K Number
K021218
Date Cleared
2002-09-09

(145 days)

Product Code
Regulation Number
862.1205
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

Immunological in vitro assay for the quantitative determination of cortisol in human serum, plasma and 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 the Roche Elecsys® 1010 / 2010 and Modular Analytics E170 (Elecsys module) Immunoassay Analyzers.

Device Description

The ELECSYS® Cortisol Assay a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve provided with the reagent bar code.

AI/ML Overview

The information provided describes the Elecsys® Cortisol Assay and its substantial equivalence to a predicate device (Bayer Diagnostics ACS:180 Cortisol Assay). It focuses on comparing the new device's performance characteristics to the predicate device to demonstrate substantial equivalence, rather than detailing a specific study proving the device meets acceptance criteria with predefined thresholds. Therefore, some of the requested information cannot be fully extracted as it pertains to a typical clinical validation study with explicitly stated acceptance criteria and a detailed study design.

Here's the breakdown of what can be extracted and what is not available in the provided text:

1. Table of acceptance criteria and the reported device performance:

The document doesn't explicitly state "acceptance criteria" through specific numerical thresholds for each performance characteristic. Instead, it demonstrates performance by comparing the new device's data directly to that of the predicate device, implying that performance comparable to the legally marketed predicate device is the de facto acceptance criteria for substantial equivalence.

FeatureAcceptance Criteria (Implied: Comparable to Predicate)New Device (ELECSYS Cortisol) Reported PerformancePredicate Device (Bayer ACS:180 Cortisol) Reported Performance
Intra-assay precision (%CV) (Urine)Comparable to Predicate's Intra-assay precision• 2.2% at 22.3 µg/dl • 2.3% at 33.2 µg/dl • 2.9% at 41.9 µg/dl • 2.3% at 61.0 µg/dl• 5.7% at 3.04 µg/dl • 5.1% at 5.43 µg/dl • 4.5% at 14.90 µg/dl • 6.4% at 18.98 µg/dl • 7.0% at 31.79 µg/dl • 7.5% at 38.67 µg/dl
Interassay precision (%CV) (Urine)N/A (Predicate data not fully provided)• 2.5% at 23.2 µg/dl • 3.2% at 33.4 µg/dl • 2.5% at 42.1 µg/dl • 1.8% at 58.9 µg/dl Control: 4.7% at 2.82 µg/dlN/A
Total precision (%CV)Comparable to Predicate's Total precisionN/A• 9.1% at 3.04 µg/dl • 8.0% at 5.43 µg/dl • 6.4% at 14.90 µg/dl • 8.2% at 18.98 µg/dl • 9.2% at 31.79 µg/dl • 9.7% at 38.67 µg/dl
Functional sensitivityComparable or better than Predicate's functional sensitivity< 0.29 µg/dl0.2 µg/dl
Measuring rangeComparable to Predicate's measuring range1.0 - 1750 nmol/L5.5 - 2069 nmol/L
Limitations (Interference in Urine)Unaffected by specified concentrations of substances as per Predicate• 60 mg/dl protein • 750 mmol/l NaCl • 350 mmol/l urea • 5 mmol/l creatinine • 2 mmol/l glucose• 60 mg/dl protein • 750 mmol/l NaCl • 350 mmol/l urea • 5 mmol/l creatinine • 2 mmol/l glucose
On-board stabilitySufficient for clinical use, comparable to predicateElecsys® 2010 / E170: 6 weeks Elecsys® 1010: 6 weeks (stored alternately in refrigerator and analyzer at ambient temperature 20-25 C) Up to 20 hr. opened in totaluntil expiration date on the vial label or cumulative 32 hrs at room temperature.
Calibration frequencyAppropriate for maintaining accuracy, comparable to predicateElecsys® 2010 / E170: Once per lot, after one month, after 7 days, controls out of range Elecsys® 1010: With every kit, after 7 days (20-25°C), after 3 days (25-32°C), controls out of rangeEvery 7 days, when changing lot numbers, when replacing system components, when QC results are out of range

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

This information is not provided in the given text. The document refers to "performance characteristics" but does not detail the specific study designs, sample sizes, or data provenance (e.g., retrospective/prospective, country of origin) for the tests conducted to derive these characteristics.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This is a an in vitro diagnostic (IVD) device for quantitative determination of cortisol. The ground truth for such devices is typically established through analytical methods and reference materials, not through expert reading or consensus in the way a diagnostic imaging device would require. Therefore, this question is not applicable in the context of this device and information is not provided.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

As this is an IVD device measuring an analyte, adjudication methods involving human experts (like 2+1 for radiology images) are not applicable. The ground truth is analytical.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

This is an IVD assay, not an AI-powered diagnostic imaging device that assists human readers. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable.

