ELITech Clinical Systems BILIRUBIN DIRECT 4+1 is intended for the quantitative in vitro diagnostic determination of direct bilirubin in human serum and plasma on ELITech Clinical Systems Selectra Pro Series Analyzers.

It is not intended for use in Point of Care settings.

Measurements of the levels of bilirubin (direct or total), an organic compound formed during the normal and abnormal distruction of red blood cells, are used in the diagnosis and treatment of liver, hematological, and metabolic disorders, including hepatitis and gall bladder block.

Device Description

ELITech Clinical Systems BILIRUBIN TOTAL 4+1 and ELITech Clinical Systems BILIRUBIN DIRECT 4+1 are available as a kit only. Each kit consists of a bi-reagent R1 & R2.

ELITech Clinical Systems BILIRUBIN TOTAL 4+1:
Reagent 1: R1 Sulphanilic acid 29 mmol/L, Cetrimide 29 mmol/L.
Reagent 2: R2 Sodium nitrite 11 mmol/L.

ELITech Clinical Systems BILIRUBIN DIRECT 4+1:
Reagent 1: R1 Sulphanilic acid 29 mmol/L,
Reagent 2: R2 Sodium nitrite 11 mmol/L.

AI/ML Overview

The document describes the analytical performance and comparison studies for the ELITech Clinical Systems BILIRUBIN TOTAL 4+1 and ELITech Clinical Systems BILIRUBIN DIRECT 4+1 devices. These devices are intended for the quantitative in vitro diagnostic determination of total and direct bilirubin, respectively, in human serum and plasma. The studies aim to demonstrate substantial equivalence to predicate devices (ABX Pentra Bilirubin, Total CP & ABX Pentra Bilirubin, Direct CP).

Here's the breakdown of the information based on your request:

1. Table of Acceptance Criteria and Reported Device Performance

For ELITech Clinical Systems BILIRUBIN TOTAL 4+1:

Acceptance Criteria Category	Specific Metric	Acceptance Criteria	Reported Device Performance
Precision	Within-run CV%	Not explicitly stated as a numerical criterion, but evaluated by comparing with predicate device and clinical requirements for bilirubin assays.	Level 1 (1.15 mg/dL): 1.8%Level 2 (4.08 mg/dL): 0.4%Level 3 (14.61 mg/dL): 0.5%
	Total CV%	Not explicitly stated as a numerical criterion.	Level 1 (1.15 mg/dL): 5.0%Level 2 (4.08 mg/dL): 3.1%Level 3 (14.61 mg/dL): 2.9%
Linearity/Reportable Range	Measuring Range	Not explicitly stated as a numerical criterion, but evaluated to cover clinically relevant range.	0.25 - 25 mg/dL (up to 60.00 mg/dL with auto-dilution)
Detection Limit	Limit of Detection (LoD)	Not explicitly stated as a numerical criterion.	0.04 mg/dL (0.7 µmol/L)
Quantification Limit	Limit of Quantification (LoQ)	≤ 0.07 mg/dL Total Error, and ≥ LoD.	0.15 mg/dL (2.6 µmol/L)
Interference	Bias	Acceptance criterion: ±10% bias for nominal activities of 1.00 mg/dL and 15.00 mg/dL.	Triglycerides: No significant interference up to 2100 mg/dLHemoglobin: No significant interference up to 500 mg/dLAcetaminophen: No significant interference up to 30 mg/dLAscorbic acid: No significant interference up to 4 mg/dLAcetylsalicylic acid: No significant interference up to 200 mg/dL
Method Comparison	Correlation (r)	Not explicitly stated as a numerical criterion, but assessed for strong correlation with predicate.	r = 0.999
	Coefficient of Determination (r²)	Not explicitly stated as a numerical criterion.	r² = 0.999
	Standard error of the estimate (Sy.x)	Not explicitly stated as a numerical criterion.	0.19 mg/dL
Matrix Comparison	Correlation (r)	Not explicitly stated as a numerical criterion.	r = 0.998
	Coefficient of Determination (r²)	Not explicitly stated as a numerical criterion.	r² = 0.997
	Standard error of the estimate (Sy.x)	Not explicitly stated as a numerical criterion.	0.36 mg/dL

For ELITech Clinical Systems BILIRUBIN DIRECT 4+1:

