Yumizen C1200 ALP reagent is intended for the quantitative in vitro diagnostic determination of alkaline phosphatase in human serum and plasma based on a kinetic photometric test using p-Nitropherylphosphate. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.

Yumizen C1200 Albumin reagent is intended for the quantitative in vitro diagnostic determination of albumin in human serum and plasma by colorimetry. Albumin measurements are used in the diagnosis and treatment of numerous diseases involving primarily the liver or kidneys.

Device Description

Not Found

AI/ML Overview

The provided text describes analytical performance characteristics and comparison studies for two in vitro diagnostic reagents, Yumizen C1200 ALP and Yumizen C1200 Albumin, intended for use on the Yumizen C1200 clinical chemistry analyzer. The document is a 510(k) summary, demonstrating substantial equivalence to predicate devices.

Here's an analysis of the acceptance criteria and the studies performed, structured according to your request:

Acceptance Criteria and Reported Device Performance

For both assays, the acceptance criteria are implicitly defined by the successful demonstration of performance characteristics within established guidelines (CLSI) and comparison to their respective predicate devices. The "Results are within predefined acceptance criteria" statements affirm that the tested parameters met the company's internal benchmarks, which are aligned with industry standards for analytical performance.

Here's a table summarizing the reported device performance for key analytical characteristics:

Acceptance Criteria Category	Yumizen C1200 ALP Reported Performance	Yumizen C1200 Albumin Reported Performance
Measuring Range	LoD = 1.40 U/L, LoQ = 5.85 U/L, Linearity 0-1620 U/L. Measuring Range: 6 to 1200 U/L (up to 4800 U/L with post-dilution)	LoD = 0.57 g/L, LoQ = 3.34 g/L, Linearity 0-60.2 g/L. Measuring Range: 4.6 to 56 g/L (up to 112 g/L with post-dilution)
Precision (Within-Run CV)	Single Site: Low: 3.3%, Mid: 1.0%, High: 0.5% (Sample 1, 3, 5)	Single Site: Low: 0.7%, Mid: 0.4%, High: 0.4% (Sample L, M, H)
	Multi Site: Low: 2.7%, Mid: 1.3%, High: 2.0% (Sample 1, 3, 5 - listed as Within-Day)	Multi Site: Low: 2.2%, Mid: 1.4%, High: 0.6% (Sample 1, 2, 3 - listed as Within-Day)
Precision (Total CV)	Single Site: Low: 7.2%, Mid: 6.8%, High: 2.5% (Sample 1, 3, 5)	Single Site: Low: 3.3%, Mid: 2.3%, High: 2.1% (Sample L, M, H)
	Multi Site: Low: 3.9%, Mid: 2.5%, High: 3.6% (Sample 1, 3, 5)	Multi Site: Low: 3.4%, Mid: 1.8%, High: 0.8% (Sample 1, 2, 3)
Interferences (Analyte values not showing >10% interference)	Hemoglobin: 500 mg/dL, Triglycerides: 504.88 mg/dL, Total Bilirubin: 28.84 mg/dL, Direct Bilirubin: 26.36 mg/dL, Acetylsalicylic Acid: 65.16 mg/dL, Ascorbic Acid: 5.98 mg/dL, Ibuprofen: 50.10 mg/dL, Acetaminophen: 20 mg/dL	Hemoglobin: 375 mg/dL, Triglycerides: 463.75 mg/dL, Total Bilirubin: 31.39 mg/dL, Direct Bilirubin: 26.27 mg/dL, Acetylsalicylic Acid: 65.16 mg/dL, Ascorbic Acid: 5.98 mg/dL, Ibuprofen: 50.10 mg/dL, Acetaminophen: 20 mg/dL
Method Comparison (with predicate device)	N=165 serum samples. Intercept: +3.907, Slope: 0.940, Correlation R²: 0.993 (against COBAS INTEGRA systems ALP IFCC Gen.2)	N=111 serum samples. Intercept: +0.421, Slope: 0.963, Correlation R²: 0.990 (against ABX Pentra 400 ABX Pentra Albumin CP)
Matrix Comparison (Plasma vs. Serum)	N=40 lithium-heparin plasma samples. Intercept: 0.3709, Slope: +1.013, Correlation: 0.993 (against Cobas800 with c502 module)	N=70 lithium-heparin plasma samples. Intercept: 0.769, Slope: +1.009, Correlation: 0.988 (against Pentra C400)
Reagent Stability	Closed: 15 months (2-8°C). On-board: 1 week	Closed: 24 months (2-8°C). On-board: 6 weeks
Reference Range	Verified against literature and limited study. Adults (Men: 40-129 U/L, Women: 35-104 U/L). Children data from literature.	Verified against literature and limited study. Adults: 35-52 g/L. Children data from literature.

