The cassette COBAS Integra Serum Barbiturates contains and in vitro diagnostic reagent system intended for use on the COBAS INTEGRA analyzer for the detection of barbiturates and their metabolites in human serum, heparinized plasma or urine. This reagent system is intended for use in toxicological screenings where the analytical result is used in the management of barbiturate use or overdose.

Device Description

The COBAS INTEGRA Serum Barbiturates assay is an in vitro diagnostic reagent for use on the COBAS INTEGRA systems for the detection of barbiturates and their metabolites in plasma, serum or urine. This reagent system is intended for use in toxicological screenings where the analytical result is used in the management of barbiturate use or overdose. The COBAS INTEGRA Serum Barbiturates assay is based on fluorescence polarization (FP) methodology. Fluorescence polarization measures the change in angle of polarized light emitted by a fluorescent molecule. This change in polarization is dependent on molecule rotation, which is dependent on molecule size. FP utilizes a homogeneous competitive binding immunoassay with particle-bound fluorescein-labeled drug derivative to detect barbiturates and their metabolites in unknown samples. In the absence of sample drug, free antibody (R1) binds to fluorescein-labeled drug derivative (R3), causing the fluorescein-labeled drug derivative to rotate slowly. The large complex rotates more slowly than the free fluoresceinlabeled drug derivative in solution, thereby causing the light emitted to remain highly polarized. When a urine sample contains the drug in question, this drug competes with the fluorescein-labeled drug derivative for antibody. The small fluoresceinlabeled drug derivative molecules will rotate rapidly in solution and the emitted light will be depolarized. The large molecules (antibody bound to fluorescein labeled drug) will rotate slowly and the light emitted will remain highly polarized. Large molecules = slow rotation = polarized light retained = high polarization Small molecules = rapid rotation = depolarized light = low polarization Unknown sample drug content is determined relative to the value obtained from samples of known drug content, which have been used to establish a standard curve. The presence of drug decreases polarization in proportion to the concentration of drug in the sample.

AI/ML Overview

The provided text does not contain detailed information about the acceptance criteria or a specific study proving the device meets these criteria. The document is primarily a 510(k) summary for the Roche COBAS INTEGRA Serum Barbiturates assay, focusing on its substantial equivalence to a predicate device and its intended use.

However, based on the information provided, here's what can be inferred and what is missing:

Acceptance Criteria and Device Performance

The document does not explicitly state acceptance criteria in a table format or present specific performance metrics from a study to demonstrate compliance. It generally states that "The assay performance characteristics for urine and serum samples are extremely similar" to the predicate device.

Missing Information:

Specific quantitative acceptance criteria (e.g., sensitivity, specificity, accuracy against a gold standard, precision, linearity ranges, cutoff values).
Detailed performance data (e.g., test results, statistical analysis) that would show the device meets these unstated criteria.

Study Details

Given the nature of a 510(k) summary for an in vitro diagnostic device, the "study" demonstrating performance would typically involve analytical and possibly some clinical validation against a known ground truth. However, specific details of such studies are largely absent.

1. A table of acceptance criteria and the reported device performance:

Acceptance Criteria (Inferred from common IVD submissions)	Reported Device Performance (as stated in the document)
Analytical performance similar to predicate device	"The assay performance characteristics for urine and serum samples are extremely similar [to the predicate device]."

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

Sample Size for Test Set: Not specified.
Data Provenance (e.g., country of origin, retrospective or prospective): Not specified.

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

Number of Experts: Not specified.
Qualifications of Experts: Not specified. (For an IVD like this, ground truth is typically established by reference methods or clinical diagnosis, not necessarily by "experts" in the sense of image interpretation).

4. Adjudication method for the test set:

Adjudication Method: Not specified.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done:

No, an MRMC study is not typically applicable or mentioned for this type of in vitro diagnostic assay. MRMC studies are usually relevant for imaging devices where human readers interpret results, and the AI's impact on their performance is evaluated.

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

Yes, for an in vitro diagnostic device, the performance characteristics described are inherently "standalone," meaning they represent the algorithm (assay system) itself determining the presence or concentration of barbiturates in a sample. The device operates without human-in-the-loop decision making for the analytical result.

7. The type of ground truth used:

Type of Ground Truth: Not explicitly stated. For in vitro diagnostic assays, ground truth is typically established against:
- Reference Methods: Such as Gas Chromatography-Mass Spectrometry (GC-MS) or Liquid Chromatography-Mass Spectrometry (LC-MS) for drug detection.
- Clinically Confirmed Samples: Samples from patients with known barbiturate use or overdose, or samples spiked with known concentrations of barbiturates.
  While not explicitly mentioned, it can be inferred that a combination of these methods would have been used for an IVD.

8. The sample size for the training set:

Sample Size for Training Set: Not specified. For this type of homogeneous fluorescence immunoassay, "training" is less about machine learning algorithms and more about establishing standard curves and calibrating the instrument. The "training set" would correspond to the samples used to establish these curves and confirm assay parameters.

