(89 days)
The ONLINE TDM Carbamazepine assay is for the quantitative determination of carbamazepine in human serum or plasma on automated clinical chemistry analyzers. This neuroleptic drug assay test system is a device intended to measure in serum or plasma the dopamine receptor blocking activity of carbamazepine.
The ONLINE TDM Carbamazepine assay is for the quantitative determination of carbamazepine in human serum or plasma on automated clinical chemistry analyzers. In combination with other clinical information, monitoring carbamazepine levels provides physicians with an effective tool to aid in adjusting dosage and achieving optimal therapeutic effect while avoiding both sub-therapeutic and toxic drug levels. The proposed labeling indicates the Roche Hitachi 911, 912, 917 and Modular P analyzers can be used with the Roche ONLINE TDM Carbamazepine reagent kits.
The ONLINE TDM Carbamazepine assay is a homogeneous microparticle agglutination immunoassay. It is a two-reagent system used for the detection of carbamazepine in serum. Kinetic interaction of microparticles (KIMS) will be measured using Roche Diagnostics / Hitachi families of automated analyzers. In this technology biotinylated drug hapten serves as the binding partner to 1.) anti-carbamazepine antibody and 2.) streptavidin coated latex A competitive reaction to a limited amount of specific antibeads. carbamazepine antibody takes place between the hapten and free carbamazepine in the serum sample. A decrease in the apparent signal is proportional to the amount of drug present in the sample.
Here's an analysis of the acceptance criteria and study details for the Roche ONLINE TDM Carbamazepine assay, based on the provided 510(k) summary:
The device being assessed is the Roche ONLINE TDM Carbamazepine assay.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Roche ONLINE TDM Carbamazepine assay are primarily inferred through comparison to its predicate device, the Roche COBAS INTEGRA Carbamazepine assay (K951595). The study aims to demonstrate substantial equivalence across key performance characteristics. The document doesn't explicitly state numerical "acceptance criteria" but rather presents the performance of both the new device and the predicate for direct comparison.
| Performance Characteristic | Acceptance Criteria (Inferred from Predicate Performance or General Standards for Substantial Equivalence) | Roche ONLINE TDM Carbamazepine Performance (New Device) |
|---|---|---|
| Precision (Within run) | Comparable to predicate: | Control 1 (2.8 µg/ml): SD 0.05, CV% 1.7 |
| - SD (µg/ml) | - Control 1: 0.08 | Control 2 (8.3 µg/ml): SD 0.13, CV% 1.5 |
| - CV% | - Control 2: 0.17 | Control 3 (14.1 µg/ml): SD 0.21, CV% 1.5 |
| - Control 3: 0.31 | ||
| Precision (Total) | Comparable to predicate: | Control 1 (2.8 µg/ml): SD 0.15, CV% 5.6 |
| - SD (µg/ml) | - Control 1: 0.12 | Control 2 (8.3 µg/ml): SD 0.36, CV% 4.3 |
| - CV% | - Control 2: 0.24 | Control 3 (14.1 µg/ml): SD 0.55, CV% 3.9 |
| - Control 3: 0.52 | ||
| Method Comparison | High correlation to predicate and linearity over relevant range (e.g., r > 0.95) | y=1.062x - 0.16, r=0.985 (N=103, Range = 0.5-11.93 µg/ml) |
| - Correlation (r) | ||
| - Regression Equation | ||
| Other (General) | Acceptable results provided for: Lower detection limit, specificity, interfering substances | "All of the evaluation studies gave acceptable results compared to the predicate device." |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Method Comparison (Test Set):
- N = 103 for the comparison between the ONLINE TDM Carbamazepine and the COBAS INTEGRA Carbamazepine (FPIA) method.
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the nature of a 510(k) submission for an in-vitro diagnostic, it is highly likely these were prospective clinical laboratory evaluations conducted as part of the validation process.
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 summary. For an in-vitro diagnostic device like this, the "ground truth" would typically refer to the reference method or comparative method results, which are obtained directly from laboratory measurements rather than expert consensus on images or clinical assessments.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1) are typically used in studies involving human interpretation (e.g., radiology reads). This is an in-vitro diagnostic device (immunoassay) for quantitative determination of a drug level. Therefore, no adjudication method (in the sense of human expert disagreement resolution) was used or is relevant for this type of device performance evaluation. The "ground truth" is established through other laboratory methods.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. MRMC studies are relevant for medical imaging devices where multiple human readers interpret cases. This device is an automated immunoassay, not an imaging device.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the primary evaluation presented is a standalone (algorithm only) performance study. The device is an automated clinical chemistry analyzer for quantitative determination of carbamazepine. Its performance (precision, method comparison) is assessed as a direct output of the instrument without human interpretation playing a role in the measurement itself, beyond standard laboratory procedures and quality control.
7. The Type of Ground Truth Used
The "ground truth" for the test set (method comparison) was established by using the predicate device's measurement (Roche COBAS INTEGRA Carbamazepine assay, specifically its FPIA method) as the comparative standard. The new device's results are then correlated against these predicate results. This is a common approach for demonstrating substantial equivalence for IVDs.
8. The Sample Size for the Training Set
The document does not provide information on a training set size. For an immunoassay, particularly one demonstrating substantial equivalence to a predicate, the development process might involve internal optimization and validation, but the 510(k) summary focuses on the final performance evaluation data presented to demonstrate equivalence. It's not a machine learning model that would typically have a distinct 'training set' in the way an AI algorithm does.
9. How the Ground Truth for the Training Set Was Established
As no specific "training set" (in the context of AI/ML) is mentioned, the method for establishing its ground truth is not applicable/not provided in this summary. Any internal development or optimization would rely on established laboratory reference methods for carbamazepine quantification.
