The ONLINE TDM Tobramycin assay is a device intended to measure tobramycin, an aminoglycoside antibiotic drug, in human 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.

Device Description

The ONLINE TDM Tobramycin assay is for the quantitative determination of tobramycin in human serum or plasma on Roche automated clinical chemistry analyzers. The proposed labeling indicates the Roche Hitachi 911, 912, 917 and Modular P analyzers can be used with the Roche ONLINE TDM Tobramycin reagent kits.

AI/ML Overview

This document describes the acceptance criteria and the study conducted to demonstrate the substantial equivalence of the "ONLINE TDM Tobramycin" assay to a predicate device.

1. Table of acceptance criteria and reported device performance:

The document doesn't explicitly state quantitative acceptance criteria for all performance characteristics. However, it states that "All of the evaluation studies gave acceptable results compared to the predicate device." The table below summarizes the reported performance for precision and method comparison.

Performance Characteristic	Acceptance Criteria (Implied by Comparison to Predicate)	ONLINE TDM Tobramycin Performance	Predicate Device (COBAS INTEGRA Tobramycin) Performance
NCCLS Precision, Within run	Expected to be comparable or better than the predicate
Control 1 Mean (µg/ml)	N/A	1.3	1.4
Control 1 SD (µg/ml)	N/A	0.05	0.04
Control 1 CV%	N/A	3.9	2.6
Control 2 Mean (µg/ml)	N/A	4.2	3.5
Control 2 SD (µg/ml)	N/A	0.04	0.07
Control 2 CV%	N/A	0.9	2.1
Control 3 Mean (µg/ml)	N/A	7.1	7.5
Control 3 SD (µg/ml)	N/A	0.04	0.14
Control 3 CV%	N/A	0.6	1.9
NCCLS Precision, Total	Expected to be comparable or better than the predicate
Control 1 Mean (µg/ml)	N/A	1.3	1.4
Control 1 SD (µg/ml)	N/A	0.07	0.09
Control 1 CV%	N/A	5.2	6.0
Control 2 Mean (µg/ml)	N/A	4.2	3.5
Control 2 SD (µg/ml)	N/A	0.07	0.16
Control 2 CV%	N/A	1.7	4.5
Control 3 Mean (µg/ml)	N/A	7.1	7.5
Control 3 SD (µg/ml)	N/A	0.09	0.30
Control 3 CV%	N/A	1.3	4.0
Method Comparison	Strong correlation (r close to 1) and linear relationship (slope near 1, intercept near 0) with the predicate.
Linear Regression: ONLINE TDM Tobramycin Vs. COBAS FP Tobramycin	N/A	y = 1.04x + 0.20 r = 0.996 SD (md 95) = 0.393	N/A

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

Method Comparison Test Set (ONLINE TDM Tobramycin Vs. COBAS FP Tobramycin):
- Sample Size: N=55
- Range: 0.2 - 9 µg/ml
- Data Provenance: Not explicitly stated, but typically these studies are conducted with human serum or plasma samples within a lab setting. It is not specified if the data is retrospective or prospective.
Method Comparison Test Set (COBAS FP Tobramycin Vs. COBAS FARA II - likely predicate's original validation data, included for context):
- Sample Size: N=196
- Range: 0.23 - 10 ug/ml
- Data Provenance: Not explicitly stated.

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

This information is not provided in the document. For in vitro diagnostic assays, "ground truth" is typically established by reference methods or comparison to a well-established, legally marketed predicate device, rather than expert consensus on individual cases.

4. Adjudication method for the test set:

This information is not applicable/not provided as the study design focuses on quantitative comparison of assay results rather than subjective interpretations requiring 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:

This is not an MRMC comparative effectiveness study involving human readers and AI assistance. The device is an in vitro diagnostic assay for quantitative measurement, not an imaging or interpretive AI device.

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

Yes, the performance data presented (precision, method comparison) represents the standalone performance of the ONLINE TDM Tobramycin assay (algorithm/assay only) without human intervention in the result generation process, beyond standard laboratory procedures for running the assay.

7. The type of ground truth used:

The ground truth (or reference standard) for evaluating the ONLINE TDM Tobramycin assay was the results obtained from the predicate device, COBAS INTEGRA Tobramycin (K964457). For method comparison, the predicate device's results are treated as the reference against which the new device's results are compared.

8. The sample size for the training set:

This information is not applicable/not provided. The ONLINE TDM Tobramycin assay is a chemical assay, not an AI or machine learning model that requires a "training set" in the conventional sense. The "training" for such an assay involves the development and optimization of the reagent formulation and assay protocols, which is not quantified by a "sample size."

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

This information is not applicable/not provided as the concept of a "training set" and "ground truth for training" does not directly apply to the development of this type of chemical assay. Assay development involves analytical validation against known standards and reference materials to ensure accuracy and precision.

