The Bayer ADVIA Chemistry Alpha-1-antitrypsin assay is an in vitro diagnostic device intended to quantitatively measure Alpha-1-antitrypsin concentration in human serum and plasma on the ADVIA® Chemistry system. Measurement of alpha-1-antitrypsin levels aid in the diagnosis of juvenile and adult cirrhosis of the liver. In addition, alpha-1-antitrypsin deficiency has been associated with pulmonary emphysema.

Device Description

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AI/ML Overview

Here's an analysis of the provided text, focusing on acceptance criteria and the study proving device performance:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria with specific numerical thresholds for performance metrics. Instead, it presents performance data for the new device alongside a predicate device (Roche) for comparison (for imprecision) and reports correlation with another comparison system (Hitachi) without direct acceptance values. The "acceptance" can be inferred by the FDA's clearance, which implies the device's performance was deemed substantially equivalent to a legally marketed predicate.

However, we can infer some criteria from the data provided:

Performance Metric	Inferred Acceptance Criteria (Implicit)	Reported Device Performance (ADVIA 1650)	Comparison/Predicate Performance
Imprecision (CV%)	Similar or better within-run CV% compared to predicate, and generally low.	Level 91.83: 1.1%	Roche Level 67.5: 3.9%
		Level 188.39: 0.83%	Roche Level 496.8: 0.7%
		Level 346.99: 0.85%	Roche Level 574.8: 7.33%
Correlation ($R^2$) vs. a comparison system	Strong linear correlation (r value close to 1)	r = 0.965	Not applicable (comparison system)
Interference (% Recovery)	% Recovery close to 100% (within a reasonable range, e.g., 90-110%)	Hemoglobin: 109.88%	Not applicable
		Bilirubin conj: 102.83%	Not applicable
		Bilirubin unconj: 98.84%	Not applicable
		Intralipid: 109.05%	Not applicable
		TRIG concentrate: 106.37%	Not applicable
Analytical Range	A suitable range for clinical diagnostic use.	5.37 mg/dL to 510 mg/dL	Not applicable

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

Imprecision: Not explicitly stated, but typically involves multiple replicates over several runs. The levels noted (e.g., 91.83 ug/dL) likely represent specific control or patient samples tested multiple times.
Correlation:
- Sample Size: N = 44 (for serum specimens)
- Data Provenance: Not explicitly stated (e.g., country of origin). It is retrospective as these are existing samples being tested on two different systems.
Interference: Not explicitly stated, but based on the table, 5 different interfering substances were tested. For each substance, it appears one AAT concentration was spiked with the interferent.
Analytical Range: Not explicitly stated, but typically involves testing a series of diluted and concentrated samples to determine linearity.

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

This type of in vitro diagnostic device (IVD) for quantitative measurement of a biomarker does not rely on expert interpretation for ground truth in the same way an imaging AI or diagnostic algorithm might.

For Imprecision, the "ground truth" is the established reference value of the control material or the sample's true concentration, measured meticulously in a laboratory setting.
For Correlation, the "ground truth" for the comparison is the measurement obtained from the chosen comparison system (Hitachi AAT in this case).
For Interference, the "ground truth" is the known concentration of alpha-1-antitrypsin in the sample before the interferent is added.
For Analytical Range, the "ground truth" is the known concentration of standard solutions or diluted samples.

Therefore, the concept of "experts establishing ground truth" as it applies to diagnostic interpretation is not relevant here. The ground truth is inherent in the chemical and analytical properties of the samples and the established reference methods.

4. Adjudication Method for the Test Set

Not applicable. As explained above, this is a quantitative measurement, not a diagnostic interpretation that requires adjudication among experts.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

Not applicable. This is an in vitro diagnostic assay (a laboratory test), not an AI-assisted diagnostic imaging or interpretation system that involves human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the studies presented (imprecision, correlation, interference, analytical range) reflect the standalone performance of the device/method (Bayer ADVIA Chemistry Alpha-1-antitrypsin assay). This device is an automated chemical analyzer component, and its "performance" is its ability to accurately and precisely measure the analyte without human interpretive intervention.

