ENZYME IMMUNOASSAY, VANCOMYCIN by ROCHE DIAGNOSTICS CORP.

The ONLINE TDM Vancomycin assay is for the quantitative determination of vancomycin in human serum or plasma on Roche automated clinical chemistry analyzers. Measurements obtained by this device are used in the diagnosis and treatment of vancomycin overdose and in monitoring the level of vancomycin to ensure appropriate therapy.

Device Description

The ONLINE TDM Vancomycin assay is for the quantitative determination of vancomycin 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 Vancomycin reagent kits. The assay is based on a homogeneous enzyme immunoassay technique used for the quantitative analysis of vancomycin in human serum or plasma. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the sample can be measured in terms of enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that is measured spectrophotometrically. Endogenous serum G6PDH does not interfere because the coenzyme functions only with the bacterial (Leuconostoc mesenteroids) enzyme employed in the assay.

AI/ML Overview

The provided document describes the ONLINE TDM Vancomycin assay, intended for the quantitative determination of vancomycin in human serum or plasma.

Here's an analysis of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" as a set of predefined thresholds that the device must meet. Instead, it presents performance characteristics (precision and method comparison) and states that "All of the evaluation studies gave acceptable results compared to the predicate device." The comparison is implicitly against the performance of the predicate device, COBAS INTEGRA Vancomycin (K954992).

The table below summarizes the reported performance of the new device and the predicate device for comparison:

Performance Characteristic	ONLINE TDM Vancomycin (New Device)	COBAS INTEGRA Vancomycin (Predicate Device)	Implied Acceptance/Description
NCCLS Precision, Within run			"Acceptable results compared to the predicate device."
Control 1 Mean (µg/ml)	6.8	3.8
Control 1 SD (µg/ml)	0.34	0.08
Control 1 CV%	4.9	2.2
Control 2 Mean (µg/ml)	21.0	8.6
Control 2 SD (µg/ml)	0.29	0.17
Control 2 CV%	1.4	1.9
Control 3 Mean (µg/ml)	39.1	14.7
Control 3 SD (µg/ml)	0.45	0.31
Control 3 CV%	1.1	2.1
NCCLS Precision, Total			"Acceptable results compared to the predicate device."
Control 1 Mean (µg/ml)	6.8	3.8
Control 1 SD (µg/ml)	0.40	0.12
Control 1 CV%	5.8	3.0
Control 2 Mean (µg/ml)	21.0	8.6
Control 2 SD (µg/ml)	0.60	0.24
Control 2 CV%	2.9	2.8
Control 3 Mean (µg/ml)	39.1	14.7
Control 3 SD (µg/ml)	1.04	0.52
Control 3 CV%	2.7	3.6
Method Comparison (ONLINE TDM Vancomycin Vs. COBAS INTEGRA Vancomycin)	Sample Size (N)=55, Range = 5.0-67.2 µg/ml		"Acceptable results compared to the predicate device."
Linear Regression	y=1.038x - 0.094		Desired: closer to y=x (slope 1, intercept 0).
Correlation Coefficient (r)	0.991		Desired: closer to 1.0.

Note on Method Comparison Table: The document's method comparison section is a bit confusing. It lists a "Linear Regression: ONLINE TDM Carbamazepine Vs. COBAS INTEGRA Carbamazepine (FPIA) method" for the new device and then "Linear Regression: COBAS INTEGRA Carbamazepine (FPIA) Vs. COBAS FARA II" for the predicate. Since the device under review is for Vancomycin, the listing of "Carbamazepine" in the method comparison for the new device appears to be a typographical error or an irrelevant comparison. Assuming this is a typo and should refer to Vancomycin, the listed regression equation and correlation coefficient are for the new device against the predicate.

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

Sample Size for Method Comparison (Test Set): N=55
Data Provenance: Not explicitly stated in the document (e.g., country of origin, retrospective or prospective).

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

This information is not provided in the document. The studies listed are analytical performance studies (precision, method comparison) comparing the new device against a predicate device, not clinical studies involving expert interpretation of patient samples where "ground truth" would be established by experts.

4. Adjudication Method for the Test Set

This information is not applicable/provided. The studies are analytical performance comparisons, not clinical evaluations requiring adjudication of expert interpretations.

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

An MRMC study was not done for this device submission. This is an in-vitro diagnostic device measuring a chemical analyte, not an imaging or diagnostic interpretation device where human readers would be involved.

