The ARCHITECT 2nd Generation Testosterone assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of testosterone in human serum and plasma.

Measurements 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) due to tumors, polycystic ovaries, and adrenogenital syndromes.

Device Description

The ARCHITECT 2nd Generation Testosterone assay is a delayed one-step immunoassay for the quantitative determination of testosterone in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology with flexible assay protocols, referred to as Chemiflex.

In the first step, sample, assay specific diluent, and anti-testosterone (sheep, monoclonal) coated paramagnetic microparticles are combined. Testosterone present in the sample binds to the anti-testosterone coated microparticles. After incubation, testosterone acridinium-labeled conjugate is added to the reaction mixture. After further incubation and washing, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). An inverse relationship exists between the amount of testosterone in the sample and the RLUs detected by the ARCHITECT i System optics. The concentration of testosterone is interpolated from a calibration curve established with calibrators of known testosterone concentration.

AI/ML Overview

The provided text is related to the Abbott Laboratories ARCHITECT 2nd Generation Testosterone assay (K152155). This 510(k) summary is for a labeling change to include Free Testosterone Index (FTI) or Free Androgen Index (FAI) expected values, not for a new device or a change in the device's fundamental performance. Therefore, the information typically requested in questions 1-9 for device performance and acceptance criteria is not directly applicable to this submission, as the core assay performance data was established in the prior clearance (K120009).

However, I can extract information related to the newly included FTI/FAI expected values study and how it was conducted, aligning it as much as possible with your request structure.

Here's a breakdown based on the provided text, focusing on the FTI/FAI study:

1. A table of acceptance criteria and the reported device performance

Acceptance Criteria: The document does not explicitly state formal acceptance criteria (e.g., specific thresholds for accuracy, precision) for the FTI/FAI expected values study. The study's purpose was to calculate and summarize expected values for different demographic groups. The implicit acceptance was that the calculated FTI/FAI ranges would be provided in the labeling.
Reported Device Performance (FTI/FAI Expected Values):

Category	N	Median (%)	2.5th Percentile (%)	97.5th Percentile (%)
Males (21-49 years of age)	163	46.6	24.5	113.3
Males (≥ 50 years of age)	144	40.7	19.3	118.4
Females (Premenopausal, 21-49 years of age)	174	2.0	0.7	8.7
Females (Postmenopausal, ≥ 50 years of age)	175	1.5	0.5	4.7

2. Sample size used for the test set and the data provenance

Sample Size for the FTI/FAI Study (effectively the test set for new expected values):
- Normal males 21-49 years of age: N=163
- Normal males ≥ 50 years of age: N=144
- Premenopausal normal females 21-49 years of age: N=174
- Postmenopausal normal females ≥ 50 years of age: N=175
- Total N = 556
Data Provenance: The document does not explicitly state the country of origin. It indicates the study was conducted in 2014. It is an internal study by Abbott, likely involving prospective sample collection for the purpose of establishing these expected values, as described by the "inclusion/exclusion criteria."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not applicable. For in vitro diagnostic assays measuring specific analytes like Testosterone and SHBG, the "ground truth" for the test set is established by the assay's quantitative measurement itself, not by expert interpretation of images or clinical data. The FTI/FAI are calculated from these quantitative measurements. The classification of individuals into "normal males/females" etc., would have followed standard clinical criteria, but no "experts" for ground truth establishment in the traditional sense (e.g., radiologist consensus) are mentioned or typically used for this type of IVD study.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. Adjudication methods are typically used in studies involving subjective interpretation (e.g., image reading) where multiple readers disagree. This is a quantitative assay study where numerical results are generated and then used to calculate an index.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This submission is for an in vitro diagnostic (IVD) assay, not an AI-assisted diagnostic tool. No human reader performance improvement is relevant.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, in essence. The ARCHITECT 2nd Generation Testosterone assay (and ARCHITECT SHBG assay) operate as standalone automated systems. The performance data for the core assays (which were part of K120009 and are referenced as still applying) represent the algorithm's (instrument's) performance in quantifying testosterone and SHBG. The FTI/FAI itself is a calculation based on these standalone measurements.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

For the FTI/FAI study, the "ground truth" for each individual sample's testosterone and SHBG levels was the quantitative result provided by the ARCHITECT 2nd Generation Testosterone assay and the ARCHITECT SHBG assay, respectively. These assays are designed to directly measure the analyte concentration. The classification of individuals into demographic groups (e.g., "normal males," "premenopausal females") would rely on self-reported data and/or clinical assessment to ensure they fit the "normal" criteria used for establishing expected values.

8. The sample size for the training set

Not explicitly stated as a separate "training set" for the FTI/FAI expected values study. The study described (with N=556 across categories) generated the expected values directly. For the original ARCHITECT 2nd Generation Testosterone assay (K120009), there would have been extensive datasets used for calibration and method development, but those details are not in this document. This specific submission focuses on new expected values based on a defined cohort.

