PRECISET TDM I AND PRECISET TDM II CALIBRATORS

K031856 · Roche Diagnostics Corp. · DKB · Aug 6, 2003 · Clinical Toxicology

Device Facts

• Record ID: K031856
• Device Name: PRECISET TDM I AND PRECISET TDM II CALIBRATORS
• Applicant: Roche Diagnostics Corp.
• Product Code: DKB · Clinical Toxicology
• Decision Date: Aug 6, 2003
• Decision: SESE
• Submission Type: Abbreviated
• Regulation: 21 CFR 862.3200
• Device Class: Class 2

Intended Use

The Roche Preciset TDM I calibrators are designed for the calibration of the Roche assay for the quantitative determination of digoxin, carbamazepine, gentamicin, phenytoin, phenobarbital, primidone, theophylline, tobramycin, valproic acid, and vancomycin in human serum and plasma on automated clinical chemistry analyzers. The Roche Preciset TDM II calibrators are designed for the calibration of the Roche assay for the quantitative determination of digitoxin, amikacin, lidocaine, N-acetylprocainamide, procainamide, and quinidine in human serum and plasma on automated clinical chemistry analyzers.

Device Story

Preciset TDM I and II are multi-analyte calibrator sets used to calibrate Roche therapeutic drug monitoring (TDM) assays on automated clinical chemistry analyzers. Each set consists of six levels (A-F) of human serum spiked with specific drug concentrations, plus a drug-free diluent. Bottle A is negative; bottles B-F contain increasing concentrations of the target analytes. Stabilizers and preservatives are added. These calibrators are used by laboratory technicians in clinical settings to establish a calibration curve for quantitative drug measurement. By providing multiple analytes in a single set, the device improves laboratory workflow efficiency compared to using individual single-analyte calibrators. The output is a calibration curve used by the analyzer to calculate patient drug levels, aiding clinicians in therapeutic drug monitoring and dosage adjustment.

Clinical Evidence

No clinical data. Bench testing only. Traceability established to single analyte primary master calibrators prepared gravimetrically and by dilution from pure drugs of the highest metrological order.

Technological Characteristics

Multi-analyte calibrator sets consisting of human serum base, stabilizers, and preservatives. Six-level concentration gradient (0 to high-range) for each drug. Designed for use on automated clinical chemistry analyzers. No electronic or software components; purely chemical/biological reagent calibrators.

Indications for Use

Indicated for the calibration of Roche assays for quantitative determination of therapeutic drugs (digoxin, carbamazepine, gentamicin, phenytoin, phenobarbital, primidone, theophylline, tobramycin, valproic acid, vancomycin, digitoxin, amikacin, lidocaine, N-acetylprocainamide, procainamide, quinidine) in human serum and plasma using automated clinical chemistry analyzers.

Regulatory Classification

Identification

A clinical toxicology calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. A clinical toxicology calibrator can be a mixture of drugs or a specific material for a particular drug (e.g., ethanol, lidocaine, etc.). (See also § 862.2 in this part.)

Special Controls

*Classification.* Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.

Predicate Devices

• Roche COBAS-FP Reagents and Calibrators for Digoxin (K851032)
• Roche COBAS-FP Reagents and Calibrators for Carbamazepine (K850807)
• Roche COBAS-FP Reagents and Calibrators for Gentamicin (K843827, K945523)
• Roche COBAS-FP Reagents and Calibrators for Phenytoin (K936131)
• Roche COBAS-FP Reagents and Calibrators for Phenobarbital (K936130)
• Roche COBAS-FP Reagents and Calibrators for Primidone (K852318)
• Roche COBAS-FP Reagents and Calibrators for Theophylline (K871484)
• Roche COBAS-FP Reagents and Calibrators for Tobramycin (K843828)
• Roche COBAS-FP Reagents and Calibrators for Valproic Acid (K925003)
• Roche COBAS-FP Reagents and Calibrators for Vancomycin (K901759)
• COBAS INTEGRA, Calibrators & Controls (K972250)
• Roche COBAS-FP Reagents and Calibrators for Amikacin (852317)
• Roche COBAS-FP Reagents and Calibrators for Lidocaine (K853010)
• Roche COBAS-FP Reagents and Calibrators for NAPA (K871680)
• Roche COBAS-FP Reagents and Calibrators for Procainamide (K852320, K942847/S2)
• Roche COBAS-FP Reagents and Calibrators for Quinidine (K941440)

Submission Summary (Full Text)

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AUG = 6 2003

| 510(k) Summary | AUG - 6 2003<br>K031856 |
|-------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Introduction | According to the requirements of 21 CFR 807.92, the following information<br>provides sufficient detail to understand the basis for a determination of<br>substantial equivalence. |
| 1) Submitter<br>name, address,<br>contact | Roche Diagnostics Corporation<br>9115 Hague Rd.<br>Indianapolis, IN 46250<br>[phone]<br><br>Contact Person: Kerwin Kaufman<br><br>Date Prepared: June 13, 2003 |
| 2) Device name | Proprietary name: Preciset TDM I and Preciset TDM II Calibrators<br>Common name: Calibrators, Drug Mixture<br>Classification name: Clinical Toxicology Calibrator |
| 3) Predicate<br>devices | We claim substantial equivalence to the currently marketed Roche calibrators:<br><br>Cobas-FP Digoxin Calibrators, K851032<br>Cobas-FP Carbamazepine Calibrators, K850807<br>Cobas-FP Gentamicin Calibrators, K843827 and K945523<br>Cobas-FP Phenytoin Calibrators, K936131<br>Cobas-FP Phenobarbital Calibrators, K936130<br>Cobas-FP Primidone Calibrators, K852318<br>Cobas-FP Theophylline Calibrators, K871484<br>Cobas-FP Tobramycin Calibrators, K843828<br>Cobas-FP Valproic Acid Calibrators, K925003<br>Cobas-FP Vancomycin Calibrators, K901759<br>Roche TDM ONLINE Digitoxin Calibrators, K972250<br>Cobas-FP Amikacin Calibrators, K852317<br>Cobas-FP Lidocaine Calibrators, K853010<br>Cobas-FP NAPA Calibrators, K871680<br>Cobas-FP Procainamide Calibrators, K852320 and K942847/S2 |

