TINA-QUANT ALPHA PARTICLE-1-ANTITRYPSIN ASSAY

K972640 · Boehringer Mannheim Corp. · DEM · Jan 9, 1998 · Immunology

Device Facts

• Record ID: K972640
• Device Name: TINA-QUANT ALPHA PARTICLE-1-ANTITRYPSIN ASSAY
• Applicant: Boehringer Mannheim Corp.
• Product Code: DEM · Immunology
• Decision Date: Jan 9, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5130
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

Immunological in vitro immunoturbidometric test for the quantitative determination of x -1antitrypsin in human serum and plasma. The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition, alpha-1-antitrypsin deficiency has been associated with pulmonary emphysema.

Device Story

The Tina-quant® α-1-Antitrypsin Assay is an in vitro diagnostic test used to measure alpha-1-antitrypsin levels in human serum or plasma. The device operates via turbidimetric immunoinhibition (TINIA). A patient sample is mixed with a TRIS buffer (R1 reagent), followed by the addition of polyclonal anti-human α-1-antitrypsin antibodies (R2 reagent). These antibodies bind to the α-1-antitrypsin in the sample, forming immune complex aggregates. The amount of aggregate formed is directly proportional to the concentration of α-1-antitrypsin in the sample. This complex increases the turbidity of the solution, which is measured as an increase in optical density using a Hitachi instrument. The assay is intended for professional use in clinical laboratory settings. Healthcare providers use the resulting quantitative values to assist in diagnosing liver cirrhosis and pulmonary emphysema associated with alpha-1-antitrypsin deficiency.

Clinical Evidence

Bench testing only. Performance evaluated via precision studies (intra-assay %CV 2.5-3.1%; inter-assay %CV 2.0-2.1%) and method comparison against the predicate. Method comparison (N=123) yielded a correlation coefficient (r) of 0.967. Interference testing showed no significant interference (≤ 10% error) from bilirubin (60 mg/dL), hemoglobin (1000 mg/dL), lipemia (1000 mg/dL), or rheumatoid factor (100 IU/mL).

Technological Characteristics

Immunoturbidimetric assay using polyclonal anti-human α-1-antitrypsin antibodies. Reagents include TRIS buffer (R1) and antibody solution (R2). Measures optical density changes proportional to immune complex formation. Designed for use on Hitachi clinical chemistry analyzers. Specific for α-1-antitrypsin.

Indications for Use

Indicated for the quantitative determination of alpha-1-antitrypsin in human serum and plasma to aid in the diagnosis of conditions including juvenile and adult cirrhosis of the liver and pulmonary emphysema.

Regulatory Classification

Identification

An alpha-1-antitrypsin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the alpha-1-antitrypsin (a plasma protein) in serum, other body fluids, and tissues. The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition, alpha-1-antitrypsin deficiency has been associated with pulmonary emphysema.

Predicate Devices

• Behring BN® α-1-Antitrypsin assay

Submission Summary (Full Text)

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Telephone: [phone] Fax: [phone]

Boehringer Mannheim Corporation Laboratory Diagnostics 2400 Bisso Lañe PO Box 4117 Concord CA 94524-4117

K972640

Image /page/0/Picture/4 description: The image shows the date "JAN - 9 1998" in bold, black font. The month is abbreviated to "JAN", followed by a hyphen, the number 9, and the year 1998. The text is clear and easily readable against the white background. There is also a black rectangle on the right side of the image.

## 510(k) Summary

According to the requirements of 21 CFR 807.92, the following information Introduction According to the requirements.issderstand the basis for a determination of substantial equivalence.

1. Submitter name, address, contact

Boehringer Mannheim Corporation 135 Sandberg Street Thousand Oaks, CA 91360 (805) 241 - 7575

Contact Person: Mary Koning

Date Prepared: July 13, 1997

Proprietary name: Tina-quant® a -1-Antitrypsin Assay

2. Device name

> Common name: Immunoturbidometric assay for the determination of x -1antitrypsin.

Classification name: α -1-antitrypsin immunological test system

3. Predicate device

The Boehringer Mannheim Tina-quant® a-1-Antitrypsin is substantially The Dochings Maximal in commercial distribution intended for similar cquivalent to other processionially equivalent to the currently marketed Behring BN® α-1-Antitrypsin assay.

