Who is the manufacturer of Yumizen C1200 ALP, Yumizen C1200 Albumin?

HORIBA ABX SAS filed the 510(k) submission for Yumizen C1200 ALP, Yumizen C1200 Albumin (K191245).

What is the FDA product code for Yumizen C1200 ALP, Yumizen C1200 Albumin?

CJE. It is classified under 21 CFR 862.1050 as a Class 2 device in the Clinical Chemistry panel.

What is the regulatory pathway for Yumizen C1200 ALP, Yumizen C1200 Albumin?

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

What are the predicate devices for Yumizen C1200 ALP, Yumizen C1200 Albumin?

ALP IFCC Gen2 (K171080); ABX Pentra Albumin CP (K060434).

Who can help prepare an FDA 510(k) submission like Yumizen C1200 ALP, Yumizen C1200 Albumin?

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 ALP, Yumizen C1200 Albumin

K191245 · HORIBA ABX SAS · CJE · Aug 30, 2019 · Clinical Chemistry

Device Facts

Record ID	K191245
Device Name	Yumizen C1200 ALP, Yumizen C1200 Albumin
Applicant	HORIBA ABX SAS
Product Code	CJE · Clinical Chemistry
Decision Date	Aug 30, 2019
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.1050
Device Class	Class 2

Intended Use

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-nitrophenylphosphate. 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 Story

Yumizen C1200 ALP and Albumin reagents are liquid, in vitro diagnostic assays for use on the Yumizen C1200 analyzer. ALP assay uses kinetic photometric method with p-nitrophenylphosphate to measure catalytic activity; Albumin assay uses colorimetric bromocresol green dye-binding procedure. Analyzers process human serum or lithium heparin plasma samples. Output is quantitative concentration of ALP (U/L) or Albumin (g/dL). Healthcare providers use results to diagnose and monitor liver, bone, parathyroid, and kidney conditions. Device is intended for clinical laboratory use by trained personnel.

Clinical Evidence

Bench testing only. Performance validated via CLSI guidelines (EP05-A3, EP17-A2, EP09-A3, EP06-A, EP25-A). Precision studies (within-run/total) showed CVs within limits. Method comparison against predicates (Passing-Bablok regression) showed high correlation (r²=0.993 for ALP; r²=0.990 for Albumin). Interference testing confirmed no significant bias (>10%) for common substances. Linearity and LoD/LoQ established for claimed measuring ranges.

Technological Characteristics

Liquid reagents. ALP: 2-amino-2-methyl-1-propanol, magnesium acetate, zinc sulphate, HEDTA, p-nitrophenylphosphate. Albumin: citrate buffer, bromocresol green. Measurement: kinetic photometry (ALP) and colorimetry (Albumin). Instrument: Yumizen C1200. Traceability: IFCC reference procedure (ALP), ERM-DA470 (Albumin).

Indications for Use

Indicated for quantitative in vitro diagnostic determination of alkaline phosphatase and albumin in human serum and plasma for diagnosis and treatment of liver, bone, parathyroid, intestinal, and kidney diseases. Prescription use only; not for point-of-care use.

Regulatory Classification

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.

Predicate Devices

ALP IFCC Gen2 (K171080)
ABX Pentra Albumin CP (K060434)

Related Devices

K991762 — ALKALINE PHOPHATASE (ALP), PRODUCT NO'S 118-01, 118-02 · A.P. Total Care, Inc. · Sep 2, 1999
K101090 — EASYRA ALKALINE PHOSPHATASE, ASPARTATE AMINOTRANSFERASE AND AMYLASE REAGENTS · Medica Corp. · May 20, 2011

Submission Summary (Full Text)

