(47 days)
The CMV IgM ELISA test system is and enzyme-linked immunosorbent assay (ELISA) designed for the manual or automated (Aptus) qualitative determination of IgM antibodies to cytomegalovirus in human serum. The test is intended to be used to evaluate serologic evidence of primary or reactivated infection with CMV and is for in vitro diagnostic use. This product is not FDA deared (approved) for use in testing (i.e., screening) blood or plasma donors.
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This looks like a 510(k) clearance letter and an Indications for Use statement for an in-vitro diagnostic (IVD) device, specifically an ELISA test. It doesn't contain the detailed study information typically found in a clinical study report or a 510(k) summary. Therefore, many of your requested details cannot be extracted from this document.
However, I can provide what is available, inferring acceptance criteria from the nature of an ELISA test, and outlining what is missing.
Overall Summary:
The provided document describes the FDA clearance of the Aptus (Automated) Application of the CMV IgM ELISA Test, a device designed for the qualitative determination of IgM antibodies to cytomegalovirus in human serum. The clearance is based on substantial equivalence to a predicate device. The document does not contain specific acceptance criteria, study design details, performance metrics, sample sizes, or information about ground truth establishment.
Here's a breakdown of the available and missing information based on your request:
1. Table of Acceptance Criteria and Reported Device Performance
Cannot be fully extracted from the provided text.
For an ELISA test, typical acceptance criteria relate to sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) or agreement with a reference method. The document does not provide these values.
| Metric | Acceptance Criteria (Inferred for ELISA) | Reported Device Performance |
|---|---|---|
| Sensitivity | (Typically a high percentage, e.g., >95% agreement with reference method) | Not provided |
| Specificity | (Typically a high percentage, e.g., >95% agreement with reference method) | Not provided |
| Positive Predictive Value | (Often evaluated for clinical utility, may not be a primary clearance metric) | Not provided |
| Negative Predictive Value | (Often evaluated for clinical utility, may not be a primary clearance metric) | Not provided |
| Overall Agreement | (Often a primary metric for IVD substantial equivalence, e.g., >90%) | Not provided |
| Precision/Reproducibility | (Within-run, between-run, between-lot variability) | Not provided |
| Accuracy | (Agreement with a "gold standard" or predicate device) | Not provided |
2. Sample Size Used for the Test Set and Data Provenance
Not provided in the document.
For typical IVD studies, sample sizes would be detailed, often stratified by patient population (e.g., symptomatic, asymptomatic, different risk groups). The origin of the data (e.g., specific countries, US-based, multi-center) and whether it was retrospective or prospective would also be specified.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
Not applicable/Not provided.
For an ELISA test, "ground truth" is typically established by:
- Confirmed clinical diagnosis (e.g., patient symptoms, other diagnostic tests).
- Results from a well-established, previously cleared or "gold standard" reference assay for CMV IgM.
- In some cases, samples from well-characterized patient panels (e.g., established positive or negative for CMV IgM).
The concept of "experts" to establish ground truth as described (e.g., radiologists) is more relevant to image-based diagnostics.
4. Adjudication Method for the Test Set
Not applicable/Not provided.
Adjudication methods like 2+1 or 3+1 are typically used in studies where multiple human readers are interpreting complex data (e.g., medical images) and their agreement needs to be resolved to establish ground truth or assess reader performance. This is not directly relevant to an automated ELISA test's performance evaluation against a reference.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, not applicable to this device type.
MRMC studies are designed to assess how human readers' performance (e.g., accuracy, efficiency) is affected by the assistance of an AI algorithm. The Aptus device is an automated ELISA test, not an AI-assisted diagnostic tool that helps human readers interpret data. Its performance is typically assessed in standalone mode against a reference method or clinical outcome.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, implicitly.
An ELISA test, especially an "automated application" like the Aptus, is inherently a standalone diagnostic device. Its performance is measured by its ability to correctly identify the presence or absence of CMV IgM antibodies in a sample, independent of human interpretation of the assay results themselves (though a human still interprets the final qualitative result of "positive" or "negative"). The efficacy study for this type of device would assess its analytical and clinical performance as a standalone test. The document, however, does not provide performance metrics from such a study.
7. The Type of Ground Truth Used
Not explicitly stated, but inferred.
For an in vitro diagnostic (IVD) device like this, common ground truths include:
- Reference Method/Predicate Device Results: Comparison against a well-established, often FDA-cleared, CMV IgM ELISA test.
- Clinical Diagnosis: Correlating test results with a patient's overall clinical picture, including other laboratory tests and symptoms, to determine true CMV infection status.
- Well-Characterized Sample Panels: Using samples from individuals with known CMV IgM status.
Given this is a 510(k) for substantial equivalence, the primary ground truth would likely be comparison to the predicate device's results on a set of patient samples.
8. The Sample Size for the Training Set
Not applicable/Not provided.
ELISA tests are biochemical assays, not typically machine learning algorithms that require a "training set" in the computational sense. The "development" or "optimization" of an ELISA assay involves biochemical formulation, reagent stability studies, and assay parameter optimization, rather than machine learning training. If the "automated application" refers to a software component that interprets raw signal data, then there might be a training aspect to that software, but it's highly unlikely to be described in these terms for a traditional ELISA.
9. How the Ground Truth for the Training Set Was Established
Not applicable/Not provided. (See point 8)
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Image /page/0/Picture/2 description: The image is a black and white seal for the Department of Health & Human Services - USA. The seal is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an abstract symbol that resembles a stylized caduceus or a family of three figures.
DEC 1 4 1998
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mark J. Kopnitsky Vice President of Research & Development Zeus Scientific, Inc. P.O. Box 38 Raritan, NJ 08869
Re: K983803 Trade Name: Aptus (Automated) Application of the CMV IgM ELISA Test Regulatory Class: II Product Code: LFZ Dated: October 22, 1998 Received: October 28, 1998
Dear Mr. Kopnitsky:
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 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). 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 requirements, as set forth in the Quality System Regulation (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic OS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in 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.
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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 Sutman
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): ____________________________________________________________________________________________________________________________________________________
Aptus (automated) Application for the CMV IgM ELISA Test Device Name: System
Indications for Use:
The CMV IgM ELISA test system is and enzyme-linked immunosorbent assay (ELISA) designed for the manual or automated (Aptus) qualitative determination of IgM antibodies to cytomegalovirus in human serum. The test is intended to be used to evaluate serologic evidence of primary or reactivated infection with CMV and is for in vitro diagnostic use. This product is not FDA deared (approved) for use in testing (i.e., screening) blood or plasma donors.
Revised 11-19-98
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use
OR
Over-The-Counter Use
(Per 21 CFR 801,109)
2-96)
Wooley Dubois
(Optional Format 1-
Division of Clinical Laboratory Devices
510(k) Number K983803
§ 866.3175 Cytomegalovirus serological reagents.
(a)
Identification. Cytomegalovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to cytomegalovirus in serum. The identification aids in the diagnosis of diseases caused by cytomegaloviruses (principally cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal infection with the virus. The disease may cause severe congenital abnormalities, such as microcephaly (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection has also been associated with acquired hemolytic anemia, acute and chronic hepatitis, and an infectious mononucleosis-like syndrome.(b)
Classification. Class II (performance standards).