The AxSYM Rubella IgM Antibody assay is a Microparticle Enzyme Immunoassay (MEIA) for the qualitative measurement of IgM antibodies to rubella virus in human serum and plasma (EDTA, heparin or sodium citrate) to aid in the diagnosis of primary or acute infection. The AxSYM Rubella IgM assay is not for use with cord blood or neonatal specimens.

Device Description

The AxSYM Rubella IgM Antibody assay is an automated microparticle enzyme immunoassay performed with the AxSYM, a random and continuously accessed automated immunoassay analyzer. It is an in vitro immunologic test method intended for use in the detection of IgM antibody to rubella virus in human serum or plasma (EDTA, heparin or sodium citrate). It is based on the formation of immune complexes between rubella virus antigens and antibody, uses a polystyrene microparticle solid phase coated with antigen from rubella virus strain HPV-77 grown in Vero cell culture, and uses goat anti-human IgM antibody conjugated to alkaline phosphatase with MUP as the enzyme substrate. The AxSYM Rubella IgM Antibody assay pretreats all samples with an RF neutralization buffer.

AI/ML Overview

The provided 510(k) summary describes the Abbott Laboratories AxSYM Rubella IgM Antibody Assay.

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" but rather describes the performance of the new device (AxSYM) in comparison to a predicate device (IMx). The implicit acceptance criteria appear to be substantial equivalence, meaning the performance metrics of the AxSYM assay should be comparable to or better than the predicate IMx assay.

Metric	AxSYM Rubella IgM (Reported Performance)	IMx Rubella IgM (Predicate Device Performance)
Relative Sensitivity	95.7%	95.4%
Relative Specificity	99.4%	99.4%
Relative Agreement	99.1%	Not explicitly stated for IMx, but the comparison implies this is the target.
Percent CV's on positive panel members and positive controls	6.9% to 12.6%	Not explicitly stated for IMx, but satisfactory according to regulatory standards.

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

Sample Size: 1300 samples
Data Provenance: The study was conducted retrospectively using samples from three clinical sites. The document does not specify the country of origin, but given it's an Abbott Laboratories submission, it's likely primarily US-based, though not explicitly stated. The samples were from pregnant women, non-pregnant individuals, and individuals positive for IgM antibodies to rubella.

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 a "ground truth" for the test set in the traditional sense of a diagnostic interpretation. Instead, the predicate device, Abbott's IMx Rubella IgM Antibody assay, served as the primary reference for comparison.

For the 11 discordant specimens, two additional legally marketed assays (Abbott Rubazyme M EIA and BioWhittaker RUBASTAT M) were used for further evaluation. However, the document does not specify human experts or their qualifications involved in interpreting these additional assay results to resolve discrepancies.

4. Adjudication Method for the Test Set:

For the initial comparison, the IMx Rubella IgM Antibody assay served as the reference. For discordant specimens (n=11), a method involving two additional legally marketed assays (Abbott Rubazyme M EIA and BioWhittaker RUBASTAT M) was used. The results from these additional assays were used to classify the discordant samples.

If two assays agreed (e.g., AxSYM positive, IMx negative, and one of the other assays positive), that result likely informed the adjudication.
Samples that remained equivocal after the additional testing were excluded from the calculation of relative agreement, sensitivity, and specificity. This indicates a form of adjudication where inconclusive results were set aside.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly described. This study focuses on the performance of an automated assay (AxSYM) compared to another automated assay (IMx) using existing samples, not on human reader performance with or without AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

Yes, a standalone performance evaluation was done. The study directly compares the performance of the AxSYM Rubella IgM Antibody assay (an automated algorithm/device) against the IMx Rubella IgM Antibody assay (another automated device). There is no mention of human interpretation or involvement in the diagnostic output generation of either assay.

7. The Type of Ground Truth Used:

The ground truth for the study was established using the results of a predicate device (Abbott's IMx Rubella IgM Antibody assay). For discordant cases, further adjudication was performed using two other legally marketed assays. While these are "legally marketed assays," they serve as a form of "reference standard" or "consensus of commercial assays," rather than a gold standard such as pathology or long-term clinical outcomes. No mention of pathology or clinical outcomes data is made.

