The Roche ONLINE TDM Valproic Acid assay contains an in vitro diagnostic reagent system indicated for the quantitative determination of valproic acid in human serum or plasma on automated clinical chemistry analyzers. Valproic acid is primarily used in the treatment of petit mal seizures and other generalized and partial complex seizures.

Device Description

The assay is a homogeneous immunoassay based on the principle of measuring changes in scattered light or absorbance which result when activated microparticles aggregate. The microparticles are coated with valproic acid and rapidly aggregate in the presence of a valproic acid antibody solution. When a sample containing valproic acid is introduced, the aggregation reaction is partially inhibited, slowing the rate of the aggregation process. Antibody bound to sample drug is no longer available to promote microparticle aggregation, and subsequent particle lattice formulation is inhibited. Thus, a classic inhibition curve with respect to valproic acid concentration is obtained, with the maximum rate of aggregation at the lowest valproic acid concentration. By monitoring the change in scattered light or absorbance, a concentration-dependent curve is obtained.

AI/ML Overview

The provided text describes the Roche ONLINE Valproic Acid Assay. Here's a breakdown based on your request:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a separate section. However, the comparison to the predicate device and the discussion of "acceptable results" imply that performance characteristics aligning with or improving upon the predicate device's performance serve as the de facto acceptance criteria.

Performance Characteristic	Acceptance Criteria (Implied by Predicate Performance)	Reported Device Performance (Roche ONLINE TDM Valproic Acid Assay)
Method Comparison	R value comparable to predicate (Roche Valproic Acid II or Abbott TDx)	Versus Roche Valproic Acid II: N = 75, Y = 0.969X + 3.003, R = 0.992
		Versus Abbott TDx Valproic Acid Assay: N = 77, Y = 1.08X - 0.61, R = 0.972
Precision (CV%)	Lower or comparable CV% to predicate device	Level 1: Within Run CV% = 0.8, Total CV% = 2.1
		Level 2: Within Run CV% = 0.6, Total CV% = 2.4
		Level 3: Within Run CV% = 0.6, Total CV% = 1.9
Range	Comparable to predicate device	11.3 to 144.2 µg/mL
Other (General)	Acceptable results compared to the predicate device for lower detection limit, specificity, and interfering substances	"All of the evaluation studies gave acceptable results compared to the predicate device."

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

Sample Size for Method Comparison:
- N = 75 for comparison against Roche Valproic Acid II Assay.
- N = 77 for comparison against Abbott TDx Valproic Acid Assay.
Data Provenance: The document does not specify the country of origin of the data or whether the data was retrospective or prospective.

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. The study involves comparing a new assay to existing predicate assays, which are themselves considered established methods for measuring valproic acid. Ground truth, in this context, is implicitly defined by the results of the predicate devices.

4. Adjudication Method for the Test Set:

This information is not provided in the document. Given the nature of a quantitative immunoassay comparison, typical adjudication methods used in image interpretation or diagnostic agreement studies (like 2+1 or 3+1) are not directly applicable. The "adjudication" is essentially the statistical comparison between the new assay's results and the predicate assay's results.

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 is not applicable to this device. The Roche ONLINE Valproic Acid Assay is an in vitro diagnostic reagent system for quantitative determination, not an AI-assisted diagnostic tool that aids human readers.

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

The device itself is a standalone assay (reagent system run on automated clinical chemistry analyzers); there is no "human-in-the-loop" performance in its direct function. The performance described (precision, method comparison) reflects the algorithm's (assay's) standalone accuracy and reproducibility.

7. The Type of Ground Truth Used:

The ground truth for the performance evaluation was the results obtained from the legally marketed predicate devices, specifically:

Roche Valproic Acid II Assay (K930734)
Abbott TDx Valproic Acid Assay

These predicate devices are assumed to provide accurate measurements of valproic acid.

8. The Sample Size for the Training Set:

This information is not applicable and not provided. This device is a chemical immunoassay, not a machine learning or AI-based algorithm that requires a "training set" in the computational sense. The "development" of the assay would involve chemical formulation and optimization, not algorithmic training on data.

