The Access TPO Antibody assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroperoxidase antibody (TPOAb) levels in human serum and plasma using the Access Immunoassay Systems.

The detection of TPOAb is an aid in the diagnosis of thyroid autoimmune disorders.

Device Description

The Access TPO Antibody assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroperoxidase antibody (TPO Ab) levels in human serum and plasma using the Access Immunoassay Systems.

The Access TPO Antibody Calibrators are intended to calibrate the Access TPO Antibody assay for the quantitative determination of TPO Antibody levels in human serum and plasma using the Access Immunoassay Systems.

The Access TPO Antibody assay is a sequential two-step immunoenzymatic ("sandwich") assay. A sample is added to a reaction vessel with paramagnetic particles coated with thyroperoxidase protein. The serum or plasma TPO Ab binds to the thyroperoxidase. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of analyte in the sample. Analyte concentration is automatically determined from a stored calibration.

AI/ML Overview

The provided document, a 510(k) summary for the Beckman Coulter Access TPO Antibody assay, describes the analytical performance studies conducted to demonstrate substantial equivalence to a predicate device. This is a common regulatory pathway for in vitro diagnostic devices, focusing on demonstrating that the new device is as safe and effective as a legally marketed predicate device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

The document presents acceptance criteria implicitly through the study designs and results, as it's a submission for an IVD kit rather than an AI/ML algorithm. The performance is assessed by comparing the new device (Access TPO Antibody Assay on Dxl 9000 Access Immunoassay System) to its predicate device (Access TPO Antibody Assay on Access 2 Immunoassay System).

Table of Acceptance Criteria and Reported Device Performance:

Performance Characteristic	Acceptance Criteria (Implicit from Study Design/Goal)	Reported Device Performance (Access TPO Antibody Assay on Dxl 9000)	Study Method/Description
Method Comparison (Agreement with Predicate)	A strong correlation and minimal bias between results from the new device and the predicate device, demonstrated by slope and intercept close to 1 and 0 respectively, and a high correlation coefficient.	Slope: 1.06 (95% CI: 1.04 - 1.08) Intercept: -0.26 (95% CI: -0.32 - -0.22) Correlation Coefficient (R): -0.978 (Note: The negative sign for R with a positive slope is unusual and might be a typo in the document; typically, a strong positive correlation is indicated by R closer to +1 for agreement studies).	CLSI EP09c, 3rd Edition; Passing-Bablok regression.
Imprecision (Repeatability and Reproducibility)	Within-laboratory imprecision meeting predefined thresholds: - < 0.07 IU/mL SD at concentrations < 0.6 IU/mL - < 12.0% CV at concentrations ≥ 0.6 IU/mL and < 450.0 IU/mL - < 15.0% CV at concentrations ≥ 450.0 IU/mL	Sample 1 (0.35 IU/mL): Within-Laboratory SD: 0.02, %CV: 6.9 (Meets <0.07 SD) Sample 2 (5.5 IU/mL): Within-Laboratory SD: 0.36, %CV: 6.7 (Meets <12.0% CV) Sample 3 (20 IU/mL): Within-Laboratory SD: 1.23, %CV: 6.2 (Meets <12.0% CV) Sample 4 (318 IU/mL): Within-Laboratory SD: 21.35, %CV: 6.7 (Meets <12.0% CV) Sample 5 (747 IU/mL): Within-Laboratory SD: 96.48, %CV: 12.9 (Meets <15.0% CV)	CLSI EP05-A3; multiple samples in duplicate for 2 runs/day over ≥20 days.
Linearity	Assay demonstrates linearity across the claimed measuring interval (0.25 - 1,000 IU/mL).	"the assay demonstrated linearity across the measuring interval."	CLSI EP06-Ed2
Detection Capability (LoB, LoD, LoQ)	Established quantitative limits relevant for clinical use, demonstrating the ability to detect and quantify low concentrations of the analyte.	Limit of Blank (LoB): 0.19 IU/mL Limit of Detection (LoD): 0.23 IU/mL Limit of Quantitation (LoQ): 0.25 IU/mL	CLSI EP17-A2

Study Details:

This submission focuses on an In Vitro Diagnostic (IVD) assay (Access TPO Antibody), not an AI/ML algorithm. Therefore, many of the questions related to AI/ML development (training set, experts for ground truth, MRMC studies) are not directly applicable in the way they would be for an AI-based medical device. However, I will interpret them in the context of an IVD assay where possible, based on standard IVD validation practices.

