The VIDAS® RUB IgG (RBG) assay uses Enzyme Linked Fluorescent Assay (ELFA) technology on the VIDAS® automated instruments for the in vitro quantitative and qualitative measurement of IgG antibodies to rubella virus in human serum. The VIDAS® RUB IgG assay is intended as an aid in the determination of immune status to rubella. The performance of this device has not been established for screening of cord blood, or for neonatal samples. Likewise, performance characteristics of the assay have not been established for immunocompromised or immunosuppressed individuals.

Device Description

The assay principle combines a 2-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR®) serves as the solid phase as well as the pipetting device for the assay. It is coated with Rubella antigen. The other reagents for the assay are ready-to-use and pre-dispensed in the sealed reagent strips. The individual kit components are described in detail on the following pages.

All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times. This operation enables the Rubella antigen fixed onto the interior wall of the SPR to capture the Rubella antibodies present in the sample. After dilution, the sample is incubated with the SPR. Rubella IgG antibodies present in the specimen bind to the Rubella antigen coating the interior of the SPR. Unbound components are eliminated during the preliminary wash step.

A second incubation step is then performed using alkaline phosphatase labeled monoclonal anti-human IgG antibodies (mouse), followed by a second wash step.

During the final detection step, the substrate (4-Methyl-umbellifery) phosphate) is cycled in and out of the SPR. The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone), the fluorescence of which is measured at 450 nm.

The intensity of the fluorescence is proportional to the concentration of antibodies present in the sample. At the end of the assay, results are automatically calculated by the instrument in relation to the calibration curve stored in memory, and then printed out.

AI/ML Overview

This submission describes the VIDAS® RUB IgG Assay, an in vitro diagnostic device for the quantitative and qualitative measurement of IgG antibodies to rubella virus in human serum, intended as an aid in determining immune status to rubella. The study presented aims to demonstrate substantial equivalence to the predicate device, the Abbott's AxSYM Rubella IgG Antibody Assay.

Here's an analysis of the acceptance criteria and study detailed in the provided documentation:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria (e.g., minimum percentage agreement for positive or negative results). Instead, it presents the performance data and implies that these results are considered acceptable for demonstrating substantial equivalence to the predicate device.

For the purpose of this analysis, we will infer the "reported device performance" directly from the clinical performance tables provided. The study compares the VIDAS® RUB IgG assay's results against a "2/3 Consensus" method, which serves as the ground truth.

Performance Metric	Acceptance Criteria (Inferred Best Case)	Reported Device Performance (Worst Case CI Lower Bound)
Prospective Pregnant Women
Positive Agreement	As high as possible (e.g., >95%)	94.3% (Lower 95% CI for Positive Agreement)
Negative Agreement	As high as possible (e.g., >95%)	9.4% (Lower 95% CI for Negative Agreement)
Prospective General Population
Positive Agreement	As high as possible (e.g., >95%)	93.5% (Lower 95% CI for Positive Agreement)
Negative Agreement	As high as possible (e.g., >95%)	9.4% (Lower 95% CI for Negative Agreement)
Retrospective Pregnant Women
Positive Agreement	As high as possible (e.g., >95%)	88.1% (Lower 95% CI for Positive Agreement)
Negative Agreement	As high as possible (e.g., >95%)	29.2% (Lower 95% CI for Negative Agreement)
Retrospective General Population
Positive Agreement	As high as possible (e.g., >95%)	87.5% (Lower 95% CI for Positive Agreement)
Negative Agreement	As high as possible (e.g., >95%)	96.5% (Lower 95% CI for Negative Agreement)
Pre-selected Pregnant Women
Positive Agreement	As high as possible (e.9., >95%)	74.0% (Lower 95% CI for Positive Agreement)
Negative Agreement	As high as possible (e.9., >95%)	96.4% (Lower 95% CI for Negative Agreement)

Note: The wide confidence intervals for negative agreement, especially in prospective populations and retrospective pregnant women, suggest small sample sizes for negative cases in those cohorts. The "Worst Case CI Lower Bound" is used as a conservative measure, as the actual point estimate for agreement is higher in most cases.

2. Sample Sizes and Data Provenance

The study utilized a combination of prospective and retrospective samples from various populations.

Prospective Pregnant Women: 325 samples
Prospective General Population: 179 samples (1 sample was QNS and excluded from analysis)
Retrospective Pregnant Women: 200 samples
Retrospective General Population: 291 samples (5 samples were QNS and excluded from analysis)
Pre-selected Pregnant Women Population: 127 samples (2 samples were QNS and excluded from analysis)

Data Provenance: The document does not explicitly state the country of origin for the data. Given the submitter's address in Hazelwood, MO, USA, and the FDA's regulatory context, it is highly probable that the studies were conducted in the United States or followed U.S. regulatory guidelines for data collection. The data included both retrospective and prospective samples.

