The ACS:180 and ADVIA Centaur anti-Tg Immunoassays are competitive, chemiluminescence immunoassay for the quantitative determination of autoantibodies against thyroglobulin (TG) in human serum and plasma for use on the automated analyzer marketed by Bayer Corporation. The ACS:180 and ADVIA Centaur anti-Tg Immunoassays are intended for use in the diagnosis of Hashimoto's and Graves' autoimmune diseases affecting the thyroid gland.

Device Description

The ACS:180 and ADVIA Centaur anti-Tg are a competitive chemiluminescence immunoassay intended for the quantitative determination of autoantibodies against thyroglobulin in human serum and plasma. A polyclonal human anti-Tg antibody is bound to a solid phase. Patient samples, standards, and controls are incubated with labeled native human thyroglobulin. Autoimmune anti-thyroglobulin antibodies in patient samples compete with the solid phase antibody for the labeled thyroglobulin. Following incubation, unreacted labeled thyroglobulin and unreacted antibodies from the sample are removed by washing. The chemiluminescence of the reacted, labeled thyroglobulin bound to the solid phase is measured in a luminometer. The amount of chemiluminescence is inversely proportional to the concentration of anti-thyroglobulin antibody in the sample.

AI/ML Overview

Here's an analysis of the provided 510(k) summary, extracting the requested information about acceptance criteria and the supporting study:

The provided document describes the Bayer Diagnostics ACS:180 and ADVIA Centaur anti-Tg Immunoassay, seeking substantial equivalence to the predicate device DYNOTest® anti-Tgn. The acceptance criteria are implicitly defined by demonstrating substantial equivalence through specific performance targets, primarily agreement percentages with the predicate device.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are inferred from the documented comparison studies against the predicate device. While explicit "acceptance criteria" are not listed as numerical thresholds, substantial equivalence is claimed based on the achieved agreement percentages.

Performance Metric	Acceptance Criteria (Inferred from Predicate Equivalence)	Reported ACS:180 Performance (vs. DYNOTest anti-Tgn)	Reported ADVIA Centaur Performance (vs. ACS:180)
Overall Agreement	Statistically significant agreement for substantial equivalence	97.6% (286/293) for Normal Patients	98% (250/255)
		87.9% (87/99) for Graves Patients
		70.9% (134/189) for Hashimoto's Patients
Correlation Coefficient (r)	N/A (for ACS:180 vs. DYNOTest)	N/A	0.989
Sensitivity (vs predicate)	Greater sensitivity is a positive indicator (not a firm threshold)	Graves: 39.9% (ACS:180) vs. 29.3% (DYNOTest)	N/A
		Hashimoto's: 70.4% (ACS:180) vs. 41.2% (DYNOTest)	N/A

2. Sample Sizes and Data Provenance

The study involved two main comparisons:

ACS:180 vs. DYNOTest anti-Tgn (Predicate device):
- Test Set Sample Size:
  - Normal patients: 293 samples
  - Graves patients: 99 samples
  - Hashimoto's patients: 189 samples
  - Total for this comparison: 581 samples
- Data Provenance: Not explicitly stated (e.g., country of origin). The study design appears to be retrospective, using collected serum samples.
ADVIA Centaur vs. ACS:180 (Transference Study):
- Test Set Sample Size: 255 serum samples (in the range of 10 to 500 U/mL)
- Data Provenance: Not explicitly stated, likely retrospective.

3. Number of Experts and their Qualifications for Ground Truth

Number of Experts: Not specified.
Qualifications of Experts: Not specified. The "ground truth" for the comparison study appears to be defined by the results of the predicate device (DYNOTest anti-Tgn), which itself would have been established through clinical validation involving medical expertise, but this document does not detail the predicate's ground truth establishment.

4. Adjudication Method for the Test Set

Adjudication Method: Not specified. The comparisons are presented as direct agreements between the devices' classifications (positive/negative) against each other, rather than against an external gold standard that would require adjudication.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Was an MRMC study done? No. This submission pertains to in vitro diagnostic (IVD) immunoassays, which are laboratory tests measuring biomarkers, not imaging or subjective diagnostic assessments that typically involve multiple human readers. Therefore, an MRMC study is not applicable.

6. Standalone (Algorithm Only) Performance Study

Was a standalone study done? Yes, in essence. The entire comparison study for both the ACS:180 and ADVIA Centaur devices against their predicate or each other constitutes a standalone performance evaluation. Immunoassays are "algorithm only" in the sense that they provide quantitative results based on chemical reactions and signal detection, without human interpretation of subjective data like images. The reported agreement percentages reflect the standalone performance of the devices relative to other devices.