Acceptance Criteria Category	Specific Metric	Acceptance Criteria	Reported Device Performance
Precision	Within-run CV%	Not explicitly stated as a numerical criterion.	Level 1 (0.36 mg/dL): 3.8%Level 2 (1.51 mg/dL): 1.9%Level 3 (3.99 mg/dL): 0.9%
	Total CV%	Not explicitly stated as a numerical criterion.	Level 1 (0.36 mg/dL): 5.2%Level 2 (1.51 mg/dL): 5.3%Level 3 (3.99 mg/dL): 4.7%
Linearity/Reportable Range	Measuring Range	Not explicitly stated as a numerical criterion.	0.08 - 10.55 mg/dL (up to 50.00 mg/dL with auto-dilution)
Detection Limit	Limit of Detection (LoD)	Not explicitly stated as a numerical criterion.	0.01 mg/dL (0.2 µmol/L)
Quantification Limit	Limit of Quantification (LoQ)	≤ 0.05 mg/dL Total Error, and ≥ LoD.	0.08 mg/dL (1.4 µmol/L)
Interference	Bias	Acceptance criterion: ±10% bias for nominal activities of 0.40 mg/dL and 4.00 mg/dL.	Triglycerides: No significant interference up to 2000 mg/dLHemoglobin: No significant interference up to 125 mg/dLAcetaminophen: No significant interference up to 30 mg/dLAscorbic acid: No significant interference up to 0.5 mg/dLAcetylsalicylic acid: No significant interference up to 200 mg/dL
Method Comparison	Correlation (r)	Not explicitly stated as a numerical criterion.	r = 0.998
	Coefficient of Determination (r²)	Not explicitly stated as a numerical criterion.	r² = 0.995
	Standard error of the estimate (Sy.x)	Not explicitly stated as a numerical criterion.	0.15 mg/dL
Matrix Comparison	Correlation (r)	Not explicitly stated as a numerical criterion.	r = 0.999
	Coefficient of Determination (r²)	Not explicitly stated as a numerical criterion.	r² = 0.997
	Standard error of the estimate (Sy.x)	Not explicitly stated as a numerical criterion.	0.14 mg/dL

2. Sample Size Used for the Test Set and Data Provenance

Precision (Test Set):
- Sample Size: 80 measurements for each of 3 levels of samples (total 240 measurements per device) per instrument (2 instruments used).
- Data Provenance: Not explicitly stated (e.g., country of origin). The samples are referred to as "samples" or "patient samples." The study was prospective in the sense that controlled experiments were performed to gather data for precision.
Linearity (Test Set):
- ELITech Clinical Systems BILIRUBIN TOTAL 4+1: 11 levels of mixed samples.
- ELITech Clinical Systems BILIRUBIN DIRECT 4+1: 11 levels of mixed samples.
- Data Provenance: Not explicitly stated. Likely prepared in a laboratory setting.
Detection Limit (Test Set):
- Sample Size: 15 measurements of 4 samples for each device.
- Data Provenance: Prepared from patient samples and diluted with Albumin 6 g/dL - NaCl 0.9 %.
Interference (Test Set):
- Sample Size: For each potential interferent, 2 serum sample pools (low and high concentration), with aliquots spiked at various interferent concentrations (9 or 7 or 8 different concentrations). Each point was measured in triplicate per run. Two levels of control were also tested. A control sample was prepared from the sample pool diluted in appropriate diluent.
- Data Provenance: "Serum sample pools." Not explicitly stated.
Method Comparison (Test Set):
- Sample Size: 100 serum patient samples for each device.
- Data Provenance: "Serum patient samples." Not explicitly stated, but likely from a clinical laboratory or hospital in the country where the studies were conducted (France or USA, as these are locations given for the submitter and contact person). The study was likely prospective in nature for collecting these samples for comparison against the predicate.
Matrix Comparison (Test Set):
- Sample Size: 40 plasma patients (lithium heparin samples) for each device.
- Data Provenance: "Plasma patients." Not explicitly stated. Likely from a clinical laboratory or hospital.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

For this type of in vitro diagnostic device (quantitative measurement of bilirubin), the "ground truth" is typically established by reference methods or comparison to legally marketed predicate devices, not by expert interpretation. The predicate devices are considered the "ground truth" for the method comparison studies. The document implicitly uses the performance of the legally marketed predicate device (ABX Pentra Bilirubin, Total CP & ABX Pentra Bilirubin, Direct CP) as the standard against which the new device's performance is compared for substantial equivalence.

