The Vitalab Direct Bilirubin Reagent is intended for use with the Vitalab Selectra Analyzer for the quantitative determination of conjugated (direct) bilirubin in serum and plasma. Direct bilirubin results may be used for the diagnosis and treatment of liver, hematological, and metabolic disorders, including hepatitis and gall bladder block.

The Vitalab Total Bilirubin Reagent is intended for use with the Vitalab Selectra Analyzer for the quantitative determination of total bilirubin in serum and plasma. Total bilirubin results may be used for the diagnosis and treatment af liver, hemolytic hematological, and metabolic disorders, including hepatitis and gall bladder block.

The Vitalab Bilirubin Calibrator is intended to calibrate the Vitalab Selectra Analyzer for the quantitative determination of total and direct bilirubin in serum and plasma.

Device Description

The Vitalab Direct Bilirubin Reagent is a two-part reagent for use with the Vitalab Selectra Analyzer. This reagent determines conjugated bilirubin through a reaction with diazotized 2,4-dichloroanaline to produce a colored chromogen in acidic solution.

The Vitalab Total Bilirubin Reagent is a two-part reagent for use with the Vitalab Selectra Analyzer. This reagent determines total bilirubin through a reaction with diazotized 2,4-dichloroanaline in the presence of detergents to produce a colored chromogen in acidic solution.

The Vitalab Bilirubin Calibrator is a liquid stable bilirubin calibrator prepared from purified components in a human serum albumin matrix. Bilirubin set points are traceable to NIST reference materials.

AI/ML Overview

Below is a summary of the acceptance criteria and performance study details for the Vitalab Direct Bilirubin Reagent, Vitalab Total Bilirubin Reagent, and Vitalab Bilirubin Calibrator, based on the provided text.

1. Table of Acceptance Criteria and Reported Device Performance:

Performance Metric	Vitalab Direct Bilirubin Reagent Acceptance Criteria / Predicate Performance (Implicit)	Vitalab Direct Bilirubin Reagent Reported Performance	Vitalab Total Bilirubin Reagent Acceptance Criteria / Predicate Performance (Implicit)	Vitalab Total Bilirubin Reagent Reported Performance
Linearity/Usable Range	Sufficiently linear to meet clinical needs (implicit, typically based on predicate).	Linear to at least 10.0 mg/dL.	Sufficiently linear to meet clinical needs (implicit, typically based on predicate).	Linear to at least 25.0 mg/dL.
Detection Limit	Low enough for clinical utility (implicit).	0.0 mg/dL.	Low enough for clinical utility (implicit).	0.0 mg/dL.
Precision	Acceptable within-run and total precision for clinical use (implicit, often referenced to NCCLS guidelines).	Serum 1 (0.3 mg/dL): Within Run 1SD = 0.03, %CV = 11.3%; Total 1SD = 0.03, %CV = 11.4%.Serum 2 (1.7 mg/dL): Within Run 1SD = 0.02, %CV = 1.3%; Total 1SD = 0.05, %CV = 2.8%.Serum 3 (4.0 mg/dL): Within Run 1SD = 0.02, %CV = 0.5%; Total 1SD = 0.10, %CV = 2.6%.	Acceptable within-run and total precision for clinical use (implicit, often referenced to NCCLS guidelines).	Serum 1 (0.4 mg/dL): Within Run 1SD = 0.02, %CV = 5.8%; Total 1SD = 0.03, %CV = 6.7%.Serum 2 (1.4 mg/dL): Within Run 1SD = 0.04, %CV = 3.1%; Total 1SD = 0.07, %CV = 4.8%.Serum 3 (5.8 mg/dL): Within Run 1SD = 0.07, %CV = 1.1%; Total 1SD = 0.15, %CV = 2.5%.
Correlation/Method Comparison	Substantially equivalent to predicate device (implicit standard for 510(k)).	Selectra = 0.05 mg/dL + 0.832 x Competitive Reagent (r=0.9995, syx = 0.12 mg/dL if we assume the r and syx from linearity applies to correlation, which is probably incorrect, but no other value given for correlation specific r, syx). Range = 0.1 - 11.6 mg/dL. syx = 0.14 mg/dL (from calibration section, which seems to refer back to this data).	Substantially equivalent to predicate device (implicit standard for 510(k)).	Selectra = -0.4 mg/dL + 1.037 x Competitive Reagent. Range = 0.1 - 25.9 mg/dL. syx = 0.20 mg/dL.
Stability (Onboard Reagent & Calibration)	Meet claimed stability (implicit).	14 day onboard reagent stability and 7 day calibration stability met (total imprecision < 0.2 mg/dL).	Meet claimed stability (implicit).	7 day onboard reagent stability and 7 day calibration stability met (total imprecision < 0.2 mg/dL).
Calibrator Accuracy	Assigned set points documented through method comparison (implicit, comparable to predicate).	Direct Bilirubin: Selectra = 0.05 mg/dL + 0.832 x Competitive Reagent, syx = 0.14 mg/dL, n = 90, range= 0.1-11.6 mg/dL. Total Bilirubin: Selectra = - 0.4 mg/dL + 1.037 x Competitive Reagent, syx = 0.20 mg/dL, n = 103, range = 0.1 - 25.9 mg/dL.	N/A	N/A
Calibrator Open Stability	Meet claimed open stability (implicit).	Open stability confirmed for 3 days at 2℃ to 8℃ (changes < 0.03 mg/dL).	N/A	N/A