3. Number of Experts and Qualifications for Ground Truth

The document states that the ground truth for the clinical performance evaluation was established using a "2/3 Consensus" method. This implies that at least three reference methods or expert readers were used, and the final classification (Positive, Equivocal, or Negative) was based on agreement from at least two out of three.

Qualifications of Experts: The document does not explicitly state the qualifications of the "experts" or the nature of the "reference methods" used to form the consensus. Typically, for serological assays, this consensus would involve results from established reference assays or expert interpretation of multiple existing test results, rather than human "readers" in the context of imaging.

4. Adjudication Method

The adjudication method used for establishing the ground truth for the test set was a "2/3 Consensus". This means that for a sample to be classified as Positive, Equivocal, or Negative, at least two out of three independent comparators (presumably other rubella IgG assays or a panel with known status) had to agree on that classification.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly mentioned or presented in the provided text. This type of study typically involves human readers (e.g., radiologists, pathologists) interpreting medical images or data, with and without AI assistance, to measure the impact of AI on their performance. The VIDAS® RUB IgG Assay is an automated immunoassay, designed to directly provide quantitative and qualitative results, rather than assisting human interpretation of complex medical cases. Therefore, an MRMC study is not applicable here.

6. Standalone Performance Study

Yes, a standalone performance study was done. The clinical performance data presented (Prospective, Retrospective, and Pre-selected populations) directly reflects the algorithm's (VIDAS® RUB IgG Assay) performance in classifying samples as Positive, Equivocal, or Negative, compared to the established "2/3 Consensus" ground truth. The tables explicitly show the agreement rates of the VIDAS® assay alone against the consensus.

7. Type of Ground Truth Used

The type of ground truth used for the test set was expert consensus, specifically a "2/3 Consensus" method. While the specifics of what constituted this consensus (e.g., comparison to a gold standard assay, multiple predicate assays, or a well-characterized reference panel) are not detailed, it implies an agreement among a minimum of two out of three established methods or experts.

8. Sample Size for the Training Set

The document does not provide information on the sample size used for the training set. Immunoassays like the VIDAS® system are typically developed and optimized through extensive R&D, including reagent formulation, calibration curve development, and internal validation, rather than "training" in the same sense as machine learning algorithms. If any computational models were involved in the assay's development or calibration, the training data for those are not described. The provided data is for the validation or test sets used to demonstrate clinical performance.

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

As no training set information is provided, the method for establishing its ground truth is also not described. For laboratory assays, "ground truth" during development often comes from well-characterized reference materials, spiked samples, or comparison to established gold standard methods.

Summary

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K080766 510(k) SUMMARY

VIDAS® RUB IgG Assay

DEC 2 3 2008

A. Submitter Information

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Sandra PerreandSr. Director, North American Regulatory Affairs
Phone Number:	314-731-8594
Fax Number:	314-731-8689
Date of Preparation:	December 2008
B. Device NameTrade Name:	VIDAS® RUB IgG Assay

	1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1
Common Name:	Rubella IqG Antibody
Classification Name:	Enzyme Linked Immunoabsorbent Assay, Rubella

C. Predicate Device Name Trade Name:

AxSYM Rubella IgG Antibody Assay

D. Device Description

A second incubation step is then performed using alkaline phosphatase labeled monoclonal anti-human IgG antibodies (mouse), followed by a second wash step.

E. Intended Use

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F. Technological Characteristics Summary

A general comparison of the similarities and differences of the VIDAS RUB IgG assay to the predicate
device is presented in the table below.

Item	VIDAS® RUB IgG Assay	Abbott'sAxSYM Rubella IgG Antibody Assay(K954045)
General Comparison
Intended Use	The VIDAS® RUB IgG (RBG) assay usesEnzyme Linked Fluorescent Assay(ELFA) technology on the VIDAS®automated instruments for the in vitroquantitative and qualitative measurementof IgG antibodies to rubella virus inhuman serum. The VIDAS® RUB IgGassay is intended as an aid in thedetermination of immune status to rubella.The performance of this device has notbeen established for screening of cordblood, or for neonatal samples. Likewise,performance characteristics of the assayhave not been established forimmunocompromised orimmunosuppressed individuals.	The AxSYM Rubella IgG assay is aMicroparticle Enzyme Immunoassay(MEIA) for the quantitative andqualitative measurement of IgGantibodies to rubella virus in humanserum or plasma (EDTA, heparin orsodium citrate) to aid in thedetermination of immune status torubella.
Specimen	Serum	Serum or plasma (EDTA, heparin orsodium citrate)
Analyte	Rubella IgG	Rubella IgG
Antibody	Mouse monoclonal anti-human IgG	Goat anti-human IgG
Assay Principle	Two step antibody binding of Rubellaantibodies. An antigen is bound to a solidphase and anti-human IgG is in liquidform and is labeled with fluorescentcompound	Twostep antibody binding of Rubellaantibodies. An antigen is bound to asolid phase and anti-human IgG is inliquid form and is labeled withfluorescent compound
Automated	Yes	Yes
Assay Technique	Enzyme-linked fluorescent assay (ELFA)	Microparticle enzyme immunoassay(MEIA)
Sample Volume	100 μL	180 μL
Traceability/Standardization	Master curve for each kit lot and eachcalibrator lot are traceable to the 2ndpreparation of the World HealthOrganization (WHO) 1st InternationalRubella Reference Standard	Each calibrator lot is traceable to theWorld Health Organization (W.H.O.)2nd International Standard for Anti-Rubella Immunoglobulin
Measurement range	0 - 400 IU/mL	0 - 500.0 IU/mL

