 | 0.056 | 1.1 | 0.064 | 1.2 | 0.085 | 1.6 | 0.080 | 1.5 | 0.117 | 2.2 |
| 2 | 90 | 9.74 | 0.119 | 1.2 | 0.019 | 0.2 | 0.120 | 1.2 | 0.178 | 1.8 | 0.215 | 2.2 |
| 3 | 90 | 24.70 | 0.273 | 1.1 | 0.207 | 0.8 | 0.343 | 1.4 | 0.273 | 1.1 | 0.438 | 1.8 |
| 4 | 90 | 71.70 | 0.701 | 1.0 | 1.143 | 1.6 | 1.341 | 1.9 | 1.493 | 2.1 | 2.007 | 2.8 |
| 5 | 90 | 95.65 | 0.939 | 1.0 | 1.236 | 1.3 | 1.552 | 1.6 | 0.603 | 0.6 | 1.665 | 1.7 |
| 6 | 90 | 139.38 | 1.833 | 1.3 | 1.588 | 1.1 | 2.425 | 1.7 | 1.177 | 0.8 | 2.696 | 1.9 |
| Control 1 | 90 | 13.95 | 0.126 | 0.9 | 0.187 | 1.3 | 0.226 | 1.6 | 0.112 | 0.8 | 0.252 | 1.8 |
| Control 2 | 90 | 72.78 | 0.974 | 1.3 | 1.025 | 1.4 | 1.414 | 1.9 | 1.268 | 1.7 | 1.899 | 2.6 |
The results are within the specifications.
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9.3 Interferences
The Interferences were determined according to the CLSI guideline EP07-A2.
Study of the interferences from the hemolysis, triglycerides, icteria (total and direct bilirubin) samples and from Ascorbic Acid, Acetylsalicylic Acid, Ibuprofen, Acetaminophen, rheumatoid factor (RF), Erythromycin, Gentamycin, Ampicillin, Prednisone, Methotrexate, Etanercept, Simvastatin and Omeprazole on the CRP assay with the Yumizen C1200 CRP reagent on the Yumizen C1200.
Description of Test Procedure/Method
Study materials: Pooled Human sera. Substances were added to the base sera at two different CRP concentrations (normal and high). The base sera with each substance was then serially diluted with the same base sera for which same volume of diluent was added instead of substance to adjust CRP concentration.
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 | 5.77 mmol/L | 504 mg/dL |
| Total Bilirubin | 607 µmol/ | 35.53 mg/dL |
| Direct Bilirubin | 393 µmol/L | 22.97 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 |
| Erythromycin | 200 µmol/L | 14.71 mg/dL |
| Gentamycin | 65 µmol/L | 3.11 mg/dL |
| Ampicillin | 250 µmol/L | 8.7 mg/dL |
| Prednisone | 0.500 µmol/L | 0.018 mg/dL |
| Methotrexate | 3000 µmol/L | 136 mg/dL |
| Etanercept | 0.05 µmol/L | 0.75 mg/dL |
| Simvastatin | 5 µmol/L | 0.21 mg/dL |
| Omeprazole | 25 µmol/L | 0.86 mg/dL |
| RheumatoidFactor | Up to 400 IU/mL |
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9.4 Exogenous interferences- Study of the coagulation effect on the CRP assay Matrix comparison
Study materials : Anticoagulant : heparin-lithium Samples: individual donors from blood bank
Description:
38 samples were evaluated on Yumizen C1200 analyser using Yumizen C1200 CRP reagent. For this study, each paired samples (sera and heparinized plasma) has been obtained from single donor.
Only native samples have been used for this study.
| Sample (N) | Range (mg/L) | Slope(95%CI) | Intercept(95% CI) | R |
|---|---|---|---|---|
| 38 | 5.09–133.86 | 0.9398(0.8973 – 1.007) | 0.3413(-0.1611 – +0.6459) | 0.996 |
Conclusion :
The results show there is not significative difference between serum and plasma with heparin specimens
-> coagulation does not have an impact on CRP determination.
9.5 Method comparison with a comparator device
Study materials :
Samples: Anonymous remnants of human serum specimens collected from routine clinical laboratory.
Description:
This study has been carried out using recommendations found in the NCCLS (CLSI) EP-9A3 guidance.
These samples are in the candidate measuring range and comparator measuring range.
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102 native samples have been assayed in duplicate, in ascendant order and descendant order on 6 working days.
Only the first replicate of each method will be used for the data analysis reported below. The equation for the regression line using Passing Bablok was obtained.
Passing Bablok
| Sample (N) | Range(mg/L) | Slope(95%CI) | Intercept(95% CI) | R2 |
|---|---|---|---|---|
| 102 | 5.25–144.48 | 0.9814(0.9680 – 0.9976) | 0.1305(-0.1357 – +0.6287) | 0.998 |
9.6 Reagent Stability
8.6.1. Closed stability
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 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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9.7 Reference range
The Reference Range was determined according to the CLSI guideline EP28-A3.
- CRP
Serum
- A Adults data
80 "normal samples" from blood bank have been assayed with the method in evaluation. Each sample is assayed in duplicates.
The mean of the duplicate results for each subject was compared against reference ranges cited in literature. The verification studies support in the following reference ranges which were established through literature.
Adults: 20-60 years < 5 mg/L
Reference.:
Roberts WL, McMillin GA, Burtis CA, Bruns DE. Reference Information for the Clinical Laboratory, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics; 4th Ed., Burtis CA, Ashwood ER, Bruns DE (Elsevier Saunders eds., St Louis, USA), (2006): 2263.
9.8 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.
9.9 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 each device is substantially equivalent to its predicate device.
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Yumizen C1200 Reagents
§ 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).