The Nichols Advantage® Cortisol assay is intended for use with the Nichols Advantage® Specialty System for the quantitative determination of cortisol concentrations in human serum, EDTA plasma and urine. Measurements of cortisol are used in the diagnosis and treatment of disorders of the adrenal gland.

The Nichols Advantage Cortisol Assay Calibrators are intended for adjustment of the stored curve for the Nichols Advantage Cortisol assay.

Device Description

The Nichols Advantage Cortisol assay contains sufficient reagents for 100 tests. The assay is a chemiluminescent competitive binding assay for cortisol in human serum, plasma, and urine.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Nichols Advantage® Cortisol assay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a formal, quantifiable manner for the overall device's performance. Instead, it compares the performance characteristics of the new device (Nichols Advantage Cortisol) to a predicate device (DPC Coat-A-Count Cortisol RIA). The implicit acceptance criterion appears to be "substantial equivalence" to the predicate device across various performance metrics.

Feature	Predicate Device (DPC Coat-A-Count Cortisol)	New Device (Nichols Advantage Cortisol)	Comparison/Acceptance Status
Method Comparison
Pearson's r	Not applicable	0.97	Considered good correlation
Deming Regression	Not applicable	Y = 0.70X + 2.5	Considered equivalent
Range (Method X)	1.9 to 68.2 µg/dL	Not applicable
Range (Method Y)	Not applicable	2.8 to 49.5 µg/dL
Performance Characteristics
Within-Run Precision (%CV)	3.0-5.1%	3.6-8.7%	Comparable
Total Precision (%CV)	4.0-6.4%	7.1-17.4%	Comparable
Recovery	91-100%	97-109%	Comparable
Linearity	92-101%	94-107%	Comparable
Analytical Sensitivity	0.2 µg/dL	≤0.8 µg/dL	Comparable

Note: The conclusion states: "These data... demonstrate safety and effectiveness of the Nichols Advantage Cortisol for its intended in vitro diagnostic use. Furthermore, based on performance characteristics, the Nichols Advantage Cortisol assay is substantially equivalent to the predicate method." This implies the reported performance values fell within acceptable limits relative to the predicate device for FDA clearance.

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

Sample Size: 150 serum samples
Data Provenance: The document states the samples were "human serum samples in which the clinical diagnosis were unknown." It does not specify the country of origin. Given the manufacturer's address in San Clemente, CA, United States, it's reasonable to infer a U.S. origin, though not explicitly stated. The study appears to be retrospective as it uses existing "serum samples."

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

The document does not mention the use of experts to establish ground truth for the test set. The comparison is made against a legally marketed predicate device, where the predicate device's results serve as the reference for comparison.

4. Adjudication Method for the Test Set

Not applicable. There was no mention of an adjudication process as the comparison was against a predicate device's quantitative measurements.

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

No, an MRMC comparative effectiveness study was not done. This study focuses on the analytical performance of an in vitro diagnostic assay, comparing it to an existing assay, rather than assessing human reader performance.

6. If a Standalone Study Was Done

Yes, a standalone study was performed to characterize the performance of the Nichols Advantage Cortisol assay on its own (e.g., within-run precision, total precision, recovery, linearity, analytical sensitivity). The results of these intrinsic performance metrics are reported in the "Comparison of Performance Characteristics" table.

7. The Type of Ground Truth Used

The "ground truth" for the comparative study was the results obtained from the predicate device, DPC Coat-A-Count Cortisol RIA. This is a common approach for demonstrating substantial equivalence for in vitro diagnostic assays.

8. The Sample Size for the Training Set

The document does not provide information about a separate "training set" or its size. In the context of IVD assays like this, the "development" or "training" might involve internal validation and optimization, but specific training set sizes are not typically reported in 510(k) summaries for device performance. The reported study of 150 samples appears to be the primary validation data.

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

As no specific training set is mentioned, the method for establishing its ground truth is also not described. If there was an internal development phase, the ground truth for any optimization would likely be established in a similar manner to the reported comparison study (i.e., comparison to established methods or reference standards).

