Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on a standard enzymatic photometric method for quantitative measurement, with no mention of AI or ML techniques.

Therapeutic

No.
This device is an in vitro diagnostic reagent used to quantify Creatinine, which aids in the diagnosis and treatment of renal diseases; it does not directly treat or restore health.

Diagnostic

Yes
The "Intended Use / Indications for Use" section explicitly states that the reagent is for "quantitative in vitro diagnostic determination of Creatinine" and that "Creatinine measurements are used in the diagnosis and treatment of renal diseases." This clearly indicates its role in disease diagnosis.

SaMD (Software as a Medical Device)

No

The device is a reagent for a photometric end-point reaction, which is a chemical substance used in a laboratory test, not a software program.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use/Indications for Use: The document explicitly states the reagent is "intended for the quantitative in vitro diagnostic determination of Creatinine in human serum, plasma and urine". This directly aligns with the definition of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnosis, monitoring, or treatment.
Device Description: The description reiterates the intended use for "quantitative in vitro diagnostic determination of Creatinine".
Performance Studies: The performance studies described (measuring range, accuracy, precision, interferences, matrix comparison, method comparison with a predicate device, reagent stability, reference range) are all typical evaluations performed for IVD devices to demonstrate their analytical performance and suitability for clinical use.
Predicate Device: The mention of a "Predicate Device(s)" with a K number (K110137) is a strong indicator that this device is being submitted for regulatory clearance as an IVD, as predicate devices are used for comparison in the 510(k) submission process for medical devices, including IVDs.

Therefore, based on the provided information, the Yumizen C1200 Creatinine PAP reagent is clearly an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

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.

Product codes (comma separated list FDA assigned to the subject device)

JFY

Device Description

Not Found

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

0-18 years for Children in Serum/Plasma based on reference range, but also includes Men and Women, implying adult use.

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Description of the test set (Method comparison with a predicate device - Serum/Plasma):
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.
Sample size: 103 native samples
Annotation protocol: Not Found

Description of the test set (Method comparison with a predicate device - Urine):
Samples: Anonymous remnants of human urine specimens collected from routine clinical laboratory. These samples are in the candidate measuring range and predicate measuring range.
Sample size: 129 native samples
Annotation protocol: Not Found

Description of the test set (Reference range - Serum/Plasma - Men):
Sample size: 45 "normal samples"
Data source: blood bank
Annotation protocol: 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.

Description of the test set (Reference range - Serum/Plasma - Women):
Sample size: 41 "normal samples"
Data source: blood bank
Annotation protocol: 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.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Study type: Analytical Performance Characteristics - Measuring Range
Sample size: Not specified
Key results:
Serum: Limit of detection: 0.03 mg/dL, Limit of quantitation: 0.11 mg/dL, Linearity: 0.04 - 19.93 mg/dL, Measuring range: 0.11 - 16.95 mg/dL. Serum Post-dilution measuring range: until 50.85 mg/dL with the automatic post-dilution.
Urine: Limit of detection: 0.16 mg/dL, Limit of quantitation: 1.13 mg/dL, Linearity: 0.00 - 327.60 mg/dL, Measuring range: 3.56 - 175 mg/dL. Urine Post-dilution measuring range: until 525 mg/dL with the automatic post-dilution.

Study type: Analytical Performance Characteristics - Accuracy and Precision (Serum/Plasma - Instrument variability)
Sample size: 240 for each sample (Yumizen C1200 N Multi Control, Yumizen C1200 P Multi Control, Sample 1, Sample 2, Sample 3)
Key results:
Yumizen C1200 N Multi Control: Mean (mg/dL) 1.50, Within-Run (%CV) 0.5, Between-Run (%CV) 0.7, Between-Day (%CV) 0.8, Between-Instrument (%CV) 0.9, Total (%CV) 1.5.
Yumizen C1200 P Multi Control: Mean (mg/dL) 4.48, Within-Run (%CV) 0.3, Between-Run (%CV) 0.8, Between-Day (%CV) 0.5, Between-Instrument (%CV) 0.9, Total (%CV) 1.3.
Sample 1: Mean (mg/dL) 0.43, Within-Run (%CV) 1.4, Between-Run (%CV) 1.2, Between-Day (%CV) 2.2, Between-Instrument (%CV) 0.6, Total (%CV) 2.9.
Sample 2: Mean (mg/dL) 0.91, Within-Run (%CV) 0.5, Between-Run (%CV) 1.2, Between-Day (%CV) 1.3, Between-Instrument (%CV) 0.8, Total (%CV) 2.0.
Sample 3: Mean (mg/dL) 8.89, Within-Run (%CV) 0.3, Between-Run (%CV) 0.6, Between-Day (%CV) 0.6, Between-Instrument (%CV) 1.0, Total (%CV) 1.3.
The results are within the specifications.

