(8 days)
The Elecsys Cortisol is an immunoassay for the in-vitro quantitative determination of cortisol in 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 the Roche Elecsys 1010/2010 and MODULAR ANALYTICS E170 (Elecsys module) immunoassay analyzers.
The Elecsys Cortisol Assay is 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.
Here's an analysis of the acceptance criteria and supporting study for the Elecsys® Cortisol Immunoassay System, based on the provided 510(k) summary:
Device: Elecsys® Cortisol Immunoassay System
1. Table of Acceptance Criteria and Reported Device Performance
The submission focuses on demonstrating substantial equivalence to a predicate device rather than setting explicit acceptance criteria in the way a clinical trial might for a new drug. Instead, it provides performance characteristics of the new device and compares them to the predicate, implying that performance comparable to the predicate (and within acceptable analytical ranges for this type of test) is the "acceptance criteria."
| Feature | Acceptance Criteria (Implied by Predicate Performance / Clinical Acceptability for Cortisol Assays) | Reported Device Performance (Elecsys Cortisol Immunoassay) |
|---|---|---|
| Precision | Comparable to or better than the predicate's intra-assay CVs (4.25% CV @ 1.591 ug/dL, 4.97% CV @ 0.702 ug/dL, 5.73% CV @ 0.188 ug/dL, 5.28% CV @ 0.115 ug/dL) and generally acceptable for quantitative immunoassays. | Within-run (E2010):6.1% CV @ 0.170 ug/dL2.7% CV @ 0.417 ug/dL4.0% CV @ 0.547 ug/dL1.5% CV @ 0.576 ug/dL2.8% CV @ 0.718 ug/dLBetween Run:37.1% CV @ 0.034 ug/dL (Note: sample concentration below functional claim of assay)7.2% CV @ 0.280 ug/dL6.2% CV @ 0.613 ug/dL4.9% CV @ 1.25 ug/dL4.1% CV @ 1.54 ug/dL |
| Functional Sensitivity | Clinically relevant detection limit for cortisol in saliva. The predicate did not explicitly state this, but a value < 2.0 nmol/L (< 0.07 ug/dL) is generally considered good for salivary cortisol. | < 2.0 nmol/L (< 0.07 ug/dL) |
| Analytical Sensitivity (LDL) | Comparable to or better than the predicate's LDL (< 0.007 ug/dL) and sufficient for accurate measurement at low physiological levels. | < 0.500 nmoL/L (< 0.018 ug/dL) |
| Method Comparison (Correlation) | Strong correlation (high 'r' value, ideally > 0.9) and good agreement (slope close to 1, intercept close to 0) between the new device and the predicate device across a clinically relevant range of concentrations. | Elecsys Cortisol vs. Salimetrics:Slope = 0.90 (95% CI 0.87-0.94)Intercept= 1.71 (95% CI 1.47-1.96)r= 0.942 |
| Measuring Range | Adequate to cover both normal and pathological cortisol levels. For Elecsys, the range is 1.00 - 1750 nmol/L (0.036 - 63 ug/dL). The predicate's calibrator range was 0.007-1.800 ug/dl. The Elecsys measured range is significantly wider. | 1.00 - 1750 nmol/L (0.036 - 63 ug/dL) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Method Comparison): 326 samples
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It is implied to be a direct comparison of patient samples run on both systems.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of immunoassay does not typically involve expert readers for establishing ground truth in the way medical imaging devices do. The "ground truth" for the method comparison is the measurement obtained from the predicate device (Salimetrics HS Salivary Cortisol Enzyme). The results are compared statistically, not against a human interpretation.
4. Adjudication Method for the Test Set
Not applicable for this type of quantitative immunoassay comparison. Adjudication is typically used in subjective interpretation tasks (e.g., radiology readings) to reconcile differing expert opinions. Here, the comparison is direct numerical data.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC study was not done. MRMC studies are relevant for devices that involve human interpretation, often assisted by AI, to assess the impact of the device on human performance. This is a standalone quantitative assay.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
Yes, the device is a standalone quantitative immunoassay platform. Its performance characteristics (precision, sensitivity, method comparison) are inherently "standalone," meaning they represent the device's performance without human interpretive intervention.
