(197 days)
Immunoassay 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.
Elecsys Cortisol CalSet is used for calibrating the quantitative Elecsys Cortisol assay on the Elecsys immunoassay analyzers.
(1) The Elecsys Cortisol Assay is a two step competitive 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.
(2) The Elecsys Cortisol CalSet is a lyophilized product consisting of human serum with added cortisol (synthetic) in two concentration ranges. During manufacture, the analyte is spiked into the matrix at the desired concentration levels.
The provided text describes a 510(k) summary for the Elecsys Cortisol Test System (K070788), a modified device, comparing it to a predicate device (K043175). The key modifications appear to be the addition of new platforms (cobas e 411 and cobas e 601 analyzers) and some refined details regarding sensitivity and expected values for saliva.
Since this is an in-vitro diagnostic (IVD) device, the acceptance criteria are related to analytical performance characteristics rather than clinical outcomes or diagnostic accuracy in the way a medical imaging AI would be. The "study" mentioned isn't a single large clinical trial in the traditional sense, but rather a series of analytical performance evaluations summarized in the comparison tables.
Here's a breakdown of the requested information based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the performance of the predicate device (K043175), with the modified device (K070788) aiming to demonstrate "substantial equivalence." The table below highlights key performance characteristics where data or changes are specifically mentioned. For many features, the modified device performance is simply stated as "Same" as the predicate.
| Acceptance Criteria Category | Specific Metric | Predicate Device (K043175) Performance | Modified Device (K070788) Performance |
|---|---|---|---|
| Measuring Range | Lower limit | 1.00 nmol/L or 0.036 µg/dL (defined by LDL) | 1.00 nmol/L or 0.036 µg/dL (defined by LoD) |
| Upper limit | 1750 nmol/L or 63 µg/dL (max of master curve) | 1750 nmol/L or 63.0 µg/dL (max of master curve) | |
| Values below detection | < 1.0 nmol/L (<0.036 µg/dL) | < 0.50 nmol/L (< 0.018 µg/dL) (Limit of Blank) | |
| Sensitivity | Analytical (LDL) | < 0.500 nmol/L | ≤ 0.5 nmol/L (LoB) |
| Functional | < 2.0 nmol/L | < 1.0 nmol/L (LoD) | |
| Limit of Quantitation | Not explicitly detailed | 8.5 nmol/L (LoQ) | |
| Precision (Saliva) | Within-run CV @ various concentrations | 6.1% CV @ 4.68 nmol/L, 2.7% CV @ 11.5 nmol/L, etc. | SAME |
| Between-run CV @ 0.93 nmol/L | 37.1% CV @ 0.93 nmol/L | 33.4% CV @ 2.08 nmol/L | |
| Between-run CV @ 7.72 nmol/L | 7.2% CV @ 7.72 nmol/L | 11.5% CV @ 8.05 nmol/L | |
| Between-run CV @ 16.9 nmol/L | 6.2% CV @ 16.9 nmol/L | 7.1% CV @ 13.1 nmol/L | |
| Between-run CV @ 34.6 nmol/L | 4.9% CV @ 34.6 nmol/L | 4.9% CV @ 34.6 nmol/L | |
| Between-run CV @ 42.5 nmol/L | 4.1% CV @ 42.5 nmol/L | 4.1% CV @ 42.5 nmol/L | |
| Expected Values (Saliva) | Morning hours (5th-95th percentile) | 1.90-19.1 nmol/L (0.07-0.69 µg/dl) | <19.1 nmol/L (<0.69 µg/dl) (95th percentile) |
| Afternoon hours (5th-95th percentile) | 2.05-11.9 nmol/L (0.07-0.43 µg/dl) | <11.9 nmol/L (<0.43 µg/dl) (95th percentile) |
Study Proving Acceptance Criteria:
The study that proves the device meets the acceptance criteria is the comparison study detailed in the 510(k) submission, which involved generating the performance data for the modified Elecsys Cortisol Test System (K070788) on the new platforms (cobas e 411 and cobas e 601 analyzers) and ensuring these results are substantially equivalent to the predicate device (K043175). The text explicitly states: "The Elecsys Cortisol Test System (modified) is substantially equivalent to other devices legally marketed in the United States. The Elecsys Cortisol Test System (modified) is equivalent to the Elecsys Cortisol Test System (K043175)." The comparison table provides the evidence for this claim, showing "Same" for many features, or updated, comparable data for others (e.g., precision, sensitivity, expected values).