Study type: Analytical Performance Characteristics - Accuracy and Precision (Serum/Plasma - Lot to lot variability)
Sample size: 90 for each sample (Yumizen C1200 N Multi Control, Yumizen C1200 P Multi Control, Sample 1, Sample 2, Sample 3, Sample 4)
Key results:
Yumizen C1200 N Multi Control: Mean (mg/dL) 1.54, Within-Day (%CV) 0.6, Between-Day (%CV) 0.6, Within-Lot (%CV) 0.9, Between-Lot (%CV) 0.0, Total (%CV) 0.9.
Yumizen C1200 P Multi Control: Mean (mg/dL) 4.54, Within-Day (%CV) 0.4, Between-Day (%CV) 0.4, Within-Lot (%CV) 0.6, Between-Lot (%CV) 0.0, Total (%CV) 0.6.
Sample 1: Mean (mg/dL) 0.21, Within-Day (%CV) 1.7, Between-Day (%CV) 4.3, Within-Lot (%CV) 4.6, Between-Lot (%CV) 0.0, Total (%CV) 4.6.
Sample 2: Mean (mg/dL) 0.55, Within-Day (%CV) 0.9, Between-Day (%CV) 1.7, Within-Lot (%CV) 2.0, Between-Lot (%CV) 0.0, Total (%CV) 2.0.
Sample 3: Mean (mg/dL) 1.79, Within-Day (%CV) 0.4, Between-Day (%CV) 0.6, Within-Lot (%CV) 0.7, Between-Lot (%CV) 0.0, Total (%CV) 0.7.
Sample 4: Mean (mg/dL) 7.15, Within-Day (%CV) 0.4, Between-Day (%CV) 0.3, Within-Lot (%CV) 0.5, Between-Lot (%CV) 0.0, Total (%CV) 0.5.
The results are within the specifications.

Study type: Analytical Performance Characteristics - Accuracy and Precision (Urine - Instruments variability)
Sample size: 240 for each sample (Yumizen C1200 Urine Level 1 Control, Yumizen C1200 Urine Level 2 Control, Sample 1, Sample 2, Sample 3, Sample 4)
Key results:
Yumizen C1200 Urine Level 1 Control: Mean (mg/dL) 72.50, Within-Run (%CV) 0.8, Between-Run (%CV) 2.0, Between-Day (%CV) 2.1, Between-Instrument (%CV) 2.3, Total (%CV) 3.8.
Yumizen C1200 Urine Level 2 Control: Mean (mg/dL) 156.04, Within-Run (%CV) 1.0, Between-Run (%CV) 2.4, Between-Day (%CV) 1.3, Between-Instrument (%CV) 2.1, Total (%CV) 3.6.
Sample 1: Mean (mg/dL) 7.21, Within-Run (%CV) 1.2, Between-Run (%CV) 1.9, Between-Day (%CV) 2.1, Between-Instrument (%CV) 2.8, Total (%CV) 4.2.
Sample 2: Mean (mg/dL) 11.86, Within-Run (%CV) 0.8, Between-Run (%CV) 2.2, Between-Day (%CV) 1.7, Between-Instrument (%CV) 3.2, Total (%CV) 4.3.
Sample 3: Mean (mg/dL) 95.18, Within-Run (%CV) 0.8, Between-Run (%CV) 2.2, Between-Day (%CV) 1.3, Between-Instrument (%CV) 2.8, Total (%CV) 3.9.
Sample 4: Mean (mg/dL) 144.21, Within-Run (%CV) 1.2, Between-Run (%CV) 2.0, Between-Day (%CV) 1.4, Between-Instrument (%CV) 2.3, Total (%CV) 3.6.
The results are within the specifications.