Summary

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JUN - 9 2006

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510(k) Summary

Introduction	According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
1) Submitter name, address, contact	Roche Diagnostics Corporation 9115 Hague Rd. Indianapolis, IN 46250 (317) 521-7688 Contact Person: Dimitris Demirtzoglou
2) Device name	Proprietary name: ONLINE TDM Tobramycin
	Common name: RADIOIMMUNOASSAY, TOBRAMYCIN
	Classification name: RADIOIMMUNOASSAY, TOBRAMYCIN
3) Predicate device	We claim substantial equivalence to the currently marketed COBAS INTEGRA Tobramycin (K964457).

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510(k) Summary, Continued

4) Device Description

Tobramycin is an aminoglycoside antibiotic used in the treatment of infections caused by Pseudomonas aeruginosa, Proteus species, E. coli, Klebsiella, Serratia, Citrobacter, Staphylococcus aureus, Enterobacter and other microorganisms. Tobramycin's toxic effect is produced by interfering with ribosomal protein synthesis. Tobramycin undergoes very little, if any, metabolization and is, therefore, eliminated as the parent drug by glomerular filtration. The half-life of tobramycin in serum or plasma correlates closely with renal function and thus is quite variable between individuals and within one individual over time.2,3 Serum or plasma tobramycin concentration is also impacted by mode of administration, the volume of extracellular fluid, the duration of the treatment and physiological changes during the illness and therapy. The therapeutic range of tobramycin should be measured at peak as well as trough concentrations. In patients with pre-existing renal damage or those to whom tobramycin has been administered for prolonged periods or in doses above the therapeutic range, hearing impairment and/or nephrotoxicity may develop. Therefore, monitoring of peak and trough tobramycin serum or plasma levels is critical in the prevention of these serious complications with the adjustment of dosage administration as indicated.

5.) Intended Use

The ONLINE TDM Tobramycin assay is for the quantitative determination of tobramycin in human serum or plasma on Roche automated clinical chemistry analyzers.

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510(k) Summary, Continued

The Roche ONLINE TDM Tobramycin assay is substantially equivalent to 6.) Comparison to the Predicate other products in commercial distribution intended for similar use. Most Device notably, it is substantially equivalent to the currently marketed Roche COBAS INTEGRA Tobramycin (K964457).

The Roche ONLINE TDM Tobramycin assay was evaluated for several performance characteristics including precision, lower detection limit, method comparison, specificity, and interfering substances. All of the evaluation studies gave acceptableresults compared to the predicate device. These experiments provide evidence that the Roche ONLINE TDM Tobramycin assay is substantially equivalent to the currently marketed Roche COBAS INTEGRA Tobramycinassay. The following table summarizes the precision and method comparison results.

	Roche ONLINE TDM N-			Roche COBAS FP
	acetylTobramycin			Tobramycin(Predicate)
NCCLS Precision,	Control 1	Control 2	Control 3	Control 1	Control 2	Control 3
Within run
Mean (µg/ml)	1.3	4.2	7.1	1.4	3.5	7.5
SD (µg/ml)	0.05	0.04	0.04	0.04	0.07	0.14
CV%	3.9	0.9	0.6	2.6	2.1	1.9
NCCLS Precision,	Control 1	Control 2	Control 3	Control 1	Control 2	Control 3
Total
Mean (µg/ml)	1.3	4.2	7.1	1.4	3.5	7.5
SD (µg/ml)	0.07	0.07	0.09	0.09	0.16	0.30
CV%	5.2	1.7	1.3	6.0	4.5	4.0
Method	Linear Regression: ONLINE TDM			Linear Regression: COBAS FP Tobramycin
Comparison	Tobramycin Vs. COBAS FP Tobramycin			Vs. COBAS FARA II

	N=55, Range = 0.2 - 9 µg/ml
	y = 1.04x + 0.20			N=196, Range = 0.23 - 10 ug/ml
	r = 0.996			y=0.930x - 0.090
	SD (md 95) = 0.393			r=0.995

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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 caduceus symbol, which is a staff with two snakes coiled around it. The logo is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement. The text is in all capital letters and is evenly spaced around the logo.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN - 9 2006

Mr. Dimitris Demirtzoglou Regulatory Affairs Consultant Roche Diagnostics Corp. 9115 Hague Road Indianapolis, IN 46250-0457

Re: K060853

Trade/Device Name: ONLINE TDM Tobramycin Regulation Number: 21 CFR §862.3900 Regulation Name: Tobramycin test system Regulatory Class: Class II Product Code: KLB Dated: March 28, 2006 Received: March 29, 2006

Dear Mr. Demirtzoglou:

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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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 vours.

Alberto Gutierrez, Ph.D.

Alberto Gutierrez, Ph.D. 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): K O60 & S

Device Name: ONLINE TDM Tobramycin

Indications For Use:

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 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)

CLC

Office
Device

Diagnostic
and Safety

00000 Kolo0853

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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.