ONLINE VALPROIC ACID

K060690 · Roche Diagnostics Corp. · LEG · Aug 8, 2006 · Clinical Toxicology

Device Facts

• Record ID: K060690
• Device Name: ONLINE VALPROIC ACID
• Applicant: Roche Diagnostics Corp.
• Product Code: LEG · Clinical Toxicology
• Decision Date: Aug 8, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3645
• Device Class: Class 2

Intended Use

The ONLINE TDM Valproic Acid assay is for the quantitative determination of valproic acid in human serum or plasma on Roche automated clinical chemistry analyzers. Measurements obtained from this device are used in the diagnosis and treatment of valproic acid overdose and to help ensure appropriate therapy.

Device Story

The ONLINE TDM Valproic Acid assay is a homogeneous enzyme immunoassay for quantitative measurement of valproic acid (free and protein-bound) in human serum or plasma. It utilizes competition between drug in the patient sample and drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites. Binding to the antibody decreases enzyme activity; the resulting change in activity is measured spectrophotometrically via the conversion of NAD to NADH. The assay is performed on Roche automated clinical chemistry analyzers (Hitachi 911, 912, 917, and Modular P) in clinical laboratory settings. Healthcare providers use the resulting concentration values to manage patient therapy and assess potential overdose. The assay benefits patients by providing automated, rapid monitoring of therapeutic drug levels.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP-5A on Hitachi 911/917 analyzers; total imprecision CVs ranged from 4.6% to 6.2%. Linearity established from 2.8 to 150.0 µg/mL. Method comparison against predicate and other commercial assays showed high correlation (r=0.997, r=0.995). Analytical specificity tested against various drugs and endogenous substances; no significant interference observed. Matrix comparison confirmed suitability for serum, Li-Heparin, Na-Heparin, K2-EDTA, and K3-EDTA plasma.

Technological Characteristics

Homogeneous enzyme immunoassay; utilizes bacterial G6PDH (Leuconostoc mesenteroids) to avoid interference from endogenous serum G6PDH. Operates on Roche automated clinical chemistry analyzers (Hitachi 911, 912, 917, Modular P). Detection via spectrophotometric measurement of NADH absorbance change.

Indications for Use

Indicated for the quantitative determination of valproic acid in human serum or plasma to aid in the diagnosis and treatment of valproic acid overdose and to monitor valproic acid levels to ensure appropriate therapy.

Regulatory Classification

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.

Predicate Devices

• COBAS Integra Valproic Acid (k951595)

Submission Summary (Full Text)

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K060690

AUG – 8 2006

# 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 Corporation<br>9115 Hague Rd.<br>Indianapolis, IN 46250<br>[phone]<br>Contact Person: Dimitris Demirtzoglou<br>Date Prepared: March 10, 2006 |
|-------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 2) Device name | Proprietary name: ONLINE TDM Valproic Acid<br>Common name: Enzyme Immunoassay, Valproic acid<br>Classification name: Enzyme Immunoassay, Valproic acid |
| 3) Predicate device | We claim substantial equivalence to the currently marketed COBAS INTEGRA Valproic Acid (K951595). |

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## 510(k) Summary, Continued

| 4) Device Description | The ONLINE TDM Valproic Acid assay is for the quantitative determination of valproic acid in human serum or plasma on Roche automated clinical chemistry analyzers. The proposed labeling indicates the Roche Hitachi 911, 912, 917 and Modular P analyzers can be used with the Roche ONLINE TDM Valproic Acid reagent kits. The assay is based on a homogeneous enzyme immunoassay technique used for the quantitative analysis of valproic acid (free and protein-bound) in human serum or plasma. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the sample can be measured in terms of enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that is measured spectrophotometrically. Endogenous serum G6PDH does not interfere because the coenzyme functions only with the bacterial (Leuconostoc mesenteroids) enzyme employed in the assay. |
|-----------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 5.) Intended Use | The ONLINE TDM Valproic Acid assay is for the quantitative determination of valproic acid in human serum or plasma on Roche automated clinical chemistry analyzers. |

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### 510(k) Summary, Continued

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

> The Roche ONLINE TDM Valproic Acid 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 Valproic Acid assay is substantially equivalent to the currently marketed Roche COBAS INTEGRA Valproic Acid assay. The following table summarizes the precision and method comparison results.

| Roche ONLINE TDM Valproic Acid | | | Roche COBAS FP Valproic Acid<br>(Predicate) | | | |
|--------------------------------|-------------------------------------------------------------------------------------------|-----------|---------------------------------------------|----------------------------------------------------------------|-----------|-----------|
| NCCLS Precision,<br>Within run | Control 1 | Control 2 | Control 3 | Control 1 | Control 2 | Control 3 |
| Mean (µg/ml) | 33.3 | 74.9 | 107.8 | 26.2 | 60.1 | 102.0 |
| SD (µg/ml) | 0.69 | 1.42 | 2.11 | 0.46 | 1.05 | 2.46 |
| CV% | 2.1 | 1.9 | 2.0 | 1.7 | 1.7 | 2.4 |
| NCCLS Precision,<br>Total | Control 1 | Control 2 | Control 3 | Control 1 | Control 2 | Control 3 |
| Mean (µg/ml) | 33.3 | 74.9 | 107.8 | 26.2 | 60.1 | 102.0 |
| SD (µg/ml) | 2.07 | 3.75 | 5.02 | 0.61 | 1.26 | 2.46 |
| CV% | 6.2 | 5.0 | 4.7 | 2.3 | 2.1 | 2.4 |
| Method<br>Comparison | Linear Regression: ONLINE TDM<br>Valproic acid Vs. COBAS FP Valproic acid | | | Linear Regression: COBAS FP Valproic<br>acid Vs. COBAS FARA II | | |
| | N=54, Range = 15.0 -132.1 µg/ml<br>y = 1.017 x - 0.053<br>r = 0.995<br>SD (md 95) = 4.801 | | | N=207, Range = 3.2 - =150 µg/ml<br>y=1.041x - 1.365<br>r=0.998 | | |

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The eagle is black, and the text is also black.

Re:

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Dimitris Demirtzoglou Regulatory Affairs Consultant Roche Diagnostics, Inc. 9115 Hague Road Indianapolis, IN 46250-0457

AUG - 8 2006

k060690 Trade/Device Name: ONLINE TDM Valproic Acid Regulation Number: 21 CFR§ 862.3645 Regulation Name: Neuroleptic drugs radioreceptor assay test system Regulatory Class: Class II Product Code: LEG Dated: July 19, 2006 Received: July 20, 2006

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 [phone]. 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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Alberto G

Alberto Guticarez, Ph.D. 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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### Indications for Use

KOGGG 510(k) Number (if known):

Device Name: ONLINE TDM Valproic Acid

Indications For Use:

The ONLINE TDM Valproic Acid assay is for the quantitative determination of valproic acid in human serum or plasma on Roche automated clinical chemistry analyzers. Measurements muman serain of paintine were used in the diagnosis and treatement of valproic acid overdose and in monitoring the levels of valproic acid to help ensure appropriate therapy.

Prescription Use _ (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

AC

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Office of the Vitro Diagnostic Device Evaluation and Safety

060690

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