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

Device Description

The Nichols Advantage® Chemiluminescence Cortisol Immunoassay (hereinafter referred to as the Assay) is a Chemilumeniscence assay intended for use with the Nichols Advantage® Specialty System.

AI/ML Overview

The provided text describes the Nichols Advantage® Chemiluminescence Cortisol Immunoassay. While it lists performance characteristics, it does not present a formal "acceptance criteria" table or a specific "study" with a comparative effectiveness design that would typically be seen for AI/ML devices. Instead, it details various analytical performance studies conducted to demonstrate the assay's suitability for its intended use and its substantial equivalence to a predicate device.

Here's an attempt to structure the information based on your request, highlighting where the provided text does not contain the requested details (especially for AI-specific questions):

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a tabular format for each specific test. However, it presents the results of several analytical performance studies, implying that these results met internal criteria for demonstrating the assay's performance.

Performance Characteristic	Reported Device Performance
Reproducibility	Inter-assay precision: 8.6-10.3% CV
Recovery	Mean extraction recovery (spiked urine): 102% Analytical recovery (mixed high/low cortisol samples): 98 ± 5% (mean ± SD)
Linearity/Recovery	Linearity/recovery (diluted urine after extraction): 99 ± 9% (mean ± SD)
Extraction Efficiency	Mean extraction recovery (spiked urine): 102% (indicating efficient, complete, and reproducible extraction)
Parallelism	Mentioned as studied, but no specific quantitative result provided.
Effect of Interferents	No observed interference at pathological concentrations for protein, urea, creatinine, glucose, and sodium chloride.
Expected Values	Mentioned as studied for normal individuals, but no specific quantitative results provided.
Sensitivity	Sufficient to measure Cortisol found in patients with disorders of the adrenal gland.

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

The document does not explicitly state the sample sizes used for each specific test (reproducibility, recovery, interference, etc.). It describes the types of samples used (human serum, EDTA plasma, urine) but does not provide details on their provenance (e.g., country of origin, retrospective or prospective collection).

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

This information is not applicable as the device is a laboratory immunoassay for quantitative determination of cortisol, not an AI/ML device requiring expert interpretation of images or other complex data for ground truth establishment. The "ground truth" for this type of device is typically established through reference methods or known concentrations in spiked samples.

4. Adjudication Method for the Test Set:

This information is not applicable for a quantitative immunoassay. Adjudication methods like 2+1 or 3+1 are typically used for expert consensus in AI/ML performance evaluations, not for validating chemical assays.

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. This type of study is relevant for AI/ML devices where the AI is intended to assist human readers (e.g., radiologists interpreting images). This device is a standalone diagnostic assay.

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

While the term "standalone" in the context of AI refers to the algorithm's performance without human intervention, in the context of this immunoassay, it inherently operates as "standalone" in the sense that it provides a quantitative result without requiring human interpretive intervention in the measurement process itself. The reported performance characteristics (reproducibility, recovery, etc.) reflect the device's inherent analytical capabilities.

7. The Type of Ground Truth Used:

The ground truth for this device (a quantitative immunoassay) is established through:

Known concentrations: For spiked urine samples (e.g., to determine extraction recovery).
Reference methods: Implicitly, the comparison to a predicate device (Nichols Advantage® Chemiluminescence Cortisol Assay K962208) suggests that the underlying principles and expected performance are aligned with established methods.
Mixing experiments: For calculating analytical recovery.

8. The Sample Size for the Training Set:

This information is not applicable as this is not an AI/ML device that requires a "training set." The assay's performance is based on chemical and immunological principles, not on learned patterns from a training dataset.

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

This information is not applicable for the same reason as point 8.

Summary

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

KG84520

510(K) Notification Page 91 of 91

510(k) SAFETY AND EFFECTIVENESS SUMMARY

Nichols Advantage® Chemiluminescence Cortisol Immunoassay TRADE NAME:

COMMON NAME: Cortisol

CLASSIFICATION NAME: Cortisol (21 CFR 862.1205)

The Nichols Advantage® Chemiluminescence Cortisol Immunoassay (hereinafter referred to as the Assay) is a Chemilumeniscence assay intended for use with the Nichols Advantage® Specialty System.

INTENDED USE

The Assay is intended for the quantitative determination of cortisol concentration in human serum. EDTA plasma, and urine. Measurements of cortisol are used in the diagnosis and treatment of disorders of the adrenal gland.

SUBSTANTIAL EQUIVALENECE

The Assay is identical to the Nichols Advantage® Chemiluminescence Cortisol Assay (K962208 cleared 4/8/97) in its intended use; the use of human serum and EDTA plasma with the added intended use of urine, and sensitivity which is sufficient to measure Cortisol found in patients with disorders of the adrenal gland. Studies were performed to show the reproducibility, recovery, extraction efficiency, parallelism, effect of potential interferents in urine, and the expected values in normal individuals. The method we use to extract cortisol from urine is accepted and recognized in the literature. The inter-assay precision estimates of 8.6-10.3% CV are typical for an assay that includes a pre-assay organic solvent extraction step. When urine was analytically spiked with known amounts of cortisol. the mean extraction recovery was 102% indicating that the method to extract cortisol from urine is efficient, complete and reproducible. When various quantities of a high and low cortisol sample were mixed, the analytical recovery across the ranges studied showed recoveries of 98 ± 5% (mean ± SD). When urine was diluted after extraction, the linearity/recovery was 99 ± 9% (mean ± SD) across the ranges studied. Potential interference due to protein, urea, creatinine, glucose and sodium chloride were studied, and the data show no observed interference at the pathological concentrations studied. All these studies document the performance characteristics of measuring urine cortisol by this assay.

Submitted By: Jimmy Wong Manager, Clinical and Technical Affairs Nichols Institute Diagnostics 33051 Calle Aviador San Juan Capistrano, CA 92675-4703 (949) 240-5260

Contact Person: Jimmy Wong

Date: December 15, 1998

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

Image /page/1/Picture/0 description: The image is a black and white seal for the Department of Health & Human Services - USA. The seal is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the edge. In the center of the seal is a stylized image of three human profiles facing right, with a wing-like shape above them.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB 5 1999

Mr. Jimmy Wong Manager, Clinical and Technical Affairs Nichols Institute Diagnostics 33051 Calle Aviador San Juan Capistrano, California 92675-4703

Re: K984520

Trade Name: Nichols Advantage® Chemiluminescence Cortisol Immunoassay Regulatory Class: II Product Code: CGR Dated: December 15, 1998 Received: December 21, 1998

Dear Mr. Wong:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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

Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers 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 Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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

Nichols Institute Diagnostics Nichols Advantage® Chemiluminescence Cortisol 510(K) Notification Page 5 of 91

INDICATIONS FOR USE STATEMENT

984520

510(k) NUMBER (If Known): Koozzoo (Cicared -

DEVICE NAME: Nichols Advantage® Chemiluminescence Cortisol Immunoassay

INDICATIONS FOR USE:

Kan. Cooper

(Division Sign-Off) Division of Clinical Laboratory Devices K984520 510(k) Number.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21CFR 801.109)

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

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.