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## 510(k) Summary, Continued

Roche Preciset TDM I calibrators contain a mixture of 10 different drugs, 4) Device prepared by the quantitative addition of drug to human serum, with the Description addition of a stabilizer and preservative. The calibrator set contains six levels for each drug contained in bottles A-F. Bottle A is negative (drug free) human serum, followed by bottles B-F containing increasing amounts of each drug in a multi-analyte mixture. A single bottle containing 10 ml of drug-free human serum is also provided as a diluent. Drugs and their respective levels included are as follows:

> Digoxin: 0, 0.5, 1, 2, 3, 5 ng/ml Carbamazepine: 0, 1.25, 2.5, 5, 10, 20 µg/ml Gentamicin: 0, 0.5, 1.5, 4, 7, 10 µg/ml Phenytoin: 0, 2.5, 5, 10, 20, 40 µg/ml Phenobarbital: 0. 5, 10, 20, 40, 60 µg/ml Primidone: 0, 2, 4, 8, 16, 24 µg/ml Theophylline: 0, 2.5, 5, 10, 20, 40 µg/ml Tobramycin: 0, 1, 2, 4, 7, 10 µg/ml Valproic Acid: 0, 12.5, 25, 50, 100, 150 µg/ml Vancomycin: 0, 5, 10, 20, 40, 80 µg/ml

Roche Preciset TDM II calibrators contain a mixture of 6 different drugs, prepared by the quantitative addition of drug to human serum, with the addition of a stabilizer and preservative. Drugs included are Digitoxin, Amikacin, Lidocaine, NAPA, Procainamide, and Quinidine. This calibrator set also provides six levels for each drug contained in bottles A-F. Bottle A is negative (drug free) human serum, followed by bottles B-F containing increasing amounts of each drug in a multi-analyte mixture. A single bottle containing 10 ml of drug-free human serum is also provided as a diluent. Drugs and their respective levels included are as follows:

Digitoxin: 0, 7.5, 15, 30, 45, 65 ng/ml Amikacin: 0, 2.5, 5, 10, 20, 40 µg/ml Lidocaine: 0, 0.5, 1, 2.5, 5, 10 ug/ml NAPA: 0, 2.5, 5, 10, 20, 30 µg/ml Procainamide: 0, 1, 2, 4, 8, 16 ug/ml Quinidine: 0, 0.5, 1, 2, 4, 8 µg/ml

Continued on next page

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## 510(k) Summary, Continued

| 5.) Intended<br>Use | The Preciset TDM I calibrators are designed for the calibration of the Roche assays for the quantitative determination of digoxin, carbamazepine, gentamicin, phenytoin, phenobarbital, primidone, theophylline, tobramycin, valproic acid and vancomycin in human serum and plasma on automated clinical chemistry analyzers.<br>The Preciset TDM II calibrators are designed for the calibration of the Roche assays for the quantitative determination of digitoxin, amikacin, lidocaine, N- acetylprocainamide, procainamide and quinidine in human serum and plasma on automated clinical chemistry analyzers. |
|----------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 6.) Comparison<br>to the Predicate<br>Device | The Roche Preciset TDM I and Preciset TDM II multianalyte calibrators are substantially equivalent to other products in commercial distribution intended for similar use. Most notably, they are substantially equivalent to the currently marketed Roche single analyte TDM calibrators (listed in section 3 above) for the same drugs and at the same levels.<br>The Roche Preciset TDM I and Preciset TDM II multianalyte calibrators are prepared by the quantitative addition of drugs to human serum with an added stabilizer and preservative. Drugs are added in the same quantities as the predicate, single analyte TDM calibrators. The new multianalyte calibrators provide a more convenient calibrator set for multiple TDM assays than the predicate, single analyte TDM calibrator sets. |

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## DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the circumference. Inside the circle is a stylized symbol that resembles an abstract bird or a series of flowing lines, possibly representing movement or progress.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

AUG - 6 2003

Re: k031856

> Trade/Device Name: Roche Preciset TDM I and Preciset TDM II Calibrators Regulation Number: 21 CFR § 862.3200 Regulation Name: Clinical toxicology calibrator Regulatory Class: II Product Code: DKB Dated: June 13, 2003 Received: June 16, 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). 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.

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Page 2 -

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/dsma/dsmamain.html.

Sincerely yours,

iteven 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): | K031856 |
|---------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Name: | Roche Preciset TDM I and Preciset TDM II Calibrators |
| Indications for Use: | The Preciset TDM I calibrators are designed for the calibration of the Roche assays for the quantitative determination of digoxin, carbamazepine, gentamicin, phenytoin, phenobarbital, primidone, theophylline, tobramycin, valproic acid and vancomycin in human serum and plasma on automated clinical chemistry analyzers. |
| | The Preciset TDM II calibrators are designed for the calibration of the Roche assays for the quantitative determination of digitoxin, amikacin, lidocaine, N-acetylprocainamide, procainamide and quinidine in human serum and plasma on automated clinical chemistry analyzers. |

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use X OR Over-the-Counter Use

(Per 21 CFR 801.109)

(Optional format 1-2-96)

*Division Sign-Off*

Office of In Vitro Diagnostic Devic Evaluation and Safety

| 510(k) | K031856 |
|--------|---------|
|--------|---------|