CHIRON DIAGNOSTICS ACS: 180 FT3

K991692 · Chiron Diagnostics Corp. · CDP · Jun 18, 1999 · Clinical Chemistry

Device Facts

• Record ID: K991692
• Device Name: CHIRON DIAGNOSTICS ACS: 180 FT3
• Applicant: Chiron Diagnostics Corp.
• Product Code: CDP · Clinical Chemistry
• Decision Date: Jun 18, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1710
• Device Class: Class 2

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 Story

The Chiron Diagnostics ACS:180 FT3 is an automated in vitro diagnostic assay for measuring free triiodothyronine (FT3) in serum. The device utilizes a competitive chemiluminescent immunoassay principle; patient serum sample competes with a T3 analog coupled to paramagnetic particles for binding to acridinium ester-labeled monoclonal mouse anti-T3 antibodies. The system performs automated sample dispensing, incubation, separation, washing, and chemiluminescent signal detection. The system measures relative light units (RLUs), which are inversely proportional to the FT3 concentration in the sample. Used in clinical laboratory settings, the system provides quantitative results to clinicians to assist in diagnosing and managing thyroid disorders, particularly when total T3 levels are affected by changes in binding proteins like TBG.

Clinical Evidence

Bench testing only. Performance evaluated using 594 apparently healthy individuals to establish a reference range of 2.3 to 4.2 pg/mL. Analytical sensitivity (minimum detectable concentration) is 0.5 pg/mL. Method comparison against an alternate method (n=359) showed a correlation coefficient (r) of 0.99. Precision studies across 4 systems demonstrated within-run CVs of 1.36%–2.03% and total CVs of 1.65%–2.88%.

Technological Characteristics

Competitive chemiluminescent immunoassay. Components: paramagnetic particles (solid phase), acridinium ester-labeled monoclonal mouse anti-T3 antibodies (lite reagent). Automated system performs incubation at 37°C, magnetic separation, and chemiluminescent detection. Measures FT3 up to 20 pg/mL. System is an automated analyzer platform.

Indications for Use

Indicated for the quantitative determination of free triiodothyronine (FT3) in serum to aid in the diagnosis and treatment of thyroid diseases in patients.

Regulatory Classification

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.

Predicate Devices

• Chiron Diagnostics ACS: 180 FT3 Immunoassay

Submission Summary (Full Text)

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#### 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. Pignato<br>Director of Regulatory Affairs |
|-----------------|-------------------------------------------------------------------------|
| Address: | Chiron Diagnostics Corporation<br>63 North Street<br>Medfield, MA 02052 |
| Phone: | [phone] |
| Fax | [phone] |
| e-mail | [e-mail] |

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

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.

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## 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 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.

# 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.

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## 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 |

:

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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 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.

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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 [phone].

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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. 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 [phone] or [phone], 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

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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

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| Concurrence of CDRH, Office of Device Evaluation (ODE) |
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| Prescription Use | <div style="text-align: center;">✓</div> | OR | Over-The-Counter Use |
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| (Per 21 CFR 801.109) | | | (Optional Format) |