For in vitro diagnostic use only. VITROS Chemistry Products VALP Reagent is used on the VITROS 5,1 FS Chemistry System to quantitatively measure valproic acid (VALP) concentration in human serum and plasma. Serum or plasma valproic acid measurements are used in the diagnosis and treatment of valproic acid overdose and in monitoring levels of valproic acid to ensure appropriate therapy.
For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 12 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of valproic acid (VALP).
For in vitro diagnostic use only. VITROS TDM Performance Verifier is an assayed control used to monitor performance of ACET, CRBM, DGXN, PHBR, PHYT and VALP on VITROS Chemistry Systems.

Device Description

The VITROS Chemistry Products VALP Reagent, VITROS Chemistry Products Calibrator Kit 12, and the VITROS Chemistry Products TDM Performance Verifiers are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS VALP assay. VITROS Chemistry Products VALP Reagent is a dual chambered package containing ready-to-use liquid reagents that are used in a two-step reaction to quantitatively measure valproic acid.

VITROS Chemistry Products Calibrator Kit 12 and TDM Performance Verifiers are packaged and sold separately.

VITROS Chemistry Products Calibrator Kit 12 is a liquid ready to use calibrator set for valproic acid. Each kit contains one bottle each of six (6) levels. The level 1 bottle (zero level) contains 5 milliliters. The level 2 through 6 bottles each contain 2 milliliters.

VITROS Chemistry Products TDM Performance Verifier I, II and III are liquid ready to use controls with assaved values published for each lot. The controls are prepared from bovine serum with therapeutic drugs and preservatives added. The product is sold in separate kits of Level I, II and III. Each kit contains 6 vials (2 mL each).

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the VITROS Chemistry Products VALP Assay.

It's important to note that this document is a 510(k) summary, which provides a high-level overview. Detailed performance data and acceptance criteria are typically found in the full 510(k) submission, not fully detailed in this summary.

Based on the provided text, the primary "acceptance criterion" for this device is substantial equivalence to a predicate device. This is a regulatory pathway for medical devices in the US, where a new device is deemed safe and effective if it can be shown to be at least as safe and effective as a legally marketed device (the predicate).

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implied by Substantial Equivalence to Predicate)	Reported Device Performance (VITROS VALP Assay)
Accuracy (Correlation to Predicate): Demonstrated by a strong linear relationship and high correlation coefficient.	Correlation to Predicate: VITROS VALP assay = 0.969 X + 1.339 ug/mL (where X is the predicate device)Correlation coefficient: 0.992
Intended Use: Same as predicate.	Quantitative measurement of valproic acid in human serum and plasma for diagnosis, treatment monitoring, and overdose. (Matches predicate)
Basic Principle: Same as predicate.	Homogeneous enzyme immunoassay. (Matches predicate)
Reportable Range: Comparable to predicate.	10 – 150 µg/mL. (Predicate: 1 - 150 µg/mL; difference noted but likely deemed acceptable for substantial equivalence)
Reagents: Same form as predicate.	Liquid ready to use. (Matches predicate)
Instrumentation: Specified as the VITROS 5,1 FS Chemistry System. (Predicate uses SYVA-30R Biochemical System)	Exclusive to VITROS 5,1 FS Chemistry System.
Sample Type: Same as predicate.	Serum and plasma. (Matches predicate)
Precision: Must be acceptable.	"Studies were performed to determine the precision..." (Detailed results not provided in the summary)
Expected Values: Must be acceptable.	"Studies were performed to determine the expected values..." (Detailed results not provided in the summary)
Linearity: Must be acceptable.	"Studies were performed to determine the linearity..." (Detailed results not provided in the summary)
Specificity: Must be acceptable.	"Studies were performed to determine the specificity..." (Detailed results not provided in the summary)

Note on Performance Verifiers: For the TDM Performance Verifiers, the acceptance criterion was "identical in intended use, base matrix, storage and handling and instructions for use" to previously cleared verifiers, with the only difference being the addition of valproic acid as a constituent.

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

Sample Size: The document explicitly states "patient samples" were used for the correlation study to the predicate device. However, the specific number of patient samples is not provided in this 510(k) summary.
Data Provenance: Not explicitly stated (e.g., country of origin). The document refers to "patient samples," implying clinical samples. It is a retrospective analysis in the sense that the samples are collected and then tested with both the new device and the predicate device.

