(49 days)
The ADVIA IMS® Digoxin method is for in vitro diagnostic use to quantitatively measure digoxin, a cardioactive drug, in human serum. Measurements obtained are used as an aid in the diagnosis of digoxin overdose and in monitoring therapeutic levels of digoxin to ensure appropriate therapy.
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The Bayer ADVIA IMS® Digoxin assay is intended for in vitro diagnostic use to quantitatively measure digoxin, a cardioactive drug, in human serum. This product is used as an aid in diagnosing digoxin overdose and monitoring therapeutic levels of digoxin for appropriate therapy.
Here's an analysis of the provided information regarding the acceptance criteria and the study proving the device meets these criteria:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal "acceptance criteria" with numerical thresholds for performance metrics. However, the study aims to demonstrate substantial equivalence to the predicate device, the Immuno 1 Digoxin Assay. Therefore, the "reported device performance" is compared directly against the predicate device's performance, implying that performance comparable to or better than the predicate is the de facto acceptance criterion.
| Performance Characteristic | Acceptance Criteria (Implied: Comparable to Immuno 1) | Reported Device Performance (ADVIA IMS) | Predicate Device Performance (Immuno 1) |
|---|---|---|---|
| Imprecision (Total CV%) | Comparable to or better than Immuno 1 | Level 0.75 ng/mL: 6.0% | Level 0.7 ng/mL: 8.2% |
| Level 1.9 ng/mL: 5.9% | Level 2.2 ng/mL: 4.2% | ||
| Level 3.3 ng/mL: 3.8% | Level 3.4 ng/mL: 3.6% | ||
| Correlation (vs. Immuno 1) | Strong correlation (R-value close to 1) | Regression: Y=1.017X+0.055 | N/A (Immuno 1 is the comparison) |
| Low Syx | Syx: 0.265 ng/mL | N/A | |
| R-value close to 1 | R: 0.985 | N/A | |
| Interference (Bilirubin) | % Deviation within acceptable limits (likely < ±10%) | 3.6%, 0.7%, 6.2% | Not specified |
| Interference (Triglycerides) | % Deviation within acceptable limits (likely < ±10%) | -1.7%, 0.1%, 3.0% | Not specified |
| Interference (Hemoglobin) | % Deviation within acceptable limits (likely < ±10%) | -4.0%, -6.9%, -3.6% | Not specified |
| Analytical Range | Similar to Immuno 1 | 0.04 - 6 ng/mL | Not explicitly stated for Immuno 1, but "Minimum Detectable Concentration" is 0.04 ng/mL |
| Minimum Detectable Concentration | Similar to Immuno 1 | 0.04 ng/mL | 0.04 ng/mL |
2. Sample Size Used for the Test Set and Data Provenance
-
Correlation Study (test set):
- Sample Size: 72 serum specimens.
- Data Provenance: Not explicitly stated, but clinical specimens are typically derived from human subjects. The document does not specify country of origin or whether the data was retrospective or prospective.
-
Imprecision Study: The sample size isn't explicitly stated as a number of individual patient samples, but rather as "levels" (0.75, 1.9, 3.3 ng/mL). Imprecision studies typically involve multiple replicates of samples at different concentrations. The data provenance is not specified.
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Interference Study: The sample size for each interferant condition is not explicitly stated. It involves spiked concentrations, implying controlled laboratory conditions rather than patient samples. Data provenance is not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
- This is a submission for an in vitro diagnostic (IVD) assay, not an AI/imaging device that requires expert review for ground truth.
- The "ground truth" for this type of device is established by the reference method or predicate device results. In this case, the Immuno 1 Digoxin Assay serves as the comparison system (X) for the correlation study, establishing the "ground truth" against which the ADVIA IMS device (Y) is evaluated.
- No human experts are mentioned as establishing ground truth in this context.
4. Adjudication Method for the Test Set
- Not applicable. This is an IVD assay, and the "ground truth" (reference measurement) does not require expert adjudication in the way an imaging study or clinical diagnosis might. The results from the Immuno 1 assay are taken as the comparative standard.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, an MRMC comparative effectiveness study was not done. This type of study is relevant for AI-powered diagnostic aids, particularly in imaging, where human readers interact with the AI. This submission is for an IVD assay, which is an automated chemical analysis, not an AI or imaging device involving human readers.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
- Yes, the performance data presented (imprecision, correlation, interference) reflects the standalone performance of the ADVIA IMS Digoxin Assay. As an IVD assay, it operates as an "algorithm only" or automated system without human intervention in the measurement process itself, beyond sample loading and general operation.
7. The Type of Ground Truth Used
- The ground truth (or more accurately, the reference method/comparison method) used for evaluating the ADVIA IMS Digoxin Assay in the correlation study was the Immuno 1 Digoxin Assay. This is a predicate device which is already legally marketed and presumed to provide accurate measurements of digoxin in human serum.
- For imprecision and interference, the "ground truth" is based on the known concentrations of controls or spiked samples.
8. The Sample Size for the Training Set
- This document is a 510(k) summary for an IVD assay, which is based on chemical reactions rather than machine learning or AI models that require "training sets." Therefore, the concept of a training set as understood in AI/ML is not applicable here.
9. How the Ground Truth for the Training Set Was Established
- Not applicable, as there is no "training set" in the context of an IVD assay's development described here.