Note on Acceptance Criteria: The document primarily describes the study results ("reported device performance") rather than explicitly stating pre-defined "acceptance criteria" with numerical thresholds for each metric. The implicit acceptance criterion for a 510(k) submission is that the device is "substantially equivalent" to a legally marketed predicate device, meaning its performance must be comparable and demonstrate safety and effectiveness for its intended use. Therefore, the reported performance is compared against what would be considered acceptable for such a device in the market.

2. Sample Sizes Used for the Test Set and Data Provenance:

Vitalab Direct Bilirubin Reagent (Correlation):
- Sample Size: 49 serum and 41 plasma specimens (total n = 90).
- Data Provenance: Adult patients, specific country of origin not stated, but generally assumed to be within North America or where Clinical Data, Inc. operates. The data is retrospective, as specimens are “assayed,” implying they were collected prior to the study.
Vitalab Total Bilirubin Reagent (Correlation):
- Sample Size: 59 serum and 44 heparinized plasma specimens (total n = 103).
- Data Provenance: Adult patients, specific country of origin not stated. The data is retrospective.
Vitalab Bilirubin Calibrator (Accuracy):
- Sample Size: At least 40 serum and plasma specimens (for both total and direct bilirubin).
- Data Provenance: Adult patient specimens. The data is retrospective.

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

Not applicable. This device is an in vitro diagnostic (IVD) reagent for quantitative biochemical analysis, not an imaging or AI diagnostic device requiring expert interpretation for ground truth. The "ground truth" for method comparison studies is established by the results from a legally marketed, predicate/competitive reagent method.

4. Adjudication Method for the Test Set:

Not applicable. Ground truth for these types of studies is not established by expert consensus or adjudication but by comparison to an established, legally marketed method.

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

No. These are IVD reagents; MRMC studies are typically for imaging/AI-assisted diagnostic devices involving human reader interpretation.

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 reagents on the Vitalab Selectra Analyzer. There is no human-in-the-loop component for the interpretation of results beyond standard laboratory technician handling and quality control.

7. The Type of Ground Truth Used:

The ground truth was established by comparison to results obtained using commercially available (predicate or competitive) methods for direct and total bilirubin. This is the standard for demonstrating substantial equivalence for IVD reagents. For the calibrator, the bilirubin set points are traceable to NIST reference materials.

8. The Sample Size for the Training Set:

Not applicable. This is not an AI/machine learning device that requires a "training set." The performance evaluation focuses on the analytical performance of the chemical reagents.

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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MAR 1 8 2004

Summary of 510(k) Safety and Effectiveness Information Vitalab Direct Bilirubin Reagent

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.

