Access Thyroglobulin assay is a paramagetic particle, chemiluminescent immunossay for the quantitative determination of thyroglobulin levels in human serum and plasma using the Access Immunoassay Systems. This device is intended to aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy), and who lack serum thyroglobulin antibodies.

Device Description

The Access Thyroqlobulin assay consists of the reagent pack and calibrators. Other items needed to run the assay include the Access Thyroglobulin Sample Diluent, substrate and wash buffer. The Access Tq assay along with the Access wash buffer and substrate are designed for use with the Access Immunoassay Systems in a clinical laboratory setting.

The change does not impact or change the other components that are used with this reagent pack. The modification does not affect the indications of the device or alter the fundamental scientific technology of the device.

A description of the reagent pack is provided below.

Well	Ingredients
R1a:	Dynabeads* paramagnetic particles coated with streptavidinand coupled to biotinylated mouse monoclonalantithyroglobulin antibodies, suspended in a TRIS buffer withprotein (bovine), < 0.1% sodium azide, and 0.1% ProClin**300.
R1b:	Mouse monoclonal anti-thyroglobulin-alkaline phosphatase(bovine) conjugate in a TRIS buffer with protein (bovine,murine), < 0.1% sodium azide, and 0.1% ProClin 300.
R1c:	HEPES buffer with protein (bovine and mouse), < 0.1% sodiumazide, and 0.5% ProClin 300.

AI/ML Overview

The provided document is a 510(k) Premarket Notification from the FDA for the Access Thyroglobulin assay. It does not describe an AI/ML-based medical device. Therefore, many of the requested criteria about AI/ML studies (such as MRMC studies, ground truth establishment for training sets, number of experts for test set ground truth, etc.) are not applicable to this submission.

The acceptance criteria and study proving the device meets them are related to the analytical performance of an immunoassay, not a software algorithm.

Here's a breakdown based on the provided text, addressing the applicable points and noting where information is not present or not relevant to AI/ML:

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

The document focuses on demonstrating substantial equivalence to a predicate device, primarily through a matrix comparison study for a new sample type (plasma in addition to serum). The "acceptance criteria" are implied by the statistical analyses and acceptable ranges for slope, intercept, and correlation coefficient in the matrix comparison, aiming for agreement between the new sample type and the established serum sample type.

Acceptance Criteria (Implied by Study Design for Matrix Comparison):
For the Matrix Comparison study, the implicit acceptance criteria are that the Passing-Bablok linear regression results (slope, intercept, and correlation coefficient) demonstrate substantial equivalence between the new sample types (Li-heparin plasma, Na-heparin plasma) and serum. While explicit numeric acceptance criteria are not stated, typically for such comparisons, a slope close to 1, an intercept close to 0, and a high correlation coefficient (e.g., >0.97) are expected within their confidence intervals.

Reported Device Performance (Matrix Comparison):

Plasma/Serum	N	Range (ng/mL)	Slope (95% CI)	Intercept (95% CI)	Correlation Coefficient (r)
Li-heparin plasma vs Serum	45	0.227 to 494.070	1.000 (0.983; 1.015)	0.163 (-0.212; 0.712)	0.999
Na-heparin plasma vs Serum	45	0.227 to 494.070	1.021 (1.010; 1.039)	0.147 (-0.246; 0.952)	0.999

Other Performance Claims Transferred from Predicate:
The document states that claims for "method comparison, imprecision, reproducibility, high-dose hook effect, linearity, dilution recovery, detection capability and analytical specificity are being transferred from file K220972." This implies these studies were performed and met acceptance criteria for the predicate device, and the current modification (addition of plasma sample type) does not invalidate them. Explicit tables for these are not in the provided text.

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

Test Set Sample Size: For the Matrix Comparison study, 45 matched sets of serum and plasma samples were used for each comparison (Li-heparin plasma vs Serum, and Na-heparin plasma vs Serum). The minimum specified was 40 matched sets.
Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. Given it's a clinical lab device, the samples would typically be from clinical settings.

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

This is not applicable as the device is an immunoassay, not an AI/ML device relying on human interpretation of images or other complex data for ground truth. The "ground truth" here is the quantitative measurement of thyroglobulin by the predicate method (serum measurement) against which the new sample type (plasma measurement) is compared. The reference values are analytical measurements, not expert consensus.

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

Not applicable for an immunoassay analytical validation. The ground truth (serum concentration) is established by the assay itself, not by human adjudication.

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 is not an AI/ML device, and there are no "human readers" interpreting images assisted by AI.

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

Yes, in a sense. The "standalone" performance for this device refers to its analytical performance as a laboratory test. The Matrix Comparison study assesses the device's capability to accurately measure thyroglobulin in plasma samples compared to serum samples, without human interpretive input affecting the measurement itself. The results shown in point 1 demonstrate this "standalone" analytical performance.

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

The ground truth for the matrix comparison study was the quantitative thyroglobulin concentration measured in human serum using the previously cleared Access Thyroglobulin assay. The new sample types (plasma) were compared to these established serum values.

8. The sample size for the training set

Not applicable. This is not an AI/ML device that requires a training set. The assay's parameters are determined through reagent development and analytical validation, not machine learning training.

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

Not applicable, as there is no training set for this type of device.

Summary

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June 7, 2024

Beckman Coulter, Inc. Muhammad Sheikh Staff Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318

Re: K241423

Trade/Device Name: Access Thyroglobulin Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: MSW Dated: May 20, 2024 Received: May 20, 2024

Dear Muhammad Sheikh:

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 medical devices and radiation-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) K241423

Device Name Access Thyroglobulin

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 Tg 510(K) Summary

Immunodiagnostic Development Center

1000 Lake Hazeltine Drive Chaska, Minnesota 55318-1084

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.

