The Roche ONLINE Phenytoin assay contains an in vitro diagnostic reagent system indicated for the quantitative determination of phenytoin, an anti-convulsant drug, in human serum or plasma on automated clinical chemistry analyzers. Measurements obtained by the device are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels of phenytoin to ensure appropriate therapy.

Device Description

AI/ML Overview

Acceptance Criteria and Study for Roche ONLINE Phenytoin Assay

1. Table of Acceptance Criteria and Reported Device Performance

The provided document describes a comparison to a predicate device (Roche CEDIA Phenytoin II Assay), not a study against pre-defined acceptance criteria for a novel device. The "acceptable results compared to the predicate device" serves as the implicit acceptance criterion. The key performance metrics reported are for precision and method comparison.

Performance Metric	Acceptance Criteria (Implicit - Comparison to Predicate)	Roche ONLINE Phenytoin Assay Performance	Roche CEDIA Phenytoin II Assay Performance (Predicate)
Method Comparison	To be substantially equivalent to the predicate device when compared against the Abbott TDx Phenytoin Assay.	Y = 0.99X - 0.865 (vs Abbott TDx)	Y = 0.99X - 1.43 (vs Abbott TDx)
Correlation Coefficient (R)	To be substantially equivalent to the predicate device.	R = 0.992 (vs Abbott TDx)	R = 0.993 (vs Abbott TDx)
Measurement Range	To be substantially equivalent to the predicate device.	1.68 to 40.0 µg/mL	1.1 to 40.0 µg/mL
Precision (Level 1: Mean)	To be substantially equivalent to the predicate device.	6.49 µg/mL	6.3 µg/mL
Precision (Level 1: CV% within run)	To be substantially equivalent to the predicate device.	2.7%	3.2%
Precision (Level 1: CV% total)	To be substantially equivalent to the predicate device.	6.1%	5.1%
Precision (Level 2: Mean)	To be substantially equivalent to the predicate device.	13.39 µg/mL	14.8 µg/mL
Precision (Level 2: CV% within run)	To be substantially equivalent to the predicate device.	1.4%	2.0%
Precision (Level 2: CV% total)	To be substantially equivalent to the predicate device.	4.5%	3.1%
Precision (Level 3: Mean)	To be substantially equivalent to the predicate device.	22.87 µg/mL	26.8 µg/mL
Precision (Level 3: CV% within run)	To be substantially equivalent to the predicate device.	1.5%	1.3%
Precision (Level 3: CV% total)	To be substantially equivalent to the predicate device.	4.3%	2.3%

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

Sample Size for Test Set (Method Comparison):
- Roche ONLINE Phenytoin vs. Abbott TDx Phenytoin Assay: N = 106
- Roche CEDIA Phenytoin II vs. Abbott TDx Phenytoin Assay: N = 108
Data Provenance: The document does not specify the country of origin of the data. It also does not explicitly state whether the data was retrospective or prospective, though clinical diagnostic assay comparisons are typically prospective clinical performance evaluations or studies on patient samples.

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

This is a clinical chemistry assay for quantitative determination of phenytoin. Ground truth for such assays is typically established by comparing the device's results to a recognized, accurate reference method or a legally marketed predicate device. In this case, the Abbott TDx Phenytoin Assay served as the reference method against which both the new device and the predicate device were compared. No "experts" in the sense of physicians reviewing images or cases are usually involved in establishing ground truth for quantitative laboratory assays; the ground truth is the result from the reference method.

4. Adjudication Method for the Test Set

Not applicable. This is a quantitative laboratory assay comparison, not a diagnostic imaging or qualitative assessment requiring adjudication of results from multiple observers. The comparison is against a reference assay.

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 a clinical chemistry assay for quantitative determination of a drug in human samples, not an AI-assisted diagnostic imaging device or a device involving human readers.

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

Yes, the study describes the standalone performance of the Roche ONLINE Phenytoin assay. It quantifies the level of phenytoin directly from human serum or plasma samples on automated clinical chemistry analyzers. There is no human-in-the-loop performance described for the assay itself; the human involvement is in interpreting the quantitative results for clinical decision-making.

