VIDAS® CA 15-3 is an automated quantitative test for use on the VIDAS instruments for the quantitative measurement of CA 15-3 reactive antigenic determinants in human serum using the ELFA technique (Enzyme Linked Fluorescent Assay). The VIDAS CA 15-3 is indicated for the serial measurement of CA 15-3 reactive antigenic determinants as an aid in the monitoring of patients previously diagnosed with breast cancer for disease progression or response to therapy in conjunction with other clinical methods. The VIDAS CA 15-3 assay can also be used as an aid in the detection of recurrence in previously treated Stage II and III breast cancer patients.

Device Description

VIDAS CA 15-3 is an automated quantitative test for use on the VIDAS instruments for the quantitative measurement of CA 15-3 levels in human serum using the ELFA technique (Enzyme Linked Fluorescent Assay). The VIDAS CA 15-3 assay is indicated for the serial measurement of CA 15-3 as an aid in the monitoring of disease progression or response to therapy in patients previously diagnosed with breast cancer.

The assay principle combines a two-step immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR), a pipette tip-like device, serves as the solid phase as well as the pipetting device for the assay. It is coated with mouse monoclonal 115D8 antibodies. The other assay reagents are ready-to-use and pre-dispensed in the sealed reagent strips (STRs).

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 monoclonal 115D8 antibody fixed onto the interior wall of the SPR to capture the reactive antigenic determinants present in the sample. Unbound components are eliminated during the washing steps. Alkaline phosphatase labeled monoclonal DF3 antibody (conjugate) is then incubated in the SPR where it binds with the CA 15-3 reactive antigenic determinant. Unbound conjugate is then eliminated during the washing steps.

During the final detection step, the substrate (4-Methyl-umbellifery| phosphate) is cycled in and out of the SPR. The conjuqate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methy)-umbelliferone) the fluorescence of which is measured at 450 nm. The intensity of the fluorescence is proportional to the concentration of CA 15-3 reactive antigenic determinants 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

Here's a summary of the acceptance criteria and study details for the VIDAS® CA 15-3 Assay, based on the provided text:

Acceptance Criteria and Device Performance for VIDAS® CA 15-3 Assay

The device acceptance was based on demonstrating substantial equivalence to a predicate device (TOSOH ST AIA-PACK BRCA) through performance data, including analytical and clinical comparisons. The summary does not explicitly state acceptance criteria in terms of target values for slope or intercept; rather, it presents the results of the comparison to support substantial equivalence.

1. Table of Acceptance Criteria and Reported Device Performance:

Test	Acceptance Criteria (Implied by Predicate Performance)	Reported VIDAS® CA 15-3 Assay Performance
Intra-Assay Precision	CV comparable to predicate (2.2% - 1.4%)	Pool A: 2.1 - 4.0% CV (Mean 270.0 U/mL)
		Pool B: 3.2 - 4.5% CV (Mean 67.7 U/mL)
		Pool C: 2.3 - 4.1% CV (Mean 21.4 U/mL)
Inter-Run Precision	CV comparable to predicate (2.2%)	Pool A: 0.0 - 1.2% CV (Mean 270.0 U/mL)
		Pool B: 0.0 - 1.4% CV (Mean 67.7 U/mL)
		Pool C: 0.6 - 2.2% CV (Mean 21.4 U/mL)
Limits of Detection	Comparable to predicate (2.0 U/mL)	0.724 U/mL (< 2.0 U/mL)
Method Comparison	Strong correlation with predicate	Slope = 0.96 (95% CI: 0.83 to 1.09)
		Intercept = -1.94 (95% CI: -4.90 to +1.01)

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

Test Set Sample Size:
- Analytical Precision: 40 replicates (for intra-assay), number of replicates not specified for inter-run but based on 20 runs.
- Clinical Method Comparison: 1,035 samples.
Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be prospective or designed for the specific purpose of this submission, as they involve testing the VIDAS® CA 15-3 Assay against the predicate and established pools.

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

The document does not describe the use of experts to establish a "ground truth" for the test set in the conventional sense (e.g., for image interpretation). Instead, the performance studies compare the device's measurements against established methods (predicate device measurements) and known concentrations of CA 15-3 in control pools.

4. Adjudication Method for the Test Set:

Not applicable. The study involves quantitative measurements and comparisons to a predicate device and known control values, not subjective assessments requiring adjudication.

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

No, an MRMC comparative effectiveness study was not done. This type of study is typically for diagnostic imaging or interpretation where multiple human readers assess cases. The VIDAS® CA 15-3 Assay is an automated quantitative laboratory test.