Study Details:

Sample Size Used for the Test Set and Data Provenance:
- Yumizen C1200 ALP:
  - Measuring Range/Linearity: Data not explicitly stated for individual samples, but the study showed linearity from 0 to 1620 U/L.
  - Precision: "Single site: 20x2x2" and "Multi site: 3x5x2x3". This notation often refers to runs x replicates x instrument/lots, but the exact number of unique "samples" (control and general) for precision is stated as N=240 for single site, and N=90 for multi-site across various levels (control and patient samples). The provenance of these samples is not specified (e.g., country of origin) but they are "control" or "patient" samples. It's an analytical performance study, not a clinical study on specific patient populations.
  - Interferences: Specific sample numbers for this study are not provided, but the tested interferent concentrations are listed.
  - Method Comparison: 165 native serum samples.
  - Matrix Comparison: 40 lithium-heparin plasma samples (individual donors).
- Yumizen C1200 Albumin:
  - Measuring Range/Linearity: Data not explicitly stated for individual samples, but the study showed linearity from 0 to 60.2 g/L.
  - Precision: "Single site: 20x2x2" and "Multi site: 3x5x2x3". Again, N=240 for single site and N=90 for multi-site across various levels.
  - Interferences: Specific sample numbers for this study are not provided.
  - Method Comparison: 111 native serum samples.
  - Matrix Comparison: 70 lithium-heparin plasma samples (individual donors).
- Data Provenance: The document does not specify the country of origin for the samples. The studies are described as analytical performance validations, which are typically retrospective using banked/collected samples. The term "native serum samples" and "individual donors" implies real patient samples.
Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- This is an in vitro diagnostic device (measurement of lab analytes), not an imaging AI or diagnostic AI device where human experts establish "ground truth" in the typical sense of clinical interpretation.
- The ground truth for the test set is established by the predicate devices (Roche Diagnostics ALP IFCC Gen2 on COBAS INTEGRA systems, and HORIBA ABX SAS ABX Pentra Albumin CP on ABX Pentra 400/Pentra C400) or by established analytical methods for measuring concentrations (e.g., gravimetric for linearity, standard additions for LoD/LoQ).
- The "experts" involved are likely laboratory professionals, biochemists, and statisticians who design and execute these analytical validation studies according to CLSI (Clinical and Laboratory Standards Institute) guidelines. Their specific qualifications (e.g., MD, PhD) or number are not explicitly stated in this document but are assumed to be standard for medical device development.
Adjudication Method for the Test Set:
- Not applicable in the context of analytical performance studies of laboratory reagents. Adjudication (e.g., 2+1, 3+1 consensus) is typical for clinical studies involving subjective interpretations (e.g., radiology reads). For a quantitative IVD, the "truth" is the measured value from a reference method or known concentration.
If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:
- No, an MRMC study was not done. This type of study is relevant for diagnostic imaging interpretation or other scenarios where human readers make subjective judgments, and AI provides assistance. This document is for quantitative lab reagents, where the assessment is about the accuracy and precision of the measurement itself.
If a Standalone Performance Study Was Done:
- Yes, the entire document describes standalone performance of the Yumizen C1200 ALP and Albumin reagents on the Yumizen C1200 analyzer. This is not an "algorithm only without human-in-the-loop" performance as the device itself is an integrated system of reagent, instrument, and software. "Standalone" in this context means the performance of the new device/reagent system as a complete unit, not in comparison to human interpretation.
The Type of Ground Truth Used:
- External Reference Measurement: For method comparison studies, the "ground truth" is the result obtained from the legally marketed predicate device (Roche Diagnostics ALP IFCC Gen2 for ALP, and HORIBA ABX SAS ABX Pentra Albumin CP for Albumin).
- Known Concentrations/Standards: For linearity, limit of detection/quantitation, and interference studies, the ground truth is established by preparing samples with known concentrations of analytes and/or interferents.
- Consensus/Literature: For reference ranges, the ground truth is based on established bibliographic references and a verification study using "normal samples" from a blood bank.
The Sample Size for the Training Set:
- This document describes the validation/test phase for regulatory submission (510(k)). It does not detail the training set used for the development of the reagents or the analyzer's measurement algorithms. For IVDs, the "training" analogous to machine learning often involves extensive R&D, chemical optimization, and instrument calibration development using a variety of samples, but these are not explicitly quantified in terms of a "training set" size in this regulatory summary.
How the Ground Truth for the Training Set Was Established:
- As above, details about the "training set" are not provided. However, for the development of quantitative IVD assays, ground truth for initial development/training would typically be established through:
  - Primary Reference Methods: Highly accurate and precise methods (e.g., isotope-dilution mass spectrometry) for specific analytes, often used for calibrator assignment.
  - Certified Reference Materials: Materials with an assigned value and uncertainty for an analyte, traceable to recognized metrological standards.
  - Large Sample Cohorts: A diverse range of clinical samples (with values determined by established methods) to ensure robustness across different patient populations and disease states.
  - Experimental Design: Controlled experiments to characterize reagent stability, reaction kinetics, and potential interferents.

