IMMULITE® Rubella IgG is designed for the qualitative detection of IgG antibodies to Rubella virus in human serum. It is intended strictly for in vitro diagnostic use as an aid in the determination of immune status to rubella. This assay is particularly useful as an indicator of immune status for women of childbearing age.

Device Description

IMMULITE® Rubella IgG is a solid-phasc, two-step, chemiluminescent enzyme immunoassay The solid phase, a polystyrene bead enclosed within an IMMULITE® Test Unit, is coated with partially purified rubella antigen. Prediluted patient sample (1-in-21 dilution) and a protein-based buffer are simultaneously introduced into the Test Unit, and incubated for approximately 30 minutes at 37°C with intermittent agitation. During this time, rubella IgG in the sample binds to the rubella antigen-coated bead. Unbound serum is then removed by a centrifugal wash. An alkaline phosphatase-labeled anti-human IgG antibody is introduced, and the Test Unit is incubated for another 30-minute cycle. The unbound enzyme conjugate is removed by a centrifugal wash. Substrate is then added, and the Test Unit is incubated for an additional 10 minutes. The chemiluminescent substrate, a phosphate cster 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 by providing a window for multiple readings. The bound complex - and thus the photon output, as measured by the luminometer - is directly related to the presence of rubella IgG in the sample. A qualitative result is then obtained by comparing the patient result to an established Cutoff.

AI/ML Overview

Here's an analysis of the provided text regarding the IMMULITE® Rubella IgG device, broken down by your requested categories:

Acceptance Criteria and Device Performance

Acceptance Criteria (Implied)	Reported Device Performance
Agreement with established Rubella immune status (CDC panel)	98% total agreement with CDC results. 98% agreement with positive specimens in CDC panel. 100% agreement with negative specimens in CDC panel.
Agreement with Predicate Device (IMx Rubella IgG) in clinical study	98.6% overall agreement. Relative Sensitivity: 99.3% (95% CI: 97.4% - 99.9%) Relative Specificity: 91.3% (95% CI: 72.0% - 98.9%)
Qualitative Detection of IgG antibodies to Rubella virus	The device is designed for the qualitative detection of IgG antibodies to Rubella virus. The performance metrics (sensitivity, specificity, agreement) demonstrate its ability to classify samples as positive, indeterminate, or negative for rubella IgG.
Aid in determination of immune status to rubella	The study results, particularly the high agreement with the CDC panel and predicate device, support its use as an aid in determining immune status.
Safety and Effectiveness	The conclusion states: "The conclusions drawn from the clinical and nonclinical studies demonstrate that the device is safe, effective, and performs as well as, or better, than the current legally marketed devices." This is a general statement inferred from the performance data presented. Specific safety data is not detailed in this summary.

Study Details

2. Sample size used for the test set and the data provenance:

CDC Proficiency Panel Study:
- Sample Size: Not explicitly stated, but the panel "consisted of 82% positive and 18% negative samples." To determine the number of samples, we'd need the total size of the CDC panel.
- Data Provenance: United States (Centers for Disease Control and Prevention - CDC). Retrospective.
University Medical Center Clinical Study:
- Sample Size: 300 serum specimens.
- Data Provenance: Northwestern United States (university medical center). Prospective (specimens "previously collected and frozen by the investigators").

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

CDC Proficiency Panel Study: The ground truth was established by the CDC. The text doesn't specify the number or qualifications of experts involved in creating this "characterized serum panel," but implies it's a reference standard from a reputable public health organization.
University Medical Center Clinical Study: The ground truth for this study was established by the predicate device, IMx® Rubella IgG. No human experts were explicitly stated as establishing ground truth for the test set in this particular study, as it was a device-to-device comparison.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

CDC Proficiency Panel Study: No adjudication method is described. The CDC panel results were considered the "unmasked" ground truth.
University Medical Center Clinical Study: No adjudication method is described. The IMx® Rubella IgG results were used as the comparator.

