K Number
K152227
Device Name
Elecsys Cortisol II, Cortisol II CalSet
Manufacturer
Date Cleared
2016-04-27

(264 days)

Product Code
Regulation Number
862.1205
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended Use
Immunoassay for the in vitro quantitative determination of cortisol in human serum, and plasma. 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 Elecsys and cobas e immunoassay analyzers. Cortisol II CalSet is used for calibrating the quantitative Elecsys Cortisol II assay on the Elecsys and cobas e immunoassay analyzers.
Device Description
The Elecsys Cortisol II assay makes use of a competition test principle using a monoclonal antibody which is specifically directed against cortisol. Endogenous cortisol which has been liberated from binding proteins with danazol competes with exogenous cortisol derivative in the test which has been labeled with ruthenium complex for the binding sites on the biotinylated antibody. Results are determined via a calibration curve which is instrument specifically generated by 2point calibration and a master curve provided via reagent barcode. The reagent working solutions include: - rackpack (kit placed on instrument) . - Streptavidin coated microparticles, ş - Reagent 1 (Anti-cortisol-Ab~biotin) and ş - Reagent 2 (Cortisol-peptide~Ru(bpy)2+3). ş The Cortisol II CalSet is a lyophilized human serum with added cortisol in two concentration ranges. The CalSet includes: - Cal 1 (approximately 12.5 nmol/L cortisol in a human serum matrix) . - Cal 2 (approximately 1000 nmol/L cortisol in a human serum matrix) .
More Information

No
The description details a standard immunoassay using chemical reactions and a calibration curve for quantitative determination. There is no mention of AI or ML in the device description, intended use, or performance studies.

No.
This device is an in vitro diagnostic (IVD) immunoassay that quantitatively measures cortisol levels in human serum and plasma. It aids in the recognition and treatment of adrenal gland disorders but does not directly deliver therapy or perform a therapeutic function on the patient.

Yes

This device is a diagnostic device because its intended use is for the quantitative determination of cortisol in human serum and plasma, which is explicitly stated to be "used for the recognition and treatment of functional disorders of the adrenal gland." This directly indicates its role in diagnosing medical conditions.

No

The device is an immunoassay kit and calibrator used on specific immunoassay analyzers, which are hardware devices. The description details chemical reagents and their interaction, not solely software functionality.

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

  • Intended Use: The "Intended Use / Indications for Use" section explicitly states "Immunoassay for the in vitro quantitative determination of cortisol in human serum, and plasma." The phrase "in vitro" is a key indicator of an IVD.
  • Sample Type: The device analyzes human serum and plasma, which are biological specimens taken from the body.
  • Purpose: The determination of cortisol is used for the "recognition and treatment of functional disorders of the adrenal gland," indicating a medical purpose for diagnosis and monitoring.
  • Device Description: The description details reagents and a calibration set used to perform the assay on specific immunoassay analyzers. This aligns with the components of an IVD system.
  • Performance Studies: The document includes summaries of performance studies like precision, linearity, analytical specificity, and method comparison, which are standard evaluations for IVD devices to demonstrate their analytical performance.
  • Predicate Device: The mention of a predicate device (K070788 Elecsys Cortisol) further confirms its classification as a medical device, specifically an IVD, as predicate devices are used for comparison in regulatory submissions for new IVDs.

N/A

Intended Use / Indications for Use

Immunoassay for the in vitro quantitative determination of cortisol in human serum, and plasma. 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 Elecsys and cobas e immunoassay analyzers.

Cortisol II CalSet is used for calibrating the quantitative Elecsys Cortisol II assay on the Elecsys and cobas e immunoassay analyzers.

Product codes (comma separated list FDA assigned to the subject device)

JFT, JIT

Device Description

The Elecsys Cortisol II assay makes use of a competition test principle using a monoclonal antibody which is specifically directed against cortisol. Endogenous cortisol which has been liberated from binding proteins with danazol competes with exogenous cortisol derivative in the test which has been labeled with ruthenium complex for the binding sites on the biotinylated antibody. Results are determined via a calibration curve which is instrument specifically generated by 2point calibration and a master curve provided via reagent barcode.

