(497 days)
Yumizen C1200 Creatinine PAP reagent is intended for the quantitative in vitro diagnostic determination of Creatinine in human serum, plasma and urine based on an enzymatic method using a multi- step approach ending with a photometric end-point reaction. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
Yumizen C1200 Creatinine PAP reagent is intended for the quantitative in vitro diagnostic determination of Creatinine in human serum, plasma and urine based on an enzymatic method using a multi- step approach ending with a photometric end-point reaction.
The Horiba ABX SAS Yumizen C1200 Creatinine PAP device is an in vitro diagnostic intended for the quantitative determination of Creatinine in human serum, plasma, and urine. Its performance was evaluated through various analytical studies to demonstrate substantial equivalence to its predicate device, the ABX Pentra Enzymatic Creatinine CP.
Here's a breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implicit from "within specifications") | Reported Device Performance (Yumizen C1200 Creatinine PAP) |
|---|---|---|
| Measuring Range | ||
| Serum Limit of Quantitation | Not explicitly stated, but implies the lowest concentration measurable with acceptable precision. | 0.11 mg/dL |
| Serum Linearity | Not explicitly stated, but implies correlation across range. | 0.04 - 19.93 mg/dL |
| Serum Measuring Range | Not explicitly stated, but likely the linear range with acceptable bias. | 0.11 - 16.95 mg/dL (up to 50.85 mg/dL with post-dilution) |
| Urine Limit of Quantitation | Not explicitly stated, but implies the lowest concentration measurable with acceptable precision. | 1.13 mg/dL |
| Urine Linearity | Not explicitly stated, but implies correlation across range. | 0.00 - 327.60 mg/dL |
| Urine Measuring Range | Not explicitly stated, but likely the linear range with acceptable bias. | 3.56 - 175 mg/dL (up to 525 mg/dL with post-dilution) |
| Accuracy and Precision (Instrument Variability - Serum/Plasma) | ||
| Within-run CV (low level) | ≤ 4.5 % | 0.5% (Yumizen N Multi Control), 1.4% (Sample 1) |
| Within-run CV (middle level) | ≤ 3.4 % | 0.3% (Yumizen P Multi Control), 0.5% (Sample 2) |
| Within-run CV (high level) | ≤ 1.8 % | 0.3% (Sample 3) |
| Total CV (low level) | ≤ 6.0 % | 1.5% (Yumizen N Multi Control), 2.9% (Sample 1) |
| Total CV (middle level) | ≤ 4.5 % | 1.3% (Yumizen P Multi Control), 2.0% (Sample 2) |
| Total CV (high level) | ≤ 2.4 % | 1.3% (Sample 3) |
| Accuracy and Precision (Lot to Lot Variability - Serum/Plasma) | ||
| Within-run CV (low level) | ≤ 4.5 % | Not reported separately, but "Within-Day (%CV)" for Sample 1 (1.7%) is shown |
| Within-run CV (middle level) | ≤ 3.4 % | Not reported separately, but "Within-Day (%CV)" for Sample 2 (0.9%) is shown |
| Within-run CV (high level) | ≤ 1.8 % | Not reported separately, but "Within-Day (%CV)" for Sample 4 (0.4%) is shown |
| Total CV (low level) | ≤ 6.0 % | 4.6% (Sample 1) |
| Total CV (middle level) | ≤ 4.5 % | 2.0% (Sample 2) |
| Total CV (high level) | ≤ 2.4 % | 0.5% (Sample 4) |
| Accuracy and Precision (Instrument Variability - Urine) | ||
| Within-run CV (low level) | ≤ 4.5 % | 1.2% (Sample 1) |
| Within-run CV (middle level) | ≤ 3.8 % | 0.8% (Sample 2) |
| Within-run CV (high level) | ≤ 3.8 % | 0.8% (Sample 3) |
| Total CV (low level) | ≤ 6.0 % | 4.2% (Sample 1) |
| Total CV (middle level) | ≤ 5.0 % | 4.3% (Sample 2) |
| Total CV (high level) | ≤ 5.0 % | 3.9% (Sample 3) |
| Accuracy and Precision (Lot to Lot Variability - Urine) | ||
| Within-run CV (low level) | ≤ 4.5 % | Not reported separately, but "Within-Day (%CV)" for Sample 1 (1.1%) is shown |
