CMVgen is an in vitro diagnostic, rapid latex particle agglutination test for the qualitative and semiquantitative determination of total antibodies (IgG and IgM) to cytomegalovirus (CMV) in human serum or plasma (EDTA) to determine prior exposure to cytomegalovirus. This product is not FDA cleared for use in screening blood or plasma (EDTA) donors.

Device Description

AI/ML Overview

The provided text describes the CMVgen device, an in vitro diagnostic test for Cytomegalovirus (CMV) antibodies. However, the document does not explicitly state "acceptance criteria" for the device's performance. Instead, it presents performance data from method comparison studies and a reproducibility study.

Here's an analysis of the provided information, structured to address your questions based on the available text:

Acceptance Criteria and Device Performance

The document does not explicitly define "acceptance criteria" with numerical thresholds for sensitivity, specificity, or other metrics. Instead, it reports the performance of CMVgen against commercially available predicate or reference tests. We can infer that the reported sensitivities were considered acceptable for the 510(k) clearance process.

Table of Performance (Inferred from Study Results)

Performance Metric	Study 1: Against a commercially available total antibody test	Study 2: Against a commercially available IgG EIA test (in organ transplant recipients)	Reproducibility
Reported Device Performance:
Sensitivity	97.5%	91.1%	Not applicable
Reproducibility	Not applicable	Not applicable	100%

Study Details

Sample sizes used for the test set and the data provenance:
- Study 1: 165 serum samples.
  - Provenance: Performed at UMMC Clinical Microbiology Laboratories (Massachusetts). This indicates data from the USA and is retrospective as it refers to collected samples being evaluated.
- Study 2: 131 serum samples.
  - Provenance: Performed at Cambridge University (U.K.). This indicates data from the UK. Ninety of these samples were collected from 31 organ transplant recipients who had experienced either a primary CMV infection or a reactivation of CMV post-transplant. This suggests a mix of retrospective and potentially prospective collection for the transplant recipient cohort, though the overall study presented is an evaluation of existing samples.
- Reproducibility Study: Panels of 10 serum and plasma samples.
  - Provenance: Not explicitly stated, but likely conducted by the manufacturer or a collaborating lab.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The studies described are method comparison studies and a reproducibility study. The "ground truth" was established by commercially available, established assays (a "commercially available total antibody test" and a "commercially available IgG EIA test"), not by independent expert interpretation for each case. Therefore, the concept of "number of experts" or their qualifications for establishing ground truth in this context is not directly applicable.
Adjudication method for the test set:
Not applicable, as ground truth was established by reference assays, not by subjective expert review requiring adjudication among multiple readers.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, if so, what was the effect size of how much human readers improve with AI vs without AI assistance:
No, this is not an MRMC study. The CMVgen device is an in vitro diagnostic (IVD) assay, not an AI or imaging-based device requiring human reader interpretation or assistance. Therefore, this question is not relevant to the provided information.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the performance presented for CMVgen is its standalone performance as an assay. It is inherently an "algorithm only" in the sense of a chemical/biological reaction and readout, without human-in-the-loop performance influencing the assay's result. The human reads the result of the assay.
The type of ground truth used:
The ground truth was established by comparison to commercially available, established assays (reference tests). This is a common method for validating new IVD assays.
The sample size for the training set:
The document does not mention a "training set" in the context of machine learning or AI. For IVD assays, products are typically developed and optimized using various samples, but these are not usually formally designated as "training sets" in the same way as in AI/ML validation. The samples mentioned (165 and 131 samples) are referred to as evaluation or test samples for performance assessment.
How the ground truth for the training set was established:
Not applicable, as there is no explicitly defined "training set" as understood in AI/ML, nor is there a described process for establishing ground truth for such a set. Development and optimization of an IVD assay would involve a range of known positive and negative samples, but the method for establishing their "truth" is not detailed in this summary. It would typically involve clinical diagnosis, other gold-standard assays, or well-characterized patient cohorts.

Summary

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K974456

1 1998 MAY

SECTION 3 CMVgen - 510(k) SUMMARY (Summary of Safety and Effectiveness)

Submitted by:

Carol Marble Regulatory Affairs Engineer Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, MA 02173 Phone: (781) 861-4467 (781) 861-4464 Fax:

Contact Persons:

Carol Marble Phone: (781) 861-4467

Summary Prepared:

November 24, 1997 (Revised on February 23, 1998)

Name of the device:

CMVgen

Classification name(s):

866.3175	Cytomegalovirus serological reagents
83LJO	Antigen, IHA, Cytomegalovirus

Class II

Identification of predicate device(s):

K841520 CMVscan

Description of the device/intended use(s):

Statement of How the Technological Characteristics of the Device compare to the Predicate Device:

CMV gen uses the same test principle (passive latex agglutination) as the predicate CMVscan and is substantially equivalent in performance, intended use, and safety and effectiveness with the exception that CMVscan is labeled for use to screen donor specimens.

Summary of Performance Data:

In a method comparison study performed at UMMC Clinical Microbiology Laboratories (Massachusetts) evaluating 165 serum samples, the sensitivity of CMVgen as compared to a commercially available total antibody test was 97.5%. In a separate study performed at Cambridge University (U.K.) evaluating 131 serum samples (ninety of which were collected from 31 organ transplant recipients who had experienced either a primary CMV infection or a reactivation of CMV post-transplant), the sensitivity of CMVgen as compared to a commercially available IgG EIA test was 91.1%.

In a reproducibility study, panels of 10 serum and plasma samples were tested on 3 consecutive days using the semiquantitative procedure for CMVgen. The results, as defined by the ability to give agreement to within one 2-fold dilution on the replicates, indicated 100% reproducibility.

Section 3

CMVgen 510(k)

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Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

1 1658 MAY

Carol Marble Senior Regulatory Affairs Specialist Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, MA 02173-3190

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K974456 Re: Trade Name: CMVgen Regulatory Class: II Product Code: LJO Dated: February 23, 1998 Received: February 24, 1998

Dear Ms. Marble:

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 QS 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 Butman

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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Indications for Use Statement

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: CMVgen

Indications for Use:

CMVgen is an in virro diagnostic, rapid latex particle agglutination test for the qualitative and semiquantitative determination of total antibodies (IgG and IgM) to cytomegalovirus (CMV) in human serum or plasma to determine prior exposure to cytomegalovirus.

This assay has not been FDA cleared for use in screening blood or plasma donors.

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

signature

(Division Sign-Off) Division of Clinical Laboratory Device 510(k) Number _

Prescription Use
(Per 21 CFR 801.019)

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

Section 2

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CMVgen 510(k)

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Regulation Number and Section

§ 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).