Summary

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Image /page/0/Picture/0 description: The image contains the logos of the Department of Health and Human Services and the Food and Drug Administration (FDA). The Department of Health and Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

August 30, 2019

Horiba ABX SAS Caroline Ferrer Regulatory Affairs Manager Parc Euromedecine Montpellier Cedex 4, 341184 France

Re: K191245

Trade/Device Name: Yumizen C1200 ALP, Yumizen C1200 Albumin Regulation Number: 21 CFR 862.1050 Regulation Name: Alkaline phosphatase or isoenzymes test system Regulatory Class: Class II Product Code: CJE, CIX Dated: July 18, 2019 Received: July 19, 2019

Dear Caroline Ferrer:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal

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statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Kellie B. Kelm, Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2020 See PRA Statement below

510(k) Number (if known)

K191245

Device Name Yumizen C1200 ALP Yumizen C1200 Albumin

Indications for Use (Describe)

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)

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."

FORM FDA 3881 (7/17)

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Image /page/3/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". The logo is simple and clean, with a focus on the company name.

510(k) Summary : K191245

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

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1- Date of Summary Date submitted: 27th August, 2019

2- Company

HORIBA ABX SAS HORIBA MEDICAL Parc Euromédecine Rue du Caducée – BP 7290 34184 Montpellier cedex 4 France

3- Contact person

Contact Person: Caroline Ferrer (caroline.ferrer@horiba.com) Telephone: + (33) 4 67 14 18 43 Fax: + (33) 4 67 14 15 17

4- Product Name

Yumizen C1200 ALP(1300023830) Yumizen C1200 Albumin (1300023798/1300023799)

5- Device Name and Classification

. Intended use

The devices involved by the 510(k) submission file are the following:

Device's names	Intended Use
Yumizen C1200 ALP	Yumizen C1200 ALP reagent is intended for the quantitative in vitrodiagnostic determination of alkaline phosphatase in human serum andplasma based on a kinetic photometric test using p-Nitrophenylphosphate.Measurements of alkaline phosphatase or its isoenzymes are used in thediagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.
Yumizen C1200 Albumin	Yumizen C1200 Albumin reagent is intended for the quantitative in vitrodiagnostic determination of albumin in human serum and plasma bycolorimetry. Albumin measurements are used in the diagnosis and treatmentof numerous diseases involving primarily the liver or kidneys.

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Classification and Description .

Trade/Proprietary Name:	Yumizen C1200 ALP
Device Class:	Class II / 510(k) required
Classification Name:	§862.1050: Alkaline phosphatase or isoenzymes test system
Product Code:	CJE
Panel:	Clinical Chemistry (75)

Trade/Proprietary Name:	Yumizen C1200 Albumin
Device Class:	Class II / 510(k) required
Classification Name:	§862.1035: Albumin test system
Product Code:	CIX
Panel:	Clinical Chemistry (75)

6- Substantial Equivalence Information

The following tables show the similarities and differences and demonstrates substantial equivalence between the candidate device and its predicate device identified below.

a. Predicate Device Name and 510(k) number

Candidate device	Predicate device	Predicate Manufacturer	Predicate510(k)number
Yumizen C1200ALP	ALP IFCC Gen2	COBAS 8000/Roche Diagnostics	K171080
Yumizen C1200Albumin	ABX Pentra Albumin CP	ABX Pentra 400/Pentra C400 /HORIBA ABX SAS	K060434

The following tables show the similarities and differences and demonstrates substantial equivalence between the candidate device and its predicate device identified below.

