for the semi-quantitative measurement of IgG antibodies to cytomeqalovirus in serum and plasma (EDTA, heparin or sodium citrate) as an indication of past or current infection with cytomegalovirus. This product is not FDA cleared for use in testing blood or plasma donors.

Device Description

The AxSYM CMV IgG assav is a Microparticle Enzyme Immunoassay (MEIA) for the semi-quantitative measurement of IgG antibodies to cytomeqalovirus in serum and plasma (EDTA, heparin or sodium citrate) as an indication of past or current infection with cytomegalovirus.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study proving device performance, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance (AxSYM CMV IgG)
Relative Agreement	99.8% (1194/1197)
Relative Sensitivity	99.5% (589/592)
Relative Specificity	100% (605/605)

Note: The document states that the predicate device (Vidas CMV IgG) has a "Relative Specificity" of 98.1% and a "Relative Sensitivity" of 100%. While the AxSYM device's performance is compared against the predicate as part of establishing substantial equivalence, the text doesn't explicitly state what the acceptance criteria for these metrics were for the AxSYM device itself, beyond demonstrating close proximity or superiority to the predicate. However, given the reported performance numbers, it implies the acceptance criteria were met by showing comparable or better performance.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size: 1200 patient specimens.
Data Provenance: The specimens were evaluated at "2 U.S. laboratories and 1 European laboratory," indicating a multi-center study across different geographic regions. The text refers to "patient specimens," suggesting they are from real patients, but it does not specify whether they were collected retrospectively or prospectively.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not mention the use of experts to establish ground truth. Instead, it compares the AxSYM device's performance against a "legally marketed EIA (ELFA)" which serves as the comparator or "reference" method. For resolving discordant results, "2 additional legally marketed assays" were used, effectively acting as a 'tie-breaker' or confirmation.

4. Adjudication Method for the Test Set

For discordance, a method akin to a "2+1" or "3+1" adjudication was used.

Initial Comparison: AxSYM vs. legally marketed EIA (ELFA).
Discordance Resolution: If there was a difference between AxSYM and the initial EIA (ELFA), the specimen was re-evaluated using "2 additional legally marketed assays." The outcome of these two additional assays determined the 'resolved' truth.
Specific Example: "Of the 3 specimens positive by EIA (ELFA) and negative by AxSYM, all 3 were negative after resolution," implying that both additional assays agreed with the AxSYM result (negative) over the initial EIA (ELFA) result (positive).

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study was not done. This study is for an in vitro diagnostic (IVD) device (a laboratory test) that measures antibodies, not an imaging device requiring human interpretation of images. Therefore, the concept of "human readers" or "AI assistance" in that context does not apply.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the study describes the standalone performance of the AxSYM CMV IgG assay. This is an automated immunoassay where the device itself performs the measurement and provides a semi-quantitative result without real-time human interpretation affecting the immediate outcome. The results presented (Relative Agreement, Sensitivity, Specificity) are direct outputs of the device's performance compared to a reference method.

7. The Type of Ground Truth Used

The ground truth was established by:

Initially, a "legally marketed EIA (ELFA)" served as the primary comparator.
For discordant results, "2 additional legally marketed assays" were used for resolution. This indicates a consensus or reconciliation of established, legally marketed diagnostic assays rather than pathology, expert consensus, or outcomes data in the traditional sense for image interpretation.

8. The Sample Size for the Training Set

The document does not provide information about a specific "training set" or its size for the AxSYM CMV IgG assay. This type of in vitro diagnostic device typically undergoes substantial development and analytical validation, but the summary mainly focuses on the clinical performance study (the "test set" described above) used for regulatory submission.

9. How the Ground Truth for the Training Set Was Established

As no training set information is provided, there is no description of how its ground truth was established.

Summary

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ATTACHMENT A

[510(k)] Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination

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[510(K)] Summary Of Safety And Effectiveness Information Supporting A Substantially Equivalent Determination

The following information as presented in the [510(k)] notification for the AxSYM CMV lgG assay constitutes data supporting a substantially equivalent determination.