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

Not Applicable (N/A) / Not Specified: For this type of chemical assay (quantitatively measuring a substance like valproic acid), "ground truth" is typically established by comparative measurement against a well-accepted, often reference standard, method or a legally marketed predicate device. The concept of "experts establishing ground truth" as it applies to subjective interpretations (e.g., radiologists reading images) is not directly relevant here. The predicate device itself serves as the benchmark.

4. Adjudication Method for the Test Set

Not Applicable (N/A) / None: Adjudication methods like 2+1 or 3+1 are used for subjective assessments where multiple readers might disagree (e.g., medical image interpretation). For a quantitative chemical assay comparing results to a predicate device, such an adjudication method is not used. The comparison is direct and numerical.

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

No: An MRMC study is not relevant for this type of quantitative chemical assay. These studies are typically performed for devices that involve human interpretation of complex data (e.g., imaging devices) to assess the impact of AI on human reader performance. This device is an automated chemical analyzer.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, implicitly: This device is an automated in vitro diagnostic (IVD) assay designed to provide a quantitative result without human subjective interpretation influencing the measurement itself. The "algorithm" here is the chemical reaction and detection process performed by the VITROS 5,1 FS Chemistry System. The comparison study to the predicate device demonstrates its standalone performance. The results (concentration of valproic acid) are then used by clinicians for diagnosis and treatment.

7. The Type of Ground Truth Used

Predicate Device Measurement / Commmercially Available Assay: The ground truth for evaluating the VITROS VALP assay was essentially the measurements obtained from the SYVA® Emit® 2000 Valproic Acid Assay, which is a legally marketed and established device (the predicate). The study established the relationship between the new device's readings and the predicate device's readings using patient samples. The term "ground truth" in this context refers to the accepted standard for measuring valproic acid.

8. The Sample Size for the Training Set

Not applicable / Not specified: This document describes a traditional in vitro diagnostic device, not an AI/Machine Learning device that typically has a distinct "training set." The performance characteristics (precision, linearity, specificity, correlation) are established through analytical studies and clinical sample testing, not through an iterative machine learning training process with a dedicated training set. The development of such an assay involves extensive R&D and validation, but not in the "training set" sense common in AI.

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

Not applicable / Not specified: As explained in point 8, the concept of a "training set" with established ground truth in the context of machine learning does not directly apply to this traditional IVD device. The "truth" in development would stem from reference methods, internal standards, and established analytical chemistry principles during assay design and optimization.

Summary

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DEC - 1 2004

1.0 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K042476

1.1 Submitter name, address, contact

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 Phone: (585) 453-3482 Fax: (585) 453-3368 Contact Person: Carey A. Mayo, M.S., RAC

1.2 Date of Preparation: September 9, 2004

1.3 Device Proprietary Name(s)

Trade Name(s) VITROS Chemistry Products VALP Reagent VITROS Chemistry Products Calibrator Kit 12 VITROS Chemistry Products TDM Performance Verifier I, II, and III

Common Name Valproic acid assay and controls

1.4 Classification Name(s)

There is no classification regulation for valproic acid. The product code is LEG. Calibrators: Class II (21 CFR 862.3200) Assayed Controls: Class I (21 CFR 862. 3280)

1.5 Predicate device

The VITROS Chemistry Products VALP Reagent and Calibrator Kit 12 are substantially equivalent to the SYVA® Emit® 2000 Valproic Acid Assay and the SYVA® Emit® 2000 Valproic Acid Calibrators (Dade Behring, Inc.) The VITROS Chemistry Products TDM Performance Verifiers are substantially equivalent to the VITROS Chemistry Products TDM Performance Verifiers currently in commercial distribution.

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Device description 1.6

VITROS Chemistry Products Calibrator Kit 12 and TDM Performance Verifiers are packaged and sold separately.

1.7 Device intended use

VITROS Chemistry Products VALP Reagent: For in vitro diagnostic use only. VITROS Chemistry Products VALP Reagent is used on the VITROS 5,1 FS Chemistry System to quantitatively measure valproic acid (VALP) concentration in human serum and plasma. Serum or plasma valproic acid measurements are used in the diagnosis and treatment of valproic acid overdose and in monitoring levels of valproic acid to ensure appropriate therapy.

VITROS Chemistry Products Calibrator Kit 12: For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 12 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of valproic acid (VALP).

VITROS Chemistry Products TDM Performance Verifier I, II and III: For in vitro diagnostic use only. VITROS TDM Performance Verifier is an assayed control used to monitor performance of ACET, CRBM, DGXN, PHBR, PHYT and VALP on VITROS Chemistry Systems.

