For in vitro diagnostic use only. VITROS Chemistry Products TOBRA Reagent is used on the VITROS 5,1 FS Chemistry System to quantitatively measure tobramycin (TOBRA) concentration in human serum and plasma. Serum or plasma tobramycin measurements are used in the diagnosis and treatment of tobramycin overdose and in monitoring levels of tobramycin to ensure appropriate therapy.
For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 14 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of tobramycin (TOBRA).
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 TOBRA on VITROS Chemistry Systems.

Device Description

The VITROS Chemistry Products TOBRA Reagent, VITROS Chemistry Products Calibrator Kit 14, and the VITROS Chemistry Products TDM Performance Verifiers are combined by the VITROS 5,1 FS Chemistry System to perform the VITROS TOBRA assay. VITROS Chemistry Products TOBRA Reagent is a dual chambered package containing ready-to-use liquid reagents that are used in a two-step reaction to quantitatively measure tobramycin.

VITROS Chemistry Products Calibrator Kit 14 and TDM Performance Verifiers are packaged and sold separately.

VITROS Chemistry Products Calibrator Kit 14 is a liquid ready to use calibrator set for tobramycin. 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 assayed 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 a breakdown of the acceptance criteria and study information based on the provided text, focusing on the VITROS Chemistry Products TOBRA Reagent:

1. Table of Acceptance Criteria and Reported Device Performance

Device Characteristic	Acceptance Criteria (Predicate Device Performance)	Reported Device Performance (VITROS TOBRA Assay)
Intended Use	Quantitative measurement of tobramycin	Quantitative measurement of tobramycin
Basic Principle	Homogeneous enzyme immunoassay	Homogeneous enzyme immunoassay
Reportable Range	0.6 – 10 µg/mL	0.6 – 10 µg/mL
Reagents	Liquid ready to use	Liquid ready to use
Instrumentation	SYVA-30R Biochemical System	VITROS 5,1 FS Chemistry System
Sample Type	Serum and plasma	Serum and plasma
Correlation (vs. Predicate)	Implicitly 0.997 (achieved by predicate)	0.997 (correlation coefficient)
Regression Slope	Implicitly 1.01 (achieved by predicate)	1.01 (from VITROS TOBRA assay = 1.01 X + 0.00)
Regression Intercept	Implicitly 0.00 µg/mL (achieved by predicate)	0.00 µg/mL (from VITROS TOBRA assay = 1.01 X + 0.00)

Notes on Acceptance Criteria: The document primarily uses the predicate device's characteristics and performance as the benchmark for demonstrating substantial equivalence. The specific "acceptance criteria" are therefore derived from the predicate's known performance and characteristics.

2. Sample size used for the test set and the data provenance

Sample Size: Not explicitly stated as a number but refers to "patient samples."
Data Provenance: Not explicitly stated (e.g., country of origin). The study is retrospective in the sense that it compares performance to an existing predicate device using a set of samples. Given the submission date and the context, it's highly likely to be US-based, but this is not confirmed.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not applicable. This is an IVD device measuring a chemical substance. The "ground truth" for the test set would be established by the reference method (the predicate device) or a known reference standard, not by human expert consensus or interpretation.

4. Adjudication method for the test set

Not applicable. Refer to point 3.

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 is an In Vitro Diagnostic (IVD) device for quantitative measurement of a substance, not an imaging or diagnostic aid for human readers/clinicians, nor does it typically involve AI assistance in the context of human interpretation.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the study describes the standalone performance of the VITROS TOBRA assay. The device measures tobramycin concentration without direct human-in-the-loop diagnostic interpretation of results (though results are interpreted by healthcare professionals). The performance evaluation involved comparing its measurements directly to those of the predicate device and assessing core analytical performance characteristics.

7. The type of ground truth used

The primary "ground truth" for comparison was assumed to be the readings from the predicate device (SYVA Emit 2000 Tobramycin Assay) using patient samples. Additionally, analytical studies (precision, linearity, specificity) would rely on known concentrations of tobramycin standards/samples.

8. The sample size for the training set

Not applicable in the context of this traditional IVD device. The VITROS TOBRA assay is based on a homogeneous enzyme immunoassay principle, not a machine learning algorithm that requires a "training set" in the conventional sense. Its "training" is inherent in its chemical design and calibration process.

9. How the ground truth for the training set was established

Not applicable. Refer to point 8.

Summary

{0}------------------------------------------------

FEB - 7 2005 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: _______________________________________________________________________________________________________________________________________________

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: December 8, 2004

1.3 Device Proprietary Name(s)

Trade Name(s):

VITROS Chemistry Products TOBRA Reagent

VITROS Chemistry Products Calibrator Kit 14

VITROS Chemistry Products TDM Performance Verifier I, II, and III

Common Name(s): Tobramycin assay and controls

1.4 Classification Name(s)

Tobramycin Test System: Class II (21 CFR 862.3900) Calibrators: Class II (21 CFR 862.3200) Assayed Controls: Class I (21 CFR 862. 3280)

1.5 Predicate device

The VITROS Chemistry Products TOBRA reagent and calibrators are substantially equivalent to the SYVA® Emit® 2000 Tobramycin Assay and Calibrators (Dade Behring, Inc.).

