(51 days)
ACE® Valproic Acid Reagent is intended for use in the quantitative determination of valproic acid in human serum.
ACE® Valproic Acid Reagent is intended for the quantitative determination of valproic acid in serum using the ACE® clinical chemistry analyzer.
The ACE® Valproic Acid Reagent contains two reagents, an Antibody/Substrate reagent and an Enzyme Conjugate reagent. The assay uses specific antibodies to valproic acid 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.
The ACE® Valproic Acid Reagent is an enzyme immunoassay intended for the quantitative determination of valproic acid in human serum. The study demonstrated its substantial equivalence to a predicate device, the DRI Valproic Acid Enzyme Immunoassay, based on performance parameters such as assay range, precision, and correlation with another commercial valproic acid assay.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by demonstrating substantial equivalence to the predicate device and showing comparable performance. The performance metrics of the predicate device serve as the de facto acceptance criteria.
| Parameter | Acceptance Criteria (Predicate Device) | Reported Device Performance (Proposed Device) |
|---|---|---|
| Assay Range | 3 µg/mL to 150 µg/mL | 3.1 µg/mL to 150 µg/mL |
| Precision | ||
| Within-Run %CV | <3.4 %CV | <5.9 %CV |
| Between-Run %CV | <2.7 %CV | <7.5 %CV |
| Correlation vs. | Commercial valproic acid assay | Hitachi 717 |
| Slope | 1.1 | 1.079 |
| Intercept | -5.8 | 7.33 |
| r (Correlation) | 0.981 | 0.979 |
| N (Sample Size) | 88 | 49 |
2. Sample Sizes Used for the Test Set and Data Provenance
The document provides the sample sizes for the correlation studies:
- For the correlation against the "Commercial valproic acid assay" (predicate device's correlation), the sample size (N) was 88.
- For the proposed device's correlation against the "Hitachi 717" analyzer, the sample size (N) was 49.
The data provenance (country of origin, retrospective/prospective) is not explicitly stated in the provided summary. However, given that this is a 510(k) submission to the FDA in the United States, it is highly probable the data was generated in the US. The nature of "method correlation" and "within-run and between-run precision" studies typically involves prospective laboratory testing using patient samples or control materials.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information is not applicable for this device and study. The device is a quantitative diagnostic reagent, where the "ground truth" for method correlation is typically established by comparative measurements against a well-characterized reference method or an existing, clinically accepted method (like the Hitachi 717 or the "Commercial valproic acid assay"). This does not involve expert consensus in the same way an imaging or diagnostic AI device does.
4. Adjudication Method for the Test Set
Not applicable for this type of quantitative diagnostic device. Adjudication methods like 2+1 or 3+1 are typically used for assessing qualitative or semi-quantitative results, often involving human interpretation of images or clinical findings, which is not the case here.
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
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study design is relevant for AI-powered diagnostic tools that assist human interpreters (e.g., radiologists, pathologists). The ACE® Valproic Acid Reagent is a standalone quantitative assay and does not involve human interpretation in the same manner.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, a standalone performance assessment was conducted. The "Performance Summary" and "Correlation" data presented are for the device's performance as an algorithm only (reagent on an analyzer), without human-in-the-loop performance influencing the quantitative measurement of valproic acid.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The ground truth for the performance assessment was established by comparison against established, commercially available methods that are presumed to be accurate and clinically accepted. Specifically:
- The predicate device's performance (used as a benchmark) was shown in correlation against a "Commercial valproic acid assay."
- The proposed device's performance was shown in correlation against a "Hitachi 717" analyzer.
These methods themselves serve as the "ground truth" for determining the accuracy and reliability of valproic acid measurements.
8. The Sample Size for the Training Set
The document does not explicitly mention a separate "training set" or its sample size. This is typical for a diagnostic reagent where the assay parameters are generally optimized during research and development, and the validation studies (precision, correlation) are akin to a "test set" for regulatory submission.
9. How the Ground Truth for the Training Set Was Established
As no explicit training set is mentioned in the regulatory summary, information on how its "ground truth" was established is not provided. If an internal optimization process involved various samples, their "true" valproic acid concentrations would have been determined using highly reliable, possibly reference, methods.
