ACS 180 AND ADVIA CENTAUR FT4 IMMUNOASSAYS

K080167 · Siemens Healthcare Diagnostics · CEC · Aug 8, 2008 · Clinical Chemistry

Device Facts

• Record ID: K080167
• Device Name: ACS 180 AND ADVIA CENTAUR FT4 IMMUNOASSAYS
• Applicant: Siemens Healthcare Diagnostics
• Product Code: CEC · Clinical Chemistry
• Decision Date: Aug 8, 2008
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1695
• Device Class: Class 2

Intended Use

The ADVIA Centaur FT4 Immunoassay is for in vitro diagnostic use in the quantitative determination of free thyroxine (FT4) in serum or plasma (heparinized or EDTA) using the ADVIA Centaur and ADVIA Centaur XP Systems. Measurements of free thyroxine are used in the diagnosis and treatment of thyroid diseases.

Device Story

ADVIA Centaur FT4 is a competitive chemiluminescent immunoassay for quantitative FT4 measurement in serum/plasma. Patient sample competes with acridinium ester-labeled T4 for biotinylated polyclonal rabbit anti-T4 antibody bound to avidin-coated paramagnetic particles. Inverse relationship exists between FT4 concentration and relative light units. Used on ADVIA Centaur and ADVIA Centaur XP systems in clinical laboratory settings by trained technicians. Output is a numerical FT4 concentration (ng/dL) used by clinicians to assess thyroid function and guide treatment decisions. Benefits include rapid, automated diagnostic testing for thyroid disease management.

Clinical Evidence

Bench testing only. Precision study (n=81 per sample) showed total CVs ranging from 3.98% to 11.2%. Linearity verified across 0.0825–12.5 ng/dL range. Method comparison with predicate (n=283) yielded y = 0.973x + 0.016, r^2 = 0.995. Matrix comparison (n=91 heparinized plasma, n=73 K2EDTA plasma) showed high correlation (r=0.997 and r=0.998 respectively) with serum. Analytical specificity studies confirmed no significant interference from endogenous substances or common drugs (propylthiouracil, methimazole, etc.) at tested levels.

Technological Characteristics

Competitive chemiluminescent immunoassay. Reagents: acridinium ester-labeled T4 and biotinylated polyclonal rabbit anti-T4 antibody on avidin-coupled paramagnetic particles. Assay range: 0.1–12.0 ng/dL. Automated system-based processing. Standardized against USP internal standards.

Indications for Use

Indicated for the quantitative determination of free thyroxine (FT4) in human serum or plasma (heparinized or EDTA) to aid in the diagnosis and treatment of thyroid diseases.

Regulatory Classification

Identification

A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.

Predicate Devices

• ACS:180 Free T4 Assay (k961510)

Submission Summary (Full Text)

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Koro167

## 510(k) Summary

# AUG - 8 2008

| Submitter information<br>Contact person: | Philip Liu, Ph.D.<br>Manager, Regulatory Affairs & Compliance |
|-----------------------------------------------------|------------------------------------------------------------------------------|
| Address: | Siemens Healthcare Diagnostics<br>511 Benedict Avenue<br>Tarrytown, NY 10591 |
| Phone: | 914-524-2443<br>914-524-2500 (fax) |
| Date summary prepared: | July 10, 2008 |
| Device Trade or Proprietary Names: | ADVIA Centaur FT4 Immunoassay |
| Device Common/Usual Name or<br>Classification Name: | Free Thyroxine test system |
| Classification Number / Class: | 21CFR 862.1695 / Class II |

This 510(k) summary of safety and effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92.

The assigned 510(k) number is: k080167

#### Assay Predicate Device:

| | Predicate Device | |
|---------------|------------------------------------------------------------------------------------|--|
| Device Name | ACS:180 Free T4 Assay | |
| Common name | ACS FrT4 | |
| 510(k) Number | k961510 | |
| Manufacturer | Siemens Healthcare Diagnostics<br>(formerly Siemens Medical Solutions Diagnostics) | |

#### Device Description:

The ADVIA Centaur FT4 assay is a competitive immunoassay using direct, chemiluminescent technology. Free thyroxine in the patient sample competes with acridinium ester-labeled T4 in the Lite Reagent for a limited amount of biotinylated polyclonal rabbit anti-T4 antibody that is bound to avidin that is covalently coupled to

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paramagnetic particles in the Solid Phase. There is an inverse relationship between the concentration of free thyroxine in the sample and relative light units (chemiluminescence).

