ATAC TOTAL BILIRUBIN REAGENT by ELAN DIAGNOSTICS

The ATAC Total Bilirubin Reagent Kit is intended for use with the ATAC Calibrator and the ATAC 8000 Random Access Chemistry System as a system for the quantitative determination of total bilirubin in serum and plasma. Total bilirubin results are used for the diagnosis and treatment of liver, hematological, and metabolic disorders, including hepatitis and gall bladder block.

This reagent is intended to be used by trained personnel in a professional setting and is not intended for home use.

Device Description

The ATAC Total Bilirubin Reagent determines total bilirubin through its reaction with diazotized sulfanilic acid in the presence of dimethylsulfoxide to form a red-purplex. The resulting increase in absorbance at 546 nm is proportional to the total bilirubin concentration in the sample.

AI/ML Overview

The "ATAC Total Bilirubin Reagent Kit" is a device intended for the quantitative determination of total bilirubin in serum and plasma. The following information outlines its acceptance criteria and the studies performed to demonstrate its effectiveness.

1. Acceptance Criteria and Reported Device Performance

Feature/Study	Acceptance Criteria (Implied)	Reported Device Performance
Linearity/Recovery	Linear recovery across the usable range (0.1 to 25 mg/dL) with good correlation to standard values.	Recovery of linearity standards: (ATAC Recoveries) = 0.3 mg/dL + 0.87 x (Standard Factors), Sy.x = 0.28 mg/dL, r = 1.000, n = 18. This demonstrates linearity from 0.1 to 25 mg/dL.
Precision	Acceptable within-run and total precision for control serum.	Precision statistics (NCCLS Guideline EP3-T analogous method): Serum 1 (mean 0.6 mg/dL): Within Run 1SD = 0.04 mg/dL (6.5%CV), Total 1SD = 0.10 mg/dL (16.3%CV)Serum 2 (mean 3.4 mg/dL): Within Run 1SD = 0.06 mg/dL (1.6%CV), Total 1SD = 0.11 mg/dL (3.1%CV)Serum 3 (mean 6.3 mg/dL): Within Run 1SD = 0.12 mg/dL (1.9%CV), Total 1SD = 0.17 mg/dL (2.7%CV)
Method Comparison	Good correlation and agreement with a commercially available comparative reagent.	Deming regression comparison with Competitive Reagent: ATAC 8000 = -0.05 mg/dL + 1.003 x Competitive Reagent, sy.x = 0.20 mg/dL, range = 0.2 - 25.7 mg/dL, n = 107. This shows excellent agreement.
Detection Limit	Quantifiable detection limit.	Detection limit: 0.1 mg/dL. Documented through repetitive assay of a diluted serum pool; observed standard deviation of a 30-replicate within-run precision study was 0.49 mg/dL. The detection limit is reported as the round-off error of the assay.
Onboard Reagent Stability	Stable for 5 days.	5 day onboard reagent stability: Estimates of bilirubin recoveries over the test period are less than 0.15 mg/dL.
Calibration Stability	Stable for 24 hours.	24 hour calibration stability: Observed shifts in recoveries over the 24-hour period average less than 0.1 mg/dL.
Reconstituted Stability	Stable for 14 days.	14 day reconstituted stability: Observed shifts in recoveries over the 14-day period are less than 0.1 mg/dL or 2.5%.

2. Sample Sizes and Data Provenance

Test Set for Linearity: n = 18 (for the linear regression of standard factors). The data provenance is not explicitly stated as country of origin, but it is for "linearity standards," implying laboratory-prepared standards.
Test Set for Precision: n = 36 for each of the three serum samples tested (total of 108 replicates). The data provenance is "commercially available control serum."
Test Set for Method Comparison: n = 107. The data provenance is "Mixed serum and plasma specimens, collected from adult patients." The country of origin is not specified. It is likely prospective for the purpose of the study.
Test Set for Detection Limit: 30 replicates of a diluted serum pool.

3. Number of Experts and Qualifications for Ground Truth

This document describes the performance characteristics of an in-vitro diagnostic reagent kit (ATAC Total Bilirubin Reagent Kit) and does not involve image analysis or clinical interpretation by human experts to establish ground truth in the typical sense for a medical device that outputs diagnoses or classifications.
The ground truth for the performance studies (linearity, precision, method comparison, detection limit, stability) is based on:
- Known concentrations for linearity standards.
- Assigned values for commercially available control serum.
- Results from a "commercially available method" (predicate device or similar) for method comparison.
Therefore, the concept of "number of experts" and their "qualifications" for establishing ground truth as it applies to image interpretation or clinical diagnosis does not directly apply here. The "experts" are the analytical chemists and laboratory professionals who establish the values of standards and controls, and run the comparative assays.

4. Adjudication Method

Adjudication methods like 2+1 or 3+1 are typically used in studies where there is subjective human interpretation involved (e.g., radiologists reviewing images).
For the performance studies of this in-vitro diagnostic reagent, the "ground truth" or reference values are established through quantitative chemical analysis and metrological traceability. Therefore, an adjudication method in the human consensus sense is not applicable. Discrepancies would be resolved through re-testing, calibration verification, or investigation of analytical errors, not expert consensus.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

An MRMC study is not mentioned and is not applicable to the evaluation of an in-vitro diagnostic reagent kit like the ATAC Total Bilirubin Reagent Kit. These studies are relevant for devices that assist human readers in tasks like image interpretation or clinical decision-making.

6. Standalone Performance

Yes, this document primarily reports on the standalone performance of the ATAC Total Bilirubin Reagent Kit when used with the ATAC 8000 Random Access Chemistry System. The results presented (linearity, precision, detection limit, stability) are measures of the algorithm's (reagent kit's) performance independent of human-in-the-loop diagnostic interpretation.
The "method comparison" study essentially compares the standalone performance of the ATAC kit to another standalone, commercially available method.

