(61 days)
The IMMULITE® 2000 Digoxin assay is for in vitro diagnostic use with the IMMULITE® 2000 Analyzer -- for the quantitative measurement of digoxin in serum or heparinized plasma, as an aid in monitoring the therapeutic administration of this cardioglycoside, while avoiding toxicity.
IMMULITE® 2000 Digoxin is a solid phase, chemiluminescent enzyme-labeled competitive immunoassay for use with the IMMULITE® 2000 Automated Analyzer. The solid phase is a polystyrene bead coated with a monoclonal murine anti-digoxin antibody. The patient sample and alkaline phosphatase-conjugated digoxin are simultaneously introduced into the Reaction Tube containing the bead, and incubated for approximately 30 minutes at 37 degrees C with intermittent agitation. During this time, digoxin in the sample competes with the enzyme-fairched digoxin for a limited number of antibody binding sites on the bead. Unbound enzyme conjugate is then removed by a centrifugal wash, after which substrate is added and the Reaction Tube is incubated for a further 5 minutes. The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to yield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision by providing a window for multiple readings. The bound complex - and thus also the photon output, as measured by the luminometer - is inversely proportional to the concentration of digoxin in the sample.
Here's a breakdown of the acceptance criteria and study information based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal "acceptance criteria" in terms of predefined thresholds for performance metrics. Instead, it demonstrates performance equivalence to a predicate device. The performance is presented as a method comparison, and the acceptance is implied by the FDA's granting of substantial equivalence.
| Metric (Implicit Acceptance Criteria) | Reported Device Performance |
|---|---|
| Correlation (r) | 0.977 |
| Slope (IMMULITE 2000 vs. IMMULITE) | 0.94 |
| Y-intercept (IMMULITE 2000 vs. IMMULITE) | 0.097 ng/mL |
| Mean (IMMULITE 2000) | 1.4 ng/mL |
| Mean (IMMULITE) | 1.4 ng/mL |
2. Sample Size and Data Provenance for the Test Set
- Sample Size: 97 samples
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). This is a common omission in older 510(k) summaries for in-vitro diagnostics where the focus is on analytical performance, not clinical data from specific populations. It's safe to assume the samples were collected specifically for this method comparison study.
3. Number of Experts and Qualifications for Ground Truth
This type of study (method comparison for an in-vitro diagnostic device) does not typically involve human experts establishing ground truth in the way an imaging algorithm might. The "ground truth" for this test set is the measurement provided by the established, commercially available predicate device (IMMULITE® Digoxin).
4. Adjudication Method for the Test Set
Not applicable. As described above, this is a direct comparison to a reference method, not an expert-based adjudication process.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done. This device is an automated in-vitro diagnostic assay, not an imaging or diagnostic aid that involves human readers.
6. Standalone Performance Study
Yes, a standalone study was performed. The "Method Comparison" section directly evaluates the IMMULITE® 2000 Digoxin's performance against a predicate device using analytical samples. This is an assessment of the algorithm/device itself without human-in-the-loop interaction for interpretation.
7. Type of Ground Truth Used
The ground truth used was the results from a legally marketed predicate device (IMMULITE® Digoxin). This is a common and accepted method for demonstrating substantial equivalence for new in-vitro diagnostic devices.
8. Sample Size for the Training Set
The document does not mention a separate "training set" or its size. For this type of competitive immunoassay, training would typically refer to the internal development and calibration of the assay. The 97 samples mentioned are for the method comparison (often considered a validation or test set), not an explicitly stated training set for an AI/algorithm.
9. How the Ground Truth for the Training Set Was Established
Not applicable/not explicitly stated as a distinct "training set" with established ground truth in the same way an AI model would have. The "training" in the context of an immunoassay development involves optimizing reagent concentrations, reaction conditions, and calibration procedures to achieve desired analytical performance characteristics. The "ground truth" for calibration would be provided by purified digoxin standards of known concentrations.
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SEP 1 9 2001
510(k) Summary of Safety and Effectiveness
This summary of safety and effectiveness information has been prepared in accordance with the requirements of SMDA 1990 and 21 CFR Part 807.92.