The reagent working solutions include:

  • rackpack (kit placed on instrument) .
  • Streptavidin coated microparticles, ş
  • Reagent 1 (Anti-cortisol-Ab~biotin) and ş
  • Reagent 2 (Cortisol-peptide~Ru(bpy)2+3). ş

The Cortisol II CalSet is a lyophilized human serum with added cortisol in two concentration ranges. The CalSet includes:

  • Cal 1 (approximately 12.5 nmol/L cortisol in a human serum matrix) .
  • Cal 2 (approximately 1000 nmol/L cortisol in a human serum matrix) .

Mentions image processing

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Mentions AI, DNN, or ML

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Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

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Description of the training set, sample size, data source, and annotation protocol

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Description of the test set, sample size, data source, and annotation protocol

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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Precision (Human Serum):

  • Study Type: Precision study evaluated according to CLSI EP5-A2 guideline.
  • Sample Size: 2 replicates each of controls (PC Universal) and 5 human serum samples (HS) per run, 2 runs per day for 21 days.
  • Data Source: Native, diluted, and spiked human serum pools.
  • Key Results: Repeatability and Intermediate precision were calculated.

Limit of Blank (LoB):

  • Study Type: Analytical sensitivity study.
  • Sample Size: n = 60 LoB measurements (5 blank samples, 1 replicate, 2 runs per day on 2 instruments over 3 days).
  • Data Source: Native human serum pools and Universal Diluent.
  • Annotation Protocol: LoB was calculated according to CLSI EP17-A2 (non-parametric approach).

Limit of Detection (LoD):

  • Study Type: Analytical sensitivity study.
  • Sample Size: n = 60 LoD measurements (5 samples, 2 runs per day on 2 instruments over 3 days).
  • Data Source: 5 low-level human serum samples (diluted).
  • Annotation Protocol: LoD was calculated according to CLSI EP17-A2.

Limit of Quantitation (LoQ):

  • Study Type: Analytical sensitivity study.
  • Sample Size: Replicates of 2 per sample, two runs per day over 3 days.
  • Data Source: Set of nine human serum samples, three reagent lots.
  • Annotation Protocol: LoQ was determined in accordance with CLSI Guideline EP17-A2.

Linearity (Serum):

  • Study Type: Linearity study according to CLSI EP6-A.
  • Data Source: High analyte serum sample (pooled human serum sample, spiked) diluted with Diluent Universal (protein matrix). 19 concentrations (17 dilutions).
  • Annotation Protocol: Samples assayed in 3-fold determination within a single run. Data analyzed for linear, quadratic, and cubic polynomials.

Linearity (Plasma):

  • Study Type: Linearity study according to CLSI EP6-A.
  • Data Source: High analyte plasma sample (pooled human plasma sample, spiked) diluted with Diluent Universal (protein matrix). 19 concentrations (17 dilutions).
  • Annotation Protocol: Samples assayed in 3-fold determination within a single run. Data analyzed for linear, quadratic, and cubic polynomials.

Analytical Specificity (Serum/Plasma):

  • Study Type: Specificity determination.
  • Data Source: Two human serum sample pools (diluted and spiked) spiked with potential cross-reactant compounds.
  • Annotation Protocol: Analyte concentrations at approx. 60 and 300 µg/L Cortisol. Spiked and non-spiked samples tested in duplicates.

Endogenous Interferences:

  • Study Type: Effect of endogenous interfering substances on analyte quantitation.
  • Data Source: Human serum samples (single samples and pools, native, diluted and spiked).
  • Annotation Protocol: For each interfering substance, three human serum samples containing low, mid, and high concentrations of Cortisol were tested. Recovery calculated by comparison to reference sample.

HASA Effect (Human Anti-Sheep Antibodies):

  • Study Type: Assessment of HASA effect.
  • Data Source: Model system using donkey anti-sheep polyclonal antibodies (DASA) on two serum samples with cortisol concentrations of 173 and 789 nmol/L.
  • Annotation Protocol: Aliquots spiked with DASA and diluted in 10% increments. Recovery calculated by comparison to unspiked reference sample.

