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 Description

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

Assay procedure:

Incubate the sample with the antibody-coated microparticles.
Add testosterone alkaline phosphatase conjugate and incubate.
Transfer to matrix cell.
Wash to remove unbound substances.
Add substrate.
Measure fluorescent product.

AI/ML Overview

Acceptance Criteria and Device Performance Study for AxSYM® Testosterone MEIA

This document describes the acceptance criteria and the supporting study for the AxSYM® Testosterone Microparticle Enzyme Immunoassay (MEIA) device, based on the provided 510(k) summary.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document compares the AxSYM® Testosterone immunoassay (Submission Device) to the Roche Elecsys® Testosterone assay (Predicate Device). The acceptance criteria are implicitly defined by the reported performance of the predicate device and the new device's performance demonstrating substantial equivalence. Given the nature of a 510(k) equivalency claim, the "acceptance criteria" for the new device are typically that its performance characteristics are comparable or superior to the predicate device within clinically acceptable ranges.

Parameter	Acceptance Criteria (Implied by Predicate Device Performance)	Reported Device Performance (AxSYM® Testosterone)
Precision	Within-run CV of 0.9% to 4.6% Total CV of 1.6% to 7.4% (from 0.24 to 7.01 ng/mL)	Within-run CV of 3.9% to 8.3% Total CV of $\le$ 14% for samples with testosterone concentrations $\ge$ 0.85ng/ml and $\le$ 10% for samples $\ge$ 2.10ng/ml.
Functional Sensitivity	Not stated (for predicate device)	$\le$ 0.2ng/ml
Analytical Sensitivity	0.02ng/ml	$\le$ 0.1ng/ml
Analytical Specificity	Cross-reactivity ranged from 0-10.4% for 12 potential cross-reactants tested at 40ng/mL.	<1% cross reactivity observed (for 25 potential cross-reactants, dependent on cross-reactant; concentrations stated in pack leaflet).
Interfering Substances	No interference at: Bilirubin - 25mg/dL Haemoglobin - 1.0g/dL Lipemia - 1500mg/dL Biotin - 30ng/mL	<15% interference at: Bilirubin - 20mg/dL Haemoglobin - 750mg/dL Protein - 10g/dL Triglycerides - 500mg/dL SHBG - 90nmol/L

Note: For a 510(k) submission, "acceptance criteria" are often fulfilled by demonstrating substantial equivalence to a legally marketed predicate device. This means the new device must perform as safely and effectively as the predicate, even if the specific numerical values differ slightly. The provided summary focuses on demonstrating this equivalence rather than explicit acceptance "thresholds" beyond the predicate's performance.

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

The provided 510(k) summary does not explicitly state the sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective) for the performance characteristics presented. It only summarizes the results obtained from various analytical studies.

3. Number of Experts Used to Establish Ground Truth and Their Qualifications

This information is not provided in the 510(k) summary. For in vitro diagnostic devices like this testosterone assay, clinical "ground truth" for individual patient samples would typically be established through reference methods (e.g., ID-GCMS for standardization) or clinical diagnosis by healthcare professionals. The summary mentions that "Concentration is standardised gravimetrically and confirmed by GCMS (Gas Chromatography Mass Spectrometry)" and "The method has been standardised via ID-GCMS (Isotope Dilution Gas Chromatography Mass Spectrometry)" for the predicate. These are analytical reference methods, not clinical expert consensus.

4. Adjudication Method for the Test Set

The 510(k) summary does not provide information regarding any adjudication methods for establishing ground truth for the test set, as it focuses on analytical performance characteristics rather than clinical outcome studies.

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

An MRMC comparative effectiveness study was not done. This type of study involves multiple human readers interpreting cases with and without AI assistance to measure the AI's impact on human performance. The AxSYM® Testosterone MEIA is an automated in vitro diagnostic assay, not an AI-assisted diagnostic imaging or interpretation device that would typically involve human readers in that manner.

6. Standalone Performance Study

A standalone study of the algorithm's (i.e., the MEIA assay's) performance was done. The entire "Performance Characteristics" section in the comparison table details the standalone performance of the AxSYM® Testosterone MEIA, including its precision, functional sensitivity, analytical sensitivity, analytical specificity, and interference by various substances. This data directly reports the algorithm's (assay's) performance without human intervention beyond routine operational procedures.

7. Type of Ground Truth Used

The "ground truth" for the performance characteristics is established through a combination of:

Reference Methods: Concentration standardization is stated to be done gravimetrically and confirmed by GCMS (Gas Chromatography Mass Spectrometry) or ID-GCMS (Isotope Dilution Gas Chromatography Mass Spectrometry). These are highly accurate analytical methods used to define true analyte concentrations.
Controlled Experiments: For parameters like analytical specificity and interfering substances, experiments are conducted by adding known concentrations of potential cross-reactants or interferents to samples with known testosterone levels and measuring the device's response.
Internal Validation Studies: For precision, repeated measurements of samples are taken to assess the variability of the device.

8. Sample Size for the Training Set

The 510(k) summary does not specify the sample size for the training set. For an immunoassay like this, the "training set" would refer to the samples and data used during the development and optimization phases of the assay to establish parameters like reagent concentrations, incubation times, and calibration curve algorithms. This information is typically proprietary development data and is not usually detailed in a 510(k) summary.

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

The 510(k) summary does not explicitly state how the ground truth for the training set was established. However, given the nature of in vitro diagnostic assay development, it would have been established through a rigorous process involving:

Reference Standards: Use of highly pure, accurately weighed testosterone standards.
Reference Methods: Likely GCMS or ID-GCMS for initial calibration and validation of reference materials.
Spiking Studies: Adding known amounts of testosterone to matrices (e.g., serum, plasma) to create samples with defined concentrations.
Method Optimization: Iterative testing and adjustment of assay components and protocols using these known samples to achieve desired performance characteristics (e.g., sensitivity, linearity, precision) before final validation.

Summary

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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 : +44 1382 422000 Fax: +44 1382 422088

Contact Person:	Susan Leonard
Email address:	susan_leonard@uk.axis-shield.com
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.

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 DeviceAxSYM® Testosterone	Predicate DeviceElecsys® Testosterone
Technology Format	Microparticle EnzymeImmunoassay (MEIA).	ElectrochemiluminescenceImmunoassay (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.2 weeks on-board the AxSYM.	Up to stated expiration date when stored at 2-8°C.4 weeks on-board the Elecsys 1010.8 weeks on-board the E170/Elecsys 2010
Parameter	Submission DeviceAxSYM® Testosterone	Predicate DeviceElecsys® Testosterone
Precision	Within-run CV of 3.9% to 8.3%.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%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:Bilirubin - 20mg/dLHaemoglobin - 750mg/dLProtein - 10g/dLTriglycerides - 500mg/dLSHBG - 90nmol/LNot listedNot listed	No interference at:Bilirubin - 25mg/dLHaemoglobin - 1.0g/dLNot listedNot listedNot listedLipemia - 1500mg/dLBiotin - 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

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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 (301) 594-3084. 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 (800) 638-2041 or (301) 443-6597 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.

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

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K041866

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.