Sample Size Used for the Test Set and Data Provenance:
- Method Comparison: N = 219 patient samples.
- Imprecision: N = 80 replicates (for each of 5 samples).
- Linearity & Detection Capability: Sample sizes for these studies are not explicitly stated, but are governed by CLSI guidelines (EP06-Ed2 and EP17-A2 respectively), which typically involve analyzing serially diluted samples.
- Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be analytical performance studies conducted on patient samples, but whether they were retrospective or prospective is not specified. Given the nature of an IVD, these are typically conducted prospectively in a lab setting using banked or newly collected samples.
Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts:
- Not Applicable in the traditional AI/ML sense. For an IVD assay, the "ground truth" for the test set is either:
  - Clinical Diagnosis: For the diagnostic claim ("aid in the diagnosis of thyroid autoimmune disorders"), the ground truth would be established by independent clinical diagnosis (e.g., by endocrinologists) typically using a variety of clinical data and other diagnostic tests. This information is usually part of clinical utility studies, which are not detailed in this analytical performance summary.
  - Reference Method/Predicate Product: For the analytical performance studies like Method Comparison, the "ground truth" or reference is the result obtained from the predicate device (Access TPO Antibody Assay on Access 2 Immunoassay System). The predicate device itself is validated against established (often clinical) criteria.
  - Known Concentrations/Materials: For linearity, imprecision, and detection capability studies, the "ground truth" is established by using characterized materials with known concentrations, or by measuring the variability around the mean of repeated measurements. This doesn't involve medical experts in the adjudication sense.
Adjudication Method for the Test Set:
- Not Applicable. Adjudication is typically for subjective interpretations (like image reading). For an IVD, the results are quantitative measurements from an instrument. The "adjudication" is essentially the statistical analysis (e.g., Passing-Bablok regression, CV calculations) of these quantitative results against predefined criteria or a reference method.
If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
- No. An MRMC study is relevant for interpreting subjective data (like medical images) where human readers are involved. This document describes the analytical performance of an in vitro diagnostic assay that produces quantitative results, not an image interpretation or decision support AI.
If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, in the context of an IVD. The entire analytical performance evaluation (Method Comparison, Imprecision, Linearity, Detection Capability) describes the standalone performance of the Access TPO Antibody assay on the Dxl 9000 system. It functions automatically based on its chemiluminescent immunoassay technology to produce a quantitative result. There is no "human-in-the-loop" aspect to the measurement itself, though human lab personnel operate the instrument and interpret the results.
The Type of Ground Truth Used:
- Known concentrations, reference method results (predicate device), and statistical averages.
  - For Method Comparison, the "ground truth" for comparison is the result obtained from the predicate Access 2 Immunoassay System.
  - For Imprecision, the "ground truth" is the mean concentration of the samples derived from repeated measurements, and the variability around that mean.
  - For Linearity, the ground truth is derived from known dilutions of a high-concentration material.
  - For Detection Capability (LoB, LoD, LoQ), the ground truth involves the statistical analysis of measurements of blank samples and low-concentration samples.
The Sample Size for the Training Set:
- Not Applicable. This is an IVD assay relying on chemical and immunological reactions, not a machine learning algorithm that requires a "training set" in the AI/ML sense. The device's parameters are determined during its design and optimization phases by Beckman Coulter, based on established immunoassay principles.
How the Ground Truth for the Training Set was Established:
- Not Applicable. As above, there is no "training set" for this type of device in the AI/ML context. The assay's performance characteristics (e.g., reactivity, linearity, precision) are inherent to its reagent formulation and instrument design, which are optimized by the manufacturer using internal R&D processes guided by scientific principles and regulatory standards.

Summary

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August 9, 2024

Beckman Coulter Inc. Neha Desai Staff Quality and Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318

Re: K240469

Trade/Device Name: Access TPO Antibody Regulation Number: 21 CFR 866.5870 Regulation Name: Thyroid Autoantibody Immunological Test System Regulatory Class: Class II Product Code: JZO Dated: February 16, 2024 Received: February 20, 2024

Dear Neha Desai:

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 OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 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 (OS) 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,

Ying Mao -S

Ying Mao, Ph.D. Branch Chief Division of Immunology and Hematology 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) K240469

Device Name Access TPO Antibody

Indications for Use (Describe)

The detection of TPOAb is an aid in the diagnosis of thyroid autoimmune disorders.

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 K240469

Submitted Bv:

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

Primarv Contact:

Neha Desai Staff Quality and Regulatory Affairs Phone: (612) 244-9788 Email: nhdesai@beckman.com

Alternate Contact:

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

Device Name

Common Name: Access TPO Antibody Trade Name: Access TPO Antibody Reagent on Dxl 9000 Access Immunoassay Analyzer Classification Name: Thyroid Autoantibody Classification Requlation: [21 CFR 866.5870]

Predicate Device

Device Name: Access TPO Antibody 510(k) Numbers: K061382

Device Description

The Access TPO Antibody assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroperoxidase antibody (TPO Ab) levels in human serum and plasma using the Access Immunoassay Systems.