Exogenous Interferences - Drugs:

  • Study Type: Effect of drugs on analyte quantitation.
  • Data Source: Samples spiked with 16 pharmaceutical compounds into two human serum samples (native, diluted, and spiked human serum pools as well as single samples).
  • Annotation Protocol: Analyte concentrations approximately 170 and 750 nmol/L. Drug concentrations in accordance with CLSI guideline EP7-A2. Cortisol II concentration determined in 3-fold determination and compared to reference aliquot.

Exogenous Interferences - Anticoagulants:

  • Study Type: Effect of anticoagulants on analyte quantitation.
  • Data Source: Samples drawn into Serum, Li-Heparin, K2-EDTA-, K3-EDTA-plasma primary tubes and Li-Heparin Plasma Gel Separation Tubes. A minimum of 48 serum/plasma pairs per sample material.
  • Annotation Protocol: Tested in duplicate with one reagent lot. Potential effects assessed by regression analysis.

Method Comparison 1: Elecsys Cortisol II vs. LC-MS (Reference Method):

  • Study Type: Correlation study.
  • Sample Size: 208 human serum samples (native single donors).
  • Data Source: LC-MS method at UZ Gent, Lab voor Klinische Biologie (Gent, Belgium).
  • Annotation Protocol: Samples measured in singleton, covering entire measuring range.

Method Comparison 2: Elecsys Cortisol II vs. Cortisol I (K070788):

  • Study Type: Correlation study.
  • Sample Size: 536 human serum samples (native single donors).
  • Data Source: UZ Gent, LMU Großhadern, Uni Klinik Leipzig and Labor Limbach.

Reagent Stability Study 1 (onboard, 8 weeks):

  • Study Type: Reagent stability.
  • Data Source: Five human serum (HS) samples and two controls (native, diluted, and spiked).
  • Annotation Protocol: Rackpack calibrated, samples measured, rackpack stored at 20°C + 3°C. Samples measured on day 8, 36, and 64 using established calibration curves.

Reagent Stability Study 2 (after first opening at 2-8°C, 84 days):

  • Study Type: Reagent stability.
  • Data Source: Five human serum (HS) samples and two controls (native, diluted, and spiked).
  • Annotation Protocol: Rackpack calibrated, samples measured, kit stored at 2-8 °C. Kit placed on analyzer on day 29, 57, and 92, calibrated, and test samples determined.

Sample Stability Study 1 (2-8°C):

  • Study Type: Sample stability.
  • Data Source: Twelve human serum, Li-Heparin, K2-EDTA, and K3-EDTA plasma samples (native, spiked, and diluted single donors).
  • Annotation Protocol: Aliquoted and measured fresh (reference) and after storage at 2-8°C for 4 days. Measurements performed with three-fold determination.

Sample Stability Study 2 (Room Temperature 15-25°C):

  • Study Type: Sample stability.
  • Data Source: Twelve human serum, Li-Heparin, K2-EDTA, and K3-EDTA plasma samples (native, spiked, and diluted single donors).
  • Annotation Protocol: Aliquoted and measured fresh (reference) and after storage at 20-25°C for 24 hours. Measurements performed with three-fold determination.

Sample Stability Study 3 (-15 to -25°C):

  • Study Type: Sample stability.
  • Data Source: Twelve human serum, Li-Heparin, K2-EDTA, and K3-EDTA plasma samples (native, spiked, and diluted single donors).
  • Annotation Protocol: Aliquoted and measured fresh (reference) and after storage for 12 months at -15 to -25°C. Measurements performed with three-fold determination.

Calibration Stability Study 1 (Lot calibration stability):

  • Study Type: Calibration stability.
  • Data Source: Five human serum (HS) samples and two control samples (native, diluted, and spiked).
  • Annotation Protocol: Elecsys Cortisol II calibrated with fresh reagent kit on Day 1. After 29, 57, and 92 days, a new kit of the same lot was used and recovery determined using Day 1 curve. Each sample tested with two-fold determination.

Calibration Stability Study 2 (On-board calibration stability):

  • Study Type: Calibration stability.
  • Data Source: Five human serum (HS) samples and two control samples (native, diluted, and spiked).
  • Annotation Protocol: Fresh Reagent Rack-Pack calibrated. All samples measured on Day 1. On Day 8, same samples measured with same reagent kit kept at 20°C + 3°C using Day 1 calibration curves. Each sample tested with two-fold determination.

