K Number

Device Name

Manufacturer

CHIRON DIAGNOSTICS CORP.

Date Cleared

1999-06-18

(31 days)

Product Code

Regulation Number

Type

Panel

Reference & Predicate Devices

N/A

Predicate For

N/A

Intended Use

For the quantitative determination of free triiodothyronine (FT3) in serum using the Chiron Diagnostics ACS:180® Automated Chemiluminescence Systems.

Measurements obtained by this test are used in the diagnosis and treatment of thyroid diseases.

Device Description

Trilodothyronine (3,5,3'-L-triiodothyronine, T3) is a hormone synthesized and secreted from the thyroid gland, and formed by peripheral deiodination of thyroxine (T4). T3 and T4 are secreted into the circulation in response to thyroid stimulating hormone (TSH) and play an important role in requlating metabolism

In the circulation, 99.7% of T3 is reversibly bound to transport proteins, primarily thyroxinebinding globulin (TBG) and to a lesser extent albumin and prealbumin. The remaining T3 does not bind to transport proteins, but is free in the circulation. This unbound fraction of the total T3 concentration is free triiodothyronine (free T3, FT3). Unbound T3 is metabolically active.

Free T3 levels correlate with T3 secretion and metabolism. In hypothyroidism and hyperthyroidism, free T3 levels parallel changes in total T3 levels. However, measuring free T3 is useful when altered levels of total T3 occur due to changes in T3 binding proteins, especially TBG. TBG levels remain relatively constant in healthy individuals, but certain conditions such as normal pregnancy and steroid therapy can alter these levels. In these conditions, free T3 levels are unchanged, while total T3 levels parallel the changes in TBG.

The Chiron Diagnostics ACS:180 FT3 assay is a competitive immunoassay using direct, chemiluminescent technology. FT3 in the sample competes with a T3 analog, which is covalently coupled to paramagnetic particles in the Solid Phase, for a limited amount of a combination of acridinium ester-labeled monoclonal mouse anti-T3 antibodies in the Lite Reagent.

The system automatically performs the following steps:

dispenses 50 µL of sample into a cuvette ●
dispenses 100 µL of Lite Reagent and incubates for 5.0 minutes at 37 C ●
dispenses 450 µL of Solid Phase and incubates for 2.5 minutes at 37 C .
separates, aspirates, and washes the cuvettes with reagent water ●
dispenses 300 µL each of Reagent 1 and Reagent 2 to initiate the chemiluminescent . reaction
. reports the results according to the selected option, as described in the system operating instructions or in the online help system

An inverse relationship exists between the amount of FT3 present in the patient sample and the amount of relative light units (RLUs) detected by the system.

AI/ML Overview

The provided text describes the Chiron Diagnostics ACS:180 FT3 assay, a device for quantifying free triiodothyronine (FT3) in serum. The information is extracted from a 510(k) Summary for regulatory submission.

Here's a breakdown of the requested information based on the provided text:

Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined "acceptance criteria" in the form of thresholds for performance metrics. Instead, it presents the results of performance studies. The table below summarizes the reported performance characteristics.

Performance Characteristic	Acceptance Criteria (Explicit)	Reported Device Performance
Expected Results/Reference Range	Not explicitly stated.	95% of FT3 values for 594 healthy adults fell in the range of 2.3 to 4.2 pg/mL (3.5 to 6.5 pmol/L). A study of 185 healthy individuals found a normal range concurrent with this claim.
Analytical Sensitivity (Minimum Detectable Concentration)	Not explicitly stated.	0.5 pg/mL (0.8 pmol/L).
Assay Reportable Range	Not explicitly stated.	Measures FT3 concentrations up to 20 pg/mL (30.8 pmol/L).
Method Comparison (Correlation with Alternate Method)	Not explicitly stated.	For 359 samples: ACS:180 FT3 = 0.93 (alternate method) + 0.319 pg/mL. Correlation coefficient (r) = 0.99.
Precision (Within-run % CV)	Not explicitly stated.	2.029% (at 2.125 pg/mL); 1.473% (at 4.592 pg/mL); 1.359% (at 9.861 pg/mL)
Precision (Total % CV)	Not explicitly stated.	2.878% (at 2.125 pg/mL); 1.649% (at 4.592 pg/mL); 2.465% (at 9.861 pg/mL)

