(24 days)
The ACS:180 and ADVIA Centaur Theophylline 2 Immunoassays are competitive, chemiluminescence immunoassay for the quantitative determination of theophylline in human serum and plasma for use on the automated analyzer manufactured by Bayer Corporation. Theophylline (1,3-dimethylxanthine) is a potent bronchodilator and is very important in the treatment of asthma. Monitoring a patient's theophylline level is very important in reducing the risks of over or under-medication resulting from the wide inter-patient variation in theophylline absorption, metabolism and excretion. The ACS and ADVIA Centaur Theophylline 2 immunoassays are used as an aid to monitor a patient's theophylline level.
The ACS and ADVIA Centaur Theophylline 2 are competitive chemiluminescence immunoassays are intended for the quantitative determination of theophylline in human serum and plasma. Theophylline in the patient sample, calibrators, standards and controls competes with acridinium ester-labeled theophylline in the Lite Reagent for a limited amount of monoclonal mouse anti-theophylline antibody, which is covalently coupled to paramagnetic particles in the Solid Phase. Following incubation, unreacted acridinium esterlabeled theophylline and unreacted theophylline from the sample are washed from the reaction mixture. The chemiluminescence of the reacted, labeled theophylline is measured in a luminometer. The measured chemiluminescence is inversely proportional to the quantity of theophylline in the sample.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Bayer Diagnostics Theophylline 2 Immunoassays:
Acceptance Criteria and Device Performance Study for Bayer Diagnostics Theophylline 2 Immunoassays
The submission describes the substantial equivalence of the new ACS and ADVIA Centaur Theophylline 2 Immunoassays to the predicate ACS Theophylline assay. The primary method for demonstrating this equivalence is through method comparison studies, which establish correlation between the new devices and the predicate.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria here are implied by the "substantial equivalence" claim and the reported correlation results, which generally aim for a high correlation coefficient (close to 1) and slopes close to 1 with intercepts close to 0, indicating strong agreement between methods.
| Acceptance Criteria (Implied) | Reported Device Performance (Slope) | Reported Device Performance (Intercept) | Reported Device Performance (Correlation Coefficient, r) |
|---|---|---|---|
| Slope ≈ 1.00 | 0.94 (ADVIA Centaur Theophylline 2 vs. ACS Theophylline) | 1.36 | 0.99 |
| 1.00 (ACS Theophylline 2 vs. ACS Theophylline) | -0.24 | 0.99 | |
| 1.05 (ADVIA Centaur Theophylline 2 vs. ACS Theophylline 2) | -0.9 | 0.99 | |
| Intercept ≈ 0.00 | |||
| Correlation Coefficient (r) > 0.95 (Typical for substantial equivalence) | 0.99 | 0.99 | 0.99 |
Interpretation: All reported correlation coefficients are 0.99, demonstrating excellent agreement. The slopes are close to 1 (0.94, 1.00, 1.05) and intercepts are relatively small (-0.24, -0.9, 1.36), indicating that the new assays perform very similarly to the predicate and to each other.
2. Sample Size and Data Provenance
- Sample Size for Test Set: N = 138 for each comparison.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). It is implied to be human serum and plasma samples based on the intended use.
3. Number of Experts and Qualifications for Ground Truth
- This type of immunoassay study typically does not involve human experts to establish "ground truth" in the way, for example, an imaging study would for disease diagnosis.
- The "ground truth" or reference standard for comparison in this context is the predicate device's performance (ACS Theophylline Assay, K951169). The assumption is that the predicate device's measurements are a reliable reference.
4. Adjudication Method
- None applicable. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies where multiple experts independently review cases to establish a consensus ground truth, often for subjective assessments or complex diagnoses. This is not relevant for an immunoassay comparison study where numerical values are being compared.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
- No. An MRMC study is not mentioned and would not be applicable to an immunoassay device. MRMC studies are used to evaluate the impact of human readers (e.g., radiologists, pathologists) on diagnostic accuracy, often with and without AI assistance. This device is a standalone diagnostic test that produces a quantitative result.
6. Standalone (Algorithm Only) Performance
- Yes. This entire study evaluates the standalone performance of the new immunoassay devices. They are designed to provide quantitative results directly from serum or plasma samples. There is no human-in-the-loop performance component described; the devices measure theophylline levels directly.
7. Type of Ground Truth Used
- Comparison to a Predicate Device's Measurements: The ground truth for this evaluation is defined by the measurements obtained from the existing, legally marketed ACS Theophylline Assay (predicate device K951169). The study seeks to prove that the new devices provide equivalent measurements to this established predicate.
8. Sample Size for Training Set
- Not explicitly stated/not applicable in this context. Immunoassays, by their nature, are typically developed and optimized during formulation and manufacturing, and then validated through performance studies like method comparisons. The term "training set" is more commonly associated with machine learning algorithms. While there would have been internal development and validation during the assay optimization phase, it's not described as a "training set" in the context of this 510(k) submission.
9. How Ground Truth for Training Set was Established
- Not applicable/Not described. As mentioned above, the concept of a "training set ground truth" as used in machine learning is not directly applicable here. The "ground truth" in the validation study refers to the results from the established predicate device. For the development and initial calibration of the new assays, it would typically involve using reference materials with known concentrations of theophylline.