8. The Sample Size for the Training Set:

The document does not provide information about a training set or its sample size. The description pertains to the performance evaluation of an already developed device, not the development phase where a training set would typically be used. The 510(k) summary focuses on demonstrating substantial equivalence of the finished product.

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

As no training set is mentioned, information on how its ground truth was established is not provided.

Summary

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ATTACHMENT A

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

K954318

MAY 1 4 1996

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Abbott Laboratories AxSYM Rubella IgM Antibody Assay [ 510(k)] Submission

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

The following information presented in the [510(k)] Submission for the AxSYM Rubella IgM Antibody assay constitutes data supporting a substantially equivalent determination:

[510(k) ]Summary of Device Performance

The predicate device for determination of substantial equivalence is Abbott's legally marketed IMx Rubella IgM Antibody assay, a Microparticle Enzyme Immunoassay (MEIA) for the qualitative measurement of IgM antibodies to rubella virus in human serum or plasma (EDTA, heparin or sodium citrate) to aid in the diagnosis of primary infection. The IMx Rubella IgM assay is not for use with cord blood or neonate specimens.

In three clinical sites, the AxSYM Rubella IgM Antibody assay was compared to the Abbott IMx Rubella IgM Antibody assay using 1300 samples from pregnant women, non-pregnant individuals and individuals positive for IgM antibodies to rubella. The AxSYM Rubella IgM Antibody assay was shown to have a relative sensitivity of 95.7%, relative specificity of 99.4% and a relative agreement of 99.1%. Percent CV's on positive panel members and positive controls was 6.9% to 12.6%.

Further evaluation of 11 discordant specimens was performed using two additional legally marketed assays (Abbott Rubazyme M EIA and BioWhittaker RUBASTAT M). Of the seven specimens positive by AxSYM and negative by EIA, two were found to be positive, four were found to be negative and one was found to be equivocal for IgM antibody. Of the four specimens negative by AxSYM and positive by EIA, one was found to be negative and three were found to be equivocal for IgM antibody. Specimens giving equivocal results using AxSYM and/or ElA were not included in the calculation of relative agreement, relative sensitivity and relative specific ty.

In conclusion, the AxSYM Rubella IgM Antibody assay is substantially equivalent to the Abbott IMx Rubella IgM Antibody assay for the detection of IgM antibodies to rubella virus in humarı serum and plasma (EDTA, heparin or sodium citrate) specimens to aid in the diagnosis of primary or acute infection.

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[510/k)] Summary Of Technological Comparison

The AxSYM Rubella IgM Antibody Assay and the IMx Rubella IgM Antibody assay are Substantially Equivalent in that:

1. Both are in vitro immunologic test methods.
1. Both are intended for use in the detection of IgM antibody to rubella virus in human serum or plasma (EDTA, heparin or sodium citrate).
1. Both are based on the formation of immune complexes between rubella virus antigens and antibody.
1. Both use a polystyrene microparticle solid phase.
1. Both are qualitative assays.
1. Both use a solid phase coated with antigen from rubella virus strain HPV-77.
1. Both use antigen produced in Vero cell culture.
1. Both use goat anti-human IgM antibody conjugated to alkaline phosphatase.
1. Both use MUP as the enzyme substrate.
1. Both use an automated instrument.

The AxSYM Rubella IgM Antibody Assay and the IMx Rubella IgM Antibody assay Differ in that:

1. The AxSYM Rubella IgM Antibody assay is an automated microparticle enzyme immunoassay performed with the AxSYM, a random and continuously accessed automated immunoassay analyzer. The IMx Rubella IgM Antibody assay is an automated microparticle enzyme immunoassay performed with the IMx automated immunoassay analyzer.
1. The IMx Rubella IgM Antibody assay requires that all positive samples be treated (RF neutralized) with human IgG microparticles and retested due to the potential for RF interference. The AxSYM Rubella IgM Antibody assay pretreats all samples with an RF neutralization buffer and does not require additional treatment and testing of positive samples.