Study Details

2. Sample size used for the test set and the data provenance:

Expected Results/Reference Range Study:
- Sample Size: 594 apparently healthy adult individuals for the primary range determination, and an additional 185 apparently healthy individuals for a confirmatory study.
- Data Provenance: Not specified (e.g., country of origin). The studies appear to be prospective for establishing the reference range, as they studied "apparently healthy adult individuals."
Method Comparison Study:
- Sample Size: 359 samples.
- Data Provenance: Not specified (e.g., country of origin, retrospective or prospective).
Precision Study:
- Sample Size: 3 samples (each assayed 6 times in each of 12 runs, on 4 systems). This describes a robust internal validation, rather than a "test set" of patient samples in the same way as the method comparison.
- Data Provenance: Not specified.

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

This information is not provided in the document. For an in vitro diagnostic device measuring a quantitative analyte like FT3, "ground truth" is typically established by reference methods or validated laboratory measurements rather than expert consensus on images or clinical assessments. The studies appear to compare the device's measurements against themselves (precision) or against an "alternate method" (method comparison), where the "alternate method" would serve as the reference for comparison, not necessarily a human expert consensus.

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

This concept of "adjudication" is generally applicable to qualitative assessments (e.g., image interpretation) where there might be disagreement among human readers. For a quantitative immunoassay, adjudication as described (e.g., 2+1 consensus) is not applicable and therefore not mentioned. The method comparison study directly compared numerical results.

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:

This device is an automated immunoassay, not an AI-assisted diagnostic imaging system that would involve human readers interpreting cases. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and none was performed or described.

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

The device described is inherently a standalone automated system. The performance characteristics (sensitivity, reportable range, precision, method comparison) are all measurements of the algorithm's and system's performance without human intervention in the result generation or calculation process. Therefore, the presented studies are standalone performance assessments of the device.

7. The type of ground truth used:

For Expected Results/Reference Range: The "ground truth" was derived from the measured FT3 values in a large cohort of "apparently healthy adult individuals," establishing a statistical range for a healthy population.
For Analytical Sensitivity/Reportable Range: The ground truth for these metrics is inherent to the assay's ability to detect and quantify the analyte against zero standards or known concentrations.
For Method Comparison: The "ground truth" was established by an "alternate method." The specific nature or gold standard status of this alternate method is not detailed, but it serves as the reference for comparison.
For Precision: The ground truth is the inherent variability of the assay itself, measured through repeated assessments of the same samples.

8. The sample size for the training set:

The document does not specify a "training set" sample size. This is typical for a traditional immunoassay, which does not employ machine learning algorithms that require a distinct training phase with labeled data in the same way AI algorithms do. The assay is based on chemical reactions and optical detection, with internal calibration curves determining its performance characteristics.

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

As there is no mention of a "training set" in the context of machine learning, this question is not applicable to the described device. The assay's operational parameters and calibration are established through laboratory R&D and validation processes, not through a 'training set' for an algorithm.

Summary

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

Summary of Safety and Effectiveness JUN 18 1999

K99/692

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

1. Submitters Information

Contact person:	William J. PignatoDirector of Regulatory Affairs
Address:	Chiron Diagnostics Corporation63 North StreetMedfield, MA 02052
Phone:	(508) 359-3825
Fax	(508) 359-3356
e-mail	william.pignato.b@bayer.com

Date Summary Prepared: April 30, 1999

2. Device Information

Proprietary Name:	Chiron Diagnostics ACS: 180 FT3
Common Name:	Free triiodothyronine test system
Device Classification:	Class II

3. Predicate Device Information

Name:	Chiron Diagnostics ACS: 180 FT3 Immunoassay
Manufacturer:	Chiron Diagnostics Corporation

4. Device Description

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

5. Statement of Intended Use

For the quantitative determination of free triiodothyronine (FT3) in serum using the Chiron Diagnostics ACS:180® Automated Chemiluminescence Systems.