| Within-run CV (middle level) | ≤ 3.8 % | Not reported separately, but "Within-Day (%CV)" for Sample 2 (0.9%) is shown |
| Within-run CV (high level) | ≤ 3.8 % | Not reported separately, but "Within-Day (%CV)" for Sample 3 (0.9%) is shown |
| Total CV (low level) | ≤ 6.0 % | 2.1% (Sample 1) |
| Total CV (middle level) | ≤ 5.0 % | 1.3% (Sample 2) |
| Total CV (high level) | ≤ 5.0 % | 0.9% (Sample 3) |
| Interferences (Serum/Plasma) | Acceptable bias +/-10% of the value without interfering substances. | All listed interferents (Hemoglobin, Triglycerides, Total Bilirubin, Direct Bilirubin, Ascorbic Acid, Acetylsalicylic Acid, Ibuprofen, Acetaminophen, N-Acetylcystein, Glucose, Total Protein, Methyldopa, L-Dopa, Calcium Dobesilate) showed no interference higher than +/-10% at the specified concentrations. |
| Interferences (Urine) | Acceptable bias +/-10% of the value without interfering substances. | All listed interferents (Hemoglobin, Triglycerides, Direct Bilirubin, Ascorbic acid, N-Acetylcystein, pH) showed no interference higher than +/-10% at the specified concentrations. |
| Matrix Comparison (Serum/Lithium Heparin Plasma) | No significant difference between serum and plasma with heparin specimens. | Regression line: Intercept = -0.0281, Slope = 1.0008, r² = 0.995. This indicates no significant difference. |
| Method Comparison (Serum/Plasma vs. Predicate) | High correlation and acceptable agreement (implied by CLSI EP-9A3). | Regression line (Passing Bablok): Intercept = -0.0107, Slope = 0.9611, r² = 0.997. |
| Method Comparison (Urine vs. Predicate) | High correlation and acceptable agreement (implied by CLSI EP-9A3). | Regression line (Passing Bablok): Intercept = 0.2296, Slope = 0.9772, r² = 0.994. |
| Reagent Stability (Closed) | Stable up to expiry date. | 12 months (at 2-8°C). |
| Reagent Stability (Open, On-Board) | Stable for a specified period. | 6 weeks. |
| Reference Range Verification (Serum/Plasma - Men) | Consistent with established literature reference ranges. | Normal range: 0.67 - 1.17 mg/dL (consistent with Mazzachi et al. reference). |
| Reference Range Verification (Serum/Plasma - Women) | Consistent with established literature reference ranges. | Normal range: 0.51 - 0.95 mg/dL (consistent with Mazzachi et al. reference). |
2. Sample sizes used for the test set and the data provenance
- Measuring Range:
- Limit of detection and quantitation: Determined according to CLSI guideline EP17-A2. (Specific sample size not provided in the summary but typically involves multiple replicates of low-concentration samples).
- Linearity: Determined according to CLSI guideline EP06-A. (Specific sample size not provided in the summary but involves multiple concentrations with replicates).
- Accuracy and Precision:
- Instrument Variability (Serum/Plasma & Urine): 240 measurements (20x2x2 means 20 replicates for each of 3 samples, on 2 runs for 2 instruments over a certain period - or 20 days x 2 runs/day x 2 instruments). The samples were control materials and native samples.
- Lot-to-Lot Variability (Serum/Plasma & Urine): 90 measurements (3x5x2x3 implies 3 lots, 5 days, 2 runs/day, 3 samples). The samples were control materials and native samples.
- Interferences: Not explicitly stated, but typically involves testing known concentrations of interferents in base samples.
- Matrix Comparison: 84 paired samples (serum and lithium heparin plasma) from single donors.
- Method Comparison:
- Serum/Plasma: 103 native human serum samples. Data provenance: collected from CHU Nîmes (University Hospital Center). Retrospective (remnants).
- Urine: 129 native human urine samples. Data provenance: collected from routine clinical laboratory. Retrospective (remnants).
