K Number
K240996
Date Cleared
2024-07-03

(83 days)

Product Code
Regulation Number
866.5870
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The Access Thyroglobulin Antibody II assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin antibody levels in human serum and plasma using the Access Immunoassay Systems. The measurement of thyroid autoantibodies may aid in the diagnosis of Hashimoto's disease, nontoxic goiter, and Graves' disease.

Device Description

The Access Thyroqlobulin Antibody II assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin antibody levels in human serum and plasma using the Access Immunoassay Systems. The measurement of thyroid autoantibodies may aid in the diagnosis of Hashimoto's disease, nontoxic goiter, and Graves' disease.

The Access Thyroglobulin Antibody II assay is a sequential two-step immunoenzymatic ("sandwich") assay. A sample is added to a reaction vessel with paramagnetic particles coated with the thyroglobulin protein. The TgAb in the sample binds to the thyroglobulin coated on the particles. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. The thyroglobulin-alkaline phosphatase conjugate is added and binds to the TgAb.

After second 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

Here's a detailed breakdown of the acceptance criteria and study information for the Beckman Coulter Access Thyroglobulin Antibody II device, extracted from the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

ParameterAcceptance Criteria (Predicate Device)Reported Device Performance (Modified Device - Dxl 9000 Access Immunoassay Analyzer)
Intended UseQuantitative determination of thyroglobulin antibody levels in human serum and plasma to aid in the diagnosis of Hashimoto's disease, nontoxic goiter, and Graves' disease.Same (No change in Intended Use)
Analyte MeasuredThyroglobulin AntibodySame
Technology / Format / MethodSandwich immunoassay / Chemiluminescent / AutomatedSame
Sample TypeHuman serum or plasmaSame
Sample Volume10 uLSame
Measuring Range1.5 - 2,500 IU/mLSame
Blocker ReagentsBiotin and alkaline phosphatase included in reagent pack as blockersSame
Biotin InterferenceNo significant interference (± 10%) observed in samples containing up to 3,510 ng/mL of biotin.Same (Explicitly stated in the comparison table)
Imprecision (Repeatability)SD ≤ 1.5 for values < 15 IU/mL; CV ≤ 10.0% for values ≥ 15 IU/mL and < 1000 IU/mL; CV ≤ 15.0% for values ≥ 1000 IU/mLWithin-Laboratory Imprecision: - Sample 1 (2.4 IU/mL): 5.2% CV (meets ≤ 1.5 IU/mL SD, which is equivalent to 62.5% CV. The actual SD is 0.1, making the %CV 4.2% for repeatability) - Sample 2 (188 IU/mL): 4.1% CV (meets ≤ 10.0% CV) - Sample 3 (727 IU/mL): 4.2% CV (meets ≤ 10.0% CV) - (Partial data for Sample ~1000 IU/mL is cut off, but the predicate applies CV ≤ 15.0% for values ≥ 1000 IU/mL)
ReproducibilityNot explicitly stated as a separate acceptance criterion for the predicate, but implied by the imprecision criteria.Reproducibility (Overall): - Sample 1 (2.6 IU/mL): 5.8% CV (within expected range for low concentration) - Sample 2 (184 IU/mL): 3.8% CV (well within 10.0% CV) - Sample 3 (744 IU/mL): 3.1% CV (well within 10.0% CV) - Sample 4 (1503 IU/mL): 3.6% CV (well within 15.0% CV) - Sample 5 (1966 IU/mL): 6.4% CV (well within 15.0% CV)
LinearityThe assay demonstrates linearity across the measuring interval.Determined to demonstrate linearity across the measuring interval (no quantitative data given, but implied successful).
Limit of Blank (LoB)Assumed to be ≤ 0.1 IU/mL (based on reported value)0.1 IU/mL
Limit of Detection (LoD)Assumed to be ≤ 0.2 IU/mL (based on reported value)0.2 IU/mL
Limit of Quantitation (LoQ)≤ 1.5 IU/mL for ≤ 20% within-lab CV1.5 IU/mL (at ≤ 20% within-lab CV)
Method Comparison (Slope)Assumed to be close to 1.0 (for substantial equivalence to predicate)0.97 (95% CI: 0.95 – 0.99)
Method Comparison (Intercept)Assumed to be close to 0 (for substantial equivalence to predicate)-0.37 (95% CI: -0.99 – 0.047)
Method Comparison (Correlation Coefficient)Assumed to be close to 1.0 (for substantial equivalence to predicate)1.00

Note: The primary goal of this submission (K240996) is to demonstrate substantial equivalence of the same device on a new instrument platform (Dxl 9000 Access Immunoassay Analyzer) compared to its predicate on the Access 2 Immunoassay System. Therefore, the "acceptance criteria" are largely derived from the established performance of the predicate device.


