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 TPO antibodies is an aid in the diagnosis of thyroid autoimmune disorders.

Device Description

The Access TPO Antibody reagents, calibrators, and the Access Immunoassay Analyzers (Access, Access 2, Synchron LXi 725, UniCel DxC 600i, and UniCel Dxl 800) comprise the Access Immunoassay Systems for the determination of thyroperoxydase antibody (TPO) levels in human serum and plasma.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the provided device, based on the input text:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance	Study Type
Imprecision (Within-run CV)	Ranged from 2.6% CV to 7.9% CV for concentrations from approximately 0.6 to 809 IU/mL.	Analytical Study
Imprecision (Between-run CV)	Ranged from 1.3% CV to 4.9% CV.	Analytical Study
Imprecision (Total CV)	Ranged from 3.1% CV to 8.7% CV.	Analytical Study
Dilution Recovery (Linearity)	Mean % recovery ranged from 86.4% to 94.9%. Note: "Due to varying antigen specificity, and avidity of TPOAb in their epitope reactions, some samples may not dilute linearly."	Analytical Study
Methods Comparison (Against a commercially available immunoassay system)	Range of observations: 5-1000Slope: 1.0207 (95% confidence interval 0.9722 to 1.0693)Intercept: -10.9123 (95 % confidence interval -24.6421 to 2.8175)Correlation coefficient (r): 0.97Results indicate the slope and intercept are not significantly different from one and zero respectively.	Analytical Study
Analytical Specificity (Interference from potential sample contaminants)	No significant interference from bilirubin, hemoglobin, human serum albumin, and triglycerides.	Analytical Study
Stability (TPOAb reagents)	Stable for 56 days after opening.	Analytical Study
Stability (TPOAb calibrators)	Stable for 120 days after opening.	Analytical Study
Stability (Calibration)	Stable for 56 days.	Analytical Study
Expected/Normal Reference Range (Healthy males <30 years)	Upper reference limit below 9 IU/mL (95% non-parametric determination).	Clinical Study
Expected/Normal Reference Range (Normal population 18-80 years with specific screening criteria)	93% of samples fell below 9 IU/mL (out of 492 tested).	Clinical Study
Clinical Sensitivity (Hashimoto's Thyroiditis patients)	100% of 54 patients tested positive.	Clinical Study
Clinical Sensitivity (Graves' Disease patients)	77.5% of 40 patients tested positive.	Clinical Study

Study Details

Sample size used for the test set and the data provenance:
- Imprecision: Not explicitly stated as a single "test set" sample size but tested across concentrations from approximately 0.6 to 809 IU/mL. Data provenance not specified.
- Dilution Recovery (Linearity): "Multiple dilutions of serum samples were analyzed." Specific sample size not given. Data provenance not specified.
- Methods Comparison: 119 values. Data provenance not specified.
- Analytical Specificity: Not specified. Data provenance not specified.
- Stability: Specific sample sizes not given for stability testing. Data provenance not specified.
- Expected Values:
  - Healthy male population <30 years: Sample size not explicitly stated for the primary reference range establishment, but criteria outlined by NACB were followed. Data provenance: United States.
  - Normal population (18-80 years): 679 normal samples collected, with 492 samples ultimately tested after screening. Data provenance: United States.
- Clinical Sensitivity:
  - Hashimoto's Thyroiditis: 54 patients. Data provenance not specified.
  - Graves' Disease: 40 patients. Data provenance not specified.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. This device is an immunoassay designed to quantitatively measure a biomarker. "Ground truth" is based on the chemical measurement itself and comparison to established reference methods or clinical diagnosis. Clinical diagnoses (Hashimoto's Thyroiditis, Graves' Disease) forming the basis for clinical sensitivity would have been made by medical professionals, but the number and qualifications are not detailed here.
Adjudication method for the test set: Not applicable for a quantitative immunoassay. Test results are numerical outputs directly from the device.
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, not an AI-assisted diagnostic imaging or interpretation system involving human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Yes, all analytical and clinical performance studies described are for the device (Access TPO Antibody assay on Access Immunoassay Systems) operating in a standalone, automated fashion without human intervention in the result determination process itself. Human involvement is in sample collection, running the assay, and interpreting the results in a clinical context.
The type of ground truth used:
- Analytical Studies: Ground truth is based on established laboratory methodologies and expected performance characteristics for assays (e.g., linearity, precision, recovery, non-interference). For method comparison, the "ground truth" is the result from the predicate or commercially available immunoassay system.
- Clinical Studies:
  - Expected Values: Clinical criteria for healthy individuals, including TSH levels and absence of thyroid/autoimmune disease, defined the "normal" ground truth. For the <30 age group, NACB criteria were used.
  - Clinical Sensitivity: Clinical diagnosis of Hashimoto's Thyroiditis and Graves' Disease by medical professionals served as the ground truth.
The sample size for the training set: Not applicable in the context of machine learning or AI. This is a traditional immunoassay, not an algorithm that has a "training set" in that sense. The assay is developed and validated, but it doesn't "learn" from a training set in the way an AI model does.
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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JUL - 6 2006

