The Roche ONLINE TDM Lidocaine assay is for the quantitative determination of lidocaine in human serum or plasma on automated clinical chemistry analyzes. Lidocaine is an antiarrhythmic agent administered intravenously by either injection or continuous infusion. It is indicated in the acute management of ventricular arritythmias such as those occurring in relation to acute myocardial infarction, or during cardiac manipulation, such as cardiac surgery. The proposed labeling indicates the Roche/Hitachi 911, 912, 917, and Modular P analyzers can be used with the Roche ONLINE Lidocaine reagent kits.

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 lidocaine and rapidly aggregate in the presence of a lidocaine antibody solution. When a sample containing lidocaine 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 lidocaine concentration is obtained, with the maximum rate of aggregation at the lowest lidocaine concentration. By monitoring the change in scattered light or absorbance, a concentration-dependent curve is obtained.

AI/ML Overview

Acceptance Criteria and Device Performance Study for Roche ONLINE Lidocaine Assay

1. Table of Acceptance Criteria and Reported Device Performance

The provided document details a comparison study between the Roche ONLINE TDM Lidocaine assay and a predicate device (Roche COBAS INTEGRA Lidocaine), as well as a comparison to an FPIA method. The acceptance criteria are implicitly derived from the comparison to these established methods, demonstrating "acceptable results" and "substantial equivalence."

Performance Characteristic	Acceptance Criteria (Implied by Predicate Device Performance and Substantial Equivalence Goal)	Reported Device Performance (Roche ONLINE TDM Lidocaine)
Correlation to Predicate Device (Roche COBAS INTEGRA Lidocaine)	Strong linear correlation to predicate device (R-value close to 1)	Y = 1.019X - 0.044, R = 0.995 (N=99)
Correlation to FPIA Method	Strong linear correlation to FPIA method (R-value close to 1)	Y = 0.947X + 0.011, R = 0.991 (N=69)
Precision (Within Run CV%)	Comparable to or better than predicate device	Level 1: 2.7%, Level 2: 1.5%, Level 3: 1.9% (Predicate: Level 1: 1.92%, Level 2: 1.90%, Level 3: 2.99%)
Precision (Total CV%)	Comparable to or better than predicate device	Level 1: 6.0%, Level 2: 3.4%, Level 3: 3.6% (Predicate: Level 1: 2.30%, Level 2: 2.07%, Level 3: 3.75%)
Lower Detection Limit	Acceptable for clinical use (details not quantitatively specified in the provided text, but stated as "acceptable results")	Not quantitatively specified in the provided text, but implied as acceptable.
Specificity	Acceptable (details not quantitatively specified in the provided text)	Stated as "acceptable results"
Interfering Substances	Acceptable (details not quantitatively specified in the provided text)	Stated as "acceptable results"

Note: The document states that "All of the evaluation studies gave acceptable results compared to the predicate device," indicating the overall acceptance criteria were met.

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

Test Set (comparison to predicate device): N = 99
Test Set (comparison to FPIA method): N = 69
Data Provenance: Not explicitly stated regarding country of origin or specific demographic details. The studies were conducted by Roche Diagnostics Corporation in Indianapolis, IN, suggesting the data is likely from the United States. The studies are described as "evaluation studies," implying they were specifically conducted for the premarket notification and are thus prospective in nature, as they assess the performance of the new device.

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

This type of in vitro diagnostic device (immunoassay for drug concentration) does not typically rely on "experts" in the same way an imaging or diagnostic AI system would. The "ground truth" for drug concentration in serum or plasma is established by validated analytical methods. In this case, the predicate device (Roche COBAS INTEGRA Lidocaine Assay) and an FPIA method (Fluorescence Polarization Immunoassay, a common method for therapeutic drug monitoring) served as the reference or "ground truth" for comparison. Therefore, no external "experts" were used to establish ground truth in this context; rather, established and validated analytical techniques served this role.

4. Adjudication Method for the Test Set

Not applicable. As described above, the "ground truth" was established by reference analytical methods, not by human interpretation or consensus that would require adjudication.

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

No, an MRMC comparative effectiveness study was not done. This study is for an in vitro diagnostic assay, which measures a quantitative analyte concentration, not an imaging or interpretive diagnostic task that would typically involve multiple readers.