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Assay Characteristics	AxSYM Rubella IgM	IMx Rubella IgM
Assay Type	Qualitative	Qualitative
Antibody Measured	Specific IgM	Specific IgM
Assay Principle	MEIA	MEIA
Solid Phase	Polystyrenemicroparticles	Polystyrenemicroparticles
Solid Phase Coating	Rubella virus antigenstrain HPV-77grown in Vero cells	Rubella virus antigenstrain HPV-77grown in Vero cells
Conjugate	Goat anti-human IgMconjugated to alkalinephosphatase	Goat anti-human IgMconjugated to alkalinephosphatase
Specimen	Human serum andplasma (EDTA, heparinor sodium citrate)	Human serum andplasma (EDTA, heparinor sodium citrate)
Automation	Performed on automatedinstrument	Performed on automatedinstrument
Relative Sensitivity	95.7%	95.4%
Relative Specificity	99.4%	99.4%

Comparison of Methods

ﺮﻧﺎ ﻓﻲ ﺍﻟﻤﺮﻛﺰ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ

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Certification of search for adverse safety and effectiveness

The undersigned certifies to the best of his knowledge and belief that reasonable search of all information known or otherwise presently available to Abbott Laboratories has been conducted. The scope of the search was as follows:

Accuracy/Clinical Utility/Reproducibility/Safety of Rubella Immunoassays Biohazard of Rubella Antigen Adverse Effects and Safety of Sodium Az de

The searches were performed by Abbott Laboratories Information Services Department for the undersigned individual on March 2, 1995.

Dialog® Information Service was used for database searches. A list of databases is included on the following page in this section.

Conclusion: No adverse safety and effectiveness data was found in the search provided the product is used as intended for in vitro diagnostic use.

Richard M. Fleming

Richard M. Fleming Associate Scientist CRG Business Unit Abbott Laboratories One Abbott Park Road Abbott Park, IL 60064

Databases Searched:

Database File Name

5: BIOSIS PREVIEWS® 1969-1995/Feb W2 72: EMBASE 1985-1995/ISS 06 73: EMBASE 1974-1995/ISS 05 144: PASCAL 1973-1994/Aug 154: MEDLINE (R) 1985-1995/Apr W2 155: MEDLINE® 1966-1995/Apr W2 156: TOXLINE(R) 1965-1995/Jan 336: REG TOX EFF CHEM SUB 1994/Oct 434: SCISEARCH(R) 1974-1995/Jan W5

Regulation Number and Section

§ 866.3510 Rubella virus serological reagents.

(a)
Identification. Rubella virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to rubella virus in serum. The identification aids in the diagnosis of rubella (German measles) or confirmation of a person's immune status from past infections or immunizations and provides epidemiological information on German measles. Newborns infected in the uterus with rubella virus may be born with multiple congenital defects (rubella syndrome).(b)
Classification. Class II. The special controls for this device are:(1) National Committee for Clinical Laboratory Standards':
(i) 1/LA6 “Detection and Quantitation of Rubella IgG Antibody: Evaluation and Performance Criteria for Multiple Component Test Products, Speciment Handling, and Use of the Test Products in the Clinical Laboratory, October 1997,”
(ii) 1/LA18 “Specifications for Immunological Testing for Infectious Diseases, December 1994,”
(iii) D13 “Agglutination Characteristics, Methodology, Limitations, and Clinical Validation, October 1993,”
(iv) EP5 “Evaluation of Precision Performance of Clinical Chemistry Devices, February 1999,” and
(v) EP10 “Preliminary Evaluation of the Linearity of Quantitive Clinical Laboratory Methods, May 1998,”
(2) Centers for Disease Control's:
(i) Low Titer Rubella Standard,
(ii) Reference Panel of Well Characterized Rubella Sera, and
(3) World Health Organization's International Rubella Standard.