The Access TSH (3rd IS) assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of human thyroid-stimulating hormone (thyrotropin, TSH, hTSH) levels in human serum and plasma using the Access Immunoassay Systems. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders. This assay is capable of providing 3rd generation TSH results.

The DxI 9000 Access Immunoassay Analyzer is an in vitro diagnostic device used for the quantitative, semiquantitative, or qualitative determination of various analyte concentrations found in human body fluids.

Device Description

Access TSH (3rd IS) assay is a two-site immunoenzymatic ("sandwich") assay. The Access TSH (3rd IS) reagent kit is in a liquid ready-to-use format designed for optimal performance on Beckman Coulter's immunoassay analyzers. Each reagent kit contains two reagent packs. Other items needed to run the assay include substrate, calibrators and wash buffer.

The Dxl 9000 Access Immunoassay Analyzer is a fully automated, continuous, random-access sample processing and analysis instrument. The Dxl 9000 Access Immunoassay Analyzer uses enzyme immunoassays (utilizing paramagnetic particle solid phase and chemiluminescent detection) for the quantitative, semi-quantitative or qualitative determination of various analyte concentrations found in human body fluids.

AI/ML Overview

The provided text describes the performance of the Access TSH (3rd IS) Assay on the DxI 9000 Access Immunoassay Analyzer. This is an in vitro diagnostic device, and the detailed information typically provided for AI/ML devices regarding ground truth establishment, expert qualifications, and MRMC studies is not directly applicable to this type of device.

Here's a breakdown based on the information available:

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

Performance Metric	Acceptance Criteria	Reported Device Performance
Method Comparison	R² ≥ 0.90 and Slope 1.00 ± 0.10	R²: 1.00 Slope: 1.06 (95% CI: 1.04, 1.07) Intercept: -0.019 (95% CI: -0.10, -0.0037)
Imprecision (Within-laboratory/Total)	Not explicitly stated as a single overall acceptance criterion, but implied to be within acceptable limits for a diagnostic assay.	For TSH concentrations > 0.02 µlU/mL: - %CV ranged from 2.5% to 4.5%. For TSH concentrations ≤ 0.02 µlU/mL: - SD ranged from 0.0007 to 0.0014. (Detailed table with specific sample means and SD/CV values provided in the text)
Reproducibility	SD ≤ 0.0038 for values ≤ 0.02 ulU/mL CV < 13.0% for values > 0.02 ulU/mL	For values ≤ 0.02 ulU/mL (Sample 1, mean 0.024): Overall Reproducibility SD = 0.0010 (meets criteria) For values > 0.02 ulU/mL: - Sample 2 (mean 0.37): Reproducibility CV = 4.3% (meets criteria) - Sample 3 (mean 4.8): Reproducibility CV = 3.7% (meets criteria) - Sample 5 (mean 12): Reproducibility CV = 3.8% (meets criteria) - Sample 4 (mean 46): Reproducibility CV = 3.4% (meets criteria)
Linearity	Not explicitly stated as a numerical criterion, but implies demonstration of accuracy across the measuring range.	Linear throughout the analytical measuring interval of approximately 0.01 - 50.0 µIU/mL (mIU/L).
Limit of Blank (LoB)	Not explicitly stated as a numerical criterion, but implies a low detection threshold.	0.002 µIU/mL
Limit of Detection (LoD)	Not explicitly stated as a numerical criterion, but implies a low detection threshold.	0.003 µIU/mL
Limit of Quantitation (LoQ)	LoQ must be greater than or equal to LoD.	Maximum LoQ determined was 0.001 µlU/mL, but reported as 0.003 µIU/mL to align with LoD, following CLSI EP17-A2 recommendation.

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

Method Comparison Test Set: 111 serum samples.
Imprecision Test Set: 80 replicates per sample level across multiple runs/days.
Reproducibility Test Set: 75 replicates per sample level.
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). Given it's an in vitro diagnostic device, these samples are typically laboratory-generated or clinical samples collected for analytical validation.

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

This information is not applicable to the analytical performance studies conducted for this in vitro diagnostic device. The "ground truth" for these studies is established by the reference method (the predicate device for method comparison) or by known concentrations/spikes for other performance characteristics like linearity, LoB, LoD, LoQ, and imprecision.

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

Not applicable. Adjudication methods are typically used in clinical studies or for subjective interpretations of results, not for the analytical performance of an immunoassay system where quantitative measurements are directly compared.

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 device is an automated immunoassay analyzer, not an AI-assisted diagnostic tool that requires human interpretation or aids human readers.

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

Yes, the studies presented as "Summary of studies" directly represent the standalone performance of the Access TSH (3rd IS) Assay on the DxI 9000 Access Immunoassay Analyzer. The device is an automated system, and its performance is evaluated directly without human interpretation in the analytical process.