There is no mention of experts establishing ground truth in the traditional sense of medical imaging or clinical diagnosis.

4. Adjudication Method for the Test Set

Not applicable. This is an in vitro diagnostic device performing quantitative measurements, not an AI or imaging device requiring human adjudication of results. The performance is assessed by comparing quantitative results against reference or predicate methods.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is typically for imaging devices where human readers interpret medical images with and without AI assistance. The described device is an in vitro diagnostic assay.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done

Yes, the studies described are standalone performance evaluations of the device (reagents on an analyzer). The device itself (the reagent system) functions as an "algorithm only" in the sense that it performs the chemical reaction and measurement without human interpretive input for each test result. Clinical laboratory technologists would operate the analyzer and interpret the numerical results, but the analytical performance described is the device's intrinsic capability.

7. The Type of Ground Truth Used

The primary ground truth for demonstrating substantial equivalence is the performance of the legally marketed predicate devices (ABX Pentra Bilirubin, Total CP & ABX Pentra Bilirubin, Direct CP). In the method comparison studies, the results from the new devices are compared against the results from the predicate devices using patient samples.

Additionally, for analytical performance like linearity, detection limit, and interference, the "ground truth" for evaluating the performance of the device is based on prepared samples with known concentrations or expected behaviors (e.g., spiked samples with interferents, serially diluted samples).

8. The Sample Size for the Training Set

Not applicable. This device is an in vitro diagnostic reagent system, not an AI/ML-based device that requires a "training set" in the computational sense. Its performance is based on chemical reactions and instrumental measurements, which are validated through analytical studies.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as there is no "training set" for this type of device.

Summary

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular, with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. In the center of the circle is a stylized image of a caduceus, which is a symbol of medicine.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

July 11, 2017

ELITECHGROUP TERRY TRIMINGHAM, REGULATORY AFFAIRS MANAGER 21720 23RD DRIVE SE, SUITE 150 BOTHELL, WA 98021

Re: K171401 Trade/Device Name: ELITech Clinical Systems BILIRUBIN TOTAL 4+1, ELITech Clinical Systems BILIRUBIN DIRECT 4+1 Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: II Product Code: CIG Dated: May 3, 2017 Received: May 12, 2017

Dear Terry Trimingham:

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. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Kellie B. Kelm -S

for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known) K171401

Device Name

ELITech Clinical Systems BILIRUBIN TOTAL 4+1 ELITech Clinical Systems BILIRUBIN DIRECT 4+1

Indications for Use (Describe)

It is not intended for use in Point of Care settings.

Type of Use (Select one or both, as applicable)
-------------------------------------------------	--

[X] Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

ELITech Clinical Systems BILIRUBIN TOTAL 4+1 ELITech Clinical Systems BILIRUBIN DIRECT 4+1

1.	Date:	July 11, 2017
2.	Submitter:	ELITech Clinical Systems SAS
		Zone Industrielle
		61500 SEES
		FRANCE
3.	Contact Person:	Terry Trimingham
		21720 23rd Dr SE, Suite 150
		Bothell, WA 98021
		Phone: 425-482-5190
		Fax: 425-482-5550
		Email: t.trimingham@elitechgroup.com
4.	Device Description:	ELITech Clinical Systems BILIRUBIN TOTAL 4+1
	Classification	Class II
		CIG - Diazo Colorimetry, Bilirubin
		Clinical Chemistry
		21 CFR 862.1110
	Device Description:	ELITech Clinical Systems BILIRUBIN DIRECT 4+1
	Classification	Class II
		CIG - Diazo Colorimetry, Bilirubin
		Clinical Chemistry
		21 CFR 862.1110
5.	Predicate Device:	K060325
		ABX Pentra Bilirubin, Total CPABX Pentra Bilirubin, Direct CP