7. The Type of Ground Truth Used
For the method comparison, the "ground truth" was the results obtained from the predicate device (Salimetrics HS Salivary Cortisol Enzyme). For other performance metrics like precision and sensitivity, the ground truth is established through standard laboratory practices using known controls and calibrators, often with traceability to a reference method (e.g., ID-MS for the Elecsys Cortisol).
8. The Sample Size for the Training Set
The document does not specify a separate "training set" in the context of machine learning or AI. For immunoassay development, there are typically reagent optimization phases and validation studies that involve numerous samples and controls, but these are not usually referred to as "training sets" in the same way as in AI/ML development. The provided data for method comparison is a validation dataset.
9. How the Ground Truth for the Training Set Was Established
As there's no explicitly defined "training set" in the AI/ML sense, this question is not directly applicable. If considering the development and optimization of the immunoassay itself, the "ground truth" would be established using reference materials, calibrators, and possibly samples with known cortisol concentrations (e.g., measured by ID-MS or another highly accurate reference method).
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K043175
NOV 2 4 2004
510(k) Summary
According to the requirements of 21 CFR 807.92, the following information Introduction provides sufficient detail to understand the basis for a determination of substantial equivalence. Roche Diagnostics Submitter name, address, 9115 Hague Road contact Indianapolis, IN 46250 (317) 521-3544 Contact Person: Kay A. Taylor Device Name Proprietary name: Elecsys® Cortisol Immunoassay System Common name: Cortisol Test Classification name: Fluorometic, cortisol The Elecsys Cortisol Assay is a two step sandwich immunoassay with Device Description 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. Intended use For the in vitro quantitative determination of cortisol in human serum, plasma, urine and saliva. Note: Serum and plasma cleared under K000270 and urine cleared under K021218. Indications for The determination of cortisol is used for the recognition and treatment of Use functional disorders of the adrenal gland.
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510(k) Summary, Continued
| Substantialequivalence | The Elecsys Cortisol Immunoassay is substantially equivalent to otherdevices legally marketed in the United States. We claim equivalence to theSalimetrics HS (high sensitivity) Salivary Cortisol Enzyme cleared underK011323. Both products are intended for use in the quantitativedetermination of cortisol in human saliva. |
|---|---|
| ---------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
Substantial The following table compares the Roche Elecsys Cortisol Immunoassay with equivalence the predicate device. comparison
| Feature | Elecsys Cortisol Immunoassay | HS Salivary Cortisol Enzyme(predicate) |
|---|---|---|
| Intended Use | For the in-vitro quantitativedetermination of cortisol inserum, plasma, urine and saliva. | For the in vitro quantitativedetermination of cortisol insaliva. |
| Indication for Use | The determination of cortisol isused for the recognition andtreatment of functional disordersof the adrenal gland. | Used to measure adrenalcortical function and as a screenfor Cushing's and Addison'sdisease. Saliva cortisolaccurately reflects the amountof serum cortisol in thecirculation. |
| Assay Protocol | ElectrochemiluminescentImmunoassay | Competitive Solid PhaseImmunoassay |
| Traceability /Standardization | Enzymun Test Cortisol, in turnstandardized viaID-MS. | N/A |
| Calibration Interval | E170/E2010After 1 month when using thesame reagent lot After 7 days when using thesame reagent kit E1010 With every reagent kit After 7 days (20-25°C) After 3 days (25-32°C) | N/A |
| Sample Type | Serum, plasma, urine & saliva | Saliva |
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| Feature | Elecsys Cortisol Immunoassay | HS Salivary Cortisol Enzyme(predicate) |
|---|---|---|
