Immunoassay for the in vitro quantitative determination of cortisol in human urine. The determination of cortisol is used for the recognition and treatment of functional disorders of the adrenal gland.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

Device Description

The Elecsys Cortisol III immunoassay employs a competitive test principle using a cortisol-specific biotinylated monoclonal antibody and a cortisol-derivative labeled with a ruthenium complex. The Elecsys Cortisol III immunoassay is intended for the in vitro quantitative determination of cortisol in human urine. The determination of cortisol is used for the recognition and treatment of functional disorders of the adrenal gland on the cobas e immunoassay analyzers.

Results are determined via a calibration curve which is instrument-specifically generated by a two-point calibration and a master curve provided via the cobas link.

The Elecsys Cortisol III immunoassay reagent Rack Pack comprises the following:

M Streptavidin-coated microparticles (transparent cap), 1 bottle, 12.4 mL:
Streptavidin-coated microparticles 0.72 mg/mL; preservative.

R1 Anti-cortisol-Ab~biotin (gray cap), 1 bottle, 21.0 mL:
Biotinylated monoclonal anti-cortisol antibody (mouse) 18 ng/mL; danazol 20 μg/mL; MES buffer 100 mmol/L, pH 6.0; preservative.

R2 Cortisol-peptide~Ru(bpy) (black cap), 1 bottle, 21.0 mL:
Cortisol derivative (synthetic), labeled with ruthenium complex, 5 ng/mL; danazol 20 μg/mL; MES buffer 100 mmol/L, pH 6.0; preservative.

MES = 2-morpholino-ethane sulfonic acid

AI/ML Overview

The provided 510(k) summary for the Elecsys Cortisol III device focuses primarily on non-clinical performance evaluations to demonstrate substantial equivalence to a predicate device. It does not describe a study to prove performance against specific acceptance criteria for diagnostic accuracy (e.g., sensitivity, specificity, or agreement with ground truth in a clinical context) with a test set of patient samples.

Here's an analysis of the available information:

1. Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in the traditional sense for diagnostic performance metrics like sensitivity, specificity, or agreement against a clinical ground truth. Instead, it details performance specifications for various analytical aspects and states that these "met the predefined acceptance criteria." These are primarily related to the analytical performance of the assay itself.

Category	Acceptance Criteria (Not explicitly stated as clinical performance criteria, but implied as met from the document)	Reported Device Performance (Summary of findings)
Precision	Predefined acceptance criteria met.	Repeatability (cobas e 801 analyzer): CV ranges from 2.0% to 2.7% for human urine samples and controls. Intermediate Precision (cobas e 801 analyzer): CV ranges from 2.5% to 3.8% for human urine samples and controls. Reproducibility: Lot-to-lot reproducibility met predefined acceptance criteria.
Analytical Sensitivity (LoB, LoD, LoQ)	Predefined acceptance criteria met.	LoB: 4.00 nmol/L (0.145 µg/dL) LoD: 7.50 nmol/L (0.272 µg/dL) LoQ: 10.0 nmol/L (0.363 µg/dL)
Linearity/Assay Reportable Range	Predefined acceptance criteria met.	Reportable Range: 20.0 - 500 nmol/L (0.725 - 18.1 µg/dL)
Human Anti-Mouse Antibodies (HAMA)	Predefined acceptance criteria met.	Differentiation between HAMA-negative and HAMA-positive samples assessed; data met acceptance criteria.
Endogenous Interferences	No significant interference.	No significant interference observed for 13 endogenous substances (e.g., bilirubin, hemoglobin, intralipid, biotin, rheumatoid factor, various immunoglobulins, albumin, creatinine, glucose, NaCl, urea) up to the tested concentrations.
Analytical Specificity/Cross-Reactivity	Expected cross-reactivity profiles.	Cross-reactivity % reported for various related steroids, with 11-Deoxycortisol (24.3%) and Allotetrahydrocortisol (11.3%) showing the highest cross-reactivity at the tested concentration. Many common steroids showed "n.d." (not detected) or very low cross-reactivity.
Exogenous Interferences – Drugs	No interference with the assay at therapeutic concentrations for most drugs.	No interference found for 12 commonly used pharmaceuticals. Prednisolone and hydrocortisone caused elevated cortisol concentrations. No interference observed for 6 methylprednisolone ≤ 0.157 mg/dL. Additional special drugs tested (amlodipine, betamethasone, beclomethasone, etc.) showed no interference.
Method Comparison	Predefined acceptance criteria met.	Data analyzed according to CLSI EP09-A3 and met all predefined acceptance criteria when compared to the predicate device (ARCHITECT Cortisol) using native 24-hour urine samples spanning the measuring range.
Stability	Predefined acceptance criteria met.	Supports claims for unopened reagents at 2-8 °C up to the stated expiration date and 16 weeks on the analyzer.
Reference Range	Established reference range for healthy population.	2.5th percentile: 24.8 nmol/24h (8.98 µg/24h) 97.5th percentile: 238 nmol/24h (86.2 µg/24h) for a healthy US population.

