ATAC PAK CREATININE REAGENT AND ATAC CALIBRATOR by ELAN DIAGNOSTICS

The ATAC Creatinine Reagent Kit, the ATAC Calibrator and the ATAC 8000 Random Access Chemistry System are intended for use as a system for the quantitative determination of creatinine in serum, plasma and urine. Creatinine results are used in the diagnosis and treatment of renal dialysis and as a calculation basis for measuring other urine analytes.

Device Description

The ATAC PAK Creatinine Reagent Kit is intended for the quantitative determination of creatinine in serum, plasma and urine. Creatinine results are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis and as a calculation basis for measuring other urine analytes. The ATAC PAK Creatinines creatinine through the reaction of creatinine with alkaline picrate. The initial rate of absorbance increase at 510 nm is proportional to the creatinine concentration of the sample.

AI/ML Overview

The provided text describes the ATAC PAK Creatinine Reagent Kit and its performance characteristics. This is a medical device for in vitro diagnostic use, specifically a reagent kit for measuring creatinine levels. The information presented is typical for a 510(k) submission, demonstrating substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, structured as requested:

1. Table of Acceptance Criteria and Reported Device Performance

For this type of in vitro diagnostic device (reagent kit), regulatory acceptance criteria typically revolve around accuracy, precision, linearity, and stability, often in comparison to a legally marketed predicate device. The document does not explicitly state "acceptance criteria" but rather presents the results of studies designed to demonstrate the device's performance.

Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance
Linearity	Creatinine recovery should be linear across the usable range.	Linear from 0.2 to 25 mg/dL. Regression statistics forced through origin: (ATAC Recoveries) = 0.997 x (Standard Value), Sy.x = 0.19 mg/dL.
Precision	Demonstrated by replicate assay of control serum. (Implicitly, comparable to predicate).	Serum 1 (0.7 mg/dL): Within Run 1SD = 0.05, %CV = 6.9%; Total 1SD = 0.05, %CV = 7.4% Serum 2 (4.1 mg/dL): Within Run 1SD = 0.06, %CV = 1.6%; Total 1SD = 0.10, %CV = 2.5% Serum 3 (7.2 mg/dL): Within Run 1SD = 0.18, %CV = 2.5%; Total 1SD = 0.24, %CV = 3.3% Urine 1 (3.6 mg/dL): Within Run 1SD = 0.10, %CV = 2.8%; Total 1SD = 0.12, %CV = 3.3% Urine 2 (14.8 mg/dL): Within Run 1SD = 0.42, %CV = 2.9%; Total 1SD = 0.60, %CV = 4.0%
Method Comparison	Results should correlate well with a commercially available method for serum/plasma and urine.	Serum/Plasma: ATAC 8000 = 0.07 mg/dL + 0.956 x Competitive Reagent, r = 0.998 Urine: ATAC 8000 = 0.02 mg/dL + 0.960 x Competitive Reagent, r = 0.998
Calibration Stability	Total imprecision of creatinine recoveries over the claimed period should be low.	Total imprecision < 0.2 mg/dL or 5% over 24-hour calibration.
Reagent Stability	Total imprecision of creatinine recoveries over the claimed period should be low.	Total imprecision < 0.2 mg/dL or 5% over 7-day reagent stability.

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

Linearity Study: n = 27 (number of standard recoveries used for regression).
Precision Study: n = 120 for each of the 5 samples (3 serum controls, 2 urine pools). It's explicitly stated as "replicate assay," implying prospective measurement of specific control materials.
Method Comparison (Serum/Plasma): n = 200 mixed serum/plasma specimens from adult patients. The data is prospective, collected by assaying specimens using both the ATAC 8000 and another commercial method. The origin is not explicitly stated, but given the company's US address, it's likely US-based, though not definitively provided.
Method Comparison (Urine): n = 96 diluted urine specimens from adult patients. Prospective data, similar to the serum/plasma comparison, with likely US origin.
Stability Studies: Not explicitly stated, but involved assaying "serum controls and urine pools over the claimed periods."

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

This information is not applicable to this type of device and study. The "ground truth" for creatinine measurement is established by the analytical method itself, often through internal calibrators traceable to a reference standard (though not explicitly stated for this kit, it's standard practice). The comparison is against another commercially available, validated method. There are no human experts "establishing ground truth" in the diagnostic interpretation sense for a biochemical reagent kit.

4. Adjudication Method for the Test Set

This information is not applicable to this type of device and study. Adjudication processes (like 2+1, 3+1) are used in studies where human interpretation of data (e.g., images, clinical findings) is involved and a consensus "ground truth" needs to be established. For a quantitative chemical assay, the comparison is directly between the numerical results of two different analytical methods.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are typically performed for diagnostic imaging devices or other interpretation-based devices where human readers assess cases. This document describes the analytical performance of a reagent kit.