- Reagent Stability: Determined according to CLSI guideline EP25-A. (Specific sample size not provided).
- Reference Range Verification:
- Serum/Plasma - Men: 45 "normal samples" from a blood bank.
- Serum/Plasma - Women: 41 "normal samples" from a blood bank.
- Children & Urine: Verification could not be made due to lack of availability of samples from healthy pediatric patients/healthy people.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not mention the use of experts to establish ground truth for this device, which is a quantitative in vitro diagnostic for creatinine levels. For such devices, ground truth is typically established by:
- A reference method (e.g., mass spectrometry) for accuracy studies.
- The established values of control materials.
- The results from a legally marketed predicate device (as seen in method comparison).
- Literature values for reference range verification.
4. Adjudication method for the test set
Not applicable. This is a quantitative diagnostic device, not one requiring expert adjudication of results.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This is a quantitative diagnostic device, not an AI-assisted diagnostic imaging device requiring human reader interpretation. No MRMC study was performed.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
This is a standalone in vitro diagnostic device (reagent and instrument system). Its performance described above (e.g., precision, accuracy, linearity, interference) represents the algorithm-only (device-only) performance, without human interpretation of the result influencing the quantitative output.
7. The type of ground truth used
- Measuring Range, Accuracy, Precision, Interferences, Reagent Stability: Internal specifications, established reference materials (controls), and recognized scientific methods (e.g., spiked samples for linearity and interference).
- Matrix Comparison: Paired samples from the same donor, with comparison between results from serum and plasma. The expectation is that the creatinine value should be the same across matrices for the same individual.
- Method Comparison: The predicate device's results (ABX Pentra Enzymatic Creatinine CP) served as the reference for comparison using method comparison studies (Passing Bablok regression).
- Reference Range Verification: Reference ranges cited in scientific literature (e.g., Mazzachi BC et al., Schlebusch Soldin SJ et al., Roberts WL et al.) were used for verification against measured values in "normal" samples.
8. The sample size for the training set
The document describes performance evaluation studies (validation) rather than a clear "training set" for an algorithm. For a device like this, the "training" usually refers to the development and optimization of the reagent formulation and instrument parameters. The specific sample sizes used for this developmental phase are not detailed in the summary. The provided sample sizes are for the analytical performance studies which are typically considered validation.
9. How the ground truth for the training set was established
As there isn't a "training set" in the context of machine learning, this question isn't directly applicable. For the development of an IVD like this, ground truth would be established during the R&D phase through:
- Using purified creatinine standards.
- Comparison with established and highly accurate reference methods (e.g., isotope dilution mass spectrometry, IDMS).
- Clinical samples with results from well-characterized, clinically accepted methods.
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May 10, 2021
Horiba ABX SAS Caroline Ferrer Regulatory Affairs Manager Parc Euromedecine Montpellier Cedex 4, 341184 France
Re: K193649
Trade/Device Name: Yumizen C1200 Creatinine PAP Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: Class II Product Code: JFY Dated: October 7, 2020 Received: October 9, 2020
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,
Kellie B. Kelm, Ph.D. 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) K193649
Device Name Yumizen C1200 Creatinine PAP
Indications for Use (Describe)
Yumizen C1200 Creatinine PAP reagent is intended for the quantitative in vitro diagnostic determination of Creatinine in human serum, plasma and urine based on an enzymatic method using a multi- step approach ending with a photometric end-point reaction. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
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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510(k) Summary K193649
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.
1- Date of Summary
Date submitted : October 07th, 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- Device Name and Classification
. Devices Names and Intended Uses
| Device's names | Intended Use |
|---|---|
| Yumizen C1200 Creatinine PAP(1300023844/1300023843) | Yumizen C1200 Creatinine PAP reagent is intended for thequantitative in vitro diagnostic determination of Creatinine in humanserum, plasma and urine based on an enzymatic method using amulti- step approach ending with a photometric end-point reaction.Creatinine measurements are used in the diagnosis and treatment ofrenal diseases, in monitoring renal dialysis, and as a calculation basisfor measuring other urine analytes. |
Devices Classification .
