ADVIA IMS VALPROIC ACID METHOD

K042807 · Bayer Healthcare, LLC · LEG · Feb 8, 2005 · Clinical Toxicology

Device Facts

• Record ID: K042807
• Device Name: ADVIA IMS VALPROIC ACID METHOD
• Applicant: Bayer Healthcare, LLC
• Product Code: LEG · Clinical Toxicology
• Decision Date: Feb 8, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3645
• Device Class: Class 2

Intended Use

The Bayer ADVIA IMS Valproic Acid method is for in vitro diagnostic use to measure the antiepileptic drug valproic acid in human serum and plasma. Measurements of valproic acid (2-propylpentanoic acid) are used as an aid in the diagnosis and treatment of valproic acid overdose, and in monitoring therapeutic levels of valproic acid to ensure appropriate therapy.

Device Story

ADVIA IMS Valproic Acid method is an in vitro diagnostic assay for quantitative measurement of valproic acid in human serum and plasma. Used on Bayer ADVIA IMS systems; operated by laboratory personnel. Input consists of patient serum or plasma samples; device performs chemical analysis to determine drug concentration. Output is a numerical concentration value (µg/mL) provided to clinicians. Results aid in monitoring therapeutic drug levels and managing overdose cases, facilitating appropriate patient therapy. Device is intended for clinical laboratory use.

Clinical Evidence

No clinical studies were performed. Evidence is based on analytical bench testing. Method comparison study (n=50) between ADVIA IMS and Centaur systems showed high correlation (r=0.997, slope=0.98). Precision evaluated over 10 days (n=79) showed total CVs ranging from 2.0% to 4.4%. Linearity established from 6.25 to 150 μg/mL. Interference testing confirmed no significant effect from common antiepileptic drugs or endogenous substances (hemoglobin, triglycerides, bilirubin, protein). Matrix equivalency confirmed for serum, heparinized plasma, and EDTA plasma.

Technological Characteristics

In vitro diagnostic reagent system for use on ADVIA IMS automated analyzers. Quantitative assay for valproic acid. Analytical range 0.57 to 150 µg/mL. System utilizes specific calibrators for standardization.

Indications for Use

Indicated for patients requiring therapeutic drug monitoring of valproic acid or assessment of valproic acid overdose. Used for quantitative measurement in human serum and plasma.

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

• Bayer Centaur Valproic Acid (K013488)

Submission Summary (Full Text)

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# 510(k) SUMMARY OF SAFETY AND EFFECTIVENESS Valproic Acid Method for ADVIA® Modular System (IMS)™

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.

The assigned 510(k) number is: // 0 4 2 8 0 7 = (leave blank)

### 1. Intended Use

This in vitro method is intended to quantitatively measure the antiepileptic drug valproic acid in human serum and plasma on the Bayer ADVIA® IMS systems. Measurements of valproic acid are used to aid in monitoring therapeutic levels of valproic acid to ensure appropriate therapy and in the treatment of valproic acid overdose.

#### Predicate Device 2.

| Product Name | Reagent Ref # | Calibrator Ref # |
|--------------------------------|----------------------|----------------------|
| Bayer Centaur Valproic<br>Acid | 03783810<br>(129219) | 02700784<br>(129221) |

#### Device / Method 3.

| Product Name | Reagent Ref # | Calibrator Ref # |
|----------------------------|---------------|------------------|
| ADVIA IMS Valproic<br>Acid | 00329833 | 00419360 |

#### 4. Performance

#### A. Minimum Detectable Concentration

| Method | ADVIA IMS | Centaur |
|--------|-----------------|----------------|
| MDC | 0.57 $\mu$ g/mL | 1.0 $\mu$ g/mL |

#### B. Imprecision

| ADVIA IMS | | Bayer Centaur | |
|----------------|-----------------|----------------|----------------|
| Level<br>µg/mL | Total<br>CV (%) | Level<br>µg/mL | Total<br>CV(%) |
| 34.03 | 4.4 | 22.8 | 6.9 |
| 70.16 | 2.9 | 64.6 | 6.1 |
| 98.86 | 2.0 | 102.7 | 6.4 |

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### C. Correlation (Y=ADVIA IMS, X=Comparison system)

| Specimen type | Comparison System (X) | N | Regression Equation | Syx µg/mL | R | IMS Sample Range µg/mL |
|---------------|-----------------------|----|---------------------|-----------|-------|------------------------|
| Serum | Centaur | 50 | $Y=0.98X + 4.9$ | 3.1 | 0.997 | 13.4 - 144 |

### D. Interfering Substances

| Interfering<br>Substance | Interfering Sub.<br>Conc. (mg/dL) | Valproic acid<br>Concentration<br>μg/mL | Effect<br>(% change) |
|-----------------------------|-----------------------------------|-----------------------------------------|----------------------|
| Bilirubin<br>(unconjugated) | 25 | 112.01 | -3.3 |
| Bilirubin<br>(conjugated) | 25 | 108.71 | 2.3 |
| Hemoglobin | 600 | 107.13 | 3.1 |
| Lipids<br>(Triglycerides) | 750 | 102.67 | 9.8 |

### E. Analytical Range

0. 57ug/mL up to valproic acid concentration in highest calibrator (Level 6) (approximately 150 µg/mL).

Rin Ha

10/4/04

Date

Andres Holle Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York, 10591 - 5097

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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 consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized graphic of an abstract symbol, which is often interpreted as representing the human form.

FEB - 8 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Andres Holle Manager, Regulatory Affairs Bayer Healthcare, LLC. Diagnostics Division 511 Benedict Avenue Tarrytown, NY 10591

k042807 Re:

Trade/Device Name: ADVIA® IMS Valproic Acid Method ADVIA® IMS Valproic Acid Calibrator Regulation Number: 21 CFR 862.3645 Regulation Name: Neuroleptic drugs radioreceptor assay test system Regulatory Class: Class II Product Code: LEG, DKB Dated: October 4, 2004 Received: October 13, 2004

Dear Mr. Holle:

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

.

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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). 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,

Jean M. Cooper, MS, DUM

Jean M. Cooper, MS, 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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# Indications for Use

510(k) Number (if known): __K042807_

Device Name: ADVIA® IMS Valproic Acid Calibrator

Indications For Use:

The Bayer ADVIA IMS Valproic Acid calibrator is for in vitro diagnostic use in the calibration of valproic acid using the ADVIA® IMS system.

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

Over-The-Counter Use (21 CFR 807 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)

Division Sign-Off

Division Slop-02

Page 1 of ____________________________________________________________________________________________________________________________________________________________________

Office of In Vitro Diagnostic Device Evaluation and Se

51062

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# Indications for Use

510(k) Number (if known):_____________________________________________________________________________________________________________________________________________________

Device Name: ADVIA® IMS Valproic Acid Method

Indications For Use:

The Bayer ADVIA IMS Valproic Acid method is for in vitro diagnostic use to measure the antiepileptic drug valproic acid in human serum and plasma. Measurements of valproic acid (2-propylpentanoic acid) are used as an aid in the diagnosis and treatment of valproic acid overdose, and in monitoring therapeutic levels of valproic acid to ensure appropriate therapy.

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

Over-The-Counter Use (21 CFR 807 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)

Albert CR

Division Slari-Of

Page 1 of

Office of In Vitro Diagnostic Device Evaluation and Satety

Lo420807

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