Submitted by:

	Clinical Data, Inc.1075 West Lambert Road, Building DBrea, California 92861
Contact Person:	Wynn Stocking
	Regulatory Affairs Manager
Date Submitted:	January 20, 2003

Device Names:

Proprietary name:	Vitalab Direct Bilirubin Reagent
Common name:	Conjugated (direct) bilirubin reagent
Classification Name:	Diazo colorimetry, bilirubin
Proprietary name:	Vitalab Total Bilirubin Reagent

Proprietary name:	Vitalab Total Bilirubin Reagent
Common name:	Total bilirubin reagent
Classification Name:	Diazo colorimetry, bilirubin
Proprietary name:	Vitalab Bilirubin Calibrator

Classification Name: Calibrator, multi-analyte mixture

Bilirubin calibrator

Device Descriptions:

Common name:

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Intended Uses:

The Vitalab Bilirubin Calibrator is intended to calibrate the Vitalab Selectra Analyzer for the quantitative determination of total and direct bilirubin in serum and plasma.

Predicate Devices:

The Vitalab Direct Bilirubin Reagent Kit is substantially equivalent to the Roche Direct Bilirubin Reagent, product no. 0737499, which is currently marketed by Roche Diagnostics Corp. of Indianapolis, IN.

The Vitalab Total Bilirubin Reagent Kit is substantially equivalent to the Beckman Total Bilirubin Reagent, product no 442745, which is currently marketed by Beckman Coulter, Inc. of Brea, CA.

The Vitalab Bilirubin Calibrator is substantially equivalent to the Beckman Bilirubin Calibrator, product no. 465915, which is currently marketed by Beckman Coulter, Inc. of Brea, CA.

Summary of Performance Data for the Vitalab Direct Bilirubin Reagent:

The Vitalab Direct Bilirubin Reagent is linear to at least 10.0 mg/dL, as shown by the recovery of Usable Range: linearity related, human serum reference pools that span the linear range of the assay. Least squares regression statistics compare recoveries to dilution factors.
(Vitalab Recoveries) = 0.2 mg/dL + 0.834 x (Reference), r=0.9995, syx = 0.12 mg/dL, n = 32
Detection Limit: The detection limit is shown through the repetitive assay of normal saline. The observed mean and standard deviation of a 30 replicate within run precision study are both 0 mg/dL. The detection limit, calculated as the mean recovery plus two standard deviations is 0.0 mg/dL.
Precision is demonstrated by the replicate assay of control serum. Precision statistics, calculated Precision: analogous to the method described in NCCLS Guideline EP3-T, are shown below.

Sample	n	mean	Within Run		Total
			1SD	%CV	1SD	%CV
Serum 1	66	0.3	0.03	11.3%	0.03	11.4%
Serum 2	66	1.7	0.02	1.3%	0.05	2.8%
Serum 3	66	4.0	0.02	0.5%	0.10	2.6%

Forty nine serum and 41 plasma specimens from adult patients were assayed for direct bilirubin using Correlation: the Vitalab Selectra E Analyzer and another commercially available method. Results were compared by Deming regression and the following statistics were obtained.

Selectra = 0.05 mp/dL + 0.832 x Competitive Reagent range = 0.1 - 11.6 mg/dL s. = 0.14 mg/dL n = 90

The 14 day onboard reagent stability and 7 day calibration stability claims are documented through the Stability: assay of serum convols over the claimed periods. In all cases, statistical estimates of total imprecision are less than 0.2 ms/dL.

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Summary of Performance Data for the Vitalab Total Bilirubin Reagent:

The Vitalab Total Bilirubin Reagent is linear to at least 25.0 mg/dL, as shown by the recovery of Usable Range: linearity related, human serum reference pools that span the linear range of the assay. Least squares regression statistics compare recoveries to dilution factors.
(Vitalab Recoveries) = 0.2 mg/dL + 0.888 x (Reference), r = 0.9999, syx = 0.16 mg/dL, n = 36
Detection Limit: The detection limit is shown through the repetitive assay of normal saline. The observed mean and standard deviation of a 30 replicate within run precision study are both 0 mg/dL. The detection limit, calculated as the mean recovery plus two standard deviations is 0.0 mg/dL.
Precision is demonstrated by the replicate assay of control serum. Precision statistics, calculated Precision: analogous to the method described in NCCLS Guideline EP3-T, are shown below.

Sample	n	mean	Within Run		Total
			1SD	%CV	1SD	%CV
Serum 1	54	0.4	0.02	5.8%	0.03	6.7%
Serum 2	54	1.4	0.04	3.1%	0.07	4.8%
Serum 3	54	5.8	0.07	1.1%	0.15	2.5%

Fifty nine serum and 44 heparinized plasma specimens from adult patients were assayed for total Correlation: bilirubin using the Vitalab Selectra E Analyzer and another commercially available method. Results were compared by Deming regression and the following statistics were obtained.

