INNOVANCE ANTITHROMBIN WITH MODELS OPFH03, OPFHO5

K081769 · Siemens Healthcare Diagnostics · JBQ · May 28, 2009 · Hematology

Device Facts

• Record ID: K081769
• Device Name: INNOVANCE ANTITHROMBIN WITH MODELS OPFH03, OPFHO5
• Applicant: Siemens Healthcare Diagnostics
• Product Code: JBQ · Hematology
• Decision Date: May 28, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7060
• Device Class: Class 2

Intended Use

INNOVANCE™ Antithrombin is a chromogenic assay for the automated quantitation of functionally active antithrombin in human citrated plasma and can be used as an aid in the diagnosis of antithrombin deficiency.

Device Story

INNOVANCE™ Antithrombin is an in vitro diagnostic reagent used on automated coagulation analyzers (e.g., BCS®/BCS® XP System). It measures antithrombin activity in human citrated plasma samples. The assay uses a chromogenic principle: excess factor Xa is added to the sample; in the presence of heparin, antithrombin complexes with and inactivates a portion of the factor Xa. Residual uninhibited factor Xa cleaves a specific chromogenic substrate, releasing a dye. The rate of dye release, measured by absorbance at 405 nm, is inversely proportional to the antithrombin activity in the sample. Results are used by clinicians to aid in the diagnosis of antithrombin deficiency. The device is intended for professional use in clinical laboratory settings.

Clinical Evidence

Bench testing only. Method comparison study performed on 284 plasma samples comparing INNOVANCE™ Antithrombin to the predicate Berichrom™ Antithrombin III (A) on the BCS®/BCS® XP System, yielding a correlation coefficient of 0.944, slope of 1.04, and intercept of 0.34. Precision studies (N=80) conducted per CLSI EP5-A2 using normal and pathological control plasmas showed repeatability CVs of 1.9% to 2.8% and within-device/lab CVs of 3.5% to 4.5%.

Technological Characteristics

Chromogenic assay; utilizes factor Xa and heparin. Measures absorbance at 405 nm. Designed for use on automated coagulation analyzers (BCS®/BCS® XP System).

Indications for Use

Indicated for the automated quantitation of functionally active antithrombin in human citrated plasma as an aid in the diagnosis of antithrombin deficiency.

Regulatory Classification

Identification

An antithrombin III assay is a device that is used to determine the plasma level of antithrombin III (a substance which acts with the anticoagulant heparin to prevent coagulation). This determination is used to monitor the administration of heparin in the treatment of thrombosis. The determination may also be used in the diagnosis of thrombophilia (a congenital deficiency of antithrombin III).

Predicate Devices

• Dade Behring Berichrom™ Antithrombin III (A) (k933125)

Submission Summary (Full Text)

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## 510(k) Summary for INNOVANCE™ Antithrombin

MAY 28 2009

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: _______________________________________________________________________________________________________________________________________________

- Manufacturer's Name, Address, Telephone, and Contact Person, Date of Preparation: 1.

| Manufacturer: | Dade Behring Marburg GmbH |
|---------------|---------------------------|
| | A Siemens Company |
| | Emil-von-Behring Str. 76 |
| | 35041 Marburg, Germany |

- Siemens Healthcare Diagnostics Inc. Contact Information: 500 GBD Drive Newark, Delaware 19702 Attn: Radames Riesgo Tel: [phone] Fax: [phone]
May 5. 2009 Preparation date:

INNOVANCE™ Antithrombin 2. Device Name:

> Class II Classification: Product Code: JBQ Panel: Hematology

#### 3. Identification of the Legally Marketed Device:

Dade Behring Berichrom™ Antithrombin III (A) - K933125

#### Device Description: 4.

The INNOVANCE™ Antithrombin assay utilizes a chromogenic measuring principle. An excess of factor Xa is added to citrated plasma. In the presence of heparin, a portion of the enzyme is complexed and inactivated by the antithrombin present in the sample. Excess, uninhibited factor Xa then cleaves a specific chromogenic substrate, causing the release of a dye. The rate of the substrate cleavage is determined by the increase in the absorbance value at 405 nm.