2. Sample Size and Data Provenance for Test Set

Precision (Repeatability & Intermediate Precision): Human urine samples (24-hour urine) and controls. Two replicates per run, two runs per day for 21 days for each of 4 human urine samples and 2 controls. (Total of $4 \text{ samples} \times 2 \text{ replicates/run} \times 2 \text{ runs/day} \times 21 \text{ days} = 336$ measurements for human urine, plus $2 \text{ controls} \times 2 \text{ replicates/run} \times 2 \text{ runs/day} \times 21 \text{ days} = 168$ measurements for controls. Or potentially 42 total runs for each sample/control).
Analytical Sensitivity (LoB, LoD, LoQ): Not specified beyond "reagents and calibrators" likely being used.
Linearity/Assay Reportable Range: Dilution series contained a minimum of 9 concentrations. Number of samples not explicitly stated but implies a set of samples specifically created to span the measuring range.
HAMA: Not specified.
Endogenous Interferences: Human urine samples (24-hour urine) were used. The number of samples is not explicitly stated.
Analytical Specificity/Cross-Reactivity: Human urine (24-hour urine) samples. Specific numbers not provided beyond "samples were measured in the presence and absence of the potential cross-reactants."
Exogenous Interferences – Drugs: In vitro tests performed on 12 commonly used pharmaceuticals and additional special drugs. This implies spiked samples rather than a "test set" of patient samples.
Method Comparison: "Native 24 h urine samples" for comparison with the predicate device. The number of samples is not specified.
Reference Range Study: Samples collected from an "apparently healthy population in the United States" across three study sites. The exact number of samples is not provided, but it's sufficient for establishing 2.5th and 97.5th percentiles (typically requires 120+ samples according to CLSI EP28-A3c).

Data Provenance: The document explicitly states "human urine samples (24-hour urine)" for most studies and for the reference range, "collected across three study sites... in the United States." This indicates prospective collection for the reference range study specifically for generating normal values applicable to the US population. For other analytical performance claims, the sample type (human urine) is generally mentioned, suggesting a similar provenance, likely for prospective testing within the manufacturer's lab or clinical sites.

3. Number of Experts and Qualifications for Ground Truth

Not applicable for the Elecsys Cortisol III. This is an in vitro diagnostic device (IVD) that quantitatively measures a biomarker (cortisol). The "ground truth" for such devices is typically established through recognized analytical standards, reference methods, and comparison to a legally marketed predicate device, rather than expert consensus on diagnostic images or clinical assessments. The closest to "ground truth" in this context would be the accuracy against a gold standard analytical method or purified cortisol standards. These details are not provided but are implicit in the validation that relies on CLSI guidelines.

4. Adjudication Method for the Test Set

Not applicable. As this is a quantitative IVD for a biomarker, diagnostic classification and adjudication by experts are not relevant to the described analytical studies. The performance is assessed by comparison to expected analytical results or a predicate device.

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

Not applicable. MRMC studies are typically for imaging devices or software that assist human readers in making a diagnosis. The Elecsys Cortisol III is an automated in vitro diagnostic immunoassay for quantitative measurement of cortisol in urine. It does not involve human readers interpreting cases with or without AI assistance.