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Precision (Saliva): Not explicitly stated how many individual samples were used for the precision testing, but results are presented at multiple concentration levels, implying repeat measurements on specific samples/pools (e.g., "Between-run" data shows CVs at 5 different concentrations).
- Expected Values (Saliva): 154 healthy individuals.
- Specific sample sizes for other analytical performance characteristics (e.g., measuring range, sensitivity) are not explicitly provided in the summary.
- Data Provenance: Not specified in the provided text (e.g., country of origin, retrospective or prospective).
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Experts
This is an in-vitro diagnostic device (IVD) measuring a biochemical marker (cortisol). The "ground truth" for such a device is established through highly accurate reference methods and the intrinsic concentration of the analyte in samples, not typically through human expert adjudication like in diagnostic imaging. Therefore:
- Number of Experts: Not applicable in the context of IVD performance studies.
- Qualifications of Experts: Not applicable.
4. Adjudication Method for the Test Set
Not applicable for an IVD device measuring analyte concentration. Analytical performance is evaluated against quantitative measurements and statistical methods, not by human adjudication of qualitative results.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
- No, an MRMC comparative effectiveness study was not done. This type of study is typically for evaluating the diagnostic performance of systems (often imaging AI) where multiple human readers interpret cases with and without AI assistance. This device is an IVD for quantitative determination of cortisol.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
- Yes, the performance data presented is standalone algorithm performance. The Elecsys Cortisol Test System is an automated immunoassay. The reported performance characteristics (e.g., measuring range, sensitivity, precision) reflect the algorithm's direct measurement capabilities without direct human interpretation in the results generation. Humans operate the instrument and interpret the final quantitative values, but the performance metrics themselves are tied to the automated assay's analytical capabilities.
7. The Type of Ground Truth Used
- For sensitivity, measuring range, and precision, the ground truth is the known concentration of cortisol in control samples or spiked samples, or the statistical evaluation of repeated measurements of real patient samples.
- For expected values (saliva), the ground truth is derived from quantitative measurements in a population of healthy individuals.
- The "Traceability / Standardization" section states the device is "Standardized against the Enzymun-Test Cortisol method. This in turn was standardized via ID-MS." Isotope Dilution Mass Spectrometry (ID-MS) is often considered a "gold standard" or highly accurate reference method for quantitative measurements, providing the ultimate ground truth for concentration.
8. The Sample Size for the Training Set
- Not explicitly stated and likely not applicable in the same way as machine learning models. This is an immunoassay system, not a machine learning algorithm that is "trained" on a dataset in the modern sense. The "training" for such a system involves the development and optimization of the assay reagents, protocols, and calibration curves. The development would involve numerous samples, but there isn't a distinct "training set" for an algorithm in this context. The "master curve provided with the reagent bar code" is key to the assay's function, implying significant development and standardization data for its creation.
9. How the Ground Truth for the Training Set was Established
- As above, the concept of a "training set" doesn't directly apply. However, the accuracy of the assay's measurements (which forms its "ground truth" for operation) is based on:
- Standardization against ID-MS: This indicates a robust method for establishing accurate concentration values.
- Calibration curves: These are established using calibrators with known concentrations, which are themselves traceable to highly accurate methods. The Elecsys Cortisol CalSet is a "lyophilized product consisting of human serum with added cortisol (synthetic) in two concentration ranges," where the "analyte is spiked into the matrix at the desired concentration levels." These "desired concentration levels" would be the ground truth for calibration.
