VIDAS TESTOSTERONE (TES), MODEL 30 418

K021326 · bioMerieux, Inc. · CDZ · Jul 18, 2002 · Clinical Chemistry

Device Facts

• Record ID: K021326
• Device Name: VIDAS TESTOSTERONE (TES), MODEL 30 418
• Applicant: bioMerieux, Inc.
• Product Code: CDZ · Clinical Chemistry
• Decision Date: Jul 18, 2002
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1680
• Device Class: Class 1

Intended Use

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 Story

VIDAS Testosterone (TES) Assay is an automated enzyme-linked fluorescent immunoassay (ELFA) for measuring total testosterone in human serum or heparinized plasma. The device uses a Solid Phase Receptacle (SPR) as both a pipettor and solid phase. Input samples are transferred to a reagent strip containing an alkaline phosphatase-labeled testosterone derivative; testosterone in the sample competes with the derivative for anti-testosterone antibodies on the SPR. After washing, a substrate (4-Methyl-umbelliferyl phosphate) is introduced; the enzyme catalyzes its conversion to a fluorescent product (4-Methyl-umbelliferone). Fluorescence intensity, measured at 450 nm, is inversely proportional to testosterone concentration. The VIDAS instrument automatically calculates results against a stored calibration curve. Used in clinical laboratories by technicians; results assist physicians in diagnosing and managing androgen-related disorders.

Clinical Evidence

Clinical evidence includes a comparison of 216 samples between VIDAS TES and the Coat-A-Count predicate (R=0.9660). Additional clinical testing involved 183 serum samples compared with the TESTO CT2 kit (R2=0.8106). Thirteen samples were analyzed against the ID-GCMS reference method, showing good correlation (R=0.94). Non-clinical testing included precision (intra-assay 2.73-7.60% CV; total 5.80-11.93% CV), linearity/recovery (mean 100.1%), and specificity/interference studies. EDTA was identified as an interferent causing falsely increased results.

Technological Characteristics

Automated ELFA system using a Solid Phase Receptacle (SPR) for sample handling and antibody capture. Detection via fluorescence at 450 nm. Reagents are contained in sealed strips. Quantitative measurement of total testosterone. Compatible with serum and heparinized plasma. Not compatible with EDTA. Calibration curve stored in instrument memory.

Indications for Use

Indicated for the quantitative measurement of total testosterone in human serum or heparinized plasma to aid in the diagnosis and management of androgen excess or deficiency conditions. Contraindicated for use with EDTA-collected plasma due to interference.

Regulatory Classification

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.

Predicate Devices

• Coat-A-Count Total Testosterone (K813401)
• CIBA Corning ACS Testosterone Immunoassay (K934562)

Reference Devices

• TESTO CT2 Kit (Cis Bio International)
• ID-GCMS (Reference Method)

Submission Summary (Full Text)

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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

[phone] [phone] 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:

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.

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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:

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).

#### Technological Characteristic Summary:

Major Similarities:

- 1. Both are quantitative tests that measure Testosterone levels.
- 2. 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.
- 2. 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.
- 4. 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.
- 5. 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 serum<br>81 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 |
| | | | Males<br>20 - 49 years | 68 | 630 | 262-<br>1,593 | 245-<br>1,836 |
| | | | ==> 50 years | 19 | 427 | 181-<br>758 | 181-<br>772 |

J - 3

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| | presence of EDTA leads to an increase<br>VIDAS TES Assa<br>EDTA: The | entified as Specificity on package inser<br>COAT-A-COUNT Assa |
|---------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | oncentration value of testosterone. Plasma collected EDTA must not be used with the VIDAS TES Assay<br>(also noted in package insert). Heparin: No known interferences from sampl<br>collected 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 th<br>learly 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 | 9-115.29<br>89 | epicted as table located on device package inse |

Non-clinical Testing (Continued)

VIDAS Testosterone (TES) Assay
Premarket Notification
23 April 2002

J - 4

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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.

] - 6

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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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. 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 [phone] or [phone] 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:

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.

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)