The ACE® Phenobarbital Reagent contains two reagents, an Antibody/Substrate reagent and an Enzyme Conjugate reagent. The assay uses specific antibodies to phenobarbital 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 regarding the ACE® Phenobarbital Reagent, detailing its acceptance criteria and the study that proves its performance:

ACE® Phenobarbital Reagent: Acceptance Criteria and Performance Study

The ACE® Phenobarbital Reagent is an enzyme immunoassay intended for the quantitative determination of phenobarbital in human serum. This 510(k) premarket notification (K973536) demonstrates substantial equivalence to a predicate device, the DRI Phenobarbital Enzyme Immunoassay (K946210).

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly derived from the comparison to the predicate device and standard performance metrics for such assays. The reported performance of the Proposed Device (ACE® Phenobarbital Reagent) is compared against that of the Predicate Device for substantial equivalence.

Parameter	Acceptance Criteria (Implied from Predicate)	Reported Proposed Device Performance
Assay Range	0.5 µg/mL to 80 µg/mL	1.3 µg/mL to 80 µg/mL
Precision
Consistency	< 5.4 %CV (Within Run)	< 6.7 %CV (Within Run)
Repeatability	< 6.8 %CV (Between Run)	< 10.8 %CV (Between Run)
Correlation vs. Commercial Phenobarbital assay/Hitachi 717
Slope	1.00 (vs. Commercial)	1.067 (vs. Hitachi 717)
Intercept	0.9 (vs. Commercial)	-1.26 (vs. Hitachi 717)
Correlation (r)	0.992 (vs. Commercial)	0.972 (vs. Hitachi 717)

Note: The reported performance of the Proposed Device meets the general expectations for substantial equivalence, as indicated by the FDA's approval. While some metrics like %CV are slightly higher for the proposed device, the overall correlation and range are considered acceptable for its intended use.

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

Sample Size for Test Set (Correlation Study):
- For the correlation study comparing the ACE® Phenobarbital Reagent to the Hitachi 717, a sample size of N=45 was used.
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the nature of a 510(k) submission for an IVD, it is generally assumed that these studies are conducted in a controlled lab environment, likely in the country of the submitter (USA, based on the address). The studies are typically prospective evaluations of device performance.

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

This type of diagnostic device (a reagent for determining drug levels) does not typically involve human expert interpretation of results to establish ground truth in the same way an imaging device might. The "ground truth" for the test set is established by the comparative method itself (the Hitachi 717, an existing clinical chemistry analyzer), which is presumed to be accurate and reliable for phenobarbital measurement. Therefore, no human experts were involved in establishing ground truth for the test set in this context.

4. Adjudication Method for the Test Set

Not applicable. As explained in point 3, the ground truth for this type of quantitative assay is established by comparison to a reference method (the Hitachi 717), not by expert adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance

Not applicable. This device is a diagnostic reagent for measuring drug levels, not an imaging or AI-assisted diagnostic tool that would involve human readers or AI assistance.

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

Yes, in essence, the performance assessment described is a standalone evaluation of the reagent on the ACE® clinical chemistry analyzer. The results are quantitative measurements, and the accuracy is assessed by correlation with another established analytical method (Hitachi 717), not by human interpretation or intervention in the measurement process itself.

7. The Type of Ground Truth Used

The ground truth for the performance assessment was established by comparison to a recognized commercial Phenobarbital assay/Hitachi 717. This is a form of comparative analytical truth, where the performance of the new device is benchmarked against an already validated and commonly used method for measuring phenobarbital concentrations.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of a machine learning or AI algorithm. For this type of chemical assay, method development and optimization would rely on laboratory experiments and validation studies. The N=45 for the correlation study and the samples used for precision studies (not explicitly quantified beyond showing %CVs) represent the data used for performance validation, which is more akin to a test set in clinical chemistry.

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

Not applicable in the context of a traditional chemical immunoassay. The development and optimization of the ACE® Phenobarbital Reagent would involve standard chemical and analytical validation processes to ensure accurate and precise measurement of phenobarbital, rather than establishing "ground truth" for a training set in the AI sense.

Summary

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17413336

510(k) PREMARKET NOTIFICATION ACE® Phenobarbital Reagent

NOV - 6 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® Phenobarbital Reagent
Common Name:	Enzyme immunoassay for phenobarbital
Classification Name:	Phenobarbital test
Predicate Device:	Diagnostic Reagents, Inc. (DRI) - Phenobarbital Reagent [510(k) NumberK946210]

Device Description

Intended Use of the Device

ACE® Phenobarbital Reagent is intended for use in the quantitative determination of phenobarbital in human serum.

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510(k) PREMARKET NOTIFICATION ACE® Phenobarbital Reagent

SUMMARY OF SAFETY AND EFFECTIVENESS

COMPARATIVE FEATURES OF PREDICATE AND PROPOSED DEVICES

PARAMETER	PREDICATE DEVICE	PROPOSED DEVICE
Trade Name	DRI Phenobarbital EnzymeImmunoassay	ACE® Phenobarbital Reagent
Reference No.	K946210	TBD
Analyte	Phenobarbital	Phenobarbital
Intended Use	Quantitative determination ofphenobarbital	Quantitative determination ofphenobarbital
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® Phenobarbital 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	0.5 µg/mL to 80 µg/mL<5.4 %CV<6.8 %CV	1.3 µg/mL to 80 µg/mL<6.7 %CV<10.8 %CV
Correlation vsSlopeInterceptrN	Commercial Phenobarbital assay1.000.90.99280	Hitachi 7171.067-1.260.97245

Based on these data, the Schiapparelli Biosystems ACE® Phenobarbital Reagent is substantially equivalent to the predicate device (Diagnostic Reagents, Inc. Phenobarbital 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 image of an eagle with its wings spread, enclosed within a circle. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES · USA" is arranged around the upper portion of the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV - 6 1997

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

K973536 Re : ACE® Phenobarbital Reagent Requlatory Class: II Product Code: DLJ Dated: October 24, 1997 Received: October 27, 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. 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 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 requlations.

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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 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 Page Page of

510(k) Number (if known):_

Device Name:__________________________________________________________________________________________________________________________________________________________________

Indications For Use:

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

Since its discovery by Hauptmann in 1912, phenobarbital has been widely prescribed for the treatment of epilepsy, particularly for controlling focal motor or sensory and grand mal seizures. In combination with other clinical information, monitoring serum phenobarbital levels will provide physicians with an essential tool to aid in adjusting dosage and achieving optimal therapeutic effect, while avoiding both subtherapeutic and harmful toxic drug levels.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

	Patricli.Dentant
(Division Sign-Off)	(for Alum)
Division of Cardiovascular Devices
510(k) Number	K973536

Prescription Use (Per 21 CFR 801.109)	OR	Over-The-Counter Use (Optional Format 1-2-96)
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002

Regulation Number and Section

§ 862.3200 Clinical toxicology calibrator.

(a)
Identification. A clinical toxicology calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. A clinical toxicology calibrator can be a mixture of drugs or a specific material for a particular drug (e.g., ethanol, lidocaine, etc.). (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.