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Intended Use
ELITech ClinicalSystems BILIRUBINTOTAL 4+1:	ELITech Clinical Systems BILIRUBIN TOTAL 4+1 isintended for the quantitative in vitro diagnosticdetermination of total bilirubin in human serum andplasma on ELITech Clinical Systems Selectra Pro SeriesAnalyzers.Measurements of the levels of bilirubin (direct or total), anorganic compound formed during the normal andabnormal distruction of red blood cells, are used in thediagnosis and treatment of liver, hemolytic hematological,and metabolic disorders, including hepatitis and gallbladder block.It is not intended for use in Point of Care settings.
ELITech ClinicalSystems BILIRUBINDIRECT 4+1:	ELITech Clinical Systems BILIRUBIN TOTAL 4+1 isintended for the quantitative in vitro diagnosticdetermination of total bilirubin in human serum andplasma on ELITech Clinical Systems Selectra Pro SeriesAnalyzers.Measurements of the levels of bilirubin (direct or total), anorganic compound formed during the normal andabnormal distruction of red blood cells, are used in thediagnosis and treatment of liver, hemolytic hematological,and metabolic disorders, including hepatitis and gallbladder block.It is not intended for use in Point of Care settings.

Intended Use

ELITech ClinicalSystems BILIRUBINTOTAL 4+1:

ELITech Clinical Systems BILIRUBIN TOTAL 4+1 isintended for the quantitative in vitro diagnosticdetermination of total bilirubin in human serum andplasma on ELITech Clinical Systems Selectra Pro SeriesAnalyzers.Measurements of the levels of bilirubin (direct or total), anorganic compound formed during the normal andabnormal distruction of red blood cells, are used in thediagnosis and treatment of liver, hemolytic hematological,and metabolic disorders, including hepatitis and gallbladder block.It is not intended for use in Point of Care settings.

ELITech ClinicalSystems BILIRUBINDIRECT 4+1:

Special conditions for use statement(s):

Rx only.

This device is intended for prescription use and in vitro diagnostic only.

CAUTION: Federal Law restricts this device to sale by or on the order of a licensed healthcare practitioner. It is not intended for use in Point of Care settings.

Reagent Special instrument requirements:

For use with ELITech Clinical Systems Selectra Pro Series Analyzers. Performance data was obtained on the Selectra ProM Analyzer.

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7. Device Descriptions

Both ELITech Clinical Systems BILIRUBIN TOTAL 4+1 and ELITech Clinical Systems BILIRUBIN DIRECT 4+1 are available as a kit only.

Each kit consists of a bi-reagent R1 & R2 whose composition is:

ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :

Reagent 1: R1

Sulphanilic acid 29 mmol/L,

Cetrimide 29 mmol/L.

Reagent 2: R2

Sodium nitrite 11 mmol/L.

ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :

Reagent 1: R1

Sulphanilic acid 29 mmol/L,

Reagent 2: R2

Sodium nitrite 11 mmol/L.

Substantial Equivalence Information

Assay (reagent)

1. Predicate Device Name
  ABX Pentra Bilirubin, Total CP & ABX Pentra Bilirubin, Direct CP
1. K060325

Comparison with predicate ABX Pentra Bilirubin, Total CP & ABX Pentra Bilirubin, Direct CP

Similarities

Similarities

Parameter	New DeviceELITech Clinical Systems BILIRUBINTOTAL 4+1 & ELITech ClinicalSystems BILIRUBIN DIRECT 4+1	Predicate DeviceABX Pentra Bilirubin, Total CP & ABXPentra Bilirubin, Direct CP, K060325
Intended Use	ELITech Clinical SystemsBILIRUBIN TOTAL 4+1:	ABX Pentra Bilirubin, Total CP:
	ELITech Clinical Systems BILIRUBINTOTAL 4+1 is intended for thequantitative in vitro diagnosticdetermination of total bilirubin inhuman serum and plasma on ELITechClinical Systems Selectra Pro SeriesAnalyzers.	ABX Pentra Bilirubin, Total CP reagentis intended for the quantitative in vitrodiagnostic determination of totalbilirubin in human serum and plasmabased on a photometric test using 2,4-dichloroaniline (DCA) and detergents.
	It is not intended for use in Point ofCare settings.

