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.

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.

AI/ML Overview

Here's an analysis of the provided text, focusing on acceptance criteria and the supporting study, formatted as requested:

Acceptance Criteria and Device Performance Study for ACE® Theophylline Reagent

1. Table of Acceptance Criteria and Reported Device Performance

This 510(k) summary directly compares the proposed device's performance to a predicate device. The acceptance criteria are implicitly defined by the predicate device's performance characteristics, demonstrating substantial equivalence.

Parameter	Acceptance Criteria (Predicate Device Performance)	Reported Device Performance (Proposed Device)
Assay Range	0.8 µg/mL to 40 µg/mL	0.3 µg/mL to 40 µg/mL
Precision
- Within Run	< 6.1 %CV	< 5.6 %CV
- Between Run	< 9.5 %CV	< 14.0 %CV
Correlation vs	Commercial theophylline assay	Hitachi 717
- Slope	0.98	1.042
- Intercept	-0.16	0.75
- r	0.984	0.993
- N	88	50

Note: The predicate device has a slightly tighter between-run precision (%CV) than the proposed device (9.5% vs 14.0%). However, the proposed device shows better within-run precision and a wider assay range. The correlation statistics (slope, intercept, r-value) are also comparable or improved for the proposed device, especially considering the different comparison methods (Commercial theophylline assay for predicate vs. Hitachi 717 for proposed). The FDA's substantial equivalence determination indicates these differences were deemed acceptable.

2. Sample Sizes Used for the Test Set and Data Provenance

The primary test sets are used for correlation studies.

Correlation for Predicate Device: N = 88
Correlation for Proposed Device: N = 50

Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It only presents "Non-clinical test results submitted in the premarket notification include within-run and between-run precision and method correlation." Typically, such studies for regulatory submissions are prospective and conducted in a controlled environment, likely in the US where Schiapparelli Biosystems, Inc. is located. However, this is not explicitly stated.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

For this type of in vitro diagnostic device, "ground truth" for the test set is established by accepted reference methods or commercial assays. The document refers to "Commercial theophylline assay" for the predicate device and "Hitachi 717" for the proposed device. These are established laboratory methods or instruments used for quantitative determination.

There is no mention of "experts" in the sense of clinicians or radiologists establishing ground truth. The ground truth is determined by the output of these reference laboratory instruments or assays.

4. Adjudication Method for the Test Set

Not applicable. This is not an imaging or diagnostic interpretation study requiring expert adjudication. The performance is assessed against quantitative measurements from established laboratory methods.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is typically relevant for interpretative diagnostic devices (e.g., imaging AI) where multiple human readers assess cases with and without AI assistance. This device is an in vitro diagnostic reagent for quantitative measurement.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the performance assessment described (precision, correlation) represents the standalone performance of the ACE® Theophylline Reagent. It evaluates the reagent's ability to accurately and precisely determine theophylline levels without direct human interpretation influencing the measurement outcome. The role of the human is to operate the ACE® clinical chemistry analyzer and follow the assay protocol.

7. The Type of Ground Truth Used

The ground truth used for the correlation studies was quantitative results obtained from:

A "Commercial theophylline assay" for the predicate device's correlation.
A "Hitachi 717" analyzer for the proposed device's correlation.

These represent established, presumably validated, laboratory methods for theophylline measurement.

8. The Sample Size for the Training Set

The document does not provide information on a "training set" in the context of machine learning. This device is a chemical reagent for an enzyme immunoassay, not an AI/ML algorithm that requires a separate training set. The development of such a reagent involves chemical formulation, optimization, and validation, rather than algorithmic training.

9. How the Ground Truth for the Training Set Was Established

Not applicable. As noted above, this is not an AI/ML device, and thus there is no "training set" in that context. The "ground truth" for the development and optimization of the reagent would involve calibrating it against known concentrations of theophylline and ensuring its chemical and enzymatic reactions perform as expected, which is part of standard analytical chemistry and assay development.

Summary

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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: (973) 882-8630

Contact Person

Steven Dalessio Manager, Quality Assurance/Regulatory Affairs Phone: (973) 882-8630

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

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 EnzymeImmunoassay	ACE® Theophylline Reagent
Reference No.	K952596	TBD
Analyte	Theophylline	Theophylline
Intended Use	Quantitative determination oftheophylline	Quantitative determination oftheophylline
Methodology	Enzyme immunoassay	Enzyme immunoassay
ReagentsReagent 1Volume	Liquid; Antibody/Substrate210 µL	Liquid; Antibody/Substrate210 µL
Reagent 2Volume	Liquid; Enzyme conjugate70 µL	Liquid; Enzyme conjugate70 µL
SpecimenTypeVolume	Serum and plasma10 µL	Serum5 µL
Assay SystemReagent 1 + SampleReagent 2Temperature	Incubate 300 secRead 60 and 120 sec37 °C	Incubate 240 secRead 63 and 203 sec37 °C
Detection MethodTypeWavelength, nm	SpectrophotometricBichromatic: 340/505	SpectrophotometricBichromatic: 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 SummaryAssay RangePrecisionWithin RunBetween Run	0.8 µg/mL to 40 µg/mL<6.1 %CV<9.5 %CV	0.3 µg/mL to 40 µg/mL<5.6 %CV<14.0 %CV
Correlation vsSlopeInterceptrN	Commercial theophylline assay0.98-0.160.98488	Hitachi 7171.0420.750.99350

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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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes entwined around it. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the caduceus.

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 (770) 488-7655.

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 (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. 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 (800) 638-2041 or (301) 443-6597 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.

(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
(Per 21 CFR 801.109)

Over-The-Counter Use
(Optional Format 1-2-96)

Regulation Number and Section

§ 862.3880 Theophylline test system.

(a)
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.(b)
Classification. Class II.