TESTOSTERONE BY ENZYMEIMMUNOASSAY (EIA) by DIAGNOSTICS BIOCHEM CANADA, INC.

The dbc CAN-TE-250 EiAsy™ Testosterone enzymeimmunoassay (EiA) kit provides the reagents necessary for the direct determination of Testosterone in human serum The use of this assay is intended for in vitro diagnostic use only. Measurement of Testosterone are used in the diagnosis and treatment of disorders involving the male sex hormone (androgens), including primary and secondary hypogonadism, delayed or precocious puberty impotence in male and in females hirsutism (excessive hair) and virilization (masculinization) due to tumors, polycystic ovaries and adrenogenital syndromes.

Device Description

The Testosterone (total) Elisa kit consists of one polyclonal antibody which is coated on microtiter plate (96 wells per kit). The antigen Testosterone 3 carboxymethyl oxime is conjugated to an enzyme namely horse radish peroxidase. The standards are prepared from protein base matrix and all other reagents within a kit namely assay buffer, wash buffer concentrate, substrate tetramethetbenzidine (TMB) and stopping solution. The incubation time is 60 minutes at room temperature. 25 ul of patient serum , control serum and each standard are added for each assay. After incubation the plates are washed 3 times, each time with 300 ul of diluted wash buffer. The plates are dried. 150 ul of TMB is added to each well and allowed to incubate for 10 - 15 minutes. 50 ul of stopping solution is added into each well and the colour becomes yellow. The plate is read within 20 minutes in a microtiter plate reader at 450 mm.

AI/ML Overview

This document describes the dbc EiAsy™ Testosterone EiA kit, an enzyme immunoassay for determining total testosterone in human serum. The 510(k) summary focuses on demonstrating substantial equivalence to a predicate device, the DSL 10-4000 Active™ Testosterone Enzymeimmunoassay (EiA) kit (510(K) #971823).

Here's an analysis of the provided information regarding acceptance criteria and the supporting study:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria with numerical targets. Instead, it relies on demonstrating "substantial equivalency" to a predicate device. The performance characteristics are compared to those of the predicate device, implying that performance comparable to the predicate is the acceptance criterion.

Performance Characteristic	Acceptance Criteria (Implied)	Reported Device Performance (dbc EiAsy™ Testosterone EiA)
Correlation	Strong correlation with predicate device (e.g., r = 0.958)	r = 0.958 (compared to predicate device)
Sensitivity	Comparable to predicate device	Data provided in "results of performance characteristics" (not explicitly stated in summary)
Specificity	Comparable to predicate device	Data provided in "results of performance characteristics" (not explicitly stated in summary)
Intra-assay Precision	Comparable to predicate device	Data provided in "results of performance characteristics" (not explicitly stated in summary)
Inter-assay Precision	Comparable to predicate device	Data provided in "results of performance characteristics" (not explicitly stated in summary)
Recovery	Comparable to predicate device	Data provided in "results of performance characteristics" (not explicitly stated in summary)
Linearity	Comparable to predicate device	Data provided in "results of performance characteristics" (not explicitly stated in summary)

Note: The document states that "The results need not be exactly the same but a collaboration of equivalence is necessary in this case r=0.958." This implies that a correlation coefficient of 0.958 was deemed sufficient for demonstrating equivalence in terms of overall agreement between the new device and the predicate. The actual numerical values for most performance characteristics are not provided in this summary but are referenced as being available in the "results of performance characteristics."

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

Sample Size: The document mentions "the results of a number of human serum samples." It does not specify the exact number of samples used in the comparison study for the test set.
Data Provenance: The samples are described as "human serum samples." The country of origin is not explicitly stated. The study appears to be retrospective, as it's a comparison of a newly developed device against an existing, legally marketed predicate device.

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

This type of immunoassay device does not typically rely on expert human interpretation to establish a ground truth for its measurements in the same way an imaging diagnostic might. The "ground truth" for evaluating the dbc EiAsy™ Testosterone EiA kit is established by comparing its quantitative testosterone measurements against those obtained from the predicate device. Therefore, the concept of "experts" establishing a ground truth for individual cases is not directly applicable here. The predicate device's measurements serve as the reference.

4. Adjudication Method for the Test Set

Not applicable. As described above, the comparison is directly quantitative against the predicate device; there is no need for expert adjudication of results.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that involve human interpretation (e.g., radiologists reading images) and assesses the impact of AI assistance on human performance. This device is a quantitative in-vitro diagnostic test, not an interpretive one.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the primary study described is a standalone performance evaluation of the dbc EiAsy™ Testosterone EiA kit. Its performance (sensitivity, specificity, precision, recovery, linearity, and correlation) is assessed independently and then compared to the predicate device to establish substantial equivalence. Human involvement is limited to performing the assay according to the protocol, not in interpreting the results beyond reading the optical density.

7. The Type of Ground Truth Used

The "ground truth" used for comparison in this substantial equivalence determination is the measurements obtained from the predicate device, the DSL 10-4000 Active™ Testosterone Enzymeimmunoassay (EiA) kit. The assumption is that the predicate device provides accurate testosterone measurements.

