For in vitro diagnostic use only. VITROS Chemistry Products CAFFN Reagent Kit is used on the VITROS 5,1 FS Chemistry System to quantitatively measure caffeine (CAFFN) concentration in human serum and plasma of subjects undergoing therapy with caffeine, especially for cases of neonatal apnea.
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 CAFFN on VITROS Chemistry Systems.

Device Description

The VITROS 5,1 FS Chemistry System is a fully automated clinical chemistry analyzer intended for use in the in vitro determination of various analytes in human specimens. The VITROS 5,1 FS Chemistry System is designed for use with VITROS Chemistry Products MicroTip and Thin Film assays.

The system is comprised of four main elements:

The VITROS 5,1 FS Chemistry System instrumentation, which provides automated use of the chemistry reagents. The VITROS 5,1 FS Chemistry System was cleared for market by a separate 510(k) premarket notification (K031924).
The VITROS Chemistry Products range of MicroTip assays, in this case the VITROS Chemistry Products CAFFN Reagent Kit (Reagents 1 and 2, Buffer and Calibrators) and the VITROS Chemistry Products TDM Performance Verifiers, which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS CAFFN assay.
The VITROS Chemistry Products Thin Film range of products, which are dry, multilavered, analytical elements, coated on polyester supports. The thin film products each have their own 510(k) clearance numbers and were cleared for market for use on the VITROS 5.1 FS Chemistry System through submission of information required by the ODE Guidance Document: "Data For Commercialization Of Original Equipment Manufacturer, Secondary and Generic Reagents For Automated Analyzers". The required information was provided in the VITROS 5,1 FS Chemistry System premarket notification (K031924).
Common reagents used by multiple assays on the VITROS System (in this case, VITROS Chemistry Products FS Diluent Pack 3).

The VITROS System and reagents are designed specifically for use with the VITROS Chemistry Products range of products.

AI/ML Overview

This document describes a 510(k) premarket notification for the VITROS Chemistry Products CAFFN Reagent Kit and VITROS Chemistry Products TDM Performance Verifiers I, II, and III.

The primary study establishing substantial equivalence for the CAFFN Reagent Kit is a correlation study comparing its performance to a legally marketed predicate device, the SYVA® Emit® Caffeine Assay.

While the document confirms the device meets the acceptance criteria for substantial equivalence, it does not provide detailed acceptance criteria values or specific performance results in a structured table as requested. However, it does state the key finding of the correlation study.

Here's the information extracted from the provided text, structured to answer your questions:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state acceptance criteria in a numerical format. Instead, it demonstrates substantial equivalence through a correlation study and other supporting studies (precision, expected values, linearity, and specificity summaries are referenced but not detailed). The primary performance metric presented is the correlation between the new device and the predicate device.

Performance Characteristic	Acceptance Criteria (Implicit)	Reported Device Performance (VITROS CAFFN assay)
Correlation with Predicate Device	Substantially equivalent performance to predicate.	VITROS CAFFN assay = 0.9995 X - 0.04 ug/mL (where X is the predicate device)
Correlation Coefficient (R)	High correlation (e.g., >0.95 or similar for clinical assays)	0.989
Intended Use Equivalence	Matches or is substantially similar to predicate	Matches predicate's intended use for quantitative caffeine measurement, with an added specific application for neonatal apnea.
Basic Principle Equivalence	Same or similar principle of operation.	Homogeneous enzyme immunoassay (Same as predicate)
Reportable Range Equivalence	Same or similar range.	1 - 30 µg/mL (Same as predicate)
Instrumentation Compatibility	Operates on specified system.	VITROS 5,1 FS Chemistry System (Predicate operates on SYVA-30R)
Sample Type Compatibility	Handles specified sample types.	Serum and plasma (Predicate uses Serum)

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

Sample Size for Test Set: The document mentions "patient samples" were used in the equivalence study but does not specify the exact number or sample size of patients or samples.
Data Provenance: Not specified. It's implied to be retrospective or a controlled clinical sample collection, but the country of origin is not mentioned.

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

Number of Experts: Not applicable. The ground truth (or reference standard in this context) for the test set was established by the predicate device's measurements, not by human expert interpretation.
Qualifications of Experts: N/A

4. Adjudication Method for the Test Set

Adjudication Method: Not applicable. The comparison is directly between the new device's readings and the predicate device's readings. There is no human adjudication process involved as it's a quantitative chemical assay.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

MRMC Study Done: No. This is a chemical assay, not an imaging or diagnostic interpretation device that would typically involve human readers.

6. Standalone Performance Study (Algorithm only without Human-in-the-loop performance)

Standalone Study Done: Yes. The correlation study and other tests (precision, linearity, specificity) represent the standalone performance of the VITROS Chemistry Products CAFFN Reagent Kit on the VITROS 5,1 FS Chemistry System. The results are compared against the predicate device, which also operates in a standalone manner.

7. Type of Ground Truth Used

Type of Ground Truth: The "ground truth" for the comparison study was the measurements obtained from the legally marketed predicate device (SYVA® Emit® Caffeine Assay). It can also be considered an "established reference method" for comparing new devices.

8. Sample Size for the Training Set

Sample Size for Training Set: Not applicable. This device is a chemical reagent kit for an immunoassay, not a machine learning or AI algorithm that typically has a "training set" in the conventional sense. The development of such assays involves analytical validation, not statistical model training.

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

How Ground Truth for Training Set Was Established: Not applicable, as there is no training set in the AI/ML context for this type of device. The development and optimization of the assay would involve various laboratory methods and reference materials, but these are not referred to as "training sets" with associated "ground truth" in this context.