5. 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, a multi-reader multi-case (MRMC) study was not conducted. This document describes a diagnostic device (immunoassay) for detecting antibodies, not an AI-assisted diagnostic imaging or interpretation tool. Therefore, the concept of human readers improving with AI assistance is not applicable here.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

Yes, this was a standalone performance study. The IMMULITE® Rubella IgG assay is an automated immunoassay system that provides a qualitative result (positive/negative/indeterminate) based on its chemical reactions and luminometer readings. There is no human interpretation or intervention in the diagnostic process once the sample is loaded and the test is initiated.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

CDC Proficiency Panel Study: Characterized serum panel from CDC (implying an established reference standard, likely based on confirmed clinical status or a consensus of highly accurate methods).
University Medical Center Clinical Study: The ground truth was established by the results of the predicate device, Abbott Laboratories' IMx® Rubella IgG.

8. The sample size for the training set:

The document does not specify a sample size for a training set. This is typical for immunoassay devices, where "training" usually refers to assay development and optimization rather than machine learning model training in the AI sense.

9. How the ground truth for the training set was established:

Given that this is an immunoassay device and not an AI algorithm, the concept of a "training set" with established ground truth in the machine learning context is not directly applicable. Assay development would involve optimizing reagents and protocols using known positive and negative samples, but these are not explicitly detailed as a separate "training set" in this summary. The summary focuses on performance evaluation using the described test sets.

Summary

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Diagnostic Products Corporation 5700 West 96th Street Los Angeles, CA 90045-5597 Tel: (213) 776-0180 Fax: (213) 776-0204

APR - 2 1997

Image /page/0/Picture/3 description: The image shows the logo for DPC. The letters are in a bold, sans-serif font and are arranged horizontally. The letters are all capitalized and are black. There is a registered trademark symbol to the right of the letter C.

510 (k) Summary of Safety and Effectiveness

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR Part 807.92.

Name: Address:

Telephone Number: Facsimile Number:

Contact Person:

Date of Preparation:

Device Name: Trade: Catalog Number: Common:

Classification:

Manufacturer:

Establishment Registration #: Substantially Equivalent Predicate Device:

Description of Device:

Intended Use of the Device:

Diagnostic Products Corporation 5700 West 96th Street Los Angeles, California 90045

(213) 776-0180 (213) 776-0204

Edward M. Levine, Ph.D. Director of Clinical Affairs Januarv 20, 1997

IMMULITE® Rubella IgG LKRBZ (50 tests); LKRB2 (200 tests) Reagent system for the determination of rubella IgG antibodies in human serum.

Class III device (866.3510)

Diagnostic Products Corporation (DPC) 5700 West 96th Street Los Angeles, California 90045

#2017183

Abbott Laboratories' IMx® Rubella IgG K885297

IMMULITE Rubella IgG is a clinical device for use with the IMMULITE Automated Immunoassay Analyzer

IMMULITE Rubella IgG is designed for the qualitative detection of IgG antibodies to Rubella virus in human serum. It is intended strictly for in vitro diagnostic use as an aid in the determination of immune status to rubella. This assay is particularly useful as an indicator of immune status for women of childbearing age.

Image /page/0/Picture/26 description: The image shows a logo with the text "EXCELLENCE in DIAGNOSTICS" arranged in a circular fashion around a globe. The globe is stylized with visible continents and grid lines. To the left of the globe, the number "25" is prominently displayed, with the word "YEARS" underneath it. The logo appears to be for a company or organization celebrating 25 years of excellence in diagnostics.

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Diagnostic Products Corporation 700 West 96th Street geles CA 90045 (213) 776-0180 (213) 776-0204

Summary and Explanation of the Device:

Prediluted patient sample (1-in-21 dilution) and a protein-based buffer are simultaneously introduced into the Test Unit, and incubated for approximately 30 minutes at 37°C with intermittent agitation. During this time, rubella IgG in the sample binds to the rubella antigen-coated bead. Unbound serum is then removed by a centrifugal wash

An alkaline phosphatase-labeled anti-human IgG antibody is introduced, and the Test Unit is incubated for another 30-minute cycle. The unbound enzyme conjugate is removed by a centrifugal wash. Substrate is then added, and the Test Unit is incubated for an additional 10 minutes.

