VIDAS® CA 125 II is an automated quantitative test for use on the VIDAS instruments, for the measurement of OC 125 reactive antigenic determinants in human serum using the ELFA technique (Enzyme Linked Fluorescent Assay). The VIDAS CA 125 II is indicated for the serial measurement of OC 125 reactive antigenic determinants as an aid in the monitoring of patients previously diagnosed with Stage IV (metastatic) ovarian cancer for disease progression or response to therapy. The VIDAS CA 125 II assay can also be used as an aid in the early detection of recurrence in previously treated Stage II and III ovarian cancer patients.

Device Description

VIDAS® CA 125 II is an automated quantitative test for use on the VIDAS instruments, for the measurement of CA 125 reactive antigenic determinants in human serum using the ELFA technique (Enzyme Linked Fluorescent Assay). The VIDAS CA 125 II is indicated for the serial measurement of OC 125 reactive antigenic determinants as an aid in the monitoring of patients previously diagnosed with Stage IV (metastatic) ovarian cancer for disease progression or response to therapy. The VIDAS CA 125 II assay can also be used as an aid in the early detection of recurrence in previously treated Stage II and III ovarian cancer patients.

CA 125 II is a registered trademark from Fujirebio Diagnostics Inc. (formerly named Centocor Diagnostics of Pennsylvania, Inc.)

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 M 11 antibodies. The other assay reagents are ready-to-use and pre-dispensed in the sealed reagent strips (STRs). 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 monoclonal M11 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 mouse monoclonal OC 125 antibody (conjugate) is then incubated in the SPR where it binds with the OC 125 reactive antigenic determinant. Unbound conjugate is then eliminated during the washing steps.

During the final detection step, the substrate (4-Methyl-umbelliferyl 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 OC 125 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 breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

Acceptance Criteria and Device Performance for VIDAS® CA 125 II Assay

1. Table of Acceptance Criteria and Reported Device Performance

The document describes performance characteristics rather than explicit "acceptance criteria" with pass/fail thresholds. However, we can infer the tested performance against predicate device or established analytical goals.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Precision	Within acceptable ranges for clinical diagnostic assays.	Pool A (389 U/mL):- Between-site CV: 4.15%- Between-lot CV: 1.01%- Between-recalibration CV: 1.87%- Between-day CV: 0.00%- Between-run CV: 0.99%- Within-run CV: 3.40%- Total CV: 5.85%Pool B (75.3 U/mL):- Between-site CV: 2.13%- Between-lot CV: 0.00%- Between-recalibration CV: 2.26%- Between-day CV: 1.08%- Between-run CV: 2.00%- Within-run CV: 3.50%- Total CV: 5.20%Pool C (18.9 U/mL):- Between-site CV: 2.43%- Between-lot CV: 0.79%- Between-recalibration CV: 1.96%- Between-day CV: 0.74%- Between-run CV: 1.79%- Within-run CV: 3.35%- Total CV: 5.03%
Measurement Range	Clearly defined and clinically relevant.	4.00 - 600.00 U/mL
Analytical Detection Limit (LoB/LoQ)	Below the lower limit of the measurement range.	Estimated to be less than 4 U/mL.
Hook Effect	No significant hook effect at high concentrations.	No hook effect found up to 200,000 U/mL.
Method Comparison (vs. Predicate)	Strong correlation and agreement with a legally marketed predicate device (TOSOH ST AIA Pack CA 125). Implicitly, the Deming regression parameters (slope, intercept, and their confidence intervals) and overall correlation should demonstrate substantial equivalence.	Comparison Study:- N = 210 samples (including 77 ovarian cancer patients and 133 monitoring samples)- Equation: Y = 0.93X - 58.10- 95% Confidence Interval for Intercept: -169.15 to 52.95- 95% Confidence Interval for Slope: 0.61 to 1.25- Range of samples: VIDAS: 4.0 - 31801 U/mL; Predicate: 2.0 - 29940 U/mL- Conclusion: The device is considered substantially equivalent to the predicate.

2. Sample Size and Data Provenance for Test Set (Method Comparison)

Sample Size: 210 samples. This includes 77 samples from women with ovarian cancer and 133 samples for monitoring disease status.
Data Provenance: The document does not explicitly state the country of origin. It indicates the samples were serum samples from women with ovarian cancer. It implies a retrospective or a mixed prospective/retrospective design, as samples were "randomly chosen" from existing patient populations.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

Not applicable. This device is an in vitro diagnostic (IVD) for quantitative measurement of a biomarker. The "ground truth" for the method comparison study is the result obtained from the predicate device (TOSOH ST AIA Pack CA 125). There are no human experts involved in establishing a subjective ground truth for the CA 125 values.