6. Standalone Performance Study:

Yes, a standalone performance study was done for the VIDAS® CA 15-3 Assay, as evidenced by the "Non-clinical (Analytical) Comparison" which includes intra-assay and inter-run precision, and limits of detection. These metrics assess the performance of the device itself.

7. Type of Ground Truth Used:

Analytical Performance: The ground truth for analytical precision used known concentrations or pre-established values in "Pools" and "Controls" (e.g., Mean = 270.0 U/mL for Pool A).
Clinical Method Comparison: The "ground truth" for the method comparison was the measurements obtained from the predicate device, TOSOH ST AIA-PACK BRCA, with which the VIDAS® CA 15-3 Assay was directly compared using a large number of patient samples.

8. Sample Size for the Training Set:

The document does not explicitly mention a "training set" in the context of an algorithm or machine learning model. For this type of in vitro diagnostic device, "training" typically refers to the development and optimization of the assay itself, including reagent formulation, instrument parameters, and potentially curve fitting, which uses internal data during the development phase. The provided summary focuses on validation data.

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

As there's no explicit "training set" described for an algorithm, the concept of establishing ground truth for it is not directly applicable in the provided information. For the assay's development (which could be considered analogous to training if it were a machine learning model), the "Master curve for each kit lot and each calibrator lot are traceable to working standards established by bioMérieux, Inc. and value assigned by the Fujirebio Diagnostics, Inc. radioimmunoassay method." This indicates that standardization and traceability to established reference methods were used to define the assay's operational parameters and calibration.

Summary

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K080469

510(k) SUMMARY

VIDAS® CA 15-3 Assay

A. Submitter Information

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Sandra Perreand
Phone Number:	314-731-8594
Fax Number:	314-731-8689
Date of Preparation:	April 17, 2009
	JUN 22 2009

B. Device Name

Trade Name:

VIDAS® CA 15-3 Assay

Common Name: CA 15-3

Classification Name: System. Test, CA 15-3, for monitoring and management of breast cancer

C. Predicate Device Name

Trade Name:

TOSOH Medical, Inc. ST AIA Pack BRCA

D. Device Description

CA 15-3 is a registered trademark from Fujirebio Diagnostics Inc. (formerly named Centocor Diagnostics of Pennsylvania, Inc.)

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(conjugate) is then incubated in the SPR where it binds with the CA 15-3 reactive antigenic determinant. Unbound conjugate is then eliminated during the washing steps.

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.

E. Intended Use

F. Technological Characteristics Summary

A general comparison of the similarities and differences of the VIDAS CA 15-3 assay to the predicate device is presented in the table below.

Item	VIDAS® CA 15-3 Assay	TOSOH ST AIA-PACKBRCA (K010796)
General Comparison
Intended Use	VIDAS® CA 15-3 is an automatedquantitative test for use on the VIDASinstruments for the quantitativemeasurement of CA 15-3 reactiveantigenic determinants in human serumusing the ELFA technique (EnzymeLinked Fluorescent Assay). The VIDASCA 15-3 is indicated for the serialmeasurement of CA 15-3 reactiveantigenic determinants as an aid in themonitoring of patients previouslydiagnosed with breast cancer for diseaseprogression or response to therapy inconjunction with other clinical methods.The VIDAS CA 15-3 assay can also beused as an aid in the detection ofrecurrence in previously treated Stage IIand III breast cancer patients.	ST AIA-PACK BRCA is designed for INVITRO DIAGNOSTIC USE ONLY forthe quantitative measurement ofCA27.29 in human serum on TOSOHAIA Nex IA and AIA-600 IIImmunoassay analyzers. ST AIA-PACKBRCA is to be used as an aid inmonitoring response to therapy forpatients with Stage IV (metastatic)breast cancer as well as determiningearly recurrence in Stage II and Stage IIIbreast cancer patients who werepreviously treated and free of disease.Serial testing for patient CA27.29 assayvalues should be used in conjunctionwith other clinical methods used formonitoring response to therapy inpatients with Stage IV metastatic breastcancer and for detecting earlyrecurrence in Stage II and Stage IIIdisease.
Specimen	Serum	Serum
Analyte	CA 15-3	CA 27.29 (CA15-3)