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

  • Method Comparison Study (CLSI EP09c):
    • Sample Size: N = 114
    • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, such studies typically use clinical samples that may be either retrospectively collected or prospectively collected for validation purposes.
  • Imprecision Study (CLSI EP05-A3):
    • Sample Size: 3 distinct "Samples" (concentrations) were tested. Each sample was tested 80 times (duplicate R.L per day for a minimum of 20 days).
    • Data Provenance: Not explicitly stated. Assumed to be laboratory samples or controls prepared for method validation.
  • Reproducibility Study (CLSI EP05-A3):
    • Sample Size: 5 distinct "Samples" (concentrations) were tested. Each sample was tested 75 times (replicates of 5 per day for a minimum of 5 days on 3 instruments).
    • Data Provenance: Not explicitly stated. Assumed to be laboratory samples or controls prepared for method validation.
  • Detection Capability (LoB, LoD, LoQ) Study (CLSI EP17-A2):
    • Sample Size: Not explicitly stated for each determination, but these studies typically involve multiple replicates of blank, low-level, and higher-level samples.
    • Data Provenance: Not explicitly stated. Assumed to be laboratory samples or controls.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This document describes a clinical laboratory device (an immunoassay), not an AI/imaging device requiring expert interpretation of results for ground truth. Therefore, the concepts of "experts to establish ground truth" (in the context of clinical interpretation or diagnosis from an image) and their "qualifications" are not applicable here.

For this type of device, ground truth is established through:

  • Reference Methods / Predicate Devices: The Access 2 Immunoassay System (predicate) served as the comparator for the method comparison study to assess the "truth" of the Dxl 9000 system's measurements.
  • Certified Reference Materials/Standards: Calibrators and controls with known analyte concentrations, often traceable to international standards, are used to establish accuracy and calibration.
  • Clinical Diagnosis: For the "Indications for Use," the device aids in diagnosis, meaning its results are interpreted by clinicians in conjunction with other clinical information. The diagnostic accuracy studies (sensitivity, specificity) in relation to a "gold standard" clinical diagnosis are typically part of a larger clinical trial not detailed in this specific 510(k) summary for a platform change.

4. Adjudication Method for the Test Set

Not applicable. As this is an immunoassay device assessing quantitative levels of an antibody, there is no "adjudication method" in the sense of reconciling divergent expert interpretations of qualitative or semi-quantitative data. The "test set" results—the quantitative values—are compared statistically to the reference method (predicate device) and assessed against performance specifications (imprecision, linearity, detection limits).


5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for AI/imaging devices where multiple human readers interpret complex cases (e.g., medical images) and AI assistance might improve their performance. This document is for a medical laboratory immunoassay for quantitative measurement of thyroglobulin antibody, not an AI-assisted diagnostic tool for human interpretation.


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

While the device operates "standalone" in the sense that the instrument performs the assay and generates a quantitative result without human intervention during the analytical process, this is not an "algorithm-only" study in the context of AI. The performance studies (imprecision, linearity, method comparison, detection capability) represent the standalone analytical performance of the instrument/reagent system. The "human-in-the-loop" would be the clinician interpreting the numerical result in the context of a patient's overall clinical picture, but the device itself functions automatically.


7. The Type of Ground Truth Used

  • Quantitative Reference Values: For the performance studies, the ground truth is established through various means:
    • Method Comparison: The results obtained from the predicate device (Access Thyroglobulin Antibody II on the Access 2 Immunoassay System) serve as the reference standard.
    • Imprecision & Reproducibility: Derived from repeated measurements of samples (often control materials or pooled patient samples) to assess variability. The "true" value for these samples is either assigned by the manufacturer or determined through extensive testing.
    • Linearity: Determined by creating serially diluted samples from a high-concentration sample, where the expected concentration of each dilution is the "ground truth."
    • Detection Capability (LoB, LoD, LoQ): Established using blank samples and low-concentration spiked samples, with statistical methods determining the lowest detectable/quantifiable levels.

8. The Sample Size for the Training Set

This document does not describe a machine learning or AI algorithm development that would typically involve a "training set." The studies described are for analytical validation of an immunoassay on a new instrument platform, focusing on demonstrating equivalent performance to a predicate device. Therefore, a "training set" in the AI sense is not applicable.


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

Not applicable, as there is no "training set" in the context of AI or machine learning for this immunoassay device.

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA acronym along with the full name of the agency on the right. The FDA part of the logo is in blue, with the acronym in a square and the full name, "U.S. Food & Drug Administration," written out next to it.

July 3, 2024

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

Re: K240996

Trade/Device Name: Access Thyroglobulin Antibody II Regulation Number: 21 CFR 866.5870 Regulation Name: Thyroid Autoantibody Immunological Test System Regulatory Class: Class II Product Code: JNL Dated: April 11, 2024 Received: April 11, 2024

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).

{1}------------------------------------------------

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

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K240996

Device Name Access Thyroglobulin Antibody II

Indications for Use (Describe)

The Access Thyroglobulin Antibody II assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin antibody levels in human serum and plasma using the Access Immunoassay Systems. The measurement of thyroid autoantibodies may aid in the diagnosis of Hashimoto's disease, nontoxic goiter, and Graves' disease.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

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: K240996

Date Prepared: July 2, 2024

Submitted By:

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: kmoelberq@beckman.com

Alternate Contact:

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

Device Name

Proprietary/ Trade Name: Access Thyroglobulin Antibody II Common Name: Thyroid autoantibody immunological test system Classification Description: Thyroid autoantibody immunological test system. Classification Regulation: 21 CFR 866.5870 Classification Product Code: JNL

Predicate Device

Device Name: Access Thyroglobulin Antibody II 510(k) Numbers: K213517

Device Description

The Access Thyroqlobulin Antibody II assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin antibody levels in human serum and plasma using the Access Immunoassay Systems. The measurement of thyroid autoantibodies may aid in the diagnosis of Hashimoto's disease, nontoxic goiter, and Graves' disease.