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b. Yumizen C1200 ALP (1300023830)

i. Comparison with predicate Device : Similarities

Item	Predicate K171080	Candidate
Device Name	ALP IFCC Gen.2 (03333752/0333701)	Yumizen C1200 ALP (1300023830)
Intended Use	In vitro test for the quantitativedetermination of the catalytic activity ofalkaline phosphatase in humain serum andplasma on COBAS INTEGRA systems	Diagnostic reagent for quantitative in-vitro determination of AlkalinePhosphatase (ALP) in serum or plasmaby colorimetry
Sample type	Serum, plasma in lithium heparin	Same
Reagent format	Liquid	Same
Measurement	Quantitative	Same
method	Colorimetry	Same
Shelf-life	2-8℃ – see expiration date on cobas cpack label	Stable up to the expiry date on the labelif stored at 2-8°C.Store protected fromlight
Reference range	40-129 U/L (Men)35-104 U/L (Women)	40-129 U/L (Men)35-104 U/L (Women)

ii. Comparison with predicate Device: Differences

Item	Predicate K171080	Candidate
Device Name	ALP IFCC Gen.2 (03333752/0333701)	Yumizen C1200 ALP (1300023830)
Manufactured by	Roche Diagnostics	HORIBA ABX SAS
Instrument	COBAS INTEGRA systems	Yumizen C1200 Clinical chemistryanalyzer
Calibrators	Calibrator f.a.s	Yumizen C1200 Multical
Controls	PreciControl ClinChem Multi 1	Yumizen C1200 N Multi Control
		Yumizen C1200 P Multi Control
Packaging&Number of tests	200 tests ( ALP IFCC Gen.2 Small)400 tests (ALP IFCC Gen.2 Large)	6x220 tests
Reagent On boardStability	On-board in use at 10-15°C :4 weeks	Once opened, the reagent cassette placedin the refrigerated compartment is stable

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Item	Predicate K171080	Candidate
		for 1 week
	Measuring Range3.0-1200 U/L	Measuring Range6.0-1200 U/L
Analytic Range	Automatic post-dilution:Results from samples diluted using thererun function are automatically multipliedby a factor of 5.	Automatic post-dilution:6 to 1200 U/L,until 4800 U/L with the automatic post-dilution.A post-dilution (factor N = 4) will berealized in case of sample concentrationhigher than 1200 U/L

Discussion on the analysis differences :

1. Manufacturer is different because of the choice of predicate
1. Instrument: Yumizen C1200 ALP is used on Yumizen C1200 (See 2.)
1. Packaging: Yumizen C1200 ALP has one packaging. Its predicate has two packagings, one is smaller and the other is larger.
1. Reagent stability: the on board stability of Yumizen C1200 ALP is shorter. Stability depend on reagent composition and cassette capacity.
1. Analytic Range: LOQ is 6.0 U/L and this value is not clinically critical value.

c. Yumizen C1200 Albumin (1300023798/1300023799)

i. Comparison with predicate Device : Similarities

Item	Predicate K060434	Candidate
Device Name	ABX Pentra Albumin CP (A11A01664)	Yumizen C1200 Albumin(1300023798/1300023799)
Intended Use	Diagnostic reagent for quantitative in-vitrodetermination of Albumin in serum andplasma by colorimetry.	Yumizen C1200 Albumin reagent isintended for the quantitative in vitrodiagnostic determination of albumin inhuman serum and plasma by colorimetry.Albumin measurements are used in thediagnosis and treatment of numerousdiseases involving primarily the liver orkidneys.
Manufactured by	HORIBA ABX SAS	HORIBA ABX SAS
Sample type	Serum, plasma in lithium heparin	Same
Reagent format	Liquid	Same
Measurement	Quantitative	Same