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	ELITech Clinical SystemsBILIRUBIN DIRECT 4+1 :	ABX Pentra Bilirubin, Direct CP :
	ELITech Clinical Systems BILIRUBINDIRECT 4+1 is intended for thequantitative in vitro diagnosticdetermination of direct bilirubin inhuman serum and plasma on ELITechClinical Systems Selectra Pro SeriesAnalyzers.	ABX Pentra Bilirubin, Direct CP reagentis intended for the quantitative in vitrodiagnostic determination of directbilirubin in human serum and plasmabased on a photometric test using 2,4-dichloroaniline (DCA).
	It is not intended for use in Point ofCare settings.
Indication forUse	Measurements of the levels of bilirubin(direct or total), an organic compoundformed during the normal andabnormal destruction of red blood cells,are used in the diagnosis andtreatment of liver, hemolytichematological, and metabolicdisorders, including hepatitis and gallbladder block. It is not intended for usein Point of Care settings.	Same
Sample Type	Serum, plasma	Same
Appearanceof reagents	Liquid form, ready to use	Same

Differences

Parameter	New DeviceELITech Clinical Systems BILIRUBINTOTAL 4+1 & ELITech ClinicalSystems BILIRUBIN DIRECT 4+1	Predicate DeviceABX Pentra Bilirubin, Total CP & ABXPentra Bilirubin, Direct CP K060325
Assay Format	ELITech Clinical SystemsBILIRUBIN TOTAL 4+1 :R1: 8 x 20 mLR2: 8 x 5 mLELITech Clinical SystemsBILIRUBIN DIRECT 4+1 :R1: 8 x 20 mLR2: 8 x 5 mL	ABX Pentra Bilirubin, Total CP :R1 : 29.5 mLR2 : 9.8 mLABX Pentra Bilirubin, Direct CP :R1 : 24 mLR2 : 7 mL
AssayTechnology	Malloy-Evelyn modified. End point.	Photometric test using 2,4-dichloroaniline (DCA), and a specificmixture of detergents.

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ReferenceValues	ELITech Clinical SystemsBILIRUBIN TOTAL 4+1 :	ABX Pentra Bilirubin, Total CP :
	0.2-1.2 mg/dL (3.4-21 µmol/L)ELITech Clinical Systems	Adults: 0.1 - 1.2 mg/dL (1.7 - 21µmol/L)
	BILIRUBIN DIRECT 4+1 :	ABX Pentra Bilirubin, Direct CP :
	< 0.2 mg/dL (3.4 µmol/L)	Adults and children: ≤ 0.2 mg/dL (≤3.4 µmol/L).

Controls	Recommended quality controlmaterial (not included):	Recommended quality controlmaterial (not included):
		ABX Pentra N Control & ABX Pentra
	ELITech Clinical Systems ELITROL I	P Control
	(Normal control) (cleared in K110780)ELITech Clinical Systems ELITROL II
	(Pathologic control) (cleared inK110780)
Calibrator	Recommended calibration material(not included):	Recommended calibration material(not included):ABX Pentra Multical
	ELITech Clinical Systems ELICAL 2(cleared in K110780)
Limit ofDetection	ELITech Clinical SystemsBILIRUBIN TOTAL 4+1 :	ABX Pentra Bilirubin, Total CP :1.49 µmol/L (0.09 mg/dL).
	0.04 mg/dL (0.7 µmol/L)
	ELITech Clinical SystemsBILIRUBIN DIRECT 4+1 :	ABX Pentra Bilirubin, Direct CP :
	0.01 mg/dL (0.2 µmol/L)	0.69 µmol/L (0.04 mg/dL).

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Interferences	ELITech Clinical SystemsBILIRUBIN TOTAL 4+1 :Triglycerides: No significantinterference up to 2100 mg/dL (23.73mmol/L).Hemoglobin: No significantinterference up to 500 mg/dL.Acetaminophen: No significantinterference up to 30 mg/dL.Ascorbic acid: No significantinterference up to 4 mg/dL.Acetylsalicylic acid: No significantinterference up to 200 mg/dL.	ABX Pentra Bilirubin, Total CP :Haemoglobin: No significant influenceis observed up to 290 µmol/L (500mg/dL).Triglycerides: No significant influenceis observed up to 7 mmol/L (612.5mg/dL).
	ELITech Clinical SystemsBILIRUBIN DIRECT 4+1 :Triglycerides: No significantinterference up to 2000 mg/dL (22.60mmol/L)Hemoglobin: No significantinterference up to 125 mg/dL.Acetaminophen: No significantinterference up to 30 mg/dL.Ascorbic acid: No significantinterference up to 0.5 mg/dL.Acetylsalicylic acid: No significantinterference up to 200 mg/dL.	ABX Pentra Bilirubin, Direct CP :Haemoglobin: Do not use hemolysedsamples.Triglycerides: No significant influenceis observed up to an Intralipid®concentration (representative oflipemia) of 7 mmol/L (612.5 mg/dL).
On-boardstability	28 days	ABX Pentra Bilirubin, Total CP :25 daysABX Pentra Bilirubin, Direct CP :30 days
Calibrationfrequency	Calibration frequency: 28 daysRecalibrate when reagent lotschange, when quality control resultsfall outside the established range, andafter a maintenance operation.	The reagent is calibrated on Day 0.The calibration stability is checked bytesting 2 control specimens. Thecalibration stability is 10 days.Note: A recalibration is recommendedwhen reagent lots change, and whenquality control results fall outside therange established.

