The Nichols Advantage® Aldosterone assay is intended for use with the Nichols Advantage® Specialty System to quantitatively measure aldosterone in human serum and EDTA plasma. Aldosterone measurements are used in the diagnosis and treatment of primary aldosteronism (a disorder caused by excessive secretion of aldosterone by the adrenal gland), hypertension caused by primary aldosteronism, selective hypoaldosteronism, edematous states, and other conditions of electrolyte imbalance.

Device Description

The Nichols Advantage® Aldosterone assay contains sufficient reagents for 100 tests. The assay is a competitive binding assay for aldosterone in human serum or plasma.

AI/ML Overview

The Nichols Advantage® Aldosterone assay is a competitive binding immunoassay intended for quantitative measurement of aldosterone in human serum and EDTA plasma using the Nichols Advantage Specialty System. Aldosterone measurements are used in the diagnosis and treatment of conditions such as primary aldosteronism, hypertension caused by primary aldosteronism, selective hypoaldosteronism, edematous states, and other electrolyte imbalances.

The device's performance was compared to a predicate device, the DPC Coat-A-Count Aldosterone RIA (K831178), to establish substantial equivalence.

Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a quantitative sense for all features. However, it provides comparative performance characteristics between the Nichols Advantage Aldosterone and the predicate device. The implied acceptance is that the Nichols Aldosterone performs comparably to the predicate.

Feature	Predicate Device (DPC Aldosterone)	Nichols Advantage Aldosterone
Comparison Study (Quantitative)
Range (Method X - DPC)	2.7 to 125 ng/dL	Not directly stated (Y=1.04X+0.1)
Range (Method Y - Nichols)	Not directly stated	2.7 to 120 ng/dL
Regression (Passing Bablok)	Y = 1.04X + 0.1	N/A
(95% CI Slope)	(0.98 to 1.10)	N/A
(95% CI Intercept)	(-1.0 to +1.1)	N/A
Regression (Deming)	Y = 1.09X - 0.6	N/A
(95% CI Slope)	(1.03 to 1.15)	N/A
(95% CI Intercept)	(-3.2 to +2.1)	N/A
Pearson's Correlation (r)	N/A	0.96
Performance Characteristics
Within-Run Precision (%CV)	2.3-5.4%	2.9-14.0%
Total Precision (%CV)	3.8-15.7%	4.9-18.6%
Recovery	86-111%	88-110%
Linearity	100-119%	91-116%
Analytical Sensitivity	1.1 ng/dL	1.2 ng/dL

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

Sample Size: One hundred three (103) remnant serum samples.
Data Provenance: The clinical diagnosis for these samples was unknown. The document does not specify the country of origin, but given the manufacturer's location (San Clemente, CA) and the FDA submission, it's highly likely to be U.S.-based. The samples were "remnant," suggesting a retrospective collection.

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

Not applicable. This device is an in vitro diagnostic immunoassay measuring an analyte concentration. The "ground truth" for the test set was the measurement result obtained by the predicate device (DPC Coat-A-Count Aldosterone RIA), not expert consensus on an image or clinical observation.

4. Adjudication Method for the Test Set:

Not applicable. The study involved a direct comparison of quantitative measurements from two immunoassay methods on the same samples. There was no need for expert adjudication.

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

No, an MRMC comparative effectiveness study was not conducted as this is an in vitro diagnostic device for quantitative measurement, not an imaging device requiring human reader interpretation.

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

Yes, the core of the submission is a standalone performance evaluation of the Nichols Advantage Aldosterone assay, comparing its quantitative results to a legally marketed predicate device without human-in-the-loop interaction for result interpretation beyond running the assay.

7. The Type of Ground Truth Used:

The ground truth for comparison was the quantitative measurement obtained from the predicate device (DPC Coat-A-Count Aldosterone RIA) on the same serum samples. This is a common approach for demonstrating substantial equivalence for new IVD devices by comparing them to an established, legally marketed assay.

8. The Sample Size for the Training Set:

Not applicable. This document describes the validation of an immunoassay kit, not a machine learning algorithm that requires a "training set" in the conventional sense. The development of the assay would have involved internal optimization and validation, but this specific submission focuses on the performance comparison to the predicate.

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

Not applicable, as there is no mention of a "training set" in the context of an AI/ML algorithm.

Summary

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

Ko32188

JUL 3 1 2003

510(k) Notification Nichols Advantage Aldosterone Date: 07/11/03 (revised)

Concluding 510(k) Summary 12.0

This summary of safety and effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

1. Name of Manufacturer, Contact Person and Date Summary Prepared:

Nichols Institute Diagnostics 1311 Calle Batido San Clemente, CA 92673 Phone: 949-940-7260 FAX: 949-940-7313 Contact Person: Jimmy Wong, Manager of Clinical and Technical Affairs Date Prepared: July 11, 2003

FOOD AND DRUG BRANCH

2. Device Name:

Trade/Proprietary Name:	Nichols Advantage® Aldosterone
Common Name:	Aldosterone immunoassay
Classification Name:	Radioimmunoassay, Aldosterone

Classification: " Class II 3.
Requlation Number: 862.1045 Product Code: CJM, Clinical Chemistry
Diagnostic Product Corporation Coat-A-Count Aldosterone Predicate Device: 4.