| Trade/Proprietary Name: | Yumizen C1200 Creatinine PAP |
|---|---|
| Device Class: | Class II / 510(k) required |
| Classification Name: | §862.1225: Creatinine test system |
| Product Code: | JFY |
| Panel: | Clinical Chemistry (75) |
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5- 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 | PredicateManufacturer | Predicate510(k)number |
|---|---|---|---|
| Yumizen C1200 CreatininePAP (Serum/Plasma and Urineapplications) | ABX Pentra Enzymatic Creatinine CP(Serum/Plasma and Urine applications)On ABX Pentra 400 / Pentra C400 | HORIBA ABXSAS | K110137 |
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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Image /page/5/Picture/0 description: The image contains the logo for HORIBA Medical. The word "HORIBA" is written in large, bold, blue letters. Below the word "HORIBA" is the word "Medical" written in a smaller, lighter blue font. The logo is simple and clean, with a focus on the company name.
b. Yumizen C1200 Creatinine PAP (Serum/Plasma and Urine applications)
i. Comparison with predicate Device : Similarities
| Item | Predicate K110137 | Candidate |
|---|---|---|
| Device Name | ABX Pentra Enzymatic Creatinine CP(A11A01907) | Yumizen C1200 Creatinine PAP(1300023843) |
| Intended Use | ABX Pentra Enzymatic Creatinine CP reagent is intended for the quantitativein vitro diagnostic determination ofCreatinine in human serum, plasma andurine based on an enzymatic method usinga multi-step approach endingwith a photometric end-point reaction.Creatinine measurements are used in thediagnosis and treatment of renal diseases,in monitoring renal dialysis, and as acalculation basis for measuring other urineanalytes | Yumizen C1200 Creatinine PAP reagent is intended for the quantitativein vitro diagnostic determination ofCreatinine in human serum, plasma andurine based on an enzymatic methodusing a multi-step approach endingwith a photometric end-point reaction.Creatinine measurements are used in thediagnosis and treatment of renal diseases,in monitoring renal dialysis, and as acalculation basis for measuring otherurine analytes |
| Reagent format | Liquid | Same |
| Method | Enzymatic colorimetric test | Same |
| Measurement | Quantitative | Same |
| Manufactured by | HORIBA ABX SAS | Same |
| Product code | JFY | Same |
| Sample type | Serum, plasmaand Urine | Serum,Lithium heparin plasmaUrine |
| Sample Stability | Serum/Plasma :At 20-25°C :7 daysAt 4-8°C : 7 daysAt -20°C : 3 monthsUrine :At 20-25°C :2 daysAt 4-8°C : 6 daysAt -20°C : 6 months | Serum/Plasma :At 20-25°C :7 daysAt 4-8°C : 7 daysAt -20°C : 3 monthsUrine :At 20-25°C :2 daysAt 4-8°C : 6 daysAt -20°C : 6 months |
| Reagent Shelf-life | Stable up to expiry date on the label ifstored at 2-8°C. | Stable up to expiry date on the label ifstored at 2-8°C.Store protected fromlight. |
| Item | Predicate K110137 | Candidate |
| Device Name | ABX Pentra Enzymatic Creatinine CP(A11A01907) | Yumizen C1200 Creatinine PAP(1300023843) |
| Instrument | ABX Pentra 400 | Yumizen C1200 Clinical chemistryAnalyzer |
| Calibrators | ABX Pentra Multical (A11A01652) | Yumizen C1200 Multi Cal(1300023891/1300023890) |
| Controls | ABX Pentra N Control (A11A01653A)ABX Pentra P Control (A11A01654)ABX Pentra Urine Control L/H(A11A01674) | Yumizen C1200 N Multi Control(1300023938/1300023939)Yumizen C1200 P Multi Control(1300023940/1300023940)Yumizen C1200 Urine Level 1 Control(1300023946)Yumizen C1200 Urine Level 2 Control(130002347) |
| Packaging | 22 mL (R1)8 mL ( R2) | 6x35 mL (R1)6x19 mL (R2) |
| Analytical Range | Measuring RangeSerum/Plasma :0.11 - 16.95 mg/dLUrine :3.56 - 282.5 mg/dL | Measuring RangeSerum/Plasma :0.11 - 16.95 mg/dLUrine :3.56 - 175 mg/dL |