4. Adjudication Method for Test Set

Not applicable. As described above, this is a quantitative measurement comparison, not a study requiring human expert adjudication of a subjective finding. The comparison is against the predicate device's quantitative results.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for imaging or other diagnostic tools where human readers interpret results, and the AI's effect on their performance is evaluated. The VIDAS® CA 125 II Assay is a fully automated quantitative immunoassay.

6. Standalone (Algorithm Only) Performance Study

Yes, the studies described (Precision, Measurement Range, Analytical Detection Limit, Hook Effect, and Comparison with other methods like the predicate device) represent the standalone performance of the VIDAS® CA 125 II Assay. It is an automated system without a human-in-the-loop for the quantification process itself.

7. Type of Ground Truth Used

For Precision, Measurement Range, Analytical Detection Limit, Hook Effect: These are analytical performance characteristics where the "ground truth" is established through well-defined laboratory analytical methods and controls, ensuring intrinsic performance of the assay.
For Method Comparison: The "ground truth" for comparison was the quantitative results obtained from the predicate device (TOSOH ST AIA Pack CA 125 Enzyme Immunoassay). The goal was to demonstrate substantial equivalence to an already legally marketed device.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning, as this is an immunoassay, not an AI/ML-based diagnostic algorithm. However, calibration curves are established for each kit lot and calibrator lot. The number of samples used to establish these master curves is not specified, but it's an internal process traced to working standards.

9. How the Ground Truth for the Training Set (Calibration) was Established

For the VIDAS® CA 125 II Assay, the equivalent of "ground truth" for its internal calibration (referred to as master curves and calibrator lots) is established by:

Traceability to working standards established by bioMérieux, Inc.
Value assignment by the Fujirebio Diagnostics, Inc. radioimmunoassay method.

This indicates a hierarchical system where internal standards are calibrated against a recognized reference method to ensure accuracy and consistency.

Summary

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Koposia

APR 1 0 2009

510(k) SUMMARY

VIDAS® CA 125 Il 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:	October 8, 2008
Device Name	VIDAS® CA 125 II Assay

B.

Trade Name:	VIDAS® CA 125 II Assay
Common Name:	CA 125
Classification Name:	Test, Epithelial Ovarian Tumor-Associated Antigen (CA125)

C. Predicate Device Name

Trade Name:

TOSOH Medical, Inc. ST AIA Pack CA 125 Enzyme lmmunoassay

D. Device Description

CA 125 II is a registered trademark from Fujirebio Diagnostics Inc. (formerly named Centocor Diagnostics of Pennsylvania, Inc.)

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antigenic determinants present in the sample. Unbound components are eliminated during the washing steps. Alkaline phosphatase labeled mouse monoclonal OC 125 antibody (conjugate) is then incubated in the SPR where it binds with the OC 125 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

VIDAS® CA 125 II is an automated quantitative test for use on the VIDAS instruments, for the measurement of OC 125 reactive antigenic determinants in human serum using the ELFA technique (Enzyme Linked Fluorescent Assay). The VIDAS CA 125 II is indicated for the serial measurement of OC 125 reactive antigenic determinants as an aid in the monitoring of patients previously diagnosed with ovarian cancer for disease progression or response to therapy. The VIDAS CA 125 Il assay can also be used as an aid in the detection of recurrence in previously treated ovarian cancer patients.

F. Technological Characteristics Summary

A general comparison of the similarities and differences of the VIDAS CA 125 II assay to the predicate device is presented in the table below.

Item	VIDAS® CA 125 II Assay	TOSOH ST AIA-PACKCA 125 (K023891)
General Comparison
Intended Use	VIDAS® CA 125 II is an automatedquantitative test for use on the VIDASinstruments, for the measurement ofOC 125 reactive antigenic determinantsin human serum using the ELFAtechnique (Enzyme Linked FluorescentAssay). The VIDAS CA 125 II isindicated for the serial measurement ofOC 125 reactive antigenic determinantsas an aid in the monitoring of patientspreviously diagnosed with ovariancancer for disease progression orresponse to therapy. The VIDAS CA125 II assay can also be used as an aidin the detection of recurrence inpreviously treated ovarian cancerpatients.	ST AIA-PACK CA 125 is designed for INVITRO DIAGNOSTIC USE ONLY forthe quantitative measurement of CA 125in human serum on specific TOSOHAIA System analyzers. ST AIA-PACKCA 125 is to be used as an aid inmonitoring response to therapy forpatients with epithelial ovarian cancer.Serial testing for patient CA 125 assayvalues should be used in conjunctionwith other clinical methods used formonitoring ovarian cancer.
Specimen	Serum	Serum

