ELECSYS TESTOSTERONE II IMMUNOASSAY by ROCHE DIAGNOSTICS CORP.

Immunoassay for the in vitro quantitative determination of testosterone in human serum and plasma. The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.

Measurements 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 androgenital syndromes.

Device Description

The Elecsys Testosterone II immunoassay is based on a competitive test principle with streptavidin-coated 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. The Elecsys Testosterone II reagent kit consists of a Reagent Pack (R1, R2, and M[Streptavidin-coated microparticles]).

AI/ML Overview

The Elecsys® Testosterone II Immunoassay is a device for the in vitro quantitative determination of testosterone in human serum and plasma using electrochemiluminescence immunoassay (ECLIA). The study provided focuses on establishing substantial equivalence to a predicate device (Elecsys® Testosterone Assay, K964889) through method comparison tests and performance characteristic comparisons.

Here's an analysis of the provided information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a numerical format that must be met (e.g., "slope must be between 0.9 and 1.1"). Instead, it demonstrates performance through regression analysis and comparisons to the predicate device and reference methods. The implicit acceptance is that the Elecsys® Testosterone II Assay performs comparably to the predicate device and accurately against reference standards.

The table below summarizes the key performance characteristics and method comparison results for the Elecsys® Testosterone II Assay as described:

Feature	Elecsys® Testosterone II Assay Performance
Measuring Range	2.5 – 1500 ng/dL (0.087 – 52.0 nmol/L)
Precision (Intermediate Precision, Total)	18.5% CV @ 4.5 ng/dL, 8.4% CV @ 9.5 ng/dL, 3.2% CV @ 69.1 ng/dL, 2.8% CV @ 216 ng/dL, 2.8% CV @ 867 ng/dL, 3.4% CV @ 1300 ng/dL, 2.4% CV @ 1450 ng/dL
Precision (Repeatability, Within-Run)	10.2% CV @ 4.5 ng/dL, 4.7% CV @ 9.5 ng/dL, 2.1% CV @ 69.1 ng/dL, 1.9% CV @ 216 ng/dL, 2.6% CV @ 867 ng/dL, 1.2% CV @ 1300 ng/dL, 1.5% CV @ 1450 ng/dL
LoQ (Functional Sensitivity)	12.0 ng/dL
LoB (Limit of Blank)	1.2 ng/dL
LoD (Limit of Detection)	2.5 ng/dL
Method Comparison 1 (vs. validated ID/LC-MS/MS, itself validated vs ID-GC/MS)	n = 52 serum samples (8 - 1383 ng/dL) Deming Regression: Slope = 1.024, y-int = -0.060, Correlation Coefficient (r) = 0.996
Method Comparison 2 (vs. ID-GC/MS reference method)	n = 55 serum samples (7.6 - 1383 ng/dL) Deming Regression: Slope = 1.032, y-int = -0.055, Correlation Coefficient (r) = 0.999
Method Comparison 3 (vs. validated ID/LC-MS/MS for female samples)	n = 142 female serum samples (3 - 517 ng/dL) Deming Regression: Slope = 0.928, y-int = 0.047, Correlation Coefficient (r) = 0.959
Method Comparison 4 (vs. Predicate Device, Elecsys® Testosterone Assay)	Male samples: n = 239 (6.3 - 1400 ng/dL) Deming Regression: Slope = 0.971, y-int = 0.085, Correlation Coefficient (r) = 0.985 Female samples: n = 148 (2.5 - 926 ng/dL) Deming Regression: Slope = 0.984, y-int = -7.34, Correlation Coefficient (r) = 0.972 Male and Female Samples Combined: n = 387 (2.5 - 1400 ng/dL) Deming Regression: Slope = 0.989, y-int = -2.87, Correlation Coefficient (r) = 0.992

Acceptance Criteria (Implied):
While not explicitly stated as numerical acceptance criteria, the strong correlation coefficients (close to 1.0) and slopes (close to 1.0) and small y-intercepts in the regression analyses, coupled with low CVs for precision, indicate the device is performing comparably to both reference methods and the predicate device across its measuring range. This demonstrates that the new device is substantially equivalent to the legally marketed predicate.

2. Sample Sizes and Data Provenance

The studies are quantitative performance analyses of an in vitro diagnostic device, not human reader studies for image-based AI. Therefore, the "test set" concept here refers to the clinical samples used for method comparison.

Test Set (Method Comparison):
- Study 1: 52 serum samples
- Study 2: 55 serum samples
- Study 3: 142 female serum samples
- Study 4: 239 male and 148 female serum samples (total 387)
Data Provenance: Not explicitly stated, but the submission is from Roche Diagnostics, based in Indianapolis, IN, indicating a US-based submission. The nature of in vitro diagnostic device studies typically involves clinical samples, likely collected from various clinical sites. The document does not specify if the data is retrospective or prospective, but based on the type of study (method comparison), it would involve testing collected samples.