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G. Performance Data

Precision

Four serum samples were tested in duplicate twice a day (2 runs per day over 10 days) on each of the 2 reagent lots using a single instrument at each of three sites (N = 240). The repeatability (intra-run precision, between-site precision and total precision were calculated according to the CLS10 EP5-A2 document.

		Repeatability		Inter-runprecision		Between siteprecision		Total precision
Sample	Meanconcentrationon IU/mL	Standarddeviation	CV(%)	Standarddeviation	CV(%)	Standarddeviation	CV(%)	Standarddeviation	CV(%)
Sample 1	7.8	0.58	7.4	0.58	7.4	0.20	2.5	0.84	10.8
Sample 2	8.8	0.57	6.4	0.66	7.4	0.22	2.5	0.89	10.2
Sample 3	29.8	1.46	4.9	2.62	8.8	0.95	3.2	3.14	10.6
Sample 4	154.6	10.58	6.8	18.49	12.0	0.00	0.0	21.30	13.8

Clinical Performance

The following tables compare the results of the V!DAS® RUB !gG assay to the consensus comparator

Prospective populations

	Prospective Pregnant Women2/3 Consensus				Prospective General2/3 Consensus
VIDAS®	Pos	Equiv	Neg	Total	Pos	Equiv	Neg	Total
Pos	309	1	0	310	170	1	0	171
Equiv	10	3	0	13	3	1	0	4
Neg	0	0	2	2	0	2	2	4
Total	319	4	2	325	173	4	2	179*

	% Agreement	95% CI	% Agreement	95% CI
Positive	96.9% (309/319)	94.3 – 98.5	97.1% (170/175)	93.5 – 99.1
Negative	66.7% (2/3)	9.4 – 99.2	66.7% (2/3)	9.4 – 99.2

*One sample was defined as QNS (quantity not sufficient) and excluded from the analysis.

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Retrospective populations

	Retrospective Pregnant Women2/3 Consensus					Retrospective General2/3 Consensus
VIDAS®	Pos	Equiv	Neg	Total	Pos	Equiv	Neg	Total
Pos	179	0	0	179	169	0	0	169
Equiv	9	4	0	13	7	4	0	11
Neg	0	5	3	8	1	6	104	111
Total	188	9	3	200	177	10	104	291*

	% Agreement	95% CI	% Agreement	95% CI
Positive	92.7% (179/193)	88.1 –96.0	92.3% (169/183)	87.5 – 95.8
Negative	100% (3/3)	29.2 –100.0	100% (104/104)	96.5 –100.0

*Five samples were defined as QNS (quantity not sufficient) and excluded from the analysis

Pre-selected Pregnant Women Population

Pre-selected Pregnant Women2/3 Consensus Method
VIDAS®	Pos	Equiv	Neg	Total
Pos	23	0	0	23
Equiv	0	0	0	0
Neg	0	2	102	104
Total	23	2	102	127*

	% Agreement	95% CI
Positive	92.0% (23/25)	74.0 - 99.0
Negative	100% (102/102)	96.4 - 100.0

*Two samples were defined as QNS (quantity not sufficient) and excluded from the analysis.

H. Conclusion

The VIDAS® RUB IgG Assay is substantially equivalent to Abbott Laboratories AxSYM Rubella lgG Antibody Assay.

The 510(k) summary includes only information that is also covered in the body of the 510(k). The summary does not contain any puffery or unsubstantiated labeling claims. The summary does not contain any raw data, i.e., contains only summary data. The summary does not contain any trade secret or confidential commercial information. The summary does not contain any patient identification information.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular emblem with the department's name around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Sandra Perreand Sr. Director, N.A. Regulatory Affairs bioMérieux, Inc. 595 Anglum Road Hazelwood, MO 63042

DEC 2 3 2008

Re: K080766

Regulation Number: 21CFR §866.3510 Regulation Name: Regulatory Class: Product Code: Dated: Received:

Trade/Device Name: VIDAS® RUB IgG Assay Rubella virus serological reagents Class II LFX December 19, 2008 December 22, 2008

Dear Ms. Perreand:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). You may, therefore, morket the device, subject to the general controls provisions of the Act. The general controls, ontrols. 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the ruality our uns (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 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), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Sally attayma

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K080766

Device Name: VIDAS® RUB IgG

Indications For Use:

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Une Schaf

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K080766

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.