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Item	Predicate K060434	Candidate
method	Colorimetry	Same
Calibrators	ABX Pentra Multical	Yumizen C1200 Multical
Shelf-life	In onopened cassettes, stable up to theexpiry date on the label if stored at 2-8°C	Stable up to the expiry date on the labelif stored at 2-8°C. Store protected fromlight.
Analytic Range	Measuring Range0.46-5.60 g/dL	Measuring Range0.46-5.60 g/dL(= 4.6 to 56 g/L)
	Automatic post-dilution:Up to 11.20 g/dL	Automatic post-dilution:Up to 11.20 g/dL(Up to 112 g/L)
Reference range	0 - 4 days:28 - 44 g/L4 days - 14 years:38 - 54 g/L14 - 18 years:32 - 45 g/L20 - 60 years:35 - 52 g/L60 - 90 years:32 - 46 g/L> 90 years:29 - 45 g/L.	0 - 4 days:28 - 44 g/L4 days - 14 years:38 - 54 g/L14 - 18 years:32 - 45 g/L20 - 60 years:35 - 52 g/L60 - 90 years:32 - 46 g/L> 90 years:29 - 45 g/L.

ii. Comparison with predicate Device: Differences

Item	Predicate K060434	Candidate
Device Name	ABX Pentra Albumin CP (A11A01664)	Yumizen C1200 Albumin(1300023798/1300023799)
Instrument	ABX Pentra 400 Clinical ChemistryAnalyzer	Yumizen C1200 Clinical chemistryanalyzer
Controls	ABX Pentra N Control	Yumizen C1200 N Multi Control
	ABX Pentra P Control	Yumizen C1200 P Multi Control
Number of tests	327 tests	4x245 / 6x250 tests
Packaging	Cassette of 99 ml	Cassette of 90 ml
Sample Volume	2μ1	1μl/test
ReagentOn board Stability	One opened, the reagent cassette placed inthe refrigerated ABX Pentra 400compartment is stable:83 days ( 11 weeks)	Once opened, the reagent cassette placedin the refrigerator compartment is stablefor 6 weeks.
CalibrationStability	The reagent is calibrated on Day 0. Thecalibration stability is checked by testing 2	6 weeks

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Item	Predicate K060434	Candidate
	control specimens.The calibration stability is at least 14 days.
Discussion on the analysis differences.

Instrument: Yumizen C1200 Albumin is used on Yumizen C1200
Packaging: Yumizen C1200 Albumin has two packaging on, one is smaller and the other is larger.
Number of test depends on packaging and cassette capacity.
Reagent stability: the on board stability of Yumizen C1200 Albumin is shorter.

Stability depend on reagent composition and cassette capacity.

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7 - Special Control/Guidance Document Referenced

a. Standards Followed

The following standards & FDA guidance documents have been used to support this submission:

CLSI Guidelines:

CLSI EP05-A3:Evaluation of Precision of Quantitative Measurement Procedures- Third ● Edition - October 2014
CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures - Second Edition - June 2012
CLSI EP09-A3: Measurement Procedure Comparison and Biais Estimation Using Patient Samples- Third Edition -August 2013
CLSI EP06-A: Evaluation of the Linearity of Quantitative measurement Procedures A Statistical Approach - First Edition - April 2003
CLSI C28-A3: Defining, Establishing, and Verifying Reference Intervals in the Clinical laboratory- Third Edition - November 2008
CLSI EP25-A : Evaluation of Stability of In Vitro Diagnostic reagents

b. FDA Guidances Followed

Guidance for Industry and FDA Staff : Format for Traditional and Abbreviated 510(k)s - 2005
Refuse To Accept (RTA) Policy for 510(k) - Guidance for Industry and Food and Drug Administration Staff Document issued on: February 21, 2019.
. Guidance for Industry and FDA Staff : eCopy Program for Medical Device Submissions -2015

c. Others Guidances followed

Valtec guideline (Vassault et al., Ann. Biol. Clin., 1986, (44), 686-745)

d. Declaration of conformity

Please see the declaration of conformity in section 009

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8- Analytical Performance Characteristics

8.1 Measuring Range

The limit of detection and quantitation was determined according to the CLSI guideline EP17-A2. The reagent linearity was determined according to CLSI guideline EP06-A. The limit of quantitation and the linearity studies showed that claimed measuring range is appropriated Results

. Yumizen C1200 ALP :

	Limit ofdetection	Limit of quantitation	Linearity	Measuring range
Serum /plasma	LoD =1.40U/L	5.85 U/L	0 to 1620 U/L	6 to 1200 U/L
Post-dilution	NA	NA	up to 4800 U/L	up to 4800 U/L

Yumizen C1200 Albumin : .