Calibrator Studies - Value Assignment:

  • Study Type: Value assignment testing.
  • Annotation Protocol: Calibrators run in duplicate on at least three (3) cobas e 411 analyzers and at least three (3) cobas e 601/cobas e 602/MODULAR ANALYTICS E170 analyzers with all Cortisol II reagent lots available. Assigned value is mean value obtained over at least six (6) runs on at least three (3) analyzers. Pre-defined acceptance criteria for PreciControl Universal met.

Calibrator Studies - Reconstitution:

  • Study Type: Reconstitution time testing.
  • Data Source: Two sets of Cortisol II CalSet.
  • Annotation Protocol: One set reconstituted for 15 minutes, other for 30 minutes. Signal recovery after 30 minutes compared to 15 minutes. Evaluated in duplicate.

Calibrator Studies - Stability at -20°C (after reconstitution):

  • Study Type: CalSet stability.
  • Data Source: On-test and reference materials.
  • Annotation Protocol: On-test material reconstituted and stored in closed vials for 3 months at -20°C. Signal recovery calculated as percent of reference value.

Calibrator Studies - Onboard Stability at 20-25°C after reconstitution:

  • Study Type: CalSet stability.
  • Data Source: On-test and reference materials.
  • Annotation Protocol: On-test material reconstituted and stored in open vials for 4 hours at 20-25°C. Signal recovery calculated as percent of reference value.

Calibrator Studies - Real-time Stability:

  • Study Type: Real-time stability (using predicate device data).
  • Annotation Protocol: Cortisol CalSet on-test material stored at 2 - 8°C. Tested at specified intervals over shelf life. Data for time-points after manufacturing, 7, 6, 14, 13, and 19 months tested in duplicate. Stability assessed via accurate recovery of PreciControl Universal.

Clinical Performance Evaluation:

  • Study Type: Reference range establishment.
  • Sample Size: Not specified, but collected at three sites in the United States.
  • Data Source: Native human serum samples from self-reported healthy males and females.
  • Annotation Protocol: Samples measured in singleton, over 2 runs within 10 days. Reference ranges determined using median value, 5th - 95th and 2.5th - 97.5th percentiles.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Key metrics for the Elecsys Cortisol II assay from table 1:

  • Precision: Within-run CV ranged from 1.8% to 7.1%. Total CV ranged from 2.5% to 12.7%.
  • Analytical Sensitivity: Limit of Blank (LoB) = 1.0 nmol/mL, Limit of Detection (LoD) = 1.5 nmol/mL, Limit of Quantitation (LoQ) = 3.0 nmol/mL.
  • Measuring Range: 3.0 - 1750 nmol/L.
  • Linearity: 3.0 to 1750 nmol/mL.

Key metrics for the Predicate Device: Elecsys Cortisol assay from table 1:

  • Precision: Within-run CV ranged from 1.0% to 1.4%. Total CV ranged from 1.4% to 1.6%.
  • Analytical Sensitivity: Limit of Detection =

§ 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.

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Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. In the center of the circle is a stylized image of three human profiles facing to the right, stacked on top of each other.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

April 27, 2016

ROCHE DIAGNOSTICS KELLI TÜRNER REGULATORY AFFAIRS PRINCIPAL 9115 HAGUE ROAD INDIANAPOLIS IN 46250

Re: K15227

Trade/Device Name: Elecsys Cortisol II. Cortisol II CalSet Regulation Number: 21 CFR 862.1205 Regulation Name: Cortisol (hydrocortisone and hydroxycorticosterone) test system Regulatory Class: II Product Code: JFT, JIT Dated: March 24, 2016 Received: March 25, 2016

Dear Ms. Kelli Turner:

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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

1

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Katherine Serrano -S

For:

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

2

Indications for Use

510(k) Number (if known) K152227

Device Name Elecsys Cortisol II

Indications for Use (Describe)

Immunoassay for the in vitro quantitative determination of cortisol in human serum, and plasma. 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 Elecsys and cobas e immunoassay analyzers.