7. Type of Ground Truth Used

The types of ground truth used are:

Reference Standards/Known Concentrations: For linearity and stability studies, the performance is evaluated against solutions with established concentrations of total bilirubin.
Assigned Values of Control Materials: For precision studies, the device's repeatability and reproducibility are measured against commercially available control sera with pre-determined mean values.
Results from a Legally Marketed Predicate/Comparative Device: For method comparison, the results from the ATAC Total Bilirubin Reagent are compared against those obtained from the "Beckman Synchron Total Bilirubin Reagent, product 442745" or another "commercially available method," which serves as the reference ground truth for agreement.

8. Sample Size for the Training Set

This document describes validation studies of a chemical reagent kit, not a machine learning or AI model. Therefore, the concept of a "training set" in the context of AI is not applicable. The development of the reagent itself would involve formulation, optimization, and initial testing, but these are not referred to as "training sets."

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

As the concept of a "training set" for an AI model is not applicable here, the question of how its ground truth was established is also not relevant. The studies focus on verifying the analytical performance of the finished reagent kit against established laboratory and regulatory standards.

Summary

{0}------------------------------------------------

SEP 2 6 2003

Image /page/0/Picture/1 description: The image shows the word "élan" in a stylized font. The "é" has a unique design, with a diagonal line extending from the top left of the letter. The rest of the word is in a flowing, cursive-like font. The image is in black and white.

1075 W. Lambert Road Building D Brea, California 92821 T (714) 672 3553 F (714) 672 3554

SUMMARY OF 510(K) SAFETY AND EFFECTIVENESS INFORMATION

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.

The ATAC Total Bilirubin Reagent Kit is intended for the quantitative determination of total bilirubin in serum and plasma. Total bilirubin results are used for the diagnosis and treatment of liver, hematological, and metabolic disorders, including hepatitis and gall bladder block. The ATAC Total Bilirubin Reagent determines total bilirubin through its reaction with diazotized sulfanilic acid in the presence of dimethylsulfoxide to form a red-purplex. The resulting increase in absorbance at 546 nm is proportional to the total bilirubin concentration in the sample.

The ATAC Total Bilirubin Reagent Kit is substantially equivalent to the Beckman Synchron Total Bilirubin Reagent, product 442745, which is currently marketed by Beckman Coulter, Inc of Brea, CA. The effectiveness of ATAC Total Bilirubin Reagent Kit on the ATAC 8000 Random Access Chemistry System is shown by the following studies.

The recovery of total bilirubin using the ATAC Total Bilirubin Reagent is linear from 0.1 to 25 mg/dL, as shown by the recovery of linearity standards that span the usable range. Regression statistics compare standard values. These statistics are shown below.

(ATAC Recoveries) = 0.3 mg/dL + 0.87 x (Standard Factors), Sy.x = 0.28 mg/dL, r = 1.000, n = 18

Precision is demonstrated by the replicate assay of commercially available control serum. Precision statistics, calculated 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	36	0.6	0.04	6.5%	0.10	16.3%
Serum 2	36	3.4	0.06	1.6%	0.11	3.1%
Serum 3	36	6.3	0.12	1.9%	0.17	2.7%

Mixed serum and plasma specimens, collected from adult patients, were assayed for total bilirubin using the ATAC 8000 Random Access Chemistry System and another commercially available method. Results were compared by Deming regression and the following statistics were obtained.

ATAC 8000 = - 0.05 mg/dL + 1.003 x Competitive Reagent sy.x = 0.20 mg/dL range = 0.2 - 25.7 mg/dL n = 107

The detection limit of 0.1 mg/dL is documented through the repetitive assay of a diluted serum pool. The observed standard deviation of a 30 replicate within run precision study was 0.49 mg/dL. Consequently, the detection limit is reported as the round-off error of the assay.

The 5 day onboard reagent stability and 24 hour calibration stability claims are documented through the assay of serum controls over the claimed periods. In all cases, estimates of the bilirubin recoveries over the test periods are less than 0.15 mg/dL. In addition, the observed shifts in recoveries over the 24 hour calibration stability period average less than 0.1 mg/dL.

The 14 day reconstituted stability claim is documented through the assay of serum pools and linearity standards. Observed shifts in recoveries over the 14 day period are less than 0.1 mg/dL or 2.5%.

Wyman Stodden

Wynn/Stocking Manager of Regulatory Affair Elan, Brea California

510(k) Notification, ATAC Total Bilirubin Reagent Kit, 31 December, 2002, p 47

{1}------------------------------------------------

Image /page/1/Picture/0 description: The image shows the logo for the Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized eagle or bird in flight. The symbol is composed of three curved lines that converge at the top and then separate into two wavy lines at the bottom.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

SEP 2 6 2003

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Wynn Stocking Manager, Regulatory Affairs Elan Diagnostics 1075 W. Lambert Road - Suite D Brea, CA 92821

Re: K030014

Trade/Device Name: ATAC Total Bilirubin Reagent Regulation Number: 21 CFR 862.1110 Regulation Name: Bilirubin (total or direct) test system Regulatory Class: Class II Product Code: CIG Dated: June 30, 2003 Received: July 1, 2003

Dear Mr. Thiel:

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. Iisting 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).

{2}------------------------------------------------

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,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{3}------------------------------------------------

K030014

510(k) Number (if known):

Device Name:

ATAC Total Bilirubin Reagent

Indications for Use:

This reagent is intended to be used by trained personnel in a professional setting and is not intended for home use.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Jean Cooper

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K63084

Over-The-Counter Use

Prescription Use √
(Per 21 CFR 801.109)

(Optional Format 1-2-96)

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.