Study type: Analytical Performance Characteristics - Accuracy and Precision (Urine - Lot to Lot Variability)
Sample size: 90 for each sample (Yumizen C1200 Urine Level 1 Control, Yumizen C1200 Urine Level 2 Control, Sample 1, Sample 2, Sample 3, Sample 4)
Key results:
Yumizen C1200 Urine Level 1 Control: Mean (mg/dL) 73.74, Within-Day (%CV) 0.8, Between-Day (%CV) 0.6, Within-Lot (%CV) 1.0, Between-Lot (%CV) 0.0, Total (%CV) 1.0.
Yumizen C1200 Urine Level 2 Control: Mean (mg/dL) 152.45, Within-Day (%CV) 0.8, Between-Day (%CV) 0.4, Within-Lot (%CV) 0.9, Between-Lot (%CV) 0.2, Total (%CV) 0.9.
Sample 1: Mean (mg/dL) 5.62, Within-Day (%CV) 1.1, Between-Day (%CV) 1.8, Within-Lot (%CV) 2.1, Between-Lot (%CV) 0.0, Total (%CV) 2.1.
Sample 2: Mean (mg/dL) 11.45, Within-Day (%CV) 0.9, Between-Day (%CV) 1.0, Within-Lot (%CV) 1.3, Between-Lot (%CV) 0.0, Total (%CV) 1.3.
Sample 3: Mean (mg/dL) 94.11, Within-Day (%CV) 0.9, Between-Day (%CV) 0.4, Within-Lot (%CV) 0.9, Between-Lot (%CV) 0.0, Total (%CV) 0.9.
Sample 4: Mean (mg/dL) 144.31, Within-Day (%CV) 0.7, Between-Day (%CV) 0.5, Within-Lot (%CV) 0.8, Between-Lot (%CV) 0.0, Total (%CV) 0.8.
The results are within the specifications.

Study type: Interferences (Serum/Plasma)
Key results: Hemoglobin: 500 mg/dL, Triglycerides: 466.38 mg/dL, Total Bilirubin: 20.54 mg/dL, Direct Bilirubin: 11.80 mg/dL, Ascorbic Acid: 5.98 mg/dL, Acetylsalicylic Acid: 65.16 mg/dL, Ibuprofen: 50.10 mg/dL, Acetaminophen: 20 mg/dL, N-Acetylcystein: 27.5 mg/dL, Glucose: 985 mg/dL, Total Protein: from 1 to 133 g/L, Methyldopa: 0.45 mg/dL, L-Dopa: 0.40 mg/dL, Calcium Dobesilate: 1.00 mg/dL. These values represent the highest values for which no interferences higher than +/-10% have been observed.

Study type: Interferences (Urine)
Key results: Hemoglobin: 500 mg/dL, Triglycerides: 423.33 mg/dL, Direct Bilirubin: 29.35 mg/dL, Ascorbic acid: 5.98 mg/dL, N-Acetylcystein: 110 mg/dL, pH: Acidification or alcalinisation do not interfere with this test. These values represent the highest values for which no interferences higher than +/-10% have been observed.

Study type: Matrix comparison Serum /Lithium Heparin Plasma
Sample size: 84 paired samples
Key results: The regression line equation for Creatinine PAP Serum (mg/dL) vs. Creatinine PAP Plasma (mg/dL) with N=84 samples, Min=0.32, Max=13.94 (Serum) and Min=0.33, Max=14.77 (Plasma) has an intercept of -0.0281, a slope of 1.0008, and r² of 0.995. Conclusion: The results show there is no significant difference between serum specimens and plasma with heparin specimens.

Study type: Method comparison with a predicate device (Serum/Plasma)
Sample size: 103 native samples
Key results: The regression line equation using Passing Bablok for Creatinine (mg/dL) with N=103 samples, Min=0.22, Max=15.02 has an intercept of -0.0107, a slope of 0.9611, and r² of 0.997.

Study type: Method comparison with a predicate device (Urine)
Sample size: 129 native samples
Key results: The regression line equation using Passing Bablok for Creatinine (mg/dL) with N=129 samples, Min=4.19, Max=164.34 has an intercept of 0.2296, a slope of 0.9772, and r² of 0.994.

Study type: Reagent Stability - Closed stability
Key results: 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.

Study type: Reagent Stability - Open stability
Key results: On board reagent Stability: The stability claim after opening, on-Board, is 6 weeks.

Study type: Reference range verification (Serum/Plasma - Men)
Sample size: 45 "normal samples"
Key results: Normal range: 59 -104 umol/L / 0.67 -1.17 mg/dL.

Study type: Reference range verification (Serum/Plasma - Women)
Sample size: 41 "normal samples"
Key results: Normal range: 45 - 84 umol/L / 0.51 - 0.95 mg/dL.

Study type: Reference range (Serum/Plasma - Children)
Key results: Normal range:
0 – 7 days: 0.6 – 1.1 mg/dL / 53 – 97 μmol/L
1 week – 1 month: 0.3 – 0.7 mg/dL / 27 – 62 μmol/L
1 – 6 month(s): 0.2 – 0.4 mg/dL / 18 – 35 μmol/L
7 – 12 months: 0.2 – 0.4 mg/dL / 18 – 35 μmol/L
1 – 18 year(s): 0.2 – 0.7 mg/dL / 18 – 62 μmol/L

Study type: Reference range (Urine)
Key results: Normal range Creatinine - Urine (24 hours):
Men: 14 - 26 mg/kg/day / 124 - 230 μmol/kg/day
Women: 11 – 20 mg/kg/day / 97 – 177 μmol/kg/day

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K110137

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 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.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

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

2

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 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.

