The Access Cortisol assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cortisol levels in human serum, plasma (heparin, EDTA) and urine using the Access Immunoassay Systems.

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

Device Description

The Access Cortisol assay is a competitive binding immunoenzymatic assay. The Access Cortisol reagent kit is in a liquid ready-to-use format designed for optimal performance on Beckman Coulter's immunoassay analyzers. Each reagent kit contains two reagent packs. Other items needed to run the assay include Calibrators, substrate, and wash buffer. The Access Cortisol assay reagent pack, Access Cortisol assay calibrators, along with the UniCel Dxl wash buffer II are designed for use with the Dxl 9000 Access Immunoassay Analyzer in a clinical laboratory setting.

AI/ML Overview

The provided text is a 510(k) Summary for the Beckman Coulter Access Cortisol Assay, intended for in vitro diagnostic use. It describes the device, its intended use, and comparative studies to demonstrate substantial equivalence to a predicate device.

Key points regarding acceptance criteria and study data fulfillment:

This document is for an in vitro diagnostic (IVD) device, not an AI/ML-based device for image analysis. Therefore, many of the requested criteria (e.g., number of experts for ground truth, MRMC study, human-in-the-loop performance, training set details) are not applicable to this type of medical device submission. The acceptance criteria and studies for IVD devices focus on analytical performance parameters.

Here's an analysis of the existing information based on the request:

1. Table of Acceptance Criteria and Reported Device Performance:

Performance Parameter	Acceptance Criteria (Implied/Stated)	Reported Device Performance
Method Comparison	R2 ≥ 0.90, Slope 1.00 ± 0.12	Correlation Coefficient (R2): 1.00 (meets criteria) Slope: 1.01 (falls within 0.88 - 1.12 range, meets criteria) Slope 95% CI: 0.99 - 1.03 Intercept: -0.20 Intercept 95% CI: -0.41 - 0.056 (N=116 samples, concentration range 1.6 - 59 ug/dL)
Imprecision	Within-laboratory (total) %CV: ≤ 9.3% for levels > 5.0 ug/dL; SD ≤ 0.1 for levels ≤ 5.0 ug/dL (based on reported performance meeting target, specific criteria not explicitly stated but implied by acceptable results)	Within-laboratory (total) %CV: Sample 1 (0.90 ug/dL): 13.1% (SD 0.1) - Note: This sample has a higher %CV than 9.3% for a low concentration, but the SD of 0.1 meets the low concentration criteria. Sample 2 (5.7 ug/dL): 7.1% Sample 3 (19 ug/dL): 8.6% Sample 4 (29 ug/dL): 9.3% Sample 5 (49 ug/dL): 3.9% All other samples meet the stated criteria for %CV or SD. (80 replicates per sample across 20 days, 3 analyzers, 3 reagent lots, 3 calibrator lots)
Linearity	Non-linearity within ± 1 ug/dL for values ≤ 5.0 ug/dL and ± 20% for values > 5.0 ug/dL	Meets acceptance criteria, linear across 0.8 - 60 ug/dL.
Limit of Blank (LoB)	0.4 ug/dL	Assay designed to meet claimed LoB of 0.4 ug/dL.
Limit of Detection (LoD)	0.4 ug/dL	Assay designed to meet claimed LoD of 0.4 ug/dL.
Limit of Quantitation (LoQ)	0.8 ug/dL (based on 20% CV)	LoQ designed to meet claimed LoQ of 0.8 ug/dL.

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

Method Comparison: N=116 samples. Data provenance is not specified (e.g., country of origin, retrospective/prospective), but implied to be from an internal site.
Imprecision: 5 serum samples were used, with 80 replicates per sample (total 400 measurements). Data provenance is from "one internal site."
Linearity, LoB/LoD, LoQ: Sample sizes are not explicitly stated for these studies, but they are performed as verification studies following CLSI guidelines. Data provenance is implied to be from an internal site.

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

Not Applicable. This is an IVD device for quantitative determination of a biomarker (cortisol) in patient samples. The "ground truth" is established by the analytical method itself and its traceability to a reference material (USP Reference Material for cortisol). There are no human experts "establishing ground truth" in the way it would be for an AI-based imaging device interpreting images.

4. Adjudication Method for the Test Set:

Not Applicable. As per point 3, there is no expert adjudication for an IVD assay's analytical performance.

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

No. This is an IVD device measuring a biomarker, not an AI/ML-based device assisting human readers in interpreting medical images. MRMC studies are not relevant for this type of device.