7. Type of Ground Truth Used

Type of Ground Truth: The primary "ground truth" for demonstrating substantial equivalence for the new devices (ACS:180 and ADVIA Centaur) is the results of the legally marketed predicate device (DYNOTest anti-Tgn).
- For the patient classifications (Normal, Graves, Hashimoto's), these types of diagnoses are typically confirmed through a combination of clinical assessment, other laboratory tests, imaging, and sometimes pathology or long-term outcomes, but the document implicitly uses the predicate device's findings as the reference for the comparison.

8. Sample Size for the Training Set

Training Set Sample Size: Not specified. For IVD devices, a "training set" in the machine learning sense is not typically applicable. Instead, method development (optimization of reagents, conditions, algorithms for signal processing) is performed using various samples, but these are not explicitly termed "training sets" with specific sizes in this context. The document focuses on the validation and comparison of the final device.

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

How Ground Truth for Training Set Was Established: Not applicable, as there is no explicitly defined "training set" with a described ground truth establishment process in this submission. The development and optimization of such assays involve internal testing and refinement, but this information is not detailed within this 510(k) summary.

Summary

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K012777

OCT 22 2001

Bayer Diagnostics

ASC:180 and ADVIA Centaur anti-Tg Immunoassays Section 2: Summary of Safety and Effectiveness

As required by 21 CFR 807.92, the following 510(k) Summary is provided:

1. Submitter Information

Contact person:	Kenneth T. Edds Ph.D
Address:	Bayer Diagnostics Corporation511 Benedict Ave.Tarrytown, NY 10591
	Phone: (914) 524-2446FAX: (914) 524-2500e-mail: ken.edds.b.@bayer.com
Date Summary Prepared:	July 17, 2001
2. Device Information
Proprietary Name:	ADVIA Centaur and ACS:180 anti-TgImmunoassay
Common Name:	anti-Tg Immunoassay
Classification Name:	Thyroid autoantibody immunological test system
Class:	Class II
CFR:	21 CFR 866.5870
Product Code:	JZO
3. Predicate Device Information

DYNOTest® anti-Tgn Name: BRAHMS Diagnostica, GmbH Manufacturer: Neuendorfstrasse 25 D-16761 Hennigsdorf Germany

510(k) Number:

K992790

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4. Device Description

The ACS:180 and ADVIA Centaur anti-Tg are a competitive chemiluminescence immunoassay The ACS:180 and ADVIA Centaur anti-1 g are a tounist throughbulin in human serum
intended for the quantitative determination of autoantibodies against trying and intended for the quantitiative delemination of backlessing masters with and and plasma. A polyclonal human anti-1 g antibus bounds, and controls for directly
autoimmune anti-thyroglobulin antibodies in patient samples, standards and label autommune anni-inylogiouin antibodies in pation. Following incubation, unreacted labeled
labeled native human thyroglobulin the lite reagent. Following incubation mixtu labeled hative numan thyroglobulin the liter reagent. The reaction mixture. The thyroglobulin and unreacted antibodies from the outliple are neasured in a luminometer. The chemiluminescence of the reacted, labeled thyrogiousline in anti-hyroglobulin antibody in the sample.

5. Statement of Intended Use

The ACS:180 and ADVIA Centaur anti-Tg Immunoassays are competitive, chemiluminescence The ACS:180 and ADVIA Centrali ann-19 intribution of autoanist theronobulin (TG) in human
immunoassay for the quantitative determination of autoantibooking The ACS: 180 immunoassay for the quantitative detemmation or advantised by Bayer Corporation. The ACS: 180
serum and plasma for use on the automated analyzer markets of Hechimoto's and serum and plasma for use on the automated analyzed in the diagnosis of Hashimoto's and and ADVIA Oontaar ammmune diseases affecting the thyroid gland.

6. Summary of Technological Characteristics

The ACS:180 and ADVIA Centaur anti-Tg Immunoassays are similar to the BRAHMS Diagnostica The ACS.100 and ADVIA Oentain and Tig mind on tor use, format, solid phase, performance DYNOTestle anti-10 Kit (K992790) in the indications for accept official stimati-Ty tests differ from the predicate characteristics, and results. The ROO. For and ADVA ( so compared to a manual coated tube device in their lifeended use on an addiness as company as a company and the many is used to
technique. In the automated methods, a chemiluminogenic molecule (acridinium es replace the 1251 signal used in the DYNOTest anti-Tg manual assay.

