The ACS:180 and ADVIA Centaur Valproic Acid Immunoassays are competitive, chemiluminescence immunoassay for the quantitative determination of valproic acid in human serum and plasma for use on the automated analyzers marketed by Bayer Corporation. Valproic acid (2-propylpentanoic acid) is an anticonvulsant that is used alone or in combination with other anticonvulsant drugs to control seizures. Monitoring of valproic acid ensures that there is adequate drug in the blood stream without being at toxic levels. The ACS:180 and ADVIA Centaur Valproic Acid Immunoassays are used as an aid to monitor patients' valproic acid level.

Device Description

The ACS and ADVIA Centaur Valproic acid assay is a competitive chemiluminescence immunoassay intended for the quantitative determination of valproic acid in human serum and plasma. Valproic acid in the patient sample, calibrators, standards and controls competes with acridinium ester-labeled valproic acid in the Lite Reagent for a limited amount of monoclonal mouse anti-valproic acid antibody, which is covalently coupled to paramagnetic particles in the Solid Phase. Following incubation, non-reacted acridinium ester-labeled valproic acid and non-reacted valproic acid from the sample is washed from the reaction mixture. The chemiluminescence of the bound, labeled valproic acid is measured in a luminometer. The measured chemiluminescence is inversely proportional to the quantity of valproic acid in the sample.

AI/ML Overview

The document describes a 510(k) premarket notification for the ADVIA Centaur and ACS:180 Valproic Acid Immunoassays. This is not a study that uses AI. The acceptance criteria and the study presented are for establishing substantial equivalence to a predicate device, the TDx Valproic acid assay, based on method comparison using correlation studies.

Here's an analysis of the provided information within the context of your request, noting where the information is not applicable due to the nature of the device (an immunoassay, not an AI device):

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for substantial equivalence are inferred from the correlation study results, which show a strong linear relationship and high correlation coefficient between the new devices and the predicate. While explicit numerical acceptance criteria (e.g., "slope between 0.9 and 1.1") are not directly stated as "acceptance criteria," the reported performance demonstrates that these criteria were met for substantial equivalence.

Acceptance Criteria (Inferred for Substantial Equivalence via Method Comparison)	Reported Device Performance (ADVIA Centaur Valproic acid vs. TDx valproic acid)	Reported Device Performance (ACS:180 Valproic acid vs. TDx valproic acid)	Reported Device Performance (ADVIA Centaur Valproic acid vs. ACS:180 Valproic acid)
Slope close to 1.0	0.96	0.98	0.97
Intercept close to 0.0	4.03	1.37	3.37
Correlation Coefficient (r) close to 1.0 (indicating strong linear relationship)	0.99	0.99	0.99

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

The document refers to the data as "correlation studies" and does not explicitly differentiate between "test set" and "training set" in the context of machine learning. Thus, the sample sizes provided are for the datasets used in these correlation studies.

Sample sizes for correlation studies (acting as test sets):
- ADVIA Centaur Valproic acid vs. TDx valproic acid: N = 250
- ACS:180 Valproic acid vs. TDx valproic acid: N = 250
- ADVIA Centaur Valproic acid vs. ACS:180 Valproic acid: N = 253
Data Provenance: Not specified. It's common for such studies to use clinical samples, but the country of origin or whether they were retrospective/prospective is not mentioned.

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

This information is not applicable as the ground truth for an immunoassay is typically established by the reference method (the predicate device, TDx Valproic acid assay) or by laboratory standards and calibrators, not by expert human graders or consensus. The "ground truth" here is the measurement obtained from the established method.

4. Adjudication Method for the Test Set

This information is not applicable. Adjudication methods (like 2+1, 3+1) are used for resolving discrepancies among human experts (e.g., radiologists, pathologists) who are establishing ground truth for subjective interpretations, especially in AI studies. For an immunoassay, the "ground truth" is a quantitative measurement, and disputes are resolved through quality control, calibration, and repeat testing, not expert adjudication in the traditional sense.

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

This information is not applicable. The device is a quantitative immunoassay, not an AI diagnostic tool that assists human readers. Therefore, an MRMC study and analysis of human reader improvement with AI assistance were not performed.

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

This information is not applicable in the context of an AI algorithm. The performance presented is inherently "standalone" in the sense that it's the performance of the immunoassay itself in comparison to a predicate, not an AI algorithm. There is no human-in-the-loop component for reading/interpreting the immunoassay results that would be "assisted" by AI.

7. The Type of Ground Truth Used

The "ground truth" for the comparison studies was established by the predicate device, the TDx Valproic acid assay. This means the new devices (ADVIA Centaur and ACS:180) were compared against an already legally marketed and accepted method for measuring valproic acid.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of algorithm development, as this is an immunoassay, not an AI-driven device. The term "training set" is typically used for machine learning. The studies described are method comparison studies.

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

This information is not applicable as there is no "training set" for an AI algorithm described in the document.

Summary

{0}------------------------------------------------

JAN 2 9 2002

Summary of Safety and Effectiveness ASC:180 and ADVIA Centaur Valproic acid Immunoassay

K013959

As required by 21 CFR 807.92, the following 510(k) Summary is provided:

3.1 Submitter Information

Contact person:

Address:

Kenneth T. Edds, Ph.D.