{0}------------------------------------------------
KC70788
510(k) Summary - Elecsys Cortisol Test System
| 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 |
|---|---|
| Submitter name, address, contact | Roche Diagnostics9115 Hague RdIndianapolis IN 46250(317) 521-3544Contact person: Kay A. TaylorDate prepared: September 13, 2007 |
| Device name | Proprietary name: Elecsys Cortisol ImmunoassayElecsys Cortisol CalSet |
| Common name: Cortisol testCalibrator | |
| Classification name: Cortisol test systemCalibrator, Secondary | |
| Device description | (1) The Elecsys Cortisol Assay is a two step competitive 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.(2) The Elecsys Cortisol CalSet is a lyophilized product consisting of human serum with added cortisol (synthetic) in two concentration ranges. During manufacture, the analyte is spiked into the matrix at the desired concentration levels. |
:
{1}------------------------------------------------
510(k) Summary - Elecsys Cortisol Test System, Continued
| Intended use | (1) Immunoassay for the in vitro quantitative determination of cortisol inhuman serum, plasma, urine, and saliva. The determination of cortisol is usedfor the recognition and treatment of functional disorders of the adrenal gland. | |
|---|---|---|
| (2) Elecsys Cortisol CalSet is used for calibrating the quantitative ElecsysCortisol assay on the Elecsys immunoassay analyzers. | ||
| SubstantialEquivalence | The Elecsys Cortisol Test System (modified) is substantially equivalent toother devices legally marketed in the United States. The Elecsys Cortisol TestSystem (modified) is equivalent to the Elecsys Cortisol Test System(K043175). | |
| DeviceComparison | The following table compares the Elecsys Cortisol Test System (modified)and the predicate device. The predicate labeling used as the source documentfor the comparison is that provided to FDA in K043175. |
Comparison Table
| Feature | Predicate DeviceElecsys Cortisol Assay(K043175) | Modified DeviceElecsys Cortisol(K070788) |
|---|---|---|
| ReagentIntendedUse/Indications for Use | Immunoassay for the in vitroquantitative determination of cortisolin human serum, plasma, urine, andsaliva. The determination of cortisol isused for the recognition and treatmentof functional disorders of the adrenalgland. | Same |
| CalibratorIntended Use | Elecsys Cortisol CalSet is used forcalibrating the quantitative ElecsysCortisol assay on the Elecsysimmunoassay analyzers. | Same |
| Platform(s) | Elecsys 1010, Elecsys 2010, andMODULAR ANALYTICS E170,analyzers. | Elecsys 1010, Elecsys 2010, andMODULAR ANALYTICS E170,cobas e 411 and cobas e 601analyzers. |
| Assay Protocol | Competitive assay | Same |
| Feature | Predicate DeviceElecsys Cortisol Assay(K043175) | Modified DeviceElecsys Cortisol(K070788) |
| Detection | Electrochemiluminescent | Same |
| Total AssayDuration | 18 minute application | Same |
| Sample Type | Serum, plasma (Li, Na, NH4 Heparin,K2, K3, Na2 EDTA and Na citrate),saliva, urine | Same |
| MeasuringRange | 1.00- 1750 nmol/L or 0.036-63 µg/dL(defined by the lower detection limitand the maximum of the master curve).Values below the detection limit arereported as < 1.0 nmol/L (<0.036µg/dL). Values above the measuringrange are reported as > 1750 nmol/L (>63 µg/dL) (or up to 17,500 nmol/L or630 µg/dL for 10-fold diluted samples). | 1.00-1750 nmol/L or 0.036-63.0 µg/dL(defined by the limit of detection andthe maximum of the master curve).Values below the limit of blank arereported as < 0.50 nmol/L (< 0.018µg/dL). Values above the limit ofblank but below the limit of detectionwill not be flagged by the instrument.Values above the measuring range arereported as > 1750 nmol/L (> 63.0µg/dL) (or up to 17,500 nmol/L or 630µg/dL for 10-fold diluted samples). |
| Sensitivity | < 0.500 nmol/L - Analytical (LDL)<2.0 nmol/L - Functional | ≤ 0.5 nmol/L - LoB< 1.0 nmol/L - LoD8.5 nmol/L - LoQ |
| Calibrator | Elecsys Cortisol Calset | Elecsys Cortisol CalSet |
| CalSet Levels | Two | Same |
| CalSet Matrix | Human serum w/ synthetic cortisol | Same |
| CalSetStorage | Lyophilized | Same |
| CalSet TargetConc. | Cal 1: ~12.5 nmol/LCal 2: ~1000 nmol/L | Same |
| Traceability /Standardization | Standardized against the Enzymun- TestCortisol method. This in turn wasstandardized via ID-MS. | Same |
| Feature | Predicate DeviceElecsys Cortisol Assay(K043175) | Modified DeviceElecsys Cortisol(K070788) |