| ReagentOn board Stability | 30 days | 6 weeks |
| Reference range | Serum/Plasma :Men : 0.62 - 1.10 mg/dLWomen : 0.45 - 0.75 mg/dLUrine :Men :14 - 26 mg/kg/dayWomen :11 - 20 mg/kg/day | Serum/Plasma :Men : 0.67 - 1.17 mg/dLWomen : 0.51 - 0.95 mg/dLUrine :Men : 14 - 26 mg/kg/dayWomen :11 - 20 mg/kg/day |
| Discussion on the analysis differences :1.Instrument: Yumizen C1200 Creatinine PAP is used on Yumizen C1200 analyzer.2. Calibrators&Controls: Yumizen C1200 Creatinine PAP uses Yumizen C1200 Multi Cal, | ||
| Item | Predicate K110137 | Candidate |
| Yumizen C1200 N Multi Control, Yumizen C1200 P Multi Control, Yumizen C1200 Urine Level 1 Control, and Yumizen C1200 Urine Level 2 Control whereas the predicate uses its own brand calibrator and controls. | ||
| 3. Packaging is different: depends on cassette capacity. | ||
| 4. Analytical range: The measuring ranges in urine for Yumizen C1200 Creatinine PAP is reduced when compared to the predicate's. But both allow to cover the reference range of values. | ||
| 5. On board stability: The on board stability of Yumizen C1200 Creatinine PAP is longer. |
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ii. Comparison with predicate Device: Differences
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Stability depends on the reagent composition and cassette capacity.
- The reference range for serum/plasma is similar.
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6- 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 2019 ●
- . Refuse To Accept (RTA) Policy for 510(k) - Guidance for Industry and Food and Drug Administration Staff Document issued on: September 13, 2019.
- Guidance for Industry and FDA Staff : eCopy Program for Medical Device Submissions - 2015
c. Others Guidances followed
- Valtec guideline (Vassault et al., Ann. Biol. Clin., 1986, (44), 686-745) ●
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7- Analytical Performance Characteristics
8.1 Measuring Range
Yumizen C1200 Creatinine PAP .
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.
A Results :
| Limit ofdetection | Limit ofquantitation | Linearity | Measuring range | |
|---|---|---|---|---|
| Serum | 0.03 mg/dL | 0.11 mg/dL | 0.04 - 19.93 mg/dL | 0.11 - 16.95 mg/dL |
| SerumPost-dilution | NA | NA | NA | until 50.85 mg/dL with theautomatic post-dilution |
| Urine | 0.16 mg/dL | 1.13 mg/dL | 0.00 - 327.60 mg/dL | 3.56 - 175 mg/dL |
| UrinePost-dilution | NA | NA | NA | until 525 mg/dL with theautomatic post-dilution |
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Image /page/10/Picture/0 description: The image contains the logo for HORIBA Medical. The word "HORIBA" is written in large, bold, blue letters. Below the word "HORIBA" is the word "Medical" written in a smaller, lighter blue font. The logo is simple and clean, with a focus on the company name.
8.2 Accuracy and Precision
Yumizen C1200 Creatinine PAP ●
Serum/Plasma :
- Instrument variability: 20x2x2
Within run precision: CV limits, for the low, middle and high level are respectively 4.5 %, 3.4 % and 1.8 % for serum or plasma.
Total precision: CV limits, for the low, middle and high level are respectively 6.0 %, 4.5 % and 2.4 % for serum and plasma.
| Sample | N | Mean(µmol/L) | Mean(mg/dL) | Within-Run(%CV) | Between-Run(%CV) | Between-Day(%CV) | Between-Instrument(%CV) | Total(%CV) |
|---|---|---|---|---|---|---|---|---|
| Yumizen C1200N Multi Control | 240 | 132.88 | 1.50 | 0.5 | 0.7 | 0.8 | 0.9 | 1.5 |
| Yumizen C1200P Multi Control | 240 | 396.10 | 4.48 | 0.3 | 0.8 | 0.5 | 0.9 | 1.3 |
| Sample 1 | 240 | 38.35 | 0.43 | 1.4 | 1.2 | 2.2 | 0.6 | 2.9 |
| Sample 2 | 240 | 80.09 | 0.91 | 0.5 | 1.2 | 1.3 | 0.8 | 2.0 |
| Sample 3 | 240 | 786.32 | 8.89 | 0.3 | 0.6 | 0.6 | 1.0 | 1.3 |
The results are within the specifications.