9. How the ground truth for the training set was established

As above, for the FTI/FAI expected values study, the ground truth was based on the quantitative results from the ARCHITECT Testosterone and SHBG assays. The samples were selected based on inclusion/exclusion criteria to represent "normal" populations for each demographic. For the original assay development (K120009), ground truth would typically involve comparison to reference methods, established standards, and clinical samples of known concentrations, but those specifics are outside the scope of this particular 510(k) summary.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

December 17, 2015

ABBOTT LABORATORIES REGINA KUMAR DIAGNOSTICS DIVISION 100 ABBOTT PARK RD ABBOTT PARK IL 60064

Re: K152155

Trade/Device Name: ARCHITECT 2nd Generation Testosterone Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone test system Regulatory Class: I, Reserved Product Code: CDZ Dated: November 13, 2015 Received: November 16, 2015

Dear Regina Kumar:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); 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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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Katherine Serrano -S

For:

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

K152155

Device Name ARCHITECT 2nd Generation Testosterone

Indications for Use (Describe)

The ARCHITECT 2nd Generation Testosterone assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of testosterone in human serum and plasma.

Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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I. 510(k) Summary

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

Date: December 14, 2015

Applicant Name:

Regina Xavier Kumar, Regulatory Affairs Project Manager Abbott Laboratories Diagnostics Division 100 Abbott Park Road Abbott Park, IL 60064 Phone: 224-668-8093 Fax: 224-667-4836

Device Name:

Reagents

Classification Name: Radioimmunoassay, Testosterones and Dihydrotestosterones Trade Name: ARCHITECT 2nd Generation Testosterone Governing Regulation: 21 CFR 862.1680 Device Classification: Class I, Reserved Classification Panel: Clinical Chemistry Product Code: CDZ

Legally marketed device to which equivalency is claimed:

ARCHITECT 2nd Generation Testosterone (cleared under K120009 on September 11, 2012)

Intended Use/Indications for Use:

The ARCHITECT 2nd Generation Testosterone assay is a chemiluminescent microparticle

immunoassay (CMIA) for the quantitative determination of testosterone in human serum and plasma.

Measurements 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.

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Description of Device:

Comparison of Technological Characteristics:

Both the submission device (ARCHITECT 2nd Generation Testosterone) and the predicate device (ARCHITECT 2nd Generation Testosterone [K120009]) have the same technological characteristics. Both devices use a chemiluminescent microparticle immunoassay (CMIA) technology for the quantitative determination of testosterone in human serum and plasma. There are no technological differences between the submission and predicate devices.

Comparison of Assay Performance:

The reagents, calibrators, and controls for the submission device and the predicate device are the same. The submission is to update the expected values section of the labeling to include the Free Testosterone Index (FTI) (also known as Free Androgen Index [FAI]). The risk analysis was performed and there is no change in the performance of the previously cleared assay. The performance data provided in K120009 still apply.

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Summary of Supporting Data:

The ARCHITECT 2nd Generation Testosterone expected values study was conducted in 2012 and is currently provided in the existing ARCHITECT 2nd Generation Testosterone reagent insert. A second study was conducted in 2014 to calculate FTI or FAI using ARCHITECT 2nd Generation Testosterone (List Number [LN] 2P13) and ARCHITECT SHBG (LN 8K26) assay results. The %FTI or %FAI calculated as [Total Testosterone] / [SHBG] provides an index of free testosterone status. The % FTI or % FAI correlates with the value of free testosterone.

ARCHITECT 2nd Generation Testosterone FTI/FAI Performance Study

Testing was performed on a minimum of 120 samples from individuals in the following categories: normal males 21-49 vears of age, normal males > 50 years of age, premenopausal normal females 21-49 years of age, and postmenopausal normal females ≥ 50 years of age not on hormone replacement therapy.

The following inclusion/exclusion criteria apply to the study:

Samples that were within the expected values of the ARCHITECT 2nd Generation Testosterone (LN 2P13) reagent insert and the ARCHITECT SHBG (LN 8K26) reagent insert were included in the study.

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SHBG nmol/L				Testosterone nmol/L [ng/dL]
Category	N	Median	2.5thPercentile	97.5thPercentile	Median	2.5thPercentile	97.5thPercentile
Males(21-49 years of age)	163	31.1	16.2	68.5	15.33[442.07]	8.76[252.73]	27.85[803.24]
Males(≥ 50 years of age)	144	35.3	13.7	69.9	14.42[415.85]	8.58[247.50]	23.37[674.13]
Females(Premenopausal,21-49 years of age)	174	48.6	14.7	122.5	1.05[30.43]	0.52[14.92]	1.72[49.56]
Females(Postmenopausal,≥ 50 years of age)	175	49.9	16.7	124.4	0.76[21.83]	0.46[13.34]	1.18[33.90]

The data from this study are summarized in the following tables.

The % FTI or % FAI values for the different groups are summarized in the following table.

% FTI or % FAI
Category	N	Median(%)	2.5thPercentile (%)	97.5thPercentile (%)
Males (21-49 years of age)	163	46.6	24.5	113.3
Males (≥ 50 years of age)	144	40.7	19.3	118.4
Females (Premenopausal, 21-49 years of age)	174	2.0	0.7	8.7
Females (Postmenopausal, ≥ 50 years of age)	175	1.5	0.5	4.7

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Conclusion:

The submission is for a labeling change for the %FTI or %FAI Expected Values only. The risk analysis was performed and there is no change in the performance of the previously cleared assay. The performance data provided in K120009 still apply.

The ARCHITECT 2nd Generation Testosterone assay (LN 2P13) is substantially equivalent to the predicate device because the proposed labeling change does not alter the intended use, indications for use, or the fundamental scientific technology of the predicate device. Furthermore, the residual risk is low because the identified and verified control measures eliminate or reduce the potential effects of failure.

Both ARCHITECT 2nd Generation Testosterone and ARCHITECT SHBG (K152185) labeling will be updated to include the %FTI or %FAI expected values generated using these assays.

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.