#### Statements of Intended Use:

The ADVIA Centaur FT4 Immunoassay is for in vitro diagnostic use in the quantitative determination of free thyroxine (FT4) in serum or plasma (heparinized or EDTA) using the ADVIA Centaur and ADVIA Centaur XP Systems. Measurements of free thyroxine are used in the diagnosis and treatment of thyroid diseases.

#### Comparisons to the Predicate Device:

#### Assay Similarities

| | ADVIA Centaur FT4 Assay<br>(new device) | ACS:180 FrT4 Assay<br>(predicate device) |
|-------------------------------|-------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------|
| Intended Use | For in vitro diagnostic use in<br>the quantitative determination<br>of free thyroxine (FT4) in<br>serum or plasma | For in vitro diagnostic use in<br>the quantitative determination<br>of free thyroxine (FT4) in<br>serum |
| Assay Method | Competitive immunoassay | Competitive immunoassay |
| Detection | Chemiluminescence | Chemiluminescence |
| Assay Range | 0.1 - 12.0 ng/dL | 0.1 - 12.0 ng/dL |
| Calibrators | Calibrator A | Calibrator A |
| Calibration | 2 point | 2 point |
| Reagents | Two liquid reagents, ready to<br>use | Two liquid reagents, ready to<br>use |
| Lite Reagent | Acridium ester labeled T4 | Acridium ester labeled T4 |
| Expected<br>Values<br>(ng/dL) | Euthyroid 0.89 - 1.76<br>Hypothyroid < 0.89<br>Hyperthyroid >1.76 | Euthyroid 0.89 - 1.76<br>Hypothyroid < 0.89<br>Hyperthyroid >1.76 |
| Standardization | Internal Standard (USP) | Internal Standard (USP) |

#### Assay Differences

| | ADVIA Centaur FT4 Assay<br>(new device) | ACS:180 FrT4 Assay<br>(predicate device) |
|------------------------|---------------------------------------------------------------------------------|-------------------------------------------------------|
| Specimen Type | Human serum or plasma<br>(heparinized or EDTA) | Human serum |
| Solid Phase<br>Reagent | Biotin-labeled polyclonal anti-<br>T4 bound to avidin<br>paramagnetic particles | Polyclonal anti-T4 bound to<br>paramagnetic particles |

Siemens Healthcare Diagnostics (formerly Siemens Medical Solutions Diagnostics) ADVIA Centaur Free T4 Premarket Notification 510(k) 510(k) Summary (Revised, July 2008)

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## Performance:

Substantial equivalence was demonstrated by testing several method performance characteristics including imprecision, method comparison, interfering substances, and specificity. The following tables summarize the precision (total), interfering substances, specificity, serum / plasma equivalency and method comparison results.

All of the evaluation studies gave acceptable results compared to the predicate device. These studies support that the ADVIA Centaur FT4 immunoassay is substantially equivalent to the ACS:180 FrT4 immunoassay that is currently marketed.

#### Imprecision

| ADVIA Centaur FT4 | | ACS:180 FrT4 | |
|-------------------|--------------|---------------|--------------|
| Level (ng/dL) | Total CV (%) | Level (ng/dL) | Total CV (%) |
| 0.37 | 11.2 | 0.58 | 4.86 |
| 0.71 | 4.85 | -- | -- |
| 1.31 | 3.98 | 1.42 | 1.92 |
| 3.35 | 4.07 | 3.37 | 3.55 |
| 5.32 | 4.02 | -- | -- |
| 9.68 | 6.53 | -- | -- |

| ADVIA Centaur FT4 | |
|-------------------|--------------|
| Level (ng/dL) | Total CV (%) |
| 0.72 | 4.16 |
| 1.47 | 4.58 |
| 3.01 | 4.44 |

Study #2 - Multiple reagent lots, multiple systems

#### Specificity

The cross-reactivity of the ADVIA Centaur FT4 assay with a substance can be expressed as the ratio of:

