ONLINE TDM CARBAMAZEPINE

K031902 · Roche Diagnostics Corp. · KLT · Sep 17, 2003 · Clinical Toxicology

Device Facts

• Record ID: K031902
• Device Name: ONLINE TDM CARBAMAZEPINE
• Applicant: Roche Diagnostics Corp.
• Product Code: KLT · Clinical Toxicology
• Decision Date: Sep 17, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3645
• Device Class: Class 2

Intended Use

The ONLINE TDM Carbamazepine assay is for the quantitative determination of carbamazepine in human serum or plasma on automated clinical chemistry analyzers. This neuroleptic drug assay test system is a device intended to measure in serum or plasma the dopamine receptor blocking activity of carbamazepine. This device is for in vitro diagnostic use, and intended for prescription use.

Device Story

ONLINE TDM Carbamazepine is a homogeneous microparticle agglutination immunoassay (KIMS) for quantitative drug monitoring in human serum or plasma. Input: patient serum/plasma sample. Principle: competitive reaction between biotinylated drug hapten and free carbamazepine in sample for binding sites on anti-carbamazepine antibody and streptavidin-coated latex beads. Output: signal decrease proportional to drug concentration. Used in clinical laboratories on Roche Hitachi 911, 912, 917, and Modular P automated analyzers. Results interpreted by physicians to adjust dosage and maintain therapeutic drug levels, avoiding sub-therapeutic or toxic ranges.

Clinical Evidence

Bench testing only. Method comparison study (n=102) against predicate using Passing-Bablok and linear regression showed slopes of 1.068 and 1.062, respectively (r=0.984). Precision studies (within-run, day-to-day, total) performed over 21 days showed total %CV between 3.6% and 5.6%. Linearity confirmed across reportable range. Matrix comparison (serum vs. various plasmas) showed slopes 0.9-1.1 and r ≥ 0.95. Analytical specificity tested against 40+ compounds.

Technological Characteristics

Homogeneous microparticle agglutination immunoassay (KIMS). Two-reagent system. Components: biotinylated drug hapten, anti-carbamazepine antibody, streptavidin-coated latex beads. Automated clinical chemistry analyzer platform. Quantitative measurement via signal attenuation.

Indications for Use

Indicated for quantitative determination of carbamazepine in human serum or plasma to aid in monitoring drug levels, adjusting dosage, and achieving therapeutic effect while avoiding toxicity. For use on automated clinical chemistry analyzers.

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 Carbamazepine assay (K951595)

Submission Summary (Full Text)

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K031902

SEP 1 7 2003

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] |
| | Contact Person: Kerwin Kaufman |
| | Date Prepared: June 19, 2003 |

2) Device name

| Proprietary name: | ONLINE TDM Carbamazepine |
|----------------------|---------------------------------------------------|
| Common name: | Enzyme immunoassay, Carbamazepine |
| Classification name: | Neuroleptic drugs radioreceptor assay test system |

3) Predicate device

| | We claim substantial equivalence to the currently marketed COBAS INTEGRA Carbamazepine (K951595). |
|--|---------------------------------------------------------------------------------------------------|
|--|---------------------------------------------------------------------------------------------------|

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## 510(k) Summary, Continued

4) Device Description The ONLINE TDM Carbamazepine assay is for the quantitative determination of carbamazepine in human serum or plasma on automated clinical chemistry analyzers. In combination with other clinical information, monitoring carbamazepine levels provides physicians with an effective tool to aid in adjusting dosage and achieving optimal therapeutic effect while avoiding both sub-therapeutic and toxic drug levels. The proposed labeling indicates the Roche Hitachi 911, 912, 917 and Modular P analyzers can be used with the Roche ONLINE TDM Carbamazepine reagent kits.