6. Standalone Performance Study

Yes, the entire submission describes standalone performance. The Elecsys Cortisol III is an immunoassay designed to operate on cobas e immunoassay analyzers. All the performance data (precision, sensitivity, linearity, interference, cross-reactivity, method comparison) are generated directly from the device's measurement of cortisol in urine samples. The device itself performs the quantitative determination without human-in-the-loop interpretation impacting the measurement results. The method comparison study directly compares its quantitative output to the predicate device's quantitative output.

7. Type of Ground Truth Used

For an IVD like Elecsys Cortisol III, the "ground truth" for the test set is established by:

Reference standards/Calibrators: For analytical sensitivity (LoB, LoD, LoQ) and linearity studies, known concentrations of cortisol (or materials traceable to them) are used.
Predicate device comparison: For method comparison, the results from the Elecsys Cortisol III are compared to those obtained from the legally marketed ARCHITECT Cortisol (K062204), which serves as the established "truth" or benchmark for demonstrating substantial equivalence.
Spiked samples/characterized samples: For interference and cross-reactivity studies, samples with known concentrations of interferents or cross-reactants are used to determine the device's accuracy in their presence.
Clinically characterized healthy population samples: For the reference range study, samples from healthy individuals are used to establish normal ranges, though this isn't a "ground truth" for diagnostic accuracy.

8. Sample Size for the Training Set

The document does not mention "training set" in the context of an AI/ML algorithm. This device is an immunoassay, which relies on chemical reactions and optical detection, not an AI/ML model that requires a training set. The term "training set" is therefore not applicable here.

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

Not applicable. As noted above, there is no AI/ML training set for this immunoassay device.

Summary

FDA 510(k) Clearance Letter - Elecsys Cortisol III

Page 1

U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov

Doc ID # 04017.07.05

July 17, 2025

Roche Diagnostics
Chunhong (Emma) Tao
Regulatory Affairs Manager
9115 Hague Road
Indianapolis, Indiana 46250

Re: K242505
Trade/Device Name: Elecsys Cortisol III
Regulation Number: 21 CFR 862.1205
Regulation Name: Cortisol (Hydrocortisone And Hydroxycorticosterone) Test System
Regulatory Class: Class II
Product Code: JFT
Dated: July 17, 2025
Received: July 17, 2025

Dear Chunhong (Emma) Tao:

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 (the 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 available 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.

July 17, 2025

Roche Diagnostics
Chunhong (Emma) Tao
Regulatory Affairs Manager
9115 Hague Road
Indianapolis, Indiana 46250

Dear Chunhong (Emma) Tao:

U.S. Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov

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K242505 - Chunhong (Emma) Tao Page 2

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 801 and Part 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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-devices/medical-device-safety/medical-device-reporting-mdr-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/medical-devices/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-devices/device-advice-comprehensive-regulatory-

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K242505 - Chunhong (Emma) Tao Page 3

assistance/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,

Paula V. Caposino -S

Paula Caposino, Ph.D.
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

Page 4

FORM FDA 3881 (6/20) Page 1 of 1 PSC Publishing Services (301) 443-6740 EF

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120
Expiration Date: 06/30/2023
See PRA Statement below.

510(k) Number (if known)
K242505

Device Name
Elecsys Cortisol III

Indications for Use (Describe)
Immunoassay for the in vitro quantitative determination of cortisol in human urine. The determination of cortisol is used for the recognition and treatment of functional disorders of the adrenal gland.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

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."

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Form Approved: OMB No. 0910-0120
Expiration Date: 06/30/2023

Indications for Use

See PRA Statement below.

510(k) Number (if known)
K242505

Device Name
Elecsys Cortisol III

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

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.

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."

FORM FDA 3881 (6/20) Page 1 of 1 PSC Publishing Services (301) 443-6740 EF

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510k Summary Elecsys Cortisol III (K242505)

Page 1

510k Summary

Elecsys Cortisol III (K242505)

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

In accordance with 21 CFR 807.87, Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Traditional 510(k) Premarket Notification.

The purpose of this Traditional 510(k) Premarket Notification is to obtain FDA review and clearance for Elecsys Cortisol III.