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

Ground Truth for Training Set: Not specified. Similar to the test set, ground truth for calibrator and control samples would be established using highly accurate reference methods or by gravimetric preparation of known concentrations of barbiturates. This ensures the standard curve accurately reflects drug concentrations.

Summary

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JUN 2 2 1999

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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 Corporation9115 Hague RdIndianapolis, IN 46250(317) 845-3362
	Contact person: Lisa M. Gerard
	Date prepared April 23, 1999
2) Device name	Proprietary name: Roche COBAS INTEGRA Serum Barbiturates
	Common name: Homogeneous fluorescence immunoassay for the determination of barbiturates in plasma, serum and urine
	Classification name: Enzyme Immunoassay, Barbiturates test system
3) Predicate device	We claim substantial equivalence to the Roche COBAS INTEGRA Serum Barbiturates (K982551).

Continued on next page

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510(k) Summary, Continued

The COBAS INTEGRA Serum Barbiturates assay is an in vitro diagnostic 4) Device reagent for use on the COBAS INTEGRA systems for the detection of description barbiturates and their metabolites in plasma, serum or urine. This reagent system is intended for use in toxicological screenings where the analytical result is used in the management of barbiturate use or overdose. The COBAS INTEGRA Serum Barbiturates assay is based on fluorescence polarization (FP) methodology. Fluorescence polarization measures the change in angle of polarized light emitted by a fluorescent molecule. This change in polarization is dependent on molecule rotation, which is dependent on molecule size. FP utilizes a homogeneous competitive binding immunoassay with particle-bound fluorescein-labeled drug derivative to detect barbiturates and their metabolites in unknown samples. In the absence of sample drug, free antibody (R1) binds to fluorescein-labeled drug derivative (R3), causing the fluorescein-labeled drug derivative to rotate slowly. The large complex rotates more slowly than the free fluoresceinlabeled drug derivative in solution, thereby causing the light emitted to remain highly polarized. When a urine sample contains the drug in question, this drug competes with the fluorescein-labeled drug derivative for antibody. The small fluoresceinlabeled drug derivative molecules will rotate rapidly in solution and the emitted light will be depolarized. The large molecules (antibody bound to fluorescein labeled drug) will rotate slowly and the light emitted will remain highly polarized. Large molecules = slow rotation = polarized light retained = high polarization Small molecules = rapid rotation = depolarized light = low polarization Unknown sample drug content is determined relative to the value obtained from samples of known drug content, which have been used to establish a standard curve. The presence of drug decreases polarization in proportion to the concentration of drug in the sample.

Continued on next page

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510(k) Summary, Continued

The cassette COBAS INTEGA Serum Barbiturates contains an in vitro 5) Intended use diagnostic reagent intended for use on the COBAS INTEGRA analyzer for the detection of barbiturates and their metabolites in human serum, heparinized plasma or urine.

The Roche COBAS INTEGRA Serum Barbiturates and the predicate device 6) Comparison use the same reagents, on the same analyzer. The Roche COBAS INTEGRA to the predicate device, Serum Barbiturates assay has been modified to include parameters for urine similarities samples. The assay performance characteristics for urine and serum samples are extremely similar.

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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 circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, rendered in black.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 2 2 1999

Ms. Lisa M. Gerard Regulatory Affairs Consultant Roche Diagnostics Corporation 9115 Hague Road PO Box 50457 Indianapolis, Indiana 46250-0457

Re: K991440

Trade Name: Roche COBAS INTEGRA Serum Barbiturates (SBARB) Regulatory Class: II Product Code: DIS Dated: April 23, 1999 Received: April 26, 1999

Dear Ms. Gerard:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers 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,

Steven Sutman

Steven I. Gutman, M.D. M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

..............................................................................................................................................................................

510(k) Number (if known):	K991440
Device Name:	Roche COBAS INTEGRA Serum Barbiturates
Indications for Use:	The cassette COBAS Integra Serum Barbiturates contains and in vitro diagnostic reagent system intended for use on the COBAS INTEGRA analyzer for the detection of barbiturates and their metabolites in human serum, heparinized plasma or urine. This reagent system is intended for use in toxicological screenings where the analytical result is used in the management of barbiturate use or overdose.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109)	OR	Over-the-Counter Use __
(Optional format 1-2-96)	Dan Cooper (Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number K991440

Regulation Number and Section

§ 862.3150 Barbiturate test system.

(a)
Identification. A barbiturate test system is a device intended to measure barbiturates, a class of hypnotic and sedative drugs, in serum, urine, and gastric contents. Measurements obtained by this device are used in the diagnosis and treatment of barbiturate use or overdose and in monitoring levels of barbiturate to ensure appropriate therapy.(b)
Classification. Class II (special controls). A barbiturate test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).