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 is: K061382

Submitter's Name and Address

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: (952) 368-1383 Fax: (952) 368-7610 Contact: Valynda Machen

Date Prepared: June 19, 2006

Device Names

Proprietary Name:	TPO Antibody and TPO Antibody Calibrators on theAccess® Immunoassay Systems
Common Name:	Immunoassay for the determination of thyroperoxydase antibodies
Classification Name:	System, Test, Thyroid Autoantibody

Predicate Device

Immulite 2000 Anti-TPO Ab Diagnostic Products Corporation 5700 West 96th Street Los Angeles, CA 90045-5597

510(k) Number: K991096

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Device Description

Intended Use

The Access TPO Antibody assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroperoxydase antibody (TPOAb) levels in human serum and plasma using the Access Immunoassay Systems. The detection of TPO antibodies is on id in the diagnosis of autoimmune thyroid disorders.

Comparison of Technological Characteristics

Attribute	Immulite 2000 Anti-TPO Ab	Access TPO Antibody
IntendedUse	For the in vitro diagnostic use with theImmulite 2000 Analyzer-for thequantitative measurement ofantithyroid peroxidase (TPO)antibodies in serum and EDTAplasma, as an aid the clinicaldiagnosis of thyroid disease.	For the quantitative determination ofTPO antibody levels in human serumand plasma.
AssayPrinciples	Immulite 2000 Anti-TPO Ab is a solid-phase, enzyme-labeled,chemiluminescent sequentialimmunometric assay.	The Access TPO Antibody assay is asequential two-stepimmunoenzymatic ("sandwich")assay.
SolidSupport	Beads coated with highly purifiedhuman TPO.	Paramagnetic particles coated withstreptavidin and coupled tobiotinylated human recombinantTPO.
DetectionSystem	Chemiluminescent substrate.	Utilizes dioxetane-basedchemiluminescent substrate;Measures light production from achemiluminescent reaction.
Calibrator	Two levels (low and high) oflyophilized TPO autoantibodies in ahuman serum/buffer matrix, withpreservatives.	Six levels (0, ~5, ~20, ~75, ~300, and~1000 IU/mL) of rabbit TPOantiserum in a buffered proteinsolution with preservatives.

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Summary of Analytical Studies

Imprecision: Imprecision was tested for concentrations from approximately 0.6 to 809 IU/mL. The within run imprecision ranged from 2.6% CV to 7.9% CV. Between-run assay imprecision ranged from 1.3% CV to 4.9% CV. Total imprecision ranged from 3.1% CV to 8.7% CV.