Selectra = - 0.4 mg/dL + 1.037 x Competitive Reagent range = 0.1 - 25.9 mg/dL s. . = 0.20 mg/dL n = 103

The 7 day onboard reagent stability and 7 day calibration stability claims are documented through the Stability: assay of serum controls over the claimed periods. In all cases, statistical estimates of total imprecision are less than 0.2 mg/dL.
Summary of Performance Data for the Vitalab Bilirubin Calibrator:

The accuracy of the assigned set points is documented through method comparison studies. At least Accuracy: 40 serum and plasma specimens from adult patient were assayed for total and direct bilirubin over at least four analytical runs using commercially available methods and Vitalab reagents calibrated with the Vitalab Bilirubin Calibrator.

Deming regression statistics for both total and direct bilirubin are summarized below.

Direct Bilirubin Selectra = 0.05 mg/dL + 0.832 x Competitive Reagent range = 0.1 - 11.6 mg/dL n = 90 s . = 0.14 mg/dL Total Bilirubin Selectra = - 0.4 mg/dL + 1.037 x Competitive Reagent syx=0.20 mg/dL n = 103 range = 0.1 - 25.9 mg/dL

The open stability claim is confirmed by assaying the total and direct bilirubin levels in vials that have Open Stability: been open for increasing lengths of time. All observed changes in both the total and conjugated bilirubin levels over 3 days at 2℃ to 8℃ were less than 0.03 mg/dL.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is an emblem featuring a stylized eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 1 8 2004

Clinical Data, Inc. c/o Mr. Ned E. Devine Entela, Inc 3033 Madison Avenue, SE Grand Rapids, MI 49548

K040631 Re:

Trade/Device Name: Vitalab Direct Bilirubin Reagent Vitalab Total Bilirubin Reagent Vitalab Bilirubin Calibator Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: Class II

Product Code: CIG; JIT Dated: March 10, 2004

Received: March 10, 2004

Dear Mr. Devine:

We have reviewed your Section 510(k) premarket notification of intent to market the device refercnced 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Jean M. Cooper, MS, DVM.
MS, DVM.

Yean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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K040631

510(k) Number (if known):

Device Name:

Vitalab Direct Bilirubin Reagent

Indications for Use:

The Vitalab Direct Bilirdbin Reagent is intended for use with the Vitalia assults may be wed for the diamons The Vitalab Direct Bilirubin Reagent is Intil in 1 Min 1 Miro Colicioline in results may be used for the diagnosis
determination of conjugated (direct) bilinuin in serum and determination of conjugated (direct) officially in scrum and plastill. Directors, including hepatitis and gall bladder block.

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use $\underline{\checkmark}$
(Per 21 CFR 801.109)

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

(Optional Form

Optional Format P-96)

Carol C. Benson

Division Sign-Off

Office of In Vitro Diagnostic Device
Evaluation and Safety

January 20, 2004
Page 87 of 95

Clinical Data, Brea, California

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510(k) Number (if known):

K040631

Device Name:

Vitalab Total Bilirubin Reagent

Indications for Use:

The Vitalab Total Bilirubin Reagent is intended for use with the Vitalab Selectra Analyzer as a system for the quantitive The Villab Total Billirubin Reagen is millibe vilance Use and be sub coll on the plager es and geatment of uccentination of total officablic disorders, including hepatitis and gall bladder block.

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use

C(Optional Format 1-2-96)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Sat

510(k) K04 0631

January 20, 2004 Page 88 of 95

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K040631

510(k) Number (if known):

Device Name:

Vitalab Bilirubin Calibrator

Indications for Use:

The Vitalab Bilirubin Calibrator is intended for use with the Vitalab Selectra Analyzer to establish points of reference that The Vitalab Billruom Callorator is intended for ass whit no "(time specimens.

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use

Optional Format 1-2-96)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K040631

510(k) Notification, Vitalab Billirubin Reagents and Calibrator Clinical Data, Brea, California

20, 2004

January 20, 2004 Page 89 of 95

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.