	Limit ofdetection	Limit of quantitation	Linearity	Measuring range
Serum /plasma	LoD = 0.57g/L	3.34 g/L	0 to 60.2 g/L	4.6 to 56 g/L
Post-dilution	NA	NA	Up to 112 g/L	up to 112 g/L.

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8.2 Precision

Repeatability (within-run precision) and Reproducibility (total precision)

● Yumizen C1200 ALP

> Single site:20x2x2

Within run : CV limit accepted, for the low, middle and high level are respectively 4.5 %, 4.5 % and 3.8 % for serum and plasma.

Total precision : CV limit accepted, for the low, middle and high level are respectively 6 %, 6 % and 5 % for serum and plasma

Sample	N	Mean(U/L)	Within-Run(%CV)	Between-Run(%CV)	Between-Day (%CV)	Between-Instrument(%CV)	Total(%CV)
Yumizen C1200 N Multi Control	240	81.98	0.8	2.7	3.2	3.7	5.6
Yumizen C1200 P Multi Control	240	201.77	0.5	2.4	3.1	3.5	5.2
Sample 1	240	11.71	3.3	3.1	3.4	4.4	7.2
Sample 2	240	21.58	1.8	2.4	3.3	4.0	6.0
Sample 3	240	56.27	1.0	3.7	3.9	4.1	6.8
Sample 4	240	428.89	0.6	2.5	3.6	1.6	4.7
Sample 5	240	1042.42	0.5	1.1	1.3	1.7	2.5

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Image /page/13/Picture/0 description: The image shows the logo for HORIBA Medical. The word "HORIBA" is in large, bold, blue letters. Below the word "HORIBA" is the word "Medical" in a smaller, lighter blue font. The logo is simple and clean, and the colors are consistent.

Multi site : 3x5x2x3 A

Within run : CV limit accepted, for the low, middle and high level are respectively 4.5 %, 4.5 % and 3.8 % for serum and plasma.

Total precision : CV limit accepted, for the low, middle and high level are respectively 6 %, 6 % and 5 % for serum and plasma.

Sample	N	Mean (U/L)	Within-Day (%CV)	Between-Day (%CV)	Within-Lot (%CV)	Between-Lot (%CV)	Total (%CV)
Yumizen C1200 N Multi Control	90	74.44	0.7	2.7	2.8	0.0	2.8
Yumizen C1200 P Multi Control	90	165.83	0.7	2.8	2.9	0.0	2.9
Sample 1	90	10.24	2.7	2.2	3.5	1.6	3.9
Sample 2	90	21.76	1.3	3.3	3.5	0.0	3.5
Sample 3	90	46.50	1.3	2.1	2.5	0.0	2.5
Sample 4	90	438.24	1.5	2.8	3.2	0.0	3.2
Sample 5	90	1112.95	2.0	3.0	3.6	0.0	3.6

The results are within the specifications.

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Yumizen C1200 Albumin ●

> Single site : 20x2x2

Within run : CV limit, for the low, middle and high level are respectively 4.5 %, 3.8 % and 3.0 % for serum and plasma

Total precision: CV limit, for the low, middle and high level are respectively 6.0 %, 5.0 % and 4.0 % for serum and plasma.

Sample	N	Mean(g/L)	Within-Run(%CV)	Between-Run(%CV)	Between-Day (%CV)	Between-Instrument(%CV)	Total(%CV)
Yumizen C1200 NMulti Control	240	37.8	0.4	2.4	1.8	0.3	3.0
Yumizen C1200 PMulti Control	240	47.1	0.3	0.8	1.8	0.0	2.0
Sample L	240	20.1	0.7	3.2	0.8	0.0	3.3
Sample M	240	39.3	0.4	1.4	1.8	0.3	2.3
Sample H	240	54.2	0.4	1.3	1.6	0.0	2.1

The results are within the specifications.