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# 510(k) Summary, Continued

| 4. Device Description | The α -1-antitrypsin determination is based upon turbidimetric immunoinhibition (TINIA) using a serum or plasma blood sample. The sample containing α -1-antitrypsin is transferred into a TRIS buffer solution (R₁ reagent). In the second step, an aliquot of solution of polyclonal anti-human α -1-antitrypsin antibodies (R₂ reagent) is added to mixture of the first step. The antibody will bind to the α -1-antitrypsin in the sample to form “aggregates” such that the amount of aggregate formed is proportionate to the amount of α -1-antitrypsin present in the sample. The resulting agglutination complex is measured turbidimetrically whereby increased turbidity is reflected through an increase in optical density. Therefore, the amount of α-1-antitrypsin in the sample is directly proportional to the amount of turbidity formed. |
|-----------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 5. Intended use | Immunoturbidometric assay for the quantitative in-vitro determination of α -1-antitrypsin. |
| 6. Comparison to predicate device | The Boehringer Mannheim Tina-quant® α -1-antitrypsin is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Behring BN® α -1-Antitrypsin assay. |
| | <i>Continued on next page</i> |

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# 510(k) Summary, Continued

6. Comparison to predicate device cont.

The following table compares the Tina-quant® α-1-Antitrypsin with the on a I he following table compares the 11-Antitrypsin assay. Specific data on the predicate device, Belling Brive of the consided into the draft labeling in performance of the test have been incorporated into the the the more of the more of the management 6.

## Similarities:

•Intended Use: Immunoassay for the in vitro quantitative determination of α - 1-antitrypsin

·Sample type: Serum and plasma

#### Differences

| Feature | Tina-quant® α-1-<br>Antitrypsin | Behring BN® α -1-<br>Antitrypsin |
|----------------------------|---------------------------------|--------------------------------------------------------------------------------------------------------------|
| Reaction test<br>principle | Immunoturbidimetric | Latex bound antigen/antibody<br>causing visible agglutination<br>throught large immune complex<br>formation. |
| Instrument<br>required | Hitachi | Behring Nephelometer (BN) |

### Performance Characteristics:

| Feature | Tina-quant® α-1-<br>Antitrypsin | | | Behring BN® α -1-<br>Antitrypsin | |
|-------------|---------------------------------|----------|----------|----------------------------------|-----|
| Precision | Intra and InterAssay (mg/dl): | | | Within and Between (mg/dL): | |
| | Level | Low | Pool | High | |
| Intra-Assay | N | 21 | 21 | 21 | 700 |
| | Mean | 155.7 | 167.1 | 311.9 | 244 |
| | %CV | 3.1 | 2.5 | 2.5 | 3.7 |
| | Level | Sample 1 | Sample 2 | | |
| Inter-Assay | Mean | 160.7 | 307.3 | | 244 |
| | %CV | 2.1 | 2.0 | | 5.3 |

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## 510(k) Summary, Continued

- 6.
## Performance Characteristics:

Comparison
to predicate

device, (cont.)

| Feature | Tina-quant® α-1-<br>Antitrypsin | Behring BN® α -1-<br>Antitrypsin |
|---------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------|
| Lower Detection<br>Limit | 10 mg/dL | - 30 mg/dL |
| Method<br>Comparison | Vs Behring BN® α -1-<br>Antitrypsin<br>Passing/Bablok<br>y =0.993x + 9.9<br>r=0.967<br>SEE =9.7<br>N=123<br><br>Least Squares:<br>y = 0.971x + 12.2<br>r = 0.967<br>SEE = 11.4<br>N = 123 | Vs Behring LN® α -1-<br>Antitrypsin<br>Linear Regression<br>y =0.88x + 30.2<br>r=0.967<br>N=59 |
| Interfering<br>substances | No interference at:<br>(≤ 10% error)<br><br>Bilirubin 60 mg/dL<br>Hemoglobin 1000 mg/dL<br>Lipemia 1000 mg/dL<br>Rheumatoid<br>Factor 100 IU/mL | N/A |
| Specificity | Specific for α -1-antitrypsin | Specific for α -1-antitrypsin |

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three lines forming its body and wings. The eagle is enclosed in a circle, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is written around the top half of the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN - 9 1998

Ms. Mary Koning Regulatory Affairs Specialist Boehringer Mannheim Corporation 135 Sandberg Street Thousand Oaks, California 91360

Re: K972640/S1 Trade Name: Tina-quant® α -1-Antitrypsin Assay Regulatory Class: II Product Code: DEM Dated: October 20, 1997 Received: October 22, 1997

Dear Ms. Koning:

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 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, Druq, 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, goodmanufacturing practice, labeling, and prohibitions aqainst 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 requirement, as set forth in the Quality System Regulation (QS) 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 requlation 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 at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Butman

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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510(k) Number (if known): K972640

Device Name: Tina-quant® x - 1-antitrypsin Assay

Indications For Use:

Immunological in vitro immunoturbidometric test for the quantitative determination of x -1antitrypsin in human serum and plasma.

The measurements aid in the diagnosis of several conditions including juvenile and adult cirrhosis of the liver. In addition, alpha-1-antitrypsin deficiency has been associated with pulmonary emphysema.

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

| Prescription Use | <span style="text-decoration: overline;">✓</span> | OR | Over-The-Counter Use |
|----------------------|---------------------------------------------------|----|--------------------------|
| (Per 21 CFR 801.109) | | | (Optional Format 1-2-96) |

| (Division Sign-Off) | |
|-----------------------------------------|---------|
| Division of Clinical Laboratory Devices | |
| 510(k) Number | K972648 |