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

Method Comparison: The predicate device, Access TSH (3rd IS) Assay on UniCel DxI 800 Immunoassay System (K153651), served as the reference or "ground truth" for comparative performance.
Imprecision, Reproducibility, Linearity, LoB, LoD, LoQ: "Ground truth" is established by the study design, using known concentrations, spiked samples, or statistical methods (e.g., CLSI guidelines) to define true values and assess the device's ability to measure them accurately and precisely.

8. The sample size for the training set

Not applicable. This is not an AI/ML device that requires a training set in the typical sense. Its performance is based on the inherent analytical characteristics of the reagents and instrumentation.

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

Not applicable, as there is no "training set" in the context of an AI/ML algorithm.

Summary

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November 10, 2022

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

Re: K221225

Trade/Device Name: Access TSH (3rd IS) Assay, DxI 9000 Access Immunoassay Analyzer Regulation Number: 21 CFR 862.1690 Regulation Name: Thyroid Stimulating Hormone Test System Regulatory Class: Class II Product Code: JLW, JJE Dated: August 30, 2022 Received: August 30, 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

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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 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 (OS) 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,

Paula
Digitally signed by
Paula Caposino -S
Caposino -S Date: 2022.11.10
10:41:41 -05'00'

Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health 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) K221225

Device Name

Access TSH (3rd IS) Assay, DxI 9000 Access Immunoassay Analyzer

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
-------------------------------------------------	--

X 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: K221225

Date Prepared: November 09, 2022

Submitter Name and address Beckman Coulter, Inc 1000 Lake Hazeltine Drive Chaska, MN 55318

Primary Contact:	Alternate Contact:
Kuljeet Kaur	Kate Oelberg
Regulatory Affairs Manager	Senior Staff Quality and Regulatory Affairs
Email: kkaur@beckman.com	Email: kmoelberg@beckman.com
Phone: (952) 465-1914	Phone: (612)-431-7315

Trade Name: Access TSH (3rd IS) Assay Common Name: Thyroid stimulating hormone assay Classification Regulation: 21 CFR 862.1690 Classification Product Code: JLW

Trade Name: Dxl 9000 Access Immunoassay Analyzer Common Name: Discrete photometric chemistry analyzer for clinical use Classification Name: Discrete photometric chemistry analyzer for clinical use Classification Regulation:21 CFR 862.2160 Classification Product Code: JJE

Predicate Devices: Access TSH (3rd IS) Assay, 510(k) Number K153651 Access 2 Immunoassay System, 510(k) Number K121214

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Device Description

Intended Use

The Dxl 9000 Access Immunoassay Analyzer is an in vitro diagnostic device used for the quantitative, semi-quantitative or qualitative determination of various analyte concentrations found in human body fluids.

Comparison Tables:

Comparison of TSH (3rd IS) on Dxl 9000 to the predicate (Assay)

SystemAttribute /Characteristic	TSH (3rd IS)	TSH (3rd IS) K153651
Intended Use	The Access TSH (3rd IS) assay is a paramagneticparticle, chemiluminescent immunoassay for thequantitative determination of human thyroid-stimulating hormone (thyrotropin, TSH, hTSH) levelsin human serum and plasma using the AccessImmunoassay Systems. This assay is capable ofproviding 3rd generation TSH results.	Same
AnalyteMeasured	Human thyroid-stimulating hormone(thyrotropin, TSH, hTSH)	Same
Standardization	WHO 3rd International ReferencePreparation ThyroidStimulating Hormone, Human (NIBSCCoded 81/565)	Same
Technology	Sandwich immunoassay	Same
Format	Chemiluminescent	Same
Method	Automated	Same
Calibration	Utilizes a stored calibrationcurve	Same
Sample Type	Serum or plasma	Same
MeasuringRange	0.01 – 50.0 µIU/mL	Same

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SystemAttribute /Characteristic	TSH (3rd IS)	TSH (3rd IS) K153651
Stability	Stable at 2 to 10°C for 28 days after initial use	Same
Reagent Packformulation andpackaging	Access Reagent Pack formulation and packaging.	Same
Instrument	Dxl 9000 Access Immunoassay Analyzer	UniCel Dxl 800Immunoassay System
Substrate	Lumi-Phos PRO substrate	Access Substrate
ReagentConfigurations	Two configurations:1) 200 determinations, 2 packs, 100 tests/pack (predicate and candidate device)2) 400 determinations, 2 packs, 200 tests/pack (candidate only)	One Configuration:200 determinations, 2packs,100 tests/pack

Comparison of Technological Characteristics to the Predicate (Instrument)