> Multi site : 3x5x2x3

Within run : CV limit, for the low, middle and high level are respectively 4.5 %, 3.8 % and 3.0 % Total precision: CV limit, for the low, middle and high level are respectively 6.0 %, 5.0 % and 4.0 %

Sample	N	Mean(g/L)	Within-Day(%CV)	Between-Day(%CV)	Within-Lot(%CV)	Between-Lot(%CV)	Total(%CV)
Yumizen C1200N Multi Control	90	37.67	1.0	0.5	1.1	0.0	1.1
Yumizen C1200P Multi Control	90	53.24	0.9	0.5	1.0	0.0	1.0
Sample 1	90	22.07	2.2	2.5	3.4	0.0	3.4
Sample 2	90	43.41	1.4	1.0	1.7	0.5	1.8
Sample 3	90	53.52	0.6	0.5	0.8	0.2	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. These 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	5.77 mmol/l	504.88 mg/dL
Total Bilirubin	493 µmol/L	28.84 mg/dL
Direct Bilirubin	451 µmol/L	26.36 mg/dL
AcetylsalicylicAcid	3.62 mmol/L	65.16 mg/dL
Ascorbic Acid	340 µmol/L	5.98 mg/dL
Ibuprofen	2.43 mmol/L	50.10 mg/dL
Acetaminophen	1324 µmol/L	20 mg/dL

Yumizen C1200 ALP ●

Yumizen C1200 Albumin .

Serum/Plasma
Hemoglobin	218 µmol/L 375 mg/dL
Triglycerides	5.3 mmol/l 463.75 mg/dL
Total Bilirubin	537 µmol/L 31.39 mg/dL
Direct Bilirubin	449 µmol/L 26.27mg/dL
AcetylsalicylicAcid	3.62 mmol/L 65.16 mg/dL
Ascorbic Acid	340 µmol/L 5.98 mg/dL
Ibuprofen	2.43 mmol/L 50.10 mg/dL
Acetaminophen	1324 µmol/L 20 mg/dL

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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 blue letters, is the word "Medical". The logo is simple and clean, with a focus on the company name.

8.4 Method comparison with a predicate device

Yumizen C1200 ALP ●

This study has been carried out using recommendations found in the CLSI EP-9A3 guidance. Correlation of the ALP assay with the Yumizen C1200 ALP on the Yumizen C1200.

165 native serum 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
ALP (U/L)	165	17.80	920.29	+3.907	0.940	0.993

Yumizen C1200 Albumin ●

This study has been carried out using recommendations found in the CLSI EP-9A3 guidance. Correlation of the Albumin assay with the Yumizen C1200 Albumin on the Yumizen C1200. 111 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
Albumin (g/L)	111	7.2	54.8	+0.421	0.963	0.990

Conclusion : Results are within predefined acceptance criteria.

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8.5 Matrix comparison on predicate device

Yumizen C1200 ALP ●

Study materials :

Anticoagulant : heparin-lithium Samples: individual donors

Description :

40 lithium-heparin plasma samples were evaluated on Yumizen C1200 analyzer using Yumizen C1200 ALP reagent and with the US market predicate device as reference : Cobas800 with c502 module analyzer and reagent from Roche.

Passing Bablok	N	Min	Max	Intercept	Slope	Correlation
ALP (U/L)	40	20.39	116.67	0.3709	+1.013	0.993

Yumizen C1200 Albumin ●

Study materials :

Anticoagulant : heparin-lithium

Samples: individual donors

Description:

70 lithium-heparin plasma samples were evaluated on Yumizen C1200 analyzer using Yumizen C1200 Albumin reagent and with the Pentra C400 analyzer with HORIBA Albumin reagent (Predicate device).

Passing Bablok	N	Min	Max	Intercept	Slope	Correlation
Albumin (g/L)	70	14.21	55.53	0.769	+1.009	0.988

Conclusion :

This study shows that heparin lithium plsama samples are validated for these applications.

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8.6 Reagent Stability

8.6.1 Closed stability

The closed stability was determined according to the CLSI guideline EP25-A.

Stability before opening:

Stable up to the expiry date on the label if stored at 2-8℃. Store protected from light.

● ALP :

The shelf life claim for HORIBA MEDICAL reagent will be 15 months in Yumizen C1200 container.

Albumin : .