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510k Summary Elecsys Cortisol III (K242505)

| Predicate Device: | ARCHITECT Cortisol (K062204) |
| Establishment Registration | Roche Diagnostics GmbH Mannheim, Germany: 9610126Roche Diagnostics GmbH Penzberg, Germany: 9610529Roche Diagnostics Indianapolis, IN United States: 1823260 |

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510k Summary Elecsys Cortisol III (K242505)

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1. DEVICE DESCRIPTION

Results are determined via a calibration curve which is instrument-specifically generated by a two-point calibration and a master curve provided via the cobas link.

The Elecsys Cortisol III immunoassay reagent Rack Pack comprises the following:

M Streptavidin-coated microparticles (transparent cap), 1 bottle, 12.4 mL:
Streptavidin-coated microparticles 0.72 mg/mL; preservative.

R1 Anti-cortisol-Ab~biotin (gray cap), 1 bottle, 21.0 mL:
Biotinylated monoclonal anti-cortisol antibody (mouse) 18 ng/mL; danazol 20 μg/mL; MES buffer 100 mmol/L, pH 6.0; preservative.

R2 Cortisol-peptide~Ru(bpy) (black cap), 1 bottle, 21.0 mL:
Cortisol derivative (synthetic), labeled with ruthenium complex, 5 ng/mL; danazol 20 μg/mL; MES buffer 100 mmol/L, pH 6.0; preservative.

MES = 2-morpholino-ethane sulfonic acid

2. INDICATIONS FOR USE

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510k Summary Elecsys Cortisol III (K242505)

Page 4

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

3. TECHNOLOGICAL CHARACTERISTICS

The following table compares Elecsys Cortisol III with its predicate device, ARCHITECT Cortisol (K062204).

Table 1: Technical Characteristics Comparison between Elecsys Cortisol III and ARCHITECT Cortisol (K062204)

Item	Elecsys Cortisol III (Candidate Device)	ARCHITECT Cortisol (K062204, Predicate Device)
Intended Use	Immunoassay for the in vitro quantitative determination of cortisol in human urine. The determination of cortisol is used for the recognition and treatment of functional disorders of the adrenal gland.	The ARCHITECT Cortisol is a chemiluminescent microparticle immunoassay (CIMA) for the quantitative determination of cortisol in human serum, plasma or urine on the ARCHITECT i System. The ARCHITECT Cortisol assay is intended for use as an aid in the diagnosis and treatment of adrenal disorders.
Indications for Use	The results obtained are used for the recognition and treatment of functional disorders of the adrenal gland.	The results obtained are used as an aid in the diagnosis and treatment of adrenal disorders.
Detection Method	electrochemiluminescence immunoassay "ECLIA"	chemiluminescent microparticle immunoassay (CMIA)
Instrument Platform	cobas e immunoassay analyzers	ARCHITECT i System
Sample Type	Urine	Serum, plasma or urine
Expected Range	8.98 – 86.2 μg/24 h (24.8 – 238 nmol/24 h)	4.3 – 176 μg/24 h
Reportable Range	0.725 – 18.1 μg/dL (20.0 – 500 nmol/L)	0.8 – 59.8 µg/dL

4. NON-CLINICAL PERFORMANCE EVALUATION

The following performance data are provided in support of the substantial equivalence determination. All performance specifications were met.

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510k Summary Elecsys Cortisol III (K242505)

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4.1. Precision

4.1.1. Repeatability and Intermediate Precision

Precision was evaluated with human urine samples (24-hour urine) and controls by testing two replicates per run, two runs per day for 21 days. Repeatability and Intermediate precision were calculated according to CLSI EP05-A3. All data met the predefined acceptance criteria.