The chemiluminescent substrate, a phosphate cster 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 by providing a window for multiple readings. The bound complex - and thus the photon output, as measured by the luminometer - is directly related to the presence of rubella IgG in the sample. A qualitative result is then obtained by comparing the patient result to an established Cutoff.

Performance Equivalence - Technology Comparison:

Diagnostic Products Corporation (DPC) asserts that IMMULITE® Rubella IgG is substantially equivalent to the IMx® Rubella IgG kit marketed by Abbott Laboratories (Abbott Park, IL).

Each product is designed for the detection of igG antibodics to rubella virus in human serum. Each product is intended strictly for in vitro diagnostic use as an aid in the determination of immune status to rubella

IMMULITE® Rubella IgG is a chemiluminescent enzyme immunoassay, and IMx Rubella IgG is a microparticle enzyme immunoassay (MEIA) The technology in DPC's IMMULITE Rubella IgG is identical to technology used in previously cleared and commercially marketed IMMULITE® products.

In the IMx Rubella IgG assay, the patient sample and diluent buffer are added to predilution well of a reaction cell Rubella virus coated microparticles and the diluted sample are added to an incubation well. The Rubella antibody binds to the Rubella virus coated microparticles, forming an antigen-antibody complex. Diluent buffer is added to the reaction mixture and an aliquot of the antigen-antibody complex is transferred to the glass fiber matrix. The microparticles bind irreversibly to the glass fiber matrix. The matrix is washed to remove unbound materials. The anti-human IgG/alkaline phosphatase conjugate is dispensed onto the matrix and binds to the antigen-antibody complex. Finally, the matrix is washed to remove unbound materials, the substrate, 4-Methylumbellifery1 Phosphat: is added to the matrix, and the fluorescent product is measured by the optical assembly.

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Diagnostic Products Corporation 5700 West 96th Street s Angeles, CA 90045 (213) 776-0180 Fax: (213) 776-0204

Performance Equivalence - Clinical Performance:

The clinical performance of the IMMULITE Rubella IgG assay was studied at Diagnostic Products Corporation (DPC) using a Rubella proficiency panel obtained from the United States Centers for Disease Control and Prevention (CDC)

The in-house (DPC) retrospective study was conducted by assaying the CDC serum panel with the IMMULITE Rubella IgG assay, and sending the results to the CDC for unmasking. The results are presented as a means to convey further information on the performance of this assay with a masked, characterized serum panel. This does not imply an endorsement of the assay by the CDC.

The panel consisted of 82% positive and 18% negative samples. The IMMULITE Rubella IgG assay demonstrated 98% total agreement with the CDC results. Of the results obtained by DPC, there was 98% agreement with the positive specimens and 100% agreement with the negative specimens

Studies on the clinical performance of the IMMULITE Rubella IgG assay were also conducted at a university medical center located in the northwestern United States. A total of 300 serum specimens (previously collected and frozen by the investigators) were tested. Of the 300 specimens used in the prospective clinical study, 31 were from healthy, asymptomatic individuals undergoing a pre-employment screening, 256 were from pregnant women undergoing rubella screening and the remainder were obtained from female patients with miscellaneous diseases and conditions (AIDS. heart disease, unmunocompromised, kidney transplant/dialysis). There were 9 male and 291 female subjects, with ages ranging from 11 to 57 vears

All 300 specimens were evaluated with the IMMULITE Rubella IgG assay and the IMx Rubella IgG, an enzyme-linked fluorescent immunoassay (ELFA) which is commercially available on the IMx automated system

IMMULITE Rubella IgG

IMx	Positive	Indeterminate	Negative	RelativeSensitivity	RelativeSpecificity
Positive	271	1	2	99.3%	91.3%
Indeterminate	0	0	0
Negative	2	3	21

98.6% Agreement: 95% Confidence Limits for Relative Sensitivity and Specificity, respectively: 97.4% - 99.9% and 72.0% - 98.9%

Conclusion:

The conclusions drawn from the clinical and nonclinical studies demonstrate that the device is safe, effective, and performs as well as, or better, than the current legally marketed devices.

Edward R. Lewis

Edward M. Levine., Ph.I). Director of Clinical Affairs

1/23/97

Date

DPC®

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.