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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Image /page/4/Picture/0 description: The image shows the logo for HORIBA Medical. The word "HORIBA" is in large, bold, blue letters. Below it, in smaller, lighter blue letters, is the word "Medical."

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 | Predicate
Manufacturer | Predicate
510(k)
number |
|--------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------|---------------------------|-------------------------------|
| Yumizen C1200 Creatinine
PAP (Serum/Plasma and Urine
applications) | ABX Pentra Enzymatic Creatinine CP
(Serum/Plasma and Urine applications)
On ABX Pentra 400 / Pentra C400 | HORIBA ABX
SAS | 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 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.
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
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, plasma
and Urine	Serum,
Lithium heparin plasma
Urine
Sample Stability	Serum/Plasma :
At 20-25°C :7 days
At 4-8°C : 7 days
At -20°C : 3 months

Urine :
At 20-25°C :2 days
At 4-8°C : 6 days
At -20°C : 6 months | Serum/Plasma :
At 20-25°C :7 days
At 4-8°C : 7 days
At -20°C : 3 months

Urine :
At 20-25°C :2 days
At 4-8°C : 6 days
At -20°C : 6 months |
| Reagent Shelf-life | Stable up to expiry date on the label if
stored at 2-8°C. | Stable up to expiry date on the label if
stored at 2-8°C.Store protected from
light. |
| Item | Predicate K110137 | Candidate |
| Device Name | ABX Pentra Enzymatic Creatinine CP
(A11A01907) | Yumizen C1200 Creatinine PAP
(1300023843) |
| Instrument | ABX Pentra 400 | Yumizen C1200 Clinical chemistry
Analyzer |
| 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 Range
Serum/Plasma :
0.11 - 16.95 mg/dL
Urine :
3.56 - 282.5 mg/dL | Measuring Range
Serum/Plasma :
0.11 - 16.95 mg/dL
Urine :
3.56 - 175 mg/dL |
| Reagent
On board Stability | 30 days | 6 weeks |
| Reference range | Serum/Plasma :
Men : 0.62 - 1.10 mg/dL
Women : 0.45 - 0.75 mg/dL
Urine :
Men :14 - 26 mg/kg/day
Women :11 - 20 mg/kg/day | Serum/Plasma :
Men : 0.67 - 1.17 mg/dL
Women : 0.51 - 0.95 mg/dL
Urine :
Men : 14 - 26 mg/kg/day
Women :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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Image /page/6/Picture/0 description: The image shows the logo for HORIBA Medical. The word "HORIBA" is written in large, bold, blue letters. Below it, the word "Medical" is written in a smaller, lighter blue font. The logo is simple and clean, with a focus on the company name.

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 of
detection | Limit of
quantitation | Linearity | Measuring range |
|------------------------|-----------------------|--------------------------|---------------------|-------------------------------------------------------|
| Serum | 0.03 mg/dL | 0.11 mg/dL | 0.04 - 19.93 mg/dL | 0.11 - 16.95 mg/dL |
| Serum
Post-dilution | NA | NA | NA | until 50.85 mg/dL with the
automatic post-dilution |
| Urine | 0.16 mg/dL | 1.13 mg/dL | 0.00 - 327.60 mg/dL | 3.56 - 175 mg/dL |
| Urine
Post-dilution | NA | NA | NA | until 525 mg/dL with the
automatic post-dilution |

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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 C1200
N Multi Control | 240 | 132.88 | 1.50 | 0.5 | 0.7 | 0.8 | 0.9 | 1.5 |
| Yumizen C1200
P 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) |
|-------------------------------------|----|------------------|-----------------|-------------------------|-----------------------|---------------------|--------------------------|----------------|
| Yumizen
C1200 N Multi
Control | 90 | 136.04 | 1.54 | 0.6 | 0.6 | 0.9 | 0.0 | 0.9 |
| Yumizen
C1200 P Multi
Control | 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 C1200
Urine Level 1
Control | 240 | 6415.65 | 72.50 | 0.8 | 2.0 | 2.1 | 2.3 | 3.8 |
| Yumizen C1200
Urine Level 2
Control | 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 C1200
Urine Level 1
Control | 90 | 6525.73 | 73.74 | 0.8 | 0.6 | 1.0 | 0.0 | 1.0 |
| Yumizen C1200
Urine Level 2
Control | 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 PAP
Serum
(mg/dL)	84	0.32	13.94	-0.0281	1.0008	0.995
Creatinine PAP
Plasma
(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.