The Access SHBG assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of Sex Hormone Binding Globulin levels in human serum and plasma using the Access Immunoassay Systems. The Access SHBG assay is indicated for use in the assessment of androgen disorders.

Device Description

The Access SHBG assay is a sequential two-site immunoenzymatic ("sandwich") assay. The Access SHBG assay consists of the reagent pack, calibrators and QCs. Other items needed to run the assay include substrate and wash buffer. The Access SHBG assay reagent pack, Access SHBG assay calibrators, Access SHBG QCs, 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 FDA 510(k) clearance letter and accompanying summary describe the Acceptance Criteria and the study proving the Access SHBG assay meets these criteria.

Acceptance Criteria and Device Performance

The provided document focuses on the analytical performance of the Access SHBG assay on the Dxl 9000 Access Immunoassay Analyzer, comparing it to a previously cleared predicate device (Access SHBG on Access 2 instrument). The acceptance criteria are largely derived from CLSI (Clinical and Laboratory Standards Institute) guidelines for various analytical performance characteristics.

Here is a table summarizing the acceptance criteria and the reported device performance for the analytical studies:

Performance Characteristic	Acceptance Criteria (from CLSI guidelines or internal design)	Reported Device Performance (Access SHBG on Dxl 9000)
Method Comparison (compared to predicate)	R$^2$ $\ge$ 0.95 with a slope equal to 1.00 $\pm$ 0.09	R = 1.00, R$^2$ = 0.99, Slope = 1.01 (95% CI: 1.00-1.03), Intercept = -0.019 (95% CI: -0.46 - 0.29)
Precision (Within-Laboratory Imprecision)	$\le$ 0.14 nmol/L SD at concentrations $\le$ 2 nmol/L $\le$ 7.0% CV at concentrations > 2 nmol/L	Sample 1 (0.82 nmol/L): SD = 0.04, CV = 4.6% Sample 2 (18 nmol/L): SD = 0.5, CV = 2.7% Sample 3 (47 nmol/L): SD = 1.3, CV = 2.7% Sample 4 (90 nmol/L): SD = 2.6, CV = 2.9% Sample 5 (198 nmol/L): SD = 5.1, CV = 2.6%
Linearity	The assay must demonstrate linearity throughout its analytical measuring interval.	Linear throughout the analytical measuring interval of 0.33 nmol/L - 200 nmol/L.
Limit of Blank (LoB)	Not explicitly stated as a number, but derived from the study.	0.005 nmol/L (maximum observed)
Limit of Detection (LoD)	Not explicitly stated as a number, but derived from the study.	0.01 nmol/L
Limit of Quantitation (LoQ)	Not explicitly stated as a number, but derived from the study.	0.06 nmol/L

Study Details

The provided document describes analytical verification studies for the Access SHBG assay, not a clinical study involving human readers or AI. Therefore, some of the requested information (e.g., MRMC studies, human reader improvement with AI, ground truth for training AI models, number of experts for AI ground truth) is not applicable or cannot be extracted from this document as it pertains to an immunoassay device, not an AI/ML-based diagnostic system.

Here's the relevant information that can be extracted:

2. Sample Size and Data Provenance:

Method Comparison: A total of 151 samples were evaluated. The data provenance is implied to be clinical samples (patient samples are mentioned in the CLSI guideline for method comparison), though specific country of origin or whether they were retrospective/prospective is not stated. Given the context of a 510(k) submission for an in-vitro diagnostic, it is highly likely these were de-identified retrospective clinical samples.
Precision: Five serum samples with varying SHBG concentrations were used. Each sample was assayed in duplicate with two runs per day, over 20 days, on three Dxl 9000 Access Immunoassay Analyzer systems, three reagent lots, and three calibrator lots. This totals 80 measurements per sample (5 samples * 2 duplicates * 2 runs/day * 20 days / 1 instrument * 1 reagent lot * 1 calibrator lot used for reported results).
Linearity: A native low sample and a spiked high sample were used, along with seven mixtures in between.
LoB, LoD, and LoQ: Four distinct blank samples were used for LoB. Six to seven samples were used for LoD. 12-13 serum samples were used for LoQ.

