(119 days)
The Bayer ADVIA IMS Carbamazepine method is for in vitro diagnostic use to measure the antiepileptic drug carbamazepine in human serum and plasma. Measurements of carbamazepine are used as an aid in the diagnosis and treatment of carbamazepine overdose, and used as an aid in monitoring therapeutic levels of carbamazepine to ensure appropriate therapy.
The Bayer ADVIA IMS Carbamazepine calibrator is for in vitro diagnostic use in the calibration of carbamazepine using the ADVIA® IMS system.
This in vitro method is intended to quantitatively measure the antiepileptic drug carbamazepine in human serum and plasma on the Bayer ADVIA® IMS systems.
1. Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (ADVIA IMS) | Predicate Device Performance (Bayer Centaur) |
|---|---|---|---|
| Minimum Detectable Concentration (MDC) | Lower is better | 0.20 µg/mL | 0.25 µg/mL |
| Imprecision: Level 2.62 µg/mL (Total CV%) | Lower is better | 4.6% | 9.2% (at 3.28 µg/mL) |
| Imprecision: Level 5.63 µg/mL (Total CV%) | Lower is better | 2.6% | 8.2% (at 5.79 µg/mL) |
| Imprecision: Level 9.19 µg/mL (Total CV%) | Lower is better | 2.5% | 8.4% (at 9.85 µg/mL) |
| Correlation (R) | Close to 1.0 | 0.988 | - |
| Regression Equation | Close to Y=1.00X + 0.00 | Y=1.00X + 0.01 | - |
| Syx (Standard Error of the Estimate) | Lower is better | 0.80 µg/mL | - |
| Analytical Range | Wider is better | 0.20 µg/mL to 22.14 µg/mL | - |
| Interfering Substances: Bilirubin (unconjugated) % change | Minimal (e.g., < +/-10%) | 2.0% | - |
| Interfering Substances: Bilirubin (conjugated) % change | Minimal (e.g., < +/-10%) | -3.9% | - |
| Interfering Substances: Hemoglobin % change | Minimal (e.g., < +/-10%) | -0.7% | - |
| Interfering Substances: Lipids % change | Minimal (e.g., < +/-10%) | -8.4% | - |
The acceptance criteria are not explicitly stated as numerical thresholds in the provided document, but are implied by demonstrating performance that is comparable to or better than the predicate device and showing minimal impact from interfering substances. The ADVIA IMS device generally shows better or comparable performance to the Bayer Centaur predicate device across the measured metrics.
2. Sample Size and Data Provenance for the Test Set
- Sample Size for Correlation Study: 48 serum specimens were used for the correlation study against the Centaur comparison system.
- Data Provenance: The document does not explicitly state the country of origin or if the data was retrospective or prospective. It is implied to be from a laboratory setting.
3. Number of Experts and Qualifications for Ground Truth
- This type of in-vitro diagnostic device (IVD) for quantitative measurement does not typically involve expert review for ground truth in the same way imaging or diagnostic algorithms do. The "ground truth" for these studies is the measurement obtained from a well-established, often predicate, device or a reference method. Therefore, the concept of "number of experts" and their "qualifications" for establishing ground truth is not applicable here.
4. Adjudication Method for the Test Set
- Adjudication methods (like 2+1, 3+1) are typically used in studies involving subjective interpretation, often in imaging or clinical trials. For a quantitative IVD device like this, the performance is assessed against a numerical "reference standard" or a predicate device. Therefore, no adjudication method was used or needed in the traditional sense.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This type of study is relevant for diagnostic devices where human readers interpret results, and the AI's impact on their performance is being evaluated. This device is a quantitative automated assay, so human interpretation in the same manner as an imaging study is not involved.
6. Standalone (Algorithm Only) Performance Study
- Yes, the performance data presented (MDC, Imprecision, Correlation, Interfering Substances, Analytical Range) represents the standalone performance of the ADVIA IMS Carbamazepine method. It is an automated system, and these metrics directly reflect its capabilities without human intervention in the measurement process.
7. Type of Ground Truth Used
- The ground truth for this study was established using a comparison system, specifically the Bayer Centaur. For the correlation study, the measurements from the Centaur system served as the reference standard against which the ADVIA IMS system was evaluated. For other metrics like MDC and Imprecision, the reference for "truth" comes from established analytical methods and statistical calculations within the laboratory environment.
8. Sample Size for the Training Set
- The document does not provide information on the sample size used for the training set. This information is typically proprietary to the manufacturer and not always included in 510(k) summaries, especially for established IVD technologies.
9. How Ground Truth for the Training Set Was Established
- The document does not provide information on how the ground truth for the training set was established. For quantitative IVDs, the "training" (calibration and optimization) of the assay would typically involve using known concentration standards (calibrators) and reference materials with established values. These standards are rigorously prepared and validated.