- Lot to lot variability: 3x5x2x3 ●
Within run precision: CV limits, for the low, middle and high level are respectively 4.5 %, 3.4 % and 1.8 % for serum or plasma.
Total precision: CV limits, for the low, middle and high level are respectively 6.0 %, 4.5 % and 2.4 % for serum or plasma.
| Sample | N | Mean(µmol/L) | Mean(mg/dL) | Within-Day(%CV) | Between-Day (%CV) | Within-Lot(%CV) | Between-Lot(%CV) | Total(%CV) |
|---|---|---|---|---|---|---|---|---|
| YumizenC1200 N MultiControl | 90 | 136.04 | 1.54 | 0.6 | 0.6 | 0.9 | 0.0 | 0.9 |
| YumizenC1200 P MultiControl | 90 | 401.67 | 4.54 | 0.4 | 0.4 | 0.6 | 0.0 | 0.6 |
| Sample 1 | 90 | 18.92 | 0.21 | 1.7 | 4.3 | 4.6 | 0.0 | 4.6 |
| Sample 2 | 90 | 48.92 | 0.55 | 0.9 | 1.7 | 2.0 | 0.0 | 2.0 |
| Sample 3 | 90 | 158.80 | 1.79 | 0.4 | 0.6 | 0.7 | 0.0 | 0.7 |
| Sample 4 | 90 | 632.51 | 7.15 | 0.4 | 0.3 | 0.5 | 0.0 | 0.5 |
The results are within the specifications.
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Urine :
- Instruments variability: 20x2x2 ●
Within run precision: CV limits, for the low, middle and high level are respectively 4.5 %, 3.8 % and 3.8 % for urine.
Total precision: CV limits, for the low, middle and high level are respectively 6.0 %, 5.0 % and 5.0 % for urine.
| Sample | N | Mean(µmol/L) | Mean(mg/dL) | Within-Run(%CV) | Between-Run(%CV) | Between-Day(%CV) | Between-Instrument(%CV) | Total(%CV) |
|---|---|---|---|---|---|---|---|---|
| Yumizen C1200Urine Level 1Control | 240 | 6415.65 | 72.50 | 0.8 | 2.0 | 2.1 | 2.3 | 3.8 |
| Yumizen C1200Urine Level 2Control | 240 | 13808.68 | 156.04 | 1.0 | 2.4 | 1.3 | 2.1 | 3.6 |
| Sample 1 | 240 | 638.30 | 7.21 | 1.2 | 1.9 | 2.1 | 2.8 | 4.2 |
| Sample 2 | 240 | 1049.59 | 11.86 | 0.8 | 2.2 | 1.7 | 3.2 | 4.3 |
| Sample 3 | 240 | 8422.53 | 95.18 | 0.8 | 2.2 | 1.3 | 2.8 | 3.9 |
| Sample 4 | 240 | 12762.06 | 144.21 | 1.2 | 2.0 | 1.4 | 2.3 | 3.6 |
The results are within the specifications.
- Lot to Lot Variability: 3x5x2x3
Within run precision: CV limits, for the low, middle and high level are respectively 4.5 %, 3.8 % and 3.8 % for urine.