3. Number of Experts and Qualifications for Test Set Ground Truth:

This is an immunoassay device, not an image-based AI system. The ground truth for analytical studies like linearity, precision, and limits of detection is established by the assay itself (measurements of known concentrations, serial dilutions, etc.) and validated against established analytical method guidelines (CLSI). No human experts are involved in establishing ground truth for these analytical performance characteristics in the way they would be for image interpretation tasks.

4. Adjudication Method for Test Set:

Not applicable. Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies where human readers provide interpretations (e.g., radiology reads) that need to be reconciled to form a ground truth. For analytical performance studies of an immunoassay, the "truth" is based on the chemical and instrument measurements and statistical analysis against predefined acceptance criteria.

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

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for AI systems assisting human readers in diagnostic tasks, such as radiology image interpretation. This document describes the analytical performance of an immunoassay for quantitative determination of SHBG levels, which does not involve human readers interpreting AI output.

6. Standalone Performance:

Yes, the entire document focuses on the "standalone" analytical performance of the Access SHBG assay on the Dxl 9000 Access Immunoassay Analyzer. The performance described (method comparison, precision, linearity, limits) is the direct output of the instrument and reagents, without human interpretation "in the loop" beyond standard laboratory procedures for operating the instrument.

7. Type of Ground Truth Used:

For analytical performance studies, the "ground truth" is established through:
- Reference measurements/Predicate device: For method comparison, the results from the previously cleared predicate device (Access SHBG on Access 2 instrument) served as the comparative "truth."
- Known concentrations/mixtures: For linearity, samples with known or precisely diluted concentrations were used.
- Replicate measurements: For precision, repeated measurements establish the variability.
- Blank and low-level samples: For LoB, LoD, and LoQ, these are the "truth" against which the assay's detection capabilities are measured.
- CLSI Guidelines: The studies were designed and evaluated according to CLSI guidelines, which represent a form of accepted scientific and statistical "truth" for validating laboratory assays.

8. Sample Size for Training Set:

This document describes the validation of an immunoassay device, not an AI/ML model. Therefore, there isn't a "training set" in the context of machine learning. The device's underlying chemistry and physics are "trained" during its development and manufacturing process, but not through a data-driven training set in the way an AI algorithm is.

9. How Ground Truth for Training Set was Established:

Not applicable, as there is no AI/ML training set in the context of this immunoassay device.

Summary

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February 8, 2024

Beckman Coulter Inc. Kate Oelberg Senior Staff Quality and Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318

Re: K233480

Trade/Device Name: Access SHBG Regulation Number: 21 CFR 862.1680 Regulation Name: Testosterone Test System Regulatory Class: Class I, reserved Product Code: CDZ Dated: December 14, 2023 Received: December 14, 2023

Dear Kate Oelberg:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.70) and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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,

Paula V. Caposino -S

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

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Indications for Use

510(k) Number (if known) K233480

Device Name Access SHBG

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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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.

510(k) Number K233480

Date Prepared: 1/30/2024

Submitted Bv:

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

Primary Contact:

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

Alternate Contact:

Kuljeet Kaur Senior Manager, Regulatory Affairs Phone: (952) 368-7816 Email: kkaur@beckman.com

Device Name

Common Name: Access SHBG Trade Name: Access SHBG Classification Name: Alkaline phosphatase or isoenzymes test system. Classification Code: CDZ (Class 1) - Radioimmunoassay, Testosterones and Dihydrotestosterone Classification Requlation: 21 CFR 862.1680

Predicate Device Device Name: Access Sex Hormone Binding Globulin Reagent 510(k) Numbers: K083867

Device Description

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Intended Use

Indications for Use

The Access SHBG assay is indicated for use in the assessment of androgen disorders.

