The Access Testosterone assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of total testosterone levels in human serum and plasma using the Access Immunoassay Systems.

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

Device Description

The Access Testosterone assay is a competitive binding immunoenzymatic assay. The Access Testosterone assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access Testosterone assay reagent pack, Access Testosterone assay calibrators, along with the UniCel Dxl wash buffer II are designed for use with the Dxl 9000 Access Immunoassay Analyzer in a clinical laboratory setting.

AI/ML Overview

The provided text describes the analytical performance verification of an in vitro diagnostic device (Access Testosterone Assay) and its substantial equivalence to a previously cleared device, rather than an AI-powered medical device performing image analysis or similar tasks that typically involve human experts for ground truth and MRMC studies.

Therefore, many of the requested elements for an AI device (like human expert adjudication, MRMC studies, effect size of human improvement with AI, or detailed ground truth establishment for a training set) are not applicable to this document.

However, I can extract the relevant information regarding the acceptance criteria and study that proves the device meets them for this in vitro diagnostic device.

Here's the information based on the provided text:

Acceptance Criteria and Device Performance for Access Testosterone Assay

1. Table of Acceptance Criteria and Reported Device Performance

Test	Acceptance Criteria	Reported Device Performance
Method Comparison	R² ≥ 0.90 and Slope of 1.00 ± 0.14	R² = 0.98, Slope = 0.95 (95% CI: 0.93, 0.98), Intercept = 0.028 (95% CI: -0.015, 0.071)
Linearity (Analytical Measuring Interval)	Linear throughout the analytical measuring interval of 0.4 - 16.0 ng/mL	Linear throughout the analytical measuring interval of 0.4 - 16.0 ng/mL
Imprecision (Within-Laboratory)	≤ 0.14 ng/mL SD at concentrations ≤ 1.4 ng/mL	Sample 1 (0.71 ng/mL): SD = 0.04 (meets criteria)
	≤ 10.0% CV at concentrations > 1.4 ng/mL	Sample 2 (2.0 ng/mL): CV = 4.4% (meets criteria)
		Sample 3 (4.8 ng/mL): CV = 3.9% (meets criteria)
		Sample 4 (7.1 ng/mL): CV = 4.6% (meets criteria)
		Sample 5 (8.6 ng/mL): CV = 5.9% (meets criteria)
		Sample 6 (14 ng/mL): CV = 7.8% (meets criteria)
Limit of Blank (LoB)	Not explicitly stated as a numerical acceptance criterion, but determined and accepted.	LoB = 0.2 ng/mL
Limit of Detection (LoD)	Not explicitly stated as a numerical acceptance criterion, but determined and accepted.	LoD = 0.4 ng/mL
Limit of Quantitation (LoQ)	Not explicitly stated as a numerical acceptance criterion, but determined and accepted.	20% Within-Laboratory CV LoQ = 0.4 ng/mL

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

Method Comparison: 108 serum samples.
Linearity: Low sample (native serum), high sample (native serum spiked with Testosterone antigen), and mixtures of low and high samples. (Specific N not further detailed for mixtures, but implies multiple points across measuring interval).
Imprecision: Six (6) serum samples (2 native, 3 pooled native, 1 spiked native). Each tested in replicates of two (2) per run, with two (2) runs per day for a minimum of 20 days on each instrument and reagent lot combination. (N=88 for each sample shown in table corresponds to total replicates across the study design).
LoB: Four blank samples.
LoD: Seven serum samples containing low levels of Testosterone.
LoQ: Twelve serum samples containing low levels of Testosterone.
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, given it's an IVD, samples would be collected for analytical performance testing.

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

Not applicable (N/A). This device is an in vitro diagnostic assay for quantitative determination of a hormone level. Ground truth (or reference values) for analytical performance are established through established analytical methods, reference materials (e.g., USP Reference Material for Standardization and Traceability), and quantitative measurement procedures, not by human expert opinion or interpretation of images.

4. Adjudication Method for the Test Set

N/A. Adjudication by human experts is not relevant for establishing the analytical performance of an in vitro diagnostic assay.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size of human readers improve with AI vs. without AI assistance

N/A. This is not an AI-powered device involving human readers or interpretation. It's an in vitro diagnostic assay.

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

Yes, in essence. The studies described (Method Comparison, Linearity, Imprecision, LoB/LoD/LoQ) demonstrate the analytical performance of the device itself (the Access Testosterone Assay on the Dxl 9000 Access Immunoassay Analyzer) in a standalone, automated manner. There is no human interpretation component where performance needs to be evaluated.