7. The type of Ground Truth Used

The ground truth used for the method comparison study was the results obtained from the Abbott TDx Phenytoin Assay, which is a recognized method for phenytoin quantification.

8. The Sample Size for the Training Set

Not applicable. This document describes a traditional in-vitro diagnostic device (IVD) based on reagent systems, not an AI/Machine Learning algorithm that requires a training set. The "training" for such devices involves optimizing the chemical reactions and analytical parameters during development.

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

Not applicable. As noted above, this is not an AI/Machine Learning device that utilizes a training set with established ground truth in the typical computational sense. The performance characteristics of the assay are established through analytical verification and validation studies.

Summary

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APR 2 8 2003

K030428

Roche ONLINE Phenytoin 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 Flis
	Date Prepared: February 6, 2003
2) Device name	Roche ONLINE Phenytoin
3) Predicate device	We claim substantial equivalence to the Roche CEDIA Phenytoin II Assay [K963840].
4) Device Description	The Roche ONLINE Phenytoin assay contains an in vitro diagnostic reagent system indicated for the quantitative determination of phenytoin, an anti-convulsant drug, in human serum or plasma on automated clinical chemistry analyzers. Measurements obtained by the device are used in the diagnosis and treatment of phenytoin overdose and in monitoring levels of phenytoin to ensure appropriate therapy. The proposed labeling indicates the Roche/Hitachi 911, 912, 917, and Modular P analyzers can be used with the Roche ONLINE Phenytoin reagent kits.

Continued on next page

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K030428

and the comments of the country

510(k) Summary, Continued

5) Intended use	For the quantitative determination of phenytoin in human serum or plasma onautomated clinical chemistry analyzers.
6) Comparisonto predicatedevice	The Roche ONLINE Phenytoin was evaluated for several performancecharacteristics, including precision, lower detection limit, methodcomparison, specificity, and interfering substances. All of the evaluationstudies gave acceptable results compared to the predicate device. Theseexperiments provide evidence that the Roche ONLINE Phenytoin Assay issubstantially equivalent to the currently marketed Roche CEDIA PhenytoinII Assay. The following table presents the precision and method comparison results.
		Roche ONLINE Phenytoin	Roche CEDIA Phenytoin II,(Predicate)
		Versus Abbott TDx Phenytoin Assay	Versus Abbott TDx Phenytoin Assay
		N = 106	N= 108
		Y = 0.99X-0.865	Y=0.99X-1.43
		R = 0.992	R=0.993
		Range = 1.68 to 40.0 µg/mL	Range = 1.1 to 40.0 µg/mL
	NCCLSPrecision:	Level 1	Level 2	Level 3	Level 1	Level 2	Level 3
	Mean (µg/mL)	6.49	13.39	22.87	6.3	14.8	26.8
	CV% (within run)	2.7	1.4	1.5	3.2	2.0	1.3
	CV% (total)	6.1	4.5	4.3	5.1	3.1	2.3

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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APR 2 8 2003

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Mike Flis Regulatory Affairs Principal Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, IN 46250-0457

Re: K030428

Trade/Device Name: Roche ONLINE Phenytoin Assay Regulation Number: 21 CFR 862.3350 Regulation Name: Diphenlhydantoin Test System Regulatory Class: Class II Product Code: DIP Dated: February 6, 2003 Received: February 10, 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

Ko30428 510(k) Number (if known): Device Name: Roche ONLINE Phenytoin Assay Indications for Use:

Franc

(Division Sign-Off)
Division Minical Laboratory Dev
510(k) K030428

(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-Counter Use

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.3350 Diphenylhydantoin test system.

(a)
Identification. A diphenylhydantoin test system is a device intended to measure diphenylhydantoin, an antiepileptic drug, in human specimens. Measurements obtained by this device are used in the diagnosis and treatment of diphenylhydantoin overdose and in monitoring levels of diphenylhydantoin to ensure appropriate therapy.(b)
Classification. Class II.