| Name:Address: | Diagnostic Products Corporation5700 West 96th StreetLos Angeles, California 90045-5597 |
|---|---|
| Telephone Number:Facsimile Number: | (310) 645-8200(310) 645-9999 |
| Contact Person: | Edward M. Levine, Ph.D.Director, Clinical Affairs |
| Date of Preparation: | July 19, 2001 |
| Device Name:Trade: | IMMULITE® 2000 Digoxin |
| Catalog Number: | L2KDI2 (200 tests), L2KDI6 (600 tests) |
| CFR: | A digoxin test system is device intended to measure digoxin, acardiovascular drug, in serum and plasma. Measurementsobtained by this device are used in the diagnosis and treatmentof digoxin overdose and in monitoring levels of digoxin toensure appropriate therapy. |
| Common: | Reagent system for the determination of digoxin in serum andplasma. |
| Classification: | Class II device, KXT (21 CFR 862.3320) |
| Panel: | Clinical Toxicology |
| CLIA ComplexityCategory: | We believe the category to be moderate, based on previousclassification of analogous tests. |
| Manufacturer: | Diagnostic Products Corporation5700 West 96th StreetLos Angeles, California 90045-5597 |
| Establishment RegistrationNumber: | DPC's Registration Number is 2017183 |
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Substantially Equivalent Predicate Device:
IMMULITE® Digoxin (K914833)
IMMULITE® 2000 Digoxin is a solid phase, chemiluminescent Description of Device: enzyme-labeled competitive immunoassay for use with the IMMULITE® 2000 Automated Analyzer
Intended Use of the Device:
IMMULITE® 2000 Digoxin is a solid-phase, chemiluminescent enzyme-labeled competitive immunoassay for use with the IMMULITE® 2000 Automated Analyzer and is designed for the quantitative measurement of digoxin in serum or heparinized plasma, as an aid in monitoring the therapeutic administration of this cardioglycoside, while avoiding toxicity.
Technology:
IMMULITE® 2000 Digoxin is a solid-phase, chemiluminescent enzyme-labeled immunoassay The solid phase is a polystyrene bead coated with a monoclonal murine anti-digoxin antibody.
The patient sample and alkaline phosphatase-conjugated digoxin are simultaneously introduced introduced introduced introduced introduced introduced into the Reaction Tube containing the bead, and incubated for approximately 30 minutes at 37 ( ... intermittent agitation. During this time, digoxin in the sample competes with the enzyme-fairched digoxin for a limited number of antibody binding sites on the bead. Unbound enzyme conjugate is then removed by a centrifugal wash, after which substrate is added and the Reaction Tube is incubated for a further 5 minutes.
The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to vield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision bv providing a window for multiple readings. The bound complex - and thus also the photon output, as measured by the luminometer - is inversely proportional to the concentration of digoxin in the sample
IMMULITE® Digoxin is a solid-phase, chemiluminescent enzyme-labeled immunoassay. The solid phase, a polystyrene bead enclosed within an IMMULITE Test Unit, is coated with a monoclonal murine anti-digoxin antibody.
The patient sample and alkaline phosphatase-conjugated digoxin are simultaneously introduced into the Test Unit, and incubated for approximately 30 minutes at 37°C with intermittent agitation. During this time, digoxin in the sample competes with the enzyme-labeled digoxin for a limited number of antibody binding sites on the bead. Unbound enzyme conjugate is then removed ? centrifugal wash, after which substrate is added and the Test Unit is incubated for a further . minutes.
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Technology (continued):
The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis !!! the presence of alkaline phosphatase to yield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision by providing a window for multiple readings. The bound complex - and thus also the photon output, as measured by the luminometer - is inversely proportional to the concentration of digoxin in the sample.
Performance Equivalence:
Diagnostic Products Corporation asserts that IMMULITE® 2000 Digoxin produce substantialin equivalent results to other commercially marketed digoxin assays, such as IMMULITE® Digoxin
Method Comparison:
The IMMULITE® 2000 Digoxin procedure was compared to a commercially available assay, IMMULITE® Digoxin, on 97 samples, with digoxin concentrations ranging from approximately 0.5 to 6.1 ng/mL. Linear regression analysis yielded the following statistics:
(IMMULITE 2000) = 0.94 (IMMULITE) + 0.097 ng/mL = r = 0.977
1.4 ng/mL (IMMULITE 2000) Means: 1.4 ng/mL (IMMULITE)
Conclusion:
The data presented in this summary of safety and effectiveness is the data that the Food and Drug Administration used in granting DPC substantial equivalence for IMMULITE® 2000 Digoxin.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
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 stylized eagle with three stripes representing the department's mission. The eagle is enclosed in a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter.
SEP 1 9 2001
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Edward M. Levine, Ph.D. Director, Clinical Affairs Diagnostic Products Corporations 5700 West 96th Street Los Angeles, CA 90045-5597
Re: K012301
Trade/Device Name: Immulite® 2000 Digoxin Regulation Number: 21 CFR 862.3320 Regulation Name: Digoxin test system Regulatory Class: Class II Product Code: KXT Dated: July 19, 2001 Received: July 20, 2001
Dear Dr. Levine:
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 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" (21CFR 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/cdrb/dsma/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
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510(k) Number (if known): K012301 Device Name: IMMULITE® 2000 Digoxin
Indications For Use: The IMMULITE® 2000 Digoxin assay is for in vitro diagnostic use with the IMMULITE® 2000 Analyzer -- for the quantitative measurement of digoxin in serum or heparinized plasma, as an aid in monitoring the therapeutic administration of this cardioglycoside, while avoiding toxicity.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Kesia Alexander for Jean Cuypers
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number. K012301
[X]
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use
(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.