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

The entire device (ELECSYS® Cortisol Assay) operates as a standalone analytical system to quantitatively determine cortisol. The performance characteristics listed (precision, functional sensitivity, measuring range, etc.) represent the standalone performance of the algorithm and associated instrumentation.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

For an in vitro diagnostic assay like the ELECSYS® Cortisol Assay, the "ground truth" for reported performance characteristics such as precision and sensitivity is established through analytical reference methods and certified reference materials. These involve meticulously prepared samples with known concentrations of cortisol, against which the device's measurements are compared. The document does not explicitly state the specific reference methods or materials used but implies their use through the reporting of these analytical performance metrics.

8. The sample size for the training set

This information is not provided. The document is a 510(k) submission for substantial equivalence, which typically focuses on performance data for the final product, not the developmental or training data used in its creation (especially for traditional IVD assays not based on machine learning in the way a modern AI device would be).

9. How the ground truth for the training set was established

As per point 8, information about a "training set" and its ground truth establishment is not provided and likely not relevant in the context of this type of established IVD technology. The development of such assays involves rigorous analytical testing against reference standards, but this is distinct from the machine learning "training set" paradigm.

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1602/218

Introduction
According to the requirements of 21 CFR 807.92, the following information
provides sufficient detail to understand the basis for a determination of
substantial equivalence

Submittername, address,contactRoche Diagnostics Corporation9115 Hague RdIndianapolis IN 46250(317) 521-3831Contact person: Sherri L. CoenenDate prepared: April 16, 2002
Device NameProprietary name: ELECSYS® Cortisol AssayCommon name: Cortisol testClassification name: Fluorometric, cortisol
DevicedescriptionThe ELECSYS® Cortisol Assay a two step sandwich immunoassay withstreptavidin microparticles and electrochemiluminescence detection.Results are determined using a calibration curve that is generated specificallyon each instrument by a 2-point calibration and a master curve provided withthe reagent bar code.

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Intended useImmunological in vitro assay for the quantitative determination of cortisol inhuman serum, plasma and urine.
Indication foruseThe determination of cortisol is used for the recognition and treatment offunctional disorders of the adrenal gland.
SubstantialequivalenceThe ELECSYS Cortisol test is equivalent to other devices legally marketed inthe United States. We claim equivalence to the Bayer Diagnostics ACS:180Cortisol Assay (K962559).

.

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Substantial The following table compares the ELECSYS® Cortisol, with the Predicate equivalence -Devices. similarities

FeatureNew DeviceELECSYS CortisolPredicate DeviceBayer ACS:180 Cortisol
Intended useImmunological in vitro assayfor the quantitativedetermination of cortisol inhuman serum, plasma, andurine. The determination ofcortisol is used for therecognition and treatment offunctional disorders of theadrenal gland.The electrochemiluminescenceimmunoassay "ECLIA" isintended for use on RocheElecsys 1010/2010 andModular Analytics E170(Elecsys module) immunoassayanalyzers.For the quantitativedetermination of cortisol inserum or urine using theChiron DiagnosticsACS:180 AutomaticChemiluminescenceSystems.For In Vitro Diagnostic use.
Sample typeserum, plasma, urineserum, urine
Assay Protocolcompetition assaycompetition assay
DetectionProtocolelectrochemiluminescencedirect chemiluminescence

The following table compares the ELECSYS® Cortisol with the Predicate Substantial equivalence – Device. differences

FeatureNew DeviceELECSYS CortisolPredicate DeviceBayer ACS:180 Cortisol
Measuring range1.0 - 1750 nmol/L5.5 - 2069 nmol/L
Expected valuesUrine36 - 137 ug/24 hrsUrine12.1 - 103.8 ug/24 hrs
InstrumentElecsys immunoassay analyzersACS:180 automatedchemiluminescence system

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Substantial equivalence performance

The performance characteristics of the ELECSYS Cortisol and the Predicate Device are compared in the table below.