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510(k) SUMMARY OF SAFETY AND EFFECTIVENESS -- 516(R) SUMMART OF SALD For AND 21 2 000 -----------------------------------------------------------------------------------------------------------------------------------
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K042808 (leave blank)
1. Intended Use
This in vitro method is intended to quantitatively measure the antiepileptic drug carbamazepine in human serum and plasma on the Bayer ADVIA® IMS systems. Measurements of carbamazepine are used to aid in monitoring therapeutic levels of carbamazepine to ensure appropriate therapy and in the treatment of carbamazepine overdose.
Predicate Device 2.
| Product Name | Reagent Part # | Calibrator Part # |
|---|---|---|
| Bayer Centaur | 07862715 | 05706449 |
| Carbamazepine | (119933) | (107585) |
Device / Method 3.
| Product Name | Reagent | Calibrator |
|---|---|---|
| ADVIA IMSCarbamazepine | 00328780 | 00417120 |
Performance 4.
A. Minimum Detectable Concentration
| Method | ADVIA IMS | Centaur |
|---|---|---|
| MDC | $0.20 \mu g/mL$ | $0.25 \mu g/mL$ |
B. Imprecision
| ADVIA IMS | |
|---|---|
| Levelµg/mL | TotalCV (%) |
| 2.62 | 4.6 |
| 5.63 | 2.6 |
| 9.19 | 2.5 |
| Bayer Centaur | |
|---|---|
| Levelµg/mL | TotalCV(%) |
| 3.28 | 9.2 |
| 5.79 | 8.2 |
| 9.85 | 8.4 |
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| C. Correlation (Y-ADVIA IMS, X-Comparison system) | ||||||
|---|---|---|---|---|---|---|
| Specimen type | Comparison System (X) | N | Regression Equation | Syx μg/mL | R | IMS Sample Range μg/mL |
| Serum | Centaur | 48 | $Y=1.00X + 0.01$ | 0.80 | 0.988 | 1.2 to 17.6 |
C Correlation (V=ADVIA IMS. X = Comparison system)
D. Interfering Substances
| InterferingSubstance | Interfering Sub.Conc. (mg/dL) | CarbamazepineConcentrationµg/mL | Effect(% change) |
|---|---|---|---|
| Bilirubin(unconjugated) | 25 | 14.47 | 2.0 |
| Bilirubin(conjugated) | 25 | 14.64 | -3.9 |
| Hemoglobin | 600 | 14.59 | -0.7 |
| Lipids(Triglycerides) | 750 | 13.60 | -8.4 |
E. Analytical Range
0.20 µg/mL to carbamazepine concentration in highest calibrator (Level 6) (22.14 µg/mL).
A. Auda
10/4/04
Date
Date
Andres Holle Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York, 10591 - 5097
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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 and Human Services. The logo features a stylized eagle with three stripes extending from its head, representing health, human services, and the pursuit of well-being. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
FEB - 8 2005
Mr. Andres Holle Manager, Regulatory Affairs Bayer HealthCare LLC Diagnostics Division 511 Benedict Avenue Tarrytown, NY 10591
Re: K042808
Trade/Device Name: ADVIA® IMS Carbamazepine Method ADVIA® IMS Carbamazepine Calibrator Regulation Number: 21 CFR 862.3645 Regulation Name: Neuroleptic drugs radioreceptor assay test system Regulatory Class: Class II Product Code: KLT, DKB Dated: October 4, 2004 Received: October 13, 2004
Dear Mr. Holle:
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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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 number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html
Sincerely yours,
Jean M. Cooper MS, DUM
Jean M. Cooper, MS, D.V.M. 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):_____________________________________________________________________________________________________________________________________________________
Device Name: ADVIA® IMS Carbamazepine Method
Indications For Use:
The Bayer ADVIA IMS Carbamazepine method is for in vitro diagnostic use to The Bayer ADVIA The Ourbancepine in human serum and plasma. measure the anticplicplio drug carbarness, mazepine-5-carboxamide) are Measurements of ourbamazepine (17) (17) and treatment of carbamazepine overdose, and used as an ald in the diagnools and treamezepine to ensure appropriate therapy.
Prescription Use _____________________________________________________________________________________________________________________________________________________________ × (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 807 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)
Mert
Division Sign-Off
Division Sign-Off
Office of In Vitro Dia
042808
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Indications for Use
510(k) Number (if known): _ K042808
Device Name: ADVIA® IMS Carbamazepine Calibrator
Indications For Use:
The Bayer ADVIA IMS Carbamazepine calibrator is for in vitro diagnostic use in the calibration of carbamazepine using the ADVIA® IMS system.
Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 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)
Division Sign-Off
Division Sign-
Office of In Vitro Diag Device Evaluation
5100
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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.