(114 days)
Immunoassay for the in vitro quantitative determination of sex hormone-binding globulin in human serum and plasma. The Elecsys SHBG Immunoassay is intended for use as an aid in the diagnosis of androgen disorders. The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.
A device for the measurement of human SHBG in serum or plasma.
Here's a breakdown of the acceptance criteria and study information for the Elecsys SHBG Immunoassay System, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The submission primarily focuses on demonstrating substantial equivalence to a predicate device (Elecsys SHBG Assay, K031717) rather than setting distinct acceptance criteria for the new device. Therefore, the "acceptance criteria" are implicitly "same as predicate" or "comparable to predicate" for most features.
| Feature | Implicit Acceptance Criteria (based on Predicate) | Reported Device Performance (Elecsys SHBG Assay in K102814) |
|---|---|---|
| Intended Use/Indications | Immunoassay for the in vitro quantitative determination of sex hormone-binding globulin in human serum and plasma, for use on Elecsys and cobas e immunoassay analyzers. (Same as predicate) | Same |
| Assay Protocol | Sandwich assay (Same as predicate) | Same |
| Detection Protocol | Electrochemiluminescent Immunoassay (Same as predicate) | Same |
| Application | 18 Minute (Same as predicate) | Same |
| Instrument Platform | Roche Elecsys 1010, 2010/cobas e 411 and MODULAR ANALYTICS E170/cobas e 601 (Predicate) | Same, with the exception of the removal of the Elecsys 1010 analyzer. |
| Sample Volume | 10 µL (Same as predicate) | Same |
| Sample Type | Human serum and plasma treated with lithium heparin. (Same as predicate) | Same |
| Traceability | Standardized against the 1st International Standard for SHBG, NIBSC code 95/560. (Same as predicate) | Same |
| Calibrator | Elecsys SHBG CalSet (Same as predicate) | Same Sae |
| Calibration Interval | Once per reagent lot (with specific recommendations for renewed calibration based on instrument and time). (Predicate) | Same, with the exception of the removal of the Elecsys 1010 analyzer. |
| Controls | Elecsys PreciControl Universal 1 and 2 (Same as predicate) | Same |
| Reagent Stability/Storage | Specific conditions and durations (e.g., unopened, after opening, on analyzer). (Predicate) | Same, with the exception of the removal of the Elecsys 1010 analyzer. |
| Measuring Range | 0.350-200 nmol/L (Predicate) | 0.800 -200 nmol/L (Note: The lower limit has changed from the predicate. This is a key difference and implies an acceptance criterion for the new range.) |
| Expected Values | Reference ranges for various demographics (Males, Females). (Predicate) | Reference ranges for the SHBG (nmol/L): Males 20-49 years: N=136, Median=33.5, 5th Perc=16.5, 95th perc=55.9; Males ≥ 50 years: N=78, Median=40.8, 5th Perc=19.3, 95th perc=76.4; Females 21-49 years: N=89, Median=64.3, 5th Perc=24.6, 95th perc=122; Females ≥ 50 years: N=71, Median=57.4, 5th Perc=17.3, 95th perc=125. (Includes specific N, Median, 5th Perc, 95th perc for each group). |
| Precision | E1010/2010/411: Within Run 2.1 – 2.7 % CV, Total 2.6 – 5.6% CV. E170/e601: Within run 1.1 – 1.7% CV, Total 1.8 – 4.0% CV. (Predicate) | Same, with the exception of the removal of the Elecsys 1010 analyzer. |
| Analytical Sensitivity | Limit Detection Level (LDL): 0.35 nmol/L (Predicate) | Limit of Blank (LoB): 0.500 nmol/L; Limit of Detection (LoD): 0.800 nmol/L; Limit of Quantitation (LoQ): 2.00 nmol/L (Note: These are different specific metrics and values compared to the predicate's LDL. This implies an acceptance criterion for these new metrics.) |
| Hook Effect | No high-dose hook effect up to 1000 nmol/L. (Same as predicate) | Same |
| Limitations | Unaffected by certain levels of hemoglobin, bilirubin, intralipid, biotin, rheumatoid factors; no interference from 16 common pharmaceuticals; stated caveats about mouse antibodies and other interferences. (Same as predicate) | Same |
| Method Comparison | Correlation with a commercially available SHBG assay (y) vs (x) with specific statistical parameters (Slope, Intercept, Tau/r). (Predicate) | Passing/Bablok: Slope = 1.17, Intercept = -3.26; Linear Regression: Slope = 1.15, Intercept = -1.82; Tau / r = 0.909 / 0.981. (These reported values are for the new device as compared to the predicate or another commercial assay, implying that these statistics met an internal threshold for comparability to demonstrate substantial equivalence.) |
2. Sample Size Used for the Test Set and Data Provenance
The document provides specific sample sizes for particular aspects of the performance evaluation:
- Expected Values (Reference Ranges for SHBG):
- Males 20-49 years: N = 136
- Males ≥ 50 years: N = 78
- Females 21-49 years: N = 89
- Females ≥ 50 years: N = 71
- Method Comparison: n = 109 clinical samples.