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1115581
510(k) PREMARKET NOTIFICATION ACE® Valproic Acid Reagent
NOV 1 2 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® Valproic Acid Reagent |
|---|---|
| Common Name: | Enzyme immunoassay for valproic acid |
| Classification Name: | Valproic Acid test |
| Predicate Device: | Diagnostic Reagents, Inc. (DRI) - Valproic Acid Reagent [510(k) NumberK961988] |
Device Description
The ACE® Valproic Acid Reagent contains two reagents, an Antibody/Substrate reagent and an Enzyme Conjugate reagent. The assay uses specific antibodies to valproic acid 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® Valproic Acid Reagent is intended for use in the quantitative determination of valproic acid in human serum.
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510(k) PREMARKET NOTIFICATION ACE® Valproic Acid Reagent
SUMMARY OF SAFETY AND EFFECTIVENESS
COMPARATIVE FEATURES OF PREDICATE AND PROPOSED DEVICES
| PARAMETER | PREDICATE DEVICE | PROPOSED DEVICE |
|---|---|---|
| Trade Name | DRI Valproic Acid EnzymeImmunoassay | ACE® Valproic Acid Reagent |
| Reference No. | K961988 | TBD |
| Analyte | Valproic Acid | Valproic Acid |
| Intended Use | Quantitative determination ofvalproic acid | Quantitative determination ofvalproic acid |
| 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 plasma15 µL | Serum10 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® Valproic Acid 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 | 3 µg/mL to 150 µg/mL<3.4 %CV<2.7 %CV | 3.1 µg/mL to 150 µg/mL<5.9 %CV<7.5 %CV |
| Correlation vsSlopeInterceptrN | Commercial valproic acid assay1.1-5.80.98188 | Hitachi 7171.0797.330.97949 |
Based on these data, the Schiapparelli Biosystems ACE® Valproic Acid Reagent is substantially equivalent to the predicate device (Diagnostic Reagents, Inc. Valproic Acid 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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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/3/Picture/2 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features the department's name in a circular arrangement around a central graphic. The graphic consists of a stylized human figure with three faces in profile, one behind the other, creating a sense of depth and continuity.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
.. . . . . . . .
NOV 1 2 1997
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Mr. Steven Dalessio Manager, Quality Assurance/ Regulatory Affairs Schiapparelli Biosystems, Inc. 368 Passaic Avenue Fairfield, New Jersey 07004
Re : K973581/S1 Trade Name: ACE® Valproic Acid Reagent Regulatory Class: II Product Code: LEG 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, Druq, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions 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 Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, 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 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 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 at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
Steven Butman
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® Valproic Acid Reagent Device Name:__________________________________________________________________________________________________________________________________________________________________
Indications For Use:
15:39
ACE® Valproic Acid Reagent is intended for the quantitative determination of valproic acid in serum using the ACE® clinical chemistry analyzer.
Valproic acid (VPA, 2-propylpentanoic acid, Depakene®) is an anticonvulsant used chiefly for the treatment of primary and secondary generalized seizures, but is also effective against absence seizures. Valproic acid is particularly effective in myoclonus, and is the drug of choice in photosensitive epilepsy. Valproic acid can be used concurrently with other anticonvulsants or alone. Valproic acid may also be useful in the treatment of affective disorders, in particular, lithium-insensitive bipolar disorders.
(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 Devices
510(k) Number 1973581
Prescription Use $\surd$
(Per 21 CFR 801.109)
OR
Over-The-Counter Use__
(Optional Format 1-2-96)
§ 862.3645 Neuroleptic drugs radioreceptor assay test system.
(a)
Identification. A neuroleptic drugs radioceptor assay test system is a device intended to measure in serum or plasma the dopamine receptor blocking activity of neuroleptic drugs and their active metabolites. A neuroleptic drug has anti-psychotic action affecting principally psychomotor activity, is generally without hypnotic effects, and is a tranquilizer. Measurements obtained by this device are used to aid in determining whether a patient is taking the prescribed dosage level of such drugs.(b)
Classification. Class II.