ONLINE PHENOBARBITAL, MODEL 03016757190 & 03510620 by ROCHE DIAGNOSTICS CORP.

The ONLINE TDM Phenobarbital assay is for the quantitative determination of phenobarbital in human serum or plasma on Roche automated clinical chemistry analyzers. Measurements obtained by this device are used in the diagnosis and treatment of phenobarbital use or overdose and in monitoring levels of phenobarbital. The proposed labeling indicates the Roche Hitachi 912, 917 and Modular P analyzers can be used with the Roche ONLINE TDM Phenobarbital reagent kits.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the K071644 device, the ONLINE TDM Phenobarbital assay:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device appear to be implicit in its comparison to a predicate device (COBAS INTEGRA Phenobarbital) and the stated "acceptable results" from evaluation studies. The performance characteristics evaluated were precision, lower detection limit, method comparison, specificity, and interfering substances. The provided data focuses on precision and method comparison.

Performance Metric	Acceptance Criteria (Implicit - Compared to Predicate)	Reported Device Performance (ONLINE TDM Phenobarbital)	Predicate Device Performance (COBAS INTEBAS Phenobarbital)
NCCLS Precision, Within run
Control 1 Mean (µg/ml)	(To be comparable to predicate)	9.6	12.0
Control 1 SD (µg/ml)	(To be comparable to predicate)	0.13	0.25
Control 1 CV%	(To be comparable to predicate)	1.3	2.1
Control 2 Mean (µg/ml)	(To be comparable to predicate)	24.1	23.4
Control 2 SD (µg/ml)	(To be comparable to predicate)	0.18	0.51
Control 2 CV%	(To be comparable to predicate)	0.7	2.2
Control 3 Mean (µg/ml)	(To be comparable to predicate)	45.2	52.0
Control 3 SD (µg/ml)	(To be comparable to predicate)	0.37	1.52
Control 3 CV%	(To be comparable to predicate)	0.8	2.9
NCCLS Precision, Total
Control 1 Mean (µg/ml)	(To be comparable to predicate)	9.6	12.0
Control 1 SD (µg/ml)	(To be comparable to predicate)	0.34	0.26
Control 1 CV%	(To be comparable to predicate)	3.5	2.2
Control 2 Mean (µg/ml)	(To be comparable to predicate)	24.1	23.4
Control 2 SD (µg/ml)	(To be comparable to predicate)	0.59	0.62
Control 2 CV%	(To be comparable to predicate)	2.4	2.7
Control 3 Mean (µg/ml)	(To be comparable to predicate)	45.2	52.0
Control 3 SD (µg/ml)	(To be comparable to predicate)	0.82	2.04
Control 3 CV%	(To be comparable to predicate)	1.8	3.9
Method Comparison (vs. Predicate)	(High correlation, slope near 1, intercept near 0)	y = 1.047x - 0.339, r = 0.996	y = 1.036x - 1.236, r = 0.995 (vs. FPIA)

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

Precision: Not explicitly stated as a "test set" in the context of individual patient samples, but control materials were used. The sample size would refer to the number of replicates for each control level for the NCCLS precision evaluations. This information is not provided.
Method Comparison (ONLINE TDM Phenobarbital vs. COBAS FP Phenobarbital):
- Sample Size: N=53
- Data Provenance: Not specified, but generally for method comparisons in medical devices, these are laboratory samples, likely prospective. The origin (country/retrospective/prospective) is not detailed.

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

This device is an in-vitro diagnostic (IVD) for quantitative measurement. The "ground truth" is typically the measurement performed by a reference method or predicate device. There is no mention of human experts establishing ground truth in this context, as it's a quantitative chemical assay.

4. Adjudication Method for the Test Set

Not applicable. This is a quantitative chemical assay; results are compared directly, not adjudicated by experts for diagnostic interpretations.

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

No, an MRMC study was not done. This type of study is relevant for medical imaging or diagnostic devices where human readers interpret results, often with and without AI assistance. This device is a quantitative chemical analyzer.

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

Yes, this is an inherently "standalone" device in its primary function as a laboratory analyzer. It provides a numerical result without direct human interpretation in the measurement process itself. The performance described (precision, method comparison) reflects the standalone analytical capability of the device.

7. The Type of Ground Truth Used

Precision: The "ground truth" for precision is the expected value of the control material, and the device's ability to consistently measure around that value.
Method Comparison: The "ground truth" for the method comparison was the results obtained from the COBAS FP Phenobarbital (an existing and presumably validated method). The predicate device (COBAS Integra Phenobarbital) also performed a method comparison against FPIA.