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After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of analyte in the sample. Analyte concentration is automatically determined from a stored calibration.

Intended Use

The Access TPO Antibody assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroperoxidase antibody (TPO Ab) levels in human serum and plasma using the Access Immunoassay Systems. The detection of TPO Ab is an aid in the diagnosis of thyroid autoimmune disorders.

Parameter	Access TPO Antibody Assayon Access 2 ImmunoassaySystem (Predicate)	Access TPO Antibody Assay onDxl 9000 Access ImmunoassaySystem
Intended use	The Access TPO Antibody assayis a paramagnetic particle,chemiluminescent immunoassayfor the quantitativedetermination of thyroperoxidaseantibody (TPO Ab) levels inhuman serum and plasma usingthe Access ImmunoassaySystems. The detection of TPOAb is an aid in the diagnosis ofthyroid autoimmune disorders.	Same
Technology	2-site (sandwich)chemiluminescent	Same
Format	Chemiluminescent	Same
Calibration	Utilizes a stored multi-pointcalibration curve	Same
Sample Type	Serum and plasma (EDTA,Lithium heparin)	Same
Sample Volume	10 µL	Same
MeasuringRange	0.25 - 1,000 IU/mL	Same
Instrument	Access Immunoassay system	Dxl 9000 Access ImmunoassayAnalyzer
Substrate	Access Substrate	Lumi-Phos Pro Substrate

Comparison of Technological Characteristics to the Predicate

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Standard/Guidance Document Referenced (if applicable):

These standards can be copied or found from regulatory submission reports:

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

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

CLSI EP09c 3® Edition: Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Third Edition

CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition

Summary of Studies

Method Comparison:

A study based on CLSI EP09c, 3rd Edition using Passing-Bablok regression and Pearson's correlation compared the Access 2 Immunoassay System and the Dxl 9000 Access Immunoassay Analyzer.

N	ConcentrationRange*(IU/mL)	Slope	Slope95% CI	Intercept	Intercept95% CI	CorrelationCoefficientR
219	0.35 - 980.9	1.06	1.04 - 1.08	-0.26	(-0.32) - (-0.22)	-0.978

*Range is Access 2 values

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Imprecision:

The assay was designed to have within-laboratory imprecision as listed below:

· < 0.07 IU/mL SD at concentrations < 0.6 IU/mL
< 12.0% CV at concentrations ≥ 0.6 IU/mL and < 450.0 IU/mL
< 15.0% CV at concentrations ≥ 450.0 IU/mL

A study based on CLSI EP05-A3 performed on the Dxl 9000 Access Immunoassay Analyzer tested multiple samples in duplicate in 2 runs per day for a minimum of 20 days.

Concentration (IU/mL)		Repeatability(Within-Run)		Between-Run		Between-Day		Within-Laboratory
Sample	N	Mean	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 1	80	0.35	0.02	6.9	0.00	0.0	0.00	0.0	0.02	6.9
Sample 2	80	5.5	0.36	6.7	0.00	0.0	0.00	0.0	0.36	6.7
Sample 3	80	20	1.12	5.6	0.00	0.0	0.52	2.6	1.23	6.2
Sample 4	80	318	18.59	5.8	0.13	0.0	10.50	3.3	21.35	6.7
Sample 5	80	747	77.4	10.4	52.21	7.0	24.18	3.2	96.48	12.9

Linearity: A study based on CLSI EP06-Ed2 performed on the Dxl 9000 Access Immunoassay Analyzer determined the assay demonstrated linearity across the measuring interval.

Detection Capability:

Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) studies were conducted on the Dxl 9000 Access Immunoassay Analyzer following CLSI guideline EP17-A2.

	IU/mL
Limit of Blank (LoB)	0.19
Limit of Detection (LoD)	0.23
Limit of Quantitation (LoQ)	0.25

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Substantial Equivalence Comparison Conclusion

Beckman Coulter's Access TPO Antibody Assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to the Access TPO Antibody 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

§ 866.5870 Thyroid autoantibody immunological test system.

(a)
Identification. A thyroid autoantibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the thyroid autoantibodies (antibodies produced against the body's own tissues). Measurement of thyroid autoantibodies may aid in the diagnosis of certain thyroid disorders, such as Hashimoto's disease (chronic lymphocytic thyroiditis), nontoxic goiter (enlargement of thyroid gland), Grave's disease (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid.(b)
Classification. Class II (performance standards).