Summary

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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: K042520

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 15, 2004

1.3 Device Proprietary Name(s)

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

Common Name Caffeine assay and controls

1.4 Classification Name(s)

Theophylline Test System: Class II (21 CFR 862.3880) Assayed Controls: Class I, reserved (21 CFR 862.1660)

1.5 Predicate devices

The VITROS Chemistry Products CAFFN assay is substantially equivalent to the SYVA® Emit® Caffeine Assay (Dade Behring, Inc.)

The modified 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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1.6 Device description

The system is comprised of four main elements:

1. The VITROS 5,1 FS Chemistry System instrumentation, which provides automated use of the chemistry reagents. The VITROS 5,1 FS Chemistry System was cleared for market by a separate 510(k) premarket notification (K031924).
1. The VITROS Chemistry Products range of MicroTip assays, in this case the VITROS Chemistry Products CAFFN Reagent Kit (Reagents 1 and 2, Buffer and Calibrators) and the VITROS Chemistry Products TDM Performance Verifiers, which are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS CAFFN assay.
1. The VITROS Chemistry Products Thin Film range of products, which are dry, multilavered, analytical elements, coated on polyester supports. The thin film products each have their own 510(k) clearance numbers and were cleared for market for use on the VITROS 5.1 FS Chemistry System through submission of information required by the ODE Guidance Document: "Data For Commercialization Of Original Equipment Manufacturer, Secondary and Generic Reagents For Automated Analyzers". The required information was provided in the VITROS 5,1 FS Chemistry System premarket notification (K031924).
1. Common reagents used by multiple assays on the VITROS System (in this case, VITROS Chemistry Products FS Diluent Pack 3).

The VITROS System and reagents are designed specifically for use with the VITROS Chemistry Products range of products.

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Device intended use 1.7

VITROS Chemistry Products CAFFN Reagent Kit: For in vitro diagnostic use only. VITROS Chemistry Products CAFFN Reagent Kit is used on the VITROS 5,1 FS Chemistry System to quantitatively measure caffeine (CAFFN) concentration in human serum and plasma of subjects undergoing therapy with caffeine, especially for cases of neonatal apnea.

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 CAFFN on VITROS Chemistry Systems.

Comparison to predicate device: Reagent Kit 1.8

The VITROS Chemistry Products CAFFN Reagent Kit is substantially equivalent to the SYVA Emit Caffeine Assay, which was cleared by FDA (K853872) for IVD use. For this device, the intended use includes the application of the test in monitoring patients treated with caffeine as a therapeutic agent for neonatal apnea 1.2. Treatment of neonatal apnea with caffeine was approved by the FDA (9/21/99, NDA #020793).

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

VITROS CAFFN assay = 0.9995 X - 0.04 ug/mL with a correlation coefficient of 0.989, 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 CAFFN assay, (refer to the VITROS Chemistry Products CAFFN Reagent Kit Instructions for Use for summaries of the results of these studies).

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

DeviceCharacteristic	VITROS ChemistryProducts CAFFN Assay(New device #1)	SYVA Emit Caffeine Assay(Predicate device #1)
Intended Use	Quantitative measurementof caffeine concentration inhuman serum and plasma ofsubjects undergoing therapywith caffeine, especially forcases of neonatal apnea.	Quantitative measurement ofcaffeine as a metabolite.
Basic principle	Homogeneous enzymeimmunoassay	Homogeneous enzymeimmunoassay
Reportable Range	1 - 30 µg/mL	1 - 30 µg/mL
Instrumentation	VITROS 5,1 FS ChemistrySystem	SYVA-30R BiochemicalSystem
Sample type	Serum and plasma	Serum

Comparison to predicate device: Performance Verifiers 1.9

The modified 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 caffeine to the controls. The labeling will be updated to add assigned values for caffeine so that the TDM Performance Verifiers may be used with the VITROS Chemistry Products CAFFN assay.

1.10 Conclusions

The data presented in the premarket notification provide a reasonable assurance that the VITROS Chemistry Products CAFFN 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 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 coiled around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circular pattern around the symbol. The logo is black and white.

Public Health Service

NOV 3 0 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Carey A. Mayo, MS., RAC Regulatory Affairs Associate Ortho-Clinical Diagnostics 100 Indigo Creek Drive Rochester, NY 14626-5101

Re: K042520

Trade/Device Name: VITROS Chemistry Products CAFFN Reagent Kit VITROS Chemistry Products TDM Performance Verifiers, I, II, and III Regulation Number: 21 CFR 862.3880 Regulation Name: Theophylline test system Regulatory Class: Class II Product Code: KLS, DIF Dated: November 12, 2004 Received: November15, 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 vour 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) 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 information about the application of labeling requirements to your device, or questions on the promotion 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,

Cornelius B. Lotz

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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Indications for Use

510(k) Number (if known): K042520

Device Name:

1. VITROS Chemistry Products CAFFN Reagent Kit
1. VITROS Chemistry Products TDM Performance Verifiers I, II, and III

Indications For Use:

1. For in vitro diagnostic use only. VITROS Chemistry Products CAFFN Reagent Kit is used on the VITROS 5,1 FS Chemistry System to quantitatively measure caffeine (CAFFN) concentration in human serum and plasma of subjects undergoing therapy with caffeine, especially for cases of neonatal apnea.
1. 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 CAFFN on VITROS Chemistry Systems.

Prescription Use (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)

Carol C. Benner

Division Sign-Off

Office of In Vitro Diagnostla Device Evaluation and Safety

510(k) K042520

Page 1 of

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.