The shelf life claim for HORIBA MEDICAL reagent will be 24 months in Yumizen C1200 container.

8.6.2 Open stability

On board reagent Stability:

The Reagent stability claim for the Yumizen C1200 ALP is 1 week ●
. The Albumin reagent stability On Board claimed is 6 weeks.

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Image /page/19/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 the blue color gives it a professional look.

8.7 Reference range

The Reference Range was determined according to the CLSI guideline EP28-A3.

. ALP

A Adults data ( bibliographic reference and study-see below):

44 "women normal samples" and 44 "men normal samples" from blood bank have been assayed with the method in evaluation. Each sample is assayed in duplicate.

The mean of the duplicate results for each subject was compared against reference ranges cited in literature. The verification studies support in the following reference ranges which were established through literature

Adults (37°C):
	Men	40-129 U/L (0.67-2.15 µkat/L)
	Women	35-104 U/L (0.58-1.74 µkat/L)

Reference:

Abicht K, El-Samalouti V, Junge W, et al. Multicenter evaluation of new GGT and ALP reagents with new reference standardization and determination of 37 ℃ reference intervals. Clin Chem Lab Med 2001;39:Special Supplement pp S 346.

A Children data are based on bibliographic references.

Children (37°C):

Boys	0 - 14 days	83-248 U/L	(1.39-4.14 µkat/L)
	15 days - < 1 year	122-469 U/L	(2.04-7.83 µkat/L)
	1 - < 10 years	142-335 U/L	(2.37-5.59 µkat/L)
	10 - < 13 years	129-417 U/L	(2.15-6.96 µkat/L)
	13 - < 15 years	116-468 U/L	(1.94-7.82 µkat/L)
	15 - < 17 years	82-331 U/L	(1.37-5.53 µkat/L)
	17- < 19 years	55-149 U/L	(0.92-2.49 µkat/L)
Girls	0 - 14 days	83-248 U/L	(1.39-4.14 µkat/L)
	15 days - < 1 year	122-469 U/L	(2.04-7.83 µkat/L)
	1 - < 10 years	142-335 U/L	(2.37-5.59 µkat/L)
	10 - < 13 years	129-417 U/L	(2.15-6.96 µkat/L)
	13 - < 15 years	57-254 U/L	(0.95-4.24 µkat/L)
	15 - < 17 years	50-117 U/L	(0.84-1.95 µkat/L)
	17-19 years	45-87 U/L	(0.75-1.45 µkat/L)

Reference:

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Estey MP, Cohen AH, Colantonio DA, et al. CLSI-based transference of the CALIPER database of pediatric reference intervals from Abbott to Beckman. Ortho, Roche and Siemens Clinical Chemistry Assays: Direct validation using reference samples from the CALIPER cohort. Clin Biochem 2013;46:1197—1219.

● Albumin

A Adults data (bibliographic reference and study-see below):

125 "normal samples" from blood bank have been assayed with the method in evaluation. Each sample is assayed in duplicate.

Normal range study for the albumin assay with the Yumizen C1200 Albumin reagent on the Yumizen C1200.

Transference of the normal range from literature.

Adults: 35 - 52 g/L (3.5 - 5.2 g/dL)

Each laboratory should check if the reference ranges are transferable to its own patient population and determine own reference ranges if necessary.

Normal Range Albumin

20 - 60 years: 35 - 52 g/L

Reference:

Roberts WL, McMillin GA, Burtis CA, Bruns DE. Reference Information for the Clinical Laboratory. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 4th Ed., Burtis CA, Ashwood ER, Bruns DE. (Elsevier Saunders eds. St Louis USA) (2006): 2254.

> Children data are based on bibliographic references.

0 - 4 days:	28 - 44 g/L
4 days - 14 years:	38 - 54 g/L
14 - 18 years:	32 - 45 g/L

Reference:

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8.8 Proposed Labeling

The labeling is written as per the recommendations given in standard EN18113-2. It takes into account the requirements of 21 CFR Part 809.10.

8.9 Conclusions for Performance Testing

The performance testing data conclude that the safety and effectiveness of the devices are not compromised, and that they met all acceptance criteria, demonstrating that each device is substantially equivalent to its predicate device.

Regulation Number and Section

§ 862.1050 Alkaline phosphatase or isoenzymes test system.

(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.