(51 days)
Immunoassay for the in vitro quantitative determination of digoxin in human serum and plasma for the in vitro diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure proper therapy.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys 2010 immunoassay analyzer.
Competition principle. Total duration of assay: 18 minutes, 37 ℃. · 1st incubation (9 minutes): By incubating the sample (10 µL) with a digoxinspecific ruthenylated** antibody (80 uL), an immunocomplex is formed, the amount of which is dependent upon the analyte concentration in the sample. · 2nd incubation (9 minutes): After addition of streptavidin-coated microparticles (30 uL) and a digoxin derivative labeled with biotin (80 uL), the still-vacant sites of the ruthenylated antibodies become occupied, with the formation of an antibody-hapten complex. The entire complex becomes bound to the solid phase via interaction of biotin and streptavidin.
·The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier (0.4 second read frame).
·Results are determined via a calibration curve which is instrumentspecifically generated by 2-point calibration and a master curve provided via the reagent bar code.
**Tris(2,2'-bipyridyl)ruthenium(II) complex (Ru(bpy)2+3)
The Boehringer Mannheim Elecsys® Digoxin Assay is an in vitro quantitative immunoassay for digoxin in human serum and plasma, used for diagnosing and treating digoxin overdose and monitoring digoxin levels for proper therapy. It is intended for use on the Boehringer Mannheim Elecsys 2010 immunoassay analyzer.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Elecsys® Digoxin Assay are implicitly established through comparison with the predicate device, the Abbott TDx® Digoxin II Assay. The study aimed to demonstrate substantial equivalence, meaning the performance of the Elecsys® Digoxin Assay should be comparable or improved relative to the predicate device across various performance characteristics.
| Feature | Acceptance Criteria (Implied by Predicate) | Elecsys® Digoxin Performance |
|---|---|---|
| Precision | Comparable to Abbott TDx® Digoxin II Assay (e.g., %CV ranges for within-run and total precision) | Within-run %CV:Level 1: 3.57Level 2: 3.33Pool 1: 5.22Total %CV:Level 1: 5.24Level 2: 4.09Pool 1: 7.69(Note: This is compared to TDx within-run %CV of 0.70-3.66 and total %CV of 1.91-7.67 across different levels) |
| Lower Detection Limit | Not explicitly stated, but predicate has 0.2 ng/mL. Implies a comparable or lower limit. | 0.15 ng/mL (Better than predicate) |
| Linearity | Comparable to predicate (0.0 - 5.0 ng/mL) | 0.15 - 5 ng/mL (Comparable to predicate) |
| Method Comparison | Good correlation with predicate device (Abbott TDx® Digoxin II). High correlation coefficient (r) and appropriate slope/intercept values. | Vs Abbott TDx Digoxin:Least Squares: y = 1.03X + 0.10, r=0.9847, N=357Passing Bablock: y = 1.06X + 0.06, r=0.9847, N=357 |
| Interfering Substances | Demonstrate no significant interference from common substances at clinically relevant concentrations, comparable to predicate levels. | No interference at:Bilirubin: 65 mg/dL (Predicate: 20 mg/dL)Hemoglobin: 1000 mg/dL (Predicate: 1000 mg/dL)Lipemia: 1500 mg/dL (Predicate: 2500 mg/dL)Rheumatoid Factor: 1630 IU/mL (Predicate: N/A)Biotin: 100 ng/mL (Predicate: N/A) |
| Specificity | Demonstrate low cross-reactivity with structurally similar compounds and other relevant substances, comparable to predicate. | % Cross-reactivity:Digoxigenin: 14.28 (Predicate: up to 200)Digoxingenin-Mono-Digitoxiside: 55.31 (Predicate: up to 200)Digitoxin-Bis-Digitoxiside: 74.64 (Predicate: up to 200)Digitoxin: 1.13 (Predicate: 4.8)Cortisol: <0.01 (Predicate: <1.0)Many others <0.01 (Predicate: <1.0 or not tested) |
2. Sample Size for Test Set and Data Provenance
- Precision:
- For the Elecsys® Digoxin, the N value for precision testing (Levels 1, 2, and Pool 1) is 60 for each level.
- Method Comparison:
- N = 357 samples were used for the method comparison against the Abbott TDx® Digoxin.
- Interfering Substances & Specificity: Specific sample sizes for these tests are not provided, but generally, these involve a series of spiked samples or known concentrations of interfering substances.
- The provenance of the data (e.g., country of origin, retrospective/prospective) is not explicitly stated in the provided summary.
3. Number of Experts Used to Establish Ground Truth and Qualifications
This submission is for an in vitro diagnostic (IVD) immunoassay, not an imaging device or one requiring human expert interpretation for ground truth establishment. Therefore, there are no "experts" in the context of medical image interpretation (e.g., radiologists) used to establish ground truth. The ground truth for this type of device is established through laboratory reference methods or existing validated assays.