Dilution Recovery (Linearity): Multiple dilutions of serum samples were analyzed. Mean % recovery ranged from 86.4% to 94.9%. The following statement has been added to the TPOAD directional insert: "Due to varying antigen specificity, and avidity of TPOAb in their epitope reactions, some samples may not dilute linearly."

Methods Comparison: A comparison of 119 values using the Access TPOAb assay and a commercially available immunoassay system gave the following statistical data using Deming calculations: Range of observations=5-1000, Slope=1.0207 (95% confidence interval 0.9722 to 1.0693), Intercept=-10.9123 (95 % confidence interval -24.6421 to 2.8175), Correlation coefficient (r)=0.97. The results of the study indicate that the slope and intercept are not significantly different from one and zero respectively.

Analytical Specificity: There was no significant interference from potential sample contaminants (bilirubin, hemoglobin, human serum albumin, and triglycerides).

Stability: TPOAb reagents are stable for 56 days after opening. TPOAb calibrators are stable for 120 days after opening. The calibration is stable for 56 days.

Summary of Clinical Studies

Expected Values: Sera samples were obtained in the United States from a healthy male population <30 years of age following the critiera outlined by the National Academy of Clinical Biochemists (NACB) for establishing a normal reference range for the Access TPOAb assay. A 95% non-parametric determination of results gave an upper reference limit below 9 IU/mL.

Additionally, 679 normal samples were collected in the United States from both males and females ranging in age from 18-80 years old. The screening criteria included serum TSH levels between 0.5 and 2.0 mlU/L, no goiter, no personal or family history of thyroid disease, and absence of non-thyroid autoimmune disease. After completing the screen, 492 samples were tested. 93% of these samples fell below 9 IU/mL.

Qlinical Sensitivity: The Access TPO Antibody assay was evaluated using sera obtained from 54 patients diagnosed with Hashimoto's Thyroiditis and 40 patients diagnosed with Graves' Disease. 100% of the Hashimoto's Thyroiditis patients and 77.5% of the Graves' Disease samples tested positive in the Access TPO Antibody assay.

Conclusion

TPO Antibody and TPO Antibody Calibrators on the Access Immunoassay Systems is substantially equivalent to the Immulite 2000 Anti-TPO Ab for the quantitiative determiation of thyroperoxydase levels in human serum and plasma.

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Image /page/3/Picture/1 description: The image shows a circular seal with text around the perimeter and a symbol in the center. The text around the perimeter reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA". The symbol in the center appears to be three curved lines or strokes, possibly representing a stylized human figure or abstract design.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL - 6 2006

Beckman Coulter, Inc. c/o Ms. Valynda L. Machen Senior Regulatory Specialist 1000 Lake Hazeltine Dr. Chaska, MN 55318-1084

Re: K061382

Trade/Device Name: Access TPO Antibody Assay and Access TPO Antibody Calibrators Regulation Number: 21 CFR 866.5870 Regulation Name: Thyroid Autoantibody Immunological Test System Regulatory Class: Class II Product Code: JZO, JIT Dated: May 17, 2006 Received: May 18, 2006

Dear Ms. Machen:

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 indirecuse stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the cnactment date of the Medical Device Amenduments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, or a crices ma Act (Act) that do not require approval of a premarket approval application (PMA). You mav. therefore, market the device, subject to the general controls provisions of the Act. Troughneral controls provisions of the Act include requirements for annual registration. Ilsting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adultervition.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA). it may be subject to such 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 complish with all the Act s requirements, including, but not limited to: registration and listing (21 CFR Part 807).
I de line (21 QFD B = 000 labeling (21 CFR Part 801): good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820): and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act): 21 CFR 1000-1050.

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Page 2 –

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance at (240) 276-0484. Also, please note (21-011 and our), pick "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/suport/index.html.

Sincerely yours,

Robert Beckerf

Robert L. Becker, Jr., M.D., Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):

Device Name: Access TPO Antibody Assay

Indications For Use:

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

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________ (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Cham maria

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

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$\eta(k) _K(2) 1.882$

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).