3. Number of Experts and Qualifications for Ground Truth

This is not applicable as the device is an immunoassay for quantitative determination of testosterone. The "ground truth" is established by highly accurate reference methods (ID-GC/MS and validated ID/LC-MS/MS), not by human experts interpreting data or images.

4. Adjudication Method

Not applicable. Adjudication methods (e.g., 2+1) are typically used for establishing ground truth in clinical evaluations involving subjective expert interpretation (like radiology reads). For quantitative assays, ground truth is based on objective measurements from reference methods.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Not applicable. This is an immunoassay device, not an AI or imaging device that would involve human readers.

6. Standalone (Algorithm Only) Performance

Yes, the studies evaluate the standalone performance of the Elecsys® Testosterone II Immunoassay. The assay directly measures testosterone levels, and its performance is assessed by comparing its results against established reference methods and the predicate device. There is no "human-in-the-loop" once a sample is loaded into the analyzer for the measurement itself.

7. Type of Ground Truth Used

The ground truth for the test set (method comparison studies) was established using:

ID-GC/MS (Isotope Dilution Gas-Chromatography/Mass Spectrometry): This is considered a gold standard reference method for testosterone measurement, providing highly accurate and precise quantitative values.
Validated ID/LC-MS/MS (Isotope dilution/liquid chromatographic-tandem mass spectrometry): This method was validated against the ID-GC/MS reference method and used as a highly accurate comparison method.

8. Sample Size for the Training Set

The document does not specify a "training set" in the context of machine learning. For an immunoassay, the concept of a training set typically refers to samples used during the development and optimization of the assay's reagents and calibration parameters. This information is usually proprietary to the manufacturer and not detailed in a 510(k) summary, which focuses on validation studies proving performance for regulatory submission.

9. How the Ground Truth for the Training Set Was Established

As there's no explicitly defined "training set" in the provided document, the method for establishing its ground truth is not detailed. However, for an immunoassay, the development process would involve extensive use of characterized calibrators and controls, often traceable to international reference standards, to establish the assay's curve and ensure accurate measurement across its range. These calibrators would be assigned values using highly accurate reference methods (like ID-GC/MS) similar to those used for the test set ground truth.

Summary

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Elecsys® Testosterone II Immunoassay

Confidential

510(k) Summary	APR 2 8 2010
Introduction	According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence.
SubmitterName, Address,Contact	Roche Diagnostics9115 Hague RoadIndianapolis, IN 46250Contact person: Sarah BaumannPhone: (317) 521-3952Fax: (317) 521-2324Email: sarah.baumann@roche.comSecondary contact: Stephanie GreemanPhone: (317) 521-2458Fax: (317) 521-2324Email: stephanie.greeman@roche.comDate Prepared: October 23, 2009
Device Name	Proprietary name: Elecsys® Testosterone II ImmunoassayCommon name: Testosterone II AssayClassification name: Testosterone Test System
DeviceDescription	The Elecsys Testosterone II immunoassay is based on a competitive testprinciple with streptavidin-coated microparticles andelectrochemiluminescence detection. Results are determined using acalibration curve that is generated specifically on each instrument by a 2-pointcalibration and a master curve provided with the reagent bar code.The Elecsys Testosterone II reagent kit consists of a Reagent Pack (R1, R2,and M[Streptavidin-coated microparticles]).
SubstantialEquivalence	The Elecsys Testosterone II Test System is substantially equivalent to otherdevices legally marketed in the United States. We claim equivalency to thecurrently marketed Elecsys Testosterone Assay (K964889).

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The following table compares the Elecsys Testosterone II Immunoassay with Substantial Equivalencethe predicate device. Comparison