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

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known)

K152227

Device Name Cortisol II CalSet

Indications for Use (Describe)

Cortisol II CalSet is used for calibrating the quantitative Elecsys Cortisol II assay on the Elecsys and 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."

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

4

510(k) Summary

(K152227)

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

Submitter NameRoche Diagnostics
Address9115 Hague Road
Indianapolis, IN 46250
ContactKelli Turner
Phone: (317) 521-4515
FAX: (317) 521-3080
Email: kelli.turner@roche.com
Date Prepared04/22/2016
Proprietary Name1) Elecsys Cortisol II
  1. Cortisol II CalSet |
    | Common Name | 1) Cortisol II immunoassay
  2. Cortisol II CalSet |
    | Classification Name | 1) Enzyme Immunoassay, Cortisol
  3. Secondary, calibrator |
    | Product Codes | 1) JFT, 862.1205
  4. JIT, 862.1150 |
    | Predicate Devices | Elecsys Cortisol (K070788)
    Elecsys Cortisol CalSet (K070788) |
    | Establishment Registration | Roche Diagnostics GmbH in Mannheim, Germany, is 9610126
    Roche Diagnostics GmbH in Penzberg, Germany, is 9610529
    Roche Diagnostics in the United States is 1823260 |

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1. DEVICE DESCRIPTION

The Elecsys Cortisol II assay makes use of a competition test principle using a monoclonal antibody which is specifically directed against cortisol. Endogenous cortisol which has been liberated from binding proteins with danazol competes with exogenous cortisol derivative in the test which has been labeled with ruthenium complex for the binding sites on the biotinylated antibody.

Results are determined via a calibration curve which is instrument specifically generated by 2point calibration and a master curve provided via reagent barcode.

1.1. Reagents

The reagent working solutions include:

  • rackpack (kit placed on instrument) .
    • Streptavidin coated microparticles, ş
    • Reagent 1 (Anti-cortisol-Ab~biotin) and ş
    • Reagent 2 (Cortisol-peptide~Ru(bpy)2+3). ş

Calibrator 1.2.

The Cortisol II CalSet is a lyophilized human serum with added cortisol in two concentration ranges.

The CalSet includes:

  • Cal 1 (approximately 12.5 nmol/L cortisol in a human serum matrix) .
  • Cal 2 (approximately 1000 nmol/L cortisol in a human serum matrix) .

6

2. INDICATIONS FOR USE

2.1. Immunoassay

Immunoassay for the in vitro quantitative determination of cortisol in human serum, and plasma. 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 Elecsys and cobas e immunoassay analyzers.

2.2. Calibrator

Cortisol II CalSet is used for calibrating the quantitative Elecsys Cortisol II assay on the Elecsys and cobas e immunoassay analyzers.

TECHNOLOGICAL CHARACTERISTICS 3.

Table 1:Assay Comparison
------------------------------
Assay Comparison
FeaturePredicate Device: Elecsys Cortisol
(K070788)Candidate Device: Elecsys Cortisol II
General Assay Features

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Assay Comparison
Intended Use/
Indications
for UseImmunoassay for the in vitro quantitative
determination of cortisol in human serum,
plasma, urine and saliva. 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
Elecsys and cobas e immunoassay
analyzers.Immunoassay for the in vitro quantitative determination of cortisol in
human serum, and plasma. 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 Elecsys and cobas e immunoassay analyzers.
Assay
ProtocolThe Elecsys Cortisol assay makes use of a
competition test principle using a polyclonal
antibody which is specifically directed
against cortisol. Endogenous cortisol which
has been liberated from binding proteins with
danazol competes with exogenous cortisol
derivative in the test which has been labeled
with ruthenium complex for the binding sites
on the biotinylated antibody.The Elecsys Cortisol II assay makes use of a competition test
principle using a monoclonal antibody which is specifically directed
against cortisol. Endogenous cortisol which has been liberated from
binding proteins with danazol competes with exogenous cortisol
derivative in the test which has been labeled with ruthenium
complex for the binding sites on the biotinylated antibody.
Detection
ProtocolElectrochemiluminescent AssayElectrochemiluminescent Assay.
Applications18 minute application18 minute application.
Instrument
PlatformElecsys 1010, Elecsys 2010, MODULAR
ANALYTIC E170 and cobas e analyzers.cobas e 411
Sample
Volume20 µL10 µL.
Sample
TypeHuman serum, plasma, saliva and urine.Human serum, and plasma.