8. The Sample Size for the Training Set

Not applicable as this is a chemical assay, not a machine learning or AI-driven diagnostic device that typically employs a "training set." The assay's performance is based on its chemical reagents and instrument calibration, not on learning from a dataset.

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

Not applicable for the reasons stated above (not an AI/ML device with a training set).

Summary

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K071644

510(k) Summary	SEP 12 2007
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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) 521-7688
	Contact Person: Dimitris Demirtzoglou
2) Device name	Proprietary name: ONLINE TDM Phenobarbital
	Common name: Enzyme Immunoassay, Phenobarbital
	Classification name: Enzyme Immunoassay, Phenobarbital
3) Predicate device	We claim substantial equivalence to the currently marketed COBAS INTEGRA Phenobarbital (K951595).
4) Device Description	The ONLINE TDM Phenobarbital assay is for the quantitative determination of phenobarbital in human serum or plasma on Roche automated clinical chemistry analyzers. Measurements obtained by this device are used in the diagnosis and treatment of phenobarbital use or overdose and in monitoring levels of phenobarbital. The proposed labeling indicates the Roche Hitachi 912, 917 and Modular P analyzers can be used with the Roche ONLINE TDM Phenobarbital reagent kits.

Phenobarbital is one of the most commonly used drugs for the treatment of grand mal, psychomotor epilepsy, and other forms of focal epilepsy. Monitoring of the serum level of the drug is essential in order to achieve maximal seizure control while maintaining minimal blood levels to avoid negative side effects. As with other anti-convulsant drugs, it is imperative that each patient's dosage be individualized.

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The ONLINE TDM Phenobarbital assay is for the quantitative determination 5.) Intended Use of phenobarbital in human serum or plasma on Roche automated clinical chemistry analyzers.

510(k) Summary, Continued

The Roche ONLINE TDM Phenobarbital assay is substantially equivalent to 6.) Comparison to the Predicate other products in commercial distribution intended for similar use. Most Device notably, it is substantially equivalent to the currently marketed Roche COBAS INTEGRA Phenobarbital (K951595).

The Roche ONLINE TDM Phenobarbital assay was evaluated for several performance characteristics including precision, lower detection limit, 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 Phenobarbital assay is substantially equivalent to the currently marketed Roche COBAS INTEGRA Phenobarbital assay. The following table summarizes the precision and method comparison results.

Continued on next page

	Roche COBAS Integra Phenobarbital(Predicate)			Roche ONLINE TDM Phenobarbital
NCCLS Precision,Within run	Control 1	Control 2	Control 3	Control 1	Control 2	Control 3
Mean (µg/ml)	12.0	23.4	52.0	9.6	24.1	45.2
SD (µg/ml)	0.25	0.51	1.52	0.13	0.18	0.37
CV%	2.1	2.2	2.9	1.3	0.7	0.8
NCCLS Precision,Total	Control 1	Control 2	Control 3	Control 1	Control 2	Control 3
Mean (µg/ml)	12.0	23.4	52.0	9.6	24.1	45.2
SD (µg/ml)	0.26	0.62	2.04	0.34	0.59	0.82
CV%	2.2	2.7	3.9	3.5	2.4	1.8
MethodComparison	Linear Regression: COBAS IntegraPhenobarbital Vs. FPIA			Linear Regression: ONLINE TDMPhenobarbital Vs. COBAS FPPhenobarbital
	N=206, Range = 0.8 - 60 µg/ml			N=53, Range = 3.0 - 52.4 µg/ml
	y = 1.036x - 1.236			y= 1.047x - 0.339
	r = 0.995			r=0.996

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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 is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of an eagle or bird-like figure, with three stylized lines forming the body and wings.

SEP 1 2 2007

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Roche Diagnostics Corporation c/o Mr. Dimitris Demirtzoglou Regulatory Affairs Consultant 9115 Hague Road Indianapolis, IN 46250

Re: K071644 Trade/Device Name: Online TDM Phenobarbital Regulation Number: 21 CFR 862.3660 Regulation Name: Phenobarbital test system Regulatory Class: Class II Product Code: DLZ Dated: June 14, 2007 Received: June 15, 2007

Dear Mr. Demirtzoglou:

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 (240) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Jean M. Cooper, M.S., D.V.M.

Jean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indication for Use

KO71644 510(k) Number (if known):

Device Name: ONLINE TDM Phenobarbital

Indication For Use:

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use _ (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

Carol C. Benson
Revision Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

071644

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Regulation Number and Section

§ 862.3660 Phenobarbital test system.

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