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9. Test Principle:

ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :

Sulphanilic acid reacts with sodium nitrite to form diazotized sulphanilic acid. In the presence of accelerator (cetrimide), conjugated and unconjugated bilirubin react with diazotized sulphanilic acid to form azobilirubin.

The increase of absorbance at 546 nm is proportional to bilirubin concentration.

ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :

Sulphanilic acid reacts with sodium nitrite to form diazotized sulphanilic acid. In the absence of accelerator, only conjugated bilirubin reacts with diazoted sulphanilic acid to form azobilirubin.

The increase of absorbance at 546 nm is proportional to bilirubin concentration.

Performance Characteristics - Analytical Performance 10.

a. Precision/Reproducibility

Precision

Within-run and total precision results were obtained by performing two runs per day, two measures per run, for 3 concentrations of samples on 2 instruments during twenty operating days. The results are presented in the tables below:

For ELITech Clinical Systems BILIRUBIN TOTAL 4+1:

Level	n	Mean (mg/dL)	Precision %
			Within-run CV%	Total CV%
Level 1	80	1.15	1.8	5.0
Level 2	80	4.08	0.4	3.1
Level 3	80	14.61	0.5	2.9

For ELITech Clinical Systems BILIRUBIN DIRECT 4+1:

Level	n	Mean (mg/dL)	Precision %
			Within-run CV%	Total CV%
Level 1	80	0.36	3.8	5.2
Level 2	80	1.51	1.9	5.3
Level 3	80	3.99	0.9	4.7

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b. Linearity/assay reportable range

The linearity of ELITech Clinical Systems BILIRUBIN TOTAL 4+1 was studied by mixing a sample with high value (25.13 mg/dL) and a sample with low value (0.25 mg/dL) to obtain 11 levels with equidistant concentrations and then measuring the Total Bilirubin concentration of each of the 11 levels using ELITech Clinical Systems BILIRUBIN TOTAL 4+1.

From this study, a measuring range from 0.25 - 25 mg/dL has been determined. Auto-dilution 1 to 5 allows the use of the ELITech Clinical Systems BILIRUBIN TOTAL 4+1 with analyte concentration up to 60.00 mg/dL.

The linearity of ELITech Clinical Systems BILIRUBIN DIRECT 4+1 was studied by mixing a sample with high value (10.59 mg/dL) and a sample with low value (0.06 mg/dL) to obtain 11 levels with equidistant concentrations and then measuring the Direct Bilirubin concentration of each of the 11 levels using ELITech Clinical Systems BILIRUBIN DIRECT 4+1.

From this study, a measuring range from 0.08 - 10.55 mg/dL has been determined. Auto-dilution 1 to 5 allows the use of the ELITech Clinical Systems BILIRUBIN DIRECT 4+1 with analyte concentration up to 50.00 mg/dL.

c. Detection limit

Limit of Detection:

ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :

The limit of Detection was obtained from 15 measurements of 4 samples prepared from 4 patient samples measured using ELITech Clinical Systems BILIRUBIN TOTAL 4+1 and diluted with Albumin 6 q/dL - NaCl 0.9 % down to a concentration of circa 0.15 mg/dL. The data are not Gaussian. so LoD= LoB + DS.ß (where DS.ß is determined by calculating the median minus the 5th percentile of the low activity sample distribution). Limit of Detection : 0.04 mg/dL (0.7 umol/L)

ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :

The limit of Detection was obtained from 15 measurements of 4 samples prepared from 4 patient samples measured using ELITech Clinical Systems BILIRUBIN DIRECT 4+1 and diluted with Albumin 6 g/dL - NaCl 0.9 % to obtain a concentration of approximately 4 times the LoB.