Table 1. Testosterone Immunoassay Comparison
Feature	Elecsys Testosterone II Assay	Predicate DeviceElecsys Testosterone Assay(K964889)
Intended Use	Immunoassay for the in vitroquantitative determination oftestosterone in human serum andplasma. The electrochemiluminescenceimmunoassay "ECLIA" is intended foruse on Elecsys and cobas eimmunoassay analyzers.	Immunoassay for the in vitroquantitative determination oftestosterone in human serumand plasma. Theelectrochemiluminescenceimmunoassay "ECLIA" isintended for use on theBoehringer Mannheim Elecsys1010 and 2010 immunoassayanalyzers.
Indications forUse	Measurements of testosterone are usedin the diagnosis and treatment ofdisorders involving the male sexhormones (androgens), includingprimary and secondary hypogonadism,delayed or precocious puberty,impotence in males and, in femaleshirsutism (excessive hair) andvirilization (masculinization) due totumors, polycystic ovaries, andadrenogenital syndromes.	Same
Assay Protocol	Competition principle	Same
Detection Protocol	Electrochemiluminescenceimmunoassay (ECLIA)	Same
Traceability/Standardization	ID-GC/MS (Isotope Dilution Gas-Chromatography/Mass Spectrometry)	Same
Sample Type	Human serum and plasma	Same
Table 1. Testosterone Immunoassay Comparison, continued
Feature	Elecsys Testosterone II Assay	Predicate DeviceElecsys Testosterone Assay(K964889)
InstrumentPlatform	Elecsys 2010(Request for CLIA categorizationhas been made to add theMODULAR ANALYTICS E170,cobas e 411, and cobas e 601analyzers according to theReplacement Reagent andInstrument Policy).	Elecsys 2010(Elecsys 1010, MODULARANALYTICS E170, cobas e 411,and cobas e 601 analyzers addedsubsequent to clearance)
Measuring Range	2.5 – 1500 ng/dL(0.087 – 52.0 nmol/L)	2.0 – 1500 ng/dL(0.069 – 52.0 nmol/L)
Calibrator	Testosterone II CalSet IICalibrators 1 and 2The stability, value assignment andmatrix is identical to TestosteroneCalSet II (cleared on K003411).	Same
CalibrationInterval	Once per reagent lot and• After 1 month (28 days) whenusing the same reagent lot• After 7 days (when using thesame reagent kit on the analyzer)• As required: e.g. quality controlfindings outside the specifiedlimits	Same
Controls	PreciControl Universal 1 and 2(cleared on K090541)	Same
Reagent Stability	• Unopened at 2-8°C – up to theexpiration date	• Same
	• After opening at 2-8°C – 12 weeks	• After opening at 2-8°C – 8 weeks
	• Onboard the analyzer – 8 weeks	• Same
Table 2. Testosterone Immunoassay Performance Comparison
Feature	Elecsys Testosterone II Assay	Predicate DeviceElecsys Testosterone Assay(K964889)
Precision	Elecsys 2010:Intermediate Precision (Total)18.5% CV @ 4.5 ng/dL8.4% CV @ 9.5 ng/dL3.2% CV @ 69.1 ng/dL2.8% CV @ 216 ng/dL2.8% CV @ 867 ng/dL3.4% CV @ 1300 ng/dL2.4% CV @ 1450 ng/dLRepeatability (Within-Run)10.2% CV @ 4.5 ng/dL4.7% CV @ 9.5 ng/dL2.1% CV @ 69.1 ng/dL1.9% CV @ 216 ng/dL2.6% CV @ 867 ng/dL1.2% CV @ 1300 ng/dL1.5% CV @ 1450 ng/dL	Elecsys 2010:Intermediate Precision (Total)7.4% CV @ 24 ng/dL2.6% CV @ 195 ng/dL2.2% CV @ 275 ng/dL1.6% CV @ 620 ng/dL1.7% CV @ 701 ng/dLRepeatability (Within-Run)4.6% CV @ 24 ng/dL1.7% CV @ 195 ng/dL1.4% CV @ 275 ng/dL0.9% CV @ 620 ng/dL1.1% CV @ 701 ng/dL
LoQ(FunctionalSensitivity)	12.0 ng/dL	Same
LoB(Limit of Blank)	1.2 ng/dL	N/A
LoD(Limit ofDetection)	2.5 ng/dL	2.0 ng/dL(Lower Detection Limit, LDL)
Limitations	The assay is unaffected by:• Bilirubin: < 30 mg/dL• Hemoglobin: < 600 mg/dL• Intralipid: < 1000 mg/dL• Biotin: < 30 ng/mL	The assay is unaffected by:• Bilirubin: < 25 mg/dL• Hemoglobin: < 1 g/dL (1000 mg/dL)• Intralipid: < 1500 mg/dL• Biotin: < 30 ng/mL
Feature	Elecsys Testosterone II Assay	Predicate DeviceElecsys Testosterone Assay(K964889)
Limitations, continued	• In patients receiving therapy with high biotin doses (i.e. > 5 mg/day), no sample should be taken until at least 8 hours after the last biotin administration.	• In patients receiving therapy with high biotin doses (i.e. > 5 mg/day), no sample should be taken until at least 8 hours after the last biotin administration.
	• No interference was observed from rheumatoid factors up to a concentration of 1000 IU/mL.
	• In vitro tests were performed with 18 commonly used pharmaceuticals. No interference with the assay was found.	• In vitro tests were performed with 16 commonly used pharmaceuticals. No interference with the assay was found.
	• Three additional drugs were tested: heparin clexane, dexamethasone, and Nandrolone. A strong interaction with Nandrolone was found. Do not use samples from patients under Nandrolone treatment.
	• In isolated cases, elevated testosterone levels can be seen in samples from female patients with end stage renal disease (ESRD).

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Substantial Equivalence-Comparison (continued)

The following table compares the Elecsys Testosterone II Immunoassay with the predicate device.

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