VIDAS Testosterone is an automated test for use on the VIDAS analyzer for the enzyme immunoassay measure of total testosterone in human serum or plasma (heparin), using the ELFA technique (Enzyme Linked Fluorescent Assay). It is intended as an aid in the disgnosis and management of conditions involving excess or deficiency of this androgen.

Device Description

The VIDAS Testosterone (TES) Assay is an enzyme-linked fluorescent immunoassay (ELFA) performed in an automated VIDAS instrument. All assay steps and assay temperatures are controlled by the instrument. A pipette tip-like disposable device, the Solid Phase Receptacle (SPR), serves as the solid phase as well as a pipettor for the assay. Reagents for the assay are in the sealed TES Reagent Strips.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the VIDAS Testosterone (TES) Assay:

Acceptance Criteria and Device Performance for VIDAS Testosterone (TES) Assay

This document details the performance of the VIDAS Testosterone (TES) Assay, an enzyme-linked fluorescent immunoassay (ELFA), and the studies conducted to demonstrate its substantial equivalence to predicate devices.

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated in a table format with pass/fail values. Instead, the document presents performance parameters and compares them to predicate devices or general analytical quality criteria. The table below synthesizes the reported performance against implied or general acceptance for in vitro diagnostic assays.

Performance Characteristic	Acceptance Criteria (Implied/General)	Reported VIDAS TES Assay Performance
Specificity	Minimal cross-reactivity with similar compounds and no significant interference from common sample contaminants.	Tested Compounds: Testosterone (100.00%), 19-Nortestosterone (6.4%), 5α-dihydrotestosterone (0.98%), Δ4-androstenedione (0.07%), etc. (see table in source document)Interference: No significant interference from Heparin, Bilirubin, Hemoglobin, Triglycerides. Note: EDTA leads to increased testosterone, so EDTA plasma must not be used.
Limit of Detection	Low enough to detect clinically relevant concentrations.	0.1 ng/mL
Intra-Run Precision (CV%)	Typically <10-15% for immunoassays.	2.73% – 7.60% (CV%)
Inter-Run/Total Precision (CV%)	Typically <10-15% for immunoassays.	5.80% – 11.93% (CV%)
Dilution Study/Linearity	Good linearity and recovery across the assay range.	4% - 100.0% recovery in dilution study.
Recovery	Average recovery close to 100%, with a reasonable range.	Average mean recovery: 100.1%. Individual mean recoveries: 89.9% to 115.2%.
Correlation with Predicate (DPC Coat-A-Count)	Strong correlation (e.g., R-value > 0.9).	Slope: 1.0602, Ordinate: -0.137, Correlation Coefficient: 0.9660 (R-value)
Correlation with Reference Method (ID-GCMS)	Strong correlation (e.g., R-value > 0.9), potentially better than predicate.	Y(VIDAS TES) = 0.944 X (ID-GCMS) + 0.1452, R² = 0.8989, R = 0.94
Correlation with Expert Tested Kit (TESTO CT2)	Good correlation with a clinically accepted kit.	R² = 0.8106
Expected Values	Established reference ranges for healthy populations.	Provided for healthy males/females.

Conclusion on Acceptance: The reported performance metrics for specificity, limit of detection, precision, linearity, recovery, and correlation with both predicate and reference methods strongly suggest that the VIDAS Testosterone (TES) Assay meets the necessary analytical quality criteria for its intended use, as affirmed in the conclusion statement.

2. Sample Size Used for the Test Set and Data Provenance

Correlation with DPC Coat-A-Count: 216 samples.
Correlation with TESTO CT2: 183 serum samples.
Correlation with ID-GCMS: 13 sera.
Dilution Study: 3 sera collected from patients.
Recovery Test: 3 plasma samples.

The data provenance (country of origin, retrospective/prospective) is not specified in the provided text.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not specify the number or qualifications of experts used to establish the ground truth for the test set.

4. Adjudication Method for the Test Set

The adjudication method is not specified in the provided text. The studies primarily involve quantitative comparisons to reference methods and predicate devices.

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

An MRMC comparative effectiveness study was not performed as this device is an in vitro diagnostic assay (automated immunoassay) and does not involve human readers interpreting results in the same way an imaging or pathology device would. Therefore, the effect size of human readers improving with AI vs. without AI assistance is not applicable.

6. Standalone Performance Study

Yes, a standalone performance study was done. The entire document describes the standalone performance of the VIDAS TES Assay, a fully automated algorithm (ELFA technique) without human intervention in the result generation process. The correlation with the reference method (ID-GCMS) directly demonstrates the algorithm's standalone accuracy.

7. Type of Ground Truth Used

For correlation and accuracy assessment:
- Reference Method: Isotope Dilution-Gas Chromatography/Mass Spectrometry (ID-GCMS) was used as a reference method for 13 samples. ID-GCMS is widely considered a highly accurate and precise "gold standard" method for testosterone measurement.
- Predicate Devices: The DPC Coat-A-Count Total Testosterone assay and the CIBA Corning ACS Testosterone Immunoassay were used for comparison, representing legally marketed and established methods.
- Expert Tested Kit: The TESTO CT2 Kit (Cis Bio International) was also used for comparative analysis.

