The Roche ONLINE Theophylline assay contains an in vitro diagnostic reagent system indicated for the quantitative determination of theophylline, a broncodilator, widely used to treat patients with asthma, apnea (temporary asphyxia), and other obstructive lung diseases. 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.

Device Description

The Roche ONLINE Theophylline assay contains an in vitro diagnostic reagent system indicated for the quantitative determination of theophylline, a bronchodilator, widely used to treat patients with asthma, apnea (temporary asphyxia), and other obstructive lung diseases, in human serum or plasma on automated clinical chemistry analyzers. Measurements obtained by the device are used in the diagnosis and treatment of theophylline overdose and in monitoring levels of theophylline to ensure appropriate therapy. The proposed labeling indicates that the Roche/Hitachi 911, 912, 917, and Modular P analyzers can be used with the Roche ONLINE Theophylline reagent kits.

AI/ML Overview

Here's an analysis of the provided text regarding the "Roche ONLINE Theophylline Assay" and its acceptance criteria and study:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state quantitative acceptance criteria in terms of pre-defined thresholds. Instead, it states that "All of the evaluation studies gave acceptable results compared to the predicate device." This implies that the acceptance criteria were met if the performance of the new device was "substantially equivalent" to the predicate device.

To infer the acceptance criteria, we can look at the performance of the predicate device and the new device. A common approach for method comparison studies for medical diagnostics is to demonstrate a strong correlation (R-value close to 1) and a slope close to 1 with an intercept close to 0, indicating minimal proportional and constant bias. For precision, the CV% should be comparable or better.

Performance Metric	Acceptance Criteria (Inferred from Predicate)	Roche ONLINE Theophylline (New Device) Performance	Roche COBAS INTEGRA Theophylline (Predicate Device) Performance
Method Comparison
n	Sufficient sample size for statistical significance (e.g., n > 100)	103	138
Slope (y vs x)	Close to 1 (e.g., 0.95 - 1.05)	0.976	0.963
Intercept (y vs x)	Close to 0 (e.g., within +/- 0.1)	0.011	0.065
Correlation Coefficient (R)	Close to 1 (e.g., > 0.98 for strong correlation in diagnostics)	0.996	0.998
Range	Clinically relevant range and covering normal/therapeutic/toxic levels	0.62 to 39.6 µg/mL	0.16 to 36.3 µg/mL
Precision
CV% (within run)	Low, consistent across levels. Comparable to or better than predicate (Level 1, 2, 3)	L1: 1.0, L2: 0.5, L3: 0.9	L1: 1.6, L2: 1.9, L3: 1.8
CV% (total)	Low, consistent across levels. Comparable to or better than predicate (Level 1, 2, 3)	L1: 1.9, L2: 1.7, L3: 2.1	L1: 2.6, L2: 2.6, L3: 2.8

Study That Proves the Device Meets Acceptance Criteria:

The study conducted was a performance characteristic evaluation comparing the "Roche ONLINE Theophylline Assay" against the "Roche COBAS INTEGRA Theophylline Assay" (predicate device). The study assessed precision, lower detection limit, method comparison, specificity, and interfering substances. The provided data focuses on precision and method comparison.

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

Sample Size for Test Set (Method Comparison):
- Roche ONLINE Theophylline (new device): n = 103
- Roche COBAS INTEGRA Theophylline (predicate device): n = 138 (This value is for the predicate's comparison against another assay, not directly against the new device for this study. The n=103 is the relevant sample size for comparing the new device to the predicate).
Data Provenance: Not explicitly stated. However, given that this is an in-vitro diagnostic device manufactured by Roche Diagnostics Corporation in Indianapolis, IN, it is highly likely the data was collected from clinical samples, possibly from multiple sites, but the geographical origin (e.g., country) is not specified. The study is retrospective, as it compares a new assay's results to an existing, legally marketed assay.

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

This information is not provided in the document. For chemical assays like this, "ground truth" often refers to a reference method or a highly accurate, often more laborious, laboratory method. It doesn't typically involve human expert consensus in the same way as medical imaging or clinical diagnoses. The comparison here is against a legally marketed predicate device, not necessarily a "ground truth" reference method established by experts.

4. Adjudication Method for the Test Set

This information is not applicable and therefore not provided. Adjudication methods (like 2+1, 3+1) are common in studies where human interpretation of data (e.g., medical images) can be subjective and multiple readers are involved. For an automated chemical assay comparing numerical results, adjudication by experts is not a standard practice. The comparison is objective, based on direct numerical results between the new device and the predicate device.

