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

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.

AI/ML Overview

The provided document describes the ACE® Phenytoin Reagent, an enzyme immunoassay for the quantitative determination of phenytoin in human serum, and its substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and study data:

1. Table of Acceptance Criteria and Reported Device Performance

The submission relies on demonstrating substantial equivalence to a predicate device (Diagnostic Reagents, Inc. (DRI) - Phenytoin Reagent [510(k) Number K945725]). The performance parameters below are compared between the proposed device and the predicate device, implying that the predicate's performance serves as the de-facto acceptance criteria for the proposed device to be considered substantially equivalent.

Parameter	Predicate Device Performance	Proposed Device Performance	Acceptance Criteria (Implied)
Assay Range	0.3 µg/mL to 40 µg/mL	0.6 µg/mL to 40 µg/mL	Comparable to predicate
Precision
Within Run	< 5.5 %CV	< 7.9 %CV	< 5.5 %CV (or demonstrably equivalent and acceptable for clinical use)
Between Run	< 5.9 %CV	< 11.7 %CV	< 5.9 %CV (or demonstrably equivalent and acceptable for clinical use)
Correlation vs	Commercial phenytoin assay	Hitachi 717
Slope	1.01	1.119	Close to 1.0
Intercept	0.17	-0.51	Close to 0
r (correlation coefficient)	0.97	0.993	Close to 1 (high correlation)

Note on Acceptance Criteria: The document states, "Based on these data, the Schiapparelli Biosystems ACE® Phenytoin Reagent is substantially equivalent to the predicate device." This implies that the observed performance of the proposed device was deemed sufficiently similar or better than the predicate's performance to meet the regulatory standard of substantial equivalence. While some metrics for the proposed device (e.g., %CV for precision) are numerically higher than the predicate, the overall comparison including the strong correlation coefficient (0.993) was sufficient for clearance. Specific numerical acceptance cut-offs are not explicitly stated, but are inferred from the predicate's performance and the FDA's clearance decision.

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

Correlation Study: The proposed device's correlation study involved a sample size (N) of 49.
Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the context of a 510(k) submission for a clinical chemistry reagent, test samples would typically be human serum and would have been collected in a setting relevant to clinical diagnostics, likely within the United States where the company is based.

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

This type of in vitro diagnostic device (IVD) for quantitative analyte measurement (phenytoin) does not typically rely on "expert ground truth" in the same way an imaging or pathology device would.
The "ground truth" for the correlation study is established by a reference method or a standardized clinical analyzer. In this case, the proposed device's results were correlated against the Hitachi 717, which is a widely used and established clinical chemistry analyzer. The Hitachi 717's results are considered the comparative "truth" for the study.
Therefore, the concept of "number of experts" and "qualifications of experts" for ground truth establishment is not directly applicable here.

4. Adjudication Method for the Test Set

Adjudication methods (e.g., 2+1, 3+1) are typically used for subjective assessments where expert readers' interpretations need to be reconciled, such as in imaging studies.
For quantitative IVDs like this one, the "adjudication" is inherent in the performance of the reference method (Hitachi 717). There isn't an external adjudication process for reconciling conflicting quantitative readings of phenytoin concentrations because the reference method provides a single, accepted value for each sample.

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

No, an MRMC comparative effectiveness study was not done.
MRMC studies are specific to evaluating the diagnostic performance of devices (often imaging) where human readers interpret cases, and the study aims to quantify the improvement in reader performance (e.g., accuracy, sensitivity, specificity) with aid from the AI device versus without.
This device is an automated clinical chemistry reagent, not an AI-powered diagnostic imaging tool that assists human readers. Its performance is measured directly by its analytical accuracy, precision, and correlation with established methods.

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

Yes, the performance assessment described is inherently a standalone evaluation.
The ACE® Phenytoin Reagent, when used on the ACE® clinical chemistry analyzer, operates as an automated system. The reported precision (within-run, between-run) and correlation data reflect the performance of the reagent and analyzer system without direct human intervention in the result generation beyond sample loading and instrument operation.
The "algorithm" here refers to the enzyme immunoassay methodology itself and the instrument's data processing, which operates without human interpretation of the primary reaction.

7. The Type of Ground Truth Used

The ground truth used for the performance assessment, specifically the correlation study, was based on measurements from an established and validated clinical chemistry analyzer, the Hitachi 717. This serves as a "comparator method" ground truth.
For precision studies, ground truth is inferred by the statistical properties of repeated measurements on known concentrations or quality control materials.

8. The Sample Size for the Training Set

The document does not provide information on a "training set" sample size.
This is expected for an immunoassay reagent. Immunoassays are based on biochemical principles and do not typically involve machine learning algorithms that require a separate "training set" for model development in the way AI/ML devices do. The assay performance is inherent in the reagent formulation and reaction kinetics.
Any internal development or optimization prior to validation would use development samples, but these are distinct from a machine learning "training set".

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

As there is no mention of a "training set" in the context of machine learning, the question of how its ground truth was established is not applicable to this device.
The "ground truth" for developing and optimizing such a reagent would implicitly be the accurate measurement of phenytoin in samples using highly reliable, perhaps gold-standard, analytical methods (e.g., LC-MS/MS or other established clinical analyzers) to ensure the reagent accurately reflects phenytoin concentrations. However, this is part of chemical development, not statistical machine learning training.

Summary

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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: (973) 882-8630

Contact Person

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

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) NumberK945725]

Device Description

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 EnzymeImmunoassay	ACE® Phenytoin Reagent
Reference No.	K945725/S1	TBD
Analyte	Phenytoin	Phenytoin
Intended Use	Quantitative determination ofphenytoin	Quatitative determination ofphenytoin
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 plasma5 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® 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 SummaryAssay RangePrecisionWithin RunBetween Run	0.3 µg/mL to 40 µg/mL<5.5 %CV<5.9 %CV	0.6 µg/mL to 40 µg/mL<7.9 %CV<11.7 %CV
Correlation vsSlopeInterceptrN	Commercial phenytoin assay1.010.170.9790	Hitachi 7171.119-0.510.99349

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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Page 2

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 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 (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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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)

Over-The-Counter Use_

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.3350 Diphenylhydantoin test system.

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