The document does not specify the country of origin of the data or whether it was retrospective or prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not provided in the given text. The evaluations appear to be analytical performance studies of an immunoassay, typically relying on reference methods and statistical comparisons rather than expert consensus on diagnostic images or interpretations.
4. Adjudication Method for the Test Set
This information is not applicable/provided as the studies described are analytical performance studies of a quantitative immunoassay, not clinical studies requiring adjudication of diagnostic findings.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
This information is not applicable. The device is an in vitro diagnostic immunoassay, not an AI-powered diagnostic imaging tool or a device that involves human interpretation of results requiring MRMC studies.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
This information is not applicable. The Elecsys SHBG Immunoassay is a laboratory test, where the "algorithm" is the immunoassay procedure itself and the detection system on the analyzer. Its performance is by definition "standalone" in that it produces a quantitative result without human subjective interpretation of the raw signal to get that result. Human "in-the-loop" performance would relate to the interpretation of the numerical SHBG value in a clinical context, which is beyond the scope of the device's standalone performance.
7. The Type of Ground Truth Used
For the analytical performance characteristics:
- Traceability: The assay is standardized against the 1st International Standard for SHBG, NIBSC code 95/560. This serves as the ultimate "ground truth" for SHBG concentration.
- Expected Values (Reference Ranges): These are established through studies on healthy populations, deriving typical ranges.
- Method Comparison: The "ground truth" for the method comparison was a "commercially available SHBG assay (x)." This means the new device's performance was compared against an existing, likely validated, commercial assay.
8. The Sample Size for the Training Set
This information is not provided. The Elecsys SHBG Immunoassay System is a laboratory test, not a machine learning model that typically involves a distinct "training set." Its development would involve extensive R&D, assay optimization, and calibration, but the term "training set" doesn't directly apply in the same way it would for AI/ML devices.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" in the context of an immunoassay is different from AI/ML. The "ground truth" for optimizing such an assay would involve:
- Reference materials: Use of the International Standard for SHBG (NIBSC code 95/560) and other characterized control materials with known SHBG concentrations.
- Clinical samples: Testing of a broad range of patient samples (potentially used for method development and validation, which might be analogous to "training") with a reference method or validated predicate device to ensure accurate and reliable measurements across the measuring range.
The document implies this through the statements on traceability and method comparison, but does not explicitly detail the "training" process.
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510(k) Summary
JAN 2 0 2011
K10 2814
| Introduction | According to the requirements of 21 CFR 807.92, the followinginformation provides sufficient detail to understand the basis for adetermination of substantial equivalence. |
|---|---|
| SubmitterName,Address,Contact | Roche Diagnostics9115 Hague RoadIndianapolis, IN 46250Contact person: Kelly FrenchPhone: (317) 521-3208Fax: (317) 521-2324Email: kelly.french@roche.comSecondary contact: Stephanie GreemanPhone: (317) 521-2458Fax: (317) 521-2324Email: stephanie.greeman@roche.comDate Prepared: September 23, 2010 |
| Device Name | Proprietary names: Elecsys® SHBG Immunoassay SystemCommon name: SHBG testClassification name: Radioimmunoassay, Testosterones andDihydrotestosterone |
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| Device Description | A device for the measurement of human SHBG in serum or plasma. |
|---|---|
| Substantial Equivalence | The Elecsys SHBG Test System is substantially equivalent to other devices legally marketed in the United States. We claim equivalency to the currently marketed Elecsys SHBG Test System (K031717). |
Continued on next page
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ﺮ ﺍﻟﻤﺮﺍﺟﻊ
| Premarket Notification, Traditional 510(k) for | ||
|---|---|---|
| Elecsys SHBG Assay | ||
| Immunoassay Comparison | ||