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Comparison to predicate device: Reagent and Calibrators 1.8

The VITROS Chemistry Products VALP Reagent and VITROS Chemistry Products Calibrator Kit 12 and are substantially equivalent to the SYVA Emit 2000 Valproic Acid Assay and the SYVA Emit 2000 Valproic Acid Calibrators, which were cleared by FDA (K002551) for IVD use.

The relationship between the VITROS VALP assay and the predicate device, determined by least squares linear regression, is:

VITROS VALP assay = 0.969 X + 1.339 ug/mL, with a correlation coefficient of 0.992, where X is the predicate device.

In addition to the above mentioned correlation study, studies were performed to determine the precision, expected values, linearity, and specificity of the VITROS VALP assay, (refer to the VITROS Chemistry Products VALP Reagent Instructions for Use for summaries of the results of these studies).

DeviceCharacteristic	VITROS ChemistryProducts VALP Assay(New device #1)	SYVA Emit 2000 ValproicAcid Assay(Predicate device #1)
Intended Use	Quantitative measurementof valproic acid	Same
Basic principle	Homogeneous enzymeimmunoassay	Same
Reportable Range	10 – 150 µg/mL	1 - 150 µg/mL
Reagents	Liquid ready to use	Liquid ready to use
Instrumentation	VITROS 5,1 FS ChemistrySystem	SYVA-30R BiochemicalSystem
Sample type	Serum and plasma	Serum and plasma

The table below lists the characteristics of the VITROS Chemistry Products VALP Assay and the predicate device.

Comparison to predicate device: Performance Verifiers 1.9

The VITROS Chemistry Products TDM Performance Verifiers are identical in intended use, base matrix, storage and handling and instructions for use as the previously cleared VITROS Chemistry Products TDM Performance Verifiers currently in commercial distribution (K984288). The only difference is the addition of one constituent to the controls. The labeling will be updated to add assigned values for valproic acid so that the TDM Performance Verifiers may be used with the VITROS Chemistry Products VALP assay.

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1.10 Conclusions

The data presented in the premarket notification provide a reasonable assurance that the VITROS Chemistry Products VALP assay and the VITROS TDM Performance Verifiers are safe and effective for the stated intended uses and are substantially equivalent to the cleared predicate devices. Equivalence to the predicates was demonstrated using a commercially available assay along with patient samples.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows a circular logo with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter of the circle. Inside the circle is a stylized symbol that resembles a person embracing another person. The symbol is composed of several curved lines that create the shape of two figures.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC - 1 2004

Ms. Carey A. Mayo, M.S., RAC Regulatory Affairs Associate Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101

K042476 Re: Trade/Device Name: VITROS Chemistry Products VALP Reagent VITROS Chemistry Products Calibrator Kit 12 VITROS Chemistry TDM Performance Verifiers I, II, and III Regulation Number: 21 CFR 862.3645 Regulation Name: Neuroleptic drugs radioreceptor assay test system Regulatory Class: Class II Product Code: LEG, DLJ, DIF Dated: November 10, 2004 Received: November 12, 2004

Dear Ms. Mayo:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) This letter will and in your to one finding of substantial equivalence of your device to a legally premated predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or you don't epother monotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Cornelia B. Looks

Cornelia B. Rooks, MA Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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2.0 Indications for Use Statement

Page 1 of 1

510(k) Number (if known):	K042476
Device Name:	1. VITROS Chemistry Products VALP Reagent2. VITROS Chemistry Products Calibrator Kit 123. VITROS Chemistry Products TDM Performance Verifiers I, II, and III
Indications for Use:	1. For in vitro diagnostic use only. VITROS Chemistry Products VALP Reagent is used on the VITROS 5,1 FS Chemistry System to quantitatively measure valproic acid (VALP) concentration in human serum and plasma. Serum or plasma valproic acid measurements are used in the diagnosis and treatment of valproic acid overdose and in monitoring levels of valproic acid to ensure appropriate therapy.2. For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 12 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of valproic acid (VALP).3. For in vitro diagnostic use only. VITROS TDM Performance Verifier is an assayed control used to monitor performance of ACET, CRBM, DGXN, PHBR, PHYT and VALP on VITROS Chemistry Systems.
Prescription Use X(Part 21 CFR 801 Subpart D)	AND/OR	Over-The-Counter Use(21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

A2ke
Divisio Sign-Off

Office of In Vitro Diagnostic Device I valuation and

510(k. K042476

Ortho-Clinical Diagnostics, Inc.

Regulation Number and Section

§ 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.