5. Device Description:

The Nichols Advantage® Aldosterone assay contains sufficient reagents for 100 tests. The assay is a competitive binding assay for aldosterone in human serum or plasma.

Intended Use: 6.

The Nichols Advantage® Aldosterone assay is intended for use with the Nichols Advantage Specialty System to quantitatively measure aldosterone in human serum and EDTA plasma. Aldosterone measurements are used in the diagnosis and treatment of primary aldosteronism (a disorder caused by excessive secretion of aldosterone by the gland), hypertension caused by primary aldosteronism, selective adrenal hypoaldosteronism, edematous states, and other conditions of electrolyte imbalance.

7. Comparison to Predicate Device:

The Nichols Advantage® Aldosterone (Y) was compared to the DPC Coat-A-Count Aldosterone RIA (X) previously cleared by the FDA (K831178, 5/27/83). One hundred three (103) remnant serum samples in which the clinical diagnosis were unknown were assaved in duplicate by both methods following each manufacturers' directions. The range observed with method "X" was 2.7 to 125 ng/dL; range for method "Y" was 2.7 to 120 ng/dL. Passing Bablok regression analysis of these data yielded an equation of Y = 1.04X + 0.1 (95% confidence intervals for slope and intercept were 0.98 to 1.10, and -1.0 to +1.1 respectively). Deming regression analysis of these data yielded an equation of Y = 1.09X - 0.6 (95% confidence intervals for slope and intercept were 1.03 to 1.15, and -3.2 to +2.1 respectively). Pearson's correlation coefficient (r) of the paired data was 0.96.

8. Similarities:

Specimen type is identical for both methods. .
. Both assays use human aldosterone standards, and both report values using the same units: ng/dL.
Both assays use a specific antibody to aldosterone, use competitive protein binding with ● labeled aldosterone to measure the hormone directly in serum or plasma samples.

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

9. Differences:

The following differences pertain to differences in immunoassay technology and do not affect the intended uses of each assay.

Feature	Nichols Aldosterone	DPC Aldosterone
Sample Size:	250 uL serum or EDTA plasma	200 µL serum or plasma
Binding Technology	Magnetic particles - avidin coated	Antibody coated tubes
Incubation steps and temperature:	3 steps, 10 minutes each @ 37℃	18 hours @ 15-28°C
Analytical sensitivity	1.2 ng/dL	1.1 ng/dL
Sample Bias	EDTA values are lower	EDTA values are higher

10. Comparison of Performance Characteristics

Feature	Nichols Aldosterone	DPC Aldosterone
Within-Run Precision (%CV)	2.9-14.0%	2.3-5.4%
Total Precision (%CV)	4.9-18.6%	3.8-15.7%
Recovery	88-110%	86-111%
Linearity	91-116%	100-119%

Conclusions: These data, which were provided to FDA, demonstrate safety and effectiveness of the Nichols Advantage® Aldosterone for its intended in vitro diagnostic use. Furthermore, based on performance characteristics, the Nichols Advantage® Aldosterone assay is substantially equivalent to the predicate method.

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

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus, a symbol often associated with medicine and healthcare. The caduceus is composed of three parallel lines that curve and flow, resembling a stylized representation of a staff with snakes. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the caduceus.

Public Health Service

JUL 3 1 2003

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Nichols Institute Diagnostics c/o Alfredo J. Ouattrone. Ph.D., DABT California Department of Health Food & Drug Branch P.O. Box 942732 (MS-357) Sacramento, CA 94234

Re: K032188

Trade/Device Name: Nichols Advantage Aldosterone Regulation Number: 21 CFR 862,1045 Regulation Name: Aldosterone test system Regulatory Class: Class II Product Code: CJM; JIS; JJX Dated: July 15, 2003 Received: July 17, 2003

Dear Dr. Quattrone:

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).

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

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 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

{4}------------------------------------------------

510(k) Notification Nichols Advantage Aldosterone Date: 07/11/03

Indications For Use Statement 4.0

INDICATIONS FOR USE STATEMENT

510(k) Number:	K032188
----------------	---------

Nichols Advantage Aldosterone Device Name:

Indications for Use Statement: The Nichols Advantage® Aldosterone assay is intended for use with the Nichols Advantage® Specialty System to quantitatively measure aldosterone in human serum and EDTA plasma. Aldosterone measurements are used in the diagnosis and treatment of primary aldosteronism (a disorder caused by excessive secretion of aldosterone by the adrenal gland), hypertension caused by primary aldosteronism, selective hypoaldosteronism, edematous states, and other conditions of electrolyte imbalance.

Jean Cooper
Division Sign-Off
Office of In Vitro Diagnostic Device
Evaluation and Safety
510(k) K032188

(Please Do Not Write Below This Line - Continue On Another Page If Needed)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Rrescription Use (Per 21 CFR 801.109)

Over -The-Counter Use (Optional Format 1-2-96)

Regulation Number and Section

§ 862.1045 Aldosterone test system.

(a)
Identification. An aldosterone test system is a device intended to measure the hormone aldosterone in serum and urine. Aldosterone measurements are used in the diagnosis and treatment of primary aldosteronism (a disorder caused by the excessive secretion of aldosterone by the adrenal gland), hypertension caused by primary aldosteronism, selective hypoaldosteronism, edematous states, and other conditions of electrolyte imbalance.(b)
Classification. Class II.