8. Sample Size for the Training Set

The document does not specify a separate training set or its sample size. Immunoassays are typically developed and validated using a different paradigm than AI/machine learning algorithms. While there is assay development and optimization, it's not described as a distinct "training set" in the context of this 510(k) submission.

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

Since a distinct training set (at least as described for AI/ML) is not mentioned, the method for establishing its ground truth is not applicable or not specified. The product development process for an immunoassay generally involves extensive analytical validation using samples with known concentrations (often established by reference methods or gravimetric preparation) to optimize assay parameters and ensure performance characteristics.

Summary

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JUL 1 8 2002

VIDAS Testosterone (TES) Assay Premarket Notification 23 April 2002

Image /page/0/Picture/2 description: The image shows the logo for bioMérieux. The logo consists of a stylized globe split vertically, with the left half featuring horizontal lines and the right half being solid black. Above the globe is a thin, vertical line that extends upwards. Below the globe, the word "BIOMÉRIEUX" is written in a simple, sans-serif font.

510(k) SUMMARY

bioMerieux. Inc.

595 Anglum Road

Submitter's Name: Title:

Kelly J. Rowland Regulatory Affairs Specialist

Applicant Name: Address:

Contact Person: Phone Number: Fax Number: Date of Preparation: Hazelwood, MO 63042 Kelly J. Rowland

(314) 731-8386 (314) 731-8689 1 April 2002

Device Trade/Proprietary Name:

VIDAS Testosterone (TES) Assay

Device Common/Usual Name:

Classification Name:

Predicate Device Trade Name:

Enzyme-linked Fluorescent Immunoassay (ELFA) for the quantitative detection of total testosterone.

Radioimmunoassay, Testosterones and Dihydrotestosterone. 21 CFR §862.1680

Diagnostic Products Corporation Coat-A-Count® Total Testosterone (K813401)

CIBA Corning ACS Testosterone Immunoassay (K934562) (CIBA now known as Chiron)

Device Description:

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The sample is taken and transferred into the well containing the conjugate, which is an alkaline phosphatase-labeled testosterone derivative. The testosterone present in the serum and the testosterone derivative in the conjugate compete for the anti-testosterone specific antibody sites coated to the inner surface of the SPR. Unbound components are eliminated during the washing steps.

During the final detection step, the substrate (4-Methyl-umbelliferyl phosphate) is cycled in and out of the SPR. The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-embelliferone), the fluorescence of which is measured at 450 nm. The intensity of the fluorescence is inversely proportional to the concentration of testosterone present in the sample.

At the end of the assay, results are automatically calculated by VIDAS in relation to the calibration curved stored in memory, and then printed out.

Intended Use:

Technological Characteristic Summary:

Major Similarities:

1. Both are quantitative tests that measure Testosterone levels.
1. Both tests are carried out with automated systems.

Major Differences:

1. Coat-A-Count is a solid-phase radioimmunoassay with a gamma counter detector. VIDAS TES is an enzyme immunoassay sandwich method with a final fluorescence detection carried out in the VIDAS instrument.
1. Coat-A-Count antibody capture is carried out on the sample in the polypropylene tube, which is then decanted for detection. The SPR serves as the solid phase as well as the pipetting device for VIDAS TES.
Coat-A-Count requires a 3-hour specimen incubation time. VIDAS TES samples do --3. not need incubation before detection.
1. The Coat-A-Count requires multiple calibrators that must be used with every run. VIDAS TES has one calibrator included in each kit that may be run every 14 days.
1. Specimens that may be used with the Coat-A-Count assay include urine, serum or plasma. VIDAS TES specimens must be serum or plasma.

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Performance Data:

clinical Testin No

Non-clinical Testing			COAT-A-COUNT Assay
Specificity	VIDAS TES Assay			Specificity depicted as a table located in the device package insert
	Tested Compound	Cross-Reactivity %		4 ng/dL (0.14 nmol/L)
	Testosterone	100.00
	19-Nortestosterone	6.4
	5α-dihydrotestosterone	0.98
	Δ4-androstenedione	0.07
	5α-androstane-3α, 17β-diol	0.14
	5-androstene-3β, 17β-diol	0.02
	11β-hydroxytestosterone	0.85
	Deoxycorticosterone	< 0.01
	Corticosterone	< 0.01
	Progesterone	< 0.01
	sDIIA (sulfate dehydroepiandrosterone)	< 0.01
	Estradiol	< 0.01
	Estriol	< 0.01
	Estrone	< 0.01
Limit of Detection	0.1 - 1.3 ng/mL
Expected Value for healthy males/females
			87 male serum81 female serum
			n	Median (ng/dL)	Central 95% Range	Absolute Range
	Women	0.1 - 0.9 ng/mL	Females
	Men	3.0 - 10.6 ng/mL	Ovulating	41	24	22 - 80	20 - 81
			Oral contraceptive	13	15	--	10 - 28
			Postmenopausal	27	20	4.0 - 62	4.2 - 74
			Males20 - 49 years	68	630	262-1,593	245-1,836
			==> 50 years	19	427	181-758	181-772