7. The Type of Ground Truth Used

Analytical Ground Truth:
- Reference Method/Predicate Device: For method comparison, the "previously cleared system" (Access Testosterone assay on the Access 2 instrument) serves as the reference for comparison, indicating that its results are considered the comparative "ground truth."
- Known Concentrations/Standards/Reference Materials: For linearity, imprecision, and limit studies, samples with known or characterized concentrations (e.g., native serum, spiked samples, blank samples) and established reference materials (USP Reference Material) are used.
- Statistical Models/Calculations: LoB, LoD, and LoQ are determined statistically based on measurements of blank and low-level samples, following CLSI guidelines.

8. The Sample Size for the Training Set

N/A. This is an in vitro diagnostic device, not an AI/machine learning model that undergoes a "training" phase with a data set in the conventional sense. The "training" in manufacturing involves calibrating the instrument and reagents according to established protocols, not learning from a dataset.

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

N/A. As above, there is no "training set" in the context of an AI model for this device. Calibration and quality control procedures ensure the analytical performance by using calibrators and controls with known values, which are traceable to reference materials (e.g., USP Reference Material).

Summary

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January 13, 2023

Beckman Coulter, Inc. Kuljeet Kaur Regulatory Affairs Manager 1000 Lake Hazeltine Drive Chaska, MN 55318

Re: K223405

Trade/Device Name: Access Testosterone Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone test system Regulatory Class: Class I, reserved Product Code: CDZ Dated: November 7, 2022 Received: November 9, 2022

Dear Kuljeet Kaur:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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 Part

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Image /page/1/Figure/6 description: The image shows a digital signature. The signature is by Paula Caposino -S. The date of the signature is 2023.01.13 and the time is 17:18:55 -05'00'.

Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K223405

Device Name Access Testosterone

Indications for Use (Describe)

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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Access Testosterone

510(k) Summary

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

510(k) number: K223405

Submitted By:

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318

Primary Contact:

Kuljeet Kaur, Ph.D. RAC Regulatory Affairs Manager 1000 Lake Hazeltine Drive Chaska, MN 55318 Phone: (952) 465-1914 Email: kkaur@beckman.com

Alternate Contact:

Kate Oelberg Senior Staff Regulatory and Quality Affairs Office Phone: (612) 431-7315 Email: kmoelberg@beckman.com

Date Prepared:

January 5, 2023

Common Name: Access Testosterone Assay Trade Name: Access Testosterone Classification Name: Testosterone test system Product Code: CDZ Classification Regulation: 21 CFR 862.1680

Predicate Device:

Predicate Device	Manufacturer	510(k) No.
Access Testosterone assay	Beckman Coulter, Inc.	K001935

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Device Description:

Intended Use:

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.

Attribute/Characteristic	Predicate AccessTestosterone on AccessImmunoassay System	Access Testosteroneon Dxl 9000 AccessImmunoassayAnalyzer
Intended Use/Indicationsfor Use	The Access Testosterone assayis a paramagnetic particle,chemiluminescent immunoassayfor the quantitative determinationof total testosterone levels inhuman serum and plasma usingthe Access ImmunoassaySystems.	Same
Analyte Measured	Testosterone	Same
Standardization	USP Reference Material	Same
Technology	One-step competitive binding	Same

Comparison to the Predicate

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Attribute/Characteristic	Predicate AccessTestosterone on AccessImmunoassay System	Access Testosteroneon Dxl 9000 AccessImmunoassay Analyzer
Format	Chemiluminescent	Same
Method	Automated	Same
Calibration	Utilizes a stored calibration curve	Same
Traceability	USP reference material	Same
Sample Type	Serum, plasma (heparin)	Same
Stability	Stable at 2 to 10°C for 28 daysafter initial use	Same
Reagent Pack formulationand packaging	Access Reagent Packformulation and packaging.	Same
Measuring Range	0.1 – 16.0 ng/mL	0.4 – 16.0 ng/mL
Instrument	Access Immunoassay system	Dxl 9000 AccessImmunoassay Analyzer
Substrate	Access Substrate	Lumi-Phos PRO substrate

Summary of Studies:

Method Comparison: Method comparison study was performed to compare the Access Testosterone assay on Dxl 9000 Access Immunoassay Analyzer to a previously cleared system. Method comparison and bias estimation experiments were designed in accordance with the CLSI EP09c-A3 "Method Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition". A total of one hundred and eight (108) serum samples were evaluated in the method comparison study. The results of the method comparison study met the acceptance criteria of R2 ≥ 0.90 and slope of 1.00 ± 0.14 and support the equivalence of the Access Testosterone assay on Dxl 9000 Access Immunoassay Analyzer to the Access Testosterone assay on the Access 2 instrument.