8

Assay Comparison
ReagentsM Streptavidin-coated microparticles:
Streptavidin-coated microparticles;
preservative.
R1 Anti-cortisol-Ab~biotin: Biotinylated
polyclonal anti-cortisol antibody (ovine);
danazol; MES buffer; preservative.
R2 Cortisol-peptide~Ru(bpy): Cortisol
derivative (synthetic), labeled with ruthenium
complex; danazol; MES buffer; preservative.M Streptavidin-coated microparticles: Streptavidin-coated
microparticles; preservative.
R1 Anti-cortisol-Ab~biotin: Biotinylated monoclonal anti-cortisol
antibody (ovine); danazol; MES buffer; preservative.
R2 Cortisol-peptide~Ru(bpy): Cortisol derivative (synthetic),
labeled with ruthenium complex; danazol; MES buffer;
preservative.
CalibratorElecsys Cortisol CalSetElecsys Cortisol II CalSet
Calibration
IntervalCalibration must be performed once per
reagent lot using fresh reagent (i.e. not more
than 24 hours since the reagent kit was
registered on the analyzer). Renewed
calibration is recommended as follows:
After 28 days when using the same
reagent lot.
After 7 days (when using the same
reagent kit on the analyzer).
As required: e.g. quality control findings
outside the defined limitsCalibration must be performed once per reagent lot using fresh
reagent (i.e. not more than 24 hours since the reagent kit was
registered on the analyzer). Renewed calibration is recommended
as follows:
After 8 weeks when using the same reagent lot.
After 7 days (when using the same reagent kit on the analyzer).
As required: e.g. quality control findings outside the defined
limits
ControlsElecsys PreciControl UniversalElecsys PreciControl Universal
Traceability /
Standardizati
onstandardized against the Enzymun-Test
Cortisol method.Standardized against the IRMM (Institute for Reference Materials
and Measurements)/IFCC 451 panel (ID GC/MS, isotope dilution-
gas chromatography/mass spectrometry).
Reagent
StabilityWhen stored and handled as directed,
reagents are stable until the expiration date.
After Opening at 2-8°C - 30 days
On the Analyzers - 30 daysUnopened: 2-8°C - Up to the stated expiration date.
After Opening at 2-8°C - 12 weeks
On the Analyzers – 8 weeks
Measuring
Range0.5 – 1750 nmol/L3.0- 1750 nmol/L

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Assay Comparison
PrecisionElecsys 2010/cobas e 411:
Within-runcobas e 411:
Serum
Within-run (will be labeled Repeatability)
Sample Mean (nmol/L) SD %CV HS 1 208 2.76 1.3 HS 2 561 7.40 1.3 HS 3 1268 14.0 1.1 PCU* 1 363 5.08 1.4 PCU* 2 865 8.54 1.0Sample Mean (nmol/L) SD CV HS 1 3.09 0.219 7.1% HS 2 35.8 0.718 2.0% HS 3 283 7.29 2.6% HS 4 548 10.4 1.9% HS 5 1592 29.3 1.8% PCU* 1 308 4.33 1.4% PCU* 2 719 10.4 1.4%
Total Sample Mean (µg/dL) SD %CV HS 1 208 3.29 1.6 HS 2 561 8.36 1.5 HS 3 1268 19.9 1.6 PCU* 1 363 5.67 1.6 PCU* 2 865 12.5 1.4 *PreciControl UniversalTotal (will be labeled Intermediate precision) Sample Mean (nmol/L) SD CV HS 1 3.09 0.392 12.7% HS 2 35.8 1.36 3.8% HS 3 283 9.39 3.3% HS 4 548 17.4 3.2% HS 5 1592 42.7 2.7% PCU* 1 308 8.35 2.7% PCU* 2 719 18.0 2.5% *PreciControl Universal
Analytical
SensitivityLimit of Detection =