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Item	VIDAS® CA 15-3 Assay	TOSOH ST AIA-PACKBRCA (K010796)
General Comparison
Antibody	mouse monoclonal 115D8 and DF3antibodies	mouse monoclonal antibodies to CA 15-3
Assay Principle	Two antibody "sandwich" binding of CA15-3 antigen. One antibody is bound to asolid phase and the second antibody is inliquid form and is labeled with fluorescentcompound	Two antibody "sandwich" binding of CA27.29. One antibody is bound to a solidphase and the second antibody is inliquid form and is labeled withfluorescent compound
Automated	Yes	Yes
Assay Technique	Enzyme-linked fluorescent assay (ELFA)	Two-site immunoenzymometric assay
Sample Volume	100 μL	20 μL
Traceability/Standardization	Master curve for each kit lot and eachcalibrator lot are traceable to workingstandards established by bioMérieux, Inc.and value assigned by the FujirebioDiagnostics, Inc. radioimmunoassaymethod	Each calibrator lot are traceable tointernal reference standards
Measurement range	2.00 - 365 U/mL	2.0 - 400 U/mL

G. Performance Data

A summary of the non-clinical and clinical test results is presented in the table below.

Test	VIDAS® CA 15-3 Assay	TOSOH ST AIA-PACKBRCA (K010796)
Non-clinical (Analytical) Comparison
	n = 40 replicates, 2 lots, 3 sitesPool A: Mean = 270.0 U/mLCV = 2.1 - 4.0%	n = 10 replicatesControl L: Mean = 41.3 U/mLCV = 2.2%
Intra-Assay Precision	Pool B: Mean = 67.7 U/mLCV = 3.2 - 4.5%Pool C: Mean = 21.4 U/mLCV = 2.3 - 4.1%	Control H: Mean = 300.9 U/mLCV = 1.4%
Inter-Run Precision	n = 20 runsPool A: Mean = 270.0 U/mLCV = 0.0 - 1.2%Pool B: Mean = 67.7 U/mLCV = 0.0 - 1.4%Pool C: Mean = 21.4 U/mLCV = 0.6-2.2%	n = 21 runsControl L: Mean = 40.4 U/mLCV = 2.2%Control H: Mean = 301.0 U/mLCV = 2.2%
Limits of Detection	0.724 U/mL (< 2.0 U/mL)	2.0 U/mL

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Clinical Comparison
Item	VIDAS® CA 15-3 Assay	TOSOH ST AIA-PACKBRCA (K010796)
Reference Range	Females, ≤ 50 years (95% percentile) =22.07 – 24.09 U/mLFemales, > 50 years (95% percentile) =29.62 – 36.95 U/mLAll females (95% percentile) = 26.99 –32.07 U/mL	Females, pre-menopausal (99%order statistic) = 28.6 – 44.3 U/mLFemales, post-menopausal (99%order statistic) = 38.9 – 43.4 U/mLAll females (99% order statistic) =34.8 – 44.3 U/mLMale (99% order statistic) = 36.0 –84.8 U/mL
Method Comparison
Methods	X = TOSOH ST AIA-Pack BRCA; y = VIDAS® CA 15-3
Number of patients	1,035 samples
Results	Slope = 0.96 (95% confidence interval = 0.83 to 1.09)Intercept = -1.94 (95% confidence interval = -4.90 to +1.01)

H. Conclusion

The VIDAS® CA 15-3 Assay is substantially equivalent to the Tosoh Medical, Inc. TOSOH ST AIA-PACK BRCA

The 510(k) summary includes only information that is also covered in 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 U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle with its wings spread, symbolizing protection and care. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES, USA" is arranged in a circular fashion around the eagle, indicating the department's name and national affiliation. The logo is simple, using a monochromatic color scheme.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 22 2009

BioMérieux, Inc. c/o Ms. Sandra L. Perreand Senior Director, North American Regulatory Affairs 595 Anglum Rd Hazelwood, MO 63042

Re: K080469

Trade/Device Name: VIDAS® CA 15-3 Regulation Number: 21 CFR 866.6010 Regulation Name: Turnor-associated antigen immunological test system Regulatory Class: Class II Product Code: LTK Dated: February 26, 2009 Received: February 27, 2009

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, 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 (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 quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding

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Page 2 – Ms. Sandra L. Perreand

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.hhml.

Sincerely yours,

Maria M. Chan

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology 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): K080469

Device Name: VIDAS® CA 15-3

Indication for Use:

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

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

And/Or

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

Van Bui

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

510(k) K080469

Regulation Number and Section

§ 866.6010 Tumor-associated antigen immunological test system.

(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.