{0}------------------------------------------------ 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 {1}------------------------------------------------ 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 {2}------------------------------------------------ #### 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) 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. | 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) {3}------------------------------------------------ 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. {4}------------------------------------------------ Image /page/4/Picture/0 description: The image contains the logo for HORIBA Medical. The word "HORIBA" is in a large, bold, blue font. 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. 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 vitro diagnostic determination of alkaline phosphatase in human serum and plasma based on a kinetic photometric test using p-Nitrophenylphosphate. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases. | | Yumizen C1200 Albumin | 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. | {5}------------------------------------------------ Image /page/5/Picture/0 description: The image contains the logo for HORIBA Medical. The word "HORIBA" is in large, bold, blue letters. Below it, in a smaller font and lighter blue color, is the word "Medical." #### 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 | Predicate 510(k) number | |--------------------------|-----------------------|------------------------------------------------|-------------------------------| | Yumizen C1200 ALP | ALP IFCC Gen2 | COBAS 8000/Roche Diagnostics | K171080 | | Yumizen C1200 Albumin | 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. {6}------------------------------------------------ Image /page/6/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. # 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 quantitative determination of the catalytic activity of alkaline phosphatase in humain serum and plasma on COBAS INTEGRA systems | Diagnostic reagent for quantitative in- vitro determination of Alkaline Phosphatase (ALP) in serum or plasma by 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 c pack label | Stable up to the expiry date on the label if stored at 2-8°C.Store protected from light | | 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 chemistry analyzer | | 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 board Stability | On-board in use at 10-15°C : 4 weeks | Once opened, the reagent cassette placed in the refrigerated compartment is stable | {7}------------------------------------------------ Image /page/7/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 colors are consistent. | Item | Predicate k171080 | Candidate | |----------------|----------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | | | for 1 week | | | Measuring Range 3.0-1200 U/L | Measuring Range 6.0-1200 U/L | | Analytic Range | Automatic post-dilution: Results from samples diluted using the rerun function are automatically multiplied by 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 be realized in case of sample concentration higher than 1200 U/L | Discussion on the analysis differences : - 1. Manufacturer is different because of the choice of predicate - 2. Instrument: Yumizen C1200 ALP is used on Yumizen C1200 (See 2.) - 3. Packaging: Yumizen C1200 ALP has one packaging. Its predicate has two packagings, one is smaller and the other is larger. - 4. Reagent stability: the on board stability of Yumizen C1200 ALP is shorter. Stability depend on reagent composition and cassette capacity. - 5. 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-vitro determination of Albumin in serum and plasma by colorimetry. | 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. | | Manufactured by | HORIBA ABX SAS | HORIBA ABX SAS | | Sample type | Serum, plasma in lithium heparin | Same | | Reagent format | Liquid | Same | | Measurement | Quantitative | Same | {8}------------------------------------------------ Image /page/8/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." | Item | Predicate K060434 | Candidate | |-----------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | method | Colorimetry | Same | | Calibrators | ABX Pentra Multical | Yumizen C1200 Multical | | Shelf-life | In onopened cassettes, stable up to the expiry date on the label if stored at 2-8°C | Stable up to the expiry date on the label if stored at 2-8°C. Store protected from light. | | Analytic Range | Measuring Range 0.46-5.60 g/dL | Measuring Range 0.46-5.60 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/L 4 days - 14 years: 38 - 54 g/L 14 - 18 years: 32 - 45 g/L 20 - 60 years: 35 - 52 g/L 60 - 90 years: 32 - 46 g/L > 90 years: 29 - 45 g/L. | 0 - 4 days: 28 - 44 g/L 4 days - 14 years: 38 - 54 g/L 14 - 18 years: 32 - 45 g/L 20 - 60 years: 35 - 52 g/L 60 - 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 Chemistry Analyzer | Yumizen C1200 Clinical chemistry analyzer | | 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 | | Reagent On board Stability | One opened, the reagent cassette placed in the refrigerated ABX Pentra 400 compartment is stable: 83 days ( 11 weeks) | Once opened, the reagent cassette placed in the refrigerator compartment is stable for 6 weeks. | | Calibration Stability | The reagent is calibrated on Day 0. The calibration stability is checked by testing 2 | 6 weeks | {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, the word "Medical" is in a smaller, lighter blue font. The logo is simple and clean, with a focus on the company name. | Item | Predicate K060434 | Candidate | |-----------------------------------------|----------------------------------------------------------------------|-----------| | | control specimens. The calibration stability is at least 14 days. | | | Discussion on the analysis differences. | | | 1. Instrument: Yumizen C1200 Albumin is used on Yumizen C1200 2. Packaging: Yumizen C1200 Albumin has two packaging on, one is smaller and the other is larger. 3. Number of test depends on packaging and cassette capacity. 4. Reagent stability: the on board stability of Yumizen C1200 Albumin is shorter. Stability depend on reagent composition and cassette capacity. {10}------------------------------------------------ Image /page/10/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 - 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 {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, in smaller, lighter blue letters, is the word "Medical." # 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 of detection | 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 of detection | Limit of quantitation | Linearity | Measuring range | |-------------------|-----------------------|-----------------------|---------------|-----------------| | Serum / plasma | LoD = 0.57 g/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. | {12}------------------------------------------------ Image /page/12/Picture/0 description: The image contains 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." # 8.2 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 | {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 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. {14}------------------------------------------------ Image /page/14/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." #### 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 N Multi Control | 240 | 37.8 | 0.4 | 2.4 | 1.8 | 0.3 | 3.0 | | Yumizen C1200 P Multi 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 C1200 N Multi Control | 90 | 37.67 | 1.0 | 0.5 | 1.1 | 0.0 | 1.1 | | Yumizen C1200 P 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. {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." # 8.3 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 | | Acetylsalicylic Acid | 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 | | Acetylsalicylic Acid | 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 | {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 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. {17}------------------------------------------------ Image /page/17/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. # 8.5 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. {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." # 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. {19}------------------------------------------------ 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: {20}------------------------------------------------ Image /page/20/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." 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: 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. {21}------------------------------------------------ Image /page/21/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." ### 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.