The data are not Gaussian, so LoD= LoB + DS,ß (where DS,ß is determined by calculating the median minus the 5th percentile of the low activity sample distribution). Limit of Detection : 0.01 mg/dL (0.2 umol/L)

Limit of Quantification:

ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :

The limit of Quantification was obtained from 15 measurements of 4 samples prepared from 4 patient samples measured using ELITech Clinical Systems BILIRUBIN TOTAL 4+1 reagent and diluted with Albumin 6 g/dL - NaCl 0.9 % down to a concentration circa 0.15 ma/dL.

Acceptance criteria: The acceptable Total Error for the determination Limit of Quantification is ≤ 0.07 mg/dL. The value must be equal or higher than the Limit of Detection. Limit of Quantification = 0.15 mq/dL (2.6 umol/L)

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ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :

The limit of Quantification was obtained from 15 measurements of 4 samples prepared from 4 patient samples measured using ELITech Clinical Systems BILIRUBIN DIRECT 4+1 reagent and diluted with Albumin 6 g/dL - NaCl 0.9 % down to a concentration circa of 0.08 ma/dL.

Acceptance criteria: The acceptable Total Error for the determination Limit of Quantification is ≤ 0.05 mg/dL. The value must be equal or higher than the Limit of Detection. Limit of Quantification = 0.08 mg/dL (1.4 µmol/L)

d. Interference/analytical specificity

ELITech Clinical Systems BILIRUBIN TOTAL 4+1:

Interferences due to Triglycerides, Hemoglobin, Acetaminophen, Ascorbic acid, and Acetylsalicylic acid were investigated.

For each potential interferent tested, 2 serum sample pools at two Total Bilirubin levels were prepared:

-1st pool: low concentration at nominal 1.00 mg/dL

-2nd pool: high concentration at nominal 15.00 mg/dL

Aliquots of each of the serum sample pools were spiked with increasing interferent concentration. Test ranges covered at least the interferent level. Thus, there were two series of interferent spike for each potential interferent tested. A control sample was prepared from the sample pool diluted in the appropriate diluent.

Interferent	Test range	Number of differentconcentrations tested
Triglycerides	up to 3000 mg/dL	9
Hemoglobin	up to 500 mg/dL	9
Acetaminophen	up to 30 mg/dL	7
Ascorbic acid	up to 20 mg/dL	7
Acetylsalicylic acid	up to 200 mg/dL	7

Two (2) levels of control (ELITech Clinical Systems ELITROL I & II ) were tested to check the calibration.

For both sample pools for each interferent, each point was measured in triplicate per run. Acceptance criteria: an accepted bias of ±10% in sample pools with low (1.00 mg/dL) or high (15.00 mg/dL) nominal activity.

The results of testing interferences are the following:

Triglycerides concentration up to 2100 mg/dL (23.73 mmol/L), Hemoglobin up to 500 mg/dL, Acetaminophen up to 30 mg/dL, Ascorbic acid up to 4 mg/dL. Acetylsalicylic acid up to 200 mg/dL.
In very rare cases, monoclonal gammopathies (multiple myeloma), in particular IgM type (Waldenstrom's macroglobulinemia) can cause unreliable results.

The following statement will also be included in the labeling:

Many other substances and drugs may interfere. Some of them are listed in Young. -Young, D. S., Effects of preanalytical variables on clinical laboratory tests, 2nd Ed., AACC Press. (1997).

-Young, D. S., Effects of drugs on clinical laboratory tests, 4th Ed., AACC Press, (1995). -Berth, M. & Delanghe, J. Protein precipitation as a possible important pitfall in the clinical chemistry analysis of blood samples containing monoclonal immunoglobulins: 2 case reports and a review of literature, Acta Clin Belg., (2004), 59, 263.

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ELITech Clinical Systems DIRECT DIRECT 4+1:

Interferences due to Trialycerides. Hemoglobin, Acetaminophen, Ascorbic acid, and Acetylsalicylic acid were investigated.

For each potential interferent tested, 2 serum sample pools at two Direct Bilirubin levels were prepared:

-1st pool: low activity at nominal 0.40 mg/dL

-2nd pool: high activity at nominal 4.00 mg/dL

Interferent	Test range	Number of differentconcentrations tested
Triglycerides	up to 3000 mg/dL	9
Hemoglobin	up to 500 mg/dL	9
Acetaminophen	up to 30 mg/dL	7
Ascorbic acid	up to 5 mg/dL	8
Acetylsalicylic acid	up to 200 mg/dL	7

Two (2) levels of control (ELITech Clinical Systems ELITROL I & II ) were tested to check the calibration.