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Bayer Diagnostics
ASC and ADVIA Centaur Theophylline 2 Immunoassays
As required by 21 CFR 807.92, the following 510(k) Summary is provided:
4.1 Submitter Information
Kenneth T. Edds Ph.D. Contact person: Bayer Diagnostics Corporation Address: 511 Benedict Ave. Tarrytown NY 10591
Phone: 914-524-2446 FAX: 914-524-2500 e-mail: ken.edds.b@bayer.com
4.2 Modified device information
| Proprietary name: | ADVIA Centaur and ACSTheophylline 2 Immunoassays |
|---|---|
| Common name: | Theophylline immunoassay |
4.3 Predicate device:
1
| Name: | ACS Theophylline Assay |
|---|---|
| 510(k) Number: | K951169 |
| Original submitter: | Ciba Corning Diagnostics Corp63 North StreetMedfield MA 02052 |
Bayer ACS:180/ADVIA Centaur Theophylline 2 - Special 510(k) - Device Modification
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4.4 Device Description
The ACS and ADVIA Centaur Theophylline 2 are competitive chemiluminescence immunoassays are intended for the quantitative determination of theophylline in human serum and plasma. Theophylline in the patient sample, calibrators, standards and controls competes with acridinium ester-labeled theophylline in the Lite Reagent for a limited amount of monoclonal mouse anti-theophylline antibody, which is covalently coupled to paramagnetic particles in the Solid Phase. Following incubation, unreacted acridinium esterlabeled theophylline and unreacted theophylline from the sample are washed from the reaction mixture. The chemiluminescence of the reacted, labeled theophylline is measured in a luminometer. The measured chemiluminescence is inversely proportional to the quantity of theophylline in the sample.
4,5 Statements of Intended Use
. ACS Theophylline 2
"For the quantitative determination of theophylline in serum or plasma using the ACS:180 Automated Chemiluminescent Systems. For In Vitro diagnostic use."
ADVIA Centaur Theophylline 2 .
"For in vitro diagnostic use in the quantitative determination of theophylline in serum or plasma using the ADVIA Centaur System."
Summary of Technological Characteristics 4.6
The ACS and ADVIA Centaur Theophylline 2 Immunoassays are similar to ACS Theophylline assay (the predicate device) in the indications for use, format, performance characteristics, and results. The ACS and ADVIA Centaur Theophylline 2 immunoassays and the ACS Theophylline differ in method used to couple the anti-theophylline monoclonal antibody to the solid phase. In the Theophylline 2 assays, the antibody is labeled with fluorescein isothiocvanate (FITC) and bound to an anti-FITC antibody covalently coupled to the particles. In ACS Theophylline, goat anti-mouse IgG, covalently bound to the particles, binds the anti-theophylline antibody.
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4.7 Method Comparison
Substantial equivalence of the ACS and ADVIA Centaur Theophylline 2 assay to the ACS Theophylline is seen.
These correlation studies demonstrates that the ACS:180 & ADVIA Centaur Theophylline 2 assay is equivalent to each other the unmodified predicate devices, the Bayer Corporation ACS Theophylline assay.
| ReferenceAssay | TestAssay | Slope | Intercept | CorrelationCoefficient (r) | N |
|---|---|---|---|---|---|
| ACSTheophylline | ADVIA CentaurTheophylline 2 | 0.94 | 1.36 | 0.99 | 138 |
| ACSTheophylline | ACSTheophylline 2 | 1.00 | -0.24 | 0.99 | 138 |
| ACSTheophylline 2 | ADVIA CentaurTheophylline 2 | 1.05 | -0.9 | 0.99 | 138 |
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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" around the perimeter. Inside the circle is a stylized image of an eagle with three heads, representing the department's mission to protect the health of all Americans and provide essential human services.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
OCT 2 5 2001
Kenneth T. Edds, Ph.D. Manager, Regulatory Affairs Bayer Diagnostics 511 Benedict Avenue Tarrytown, NY 10591-5097
K013272 Re:
Trade/Device Name: Bayer Diagnostics ACS: 180 and ADVIA Centaur Theophylline Assay Regulation Number: 21 CFR 862.3880 Regulation Name: Theophylline test system Regulatory Class: Class II Product Code: KLS Dated: September 27, 2001 Received: October 1, 2001
Dear Dr. Edds:
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 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 (QS) 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 nouthoution. The I 211 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 1 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, (201) 59 retect 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 mouthanon on your respond and Consumer Assistance at its toll-free number (800) 638-2041 or 1101) 443-6597 or at its internet address "http://www.fda.gov/cdrb/dsma/dsmamain.html".
Sincerely yours,
Steven Butman
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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510(k) Number (if known): Page
Device Name: Bayer Diagnostics ACS:180 and ADVIA Centaur Theophylline Assay
Indications for Use:
The ACS:180 and ADVIA Centaur Theophylline 2 Immunoassays are competitive, The AGS.Too and ADVA Oentitative determination of theophyline in human serum
chemiluminescence immunoassay for the quantitative determination of the strum chemilianses cence in minutioussuly for the quartinative addition. Theophyline (1,3and plasma for use on the adtonnated andiyzer manesed by stimulant that is used for the treatment of difflethyliae is a potent brononodiate avel is very important in reducing the risks of over of asthiria. Monitoring a patient a little in viries with of theophylline absorption, metabolism and under-medication resulting wom are innex. The ACS and ADVIA Centaur Theophylline 2 immunoassays are used as an aid to monitor a patient's theophylline level.
The ACS and ADVIA CentaurTheophylline 2 assays are an enhanced version of the current ACS The ACS and ADVIA Octical moophyline = aimed at providing a more versatile assay in the clinical laboratory.
Gean Cooper
(Division S -Off)
Division of linical Laboratory
510(k) Number K013272
(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)
§ 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.