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 information is not applicable. This is an in-vitro diagnostic device (a laboratory blood test), not an AI-powered diagnostic tool for human interpretation of complex data (like radiology images). Therefore, MRMC studies and the concept of human readers improving with AI assistance are not relevant to this device.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done

Yes, this study is inherently a standalone performance study of the device (assay and associated analyzers). The "Roche ONLINE Theophylline Assay" itself is an automated chemical analysis system. The performance metrics presented (method comparison, precision) are reflective of the assay's performance without direct human intervention in the result generation process beyond operating the analyzer and collecting samples.

7. The Type of Ground Truth Used

The "ground truth" in this context is the performance of the legally marketed predicate device (Roche COBAS INTEGRA Theophylline Assay). The study seeks to establish substantial equivalence to this predicate, meaning the new device performs sufficiently similarly. It's not using an independent, gold-standard "ground truth" like pathology or long-term clinical outcomes data, but rather a comparative standard.

8. The Sample Size for the Training Set

This information is not provided and is likely not applicable in the traditional sense for this type of device. The "Roche ONLINE Theophylline Assay" is a chemical reagent system. While there would have been extensive R&D and validation during its development (which might involve testing many samples), these are not typically referred to as a "training set" for an algorithm in the way that machine learning models use them. Chemical assays are developed based on chemical principles and optimized through experimentation, not "trained" on data.

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

As explained above, the concept of a "training set" and its "ground truth" in the context of machine learning is generally not applicable to this chemical assay. The development process would have involved establishing the accuracy and reliability of the chemical reactions and measurement principles through controlled experiments and analytical studies, rather than using a labelled dataset for algorithmic training.

Summary

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APR 1 6 2002

K020740

Roche ONLINE Theophylline Assay

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) 845-2000Contact Person: Mike FlisDate Prepared: April 2, 2002
2) Device name	Roche ONLINE Theophylline
3) Predicate device	We claim substantial equivalence to the COBAS INTEGRA Theophylline assay.
4) Device Description	The Roche ONLINE Theophylline assay contains an in vitro diagnostic reagent system indicated for the quantitative determination of theophylline, a bronchodilator, widely used to treat patients with asthma, apnea (temporary asphyxia), and other obstructive lung diseases, in human serum or plasma on automated clinical chemistry analyzers. Measurements obtained by the device are used in the diagnosis and treatment of theophylline overdose and in monitoring levels of theophylline to ensure appropriate therapy. The proposed labeling indicates that the Roche/Hitachi 911, 912, 917, and Modular P analyzers can be used with the Roche ONLINE Theophylline reagent kits.
5) Intended use	For the quantitative determination of theophylline in human serum or plasma on automated clinical chemistry analyzers.

Continued on next page

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510(k) Summary, continued

The Roche ONLINE Theophylline was evaluated for several performance 6) Comparison characteristics, including precision, lower detection limit, method to predicate comparison, specificity, and interfering substances. All of the evaluation device studies gave acceptable results compared to the predicate device. These experiments provide evidence that the Roche ONLINE Theophylline Assay is substantially equivalent to the currently marketed Roche COBAS INTEGRA Theophylline Assay. The following table presents the precision and method comparison results.

Roche ONLINE Theophylline				Roche COBAS INTEGRATheophylline (Predicate)
Roche/Hitachi 917 versus Theophylline assay				Versus COBAS FARA II Theophylline
on the COBAS INTEGRA 700				assay
n = 103				n = 138
$y = 0.976x + 0.011$				$y = 0.963x + 0.065$
R = 0.996				R = 0.998
Range = 0.62 to 39.6 μg/mL				Range = 0.16 to 36.3 μg/mL
Precision:	Level 1	Level 2	Level 3	Level 1	Level 2	Level 3
Mean (μg/mL)	4.87	14.51	24.31	5.4	14.2	22.5
CV% (within run)	1.0	0.5	0.9	1.6	1.9	1.8
CV% (total)	1.9	1.7	2.1	2.6	2.6	2.8

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/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 text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with flowing lines representing hair or clothing.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Mike Flis Regulatory Affairs Principal Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, Indiana 46250-0457

Re: K020740

Trade/Device Name: Roche ONLINE Theophylline Regulation Number: 21 CFR § 862.3880 Regulation Name: Theophylline Test System Regulatory Class: II Product Code: KLS Dated: March 1, 2002 Received: March 6, 2002

Dear Mr. Flis:

This letter corrects the letter dated April 9, 2002. The indications for use, was amended by Roche and a copy of new indications for use has been added to the file. 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.

APR 2 4 2002

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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2

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" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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,

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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Roche Diagnostics Corporation

510(k) Number (if known): K020740 Device Name: Roche ONLINE Theophylline Assay Indications for Use:

Dan Cooper
(Division Sign-Off)

Division of Clinical Laboratory Devices

510(k) Number K020740

(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)

Over-The-Counter Use

(Optional Format 1-2-96)

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.