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

Yes, implicitly. The analytical performance studies (Method Comparison, Imprecision, Linearity, LoB/LoD, LoQ) evaluate the device (Access Cortisol Assay on Dxl 9000 Access Immunoassay Analyzer) in a standalone capacity, i.e., its ability to accurately and precisely measure cortisol levels. There is no "human-in-the-loop" aspect to the primary function of this diagnostic assay.

7. The Type of Ground Truth Used:

The ground truth is established by:
- Reference Method/Predicate Device: For method comparison, the predicate Access Cortisol assay on the Access Immunoassay System serves as the comparative "reference."
- Traceability to Reference Material: The calibrators and the assay itself are traceable to USP Reference Material for cortisol. This is the ultimate "ground truth" for the accuracy of the cortisol measurements.
- Defined Concentrations/Spiked Samples: For linearity and LoB/LoD/LoQ studies, samples with known or spiked concentrations are used.

8. The Sample Size for the Training Set:

Not Applicable. This is not an AI/ML device that requires a "training set" in the context of machine learning. The device is a chemiluminescent immunoassay; its analytical characteristics are determined by its chemical and biological components and the instrument's engineering.

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

Not Applicable. As per point 8, there is no "training set" or corresponding "ground truth" establishment in the AI/ML sense for this device.

Summary

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

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

February 8, 2023

Beckman Coulter, Inc Kuljeet Kaur, Ph.D. Regulatory Affairs Manager 1000 Lake Hazeltine Drive Chaska, MN 55318

Re: K223038

Trade/Device Name: Access Cortisol Regulation Number: 21 CFR 862.1205 Regulation Name: Cortisol (hydrocortisone and hydroxycorticosterone) test system Regulatory Class: Class II Product Code: CGR Dated: September 29, 2022 Received: September 29, 2022

Dear Kuljeet Kaur:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part

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

801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Image /page/1/Picture/6 description: The image shows the name "Paula Caposino -S" on the left side of the image. On the right side of the image, it says "Digitally signed by Paula Caposino -S" and "Date: 2023.02.08 17:08:10-05'00'". The text on the right side of the image indicates that the image is a digital signature.

Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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

Indications for Use

510(k) Number (if known) K223038

Device Name Access Cortisol

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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

Image /page/3/Picture/0 description: The image contains the logo for Beckman Coulter. The logo consists of a red circle with two white curved lines inside, followed by the company name "BECKMAN COULTER" in bold, black font. The two words are stacked on top of each other, with "BECKMAN" on the top and "COULTER" on the bottom.

Access Cortisol Assay 510 (k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92

510(k) number: K223038

Submitted By:

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318

Contact Person:

Kuljeet Kaur, Ph.D. Phone: (952) 465-1914 Email: kkaur@beckman.com

Alternate Contact:

Kate Oelberg Office Phone: (612) 431-7315 Email: kmoelberg@beckman.com

Date Prepared: January 30, 2023

Device Common Name: Access Cortisol Assay Trade Name: Access Cortisol Classification Name: Cortisol (hydrocortisone and hydroxycorticosterone) test system Classification Regulation: 21 CFR 862.1205

Predicate Device: Access Cortisol 510(k) Number: K050202

Device Description:

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

Intended Us

SystemAttribute/Characteristic	Predicate Access Cortisol on AccessImmunoassay System	Candidate AccessCortisol on Dxl 9000AccessImmunoassayAnalyzer
Intended Use/Indications for Use	The Access Cortisol assay is aparamagnetic particle,chemiluminescent immunoassay for thequantitative determination of cortisollevels in human serum, plasma(heparin, EDTA) and urine using theAccess Immunoassay Systems.	Same
Solid Phase	Paramagnetic particles coatedwith goat anti-rabbit IgG	Same
Conjugate	Cortisol-alkaline phosphatase(bovine) conjugate	Same
Calibrators	Human serum containingcortisol (purified chemicalcompound) at levels of 0 andapproximately 2, 5, 10, 25, and 60µg/dL 60 µg/dL	Same
Analyte Measured	Cortisol	Same
Traceability	USP Reference Material	Same
Technology	Competitive binding ImmunoassaySystem	Same
Format	Chemiluminescent	Same
Method	Automated	Same
Calibration	Utilizes a stored calibration curve	Same
Sample Type	Serum, plasma, or urine	Same