-> [antithrombin · heparin] antithrombin + heparin -[antithrombin · heparin] + FXa (excess) —> [antithrombin · heparin · FXa] + FXa (residual)

FXa (residual)

chromogenic FXa substrate ----------- > tripeptide + dye

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The release of dye is inversely proportional to the inhibiting activity of the antithrombin in the plasma sample, i.e. the smaller the concentration of functionally active antithrombin, the higher the absorbance signal per time unit.

#### 5. Device Intended Use:

INNOVANCE™ Antithrombin is a chromogenic assay for the automated quantitation of functionally active antithrombin in human citrated plasma and can be used as an aid in the diagnosis of antithrombin deficiency.

#### Medical device to which equivalence is claimed and comparison information: 6.

The INNOVANCE™ Antithrombin reagent is substantially equivalent, and has the same intended use and performance to the Dade Behring Berichrom™ Antithrombin III (A) reagent (K933125).

#### 7. Device Performance Characteristics:

The INNOVANCE™ Antithrombin reagent was compared to the Dade Behring Berichrom™ Antithrombin III (A) reagent on the BCS®/BCS® XP System by evaluating plasma samples with antithrombin activity ranging from 4.8 to 131.3% of the norm. Regression analysis of these evaluations yielded the following equation:

| Comparative Method | n | Slope | Intercept | Correlation Coefficient |
|----------------------------------------------------------------|-----|-------|-----------|-------------------------|
| BerichromTM Antithrombin III (A) on the BCS ® /BCS® XP System | 284 | 1.04 | 0.34 | 0.944 |

Method Comparison Study

Precision studies were conducted with the BCS®/BCS® XP System, as described in the CLSI Guideline EP5-A2, using Control Plasma N (control plasma in the normal range) and Control Plasma P (control plasma in the pathological range) as well as a pathological plasma pool (human plasma pool in the decision range).

| Sample | Precision (N = 80) | | |
|-----------------------------|-------------------------|-----------------------------|-----|
| Mean<br>[% of the Norm] | Repeatability CV<br>[%] | Within-device/lab CV<br>[%] | |
| Control Plasma N | 95.8 | 2.8 | 3.7 |
| Control Plasma P | 31.4 | 2.6 | 4.5 |
| Pathological<br>Plasma Pool | 61.7 | 1.9 | 3.5 |

#### 8. Conclusion:

The proposed INNOVANCE™ Antithrombin device is substantially equivalent to the legally marketed device based upon the correlation studies and the information above.

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### Public Health Service

28 2009 MAY

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Siemens Healthcare Diagnostics Inc. c/o Mr. Radames Riesgo Regulatory Affairs and Compliance Manager 500 GBD Drive MS 514 Newark, DE 19702

Re: k081769

Trade/Device Name: INNOVANCE™ Antithrombin Regulation Number: 21 CFR 864.7060 Regulation Name: Antithrombin III assay Regulatory Class: Class II Product Code: JBQ Dated: March 23, 2009 Received: March 24, 2009

Dear Mr. Riesgo:

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice

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### Page 2 - Mr. Radames Riesgo

requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). 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 In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at [phone]. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at [phone]. For more information regarding the reporting of adverse events, please go to http://www.fda.gov/cdrh/mdr/.

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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours,

・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・

ie m. chan

Maria M. Chan, 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): K081769

Device Name: INNOVANCE™ Antithrombin

## Indications for Use:

INNOVANCE™ Antithrombin is a chromogenic assay for the automated quantitation of functionally active antithrombin in human citrated plasma and can be used as an aid in the diagnosis of antithrombin deficiency.

Prescription Use _ X (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 OF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

RemelD

**Division Sign-Off**

**Office of In Vitro Diagnostic**
**Device Evaluation and Safety**
K081769

510(k)