| AnalyticalSpecificity | For the monoclonal antibodies used,the following cross-reactivities werefound: Osteocalcin, PTH fragment 1-37, bone-specific alkaline phosphatase,and β-Crosslaps: no cross-reactivitydetectable. | Same - reworded to be more clearNo cross-reactivities were found for:Osteocalcin, PTH fragment 1-37,bone-specific alkaline phosphatase,and β-CrossLaps. |
| Limitations | Limitations remain unchanged fromK043175 | Same |
| ReagentStability | Unopened:2-8°C - Up to the stated expirationdateOpened:2-8°C - 12 weeksOn the E170/ Elecsys 2010: 8 weeksOn the Elecsys 1010:2 weeks (stored alternately in therefrigerator and on the analyzer-ambient temperature 20-25°C; up to 20hours opened in total.) | Same - updated for inclusion of cobase analyzers only |
| CalibrationInterval | Calibration must be performed onceper reagent lot using fresh reagent (i.e.not more than 24 hours since thereagent kit was registered on theanalyzer).Renewed calibration is recommendedas follows:E170 and Elecsys 2010:After 1 month (28 days) when usingthe same reagent lot.After 7 days (when using the samereagent kit on the analyzer).Elecsys 1010:With every reagent kit.After 7 days (20-25°C).After 3 days (25-32°C). | Same - updated for inclusion of cobase analyzers only |
| Feature | Predicate DeviceElecsys Cortisol Assay(K043175) | Modified DeviceElecsys Cortisol(K070788) |
| Precision | Serum and urine precision data remainunchanged from K043175 | |
| Saliva | Saliva | |
| Within-run | Within-run - SAME | |
| 6.1% CV @ 4.68 nmol/L | ||
| 2.7% CV @ 11.5 nmol/L | ||
| 4.0% CV @ 15.1 nmol/L | ||
| 1.5% CV @ 15.9 nmol/L | ||
| 2.8% CV @ 19.8 nmol/L | ||
| Between-run | Between-run | |
| 37.1% CV @ 0.93 nmol/L | 33.4% CV @ 2.08 nmol/L | |
| 7.2% CV @ 7.72 nmol/L | 11.5% CV @ 8.05 nmol/L | |
| 6.2% CV @ 16.9 nmol/L | 7.1% CV @ 13.1 nmol/L | |
| 4.9% CV @ 34.6 nmol/L | 4.9% CV @ 34.6 nmol/L | |
| 4.1% CV @ 42.5 nmol/L | 4.1% CV @ 42.5 nmol/L | |
| ExpectedValues | Expected values for serum, plasma, urine remain unchanged fromK043175 | Same |
| Saliva:The following values were determinedin saliva samples from 154 healthyindividuals (5th -95th percentile). | Saliva:The following values were determinedin saliva samples from 154 healthyindividuals (95th percentile). | |
| Morning hours 8-10 a.m:1.90-19.1 nmol/L (0.07-0.69 µg/dl) | Morning hours 8-10 a.m:<19.1 nmol/L (<0.69 µg/dl) | |
| Afternoon hours 2:30-3:30 p.m.2.05-11.9 nmol/L (0.07-0.43 µg/dl) | Afternoon hours 2:30-3:30 p.m.<11.9 nmol/L (<0.43 µg/dl) |
{2}------------------------------------------------
Premarket Notification 510(k): Device Modification -- Elecsys Cortisol Test System, Continued
:
{3}------------------------------------------------
Premarket Notification 510(k): Device Modification - Elecsys Cortisol Test System, Continued
.
{4}------------------------------------------------
Premarket Notification 510(k): Device Modification – Elecsys Cortisol Test System, Continued
{5}------------------------------------------------
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 an abstract image of an eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Roche Diagnostics, Inc. c/o Ms. Kay Taylor. Regulatory Affairs Principal 9115 Hague Road Indianapolis, IN 46250-0416
OCT 5 2007
Re: K070788
Trade/Device Name: Elecsys Cortisol Immunoassay & Elecsys Cortisol CalSet Regulation Number: 21 CFR 862.1205 Regulation Name: Cortisol (hydrocortisone and hydroxycorticosterone) test system. Regulatory Class: Class II Product Code: NHG, JIT Dated: September 05, 2007 Received: September 06, 2007
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).
{6}------------------------------------------------
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 (240) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Jean M. Cooper, M.S., D.V.M.
Jean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
{7}------------------------------------------------
Indications for Use
510(k) Number (if known): K070788
Device Name: Elecsys Cortisol Test System
Indications For Use:
Elecsys Cortisol Immunoassay
Immunoassay 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.
Elecsys Cortisol CalSet
Elecsys Cortisol CalSet is used for calibrating the quantitative Elecsys Cortisol assay on the Elecsys immunoassay analyzers.
Prescription Use XXXX (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Division Sign-Off
Office of In Vitro Diagnostic Device
Evaluation and Safety
Page 1 of 1
Confidential
510(k)
§ 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.