SystemAttribute /Characteristic	Dxl 9000 Access Immunoassay Analyzer	Predicate Access 2 ImmunoassaySystem K121214
Intended Use	The Dxl 9000 Access ImmunoassayAnalyzer is an in vitro diagnosticdevice used for the quantitative, semi-quantitative, or qualitativedetermination of various analyteconcentrations found in human bodyfluids.	The Access 2 system is an in vitrodiagnostic device used for thequantitative, semi-quantitative, orqualitative determination of variousanalyte concentrations found inhuman body fluids.
Signal Source	Photons generated by chemiluminescentsubstrate reactingwith alkaline phosphatase.	Same
Signal Detector	Photomultiplier tube (PMT)	Same
Data Analysis	Internal data reduction methods viamicrocomputer	Same
Data Output	Digital display and PDF file creation	Digital display and printed alpha-numeric hard copy
TemperatureControl	The following modules are temperaturecontrolled:• Reaction build and reactionincubation• Substrate reaction zone• Reagent storage• Sample aliquot storage• Reagent pipettors• Dispense probes	The following modules aretemperature controlled:• Reaction incubation• Substrate reaction zone• Reagent storage

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SampleLoadingCapacity	133 sample containers	60 sample containers
SampleStorageCapacity (on-board)	268 sample vessels	None
ReagentCapacity	50 Access Reagent packs on board	24 Access Reagent packs on board.
Throughput(Maximumtests/hour)	Approximately 450	Approximately 100
Number ofReagentPipettors	Four	One

Summary of studies:

Method Comparison: A method comparison study was performed to compare the Access TSH (3rd IS) assay on Dxl 9000 to the predicate device. A total of one hundred and eleven (111) serum samples falling within the measuring range of the Access TSH (3rd IS) assay were evaluated. The results of the method comparison study met the acceptance criteria of R2 ≥ 0.90 and slope 1.00 ± 0.10.

No. ofsamples(N)	Access 2 VariableRange Concentration(ulU/mL)	Slope	Slope 95%CI	Intercept	Intercept 95%CI	R2
111	0.01, 47	1.06	1.04, 1.07	-0.019	-0.10, -0.0037	1.00

Imprecision: On the Dxl 9000 Access Immunoassay Analyzer, within-laboratory (total) % CV ranged from 2.5% to 4.5%, for TSH concentrations > 0.02 µlU/mL. The within-laboratory (total) SD ranged from 0.0007 to 0.0014 for TSH concentrations ≤ 0.02 mlU/mL.

Concentration (ulU/mL)		Repeatability(Within-run)		Between-run		Between-day		Within-Laboratory(Total)
Sample	N	Mean	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 1	80	0.022	0.0012	5.5	0.0003	1.5	0.0006	2.8	0.0014	6.4
Sample 2	80	0.36	0.009	2.6	0.007	2.0	0.008	2.3	0.014	4.0
Sample 3	80	4.7	0.12	2.5	0.06	1.3	0.07	1.4	0.15	3.2
Sample 5	80	12	0.4	3.8	0.0	0.1	0.2	2.1	0.5	4.3
Sample 4	80	46	1.0	2.1	0.3	0.7	0.8	1.8	1.3	2.8

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Reproducibility: The Access TSH (3rd IS) assay is designed to meet the requirements for reproducibility on the Dxl 9000 Access Immunoassay Analyzer with an SD ≤ 0.0038 for values ≤ 0.02 ulU/mL and CV < 13.0% for values > 0.02 ulU/mL.

Concentration (ulU/mL)	Repeatability(Within-run)	Between-day	Between -instrument	Reproducibility
Sample	N	Mean	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 1	75	0.024	0.0006	2.6	0.0004	1.8	0.0006	2.5	0.0010	4.0
Sample 2	75	0.37	0.012	3.3	0.010	2.8	0.000	0.0	0.016	4.3
Sample 3	75	4.8	0.11	2.3	0.14	2.8	0.04	0.7	0.18	3.7
Sample 5	75	12	0.2	2.1	0.2	2.0	0.3	2.4	0.5	3.8
Sample 4	75	46	1.1	2.4	0.5	1.1	1.0	2.1	1.6	3.4

Linearity: The Access Total TSH (3rd IS) assay is linear on the Dxl 9000 Immunoassav Analyzer throughout the analytical measuring interval of approximately 0.01 - 50.0 µIU/mL (mIU/L).

Limit of Blank (LoB): The LoB for TSH (3rd IS) is 0.002 µIU/mL on Dxl 9000 Access Immunoassay Analyzer.

Limit of Detection (LoD): The LoD estimate for the TSH (3rd IS) assav is 0.003 w/U/mL on Dxl 9000 Access Immunoassay Analyzer.

Limit of Quantitation (LoQ): The maximum LoQ determined for the TSH (3w/S) assay is 0.001 µlU/mL on Dxl 9000 Access Immunoassay Analyzer). Following the CLSI EP17-A2 recommendation that the LoQ must be greater than or equal to LoD, the LoQ value is reported as 0.003 µIU/mL to align with LoD.

Substantial Equivalence Comparison Conclusion

Beckman Coulter's TSH (3rd IS) Assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to the Access TSH (3rd IS) Assay on the Access 2 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

§ 862.1690 Thyroid stimulating hormone test system.

(a)
Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known as thyrotrophin and thyrotrophic hormone, in serum and plasma. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.(b)
Classification. Class II.