Total precision: CV limits, for the low, middle and high level are respectively 6.0 %, 5.0 % and 5.0 % for urine.
| Sample | N | Mean(umol/L) | Mean(mg/dL) | Within-Day(%CV) | Between-Day (%CV) | Within-Lot(%CV) | Between-Lot(%CV) | Total(%CV) |
|---|---|---|---|---|---|---|---|---|
| Yumizen C1200Urine Level 1Control | 90 | 6525.73 | 73.74 | 0.8 | 0.6 | 1.0 | 0.0 | 1.0 |
| Yumizen C1200Urine Level 2Control | 90 | 13490.94 | 152.45 | 0.8 | 0.4 | 0.9 | 0.2 | 0.9 |
| Sample 1 | 90 | 497.31 | 5.62 | 1.1 | 1.8 | 2.1 | 0.0 | 2.1 |
| Sample 2 | 90 | 1013.67 | 11.45 | 0.9 | 1.0 | 1.3 | 0.0 | 1.3 |
| Sample 3 | 90 | 8328.21 | 94.11 | 0.9 | 0.4 | 0.9 | 0.0 | 0.9 |
| Sample 4 | 90 | 12770.44 | 144.31 | 0.7 | 0.5 | 0.8 | 0.0 | 0.8 |
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. The data in the following table represent the highest values for which no interferences higher than +/-10% have been observed.
| Serum/Plasma | ||
|---|---|---|
| Hemoglobin | 290 µmol/L | 500 mg/dL |
| Triglycerides | 5.33 mmol/L | 466.38 mg/dL |
| Total Bilirubin | 351 µmol/L | 20.54 mg/dL |
| Direct Bilirubin | 202 µmol/L | 11.80 mg/dL |
| Ascorbic Acid | 340 µmol/L | 5.98 mg/dL |
| Acetylsalicylic Acid | 3.62 mmol/L | 65.16 mg/dL |
| Ibuprofen | 2.43 mmol/L | 50.10 mg/dL |
| Acetaminophen | 1324 µmol/L | 20 mg/dL |
| N-Acetylcystein | 275 µmol/L | 27.5 mg/dL |
| Glucose | 55 mmol/L | 985 mg/dL |
| Total Protein | from 1 to 133 g/L. | |
| Methyldopa | 21.29 µmol/L | 0.45 mg/dL |
| L-Dopa | 20.28 µmol/L | 0.40 mg/dL |
| Calcium Dobesilate | 23.9 µmol/L | 1.00 mg/dL |
. Yumizen C1200 Creatinine PAP
| Urine | ||
|---|---|---|
| Hemoglobin | 290 µmol/L | 500 mg/dL |
| Triglycerides | 4.84 mmol/L | 423.33 mg/dL |
| Direct Bilirubin | 502 µmol/L | 29.35 mg/dL |
| Ascorbic acid | 340 µmol/L | 5.98 mg/dL |
| N-Acetylcystein | 1100 mmol/L | 110 mg/dL |
| pH | Acidification or alcalinisation do not interfere with this test. |
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8.4 Matrix comparison Serum /Lithium Heparin Plasma: Yumizen C1200 Creatinine PAP
Scope of Study
Study of the coagulation effect on the creatinine measurement with the Yumizen C1200 Creatinine PAP reagent.
The goal of this study is to show that coagulation process does not change the creatinine concentration and that the anticoagulant has no interfering action.
Description:
84 paired samples were evaluated on Yumizen C1200 analyser using Yumizen C1200 Creatinine PAP reagent.
For this study, each paired sample (serum and lithium heparin plasma) has been obtained from single donor.
The equation for the regression line using mean square regression was obtained.
| Mean square regression | N | Min | Max | Intercept | Slope | r2 |
|---|---|---|---|---|---|---|
| Creatinine PAPSerum(mg/dL) | 84 | 0.32 | 13.94 | -0.0281 | 1.0008 | 0.995 |
| Creatinine PAPPlasma(mg/dL) | 0.33 | 14.77 |
Conclusion:
The results show there is no significant difference between serum specimens and plasma with heparin specimens → coagulation does not have impact on creatinine determination with Yumizen C1200 Creatinine PAP reagent.
8.5 Method comparison with a predicate device
● Yumizen C1200 Creatinine PAP
Serum/Plasma:
This study has been carried out using recommendations found in the CLSI EP-9A3 guidance. Samples: Anonymous remnants of human serum specimens collected from CHU Nîmes (University Hospital Center). These samples are in the candidate measuring range and predicate measuring range.
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103 native samples have been assayed in duplicate, in ascendant order and descendant order on 5 working days.