Parameter	Access Sex Hormone Binding GlobulinReagent Access UniCel Dxl 800Immunoassay System (Predicate)	Access SHBG on Dxl 9000Access Immunoassay System
Intended use	The Access SHBG assay is aparamagnetic particle, chemiluminescentimmunoassay for the quantitativedetermination of Sex Hormone BindingGlobulin levels in human serum andplasma using the Access ImmunoassaySystems.	Same
Technology	Two-step immunoenzymatic assay	Same
Format	Chemiluminescent	Same
Calibration	Utilizes a stored calibration curve	Same
Sample Type	Serum and lithium heparin plasma	Same
MeasuringRange	Approximately 0.33 - 200 nmol/L	Same
Instrument	Access UniCel Dxl 800 ImmunoassaySystem	Dxl 9000 Access ImmunoassayAnalyzer
Substrate	Access Substrate	Lumi-Phos Pro Substrate

Comparison of Technological Characteristics to the Predicate

Standard/Guidance Document Referenced (if applicable):

CLSI EP05-A3: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline – Third Edition

CLSI EP06-2nd Edition : Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline

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CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures: Approved Guideline - Second Edition CLSI EP09c 30 Edition: Measurement Procedure Comparison and Bias Estimation Using Patient Samples: Third Edition

Summary of Studies

Method Comparison: Method comparison study was performed to compare the Access SHBG 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 fifty-one (151) samples were evaluated in the method comparison study. The results of the method comparison study met the acceptance criteria of R2 ≥ 0.95 with a slope equal to 1.00 ± 0.09 and supports the equivalence of the Access SHBG assay on Dxl 9000 Access Immunoassay Analyzer to the Access SHBG on the Access 2 instrument.

N	ConcentrationRange*(nmol/L)	Slope	Slope95% CI	Intercept	Intercept95% CI	CorrelationCoefficientR	R2
151	0.63 - 235	1.01	1.00-1.03	-0.019	-0.46 - 0.29	1.00	0.99

*Range is Access 2 values

lmprecision: 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 Analyzer systems, three reagent lots, and three calibrator lots. Five (5) serum samples with varying SHBG concentrations, were assayed in duplicate with two runs per day, over 20 days. The assay was designed to have within-laboratory imprecision as listed below:

≤ 0.14 nmol/L SD at concentrations ≤ 2 nmol/L

≤ 7.0% CV at concentrations > 2 nmol/L

The results from a representative lot are as follows:

Concentration (nmol/L)			Repeatability(Within-run)		Between-run		Between-day		Within-Laboratory (Total)
Sample	N	Mean	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 1	80	0.82	0.02	2.3	0.01	1.5	0.03	3.7	0.04	4.6
Sample 2	80	18	0.3	1.4	0.2	1.4	0.4	1.9	0.5	2.7
Sample 3	80	47	0.7	1.6	0.6	1.6	0.8	1.8	1.3	2.7

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Sample 4	80	90	1.4	1.5	1.4	1.5	1.7	1.9	2.6	2.9
Sample 5	80	198	3.0	1.5	3.4	1.5	2.3	1.2	5.1	2.6

Limearity: A verification study was performed to evaluate the linearity of the Access SHBG 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". A native sample was obtained at the low end of the assay's measuring range. A high sample was created by spiking a low serum sample with SHBG antigen to achieve a concentration at or above the highest calibrator. In addition to the high and low SHBG concentration samples, seven mixtures were tested in this study. The Access SHBG assay is linear on the Dxl 9000 Access Immunoassay Analyzer throughout the analytical measuring interval of 0.33 nmol/L - 200 nmol/L.

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 distinct blank samples (calibrator matrix were used for the LoB determination. For estimation of LoD, six to seven samples containing low levels of SHBG analyte were measured. For estimation of LoQ, 12-13 serum samples containing low levels of SHBG analyte were measured. The LoB study included multiple reagent lots and 3 Dxl 9000 Access Immunoassay Analyzers over a minimum of 3 days. The LoQ studies included multiple reagent lots and 3 Dxl 9000 Access Immunoassay Analyzers over a minimum of 5 days. The maximum observed results for LoB for Access SHBG assay is 0.005 nmol/L, LoD is 0.01 nmol/L and LoQ is 0.06 nmol/L on Dxl 9000 Access Immunoassay Analyzer.

Other claims: The claims for the analytical specificity and reference intervals are being transferred from file K083867.

Substantial Equivalence Comparison Conclusion

Beckman Coulter's Access SHBG on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to the Access Sex Hormone Binding Globulin Reagent 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.