ACE PHENYTOIN REAGENT, AED CALIBRATORS

K973414 · Schiapparelli Biosystems, Inc. · DIP · Nov 4, 1997 · Clinical Toxicology

Device Facts

• Record ID: K973414
• Device Name: ACE PHENYTOIN REAGENT, AED CALIBRATORS
• Applicant: Schiapparelli Biosystems, Inc.
• Product Code: DIP · Clinical Toxicology
• Decision Date: Nov 4, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3350
• Device Class: Class 2

Intended Use

ACE® Phenytoin Reagent is intended for the quantitative determination of phenytoin in serum using the ACE® clinical chemistry analyzer.

Device Story

ACE® Phenytoin Reagent is an enzyme immunoassay for quantitative phenytoin measurement in human serum. It utilizes a competitive binding principle: phenytoin in the patient sample competes with G6PDH-labeled phenytoin for a fixed amount of specific antibody binding sites. In the absence of sample phenytoin, the labeled drug binds to the antibody, inhibiting enzyme activity. The resulting enzyme activity is inversely proportional to the phenytoin concentration. The assay is performed on the ACE® clinical chemistry analyzer, which measures G6PDH activity bichromatically at 340/505 nm by monitoring the conversion of NAD+ to NADH. The system is intended for use by clinical laboratory professionals. Results assist clinicians in monitoring therapeutic drug levels to manage epilepsy and seizure disorders.

Clinical Evidence

Bench testing only. Performance assessment included within-run (<7.9% CV) and between-run (<11.7% CV) precision studies. Method correlation was performed against a Hitachi 717 analyzer (N=49), yielding a slope of 1.119, intercept of -0.51, and correlation coefficient (r) of 0.993. No clinical prospective or retrospective studies were required.

Technological Characteristics

Liquid-based enzyme immunoassay reagents (Antibody/Substrate and Enzyme Conjugate). Sensing principle: competitive enzyme immunoassay using G6PDH label. Detection: bichromatic spectrophotometry at 340/505 nm. Energy source: clinical chemistry analyzer. Connectivity: standalone analyzer integration. Sterilization: not applicable (reagent kit).

Indications for Use

Indicated for the quantitative determination of phenytoin in human serum for patients requiring monitoring of anti-convulsant therapy, specifically for the treatment of epilepsy, including grand mal (major motor), cortical focal seizures, and temporal lobe epilepsy.

Regulatory Classification

Identification

A diphenylhydantoin test system is a device intended to measure diphenylhydantoin, an antiepileptic drug, in human specimens. Measurements obtained by this device are used in the diagnosis and treatment of diphenylhydantoin overdose and in monitoring levels of diphenylhydantoin to ensure appropriate therapy.

Predicate Devices

• Diagnostic Reagents, Inc. (DRI) - Phenytoin Reagent (K945725)

Submission Summary (Full Text)

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KA73414

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### 510(k) PREMARKET NOTIFICATION ACE® Phenytoin Reagent

NOV - 4 1997

# SUMMARY OF SAFETY AND EFFECTIVENESS

In lieu of a 510(k) statement under 513(i) of the Act, this Summary of Safety and Effectiveness is provided as a 510(k) summary for disclosure to any other persons/companies without specific written authorization from Schiapparelli Biosystems, Inc.

#### Submitter

Schiapparelli Biosystems, Inc. 368 Passaic Avenue Fairfield, NJ 07004 Phone: [phone]

#### Contact Person

Steven Dalessio Manager, Quality Assurance/Regulatory Affairs Phone: [phone]

Device Names

| Proprietary Name: | ACE® Phenytoin Reagent | | |
|----------------------|--------------------------------------------------------------------------------|--|--|
| Common Name: | Enzyme immunoassay for phenytoin (diphenylhydantoin or Dilantin®) | | |
| Classification Name: | Phenytoin test | | |
| Predicate Device: | Diagnostic Reagents, Inc. (DRI) - Phenytoin Reagent [510(k) Number<br>K945725] | | |

#### Device Description

The ACE® Phenytoin Reagent contains two reagents, an Antibody/Substrate reagent and an Enzyme Conjugate reagent. The assay uses specific antibodies to phenytoin and is based on the competition of an enzyme glucose-o-phosphate dehydrogenase (G6PDH) labeled drug and the free drug from the sample, for a fixed amount of specific antibody binding sites. In the absence of free drug from the sample, the drug-labeled G6PDH is bound by the specific antibody and the enzyme activity is inhibited. This phenomenon creates a relationship between drug concentration in the sample and the enzyme activity. The enzyme G6PDH activity is determined bichromatically on the ACE® at 340/505 nm by measuring its ability to convert NAD* to NADH.