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 ATAC PAK Creatinine Reagent Kit used on the ATAC 8000 Random Access Chemistry System. These are "algorithm only" in the sense that they evaluate the analytical performance of the chemical reaction and the instrument's measurement capabilities, not involving human interpretation or decision-making as a primary performance metric beyond standard laboratory practices.

7. The Type of Ground Truth Used

Linearity: The "ground truth" was established by standard values (known concentrations of creatinine standards).
Precision: The "ground truth" was the mean concentration determined for commercially available control serum and urine pools.
Method Comparison: The "ground truth" for comparison was the measurements obtained from an established, commercially available reference method (the "Competitive Reagent"). This is a form of comparative ground truth, where the new method is validated against an accepted one.

8. The Sample Size for the Training Set

This information is not explicitly provided in the document. For chemical reagent kits, there isn't typically a "training set" in the machine learning sense. Instead, development and optimization would involve numerous studies (assay development, formulation testing, preliminary performance runs) leading to the final reagent formulation and instrument protocol, but these aren't usually presented as a distinct "training set" in regulatory submissions. The studies presented are validation studies.

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

As there isn't a "training set" as understood in machine learning contexts for this type of device, this question is not applicable. The "ground truth" for developing a chemical assay is built upon fundamental chemical principles, analytical accuracy provided by known standards, and optimization processes to ensure proper reaction kinetics and measurement properties.

Summary

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FEB 1 4 2003

elan K023407

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 effectiveness of ATAC PAK Creatinine Reagent Kit on the ATAC 8000 Random Access Chemistry System is shown by the following studies.

The recovery of creatinine using the ATAC PAK Creatinine Reagent is linear from 0.2 to 25 mg/dL, as shown by the recovery of linearity standards that span the usable range. Regression statistics, which are forced through the origin, compare standard recoveries to standard values. These statistics are shown below.

(ATAC Recoveries) = 0.997 x (Standard Value), Sy.x = 0.19 mg/dL, n = 27

Precision is demonstrated by the replicate assay of commercially available control serum. Precision statistics, calculated analogous to the methods described in NCCLS Guideline EP3-T, are shown below.

Precision of Creatinine Recoveries in mg/dL

Sample	n	mean	Within Run		Total
			1SD	%CV	1SD	%CV
Serum 1	120	0.7	0.05	6.9%	0.05	7.4%
Serum 2	120	4.1	0.06	1.6%	0.10	2.5%
Serum 3	120	7.2	0.18	2.5%	0.24	3.3%
Urine 1	120	3.6	0.10	2.8%	0.12	3.3%
Urine 2	120	14.8	0.42	2.9%	0.60	4.0%

Mixed serum, plasma and diluted urine specimens, collected from adult patients, were assayed for creatinine using the ATAC 8000 Random Access Chemistry System and another commercially available method. Results were compared by least squares linear regression and the following statistics were obtained.

Serum/Plasma Comparison ATAC 8000 = 0.07 mg/dL + 0.956 x Competitive Reagent r = 0.998 n = 200 range = 0.4 - 8.7 mg/dL Urine Comparison ATAC 8000 = 0.02 mg/dL + 0.960 x Competitive Reagent

r = 0.998 n = 96 range = 0.6 - 24.7 mg/dL A specimen containing 1 mg/dL creatinine will produce an absorbance change of approximately 0.017 A on the ATAC 8000

Random Access Chemistry System.

The 24 hour calibration stability claim and the 7 day and reagent stability claims are documented through the assay of serum controls and urine pools over the claimed periods. In all cases, the total imprecision of creatinine recoveries over the test periods are less than 0.2 mg/dL or 5%.

Wynn Stocking
Wynn Stocking

Wynn Stocking Manager of Regulatory Affairs Elan Diagnostics

510(k) Notification, ATAC PAK Creatinine Reagent Kit, 9 October, 2002, p 66

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Image /page/1/Picture/1 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features a stylized eagle with three lines representing its body and wings. The eagle's head is facing left. Encircling the eagle is the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" in a circular arrangement.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB 1 4 2003

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

Re: K023407

Trade/Device Name: ATAC PAK Creatinine Reagent Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: Class II Product Code: CGX: JIS Dated: January 21, 2003 Received: January 21, 2003

Dear Mr. Stocking:

We have reviewed vour 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.

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 vour 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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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 Sutman

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

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K023407

510(k) Number (if known):

Device Name:

ATAC PAK Creatinine 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.

Jian Cooges

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K023407

(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)

Regulation Number and Section

§ 862.1225 Creatinine test system.

(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.