ACE THEOPHYLLINE REAGENT, THEO CALIBRATORS

K973583 · Schiapparelli Biosystems, Inc. · KLS · Nov 12, 1997 · Clinical Toxicology

Device Facts

• Record ID: K973583
• Device Name: ACE THEOPHYLLINE REAGENT, THEO CALIBRATORS
• Applicant: Schiapparelli Biosystems, Inc.
• Product Code: KLS · Clinical Toxicology
• Decision Date: Nov 12, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3880
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

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

Device Story

ACE® Theophylline Reagent is an enzyme immunoassay for quantitative measurement of theophylline in human serum. The device utilizes two liquid reagents: an antibody/substrate reagent and an enzyme conjugate reagent. Principle of operation involves competitive binding between theophylline in the patient sample and a G6PDH-labeled drug for a fixed amount of specific antibody binding sites. In the absence of sample drug, the labeled drug binds to the antibody, inhibiting enzyme activity. The resulting G6PDH activity is inversely proportional to theophylline concentration. The assay is performed on the ACE® clinical chemistry analyzer, which measures enzyme activity bichromatically at 340/505 nm by monitoring the conversion of NAD+ to NADH. Healthcare providers use the resulting concentration values to adjust patient dosage, aiming for optimal therapeutic effect while avoiding toxicity. The device is intended for clinical laboratory use.

Clinical Evidence

Bench testing only. Performance assessment included within-run precision (<5.6% CV) and between-run precision (<14.0% CV) over an assay range of 0.3 µg/mL to 40 µg/mL. Method correlation against a Hitachi 717 analyzer (N=50) yielded a slope of 1.042, intercept of 0.75, and correlation coefficient (r) of 0.993.

Technological Characteristics

Liquid-based enzyme immunoassay reagents. Detection via bichromatic spectrophotometry at 340/505 nm. Operates on the ACE® clinical chemistry analyzer at 37 °C. Measures G6PDH enzyme activity via NAD+ to NADH conversion. Assay range: 0.3–40 µg/mL. Sample volume: 5 µL.

Indications for Use

Indicated for the quantitative determination of theophylline in human serum to aid in monitoring dosage for patients with asthma, obstructive lung disease, or neonatal apnea.

Regulatory Classification

Identification

A theophylline test system is a device intended to measure theophylline (a drug used for stimulation of the muscles in the cardiovascular, respiratory, and central nervous systems) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of theophylline overdose or in monitoring levels of theophylline to ensure appropriate therapy.

Predicate Devices

• Diagnostic Reagents, Inc. (DRI) - Theophylline Reagent (K952596)

Submission Summary (Full Text)

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1000

#### יור אי 10 007

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

### 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® Theophylline Reagent |
|----------------------|--------------------------------------------------------------------------------|
| Common Name: | Enzyme immunoassay for theophylline |
| Classification Name: | Theophylline test |
| Predicate Device: | Diagnostic Reagents, Inc. (DRI) - Theophylline Reagent [510(k) Number K952596] |

### Device Description

The ACE® Theophylline Reagent contains two reagents, an Antibody/Substrate reagent and an Enzyme Conjugate reagent. The assay uses specific antibodies to theophylline and is based on the competition of an enzyme glucose-6-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® Theophylline Reagent is intended for use in the quantitative determination of theophylline in human serum.

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

# SUMMARY OF SAFETY AND EFFECTIVENESS

# COMPARATIVE FEATURES OF PREDICATE AND PROPOSED DEVICES

| PARAMETER | PREDICATE DEVICE | PROPOSED DEVICE |
|----------------------------------------------------------------|--------------------------------------------------|--------------------------------------------------|
| Trade Name | DRI Theophylline Enzyme<br>Immunoassay | ACE® Theophylline Reagent |
| Reference No. | K952596 | TBD |
| Analyte | Theophylline | Theophylline |
| Intended Use | Quantitative determination of<br>theophylline | Quantitative determination of<br>theophylline |
| 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>10 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® Theophylline 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 | 0.8 µg/mL to 40 µg/mL<br><6.1 %CV<br><9.5 %CV | 0.3 µg/mL to 40 µg/mL<br><5.6 %CV<br><14.0 %CV |
| Correlation vs<br>Slope<br>Intercept<br>r<br>N | Commercial theophylline assay<br>0.98<br>-0.16<br>0.984<br>88 | Hitachi 717<br>1.042<br>0.75<br>0.993<br>50 |

Based on these data, the Schiapparelli Biosystems ACE® Theophylline Reagent is substantially equivalent to the predicate device (Diagnostic Reagents, Inc. Theophylline 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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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 1 2 1997

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

Re: K973583 ACE® Theophylline Reagent Regulatory Class: II Product Code: KIS Dated: September 18, 1997 Received: September 22, 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 regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, 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 In addition, FDA may publish further announcements action. 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 requlations.

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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 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 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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Page 1 of 1

510(k) Number (if known):

ACE® Theophylline Reagent Device Name:

Indications For Use:

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

Theophylline is a methylxanthine derivative which is widely used in the treatment of asthma, obstructive lung disease and neonatal apnea. The primary therapeutic effect of theophylline is due to relaxation of bronchial smooth muscle; however, theophylline has a variety of other effects. These include stimulation of the central nervous system and medullary respiratory centers, decreased peripheral vascular resistance, cardiac stimulation, and diuresis. In combination with other clinical data, monitoring serum theophylline levels may provide the physician with useful information to aid in adjusting patient dosage to achieve optimal therapeutic effect while avoiding drug toxicity.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

| (Division Sign-Off) | |
|---------------------------------|----------|
| Division of Clinical Laboratory | services |
| 510(k) Number | K973583 |

| Prescription Use | <div> <span></span> </div> |
|----------------------|----------------------------|
| (Per 21 CFR 801.109) | |

OR

| Over-The-Counter Use | <div> <span></span> </div> |
|--------------------------|----------------------------|
| (Optional Format 1-2-96) | |