Comparison of Technological Characteristics to the Predicate

{5}------------------------------------------------

SystemAttribute/Characteristic	Predicate Access Cortisol on AccessImmunoassay System	Candidate AccessCortisol on Dxl 9000AccessImmunoassayAnalyzer
Stability	Stable at 2 to 10°C for 14 days afterinitial use	Same
Reagent Packformulation andpackaging	Access Reagent Pack formulation andpackaging.	Same
Measuring Range	0.4 - 60 µg/dL	0.8 - 60 ug/dL
Instrument	Access Immunoassay system	Dxl 9000 AccessImmunoassayAnalyzer
Substrate	Access Substrate	Lumi-Phos PROsubstrate

Summary of Studies:

Method Comparison: A method comparison study was completed to compare the Access Cortisol assay on the Dxl 9000 Access Immunoassay Analyzer to the Access Cortisol assay on the Access Immunoassay System using a protocol based on CLSI EP09c-A3. The results of the within range method comparison study met the acceptance criteria of R2 ≥ 0.90 and slope 1.00 ± 0.12 and supports the equivalence of the Access Cortisol assay on Dxl 9000 to the predicate device, the Access Cortisol assay on Access 2 Instrument.

N	ConcentrationRange (ug/dL)	Slope	Slope 95% CI	Intercept	Intercept95% CI	CorrelationCoefficientR2
116	1.6 - 59	1.01	0.99 - 1.03	-0.20	-0.41 - 0.056	1.00

Imprecision: Verification studies were performed to determine the imprecision of the Access Cortisol assay on the Dxl 9000 Access Immunoassay Analyzer using a protocol based on CLSI EP-05-A3. The study was performed within one internal site over twenty days. Three Dxl 9000 Immunoassay Analyzers were used in the study design. There were three reagent pack lots and three calibrator lots. Five (5) serum samples, with Cortisol concentrations spanning the assay range were used for this study. The within-laboratory (total) % CV ranged from 2% to 9.3%, for Cortisol

{6}------------------------------------------------

		Mean	Repeatability(Within-run)		Between-run		Between-day		Within-Laboratory
Sample	N	Concentration(ug/dL)	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 1	80	0.90	0.1	10.2	0.1	8.2	0.0	0.0	0.1	13.1
Sample 2	80	5.7	0.2	3.4	0.3	5.5	0.2	2.7	0.4	7.1
Sample 3	80	19	0.5	2.6	1.1	6.0	1.1	5.5	1.6	8.6
Sample 4	80	29	0.8	2.7	2.0	6.7	1.7	5.8	2.7	9.3
Sample 5	80	49	1.1	2.3	0.0	0.0	1.6	3.2	1.9	3.9

concentrations > 5.0 ug/dL. The within-laboratory (total) SD was 0.1 for Cortisol concentrations ≤ 5.0 uq/dL. The results from a representative lot are as follows:

Linearity: A verification study was performed to evaluate the linearity of the Access Cortisol assay on the Dxl 9000 Access Immunoassay Analyzer based on CLSI EP06-Ed2. Acceptance criteria for non-linearity within ± 1 ug/dL for values ≤ 5.0 ug/dL and ± 20% for values > 5.0 ug/dL was met and indicate that the Access Cortisol assay is linear on the Dxl 9000 Immunoassay System across the analytical measuring interval of 0.8 -60 ug/dL (22 - 1,655 nmol/L).

LoB/LoD: Verification studies were performed to determine the Limit of Blank (LoB) and Limit of Detection (LoD) for the Access Cortisol assay on the Dxl 9000 Access Immunoassay Analyzer using a protocol based on CLSI EP17-A2. The assay is designed to meet the claimed LoB of 0.4 ug/dL and LoD of 0.4 ug/dL.

LoQ: Verification studies were performed to determine the Limit of Quantitation (LoQ) of the Access Cortisol assay on the Dxl 9000 Access Immunoassay Analyzer using a protocol based on CLSI EP17- A2. The LoQ for Access Cortisol designed to meet the claimed LoQ of 0.8 ug/dL based on a 20% CV.

Other claims: The claims for the analytical specificity, reference intervals, matrix comparison are being transferred from file K050202.

Substantial Equivalence Comparison Conclusion

Beckman Coulter's Access Cortisol Assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to the Access Cortisol Assay on the Access Immunoassay System as demonstrated through the information and data provided in

{7}------------------------------------------------

this submission. The performance testing presented in this submission provides evidence that the device is safe and effective in its intended use.

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.