The ONLINE TDM Carbamazepine assay is a homogeneous microparticle agglutination immunoassay. It is a two-reagent system used for the detection of carbamazepine in serum. Kinetic interaction of microparticles (KIMS) will be measured using Roche Diagnostics / Hitachi families of automated analyzers. In this technology biotinylated drug hapten serves as the binding partner to 1.) anti-carbamazepine antibody and 2.) streptavidin coated latex A competitive reaction to a limited amount of specific antibeads. carbamazepine antibody takes place between the hapten and free carbamazepine in the serum sample. A decrease in the apparent signal is proportional to the amount of drug present in the sample.

5.) Intended Use

The ONLINE TDM Carbamazepine assay is for the quantitative determination of carbamazepine in human serum or plasma on automated clinical chemistry analyzers.

Continued on next page

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## 510(k) Summary, Continued

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

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

| | Roche ONLINE TDM Carbamazepine | | | Roche COBAS INTEGRA<br>Carbamazepine (Predicate) | | |
|----------------------|--------------------------------------------------------------------------------------------------|-----------|-----------|----------------------------------------------------------------------------------------------|-----------|-----------|
| NCCLS Precision, | Control 1 | Control 2 | Control 3 | Control 1 | Control 2 | Control 3 |
| Within run | | | | | | |
| Mean (µg/ml) | 2.8 | 8.3 | 14.1 | 3.8 | 8.6 | 14.7 |
| SD (µg/ml) | 0.05 | 0.13 | 0.21 | 0.08 | 0.17 | 0.31 |
| CV% | 1.7 | 1.5 | 1.5 | 2.2 | 1.9 | 2.1 |
| NCCLS Precision, | Control 1 | Control 2 | Control 3 | Control 1 | Control 2 | Control 3 |
| Total | | | | | | |
| Mean (µg/ml) | 2.8 | 8.3 | 14.1 | 3.8 | 8.6 | 14.7 |
| SD (µg/ml) | 0.15 | 0.36 | 0.55 | 0.12 | 0.24 | 0.52 |
| CV% | 5.6 | 4.3 | 3.9 | 3.0 | 2.8 | 3.6 |
| Method<br>Comparison | Linear Regression: ONLINE TDM<br>Carbamazepine Vs. COBAS INTEGRA<br>Carbamazepine (FPIA) method. | | | Linear Regression: COBAS INTEGRA<br>Carbamazepine Vs. commercially available<br>FPIA method. | | |
| | N=103, Range = 0.5-11.93 µg/ml<br>$y=1.062x - 0.16$<br>$r=0.985$ | | | N=205, Range = 1.6-19.6 µg/ml<br>$y=1.061x - 0.124$<br>$r=0.995$ | | |

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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SEP 1 7 2003

98 Gaither Road Rockville MD 20850

Mr. Kerwin Kaufman Regulatory Affairs Consultant Roche Diagnostics Corporation 9115 Hague Road, P.O. Box 50457 Indianapolis. IN 46250-0457

Re: k031902

> Trade/Device Name: ONLINE TDM Carbamazepine Assay Regulation Number: 21 CFR 862.3645 Regulation Name: Neuroleptic drugs radioreceptor assay test system Regulatory Class: Class II Product Code: KLT Dated: June 19, 2003 Received: June 20, 2003

Dear Mr. Kaufman:

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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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). Other general information on your responsibilities under the Act may be obtained 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/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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## Indications for Use Statement

| 510(k) Number (if known): | K031902 |
|---------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Name: | Roche Diagnostics ONLINE TDM Carbamazepine |
| Indications for Use: | The ONLINE TDM Carbamazepine assay is for the quantitative determination of carbamazepine in human serum or plasma on automated clinical chemistry analyzers. This neuroleptic drug assay test system is a device intended to measure in serum or plasma the dopamine receptor blocking activity of carbamazepine. |

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Concurrence of CDRH, Office of Device Evaluation (ODE)

| Prescription Use (Per 21 CFR 801.109) | <div> ✓ </div> | OR Over-the-Counter Use |
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(Optional format 1-2-96)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K031902

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