4. Adjudication Method for the Test Set
Not applicable. As an IVD immunoassay, the performance is assessed against established analytical methods and reference standards, not through human reader adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This is an immunoassay, not a device that involves human interpretation of cases. Therefore, an MRMC study comparing human readers with and without AI assistance is not relevant.
6. Standalone Performance Study
Yes, the performance characteristics presented (Precision, Lower Detection Limit, Linearity, Method Comparison, Interfering Substances, Specificity) represent the standalone performance of the Elecsys® Digoxin Assay (algorithm only, without human-in-the-loop performance, as it is a fully automated immunoassay). The device operates on the Elecsys® 2010 immunoassay analyzer to produce quantitative results.
7. Type of Ground Truth Used
The ground truth for this device is established through:
- Reference Methods/Predicate Device Comparison: For method comparison, the Abbott TDx® Digoxin II Assay served as a reference point.
- Analytical Standards: For precision, linearity, detection limits, interfering substances, and specificity, the "ground truth" or reference values are established using known concentrations of digoxin and potential interferents, often prepared using established analytical standards and validated laboratory procedures.
8. Sample Size for the Training Set
The provided 510(k) summary does not mention a "training set" in the context of machine learning or AI. This is a traditional immunoassay whose performance is characterized through analytical validation studies, not by training a model on a dataset.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of machine learning for this device. The assay development and calibration are based on standard immunoassay principles and established laboratory methods.
{0}------------------------------------------------
OCT 1997
| 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.Submittername,address,contact | Boehringer Mannheim Corporation2400 Bisso LaneP.O. Box 4117Concord, CA 94524-4117(510) 674 - 0690, extension 8413Fax: (510) 687-1850Contact Person: Yvette LloydDate Prepared: August 14, 1997 |
| 2.Device name | Proprietary name: Elecsys® Digoxin AssayCommon name: Electrochemiluminescent immunoassay for the determination of Digoxin.Classification name: System, Test, Digoxin |
| 3.Predicatedevice | The Boehringer Mannheim Elecsys® Digoxin is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Abbott TDx® Digoxin II Assay (K882233). |
Continued on next page
/
{1}------------------------------------------------
Image /page/1/Picture/1 description: The image shows a logo for Boehringer Mannheim. The logo is a black square with a white circle in the center. The word "boehringer" is written in white inside the circle. The word "mannheim" is written vertically in white on the left side of the square. The logo is simple and modern.
- Device Description
Competition principle. Total duration of assay: 18 minutes, 37 ℃. · 1st incubation (9 minutes): By incubating the sample (10 µL) with a digoxinspecific ruthenylated** antibody (80 uL), an immunocomplex is formed, the amount of which is dependent upon the analyte concentration in the sample. · 2nd incubation (9 minutes): After addition of streptavidin-coated microparticles (30 uL) and a digoxin derivative labeled with biotin (80 uL), the still-vacant sites of the ruthenylated antibodies become occupied, with the formation of an antibody-hapten complex. The entire complex becomes bound to the solid phase via interaction of biotin and streptavidin.
·The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier (0.4 second read frame).
·Results are determined via a calibration curve which is instrumentspecifically generated by 2-point calibration and a master curve provided via the reagent bar code.
**Tris(2,2'-bipyridyl)ruthenium(II) complex (Ru(bpy)2+3)
{2}------------------------------------------------
0(k) Summary, Continued
Image /page/2/Picture/1 description: The image shows the logo for Boehringer Mannheim. The logo consists of a black square with a white circle inside. The word "boehringer" is written in white inside the circle. The word "mannheim" is written vertically in white on the left side of the square.
| 5.Intended use | Immunoassay for the in vitro quantitative determination of Digoxin in humanserum and plasma. |
|---|---|
| -------------------- | -------------------------------------------------------------------------------------------------- |
- Comparison to predicate device
The Boehringer Mannheim Elecsys® Digoxin Assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Abbott TDx® Digoxin II Assay (K882233).
The following table compares the Elecsys® Digoxin Assay with the predicate device, Abbott TDx® Digoxin II Assay. Specific data on the performance of the test have been incorporated into the draft labeling in attachment 5. Labeling for the predicate device is provided in attachment 6.
Similarities:
·Intended Use: Immunoassay for the in vitro quantitative determination of Digoxin
·Sample type: Serum and plasma
•Assay range: 0 - 5 ng/mL
{3}------------------------------------------------
BOEHRINGENO(k) Summary, Continued MANNHEIM CORPORATION
Image /page/3/Picture/1 description: The image shows a logo with the text "mannheim" vertically aligned on the left side. To the right of this text is a black square containing a white circle. Inside the circle is the text "boehringer" in a stylized font. The logo appears to be for a company named Boehringer Mannheim.
- Comparison
to predicate device cont.