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Item	VIDAS® CA 125 II Assay	TOSOH ST AIA-PACK CA 125 (K023891)
Analyte	CA 125	CA 125
Antibody	mouse monoclonal anti-CA 125	mouse monoclonal anti-CA 125
Assay Principle	Two antibody "sandwich" binding of CA 125 antigen. One antibody is bound to a solid phase and the second antibody is in liquid form and is labeled with fluorescent compound	Two antibody "sandwich" binding of CA 125. One antibody is bound to a solid phase and the second antibody is in liquid form and is labeled with fluorescent compound
Automated	Yes	Yes
Assay Technique	Enzyme-linked fluorescent assay (ELFA)	Two-site immunoenzymometric assay
Sample Volume	200 µL	100 µL
Traceability/Standardization	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	Each calibrator lot are traceable to internal reference standards
Measurement range	4.00 - 600.00 U/mL	2.0 - 1,000 U/mL

G. Performance Data

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

Precision:

Three serum samples were tested in duplicate in 40 different runs (2 runs per day over 20 sequential days) with 2 reagent lots using one instrument at each of three sites (N = 480). The between-site precision, between-lot precision, between-recalibration precision, betweenday precision, between-run precision, repeatability (within-run precision) and total precision (within-run, between-run, between-day, between-recalibration, between-lot and between-site) were calculated using a modified protocol, which was written based on the recommendations of CLSI® EP5-A2:

Source	N	Pool A (389U/mL)	Pool B (75.3 U/mL)	Pool C (18.9 U/mL)
		CV (%)	CV (%)	CV (%)
Between-site	480	4.15	2.13	2.43
Between-lot	480	1.01	0.00	0.79
Between-recalibration	480	1.87	2.26	1.96
Between-day	480	0.00	1.08	0.74
Between-run	480	0.99	2.00	1.79
Within-run	480	3.40	3.50	3.35
Total	480	5.85	5.20	5.03

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Measurement range

The measurement range of the VIDAS CA 125 II kit is: 4-600 U/mL.

Analytical detection limit

Based on a modification of CLSI® document EP17-A , LoB and LoQ detection limit results are estimated to be less than 4 U/mL.

Hook effect

No hook effect was found up to OC 125 reactive antigenic determinant concentrations of 200,000 U/mL.

Comparison with other test methods

One serum sample randomly chosen from each of the 77 women with ovarian cancer tested Online of the disease that on the expected values (133
for the monitoring of the disease status (17 the expected values (133
samples) using the VIDAS CA (1) assay were compar equation represents the relationship between the two techniques.

n = 210 Y = 0.93X - 58.10 95% Confidence interval for the intercept: -169.15 to 52.95 95% Confidence interval for the slope: 0.61 to 1.25 Range of samples: 4.0 - 31801 U/mL (VIDAS); 2.0 - 29940 U/mL (another commercially available assay)

Image /page/3/Figure/9 description: The image is a scatter plot comparing 'vidas' and 'predicate'. The x-axis is labeled 'predicate' and ranges from 0 to 30000, while the y-axis is labeled 'vidas' and ranges from 0 to 35000. The plot includes two lines: one labeled 'Identity' and another labeled 'Deming fit (-58.10 + 0.93x)'. The Deming fit line appears to be a linear regression model fitted to the data points.

Scatter Plot with Deming Fit

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H. Conclusion

The VIDAS® CA 125 II Assay is substantially equivalent to the Tosoh Medical, Inc. ST AIA Pack CA 125 Assay. .

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three tail feathers. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES. USA" is arranged in a circular fashion around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

APR 1 0 2009

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

Re: K080561

Trade/Device Name: VIDAS® CA 125 IITM Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: Class II Product Code: LTK Dated: April 07, 2009 Received: April 08, 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

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Page 2 - Ms. Sandra L. Perreandl

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,

ia 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): K080561

Device Name: VIDAS® CA 125 II

Indication For Use:

VIDAS® CA 125 II is an automated quantitative test for use on the VIDAS instruments, for the measurement of OC 125 reactive antigenic determinants in human serum using the ELFA technique (Enzyme Linked Fluorescent Assay). The VIDAS CA 125 II is indicated for the serial measurement of OC 125 reactive antigenic determinants as an aid in the monitoring of patients previously diagnosed with ovarian cancer for disease progression or response to therapy. The VIDAS CA 125 II assay can also be used as an aid in the detection of recurrence in previously treated ovarian cancer patients.

Prescription Use × (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)

Mana M Chan.

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

510(k) K080561

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.