7. The Type of Ground Truth Used

For Imprecision: Reference material values or meticulously measured sample concentrations.
For Correlation: Measurements from a predicate/comparison device (Hitachi AAT).
For Interference: Known spiked concentrations and baseline measurements of the unspiked sample.
For Analytical Range: Gravimetrically or volumetrically prepared standard solutions.

8. The Sample Size for the Training Set

Not applicable in the context of an IVD assay's analytical validation. This device is not an AI/ML model that requires a distinct "training set." The development of the assay (e.g., reagent formulation, assay parameters) would involve extensive R&D and optimization, but not a "training set" in the machine learning sense. The data presented are for verification and validation of the final assay.

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

Not applicable, as there's no "training set" in the AI/ML context for this type of device. The accuracy of the assay itself is validated against established analytical principles and reference methods.

Summary

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SEP - 4 2003

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS Alpha-1-antitrypsin method for ADVIA® 1650TM

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.

The assigned 510(k) number is: KD3/857

1. Intended Use

2. Predicate Device

Product Name	Reagent Part #	Calibrator Part #
Roche Alpha-1-antitrypsin	1557599	1355279

3. Device / Method

Product Name	Reagent REF(part #)	Calibrator REF(part #)
Bayer ADVIA® Chemistry Alpha-1-antitrypsin	06921866(B01-4834-01)	07711199(B03-4845-01)

4. Performance:

A. Imprecision
ADVIA 1650		Roche
Level(ug/dL)	Within-runCV(%)	Level(ug/dL)	Within-runCV(%)
91.83	1.1	67.5	3.9
188.39	0.83	496.8	0.7
346.99	0.85	574.8	7.33

B. Correlation (Y=ADVIA 1650, X=comparison system)

Specimen Type	ComparisonSystem (x)	N	Regression Equation	Syx	r	Sample Rangemg/dL
Serum	Hitachi AAT	44	$Y = 0.94x + 13.1$	20.6	0.965	42.8 - 258.9

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C. Interfering Substances

Alpha-1-antitrypsin(ug/dL)	Interferent	Interferent (mg/dL)	Alpha-1-antitrypsinwith interferent(mg/dL)	% Recovery
200.5	Hemoglobin	1000	220.3	109.88%
201.6	Bilirubin conj	25	207.3	102.83%
207.3	Bilirubin unconj	25	204.9	98.84%
204.5	Intralipid	125	223	109.05%
252.8	TRIG concentrate	187.5	268.9	106.37%

D. Analytical Range

Serum/Plasma:

5.37 mg/dL to AAT concentration in highest calibrator (typically 510 mg/dL).

Aula Hues
Andrew Hues

Andres Holle Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

6/5/03
Date

Date

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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three heads, representing the department's commitment to health, human services, and science. The eagle is surrounded by the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" in a circular arrangement. The logo is simple, yet recognizable, and is used to represent the department's mission to protect the health of all Americans and provide essential human services.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Andres Holle Manager, Regulatory Affairs Bayer HealthCare LLC Diagnostics Division 511 Benedict Avenue Tarrytown, New York 10591-5097

SEP - 4 2003

Re: K031857

Trade/Device Name: Alpha-1-antitrypsin Assay for the ADVIA® Chemistry System Regulation Number: 21 CFR § 866.5130 Regulation Name: Alpha-1-antitrypsin immunological test system Regulatory Class: II Product Code: DEM Dated: August 12, 2003 Received: August 13, 2003

Dear Mr. Holle:

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). 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.

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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 (301) 594-3084. 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-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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1031857 510(k) Number:

Device Name: Alpha-1-antitrypsin Assay for the ADVIA® Chemistry System

Indications for Use:

The Bayer ADVIA Chemistry Alpha-1-antitrypsin method is an in vitro diagnostic device intended to quantitatively measure alpha-1-antitrypsin levels in human serum and plasma. Such measurements are used in the diagnosis of juvenile and adult cirrhosis of the liver. In addition, alpha-1-antitrypsin deficiency has been associated with pulmonary emphysema.

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use(Per 21 CFR 801.109)	✓	OR	Over-The-CounterUse
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(Optional Format 1-2-96)

[Signature]

Division Sign-Off for Jean Cooper

Office of In Vitro Diagnostic Device

Evaluation and Safety

510(k) K031857

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).