Differences:
| Feature | Elecsys®Digoxin | TDxDigoxin II |
|---|---|---|
| Reaction testprinciple | Electrochemiluminescence | Fluorescence Polarization |
| Instrumentrequired | Elecsys® 2010 | Abbott TDx |
Performance Characteristics:
| Feature | Elecsys®Digoxin | TDxDigoxin II | ||||
|---|---|---|---|---|---|---|
| Precision | Modified NCCLS (ng/mL): | NCCLS (ng/mL): | ||||
| Level | Level 1 | Level 2 | Pool 1 | Low | Mid | High |
| N | 60 | 60 | 60 | 50 | 50 | 50 |
| Within run | 1.34 | 3.08 | 0.85 | 0.70 | 1.44 | 3.66 |
| %CV | 3.57 | 3.33 | 5.22 | 5.75 | 3.15 | 1.87 |
| Total | 1.34 | 3.08 | 0.85 | 0.70 | 1.44 | 3.66 |
| %CV | 5.24 | 4.09 | 7.69 | 7.67 | 3.98 | 1.91 |
{4}------------------------------------------------
BOEHRINGEA 0(k) Summary, Continued MANNHEIM CORPORATION
Image /page/4/Picture/1 description: The image shows a logo with the word "boehringer" inside of a circle. To the left of the circle is the word "mannheim" written vertically. The logo is black and white and has a horizontal line underneath it.
- Comparison to predicate device, (cont.)
·
Performance Characteristics:
| Feature | Elecsys®Digoxin | TDxDigoxin II |
|---|---|---|
| LowerDetectionLimit | 0.15 ng/mL | 0.2 ng/mL |
| Linearity | 0.15 - 5 ng/mL | 0.0 - 5.0 ng/mL |
| MethodComparison | Vs Abbott TDxDigoxin | Vs Baxter Dade Stratus |
| Least Squares:$y =1.03X + 0.10$r=0.9847N=357 | $y =0.94x + 0.08$r=0.962N=200 | |
| Passing Bablock:$y=1.06X + 0.06$r=0.9847N=357 | ||
| Feature | Elecsys®Digoxin | TDxDigoxin II |
| Interfering substances | No interference at:(within 0.15 ng/ml atdigoxin level <1.5 ng/ml orwithin ±10% at digoxinlevel > 1.5 ng/ml.) | No interference at: |
| Bilirubin | ||
| Hemoglobin | 65 mg/dL | 20 mg/dL |
| Lipemia | 1000 mg/dL | 1000 mg/dL |
| Rheumatoid Factor | 1500 mg/dL | 2500 mg/dL |
| Biotin | 1630 IU/mL | N/A |
| 100 ng/ml | N/A | |
| Specificity | % Cross-reactivity | % Cross-reactivity |
| Digoxigenin | 14.28 | up to 200 |
| Digoxingenin-Mono-Digitoxiside | 55.31 | up to 200 |
| Digitoxin-Bis-Digitoxiside | 74.64 | up to 200 |
| Digitoxin | 1.13 | 4.8 |
| Cortisol | <0.01 | <1.0 |
| Canrenone | <0.01 | <1.0 |
| DHEA | 0.01 | <1.0 |
| 16-β-DHEA | <0.01 | not tested |
| Furosemide | <0.01 | <1.0 |
| Ouabain | <0.01 | <1.0 |
| Prednisolone | <0.01 | <1.0 |
| Prednisone | <0.01 | <1.0 |
| Progesterone | <0.01 | <1.0 |
| 17-Hydroxyprogesterone | <0.01 | <1.0 |
| Spironolactone | <0.01 | <1.0 |
| Testosterone | <0.01 | <1.0 |
{5}------------------------------------------------
INGE 0(k) Summary, Continued 30 ANNHEIM CORPORATION
Image /page/5/Picture/1 description: The image shows a logo for Boehringer Mannheim. The logo consists of the word "boehringer" inside of a circle. To the left of the circle, the word "mannheim" is written vertically.
- Comparison
to predicate device, (cont.)
Performance Characteristics:
{6}------------------------------------------------
Image /page/6/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features the department's symbol, which is a stylized representation of a human figure. The figure is composed of three curved lines that suggest a person in motion. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Yvette Lloyd Regulatory Affairs Specialist Boehringer Mannheim Corporation 4300 Hacienda Drive Pleasanton, California 94588-2722
OCT 1 0 1997
Re : K973112 Trade Name: Elecsys® Digoxin Assay Regulatory Class: II Product Code: KXT Dated: Auqust 14, 1997 Received: August 20, 1997
Dear Ms. Lloyd:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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 (Premarket Approval), 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 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such Failure to comply with the GMP regulation may result in assumptions. regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations.
{7}------------------------------------------------
Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.
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" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
Steven Autman
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
{8}------------------------------------------------
510(k) Number (if known): N/A
Device Name: Elecsys® Digoxin Assay
Indications For Use:
Immunoassay for the in vitro quantitative determination of digoxin in human serum and minutedssar for the in Are quarthe diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure proper therapy .
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys 2010 immunoassay analyzer.
| 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) | Division of Clinical Laboratory Devices | ||
| 510(k) Number |
§ 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.