ATAC IRON REAGENT, ATAC TIBC COLUMN KIT AND IRON CALIBRATOR (500 UG/DL) by CLINICAL DATA

The ATAC Iron Reagent Kit, which contains both reagent and calibrator, is intended for use with the ATAC 8000 Random Access Chemistry System as a system for the quantitative determination of total iron in serum. The ATAC TIBC Column Kit, which is marketed with generic labeling and an ATAC 8000 Application Sheet, is intended for use with the ATAC Iron Reagent Kit and other iron reagents for the quantitative determination of total iron binding capacity in serum.

Total iron results are used for the diagnosis and treatment of diciency anemia, hemochromatosis (a disease associated with widespread deposit in the tissues of two iron-containing pigments, and characterized by pigmentation of the skin), and chronic renal disease. Total iron binding capacity measurements are used for the diagnosis and treatment of anemia.

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 Iron Reagent measures total serum iron by stripping it from the transferrin in a low pH reagent buffer, oxidizing it to ferric ions and binding it with Ferrozine. The resulting increase in absorbance at 546 nm is proportional to the iron concentration in the sample. The ATAC TIBC Column Kit is used to pretreat serum specimens prior analysis. The iron in the saturating reagent ensures that all available iron binding sites in the serum specimen are saturated with iron. The filtrate is assayed with an iron reagent after removing the unbound iron form the sample mixture by passing it through an alumina column. The maximum amount of iron bound in the specimen is a measure of its transferrin concentration.

AI/ML Overview

The provided document describes the ATAC Iron Reagent Kit and ATAC TIBC Column Kit for quantitative determination of total iron and total iron binding capacity in serum. The study aims to demonstrate substantial equivalence to legally marketed predicate devices.

Here's an analysis of the acceptance criteria and study particulars:

1. Acceptance Criteria and Reported Device Performance:

The document does not explicitly state pre-defined acceptance criteria, but rather presents performance characteristics of the device and claims substantial equivalence to predicate devices. The "reported device performance" are the results of the effectiveness and precision studies.

ATAC Iron Reagent Kit Performance:

Performance Metric	Reported Device Performance
Linearity	25 to 500 µg/dL
Regression Error	3.1 ug/dL
Precision
Serum 1 (67 ug/dL)	Within Run: 2.2% CVTotal: 4.3% CV
Serum 2 (177 ug/dL)	Within Run: 1.1% CVTotal: 2.5% CV
Serum 3 (282 ug/dL)	Within Run: 1.5% CVTotal: 3.0% CV
Method Comparison	ATAC 8000 = 8.8 ug/dL + 0.969 x Competitive Reagent
Sy.x	3.0 µg/dL
Range Tested	31 - 165 ug/dL
Stability	< 4 ug/dL or 4% total imprecision for 14-day reagent and 7-day calibration stability

ATAC TIBC Column Kit Performance:

Performance Metric	Reported Device Performance
Linearity	125 to 500 µg/dL
Regression Error	6 µg/dL
Precision
Serum 1 (247 ug/dL)	Within Run: 1.8% CVTotal: 2.0% CV
Serum 2 (391 ug/dL)	Within Run: 1.9% CVTotal: 2.8% CV
Method Comparison	ATAC 8000 = 8.2 ug/dL + 0.964 x Competitive Reagent
Range Tested	237 - 470 ug/dL
Sy.x	7.8 µg/dL

2. Sample Size and Data Provenance (Test Set):

ATAC Iron Reagent Kit Method Comparison: n = 58 serum specimens.
ATAC TIBC Column Kit Method Comparison: n = 55 serum specimens.
Data Provenance: Serum specimens were collected from adult patients. No specific country of origin is mentioned. The studies appear to be prospective, collecting and analyzing patient samples.

3. Number of Experts and Qualifications (Ground Truth for Test Set):

Not applicable. This device is an in-vitro diagnostic assay. The "ground truth" for the test set is established by a "commercially available method" (predicate device), not by expert human interpretation.

4. Adjudication Method (Test Set):

Not applicable for this type of in-vitro diagnostic device. The comparison is between the new device and a predicate device, using objective quantitative measurements.

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

No, a MRMC comparative effectiveness study was not done. This type of study is typically relevant for interpretative diagnostic devices where human reading is involved (e.g., radiology images). This device is a quantitative assay.

6. Standalone Performance Study:

Yes, standalone performance studies were conducted. The "effectiveness" studies for both the ATAC Iron Reagent Kit and the ATAC TIBC Column Kit describe the performance of the device itself (linearity, precision) and its correlation with a comparative method. This demonstrates the algorithm-only performance, as it's a quantitative chemical assay.

7. Type of Ground Truth Used:

The ground truth for comparison in the method comparison studies was established by another "commercially available method" (i.e., the predicate device) for both total iron and TIBC. This is a common approach for demonstrating substantial equivalence for in-vitro diagnostic devices.