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

This information is not applicable for the reasons stated above (not an AI/ML device requiring a training set).

Summary

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K032049

AUG 2 2 2003

Roche ONLINE Valproic Acid Assay

510(k) Summary

Introduction

According to the requirements of 21 CFR 807.92, the following information
provides sufficient detail to understand the basis for a determination of
substantial equivalence.

1) Submitter name, address, contact	Roche Diagnostics Corporation9115 Hague Rd.Indianapolis, IN 46250(317) 845-2000Contact Person: Mike FlisDate Prepared: June 27, 2003
2) Device name	Roche ONLINE TDM Valproic Acid
3) Predicate device	We claim substantial equivalence to the Roche Valproic II Assay [K930734].
4) Device Description	The assay is a homogeneous immunoassay based on the principle of measuring changes in scattered light or absorbance which result when activated microparticles aggregate. The microparticles are coated with valproic acid and rapidly aggregate in the presence of a valproic acid antibody solution. When a sample containing valproic acid is introduced, the aggregation reaction is partially inhibited, slowing the rate of the aggregation process. Antibody bound to sample drug is no longer available to promote microparticle aggregation, and subsequent particle lattice formulation is inhibited. Thus, a classic inhibition curve with respect to valproic acid concentration is obtained, with the maximum rate of aggregation at the lowest valproic acid concentration. By monitoring the change in scattered light or absorbance, a concentration-dependent curve is obtained.

Continued on next page

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510(k) Summary, Continued

Intended use For the quantitative determination of valproic acid in human serum or plasma on automated clinical chemistry analyzers. The Roche ONLINE TDM Valproic Acid was evaluated for several 6) Comparison to predicate performance characteristics, including precision, lower detection limit, device method comparison, specificity, and interfering substances. All of the evaluation studies gave acceptable results compared to the predicate device. These experiments provide evidence that the Roche ONLINE TDM Valproic Acid Assay is substantially equivalent to the currently marketed Roche Valproic Acid II Assay. The following table presents the precision and method comparison results.

Roche ONLINE TDM Valproic Acid				Roche Valproic Acid II, (Predicate)
Versus Roche Valproic Acid II Assay(predicate device)				Versus Abbott TDx Valproic Acid Assay
N = 75				N= 77
Y = $0.969X+3.003$				Y= $1.08X-0.61$
R = 0.992				R= 0.972
Range = 11.3 to 144.2 µg/mL				Range = 2.6 to 119.8 µg/mL
NCCLSPrecision:	Level 1	Level 2	Level 3	Level 1	Level 2	Level 3
Mean (µg/mL)	34.8	74.1	118.9	20.6	65.2	118.5
CV% (within run)	0.8	0.6	0.6	2.3	1.5	1.3
CV% (total)	2.1	2.4	1.9	3.4	2.3	1.7

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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 depiction of an eagle or bird-like figure with three curved lines forming its body and wings. The logo is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES U.S.A."

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 2 2 2003

Mr. Mike Flis Regulatory Affairs Principal Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, IN 46250

K032049 Re:

Trade/Device Name: Roche ONLINE TDM Valproic Acid Assay Regulation Number: 21 CFR 862.3645 Regulation Name: Neuroleptic drugs radioreceptor assay test system Regulatory Class: Class II Product Code: LEG Dated: June 27, 2003 Received: July 11, 2003

Dear Mr. Flis:

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).

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Page 2 -

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.

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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Roche Diagnostics Corporation

510(k) Number (if known): Device Name: Roche ONLINE TDM Valproic Acid Assay Indications for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Alle to
Division Sign Off for Jean Cooker

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K032049

Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.3645 Neuroleptic drugs radioreceptor assay test system.

(a)
Identification. A neuroleptic drugs radioceptor assay test system is a device intended to measure in serum or plasma the dopamine receptor blocking activity of neuroleptic drugs and their active metabolites. A neuroleptic drug has anti-psychotic action affecting principally psychomotor activity, is generally without hypnotic effects, and is a tranquilizer. Measurements obtained by this device are used to aid in determining whether a patient is taking the prescribed dosage level of such drugs.(b)
Classification. Class II.