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	presence of EDTA leads to an increaseVIDAS TES AssaEDTA: The	entified as Specificity on package inserCOAT-A-COUNT Assa
	oncentration value of testosterone. Plasma collected EDTA must not be used with the VIDAS TES Assay(also noted in package insert). Heparin: No known interferences from samplcollected on heparir	rossreactivity with dihydrotestosterone is less than 5%. Llipemia, bilirubin nor hemologian aterferes with the assay. Heppeniaed as services as services as services as ser
	Others: Hemolysis, lipemia, and bilirubinemia (aft Illusice this assay. However, it is significantly fluence this assay. However, it is recommended thlearly hemolyzed, lipemic, or icteric samples not used and, if possible, to collect a new sample.
ra-Run Precision CV9		epicted as graph located on device package ins
nter-Run Precision CVS Reproducibility or Tota recision)	2.73 – 7.60 CV% (MDAS) 1.71 – 10.48 CCV% (maxi MPRAS) 1.71 – 10.48 CCV% (maxi MPRAS) 1.61 – 10.48 CCV% (maximi Mix Mix 1.0 2.61 – 10.48 CCV% (ministralia) 10.72 – 11.33 CV% (	9 – 12 CV%
)ilution Study 3 sera collected from m atients were diluted in erum collected from a	4 - 100.0%	ocated on device package in
emale patient (0.26 ng/m) cecovery Test (3 plasmont) amples spiked with known amples spiked with in the	9-115.2989	epicted as table located on device package inse

Non-clinical Testing (Continued)

VIDAS Testosterone (TES) Assay
Premarket Notification
23 April 2002

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Correlation: A comparison of testosterone values from 216 samples run with both VIDAS TES and DPC Coat-A-Count demonstrated good agreement with the following statistical data: slope of 1.0602, ordinate of -0.137 and a correlation coefficient of 0.9660.

Recovery: Linearity studies performed by sampling plasma samples spiked with known quantities of testosterone and tested singly in 3 series. The average mean recovery was 100.1% with individual mean recoveries ranging from 89.9% to 115.2%.

Precision: Intra-assay precision ranged from 2.73 CV% to 7.60 CV%. Total precision ranged from 5.80 CV% to 11.93 CV%

Specificity: There was no significant interference from compounds similar to testosterone. In addition, there was no significant interference from potential sample contaminants such as Heparin. Bilirubin. Hemoglobin, and Triglycerides (lipids). However, the presence of EDTA leads to an increased concentration value of testosterone. Plasma collected on EDTA must not be used with the VIDAS TES Assay (also noted in package insert).

Limit of Detection: The limit of detection is set at 0.1 ng/mL

Clinical Testing

One hundred eighty-three serum samples were assayed in parallel using VIDAS TES and TESTO CT2 and subjected to linear regression analysis. Good correlation between the two methods as the data gave an R2 = 0.8106 value.

In addition, thirteen sera assayed using the reference method (ID-GCMS) were also assayed in two different series using the VIDAS TESTOSTERONE kit and in duplicate using TESTO CT2 kit.

The results were compared using regression analysis. Both methods gave very good correlation.

Comparison of-Mass Spectrometry and VIDAS TES v (VIDAS TES) = 0.944 X (ID-GCMS) + 0.1452 R2 = 0.8989 R = 0.94

Comparison of Mass Spectrometry and Testo CT2 y (Testo CT2) = 0.8884 X (ID-GCMS) + 0.3664 R2 = 0.9649 R = 0.98

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Conclusion

Overall, the VIDAS Testosterone (TES) Assay give very similar results to those obtained with the expert tested kit (TESTO CT2 Kit - Cis Bio International).

The VIDAS Testosterone (TES) Assay give reproducible results, which correlate, closely with the results obtained using the reference method (ID-GCMS). It matches the analytical quality criteria required in the medical laboratory and it give results which are entirely consistent with the clinical picture.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features a stylized eagle-like design with three parallel lines forming the body and head. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the design.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 1 8 2002

Ms. Kelly J. Roland Specialist, Regulatory Affairs bioMerieux, Inc. 595 Anglum Road Hazelwood, MO 63042-2320

Re: K021326

Trade/Device Name: VIDAS Testosterone (TES) Assay Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone test system Regulatory Class: Class II; Product Code: CDZ, JIS, JJX Dated: April 23, 2002 Received: April 26, 2002

Dear Ms. Roland:

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 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 vour 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 Part 801); 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.

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Page 2 -

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and ' additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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/odrh/dsmaldsmamain.html".

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE FORM

510(k) Number (if known): KOZi3Z6

VIDAS Testosterone (TES) Assay Device Name:

Indications for Use:

Hanco
(División Sign-Off)
Division of Clinical Laboratory vices
510(k) Number K0213216

(PLEASE DO NOT WRITE BELOW THIS LINE--CONTINUE ON ANOTHER PAGE IF NEEDED)

Prescription Use $\underline{\hspace{2cm}}$ $\checkmark$

Concurrence of CDRH, Office of Device Evaluation (ODE) Per 21 CFR 801.109)

Regulation Number and Section

§ 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.