cobas e 801 analyzer

Sample	Mean nmol/L	Repeatability		Intermediate Precision
		SD nmol/L	CV %	SD nmol/L	CV %
Human Urine 1	88.7	2.41	2.7	3.34	3.8
Human Urine 2	236	5.46	2.3	6.90	2.9
Human Urine 3	296	5.86	2.0	9.37	3.2
Human Urine 4	453	9.39	2.1	14.5	3.2
Control 1	204	4.04	2.0	5.00	2.5
Control 2	374	8.98	2.4	11.3	3.0

cobas e 801 analyzer

Sample	Mean µg/dL	Repeatability		Intermediate Precision
		SD µg/dL	CV %	SD µg/dL	CV %
Human Urine 1	3.22	0.0873	2.7	0.121	3.8
Human Urine 2	8.56	0.198	2.3	0.250	2.9
Human Urine 3	10.7	0.212	2.0	0.340	3.2
Human Urine 4	16.4	0.340	2.1	0.525	3.2
Control 1	7.39	0.147	2.0	0.181	2.5
Control 2	13.6	0.325	2.4	0.408	3.0

4.1.2. Reproducibility

Lot-to-lot reproducibility was performed using three reagent lots according to CLSI EP05-A3. All data met the predefined acceptance criteria.

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510k Summary Elecsys Cortisol III (K242505)

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4.2. Analytical Sensitivity

4.2.1. Limit of Blank (LoB)

The Limit of Blank (LoB) was determined according to CLSI EP17-A2. The LoB claim in the labeling will be set to 4.00 nmol/L (0.145 µg/dL).

4.2.2. Limit of Detection (LoD)

The Limit of Detection (LoD) was determined according to CLSI EP17-A2. The LoD claim in the labeling will be set to 7.50 nmol/L (0.272 µg/dL).

4.2.3. Limit of Quantitation (LoQ)

The Limit of Quantitation (LoQ) was determined according to CLSI EP17-A2. The LoQ claim in the labeling will be set to 10.0 nmol/L (0.363 µg/dL).

4.3. Linearity/Assay Reportable Range

Linearity was evaluated on the cobas e 801 analyzer according to CLSI EP06-Ed2. The dilution series contained a minimum of 9 concentrations throughout the measuring range. A measuring range of 20.0-500 nmol/L or 0.725-18.1 μg/dL will be claimed in the labeling.

4.4. Human Anti-Mouse Antibodies (HAMA)

The effect of the presence of human anti-mouse antibodies (HAMA) was assessed on the cobas e 801 analyzer. The differentiation between HAMA-negative and HAMA-positive samples was assessed. Data met the predefined acceptance criteria.

4.5. Endogenous Interferences

The effect on quantitation of Cortisol in the presence of thirteen endogenous interfering substances (lipemia, biotin, bilirubin, hemoglobin, rheumatic factor, human serum albumin, human IgG, human IgM, human IgA, Sodium Chloride, Urea, glucose, and creatinine) was tested using human urine samples (24-hour urine). No significant interference for the assay was observed up to the concentrations of the potential interfering substances tested as shown in the table below.

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510k Summary Elecsys Cortisol III (K242505)

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Compound	Concentration tested
Bilirubin	≤ 1130 μmol/L or ≤ 66 mg/dL
Hemoglobin	≤ 0.621 mmol/L or ≤ 1000 mg/dL
Intralipid	≤ 2000 mg/dL
Biotin*	≤ 204658 nmol/L or ≤ 50000 ng/mL
Rheumatoid Factor	≤ 1200 IU/mL
Human IgG	≤ 7.0 g/dL
Human IgA	≤ 1.6 g/dL
Human IgM	≤ 1.0 g/dL
Human serum albumin	≤ 4.9 g/dL
Creatinine	≤ 5 mmol/L
Glucose	≤ 5 mmol/L
NaCl	≤ 750 mmol/L
Urea	≤ 350 mmol/L

*Biotin was tested at 100,000 ng/mL. The data supports no interference up to 50,000 ng/mL.

4.6. Analytical Specificity/Cross-Reactivity

A cross-reactivity study was conducted on the cobas e 801 analyzer to evaluate the potential cross-reacting compounds using human urine (24-hour urine). Samples were measured in the presence and absence of the potential cross-reactants and cross-reactivity was calculated with one lot of reagents. The following cross-reactivities (in %) were found at the respective cross-reactant concentration, tested with a cortisol concentration of approximately 17 nmol/L (0.6 µg/dL).