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SEP 1 7 2003
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) 521-7637 |
| Contact Person: Kerwin Kaufman | |
| Date Prepared: June 19, 2003 |
- Device name
| Proprietary name: | ONLINE TDM Carbamazepine |
|---|---|
| Common name: | Enzyme immunoassay, Carbamazepine |
| Classification name: | Neuroleptic drugs radioreceptor assay test system |
- Predicate device
| We claim substantial equivalence to the currently marketed COBAS INTEGRA Carbamazepine (K951595). | |
|---|---|
| -- | --------------------------------------------------------------------------------------------------- |
Continued on next page
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510(k) Summary, Continued
- Device Description The ONLINE TDM Carbamazepine assay is for the quantitative determination of carbamazepine in human serum or plasma on automated clinical chemistry analyzers. In combination with other clinical information, monitoring carbamazepine levels provides physicians with an effective tool to aid in adjusting dosage and achieving optimal therapeutic effect while avoiding both sub-therapeutic and toxic drug levels. The proposed labeling indicates the Roche Hitachi 911, 912, 917 and Modular P analyzers can be used with the Roche ONLINE TDM Carbamazepine reagent kits.
The ONLINE TDM Carbamazepine assay is a homogeneous microparticle agglutination immunoassay. It is a two-reagent system used for the detection of carbamazepine in serum. Kinetic interaction of microparticles (KIMS) will be measured using Roche Diagnostics / Hitachi families of automated analyzers. In this technology biotinylated drug hapten serves as the binding partner to 1.) anti-carbamazepine antibody and 2.) streptavidin coated latex A competitive reaction to a limited amount of specific antibeads. carbamazepine antibody takes place between the hapten and free carbamazepine in the serum sample. A decrease in the apparent signal is proportional to the amount of drug present in the sample.
5.) Intended Use
The ONLINE TDM Carbamazepine assay is for the quantitative determination of carbamazepine 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 TDM Carbamazepine assay is substantially equivalent 6.) Comparison to the Predicate to other products in commercial distribution intended for similar use. Most Device notably, it is substantially equivalent to the currently marketed Roche COBAS INTEGRA Carbamazepine assay (K951595).
The Roche ONLINE TDM Carbamazepine 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 Carbamazepine assay is substantially equivalent to the currently marketed Roche COBAS INTEGRA Carbamazepine assay. The following table summarizes the precision and method comparison results.
| Roche ONLINE TDM Carbamazepine | Roche COBAS INTEGRACarbamazepine (Predicate) | |||||
|---|---|---|---|---|---|---|
| NCCLS Precision, | Control 1 | Control 2 | Control 3 | Control 1 | Control 2 | Control 3 |
| Within run | ||||||
| Mean (µg/ml) | 2.8 | 8.3 | 14.1 | 3.8 | 8.6 | 14.7 |
| SD (µg/ml) | 0.05 | 0.13 | 0.21 | 0.08 | 0.17 | 0.31 |
| CV% | 1.7 | 1.5 | 1.5 | 2.2 | 1.9 | 2.1 |
| NCCLS Precision, | Control 1 | Control 2 | Control 3 | Control 1 | Control 2 | Control 3 |
| Total | ||||||
| Mean (µg/ml) | 2.8 | 8.3 | 14.1 | 3.8 | 8.6 | 14.7 |
| SD (µg/ml) | 0.15 | 0.36 | 0.55 | 0.12 | 0.24 | 0.52 |
| CV% | 5.6 | 4.3 | 3.9 | 3.0 | 2.8 | 3.6 |
| MethodComparison | Linear Regression: ONLINE TDMCarbamazepine Vs. COBAS INTEGRACarbamazepine (FPIA) method. | Linear Regression: COBAS INTEGRACarbamazepine Vs. commercially availableFPIA method. | ||||
| N=103, Range = 0.5-11.93 µg/ml$y=1.062x - 0.16$$r=0.985$ | N=205, Range = 1.6-19.6 µg/ml$y=1.061x - 0.124$$r=0.995$ |
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
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SEP 1 7 2003
98 Gaither Road Rockville MD 20850
Mr. Kerwin Kaufman Regulatory Affairs Consultant Roche Diagnostics Corporation 9115 Hague Road, P.O. Box 50457 Indianapolis. IN 46250-0457
Re: K031902
Trade/Device Name: ONLINE TDM Carbamazepine Assay Regulation Number: 21 CFR 862.3645 Regulation Name: Neuroleptic drugs radioreceptor assay test system Regulatory Class: Class II Product Code: KLT Dated: June 19, 2003 Received: June 20, 2003
Dear Mr. Kaufman:
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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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 (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 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 Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use Statement
| 510(k) Number (if known): | K031902 |
|---|---|
| Device Name: | Roche Diagnostics ONLINE TDM Carbamazepine |
| Indications for Use: | The ONLINE TDM Carbamazepine assay is for the quantitative determination of carbamazepine in human serum or plasma on automated clinical chemistry analyzers. This neuroleptic drug assay test system is a device intended to measure in serum or plasma the dopamine receptor blocking activity of carbamazepine. |
(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)
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K031902
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§ 862.3645 Neuroleptic drugs radioreceptor assay test system.
(a)
Identification. A neuroleptic drugs radioceptor assay test system is a device intended to measure in serum or plasma the dopamine receptor blocking activity of neuroleptic drugs and their active metabolites. A neuroleptic drug has anti-psychotic action affecting principally psychomotor activity, is generally without hypnotic effects, and is a tranquilizer. Measurements obtained by this device are used to aid in determining whether a patient is taking the prescribed dosage level of such drugs.(b)
Classification. Class II.