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characteristics

FeatureNew DeviceELECSYS CortisolPredicate DeviceBayer ACS:180 Cortisol
Intra-assayprecision (%CV)Urine• 2.2% at 22.3 µg/dl• 2.3% at 33.2 µg/dl• 2.9% at 41.9 µg/dl• 2.3% at 61.0 µg/dl• 5.7% at 3.04 µg/dl• 5.1% at 5.43 µg/dl• 4.5% at 14.90 µg/dl• 6.4% at 18.98 µg/dl• 7.0% at 31.79 µg/dl• 7.5% at 38.67 µg/dl
Interassayprecision (%CV)Urine• 2.5% at 23.2 µg/dl• 3.2% at 33.4 µg/dl• 2.5% at 42.1 µg/dl• 1.8% at 58.9 µg/dlControl• 4.7% at 2.82 µg/dlN/A
Total precision(%CV)N/A• 9.1% at 3.04 µg/dl• 8.0% at 5.43 µg/dl• 6.4% at 14.90 µg/dl• 8.2% at 18.98 µg/dl• 9.2% at 31.79 µg/dl• 9.7% at 38.67 µg/dl

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Substantial equivalence performance characteristics, continued

The performance characteristics of the ELECSYS Cortisol and the Predicate Device are compared in the table below.

FeatureNew DevicePredicate Device
FunctionalsensitivityELECSYS CortisolBayer ACS:180 Cortisol
< 0.29 µg/dl0.2 µg/dl
LimitationsWhen performed in urine, theassay is unaffected by:60 mg/dl protein 750 mmol/l NaCl 350 mmol/l urea 5 mmol/l creatinine 2 mmol/l glucoseWhen performed in urine, theassay is unaffected by:60 mg/dl protein 750 mmol/l NaCl 350 mmol/l urea 5 mmol/l creatinine 2 mmol/l glucose
On-boardstabilityElecsys® 2010 / E170: 6 weeks Elecsys® 1010: 6 weeks(stored alternately in refrigerator and analyzer atambient temperature 20-25 C) Up to 20 hr. opened in totaluntil expiration date on the viallabel or cumulative 32 hrs atroom temperature.

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Substantial equivalence performance characteristics, continued

The performance characteristics of the ELECSYS Cortisol and the Predicate Device are compared in the table below.

FeatureNew DevicePredicate Device
ELECSYS CortisolBayer ACS:180 Cortisol
CalibrationfrequencyElecsys® 2010 / E170:• Once per reagent lot• after one month (usingthe same reagent lot)• after 7 days (using thesame reagent kit on theanalyzer)Elecsys® 1010• With every reagent kit• after 7 days (using thesame reagent kit,ambient temperature 20- 25°C)• after 3 days (using thesame reagent kit,ambient temperature 25- 32°C)• Controls out of range (bothsystems)• every 7 days• when changing lotnumbers of assay reagents• when replacing systemcomponents• when quality controlresults are repeatedly outof range

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Image /page/6/Picture/0 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, with three parallel lines forming the staff and a stylized bird-like shape representing the wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the caduceus.

DEPARTMENT OF HEALTH & HUMAN SERVICES

ood and Drug Administratio 2098 Gaither Road Rockville MD 20850

Ms. Sherri L. Coenen Regulatory Submissions, Centralized Diagnostics Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, IN 46250-0457

9 2002 SEP

Re: K021218 Trade/Device Name: ELECSYS® Cortisol Test System Regulation Number: 21 CFR 862.1205 Regulation Name: Cortisol (hydrocortisone and hydroxycorticosterone) test system Regulatory Class: Class II Product Code: JFT Dated: July 19, 2002 Received: July 23, 2002

Dear Ms. Coenen:

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 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 801); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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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" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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/dsmaldsmamain.html".

Sincerely yours.

Steven Butman

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

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INDICATIONS FOR USE STATEMENT

510(k) Number (if known): N/A

Device Name: ELECSYS® Cortisol Test System

Indications For Use:

Immunological in vitro assay for the quantitative determination of cortisol in human serum, plasma and 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 the Roche Elecsys® 1010 / 2010 and Modular Analytics E170 (Elecsys module) Immunoassay Analyzers.

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K021218

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

Concurrence of CDRH, Office of Device Evaluation (ODE) Prescription Use OR Over-The-Counter Use (Per 21 CFR 801.109) (Optional Format 1-

2-96)

§ 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.