The VITROS Chemistry Products TDM Performance Verifiers are substantially equivalent to the previously cleared VITROS Chemistry Products TDM Performance Verifiers.

{1}------------------------------------------------

1.6 Device description

VITROS Chemistry Products Calibrator Kit 14 and TDM Performance Verifiers are packaged and sold separately.

1.7 Device intended use(s)

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

VITROS Chemistry Products Calibrator Kit 14: For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 14 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of tobramycin (TOBRA).

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 TOBRA on VITROS Chemistry Systems.

{2}------------------------------------------------

1.8 Comparison to predicate device: Reagent and Calibrators

The VITROS Chemistry Products TOBRA Reagent and VITROS Chemistry Products Calibrator Kit 14 are substantially equivalent to the SYVA Emit 2000 Tobramycin Assay and the SYVA Emit 2000 Tobramycin Calibrators, which were cleared by FDA (K003341) for IVD use.

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

VITROS TOBRA assay = 1.01 X + 0.00 µg/mL, with a correlation coefficient of 0.997, where X is the predicate device.

In addition to the correlation studies, studies were performed to determine the precision, expected values, linearity, and specificity of the VITROS TOBRA assay, (refer to the VITROS Chemistry Products TOBRA Reagent Instructions for Use for a summary of the results of these studies).

The table below lists the characteristics of the VITROS Chemistry Products TOBRA assay and the predicate device.

DeviceCharacteristic	VITROS TOBRA Assay(New device)	SYVA Emit 2000 Tobramycin Assay(Predicate device)
Intended Use	Quantitative measurement oftobramycin	Quantitative measurement oftobramycin
Basic principle	Homogeneous enzymeimmunoassay	Homogeneous enzyme immunoassay
ReportableRange	0.6 – 10 µg/mL	0.6 – 10 µg/mL
Reagents	Liquid ready to use	Liquid ready to use
Instrumentation	VITROS 5,1 FS ChemistrySystem	SYVA-30R Biochemical System
Sample type	Serum and plasma	Serum and plasma

1.9 Comparison to predicate device: Performance Verifiers

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 (K042476). The labeling will be updated to add assigned values for tobramycin so that the TDM Performance Verifiers may be used with the VITROS Chemistry Products TOBRA assay.

{3}------------------------------------------------

1.10 Conclusions

The data presented in the premarket notification provide a reasonable assurance that the VITROS Chemistry Products TOBRA reagent, VITROS Chemistry Products Calibrator Kits 14, and the VITROS Chemistry Products 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.

{4}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health and 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 an abstract symbol resembling an eagle or bird in flight, composed of three curved lines.

FEB - 7 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Carey A. Mayo, MS., RAC Regulatory Affairs Associate Ortho-Clinical Diagnostics, Inc. Regulatory Affairs MC00881 100 Indigo Creek Drive Rochester, NY 14626

Re: K043384

Trade/Device Name: VITROS Chemistry Products TOBRA Reagent VITROS Chemistry Products Calibrator Kit 14 VITROS Chemistry Products TDM Performance Verifiers I, II, and III

Regulation Number: 21 CFR 862.3900 Regulation Name: Tobramycin test system Regulatory Class: Class II Product Code: LDO, DLJ, DIF Dated: December 8, 2004 Received: December 9, 2004

Dear Ms. Mayo:

We have reviewed your Section 510(k) premarket notification of intent to market the devices referenced above and have determined the devices 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 devices, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your devices are 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 devices 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).

{5}------------------------------------------------

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 (240)276-0484. 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/industry/support/index.html

Sincerely yours.

Sean McCooper MS, DUM

Jean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{6}------------------------------------------------

2.0 Indications for Use

Page 1 of 1

510(k) Number (if known):	K043384
Device Name:	1. VITROS Chemistry Products TOBRA Reagent2. VITROS Chemistry Products Calibrator Kit 143. VITROS Chemistry Products TDM Performance Verifiers I, II, and III
Indications for Use:	1. For in vitro diagnostic use only. VITROS Chemistry Products TOBRA Reagent is used on the VITROS 5,1 FS Chemistry System to quantitatively measure tobramycin (TOBRA) concentration in human serum and plasma. Serum or plasma tobramycin measurements are used in the diagnosis and treatment of tobramycin overdose and in monitoring levels of tobramycin to ensure appropriate therapy.2. For in vitro diagnostic use only. VITROS Chemistry Products Calibrator Kit 14 is used to calibrate VITROS 5,1 FS Chemistry Systems for the quantitative measurement of tobramycin (TOBRA).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 TOBRA on VITROS Chemistry Systems.
Prescription Use	AND/OR Over-The-Counter Use

(Part 21 CFR 801 Subpart D)

(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. Benson
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation a nd Safety

510(k) K043384

VITROS Chemistry Products TOBRA assay and Controls Ortho-Clinical Diagnostics, Inc.

Page 5 of 45

Regulation Number and Section

§ 862.3900 Tobramycin test system.

(a)
Identification. A tobramycin test system is a device intended to measure tobramycin, an aminoglycoside antibiotic drug, in plasma and serum. Measurements obtained by this device are used in the diagnosis and treatment of tobramycin overdose and in monitoring levels of tobramycin to ensure appropriate therapy.(b)
Classification. Class II.