#### Intended Use of the Device

ACE® Phenytoin Reagent is intended for use in the quantitative determination of phenytoin in human serum.

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## 510(k) PREMARKET NOTIFICATION ACE® Phenytoin Reagent

## SUMMARY OF SAFETY AND EFFECTIVENESS

# COMPARATIVE FEATURES OF PREDICATE AND PROPOSED DEVICES

| PARAMETER | PREDICATE DEVICE | PROPOSED DEVICE |
|----------------------------------------------------------------|--------------------------------------------------|--------------------------------------------------|
| Trade Name | DRI Phenytoin Enzyme<br>Immunoassay | ACE® Phenytoin Reagent |
| Reference No. | K945725/S1 | TBD |
| Analyte | Phenytoin | Phenytoin |
| Intended Use | Quantitative determination of<br>phenytoin | Quatitative determination of<br>phenytoin |
| Methodology | Enzyme immunoassay | Enzyme immunoassay |
| Reagents<br>Reagent 1<br>Volume | Liquid; Antibody/Substrate<br>210 µL | Liquid; Antibody/Substrate<br>210 µL |
| Reagent 2<br>Volume | Liquid; Enzyme conjugate<br>70 µL | Liquid; Enzyme conjugate<br>70 µL |
| Specimen<br>Type<br>Volume | Serum and plasma<br>5 µL | Serum<br>5 µL |
| Assay System<br>Reagent 1 + Sample<br>Reagent 2<br>Temperature | Incubate 300 sec<br>Read 60 and 120 sec<br>37 °C | Incubate 240 sec<br>Read 63 and 203 sec<br>37 °C |
| Detection Method<br>Type<br>Wavelength, nm | Spectrophotometric<br>Bichromatic: 340/505 | Spectrophotometric<br>Bichromatic: 340/505 |

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### 510(k) PREMARKET NOTIFICATION ACE® Phenytoin Reagent

### SUMMARY OF SAFETY AND EFFECTIVENESS

### PERFORMANCE ASSESSMENT

Non-clinical test results submitted in the premarket notification include within-run and between-run precision and method correlation. Following is a data summary.

| PARAMETER | PREDICATE DEVICE | PROPOSED DEVICE |
|------------------------------------------------------------------------------|----------------------------------------------------------|------------------------------------------------|
| Performance Summary<br>Assay Range<br>Precision<br>Within Run<br>Between Run | 0.3 µg/mL to 40 µg/mL<br><5.5 %CV<br><5.9 %CV | 0.6 µg/mL to 40 µg/mL<br><7.9 %CV<br><11.7 %CV |
| Correlation vs<br>Slope<br>Intercept<br>r<br>N | Commercial phenytoin assay<br>1.01<br>0.17<br>0.97<br>90 | Hitachi 717<br>1.119<br>-0.51<br>0.993<br>49 |

Based on these data, the Schiapparelli Biosystems ACE® Phenytoin Reagent is substantially equivalent to the predicate device (Diagnostic Reagents, Inc. Phenytoin Enzyme Immunoassay). On this basis, the reagent is determined to be safe and effective for its intended use. Performance details are included in the reagent product labeling.

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Image /page/3/Picture/2 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" around the perimeter. Inside the circle is a stylized representation of three human figures, possibly representing individuals or families, in a flowing, abstract design.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV - 4 1997

Steven Dalessio Manager, Quality Assurance/Regulatory Affairs Schiapparelli Biosystems, Inc. 368 Passaic Avenue Fairfield, New Jersey 07004

Re : K973414 ACE® Phynetoin Reagent, AED Calibrators Requlatory Class: II Product Code: DIP Dated: September 8, 1997 Received: September 9, 1997

Dear Mr. Dalessio:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act 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 (Premarket Approval), it may be subject to such additional controls. Existing major requlations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. ਰ substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical General regulation (21 CFR Part 820) and that, Devices: through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at [phone].

This letter will allow you to begin marketing your device as described in your 510 (k) premarket notification. The FDA described in your sia (n) privalence 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to
premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number [phone] or [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Litman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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2301 594 2941

CDRH ODE

Page 1 of 1

510(k) Number (if known):

Device Name:__________________________________________________________________________________________________________________________________________________________________

Indications For Use:

ACE® Phenytoin Reagent is intended for the quantitative determination of phenytoin in serum using the ACE® clinical chemistry analyzer.

Phenytoin is one of the most widely prescribed anti-convulsant drugs for the treatment of epilepsy, particulary grand mal epilepsy (major motor), corticol focal seizures and temporal lobe epilepsy.

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number. k973414

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use_V (Per 21 CFR 801.109)

OR

Over-The-Counter Use_

(Optional Format 1-2-96)