The equation for the regression line using Passing Bablok was obtained.
| Passing Bablok | N | Min | Max | Intercept | Slope | Correlation – r² |
|---|---|---|---|---|---|---|
| Creatinine (mg/dL) | 103 | 0.22 | 15.02 | -0.0107 | 0.9611 | 0.997 |
Urine:
This study has been carried out using recommendations found in the CLSI EP-9A3 guidance. Samples: Anonymous remnants of human urine specimens collected from routine clinical laboratory. These samples are in the candidate measuring range and predicate measuring range.
129 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 |
|---|---|---|---|---|---|---|
| Creatinine (mg/dL) | 129 | 4.19 | 164.34 | 0.2296 | 0.9772 | 0.994 |
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8.6 Reagent Stability
Closed stability 8.6.1
The closed stability was determined according to the CLSI guideline EP25-A.
. Yumizen C1200 Creatinine PAP
Stability before opening: Stable up to the expiry date on the label if stored at 2-8°C.
The Shelf Life of Yumizen C1200 Creatinine PAP is 12 months.
Open stability 8.6.2
The open stability was determined according to the CLSI guideline EP25-A.
On board reagent Stability:
- . Yumizen C1200 Creatinine PAP : The stability claim after opening, on-Board, is 6 weeks
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8.7 Reference range
The Reference Ranges were verified according to the CLSI guideline EP28-A3.
Yumizen C1200 Creatinine PAP ●
Serum/Plasma:
트 Men
45 "normal samples" from blood bank have been assayed with the method in evaluation. Each sample is assayed in duplicates.
Study was performed on 2 different working days.
The first replicate result for each subject was compared against reference ranges cited in literature. The verification studies support the following reference ranges which were established through literature.
Normal range
59 -104 umol/L / 0.67 -1.17 mg/dL.
Reference:
Mazzachi BC, Peake MJ, Ehrhard V. Reference range and method comparison studies for enzymatic and Jaffe creatinine assays in plasma and serum and early morning urine. Clin. Lab. (2000) 46: 53-55.
트 Women
41 "normal samples" from blood bank have been assayed with the method in evaluation. Each sample is assayed in duplicates.
Study was performed on 2 different working days. The first result for each subject was compared against reference ranges cited in literature.
The verification studies support the following reference ranges which were established through literature.
Normal range
45 - 84 umol/L / 0.51 - 0.95 mg/dL.
Reference:
Mazzachi BC, Peake MJ, Ehrhard V. Reference range and method comparison studies for enzymatic and Jaffe creatinine assays in plasma and serum and early morning urine. Clin. Lab. (2000) 46: 53-55.
트 Children
Verification of normal values in pediatric samples could not be made due to lack of availability of samples from healthy pediatric patients.
Each laboratory should establish its own reference ranges.
Normal range
| Children | mg/dL | \mumol/L |
|---|---|---|
| 0 – 7 days | 0.6 – 1.1 | 53 – 97 |
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| 1 week – 1 month | 0.3 – 0.7 | 27 – 62 |
|---|---|---|
| 1 – 6 month(s) | 0.2 – 0.4 | 18 – 35 |
| 7 – 12 months | 0.2 – 0.4 | 18 – 35 |
| 1 – 18 year(s) | 0.2 – 0.7 | 18 – 62 |
Reference:
Schlebusch Soldin SJ, HicksJM. Pediatric reference ranges. Washington: AACC Press, 1995:50.
Urine:
Verification of normal values in urine could not be made due to lack of availability of urine samples from healthy people.
Each laboratory should establish its own reference ranges.
Normal range Creatinine - Urine (24 hours):
| Men | Women |
|---|---|
| 14 - 26 mg/kg/day | 11 – 20 mg/kg/day |
| 124 - 230 μmol/kg/day | 97 – 177 μmol/kg/day |
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): 2264
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9. 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.
10. Conclusions for Performance Testing
The performance testing data conclude that the safety and effectiveness of the device are not compromised, and that they met all acceptance criteria, demonstrating that each device is substantially equivalent to its predicate device.
§ 862.1225 Creatinine test system.
(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.