8. The Sample Size for the Training Set

The document does not specify a separate "training set" size. For an immunoassay, the concept of a "training set" as understood in machine learning (where an algorithm learns from labeled data) is not directly applicable in the same way. The development of the assay (e.g., antibody selection, reagent formulation, optimization of incubation times) involves extensive laboratory work and validation but typically doesn't refer to a distinct "training set" in the context of an FDA submission.

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

Not applicable in the machine learning sense. The "ground truth" for the development and optimization of the immunoassay itself would be based on established analytical chemistry principles, known concentrations of testosterone standards, and comparisons against reference methods during internal development. This is not detailed in the provided 510(k) summary.

Summary

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FEB 0 8 2002

dbc - DIAGNOSTICS BIOCHEM CANADA INC.

1020 Hargrieve Road, London, Ontario, Canada N6E 1P5 e-mail dbc@dbc-labs.com Tel/Fax (519) 681-8731

G. R. Dumont, M.D., M.Sc. A.J. Desrosiers, D.Sc. M.Sc. J. U. Laryea, Ph. D. M.Sc.

DATE: November 29, 2001

Contact Person: Dr. G. R. Dumont Tel (519) 681-8731

18. 510 K Summary

This summary of 510(K) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92

The assigned 510K number is KO14120
The classification name of the device: enzyme immunoassay for testosterone
Classification number 862.1680

1. Proprietary name: Testosterone By Enzymeimmunoassay (EiA) Class I
1. Use of the device

Direct determination of Testosterone (total) by enzymeimmunoassay (Elisa) in human serum

1. The predicate device's name and address of which we claim equivalence: Diagnostics System Laboratories,(DSL) 445 Medical Center Blvd. Webster, Texas, 77598 DSL 10-4000 Active™ Testosterone Enzymeimmunoassay (EiA) kit 510(K) #971823

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The Testosterone (total) Elisa kit consists of one polyclonal antibody which is coated on microtiter plate (96 wells per kit). The antigen Testosterone 3 carboxymethyl oxime is conjugated to an enzyme namely horse radish peroxidase. The standards are prepared from protein base matrix and all other reagents within a kit namely assay buffer, wash buffer concentrate, substrate tetramethytbenzidine (TMB) and stopping solution. The incubation time is 60 minutes at room temperature. 25 ul of patient serum , control serum and each standard are added for each assay. After incubation the plates are washed 3 times, each time with 300 ul of diluted wash buffer. The plates are dried. 150 ul of TMB is added to each well and allowed to incubate for 10 - 15 minutes. 50 ul of stopping solution is added into each well and the colour becomes yellow. The plate is read within 20 minutes in a microtiter plate reader at 450 mm.
Substantial equivalence:
The dbc In-vitro diagnostic device namely Testosterone (total) by enzymeimmunoassay (EiA) has the same intended use as current device on the market referred to "predicate device".
The dbc In-vitro diagnostic device namely Testosterone (total) by enzymeimmunoassay (EiA) has the same technological characteristics as predicate device namely Enzymeimmunoassay (EiA) antigen/antibody.
The dbc enzymeimmunoassay for total testosterone has no new technological feature which will raise questions of safety and effectiveness.
The data obtained help to indicate substantial equivalency and the results of a number of human serum samples. The results need not be exactly the same but a collaboration of equivalence is necessary in this case r=0.958.
The dbc total testosterone safety and effectiveness compared to the predicate devices can be found in our results of performance characteristics namely, sensitivity, specificity, Intra and Inter assay precision, Recovery and Linearity.

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dbc total testosterone intended use, methodology, reagents and materials including equipments and control necessary to perform the test are similar to the predicate device. From our assay data and protocol the safety and effectiveness of dbc total testosterone is similar to the predicate device.
Our 510K presentation demonstrates substantial equivalence to predicate device in regards:

intended use
design
performance
material and equipments
safety
effectiveness
standards
control

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Image /page/3/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 text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol resembling three stylized birds in flight, stacked vertically. The birds are depicted in black and have a flowing, wave-like design.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB 0 8 2002

G.R. Dumont, M.D., M.SC. Director of Laboratories Diagnostics Biochem Canada, Inc. 1020 Hargrieve Road London, Ontario, N6E 1P5 Canada

Re: K014120 Trade/Device Name: EiAsy™ Testosterone EiA Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone test system Regulatory Class: Class I Product Code: CDZ Dated: November 16, 2001 Received: December 17, 2001

Dear Dr. Dumont:

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 your 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 I mis letter will and w you as organisal equivalence of your device to a legally marketed nouthoution. The I Dr I 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 1 additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at additionally 607.10 for questions on the promotion and advertising of your device, (201) 594-1500. Viderator 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 nuormation on Jour responsible in Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/odrh/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

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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Statements of Indication for Use

510K number

Device Name: EiAsyTM Testosterone EiA

Indication for Use:

Alan Cooper

(Division Sign-Off)

Division of Clinical Laboratory Devices
510(k) Number K014120

Prescription USE .................................................................. (Per 21 CFR 801.109

Over-The-Counter Use ........

Susan S. Altare

rision of Clinical Laboratory Devices

510(k) Number Koi4120

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.