The assigned 510(k) number: K241423

Submitted By:

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

Primary Contact:

Muhammad Sheikh, Staff Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, MN 55318 Phone: +1 (201) 335-0632 Email:msheikh@beckman.com

Alternate Contact:

Kate Oelberg, Senior Staff Quality and Regulatory Affairs Office 1000 Lake Hazeltine Drive Chaska, MN 55318 Phone: (612) 431-7315 Email:kmoelberg@beckman.com

Date Prepared:

June 4, 2024

Device Name:

Proprietary / Trade Name: Access Thyroglobulin Common Name: Thyroglobulin Chemiluminescence Immunoassay Classification Description: Tumor-associated antigen immunological test system Classification Regulation: 21 CFR 866.6010 Classification Product Code: MSW

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Predicate Device:

The modified Access Thyroglobulin assay claims substantial equivalence to previously cleared Access Thyroglobulin assay, FDA 510(k) Number K220972, cleared September 15, 2023.

Device Description:

A description of the reagent pack is provided below.

Well	Ingredients
R1a:	Dynabeads* paramagnetic particles coated with streptavidinand coupled to biotinylated mouse monoclonalantithyroglobulin antibodies, suspended in a TRIS buffer withprotein (bovine), < 0.1% sodium azide, and 0.1% ProClin**300.
R1b:	Mouse monoclonal anti-thyroglobulin-alkaline phosphatase(bovine) conjugate in a TRIS buffer with protein (bovine,murine), < 0.1% sodium azide, and 0.1% ProClin 300.
R1c:	HEPES buffer with protein (bovine and mouse), < 0.1% sodiumazide, and 0.5% ProClin 300.

'Dynabead® is a registered trademark of Dynal A.S., Oslo, Norway

**ProClin™ is a trademark of The Dow Chemical Company ("Dow") or an affiliate company of Dow.

Intended Use:

Access Thyroglobulin assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin levels in human serum and plasma using the Access Immunoassay Systems. This device is intended to aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy), and who lack serum thyroglobulin antibodies.

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Comparison to the Predicate:

Characteristic	Predicate DeviceAccess Thyroglobulin (K220972)	Modified Device AccessThyroglobulin
Intended Use	Access Thyroglobulin assay is aparamagnetic particle,chemiluminescent immunoassay forthe quantitative determination ofthyroglobulin levels in human serumusing the Access ImmunoassaySystems. This device is intended toaid in monitoring for the presence ofpersistent or recurrent/metastaticdisease in patients who havedifferentiated thyroid cancer (DTC)and have had thyroid surgery (with orwithout ablative therapy), and wholack serum thyroglobulinantibodies.	Access Thyroglobulin assay is aparamagnetic particle,chemiluminescent immunoassay for thequantitative determination ofthyroglobulin levels in human serumand plasma using the AccessImmunoassay Systems. This device isintended to aid in monitoring for thepresence of persistent orrecurrent/metastatic disease in patientswho have differentiated thyroid cancer(DTC) and have had thyroid surgery(with or without ablative therapy), and wholack serum thyroglobulinantibodies.
AnalyteMeasured	Thyroglobulin	Same
Technology	Sandwich immunoassay	Same
Format	Chemiluminescent	Same
Method	Automated	Same
Assayarchitecture	Biotinylated mouse monoclonalantithyroglobulin antibodies pre-coupled to paramagnetic particlescoated with streptavidin	Same
Antibodies	Mouse monoclonal antibodies	Same
BiotinInterference	No significant interference (± 10%)observed in samples containing up to3,510 ng/mL of biotin.	Same
Measuring Range	0.1 - 500 ng/mL	Same
Sample Type	Human serum	Human serum or plasma
Sample Volume	40 μL	Same
Substrate	Access Substrate	Same
Instrument	Access 2 Immunoassay Analyzer	Same

The modified device and previously cleared predicate device are compared below

Standard/Guidance Document Referenced (if applicable):

CLSI EP35 Assessment of Equivalence of Suitability of Specimen Types for Medical Laboratory Measurement Procedures – First Edition

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Summary of Studies:

The claims for the method comparison, imprecision, reproducibility, high-dose hook effect, linearity, dilution recovery, detection capability and analytical specificity are being transferred from file K220972.

Matrix Comparison: A comparison of minimum of forty (40) matched sets of serum, lithium heparin plasma and sodium heparin plasma samples with thyroglobulin concentrations within assay measuring range were compared using Passing-Bablok linear regression analysis. Representative results are summarized in the table below.

Plasma/Serum	N	Range(ng/mL)	Slope(95% CI)	Intercept(95% CI)	CorrelationCoefficient(r)
Li-heparin plasmavs Serum	45	0.227 to494.070	1.000(0.983;1.015)	0.163(-0.212;0.712)	0.999
Na-heparin plasmavs Serum	45	0.227 to494.070	1.021(1.010;1.039)	0.147(-0.246;0.952)	0.999

Sample type comparison on Access 2 Immunoassay System

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Conclusion:

The modified device has the same intended use and fundamental scientific technology as the predicate device. The modified device is as safe and effective as the predicate device, as demonstrated through verification testing.

The information provided in this submission demonstrates that the modified device is substantially equivalent to the predicate device.

Regulation Number and Section

§ 866.6010 Tumor-associated antigen immunological test system.

(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.