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 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.

AI/ML Overview

The Boehringer Mannheim Tina-quant® α-1-Antitrypsin Assay is an immunoturbidometric assay for the quantitative in-vitro determination of α-1-antitrypsin. The device was deemed substantially equivalent to the currently marketed Behring BN® α-1-Antitrypsin assay.

1. Table of Acceptance Criteria and Reported Device Performance:

The document primarily focuses on comparative performance against a predicate device rather than pre-defined acceptance criteria. However, we can infer performance characteristics evaluated for equivalence.

Feature	Acceptance Criteria (Implied by Predicate Performance)	Reported Device Performance (Tina-quant® α-1-Antitrypsin)
Precision	Comparable to Behring BN® α-1-Antitrypsin	Intra-Assay (%CV): Low: 3.1, Pool: 2.5, High: 2.5
	(Behring BN® provided only a combined %CV of 5.3 for Inter-Assay)	Inter-Assay (%CV): Sample 1: 2.1, Sample 2: 2.0
Lower Detection Limit	Comparable to Behring BN® α-1-Antitrypsin (30 mg/dL)	10 mg/dL (Better than predicate)
Method Comparison	Good correlation with Behring BN® α-1-Antitrypsin	Vs Behring BN®:
	(Behring BN®: y = 0.88x + 30.2, r = 0.967, N = 59)	Passing/Bablok: y = 0.993x + 9.9, r = 0.967, SEE = 9.7, N = 123
		Least Squares: y = 0.971x + 12.2, r = 0.967, SEE = 11.4, N = 123
Interfering Substances	No significant interference with common substances	No interference (≤ 10% error) at: Bilirubin 60 mg/dL, Hemoglobin 1000 mg/dL, Lipemia 1000 mg/dL, Rheumatoid Factor 100 IU/mL
Specificity	Specific for α-1-antitrypsin	Specific for α-1-antitrypsin

2. Sample Size Used for the Test Set and Data Provenance:

Precision Test Set (Intra-Assay): N = 21 for each of the three levels (Low, Pool, High).
Precision Test Set (Inter-Assay): Not explicitly stated, but "Sample 1" and "Sample 2" are mentioned. The Behring BN® Inter-Assay tested 244 samples.
Method Comparison Test Set: N = 123 for comparison against the Behring BN® α-1-Antitrypsin.
Interfering Substances Test Set: Not explicitly stated, but specific concentrations of bilirubin, hemoglobin, lipemia, and rheumatoid factor were tested.
Data Provenance: The document does not specify the country of origin for the data or whether it was retrospective or prospective. Given the context of a 510(k) summary for a diagnostic test, it's highly likely to be prospective clinical or analytical studies conducted in a controlled lab environment.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

This information is not provided in the document. For an immunoturbidometric assay, the "ground truth" would typically be established by reference methods or validated quantitative measurements rather than expert human interpretation.

4. Adjudication Method for the Test Set:

This information is not applicable as the ground truth is established by quantitative laboratory measurements, not through expert review that would require adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for imaging or diagnostic tools that rely on human interpretation. This device is an in-vitro diagnostic assay for quantitative measurement.

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

Yes, this is a standalone performance study. The device is an automated in-vitro diagnostic assay that provides a quantitative measurement of α-1-antitrypsin. Its performance is evaluated purely based on its analytical capabilities, not on human interpretation or interaction beyond sample handling.

7. The Type of Ground Truth Used:

The ground truth used for performance evaluation is based on quantitative analytical measurements from reference methods or established predicate devices. For instance, the method comparison directly compares the results of the Tina-quant® assay to those obtained with the Behring BN® α-1-Antitrypsin assay, which serves as a widely accepted reference for this analyte.

8. The Sample Size for the Training Set:

The document does not specify a separate training set size. For an in-vitro diagnostic assay, development and calibration would involve various samples, but a distinct "training set" in the context of machine learning (where this question typically applies) is not explicitly mentioned as relevant. The performance characteristics described are typically for validation/testing.

9. How the Ground Truth for the Training Set Was Established:

As no explicit "training set" is mentioned in the context of machine learning models, the method for establishing ground truth for such a set is not applicable or described. For the development and calibration of the assay, ground truth would be established through the use of characterized calibrators and controls with known α-1-antitrypsin concentrations, often traceable to international reference standards.

Summary

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Telephone: +1 (510) 674 0667 Fax: +1 (510) 674 1680

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.

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

Device name

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

Classification name: α -1-antitrypsin immunological test system

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.
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510(k) Summary, Continued

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-Antitrypsin	Behring BN® α -1-Antitrypsin
Reaction testprinciple	Immunoturbidimetric	Latex bound antigen/antibodycausing visible agglutinationthrought large immune complexformation.
Instrumentrequired	Hitachi	Behring Nephelometer (BN)

Performance Characteristics:

Feature	Tina-quant® α-1-Antitrypsin			Behring BN® α -1-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

Performance Characteristics:

Comparison
to predicate

device, (cont.)

Feature	Tina-quant® α-1-Antitrypsin	Behring BN® α -1-Antitrypsin
Lower DetectionLimit	10 mg/dL	- 30 mg/dL
MethodComparison	Vs Behring BN® α -1-AntitrypsinPassing/Babloky =0.993x + 9.9r=0.967SEE =9.7N=123Least Squares:y = 0.971x + 12.2r = 0.967SEE = 11.4N = 123	Vs Behring LN® α -1-AntitrypsinLinear Regressiony =0.88x + 30.2r=0.967N=59
Interferingsubstances	No interference at:(≤ 10% error)Bilirubin 60 mg/dLHemoglobin 1000 mg/dLLipemia 1000 mg/dLRheumatoidFactor 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 (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 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 (800) 638-2041 or at (301) 443-6597 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.

	Concurrence of CDRH, Office of Device Evaluation (ODE)
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Prescription Use	✓	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

Regulation Number and Section

§ 866.5130

Alpha -1-antitrypsin immunological test system.(a)
Identification. Analpha -1-antitrypsin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques thealpha -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.(b)
Classification. Class II (performance standards).