The Access Thyroglobulin Antibody II assay is a sequential two-step immunoenzymatic ("sandwich") assay. A sample is added to a reaction vessel with paramagnetic particles coated with the thyroglobulin protein. The TgAb in the sample binds to the thyroglobulin coated on the

{4}------------------------------------------------

particles. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. The thyroglobulin-alkaline phosphatase conjugate is added and binds to the TgAb.

After second 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 Thyroglobulin Antibody II (TgAb) assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin antibody levels in human serum and plasma using the Access Immunoassay Systems. The measurement of thyroid autoantibodies may aid in the diagnosis of Hashimoto's disease, nontoxic goiter, and Graves' disease.

CharacteristicPredicate DeviceAccess Thyroglobulin Antibody II(K213517)Modified DeviceAccess Thyroglobulin Antibody II
Intended UseThe Access Thyroglobulin AntibodyII assay is a paramagnetic particle,chemiluminescent immunoassay forthe quantitative determination ofthyroglobulin antibody levels inhuman serum and plasma using theAccess ImmunoassaySystems. The measurement ofthyroid autoantibodies may aid inthe diagnosis of Hashimoto'sdisease, nontoxic goiter,and Graves' disease.Same
AnalyteMeasuredThyroglobulin AntibodySame
TechnologySandwich immunoassaySame
FormatChemiluminescentSame
MethodAutomatedSame
Sample TypeHuman serum or plasmaSame
Sample Volume10 uLSame
MeasuringRange1.5 -2,500 IU/mLSame
BlockerreagentsBiotin and alkaline phosphataseincluded in reagent pack as blockersSame

Comparison of Technological Characteristics to the Predicate

{5}------------------------------------------------

BiotinInterferenceNo significant interference (± 10%)observed in samples containing upto 3,510 ng/mL of biotin.Same
ImprecisionSD ≤ 1.5 for values < 15 IU/mLCV ≤ 10.0% for values ≥ 15 IU/mLand < 1000 IU/mLCV ≤ 15.0% for values ≥ 1000 IU/mLSame
InstrumentAccess Immunoassay systemDxl 9000 Access ImmunoassayAnalyzer
SubstrateAccess SubstrateLumi-Phos Pro Substrate

Standard/Guidance Document Referenced (if applicable):

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

CLSI EP06-201 Edition -: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline

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

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

NConcentrationRange*(IU/mL)SlopeSlope95% CIInterceptIntercept95% CICorrelationCoefficientR
1142.3 – 2,4630.970.95 – 0.99-0.37-0.99 –0.0471.00

*Range is Access 2 values

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

  • ≤ 1.5 IU/mL SD at concentrations < 15 IU/mL
  • ≤ 10.0% CV at concentrations ≥ 15 IU/mL and < 1,000 IU/mL
  • · ≤ 15.0% CV at concentrations ≥ 1,000 IU/mL

A study based on CLSI EP05-A312 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-runBetween-dayWithin-Laboratory
SampleNMeanSD%CVSD%CVSD%CVSD%CV
Sample 1802.40.14.20.12.50.12.00.15.2
Sample 2801886.63.50.00.03.92.17.64.1
Sample 38072722.03.00.00.021.32.930.64.2

{6}------------------------------------------------

Sample. 10039.61 1 10000001
Sample :1000G10.56.980 .and of the first of the first of the first of the first of the first of the first of the first for the first for the first for the first for the first for the first for the f

Reproducibility: A study based on CLSI EP05-A312 performed on the Dxl 9000 Access Immunoassay Analyzer tested multiple samples in replicates of 5 per day for a minimum of 5 days on 3 instruments.

Concentration (IU/mL)Repeatability(Within-run)Between-dayBetween -instrumentReproducibility
SampleNMeanSDIU/mL%CVSDIU/mL%CVSDIU/mL%CVSD IU/mL%CV
Sample 1752.60.14.70.11.90.12.80.25.8
Sample 2751844.12.22.91.64.82.66.93.8
Sample 37574419.22.612.11.62.50.322.83.1
Sample 475150343.92.915.21.026.31.853.43.6
Sample 575196668.23.5102.25.223.91.2125.16.4

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 EP17-A2.

IU/mL
Limit of Blank (LoB)0.1
Limit of Detection (LoD)0.2
Limit of Quantitation (LoQ)≤ 20% within-lab CV1.5

Substantial Equivalence Comparison Conclusion

Beckman Coulter's Access Thyroglobulin Antibody II assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to the Access Thyroglobulin Antibody II 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.

§ 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).