Cross-Reactant	Concentration tested µg/dL	Cross reactivity %
11-Deoxycorticosterone	100	0.174
11-Deoxycortisol	50	24.3
17α-Hydroxyprogesterone	1000	0.412
21-Deoxycortisol	100	2.33
Corticosterone	750	0.368
Cortisone	500	1.49
Androstenedione	100	n. d.d)
DHEAS	1000	n. d.
DHEA	1000	n. d.
Progesterone	1000	0.00930
Testosterone	1000	n. d.

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510k Summary Elecsys Cortisol III (K242505)

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Cross-Reactant	Concentration tested µg/dL	Cross reactivity %
Estradiol	1000	n. d.
Estriol	1000	n. d.
Estrone	1000	n. d.
Aldosterone	1000	n. d.
Pregnenolone	1000	n. d.
17α-Hydroxypregnenolone	1000	0.0417
11β-Hydroxyprogesterone	1000	0.0173
Pregnanetriol	1000	n. d.
6α-Hydroxycortisol	100	n. d.
6β-Hydroxycortisol	100	0.0698
Cortisol-21 glucuronide	1000	0.0301
Allotetrahydrocortisol	10	11.3
Cortisol-21-sulfate	1000	n. d.
β-Cortol	1000	n. d.
β-Cortolone	1000	n. d.
Pregnanediol	1000	n. d.
Tetrahydrocortisol	10	n. d.

4.7. Exogenous Interferences – Drugs

In vitro tests were performed on 12 commonly used pharmaceuticals. No interference with the assay was found. At concentrations corresponding to the daily therapeutic dose, the special drugs prednisolone and hydrocortisone caused elevated concentrations of cortisol. For the special drug 6 methylprednisolone, no interference was observed for concentrations ≤ 0.157 mg/dL.

In addition, the following special drugs were tested. No interference with the assay was found.

Drug	Concentration tested mg/dL
Amlodipine	0.008
Betamethasone	0.0345
Beclomethasone	0.000631
Budenoside	0.00063
Canrenone	0.075
Dexamethasone	1.20
Fludrocortisone	0.120
Fluticasone propionate	0.0003

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510k Summary Elecsys Cortisol III (K242505)

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Drug	Concentration tested mg/dL
HCT (hydrochlorothiazide)	4.77
Lisinopril	27
Losartan potassium	0.092
Metformin	850
Metoprolol	0.150
Mometasone	0.000045
Prednisone	0.010
Spironolactone	0.0555
Triamterene	0.059
Valsartan	1.17
Verapamil	0.160
Triamcinolone	0.003
Atorvastatin	0.075
Danazol	0.030
Diclofenac	2.40
β-Sitosterol	1.00

4.8. Method Comparison

Method comparison was performed between the candidate device and the predicate device using native 24 h urine samples. Samples span the measuring range. Data was analyzed according to CLSI EP09-A3 and met all predefined acceptance criteria.

4.9. Stability

The stability studies were performed and the predefined acceptance criteria were met. The stability data supports the claims as reported in labeling.

Stability:

unopened at 2-8 °C up to the stated expiration date
on the analyzer 16 weeks

5. REFERENCE RANGE STUDY

A study was performed to determine the expected values of the Elecsys Cortisol III assay in 24 h urine samples from an apparently healthy population in the United States. Samples were

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510k Summary Elecsys Cortisol III (K242505)

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collected across three study sites according to the inclusion and exclusion criteria. An additional study site did sample testing. The reference range was computed and reported as the 2.5th and 97.5th percentiles for pooled data from all study sites and with all sites combined according to CLSI EP28-A3c.

2.5th percentile	97.5th percentile	Unite
24.8	238	nmol/24h
8.98	86.2	µg/24h

6. ADDITIONAL INFORMATION

Elecsys Cortisol III is intended to be used with the following calibrators and controls:

CalSet Cortisol III Urine
PreciControl Cortisol Urine

7. CONCLUSIONS

The information provided in this 510(k) Premarket Notification supports the determination that Elecsys Cortisol III is equivalent to the predicate device, ARCHITECT Cortisol (K062204).

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.