| Feature | Predicate Device: Elecsys SHBGAssay (K031717) | Elecsys SHBG Assay |
| General Assay Features | ||
| IntendedUse/Indicationsfor Use | Immunoassay for the in vitroquantitative determination of sexhormone-binding globulin in humanserum and plasma. | Same |
| The electrochemiluminescenceimmunoassay “ECLIA” is intendedfor use on Elecsys and cobas eimmunoassay analyzers. | ||
| AssayProtocol | Sandwich assay | Same |
| DetectionProtocol | ElectrochemiluminescentImmunoassay | Same |
| Application | 18 Minute | Same |
| InstrumentPlatform | Roche Elecsys 1010, 2010/cobas e411 and MODULAR ANALYTICSE170/cobas e 601 | Same with the exception of theremoval of the Elecsys 1010analyzer |
| SampleVolume | 10 µL | Same |
| SampleType | Human serum and plasma treated withlithium heparin. | Same |
| Traceability | The Elecsys SHBG assay has beenstandardized against the 1stInternational Standard for SHBG,NIBSC code 95/560. | Same |
| Calibrator | Elecsys SHBG CalSet | Same |
| Immunoassay Comparison | ||
| Feature | Predicate Device: Elecsys SHGB Assay (K031717) | Elecsys SHBG Assay |
| General Assay Features | ||
| Calibration Interval | Calibration 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:MODULAR ANALYTICS E170, Elecsys 2010 and cobas e analyzers:After 1 month (28 days) when using the same reagent lot After 7 days (when using the same reagent kit on the analyzer) Elecsys 1010 analyzer: With every reagent kit After 7 days (ambient temperature 20-25 °C) After 3 days (ambient temperature 25-32 °C) | Same with the exception of the removal of the Elecsys 1010 analyzer. |
| Controls | Elecsys PreciControl Universal 1 and 2 | Same |
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| Immunoassay Comparison | ||
|---|---|---|
| Feature | Predicate Device: Elecsys SHBG Assay (K031717) | Elecsys SHBG Assay |
| General assay features | ||
| ReagentStability/Storage | Store at 2-8 °C. Store the Elecsys SHBG reagent kit upright in order to ensure complete availability of the microparticles during automatic mixing prior to use.Stability:Unopened at 2-8 °C—up to the stated expiration dateAfter opening at 2-8 °C—12 weeksOn MODULAR ANALYTICS E170 and cobas e 601—7 weeksOn Elecsys2010 and cobas e 411—7 weeksOn Elecsys 1010- 4 weeks (stored alternately in the refrigerator and on the analyzer – ambient temperature 20-25 °C; up to 20 hours opened in total) | Same with the exception of the removal of the Elecsys 1010 analyzer. |
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| Feature | Predicate Device: Elecsys SHBG Assay (K031717) | Elecsys SHBG Assay | ||||
|---|---|---|---|---|---|---|
| Measuring Range | 0.350-200 nmol/L | 0.800 -200 nmol/L | ||||
| Expected Values | Males: 10-80 nmol/LFemales, non-pregnant: 20-130 nmol/L | Reference ranges for the SHBG (nmol/L) | ||||
| N | Median | 5th Perc | 95th perc | |||
| Males 20-49 years | 136 | 33.5 | 16.5 | 55.9 | ||
| Males ≥ 50 years | 78 | 40.8 | 19.3 | 76.4 | ||
| Females 21-49 years | 89 | 64.3 | 24.6 | 122 | ||
| Females ≥ 50 years | 71 | 57.4 | 17.3 | 125 |
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| Feature | Immunoassay Comparison | ||||
|---|---|---|---|---|---|
| Predicate Device: ElecsysSHBG Assay (K031717)(18 Minute) | Elecsys SHBG Assay | ||||
| ExpectedValuescont. | Labeled Performance Characteristics | ||||
| Reference ranges for Testosterone II (nmol/L) | |||||
| N | Median | 5thPerc | 95thperc | ||
| Males20-49years | 136 | 18.6 | 8.64 | 29.0 | |
| Males≥ 50years | 78 | 16.5 | 6.68 | 25.7 | |
| Females21-49years | 89 | 0.941 | 0.290 | 1.67 | |
| Females≥ 50years | 71 | 0.563 | 0.101 | 1.42 | |
| Calculation for obtaining FTI (or FAI):%FTI = (Testosterone (nmol/L) ÷ SHBG (nmol/L)) x 100 | |||||
| Reference ranges for Free Testosterone Index (FTI) /Free Androgen Index (FAI) (nmol/L) | |||||
| N | Median | 5thPerc | 95thperc | ||
| Males20-49years | 136 | 57.2 | 35.0 | 92.6 | |
| Males≥ 50years | 78 | 38.2 | 24.3 | 72.1 | |
| Females21-49years | 89 | 1.53 | 0.297 | 5.62 | |
| Females≥ 50years | 71 | 1.15 | 0.187 | 3.63 |
Continued on next page
510(k) Summary, continued
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| Immunoassay Comparison | ||
|---|---|---|
| Feature | Predicate Device: Elecsys SHBG Assay (K031717) (18 Minute) | Elecsys SHBG Assay |
| Labeled Performance Characteristics | ||
| Precision | E1010/ 2010/ 411Within Run 2.1 – 2.7 % CV from 14.1 -204 nmol/L Total 2.6 -5.6% CV from 14.1 -204 nmol/L E170/ e601 Within run 1.1 – 1.7% CV from 14.9 - 219 nmol/L Total 1.8 - 4.0% CV from 14.9 -219 nmol/L | Same with the exception of the removal of the Elecsys 1010 analyzer. |