For both sample pools for each interferent, each point was measured in triplicate per run. Acceptance criteria: an accepted bias of ±10% in sample pools with low (0.40 mg/dL) or high (4.00 mg/dL) nominal activity.

The results of testing interferences are the following:

Triglycerides concentration up to 2000 mg/dL (22.60 mmol/L), Hemoglobin up to 125 mg/dL, Acetaminophen up to 30 mg/dL, Ascorbic acid up to 0.5 mg/dL, Acetylsalicy/ic acid up to 200 mg/dL.
In very rare cases, monoclonal gammopathies (multiple myeloma), in particular IgM । type (Waldenstrom's macroglobulinemia) can cause unreliable results.

The following statement will also be included in the labeling:

Many other substances and drugs may interfere. Some of them are listed in Young. -Young, D. S., Effects of preanalytical variables on clinical laboratory tests, 200 Ed., AACC Press. (1997).

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11. Performance Characteristics - Comparison Studies

a. Method comparison

Correlation studies were performed between ELITech Clinical Systems BILIRUBIN TOTAL 4+1 & ELITech Clinical Systems BILIRUBIN DIRECT 4+1 reagents on a Selectra ProM Analyzer.

ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :

This study was performed using 100 serum patient samples from 0.32 to 23.02 mg/dL over a span of 5 days. Regression analysis of the results yielded the following: y = 0.948 x - 0.11 mg/dL. r = 0.999 r2 = 0.999 Standard error of the estimate Sy.x = 0.19 mg/dL.

ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :

This study was performed using 100 serum patient samples from 0.09 to 10.52 mg/dL over a span of 5 days. Regression analysis of the results yielded the following: y = 0.926 x - 0.03 mg/dL. r = 0.998 r2 = 0.995 Standard error of the estimate Sy.x = 0.15 mg/dL.

b. Comparison study: Matrix comparison

ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :

40 plasma patients (in lithium heparin samples, ranging from 0.33 to 24.08 mg/dL), were tested on ELITech Clinical Systems Selectra ProM Analyzer. Regression analysis of the results yielded the following: y = 0.985x + 0.03 mg/dL r = 0.998 r2 = 0.997 Standard error of the estimate Sy.x = 0.36 mg/dL

ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :

40 plasma patients (in lithium heparin samples, ranging from 0.09 to 7.78 mg/dL), were tested on ELITech Clinical Systems Selectra ProM Analyzer. Regression analysis of the results yielded the following: y = 0.990x - 0.01 mg/dL r = 0.999 r2 = 0.997 Standard error of the estimate Sy.x = 0.14 mg/dL

c. Expected values/Reference Range

As indicated in the instructions for use for both ELITech Clinical Systems BILIRUBIN TOTAL 4+1 & ELITech Clinical Systems BILIRUBIN DIRECT 4+1, each laboratory should establish and maintain its own reference values. The values given are used as guidelines only.

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ELITech Clinical Systems BILIRUBIN TOTAL 4+1 :

Adults : 0.2-1.2 mg/dL ( 3.4-21 umol/L)

ELITech Clinical Systems BILIRUBIN DIRECT 4+1 :

< 0.2 mg/dL (3.4 µmol/L)

These reference values are from:

Wu, H.B., General Clinical Tests. Tietz Clinical guide to laboratory tests, 4th Ed., (W.B. Saunders eds. Philadelphia USA), (2006), 172

d. Clinical Studies:

Not applicable

e. Clinical Cut-off:

Not applicable

12. Conclusion

The information on the principle and performance of the devices contained in this premarket notification is complete and supports a decision that both ELITech Clinical Systems BILIRUBIN TOTAL 4+1 & ELITech Clinical Systems BILIRUBIN DIRECT 4+1 are substantially equivalent to their respective predicate device.

Regulation Number and Section

§ 862.1110 Bilirubin (total or direct) test system.

(a)
Identification. A bilirubin (total or direct) test system is a device intended to measure the levels of bilirubin (total or direct) in plasma or serum. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal distruction of red blood cells, if used in the diagnosis and treatment of liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.(b)
Classification. Class II.