The ADVIA 1650 Cholinesterase in vitro diagnostic procedure is intended to measure cholinesterase in human I he ADVANT 1050 Onlinesser any and 650 system. Such measurement is used in the diagnosis and treatment Scruit and pashia on the Dayer AD Previous liver diseases such as cirrhosis and acute and chronic hepatitis.

Device Description

The Cholinesterase in vitro diagnostic procedure is intended to measure cholinesterase enzyme activity in human serum, plasma (lithium heparin) on the Bayer ADVIA® 1650 Such measurement is used in the diagnosis and treatment of organophosphorus System. poisoning and certain liver diseases such as cirrhosis, acute and chronic hepatitis.

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and study details for the Bayer ADVIA® 1650 System's Cholinesterase method:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied by Predicate)	Reported Device Performance (ADVIA 1650)
Imprecision
Level 1 CV (U/L)	Predicate: 4.3% (at 4350 U/L)	1.1% (at 4235.86 U/L)
Level 2 CV (U/L)	Predicate: 4.0% (at 6310 U/L)	0.9% (at 6978.97 U/L)
Level 3 CV (U/L)	Not available for predicate	1.1% (at 12318.49 U/L)
Correlation
Serum (r)	Implied high correlation (predicate K913198, K912217)	0.994 (Y=1.325X+228.69)
Plasma vs Serum (r)	Implied high correlation	0.984 (Y=0.973X+130.33)
Interference	Implied minimal interference
Bilirubin (unconjugated, 25 mg/dL)	Implied acceptable % change	-0.70%
Bilirubin (conjugated, 25 mg/dL)	Implied acceptable % change	+0.95%
Hemoglobin (520 mg/dL)	Implied acceptable % change	+0.44%
Lipids (Intralipid, 520 mg/dL)	Implied acceptable % change	-0.13%
Analytical Range	Implied similar to predicate	1,500 - 30,000 U/L

Note on Acceptance Criteria: The document does not explicitly state numerical acceptance criteria for each metric. Instead, the demonstration of "substantial equivalence" to the predicate device (Kodak Vitros 250/ Cholinesterase) implies that the performance of the new device (ADVIA 1650 Cholinesterase) should be comparable to or better than the predicate. For imprecision, the ADVIA 1650 clearly shows lower CVs, indicating better precision than the predicate. For correlation and interference, the results are presented as positive data points supporting equivalence.

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

Imprecision: Not explicitly stated as "test set," but the data suggests it's from a study.
- Three levels were tested for the ADVIA 1650 Cholinesterase. The sample size for each level to calculate the CV is not specified (e.g., number of replicates).
- Two levels were reported for the Kodak Vitros 250 Cholinesterase. The sample size for each level to calculate the CV is not specified.
Correlation:
- Serum: N = 58
- Plasma vs Serum: N = 40
Interfering Substances: Not explicitly stated as "test set," but for each interfering substance, "control" and "test sample" values are provided, implying at least two measurements for each. The overall number of samples (e.g., healthy or spiked) for this study is not detailed.
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, given it's an in vitro diagnostic device for human serum/plasma, the samples would be human biological specimens. The study was conducted by Bayer Diagnostics, a multinational company.

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

This information is not provided in the document. For in vitro diagnostic tests like Cholinesterase, the "ground truth" is typically established by the reference method or comparison method itself, rather than expert interpretation of results. The Cholinesterase activity is a measurable analyte, and the focus is on the accuracy, precision, and correlation of the new device's measurement against a validated comparator, not subjective expert assessment.

4. Adjudication Method for the Test Set

This information is not applicable and therefore not provided. Adjudication methods (e.g., 2+1, 3+1) are typically used in studies involving subjective interpretation of medical images or clinical outcomes where there might be disagreement among reviewers, requiring a consensus or tie-breaker. For an in vitro diagnostic test measuring a specific analyte concentration, the "ground truth" or reference is the quantitative value from a comparison system.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is relevant for imaging devices or diagnostics that depend on human interpretation, where the goal is to assess how a device (often AI-assisted) impacts the diagnostic performance of multiple readers across various cases. The Cholinesterase assay is a quantitative laboratory test, not an imaging or interpretive diagnostic.

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

Yes, this entire study represents a standalone (algorithm only) performance assessment. The ADVIA 1650 Cholinesterase system is an automated in vitro diagnostic device. The performance metrics (imprecision, correlation, interference, analytical range) presented are the direct output and performance characteristics of the instrument and its associated reagents, without human interpretive involvement in the measurement itself. The "algorithm" here refers to the chemical reactions and photometric measurements performed by the ADVIA 1650 system.

7. The Type of Ground Truth Used

The ground truth used for performance evaluation was the comparison to a legally marketed predicate device/method: the Kodak Vitros 250/ Cholinesterase.