6. Summary of Technological Characteristics

The system automatically performs the following steps:

dispenses 50 µL of sample into a cuvette ●
dispenses 100 µL of Lite Reagent and incubates for 5.0 minutes at 37 C ●
dispenses 450 µL of Solid Phase and incubates for 2.5 minutes at 37 C .
separates, aspirates, and washes the cuvettes with reagent water ●
dispenses 300 µL each of Reagent 1 and Reagent 2 to initiate the chemiluminescent . reaction
. reports the results according to the selected option, as described in the system operating instructions or in the online help system

An inverse relationship exists between the amount of FT3 present in the patient sample and the amount of relative light units (RLUs) detected by the system.

6. Performance Characteristics

Expected Results

To determine the ACS:180 FT3 reference range, a study was performed on samples from 594 apparently healthy adult individuals. Ninety-five percent of the FT3 values for these individuals fell in the range of 2.3 to 4.2 pg/mL (3.5 to 6.5 pmol/L). A study of 185 apparently healthy individuals was performed and found to have a normal range concurrent with the above claim of a normal range spanning 2.3 to 4.2 pg/mL (3.5 to 6.5 pmol/L).

As with all diagnostic assays, each laboratory should determine its own reference range(s) for the diagnostic evaluation of patient results.

Sensitivity and Assay Reportable Range

The ACS:180 FT3 assay measures FT3 concentrations up to 20 pg/mL (30.8 pmol/L) with a minimum detectable concentration of 0.5 pg/mL (0.8 pmo//L). Analytical sensitivity is defined as the concentration of FT3 that corresponds to the RLUs that are two standard deviations less than the mean RLUs of multiple replicate determinations of the FT3 zero standard with multiple lots of reagents and across multiple systems.

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

Method Comparison

For 359 samples in the range of 0.68 to 17.9 pg/mL (1.05 to 27.6 pmol/L), the relationship between the ACS:180 FT3 assay and an alternate method is described by the equation: ACS:180 FT3 = 0.93 (alternate method) + 0.319 pg/mL Correlation coefficient (r) = 0.99

Precision

Three samples were assayed 6 times in each of 12 runs, on 4 systems. The following results were obtained:

Mean (pg/mL)	Mean (pmol/L)	Within-run % CV	Total % CV
2.125	3.272	2.029	2.878
4.592	7.072	1.473	1.649
9.861	15.186	1.359	2.465

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

Image /page/3/Picture/1 description: The image is a black and white logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle or bird-like figure with three curved lines representing its body and wings. The bird is positioned within a circular border, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the upper half of the circle.

Public Health Service

JUN 18 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. William J. Pignato Director of Regulatory Affairs Chiron Diagnostics Corporation 63 North Street Medfield, Maine 02052-1688

K991692 Re:

Trade Name: Chiron Diagnostics ACS:180® FT3 Assay Regulatory Class: II Product Code: CDP Dated: May 10, 1999 Received: May 18, 1999

Dear Mr. Pignato:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), 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 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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

Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

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"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers 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 Putman

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

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

Page __

< 991692 510(k) Number (if known): __

Device Name: Chiron Diagnostics ACS:180 FT3 Assay

Indications for Use:

For the quantitative determination of free triiodothyronine (FT3) in serum using the Chiron Diagnostics ACS:180® Automated Chemiluminescence Systems.

Measurements obtained by this test are used in the diagnosis and treatment of thyroid diseases.

Sean Cooper

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K99/692

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

Concurrence of CDRH, Office of Device Evaluation (ODE)
--------------------------------------------------------

Prescription Use	✓	OR	Over-The-Counter Use
(Per 21 CFR 801.109)			(Optional Format)

Regulation Number and Section

§ 862.1710 Total triiodothyronine test system.

(a)
Identification. A total triiodothyronine test system is a device intended to measure the hormone triiodothyronine in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases such as hyperthyroidism.(b)
Classification. Class II. This device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.