7. Method Comparison

The data represented in this document is organized into two components:

e data represented in this document to organized into device DYNOtest anti-Tg, (K992790).
Comparison of the ACS:180 anti-Tg to the predicate device DYNOtest anti-Tg, (K99279 1. Results in sections 3 & 4.
Results in sections S & 4.
Comparison of the ADVIA Centaur to the ACS:180 used transference. Transference is a method Companson of the ADVIA Centadi to the AOC. For association the Clinical Laboratory.
recommended by NCCLS (C28-A, How to Define Reference Intervals in the Clinical Laboratores recommended by NCCLS (O20-A, How to Boline no provides guidelines for transference of Street pother of Approved Guldelife). This document diseased by a different analytical system, different method or different instrument. Results are in section 5.

Substantial equivalence to the DYNOTest kit, cleared under K992790, is based on clinical comparison Substantial equivalence to the DTNOT of the Productions with Graves' disease using 56 i seruin samples from normal blood donors (1 200) and proup based on a 2 X 2 agreement table was 286/293 = 97.6%.

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ACS:180 vs. DYNOtest

Normal patients:

DYNOtest anti-Tgn

	Positive	Negative
ACS:180 anti-TgPositive	23	7
Negative	0	263
% Agreement = 97.6 (286/293)

Graves patients:

DYNOtest anti-Tgn

--------------

-------------****	---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
	-----------01 A oursement == 07 0 /07/00)

% Agreement = 87.9 (87/99)

Hashimoto's patients:

DYNOtest anti-Tgn

		Positive	Negative
ACS:180 anti-Tg	Positive	78	55
	Negative	0	56
% Agreement = 70.9 (134/189)

This correlation study demonstrates that the ACS:180 anti-Tg assay is substantially equivalent to the legally marketed predicate device, the BRAHMS Diagnostica DYNOTest anti-Tg assay; 510(k) legally mumotod proditor are the one it thyroid normals. The sensitivity (more diseased patients found positive) of the ACS: 180 anti-Tg assay is greater the BRAHMS Diagnostica DYNOTest anti-Tg assay; 39.9% vs. 29.3% for Graves and 70.4% vs. 41.2% for Hashimoto, respectively.

ADVIA Centaur vs. ACS:180

For 255 serum samples in the range of 10 to 500 U/mL, the relationship between the ADVIA Centaur anti-Tg assay and the ACS:180 anti-Tg assay is described by the equation:

ADVIA Centaur anti-Tg = 1.03 (ACS:180 anti-Tg) + 2.29 U/mL Correlation Coefficient ( r ) = 0.989

The diagnostic concordance between the two assays is shown in the following table:

		ACS:180 anti-Tg
		Positive	Negative
ADVIA Centaur anti-Tg	Positive	110	4
	Negative	1	140

% Agreement = 98% (250/255)

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Image /page/3/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol consisting of three overlapping profiles facing to the right, resembling a family or group of people.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 22 2001

Kenneth T. Edds, Ph.D. Manager, Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

Re: K012777

Trade/Device Name: Bayer Diagnostics ACS:180 and ADVIA Centaur anti-Tg Assay Regulation Number: 21 CFR § 866.5870 Regulation Name: Thyroid Autoantibody Immunological Test System Regulatory Class: II Product Code: JZO Dated: August 15, 2001 Received: August 20, 2001

Dear Dr. Edds:

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. 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.

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 comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); 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 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 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Autman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page _ of _

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: Bayer Diagnostics ACS:180 and ADVIA Centaur anti-Tg Assay

Indications for Use:

The ACS:180 and ADVIA Centaur anti-Tg Immunoassays are competitive, chemiluminescence The ACS:180 and ADVIA Centaur and TV inimulodies against throglobulin (TG) in human
immunoassay for the quantitative determination of autoantibodies against Corporation, The immunoassay for the quantialive delemination of acreation of Bayer Corogration. The ACS:180
serum and plasma for use on the automated analyzer marketed by Bayer of Hochimoto' serum and plasma for use on the adloniated andy of the diagnosis of Hashimoto's and and ADVIA Centadi and 19 initifatioussalys are are are a faction the thyroid gland.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109)
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Over-The-Counter Use (Optional Format 1-2-96)
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	Sousan S. Altaie
	(Division Sign-Off)
	Division of Clinical Laboratory Devices
510(k) Number	K012777

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).