For correlation studies, the measurements obtained from the Kodak Vitros 250 were effectively treated as the reference or "ground truth" against which the ADVIA 1650 results were compared.
For imprecision, the inherent variability of the predicate served as a benchmark for what's acceptable.
For interference, the "control" sample (without interferent) served as the baseline to assess the effect of the interfering substance.

8. The Sample Size for the Training Set

The document does not explicitly mention a separate "training set" for the ADVIA 1650 Cholinesterase method. This is understandable because the device is a chemical assay system, not an AI/ML algorithm that typically requires a distinct training phase on data.

If there were any internal development or optimization studies done during the method's development by Bayer, those would have used various samples, but they are not detailed in this 510(k) summary, which focuses on validation data against a predicate.

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

Since a "training set" in the context of AI/ML is not discussed, the method for establishing "ground truth" for a training set is not applicable and not provided. The development of the Cholinesterase reagent and instrument parameters would be based on established biochemical principles and extensive internal R&D, rather than a data-driven training process with externally established ground truth labels common in AI/ML.

Summary

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JAN 1 8 2002-10(k) SUMMARY OF SAFETY AND EFFECTIVENESS Cholinesterase method for Bayer ADVIA® 1650 System

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: K013750

1. Intended Use

2. Predicate Device/ Method

Product Name	Reagent Part #	Calibrator Part #	Predicate Device #
Kodak Vitros 250/ Cholinesterase	800 4707	120 4247	K913198, K912217

3. Device / Method

Product Name	REF	Calibrator Part #
ADVIA 1650 / Cholinesterase	B01-4605-01	N/A,(absolute calibrationfactor 43287)

Imprecision

ADVIA 1650Cholinesterase		Kodak Vitros 250Cholinesterase
Level(U/L)	TotalCV(%)	Level(U/L)	TotalCV(%)
4235.86	1.1	4350	4.3
6978.97	0.9	6310	4.0
12318.49	1.1

Correlation (Y=ADVIA 1650 Cholinesterase, X= Vitros 250 cholinesterase)

Specimen type	Comparison System (X)	N	Regression Equation	Syx (U/L)	r	Sample Range (U/L)
Serum	Kodax Vitros 250	58	Y=1.325X+228.69	306.57	0.994	1560.0-11090.0
Plasma(Y) vs Serum(X)	ADVIA 1650	40	Y=0.973X+130.33	359.9	0.984	5051.4-14467.1

Interfering Substances

Interfering	Interfering Sub.	Control	Test Sample	Effect
Substance	Conc. (mg/dL)	(U/L)	(U/L)	(% change)
Bilirubin (unconjugated)	25	7705.57	7651.71	-0.70
Bilirubin (conjugated)	25	7561.88	7633.48	+0.95
Hemoglobin	520	9659.20	9701.98	+0.44
Lipids (Intralipid)	520	9655.47	9643.34	-0.13

Analytical Range

Serum/Plasma: 1,500 - 30,000 U/L

Nonclinical testing demonstrates that this device is as safe and effective as the predicate device.

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Prepared by:

Kenneth T. Edds, Ph.D.
Regulatory Affairs Bayer Diagnostics 511 Benedict Avenue Tarrytown, NY 10591

On: January 15, 2002

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Image /page/2/Picture/1 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features an abstract image of an eagle with three stripes representing the department's commitment to health, human services, and well-being. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 1 8 2002

Kenneth T. Edds, Ph.D. Manager, Regulatory Affairs Bayer Diagnostic Corporation 511 Benedict Avenue Tarrytown, NY 10591-5097

Re: K013750 Trade/Device Name: Cholinesterase Assay for the Advia 1650 Regulation Number: 21 CFR 862.3240 Regulation Name: Cholinesterase Test System Regulatory Class: Class I Product Code: DIH Dated: November 12, 2001 Received: November 13, 2001

Dear Dr. Edds:

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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

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 1 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 regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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 Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page __ of _1

510(k) Number: KO13750

Device Name: Cholinesterase Assay for the Advia 1650

Indications for Use:

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K013750

(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)

Over-The-CounterUse___________________________________________________________________________________________________________________________________________________________

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.3240 Cholinesterase test system.

(a)
Identification. A cholinesterase test system is a device intended to measure cholinesterase (an enzyme that catalyzes the hydrolysis of acetylcholine to choline) in human specimens. There are two principal types of cholinesterase in human tissues. True cholinesterase is present at nerve endings and in erythrocytes (red blood cells) but is not present in plasma. Pseudo cholinesterase is present in plasma and liver but is not present in erythrocytes. Measurements obtained by this device are used in the diagnosis and treatment of cholinesterase inhibition disorders (e.g., insecticide poisoning and succinylcholine poisoning).(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.