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NOV 1 4 2003
510(k) SUMMARY OF SAFETY AND EFFECTIVENESS Digoxin Assay for Bayer ADVIA® Integrated Modular System (IMS)
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: K 033 D 07
1. Intended Use
The ADVIA IMS® Digoxin method is for in vitro diagnostic use to quantitatively measure digoxin, a cardioactive drug, in human serum. Measurements obtained are used as an aid in the diagnosis of digoxin overdose and in monitoring therapeutic levels of digoxin to ensure appropriate therapy.
2. Predicate Device
| Product Name | Reagents & Calibrators | Controls |
|---|---|---|
| Immuno 1 Digoxin Assay | K912616 | K885226 |
3. Device / Method
| Product Name |
|---|
| ADVIA IMS Digoxin Assay |
Imprecision
| ADVIA IMS | |
|---|---|
| Level(ng/mL) | TotalCV(%) |
| 0.75 | 6.0 |
| 1.9 | 5.9 |
| 3.3 | 3.8 |
| Immuno 1 | |
|---|---|
| Level(ng/mL) | TotalCV(%) |
| 0.7 | 8.2 |
| 2.2 | 4.2 |
| 3.4 | 3.6 |
Correlation (Y= ADVIA IMS, X=comparison system)
| Specimen type | Comparison System (X) | N | Regression Equation | Syx (ng/mL) | R | Sample Range (ng/mL) |
|---|---|---|---|---|---|---|
| Serum | Immuno 1 | 72 | Y=1.017X+0.055 | 0.265 | 0.985 | 0.04 to 4.73 |
Interfering Substances
| Interferant | SpikedConcentration(mg/dL) | ExpectedConcentration(ng/mL) | ObservedConcentration(ng/mL) | %Deviation |
|---|---|---|---|---|
| Bilirubin | 25.0 | 0.77 | 0.80 | 3.6 |
| Bilirubin | 25.0 | 2.03 | 2.05 | 0.7 |
| Bilirubin | 25.0 | 3.44 | 3.67 | 6.2 |
| Triglycerides | 1000.0 | 0.73 | 0.72 | -1.7 |
| Triglycerides | 1000.0 | 1.87 | 1.88 | 0.1 |
| Triglycerides | 1000.0 | 3.21 | 3.30 | 3.0 |
| Hemoglobin | 1000.0 | 0.67 | 0.64 | -4.0 |
| Hemoglobin | 1000.0 | 1.82 | 1.71 | -6.9 |
| Hemoglobin | 1000.0 | 3.18 | 3.07 | -3.6 |
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Analytical Range
0.04 - 6 ng/mL
Minimum Detectable Concentration
| ADVIA IMS(ng/mL) | Immuno 1(ng/mL) |
|---|---|
| 0.04 | 0.04 |
Table of Similarities and Differences between IMS Digoxin and Immuno 1 Digoxin assays:
| Package Insert Sections | ADVIA IMS Digoxin assay | Bayer Immuno 1 Digoxin assay(predicate device) |
|---|---|---|
| Intended Use | Similar | Similar |
| Summary | Similar | Similar |
| Principle | Heterogeneous CompetitiveMagnetic Separation Assay | Heterogeneous CompetitiveMagnetic Separation Assay |
| Reagents | Two liquid reagents contained insystem specific packaging | Two liquid reagents contained insystem specific packaging |
| Storage | 2-8 °C | 2-8 °C |
| Stability | Similar | Similar |
| Precautions | Similar | Similar |
| Indications ofDeterioration | Similar | Similar |
| PerformanceCharacteristics | Similar | Similar |
| Limitations | Similar | Similar |
| Parameters | Similar | Similar |
Clu ets tos
Kenneta T. Edds Manager, Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097
9/29/03
Date
Date
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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, which is often associated with medicine and healthcare. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the symbol. The logo is black and white.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Kenneth T. Edds, Ph.D. Manager, Regulatory Affairs Bayer HealthCare 511 Benedict Avenue Tarrytown, New York 10591-5097
NOV 1 4 2003
Re: K033007
Trade/Device Name: Digoxin Assay on the Bayer ADVIA IMS® Analyzer Regulation Number: 21 CFR § 862.3320 Regulation Name: Digoxin Test System Regulatory Class: II Product Code: KXT Dated: September 26, 2003 Received: September 26, 2003
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. Iisting 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). 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.
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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). 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/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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510(k) Number: K033007
Device Name: Digoxin Assay for the Advia IMS
Indications for Use:
The Bayer ADVIA® IMS™ Digoxin assay is for in vitro diagnostic use to quantitatively measure digoxin, a cardioactive drug, in human serum. Measurements obtained are used as an aid in the diagnosis of digoxin overdose and in monitoring therapeutic levels of digoxin to ensure appropriate therapy.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
| Concurrence of CDRH, Office of Device Evaluation (ODE) |
|---|
| -------------------------------------------------------- |
Carol Benson for Jean Cooper, DVM
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
| 510(k) | K033007 |
|---|---|
| Prescription Use (Per 21 CFR 801.109) | |
| OR Over-The-CounterUse |
(Optional Format 1-2-96)
§ 862.3320 Digoxin test system.
(a)
Identification. A digoxin test system is a device intended to measure digoxin, a cardiovascular drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure appropriate therapy.(b)
Classification. Class II.