• the amount of T4 required to displace 50% of the maximally bound labeled T4 from the anti-T4 antibody,

- · the amount of the cross-reactant to give the same 50% displacement

| Cross Reactant | % Cross Reactivity |
|--------------------------------|--------------------|
| L-Triiodothyronine | <0.02% |
| Diiodotyrosine | <0.02% |
| Monoiodotyrosine | <0.02% |
| 3,5-Diiodo-L-thyronine | <0.02% |
| Reverse Triiodothyronine (rT3) | <0.02% |

Siemens Healthcare Diagnostics (formerly Siemens Medical Solutions Diagnostics) ADVIA Centaur Free T4 Premarket Notification 510(k) 510(k) Summary (Revised, July 2008)

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### Interfering Substances

| Interfering Substance | Interferent Conc.<br>(mg/dL) | FT4 conc.<br>(ng/dL) | Effect<br>(% change) |
|-----------------------|------------------------------|----------------------|----------------------|
| Hemoglobin | 300 | 0.90 | -1.10 |
| Hemoglobin | 300 | 1.34 | -4.29 |
| Lipids (Intralipids) | 1000 | 1.10 | 3.77 |
| Lipids (Intralipids) | 1000 | 1.37 | 5.38 |
| Bilirubin, free | 20 | 1.03 | 3.00 |
| Bilirubin, free | 20 | 1.23 | 2.50 |
| Bilirubin, conjugated | 20 | 1.03 | 5.10 |
| Bilirubin, conjugated | 20 | 1.23 | 2.50 |

#### Correlation

#### (y = ADVIA Centaur FT4, x = comparison method/system)

| Specimen type,<br>System (y) | Comparison System (x) | N | Regression Equation | r | Sample Range<br>(ng/dL) |
|------------------------------|-----------------------|-----|-----------------------|-------|-------------------------|
| Serum, ADVIA<br>Centaur FT4 | Serum, ACS:180 FrT4 | 283 | $Y = 0.973 x + 0.016$ | 0.995 | 0.14 - 11.1 |

#### Serum / Plasma (Lithium heparin and EDTA)

| Specimen type (y) | Comparison System (x) | N | Regression Equation | r | Sample Range (ng/dL) |
|--------------------|-----------------------|-----|----------------------|-------|----------------------|
| Heparinized Plasma | Serum | 133 | $Y = 0.979x + 0.058$ | 0.997 | 0.17 – 11.4 |
| EDTA Plasma | Serum | 108 | $Y = 0.967x + 0.007$ | 0.998 | 0.17 – 11.4 |

#### Conclusions:

The Siemens Healthcare Diagnostics ADVIA Centaur FT4 immunoassay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Siemens Healthcare Diagnostics ACS:180 FrT4 immunoassay (k961510).

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with three stripes representing the three levels of government: federal, state, and local. The eagle is encircled by the words "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" in a circular arrangement.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Siemens Healthcare Diagnostics c/o Philip Liu, Ph.D. Manager, Regulatory Affairs & Compliance 511 Benedict Avenue Tarrytown. NY 10591

AUG - 8 2008

Re: k080167 Trade Name: ADVIA Centaur FT4 Immunoassay Regulation Number: 21 CFR 862.1695 Regulation Name: Free thyroxine test system Regulatory Class: Class II Product Codes: CEC Dated: June 16, 2008 Received: June 17, 2008

Dear Dr. Liu:

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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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 1egally marketed predicate device results in a classification for your device and thus, permits vour device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "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 the from the [phone] or [phone] or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Yéan M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology 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): k080167

Device Name: ADVIA Centaur FT4 Immunoassay

Indications For Use:

The ADVIA Centaur FT4 Immunoassay is for in vitro diagnostic use in the quantitative determination of free thyroxine (FT4) in serum or plasma (heparinized or EDTA) using the ADVIA Centaur and ADVIA Centaur XP Systems. Measurements of free thyroxine are used in the diagnosis and treatment of thyroid diseases.

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

Over-The-Counter Use (21 CFR 801 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)

Carol C. Benson
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e of In Vitro Diagnostic Device Evaluation and Saf

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