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

Yes, this study represents the standalone performance of the Roche ONLINE TDM Lidocaine assay. This is an automated immunoassay designed to provide a quantitative result without direct human interpretation of the assay's output for each measurement. Human involvement is limited to sample loading, instrument operation, and result review, but the assay itself generates the lidocaine concentration.

7. The Type of Ground Truth Used

The ground truth used was analytical reference methods:

The Roche COBAS INTEGRA Lidocaine Assay (the predicate device)
An FPIA (Fluorescence Polarization Immunoassay) method

These methods are well-established and validated for determining lidocaine concentrations in biological samples.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" for the Roche ONLINE TDM Lidocaine assay in the context of machine learning. As an immunoassay, the device's performance is based on its chemical and optical principles, not on being "trained" on a dataset in the way an AI algorithm would be. The development and optimization of the assay reagents and parameters would have occurred during the assay's R&D phase, but this is distinct from "training a model."

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

Not applicable, as there is no "training set" in the machine learning sense for this immunoassay device. The performance characteristics were evaluated against established analytical reference methods.

Summary

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JAN 1 2 2004

Roche ONLINE Lidocaine 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) 845-2000
	Contact Person: Mike Flis
	Date Prepared: July 28, 2003
2) Device name	Roche ONLINE TDM Lidocaine
3) Predicate device	We claim substantial equivalence to the Roche COBAS INTEGRA Lidocaine [K954992].
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 lidocaine and rapidly aggregate in the presence of a lidocaine antibody solution. When a sample containing lidocaine 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 lidocaine concentration is obtained, with the maximum rate of aggregation at the lowest lidocaine 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

5) Intended use	For the quantitative determination of lidocaine in human serum or plasma onautomated clinical chemistry analyzers.
6) Comparisonto predicatedevice	The Roche ONLINE TDM Lidocaine 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 TDM Lidocaine issubstantially equivalent to the currently marketed Roche COBAS INTEGRALidocaine Assay. The following table presents the precision and methodcomparison results.
	Roche ONLINE TDM Lidocaine	Roche COBAS INTEGRA Lidocaine,(Predicate labeling)

	Roche ONLINE TDM Lidocaine	Roche COBAS INTEGRA Lidocaine,(Predicate labeling)
	Versus Roche COBAS INTEGRA LidocaineAssay (predicate device)	Versus FPIA method
	N = 99	N = 69
	$Y = 1.019X-0.044$	$Y=0.947X + 0.011$
	R = 0.995	R= 0.991
	Range = 0.40 to 9.56 µg/mL
NCCLSPrecision:	Level 1	Level 2	Level 3	Level 1	Level 2	Level 3
Mean (µg/mL)	1.34	4.47	7.03	1.45	3.54	8.09
CV% (within run)	2.7	1.5	1.9	1.92	1.90	2.99
CV% (total)	6.0	3.4	3.6	2.30	2.07	3.75

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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 the department's name encircling a symbol. The symbol is a stylized representation of an eagle or bird-like figure with three curved lines forming its body and wings. The text is arranged in a circular pattern around the symbol.

Public Health Service

JAN 1 2 2004

Food and Drug Administrat 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

K032334 Re:

Trade/Device Name: Roche ONLINE TDM Lidocaine Assay Regulation Number: 21 CFR 862.3555 Regulation Name: Lidocaine test system Regulatory Class: Class II Product Code: KLR Dated: October 31, 2003 Received: November 4, 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 ror use stated or the 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 r ou may, atteres, 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 your deviloget 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 cquivalence determination does not mean r reaso be actived a determination that your device complies with other requirements of the Act that I Drillaral 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 1. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Hcalth

Enclosure

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Roche Diagnostics Corporation

510(k) Number (if known): K032334 Device Name: Roche ONLINE TDM Lidocaine 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)

Prescription Use
(Per 21 CFR 801.109) /

Over-The-Counter Use _

(Optional Format 1-2-96)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K032334

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Regulation Number and Section

§ 862.3555 Lidocaine test system.

(a)
Identification. A lidocaine test system is a device intended to measure lidocaine, an antiarrythmic and anticonvulsant drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of lidocaine overdose or in monitoring levels of lidocaine to ensure appropriate therapy.(b)
Classification. Class II.