ABBOTT AXSYM TESTOSTERONE MICROPARTICLE ENZYME IMMUNOASSAY (MEIA)

K041866 · Axis-Shield Diagnostics, Ltd. · CDZ · Sep 29, 2004 · Clinical Chemistry

Device Facts

• Record ID: K041866
• Device Name: ABBOTT AXSYM TESTOSTERONE MICROPARTICLE ENZYME IMMUNOASSAY (MEIA)
• Applicant: Axis-Shield Diagnostics, Ltd.
• Product Code: CDZ · Clinical Chemistry
• Decision Date: Sep 29, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1680
• Device Class: Class 1

Intended Use

AxSYM Testosterone is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative determination of testosterone in human serum and plasma on the AxSYM System. Testosterone monitoring is used clinically to diagnose and differentiate endocrine disorders. In males, these include hypogonadism, testicular failure, infertility, hypopituitarism, and hyperprolactinemia. In females, polycystic ovary syndrome, adrenal hyperplasia, infertility, hirsutism, amenorrhea, obesity, and virilization can cause changes in serum testosterone levels. The AxSYM Testosterone assay is used as an aid in the investigation of infertility in males and of hirsutism and virilization in females. The AxSYM Testosterone Standard Calibrators are for the standard calibration of the AxSYM system when used for the quantitative determination of testosterone in human serum and plasma.

Device Story

AxSYM Testosterone is a quantitative microparticle enzyme immunoassay (MEIA) for serum/plasma testosterone. The device uses an AxSYM analyzer to process samples via a competitive binding reaction: testosterone in the sample competes with testosterone:alkaline phosphatase conjugate for anti-testosterone coated microparticles. The mixture is transferred to a matrix cell where microparticles bind to a glass fiber matrix; unbound substances are washed away. 4-Methylumbelliferyl Phosphate substrate is added; alkaline-phosphatase conjugate catalyzes the removal of a phosphate group, yielding fluorescent 4-Methylumbelliferone. The AxSYM optical assembly measures fluorescence, which is converted to quantitative testosterone units. The device is used in clinical laboratory settings by trained technicians. Results assist clinicians in diagnosing and monitoring endocrine disorders, including infertility, hirsutism, and virilization. The system provides automated quantitative output, enabling objective assessment of testosterone levels compared to reference ranges.

Clinical Evidence

Bench testing only. Precision evaluated per NCCLS EP5-A (n=80 per panel, 20 days). Linearity assessed via serial dilutions (recovery 99.3-134.6%). Analytical sensitivity <0.1 ng/mL; functional sensitivity <0.2 ng/mL. Specificity testing showed <1% cross-reactivity with 25 potential interferents. Method comparison (n=298) vs. predicate showed Passing-Bablock slope 1.03, r=0.98. Comparison vs. GC-MS (n=100) showed slope 1.10, r=0.97. Reference range study conducted on 296 healthy donors.

Technological Characteristics

Microparticle Enzyme Immunoassay (MEIA). Components: Anti-testosterone coated microparticles, Testosterone:Alkaline Phosphatase conjugate, Wash Buffer, and 6-point calibrators (0-15 ng/mL). Sensing principle: Fluorescence measurement of 4-Methylumbelliferone. Requires Abbott AxSYM analyzer. Calibration traceable to USP grade testosterone. Software: Instrument-based 6-point standard curve generation.

Indications for Use

Indicated for quantitative testosterone measurement in human serum/plasma to aid diagnosis of endocrine disorders. Patient population: males with hypogonadism, testicular failure, infertility, hypopituitarism, or hyperprolactinemia; females with polycystic ovary syndrome, adrenal hyperplasia, infertility, hirsutism, amenorrhea, obesity, or virilization.

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

• Roche Elecsys® Testosterone assay (K964889)

Submission Summary (Full Text)

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Axis-Shield Diagnostics Ltd 7th July 2004

**SEP 2 9** 2004 k041866 - AxSYM®Testosterone
Page 1 of 4

## 510(k) Summary

# Introduction

According to the requirements of 21 CFR 807.92, the following summary of safety and effectiveness provides details to understand the basis for a determination of substantial equivalence.

## Submitter name, address, contact

Axis-Shield Diagnostics Ltd. The Technology Park Dundee DD2 1XA Scotland, UK Tel : [phone] Fax: [phone]

| Contact Person: | Susan Leonard |
|-----------------|----------------------------------|
| Email address: | [e-mail] |
| Date Prepared: | July 7th, 2004 |

#### Device Name

Abbott AxSYM® Testosterone Microparticle Enzyme Immunoassay Proprietary Name: (MEIA) test

Microparticle Enzyme Immunoassay (MEIA) for the determination Common name: of Testosterone.

Classification name: Testosterone test system

#### Predicate Device

Substantial equivalence to the Roche Elecsys® Testosterone assay (K964889) is claimed.

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Axis-Shield Diagnostics Ltd 7" July 2004

K041866 - AxSYM®Testosterone Page 2 of 4

# 510(k) Summary

#### Device Description

Competition format. Microparticle Enzyme Immunoassay (MEIA) for use on Abbott AxSYM® system.

Assay procedure:

- 트 Incubate the sample with the antibody-coated microparticles.
- Add testosterone alkaline phosphatase conjugate and incubate. 1
- Transfer to matrix cell. I
- Wash to remove unbound substances. 배
- 체 Add substrate.
- Measure fluorescent product. . lescein product.
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### Intended Use

A Microparticle Enzyme Immunoassay (MEIA) for the quantitative determination of testosterone in human serum and plasma on the AxSYM System.

### Comparison to Predicate Device

The AxSYM®Testosterone immunoassay is substantially equivalent to the Roche Elecsys Testosterone assay cleared under K964889. Both products are intended for use in the

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quantitative determination of testosterone.