Bayer Diagnostics Corporation 511 Benedict Ave. Tarrytown, NY 10591

Phone: 914-524-2446 FAX: 914-524-2500 e-mail: ken.edds.b(@bayer.com

Date Summary Prepared:

November 12, 2001

3.2 Device Information

Proprietary Name:

ADVIA Centaur and ACS:180 Valproic Acid Immunoassay

Common Name:

Valproic acid Immunoassay

3.3 Predicate Device Information

Name:

TDx Valproic acid assay

K904226

Manufacturer:

510(k) number:

Abbott Laboratories Diagnostics Division Abbott Park, IL 60064

Device Description 3.4

{1}------------------------------------------------

3.5 Statements of Intended Use - Comparison

ACS Valproic acid .

"For the quantitative determination of valproic acid in serum or plasma using the Tor the qualificacity cocci inminescent Systems. For In Vitro diagnostic use."

ADVIA Centaur Valproic acid ●

"For in vitro diagnostic use in the quantitative determination of valproic acid in serum or plasma using the ADVIA Centaur System."

TDx Valproic acid ●

"The TDx/TDxFLx Valproic acid assay is a reagent system for the quantitative measurement of valproic acid, an anticonvulsant drug, in serum or plasma. The measurements obtained are used in monitoring levels of valproic acid to ensure appropriate therapy."

Summary of Technological Characteristics 3.6

The ADVIA Centaur and ACS:180 Valproic Acid assay uses a competitive immunoassay format that employs paramagnetic particles and chemiluminescence technology. Both assays use the same reagents, standards and calibrators. In addition the sample size and reagent volumes in the sume reagens, bandards and valierers. Due to analyzer differences, the incubation time differs by approximately 15 seconds. Data from both platforms is used to file for 510(k).

3.7 Method Comparison

Substantial equivalence of the ACS and ADVIA Centaur Valproic acid assay to the predicate device is seen.

These correlation studies demonstrate that the ACS:180 & ADVIA Centaur Valproic acid assay is equivalent to each other as well as the predicate device.

ReferenceAssay	TestAssay	Slope	Intercept	CorrelationCoefficient (r)	N
TDx valproic acid	ADVIA CentaurValproic acid	0.96	4.03	0.99	250
TDx valproic acid	ACS:180 Valproicacid	0.98	1.37	0.99	250
ACS:180 Valproic acid	ADVIA CentaurValproic acid	0.97	3.37	0.99	253

{2}------------------------------------------------

Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized emblem featuring three abstract, curved lines that resemble a human figure or a symbol representing health and well-being.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 2 9 2002

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

Re: K013959

Trade/Device Name: ADVIA Centaur and ACS: 180 Valproic Acid Assay Regulation Number: 21 CFR 862.3645; 21 CFR 862.3200 Regulation Name: Neuroleptic drugs radioreceptor assay test system; Clinical toxicology calibrator Regulatory Class: Class II; Class II Product Code: LEG: DKB Dated: November 29, 2001 Received: November 30, 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. Iisting 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 (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

{3}------------------------------------------------

Page 2 -

This letter will allow you to begin marketing your device as described in your 510(k) premarketed This letter will anow you to begin maketing 5 our device of your device to a legally marketed
notification. The FDA finding of substantial equivalence of your device to notification. The FDA inding of substantial equivalise of your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (2) CFR Part 801 and If you desire specific advice for your do rooms the Office of Complising of Compliance at
additionally 809.10 for in vitro diagnostic devices), please contact the office of v additionally 809.10 for in viuo diagnostions on the promotion and advertising of your device, (301) 594-4588. Additionally, for questions on as prease note the regulation please contact the Office or Compliation and (1) rotification's (121CFR 807.97). Other general entitled, "Misbranding by relevence to promazion the Act may be obtained from the Division of Small information on your responsionals and Consumer Assistance at its toll-free number (800) 638-2041 or
Manufacturers International and Consumer Assistance at its toll-creation h Manufacturers International and Collisanter Filtp://www.fda.gov/cdrl/dsma/dsmamain.html".
(301) 443-6597 or at its internet address "http://www.fda.gov/cdrl/dsma/dsmamain.htm

Sincerely yours,

Steven Gutman

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

{4}------------------------------------------------

510(k) Number (if known): _ Ko13959

of Page

Device Name: ADVIA Centaur and ACS:180 Valproic Acid Assay

Indications for Use:

Sean Cooper

(Division Sign-Off)
Division of Clinical Laboratory Devices

510(k) Number.

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

NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE) L OR Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________ Prescription Use (Optional Format 1-2-96) (Per 21 CFR 801.109)

Bayer ADVIA Centaur and ACS:180 Valproic acid - 510(k) – Premarket notification

Regulation Number and Section

§ 862.3200 Clinical toxicology calibrator.

(a)
Identification. A clinical toxicology calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. A clinical toxicology calibrator can be a mixture of drugs or a specific material for a particular drug (e.g., ethanol, lidocaine, etc.). (See also § 862.2 in this part.)(b)
Classification. Class II (special 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.