8. Sample Size for the Training Set:

Not explicitly stated. For "linearity" studies, it mentions "linearity standards that span the usable range" (for Iron Reagent) and "diluted serum pools that span the usable range" (for TIBC). For "precision" studies, it mentions "replicate assay of commercially available control serum" (n=60 for each of three serum levels for iron, and n=60 for each of two serum levels for TIBC). These are more akin to calibration and verification samples rather than a "training set" in the machine learning sense. This device is a chemical reagent kit, not a machine learning algorithm that requires a training set.

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

Not explicitly stated regarding a "training set" in the machine learning context. For the linearity and precision studies, the "ground truth" or reference values are inherent in the linearity standards and commercially available control serums used, whose concentrations would have been established by reference methods or manufacturer's assays.

Summary

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Clinical Data

JUN 1 7 2003

1075 W. Lambert Road Suite D Brea, CA 92821 T (714) 672-3553 F (714) 672-3554

K030528

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 Iron Reagent Kit and ATAC TIBC Column Kit are intended for the quantitative determination of total iron and total iron binding capacity in serum. Total iron results are used for the diagnosis and treatment of diseases such as iron deficiency anemia, hemochromatosis (a disease associated with widespread deposit in the tissues of two iron-containing pigments, hemosiderin and hemofuscin, and characterized by pigmentation of the skin), and chronic renal iron binding capacity measurements are used for the diagnosis and treatment of anemia.

The ATAC Iron Reagent Kit, which contains the Iron Calibrator (500 ug/dL), is substantially equivalent to the Beckman Synchron Systems Iron Reagent, product 467910 and the Beckman Systems Fe/IBCT Calibrator, product 442772. The ATAC TIBC Column Kit and ATAC 8000 TIBC application is substantially equivalent to the Beckman Synchron Systems Total Iron Binding Capacity (IBCT) Column Kit, product no. 465976 (Beckman Coulter, Inc. of Brea, CA).

The effectiveness of ATAC Total Iron Reagent Kit on the ATAC 8000 Random Access Chemistry System is shown in the following studies.

The recovery of iron using the ATAC Total Iron Reagent is linear from 25 to 500 µg/dL, as shown by the recovery of linearity standards that span the usable range. Regression statistics that compare standard values yield a standard error estimate of 3.1 ug/dL.

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	60	67	1.5	2.2%	2.9	4.3%
Serum 2	60	177	1.9	1.1%	4.4	2.5%
Serum 3	60	282	4.3	1.5%	8.5	3.0%

Serum specimens, collected from adult patients, were assayed for iron 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 = 8.8 ug/dL + 0.969 x Competitive Reagent Sy.x = 3.0 µg/dL n = 58 range = 31 - 165 ug/dL

The 14 day onboard reagent stability and 7 day calibration stability claims are documented through the assay of serum controls over the claimed periods. In all cases, estimates of the total imprecision of iron recoveries over the test periods are less than the greater of 4 ug/dL or 4%.

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The effectiveness of ATAC TIBC Column Kit is shown in the following studies with the ATAC Total Iron Reagent Kit on the ATAC 8000 Random Access Chemistry System.

TIBC recoveries using the ATAC TIBC Column Kit are linear from 125 to 500 µg/dL, as shown by the recovery of diluted serum pools that span the usable range. Regression statistics that compare standard recoveries to dilution factors yield an estimate of standard error of regression of 6 µg/dL.

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	60	247	4.5	1.8%	4.9	2.0%
Serum 2	60	391	7.6	1.9%	10.7	2.8%

Serum specimens, collected from adult patients, were assayed for iron using the ATAC 8000 TIBC Application and another commercially available method. Results were compared by Deming regression and the following statistics were obtained.

ATAC 8000 = 8.2 ug/dL + 0.964 x Competitive Reagent range = 237 - 470 ug/dL Sy.x = 7.8 µg/dL n = 55

Wynne Storkey

Wynn Stocking Manager of Regulatory Affairs Elan, Brea California

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 1 7 2003

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

Re: K030528

Trade/Device Name: ATAC Iron Reagent, Iron Calibrator and TIBC Column Kit Regulation Number: 21 CFR 862.1410 Regulation Name: Iron (non-heme) test system Regulatory Class: Class I Product Code: JIY; JMO Dated: June 3, 2003 Received: June 4, 2003

Dear Mr. Stocking:

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.

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 (OS) 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.

Sincercly yours,

Steven Putman

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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510(k) Number (if known):

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Device Name:

ATAC Iron Reagent, Iron Calibrator and TIBC Column Kit

Indications for Use:

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

Jean Cooper

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K030528

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

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Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.1410 Iron (non-heme) test system.

(a)
Identification. An iron (non-heme) test system is a device intended to measure iron (non-heme) in serum and plasma. Iron (non-heme) measurements are used in the diagnosis and treatment of diseases such as iron deficiency anemia, hemochromatosis (a disease associated with widespread deposit in the tissues of two iron-containing pigments, hemosiderin and hemofuscin, and characterized by pigmentation of the skin), and chronic renal disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.