The following information is presented in the Premarket Notification [510(k)] for AxSYM Testosterone to support a substantially equivalent determination.

#### Similarities:

- Intended use
- Operating principles (competitive assay format using antigen-antibody 트 interactions)
- Sample type (serum and plasma)
- 트 Quantitative assay
- For use on automated instruments 비

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Axis-Shield Diagnostics Ltd 7" July 2004

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# 510(k) Summary

# Comparison to Predicate Device (continued)

# Differences:

:

| Parameter | Submission Device<br>AxSYM® Testosterone | Predicate Device<br>Elecsys® Testosterone |
|------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Technology Format | Microparticle Enzyme<br>Immunoassay (MEIA). | Electrochemiluminescence<br>Immunoassay (ECLIA). |
| Capture Antibody | Anti-testosterone (mouse, monoclonal) antibody coated microparticles. | Biotinylated monoclonal anti-testosterone antibody (mouse). Becomes bound to streptavidin coated microparticles. |
| Competition Antigen | Testosterone: Alkaline Phosphatase conjugate. | Testosterone derivative labelled with a ruthenium complex. |
| Substrate | 4-Methylumbelliferyl phosphate. | Not applicable. |
| Assay End-Point | Fluorescence | Electrochemiluminescence |
| Quantitation | Results are determined from a standard calibration curve (0, 0.2, 1.0, 2.5, 7.0, 15.0 ng/mL) generated and stored on the instrument. | Results are determined from a calibration curve generated on the instrument via a two-point calibration and a master curve provided via the reagent barcode. |
| Standardisation | Concentration is standardised gravimetrically and confirmed by GCMS (Gas Chromatography Mass Spectrometry). | The method has been standardised via ID-GCMS (Isotope Dilution Gas Chromatography Mass Spectrometry). |
| Reagent stability | Up to stated expiration date when stored at 2-8°C.<br>2 weeks on-board the AxSYM. | Up to stated expiration date when stored at 2-8°C.<br>4 weeks on-board the Elecsys 1010.<br>8 weeks on-board the E170/Elecsys 2010 |
| Parameter | Submission Device<br>AxSYM® Testosterone | Predicate Device<br>Elecsys® Testosterone |
| Precision | Within-run CV of 3.9% to 8.3%.<br>Total CV of $\le$ 14% for samples with testosterone concentrations $\ge$ 0.85ng/ml and $\le$ 10% for samples $\ge$ 2.10ng/ml. | Within-run CV of 0.9% to 4.6%<br>Total CV of 1.6 to 7.4 % from 0.24 to 7.01 ng/mL. |
| Functional Sensitivity | $\le$ 0.2ng/ml | Not stated |
| Analytical Sensitivity | $\le$ 0.1ng/ml | 0.02ng/ml |
| Analytical Specificity | 25 potential cross-reactants tested. <1% cross reactivity observed at the concentrations stated in the pack leaflet (dependent on cross-reactant). | 12 potential cross-reactants tested at 40ng/mL. Cross-reactivity ranged from 0-10.4%. |
| Interfering Substances | <15% interference at:<br>Bilirubin - 20mg/dL<br>Haemoglobin - 750mg/dL<br>Protein - 10g/dL<br>Triglycerides - 500mg/dL<br>SHBG - 90nmol/L<br>Not listed<br>Not listed | No interference at:<br>Bilirubin - 25mg/dL<br>Haemoglobin - 1.0g/dL<br>Not listed<br>Not listed<br>Not listed<br>Lipemia - 1500mg/dL<br>Biotin - 30ng/mL |

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Axis-Shield Diagnostics Ltd 7" July 2004

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510(k) Summary

Comparison to Predicate Device (continued)

Revised

/

Performance Characteristics:

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, composed of three parallel, curved lines.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 2 9 2004

Ms. Susan Leonard Regulatory Affairs Manager Axis-Shield Diagnostics Ltd. The Technology Park Dundee, Scotland United Kingdom DD2 1XA

k041866 Re:

Trade/Device Name: Abbott AxSYM® Testosterone Microparticle Enzyme Immunoassay (MEIA)

immunoassay (MELISA)
01-CED-862-1150

Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: Class II Product Code: JIS, CDZ Dated: July 7, 2004 Received: July 9, 2004

Dear Ms. Leonard:

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 for abound in 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 that I Dr Has Intacted and regulations administered by other Federal agencies. You must or ury 1 vith 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).

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#### 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 [phone]. 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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Jean M. Cooper, MS, DVM.

Jean M. Cooper, MS, 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

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Revised

# Indications for Use

#### 510(k) Number (if known): K041866

Device Name: Abbott AxSYM® Testosterone Microparticle Enzyme Immunoassay (MEIA)

#### Indications For Use:

AxSYM® Testosterone is a Microparticle Enzyme Immunoassay (MEIA) for the quantitative determination of testosterone in human serum and plasma on the AxSYM System.

Testosterone monitoring is used clinically to diagnose and differentiate endocrine disorders. In males, these include hypogonadism, testicular failure, infertility, hypopituitarism and hyperprolactinemia. In females, polycystic ovary syndrome, adrenal hyperplasia, infertility, hirsutism, amenorrhea, obesity and virilization can cause changes in serum testosterone levels.

The AxSYM® Testosterone assay is used as an aid in the investigation of infertility in males and of hirsutism and virilization in females.

The AxSYM® Testosterone Standard Calibrators are for the standard calibration of the AxSYM system when used for the quantitative determination of testosterone in human serum and plasma.

V Prescription Use (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)

Albert Satz
Division Sign-Off

Page 1 of 1

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Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K041866