Summary

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K04268

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: Sept. 3, 2003

2. Device Name:

Trade/Proprietary Name:	Nichols Advantage® Cortisol
Device Name:	Cortisol radioimmunoassay
Device Description:	Cortisol (hydrocortisone and hydroxycorticosterone) test system
Classification:	2
Regulation Number:	862.1205
Product Code:	CGR, Clinical Chemistry

Diagnostic Product Corporation Coat-A-Count Cortisol 3. Predicate Device:

4. Device Description:

The Nichols Advantage Cortisol assay contains sufficient reagents for 100 tests. The assay is a chemiluminescent competitive binding assay for cortisol in human serum, plasma, and urine.

5. Intended Use:

6. Comparison to Predicate Device:

The Nichols Advantage Cortisol (Y) was compared to the DPC Coat-A-Count Cortisol RIA (X) previously cleared by the FDA (K810891, 4/14/81). One hundred fifty (150) serum samples in which the clinical diagnosis were unknown were assayed in duplicate by both methods following each manufacturers' directions. The range observed with method "X" was 1.9 to 68.2 µg/dL; range for method "Y" was 2.8 to 49.5 µg/dL. Deming regression analysis of these data vielded an equation of Y = 0.70X + 2.5 (95% Cl for slope and intercept were 0.67 to 0.73, and 1.9 to 3.2, respectively). Pearson's correlation coefficient (r) of the paired data was 0.97.

7. Similarities:

Specimen type is identical for both methods. .
Both assays use cortisol calibrators, are based upon competitive binding technology, and . both report values using the same units: uq/dL.
Both assays use a specific antibody to cortisol to measure the hormone in serum or plasma ● samples, and after extraction in urine samples.

8. Differences:

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

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Feature	Nichols Advantage Cortisol	DPC Coat-A-Count Cortisol
Sample Size:	12 µL serum or EDTA plasma andextracted urine	25 µL serum or heparin plasmaand extracted urine
Binding Technology	Magnetic particles - avidin coated	Antibody coated tubes
Incubation steps and temperature:	36 minutes @ 37°C	45 minutes @ 37°C
Analytical sensitivity	≤0.8 µg/dL	0.2 µg/dL
Sample Bias	Heparinized values are lower	EDTA values are higher

Comparison of Performance Characteristics 9.

Feature	Nichols Advantage Cortisol	DPC Coat-A-Count Cortisol
Within-Run Precision (%CV)	3.6-8.7%	3.0-5.1%
Total Precision (%CV)	7.1-17.4%	4.0-6.4%
Recovery	97-109%	91-100%
Linearity	94-107%	92-101%

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

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo features the department's name in a circular arrangement around a stylized symbol. The symbol consists of three curved lines that resemble a human figure, possibly representing health and well-being. The text is in all caps and reads "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)".

Public Health Service

DEC - 9 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Jimmy Wong Manager, Clinical and Technical Affairs Nichols Institute Diagnostics 1311 Calle Batido San Clemente, CA 92673

K042689 Re: Trade/Device Name: Nichols Advantage Cortisol Regulation Number: 21 CFR 862.1205 Regulation Name: Cortisol (hydrocortisone and hydroxycorticosterone) test system Regulatory Class: Class II Product Code: CGR, JIT Dated: September 20, 2004 Received: September 29, 2004

Dear Mr. Wong:

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 cornmerce 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,

Sincerly, yours,

Cornelia B. Looks

Cornelia B. Rooks, MA Acting 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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Nichols Advantage Cortisol 510K Nov. 19, 2004

Indications for Use

510(k) Number (if known): K042689

Device Name: Nichols Advantage Cortisol

Indications For Use:

The Nichols Advantage Cortisol Assay Calibrators are intended for adjustment of the stored curve for the Nichols Advantage Cortisol assay.

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C Benson
Division Sign Off

ision Sign

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K042689

Regulation Number and Section

§ 862.1205 Cortisol (hydrocortisone and hydroxycorticosterone) test system.

(a)
Identification. A cortisol (hydrocortisone and hydroxycorticosterone) test system is a device intended to measure the cortisol hormones secreted by the adrenal gland in plasma and urine. Measurements of cortisol are used in the diagnosis and treatment of disorders of the adrenal gland.(b)
Classification. Class II.