| AnalyticalSensitivity | Limit Detection Level (LDL):0.35 nmol/L | Limit of Blank (LoB): 0.500 nmol/LLimit of Detection (LoD): 0.800 nmol/LLimit of Quantitation (LoQ): 2.00 nmol/L |
| Hook Effect | There is no high-dose hook effect at SHBG concentrations up to 1000 nmol/L | Same |
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| Immunoassay Comparison | ||
|---|---|---|
| Feature | Predicate Device: Elecsys SHBG Assay (K031717) (18 Minute) | Elecsys SHBG Assay |
| Labeled Performance Characteristics | ||
| Limitations | The assay is unaffected by:Hemoglobin < 2.9 mg/dL Bilirubin < 60 g/dL Intralipid <2700 mg/dL Biotin < 60 ng/mL Rheumatoid factors up to 1160 IU/mL In vitro tests were performed on 16 commonly used pharmaceuticals. No interference with the assay was found. As with all tests containing monoclonal mouse antibodies, erroneous findings may be obtained from samples taken from patients who have been treated with monoclonal mouse antibodies or have received them for diagnostic purposes. In rare cases, interference due to extremely high titers of antibodies to streptavidin and ruthenium can occur. These effects are minimized by suitable test design. For diagnostic purposes, the results should always be assessed in conjunction with the patient's medical history, clinical examination and other findings. | Same |
Continued on next page
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| Feature | Immunoassay Comparison | ||||
|---|---|---|---|---|---|
| Predicate Device: Elecsys SHBGAssay (K031717) (18 Minute) | Elecsys SHBG Assay | ||||
| Labeled Performance Characteristics | |||||
| MethodComparison | A comparison of the Elecsys SHBG assay (y) with a commercially availableSHBG assay (x) using clinical samples gave the following correlation:n = 109Min =11.2 nmol/LMax = 155 nmol/L | Passing/Bablok | LinearRegression | ||
| Slope | 1.17 | 1.15 | |||
| Intercept | -3.26 | -1.82 | |||
| Tau / r | 0.909 | 0.981 |
Confidentiality Roche Diagnostics Corporation requests that the FDA not disclose the nature or existence of the premarket notification until the substantial equivalence decision has been reached.
We trust that the information provided in this Premarket Notification Closing will support a determination of substantial equivalence for the Elecsys SHBG Immunoassay.
If you should have questions or require further information, please do not hesitate to contact me.
· Phone: (317) 521-3208 · FAX: (317) 521-2324 kelly.french@roche.com
Sincerely,
Kelly French, RN, BSN, RAC Regulatory Affairs Consultant US Regulatory Submissions Roche Diagnostics Corporation
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/10/Picture/1 description: The image is a seal for the Department of Health & Human Services. The seal is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an abstract image of an eagle.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Roche Diagnostics c/o Ms. Kelly French Regulatory Affairs Consultant 9115 Hague Road P.O. Box 50416 Indianapolis, IN 46250-0416 -
JAN 20 201
Re: K102814 Trade Name: Elecsys SHBG Regulation Number: 21 CFR §862.1680 Regulation Name: Radioimmunoassay, testosterone and dihydrotestosterone Regulatory Class: Class I, reserved Product Codes: CDZ Dated: December 15, 2010 Received: December 16, 2010
Dear Ms. French:
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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820): .
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Page 2 -
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Viro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
CJC.
Courtney Harper, Ph.D. 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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Indication for Use
510(k) Number (if known): K102814
Device Name: Elecsys SHBG
Indication For Use:
Immunoassay for the in vitro quantitative determination of sex hormone-binding globulin in human serum and plasma. The Elecsys SHBG Immunoassay is intended for use as an aid in the diagnosis of androgen disorders. The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.
Prescription Use X (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Signature
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K102814
§ 862.1680 Testosterone test system.
(a)
Identification. A testosterone test system is a device intended to measure testosterone (a male sex hormone) in serum, plasma, and urine. Measurement of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males and, in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.(b)
Classification. Class I.