N	ConcentrationRange (ng/mL)	Slope	Slope95% CI	Intercept	Intercept95% CI	CorrelationCoefficient R2
108	0.48, 14	0.95	0.93, 0.98	0.028	-0.015,0.071	0.98

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Linearity: A verification study was performed to evaluate the linearity of the Access Testosterone assay on the Dxl 9000 Access Immunoassay Analyzer based on CLSI EP06-Ed2 "Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline". The low sample was a native serum sample. The high sample was created by spiking a native serum sample with Testosterone antigen. All other samples tested were mixtures of the low and high sample. The Access Testosterone assay is linear on the Dxl 9000 Access Immunoassay Analyzer throughout the analytical measuring interval of 0.4 - 16.0 ng/mL.

Imprecision: Repeatability (within-run) and within-laboratory (total) precision studies were designed in accordance with the CLSI Guideline EP05-A3 "Evaluation of Precision of Quantitative Measurement Procedures: Approved Guideline - Third Edition". The study was run on three Dxl 9000 Access Immunoassay Analyzers, three reagent lots, and three calibrator lots. Six (6) serum samples with Testosterone concentrations spanning the range of the assay were each tested in replicates of two (2) per run with two (2) runs per day with a minimum of 20 days on each instrument and reagent lot combination. Two (2) samples were native serum samples from individual donors, three (3) were native pooled serum samples and one (1) sample was prepared by spiking native serum samples with an antigen to achieve adequate coverage at the high end of the analytical range. The assay was designed to have within-laboratory imprecision as listed below:

• ≤ 0.14 ng/mL (0.49 nmol/L) SD at concentrations ≤ 1.4 ng/mL (4.9 nmol/L)

• ≤ 10.0% CV at concentrations > 1.4 ng/mL (4.9 nmol/L)

Concentration (ng/mL)	Repeatability(Within-run)	Between-run		Between-day		Within-Laboratory
Sample	N	Mean	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 1	88	0.71	0.03	3.6	0.02	3.4	0.02	3.4	0.04	6.0
Sample 2	88	2.0	0.05	2.6	0.05	2.6	0.05	2.3	0.09	4.4
Sample 3	88	4.8	0.09	1.9	0.08	1.7	0.14	3.0	0.19	3.9

The results from a representative lot are as follows:

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Concentration (ng/mL)			Repeatability(Within-run)		Between-run		Between-day		Within-Laboratory
Sample 4	88	7.1	0.13	1.8	0.09	1.2	0.29	4.0	0.33	4.6
Sample 5	88	8.6	0.18	2.1	0.25	2.9	0.40	4.7	0.51	5.9
Sample 6	88	14	0.3	2.2	0.2	1.6	1.0	7.3	1.1	7.8

LoB, LoD and LoQ: Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) studies were designed from the CLSI quideline EP17-A2 "Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures Approved Guideline - Second Edition". Four blank samples (Matrix lacking Testosterone antigen) were used for LoB determination. For estimation of LoD, seven serum samples containing low levels of Testosterone analyte were measured. For estimation of LoQ, 12 serum samples containing low levels of Testosterone analyte were measured. The LoB study included multiple reagent lots and 3 Dxl 9000 Access Immunoassay Analyzers over a minimum of 3 days. The LoD and LoQ studies included multiple reagent lots and 3 Dxl 9000 Access Immunoassay Analyzers over a minimum of 5 days. The assay has an LoB of 0.2 ng/mL (0.7 nmol/L), LoD of 0.4 ng/mL (1.39 nmol/L) and 20% Within-Laboratory CV LoQ of 0.4 ng/mL (1.39 nmol/L).

Other claims: The claims for the analytical specificity, reference intervals, matrix comparison are being transferred from file K001935.

Substantial Equivalence Comparison Conclusion

Beckman Coulter's Testosterone Assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to the Access Testosterone Assay on the Access Immunoassay System as demonstrated through the information and data provided in this submission. The performance testing presented in this submission provides evidence that the device is safe and effective in its intended use.

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.