6. Standalone (Algorithm Only) Performance

The device itself is an automated assay, meaning its performance is inherently standalone (algorithm/analyzer only). The precision and method comparison studies directly evaluate this standalone performance. No human-in-the-loop performance is expected or evaluated for this type of device.

7. Type of Ground Truth Used

For the method comparison study, the "ground truth" or reference method was the predicate device, COBAS INTEGRA Vancomycin (K954992). The new device's measurements were compared against the measurements obtained by this established and legally marketed predicate device.

For the precision studies, the "ground truth" is typically the known concentration of vancomycin in control materials, against which the device's variability is assessed.

8. Sample Size for the Training Set

This information is not provided in the document. For an immunoassay like this, there isn't typically a "training set" in the machine learning sense. The device is developed and validated through analytical studies.

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

This information is not applicable/provided. As mentioned above, a "training set" in the machine learning context is not relevant for this type of immunoassay device. The assay development would involve optimizing reagents and conditions, and its performance is then characterized by analytical validation studies against known standards and comparative methods.

Summary

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Ko60586

MAY 11 2006

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 Corporation9115 Hague Rd.Indianapolis, IN 46250(317) 521-7688
	Contact Person: Dimitris Demirtzoglou
	Date Prepared: February 28, 2006
2) Device name	Proprietary name: ONLINE TDM Vancomycin
	Common name: Enzyme Immunoassay, Vancomycin
	Classification name: RADIOIMMUNOASSAY, VANCOMYCIN
3) Predicate device	We claim substantial equivalence to the currently marketed COBAS INTEGRA Vancomycin (K954992).

Continued on next page

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510(k) Summary, Continued

Device The ONLINE TDM Vancomycin assay is for the quantitative Description determination of vancomycin 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 Vancomycin reagent kits. The assay is based on a homogeneous enzyme immunoassay technique used for the quantitative analysis of vancomycin in human serum or plasma.8 The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for antibody binding sites. Enzyme activity decreases upon binding to the antibody, so the drug concentration in the sample can be measured in terms of enzyme activity. Active enzyme converts oxidized nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that is measured spectrophotometrically. Endogenous serum G6PDH does not interfere because the coenzyme functions only with the bacterial (Leuconostoc mesenteroids) enzyme employed in the assay. 5.) Intended The ONLINE TDM Vancomycin assay is for the quantitative Use determination of vancomycin in human serum or plasma on Roche automated clinical chemistry analyzers. Continued on next page

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510(k) Summary, Continued

The Roche ONLINE TDM Vancomycin 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 Vancomycin assay (K954992).

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

	Roche ONLINE TDM Vancomycin			Roche COBAS INTEGRA Vancomycin(Predicate)
NCCLS Precision,Within run	Control 1	Control 2	Control 3	Control 1	Control 2	Control 3
Mean (µg/ml)	6.8	21.0	39.1	3.8	8.6	14.7
SD (µg/ml)	0.34	0.29	0.45	0.08	0.17	0.31
CV%	4.9	1.4	1.1	2.2	1.9	2.1
NCCLS Precision,Total	Control 1	Control 2	Control 3	Control 1	Control 2	Control 3
Mean (µg/ml)	6.8	21.0	39.1	3.8	8.6	14.7
SD (µg/ml)	0.40	0.60	1.04	0.12	0.24	0.52
CV%	5.8	2.9	2.7	3.0	2.8	3.6
MethodComparison	Linear Regression: ONLINE TDMCarbamazepine Vs. COBAS INTEGRACarbamazepine (FPIA) method.			Linear Regression: COBAS INTEGRACarbamazepine (FPIA) Vs. COBAS FARA II
	N=55, Range = 5.0-67.2 µg/mly=1.038x - 0.094r=0.991			N=193, Range = 1.41-68.1 µg/mly=0.958x - 0.386r=0.995

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Dimitris Demirtzoglou Regulatory Affairs Consultant Roche Diagnostic Corp. 9115 Hague Rd. Indianapolis, IN 46250

MAY 1 1 2006

Re: K060586

Trade/Device Name: ONLINE TDM Vancomycin Regulation Number: 21 CFR8862.3950 Regulation Name: Vancomycin test system Regulatory Class: Class II Product Code: LEH Dated: March 6, 2006 Received: March 7. 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 no 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 (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 mber (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Alberto G
Alberto Gutie PhD

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):

60586

Device Name: ONLINE TDM Vancomycin

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)

A.C.W.

Not Valid Sign-Off

Office of In Vitro Diagnostic Device Brunnerion and Salery

Page 1 of

L060586

Regulation Number and Section

§ 862.3950 Vancomycin test system.

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