[510(K)] Summary Of Device Performance

The predicate device used for determination of substantial equivalence is the Vidas CMV IgG Assay, a semi-quantitative automated enzyme-linked fluorescent immunoassay (ELFA). It is intended for use in determination of CMV immunological experience from a single serum sample, or as an aid in the diagnosis of current CMV infection through evaluation of paired sera for a significant increase in CMV-specific IgG. It is not intended for use in testing (screening) blood or plasma donors.

Twelve hundred (1200) patient specimens were evaluated for the presence of IgG antibody to cytomegalovirus at 2 U.S. laboratories and 1 European laboratory using the AxSYM CMV IgG Antibody assay. In addition, each specimen was tested using a legally marketed EIA (ELFA). Of the 1200 specimens evaluated, 3 were equivocal by EIA (ELFA). Specimens giving equivocal results using EIA (ELFA) were not included in the calculation of relative agreement, relative specificity or relative sensitivity. Three specimens vielded discordant results between EIA (ELFA) and AxSYM. The relative agreement was 99.8% (1194/1197). The relative sensitivity was 99.5% (589/592) and the relative specificity was 100% (605/605). Further evaluation of the 3 discordant specimens was performed using 2 additional legally marketed assays. Of the 3 specimens positive by EIA (ELFA) and neqative by AxSYM, all 3 were negative after resolution.

In conclusion, the AxSYM CMV IqG assay is substantially equivalent to the Vidas CMV IgG assay for the detection of IgG antibodies to cytomegalovirus in human serum specimens.

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[510(K)] Summary Of Technological Comparison

The AxSYM CMV IgG Antibody Assay and the Vidas CMV IgG Assay are Substantially Equivalent in that:

1. Both are in vitro immunologic test methods.
1. Both are intended for use in the detection of IgG antibody to cytomegalovirus in human serum.
1. Both are based on the formation of immune complexes between cytomegalovirus antigens and antibody.
1. Both use antigen coated solid phases.
1. Both use a solid phase coated with cytomeqalovirus strain AD 169.
1. Both are semi-quantitative assays.
1. Both conjugates are conjugated to alkaline phosphatase.
1. Both assays are automated.

The AxSYM CMV IgG Antibody Assay and Vidas CMV IgG Assay Differ in that:

1. The AxSYM CMV IgG Antibody assay is an automated microparticle enzyme immunoassay performed with the AxSYM random and continuously accessed automated immunoassay analyzer. The Vidas CMV IgG assay is an automated enzyme-linked fluorescent immunoassay performed with a Vidas (Vitek ImmunoDiadnostic Assay System) instrument.
1. The solid phase used in the AxSYM CMV IgG Antibody assay is a polystyrene microparticle. The solid phase used in the Vidas CMV IgG assay is a Solid Phase Receptacle (SPR).
1. The conjugate in the AxSYM CMV IgG Antibody assay uses goat anti-human IgG antibody conjugated to alkaline phosphatase. The conjugate in the Vidas CMV IgG assay consists of mouse monoclonal anti-human IgG antibody conjugated to alkaline phosphatase.
1. Plasma (EDTA, sodium citrate, and heparin) specimens may be tested in the AxSYM CMV IgG Antibody assay. The use of plasma specimens has not been validated for use in the Vidas CMV IgG assay.

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Comparison of Methods

Assay Characteristics	AxSYM CMV IgG	Vidas CMV IgG
Assay Type	Semi-quantitative	Semi-quantitative
Antibody Measured	Specific IgG	Specific IgG
Assay Principle	MEIA	EIA (ELFA)
Solid Phase	polystyrene microparticles	solid phase receptacle
Solid Phase Coating	cytomegalovirus antigenstrain AD169	cytomegalovirus antigenstrain AD169
Conjugate	goat anti-human IgGconjugated toalkaline phosphatase	mouse monoclonalanti-human IgGconjugated toalkaline phosphatase
Specimen	Human serum andplasma (EDTA, sodiumcitrate, heparin)	Human serum
Automation	Performed on automatedinstrument	Performed on automatedinstrument
Relative Sensitivity	99.5%	100%
Relative Specificity	100%	98.1%

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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).