| Sample CollectionMethod | Salivettes (Sarstedt) | Salivettes (Sarstedt) |
| Reagent Stability | Unopened at 2-8°C• Up to stated expirationOpened• 12 weeks at 2-8°• 8 weeks on E170/ 2010• 2 weeks on E1010 (20-25°ambient temp - up to 20hours opened in total) | Stable at 2-8°C until kitexpiration date |
| Controls | Elecsys PreciControl Universal 1and 2 | Cortisol Controls |
| Calibrator | Elecsys Cortisol CalSet | Cortisol Standards |
| Measuring Range | 1.00 - 1750 nmol/L(0.036 - 63 ug/dL) | Calibrator range0.007-1.800 ug/dl |
| Instrument | Elecsys family of analyzers(Elecsys 1010, Elecsys 2010 andElecsys E170 MODULARAnalytics ImmunoassayAnalyzers) | Standard plate reader |
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| Expected Values | ||
|---|---|---|
| Morning hours 8-10 AM:1.90 – 19.1 nmol/L | Neonatal0.010-3.606 ug/dl | |
| Afternoon hours 2:30-3:30 PM:2.05 – 11.9 nmol/L | Age 6 months0.010-2.890 ug/dl | |
| Age 2.5-5.5 yearsAM: 0.060-0.700 ug/dlPM: 0.08-0.660 ug/dl | ||
| Age 8-11 yearsAM: 0.112-0.904 ug/dlPM: ND-0.249 ug/dl | ||
| Age 12-18 yearsAM: 0.046-0.950 ug/dlPM: ND-0.296 ug/dl | ||
| Age 21-30 years, malesAM: 0.112-0.743 ug/dlPM: ND-0.308 ug/dl | ||
| Age 21-30 years, femalesAM: 0.272-1.348 ug/dlPM: ND-0.359 ug/dl | ||
| Age 31-50 years, malesAM: 0.122-1.551 ug/dlPM: ND – 0.359 ug/dl | ||
| Age 31-50 years, femalesAM: 0.094-1.515 ug/dlPM: ND-0.181 ug/dl | ||
| Age 51-70 years, malesAM: 0.112-0.812 ug/dlPM: ND - 0.228 ug/dl | ||
| Age 51-70 years, femalesAM: 0.149-0.739 ug/dlPM: 0.022-0.254 ug/dl | ||
| All AdultsAM: 0.094-1.551 ug/dlPM: ND-0.359 ug/dlND=none detected | ||
| Normal 0.004-0.116 ug/dl | ||
| Cushing's 0.141-9.170 ug/dl |
.
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510(k) Summary, Continued
The performance characteristics of the Elecsys Cortisol Immunoassay and the Substantial predicate device are compared in the table below. equivalence – performance characteristics
| Feature | Elecsys Cortisol Immunoassay | HS Salivary Cortisol Enzyme (predicate) |
|---|---|---|
| Precision | E2010Within-run6.1% CV @ 0.170 ug/dL2.7% CV @ 0.417 ug/dL4.0% CV @ 0.547 ug/dL1.5% CV @ 0.576 ug/dL2.8% CV @ 0.718 ug/dLBetween Run*37.1% CV @ 0.034 ug/dL7.2% CV @ 0.280 ug/dL6.2% CV @ 0.613 ug/dL4.9% CV @ 1.25 ug/dL4.1% CV @ 1.54 ug/dL*sample concentration below functional claim of assay. | Intra-assay4.25% CV @ 1.591 ug/dL4.97% CV @ 0.702 ug/dL5.73% CV @ 0.188 ug/dL5.28% CV @ 0.115 ug/dL |
| FunctionalSensitivity | < 2.0 nmol/L (< 0.07 ug/dL ) | N/A |
| Analyticalsensitivity (LDL) | < 0.500 nmoL/L (< 0.018 ug/dL) | < 0.007ug/dL |
| MethodComparison | Elecsys Cortisol vs. Salimetrics326 samples (0.05-1.83 ug/dl)Slope = 0.90 (95% CI 0.87-0.94)Intercept= 1.71 (95% CI 1.47-1.96)r= 0.942 | N/A |
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of a human figure embracing a globe.
NOV 2 4 2004
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Kay A. Taylor, MT (ASCP), RAC Regulatory Program Principal, Regulatory Affairs Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, IN 46250-0457
K043175 Re:
Trade/Device Name: Elecsys Cortisol Regulation Number: 21 CFR 862.1205 Regulation Name: Coristol (hydrocortisone and hydroxycorticosterone) Test System Regulatory Class: Class II Product Code: NHG Dated: November 9, 2004 Received: November 16, 2004
Dear Ms. Taylor:
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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act 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/dsma/dsmamain.html.
Sincerely yours,
Sincerely yours,
Cornelius B. Parks
Cornelia B. Rooks, MA Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
K043175 510(k) Number (if known):
Device Name: Elecsys Cortisol
Indications For Use:
The Elecsys Cortisol is an immunoassay for the in-vitro quantitative determination of cortisol in 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 the Roche Elecsys 1010/2010 and MODULAR ANALYTICS E170 (Elecsys module) immunoassay analyzers.
Prescription Use
(Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Carol C. Benar
Division Sign-Off
sion Sign-
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K043175
Page 1 of 1
§ 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.