Who is the manufacturer of Yumizen C1200 Creatinine PAP?

HORIBA ABX SAS filed the 510(k) submission for Yumizen C1200 Creatinine PAP (K193649).

What is the FDA product code for Yumizen C1200 Creatinine PAP?

JFY. It is classified under 21 CFR 862.1225 as a Class 2 device in the Clinical Chemistry panel.

What is the regulatory pathway for Yumizen C1200 Creatinine PAP?

510(k) clearance (submission type: Traditional).

What are the predicate devices for Yumizen C1200 Creatinine PAP?

ABX Pentra Enzymatic Creatinine CP (K110137).

Who can help prepare an FDA 510(k) submission like Yumizen C1200 Creatinine PAP?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

Yumizen C1200 Creatinine PAP

K193649 · HORIBA ABX SAS · JFY · May 10, 2021 · Clinical Chemistry

Device Facts

Record ID	K193649
Device Name	Yumizen C1200 Creatinine PAP
Applicant	HORIBA ABX SAS
Product Code	JFY · Clinical Chemistry
Decision Date	May 10, 2021
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.1225
Device Class	Class 2

Intended 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.

Device Story

Yumizen C1200 Creatinine PAP is an in vitro diagnostic reagent for quantitative creatinine measurement in human serum, plasma, and urine. It utilizes an enzymatic colorimetric method with a multi-step approach, resulting in a photometric end-point reaction. The device is intended for use on the Yumizen C1200 clinical chemistry analyzer in a clinical laboratory setting by trained laboratory personnel. The analyzer processes patient samples, and the reagent facilitates the chemical reaction required for photometric detection. Healthcare providers use the resulting creatinine concentration to diagnose and treat renal diseases, monitor dialysis patients, and calculate other urine analytes. The device provides objective quantitative data to support clinical decision-making regarding kidney function and patient management.

Clinical Evidence

Bench testing only. Performance validated per CLSI guidelines (EP05-A3, EP17-A2, EP09-A3, EP06-A, EP25-A). Precision studies (N=240 for serum/plasma, N=240 for urine) showed total CVs within 1.3-4.3%. Method comparison against predicate (N=103 serum/plasma, N=129 urine) demonstrated high correlation (r²=0.997 for serum/plasma, r²=0.994 for urine). Interference testing confirmed no significant bias (>10%) for common substances. Matrix comparison (N=84) showed no significant difference between serum and lithium heparin plasma.

Technological Characteristics

Liquid enzymatic colorimetric reagent. Multi-step enzymatic reaction with photometric end-point detection. Designed for use on the Yumizen C1200 clinical chemistry analyzer. Storage at 2-8°C, protected from light. Shelf life 12 months; on-board stability 6 weeks. Measuring range: 0.11-16.95 mg/dL (serum/plasma) and 3.56-175 mg/dL (urine).

Indications for Use

Indicated for quantitative in vitro diagnostic determination of creatinine in human serum, plasma, and urine. Used for diagnosis and treatment of renal diseases, monitoring renal dialysis, and as a calculation basis for other urine analytes. No specific age or gender contraindications provided.

Regulatory Classification

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.

Predicate Devices

ABX Pentra Enzymatic Creatinine CP (K110137)

Related Devices

K103376 — ELITECH CLINICAL SYSTEMS CREATINNE PAP SL MODEL CRSL-0250, CLITECH CLINICAL SYSTEMS ELICAL 2 MODEL CALI-0580, ELITECH CL · Seppim S.A.S. · Nov 18, 2011
K110137 — ABX PENTRA ENZYMATIC CREATININE CP, ABX PENTRA MULTICAL, ABX PENTRA N CONTROL, ABX PENTRA P CONTROL, AND ABX PENTRA URIN · HORIBA ABX SAS · Aug 10, 2011
K040976 — GENCHEM CREATININE REAGENT · Genchem, Inc. · Dec 27, 2004
K061775 — WAKO L-TYPE CREATININE-M TEST, AND WAKO CREATININE CALIBRATOR · Wako Chemicals USA, Inc. · Feb 23, 2007
K061412 — THERMO ELECTRON ENZYMATIC CREATININE, MODEL TR35401 · Thermo Electron Corp. · Mar 23, 2007

Submission Summary (Full Text)

{0}------------------------------------------------ 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 {1}------------------------------------------------ #### Page 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) | <div> ☑ Prescription Use (Part 21 CFR 801 Subpart D) </div> | |----------------------------------------------------------------------------------------------------------------------------------| | <div> ☐ Over-The-Counter Use (21 CFR 801 Subpart C) </div> | #### CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {3}------------------------------------------------ # 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) | {4}------------------------------------------------ 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. {5}------------------------------------------------ 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. | | {6}------------------------------------------------ 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 {7}------------------------------------------------ Image /page/7/Picture/0 description: The image shows the logo for HORIBA Medical. The word "HORIBA" is in large, bold, blue letters. Below it, in smaller, light blue letters, is the word "Medical." Stability depends on the reagent composition and cassette capacity. 6. The reference range for serum/plasma is similar. {8}------------------------------------------------ Image /page/8/Picture/0 description: The image shows 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, and it is likely used to represent the company in its marketing and branding materials. # 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) ● {9}------------------------------------------------ Image /page/9/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." # 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 | {10}------------------------------------------------ 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 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. {11}------------------------------------------------ Image /page/11/Picture/0 description: The image shows the logo for HORIBA Medical. The word "HORIBA" is in large, bold, blue letters. Below it, the word "Medical" is in a smaller, lighter blue font. The logo is simple and clean, with a focus on the company name. # 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. {12}------------------------------------------------ Image /page/12/Picture/0 description: The image displays the logo for HORIBA Medical. The word "HORIBA" is written in a bold, sans-serif font and is colored in a bright blue. Below "HORIBA", the word "Medical" is written in a smaller, lighter blue font. The logo is simple and clean, with a focus on the company name. ## 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. | | {13}------------------------------------------------ Image /page/13/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." ## 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. {14}------------------------------------------------ Image /page/14/Picture/0 description: The image contains the logo for HORIBA Medical. The word "HORIBA" is in large, bold, blue letters. Below it, the word "Medical" is in a smaller, lighter blue font. The logo is simple and clean, with a focus on the company name. 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 | {15}------------------------------------------------ Image /page/15/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." # 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 {16}------------------------------------------------ Image /page/16/Picture/0 description: The image shows the logo for HORIBA Medical. The word "HORIBA" is in large, bold, blue letters. Below it, in smaller, light blue letters, is the word "Medical." ## 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 | <math>\mu</math>mol/L | |-----------------|--------------|-------------------------------| | 0 – 7 days | 0.6 – 1.1 | 53 – 97 | {17}------------------------------------------------ Image /page/17/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." | 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 {18}------------------------------------------------ Image /page/18/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." # 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.