The Access® OV Monitor assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CA 125 antigen levels in human serum and plasma, using the Access® Immunoassay Systems. This device is indicated for use in the measurement of CA 125 antigen to aid in the management of ovarian cancer patients. Serial testing for patient CA 125 antigen concentrations should be used in conjunction with other clinical methods used for monitoring ovarian cancer.

Device Description

AI/ML Overview

Acceptance Criteria and Device Performance for Access® OV Monitor ELISA

This document outlines the acceptance criteria and the performance of the Access® OV Monitor assay, a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CA 125 antigen levels in human serum and plasma.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Acceptance Criteria	Reported Device Performance
Analytical Performance
Specificity (Therapeutic Drugs)	No significant interference (<10% change) from specified therapeutic drugs.	Doxorubicin (100 µg/mL), Amthopterin (500 μg/mL), Carboplatin (1000 μg/mL), Cyclophosphamide (1000 μg/mL), 5-Fluorouracil (1000 µg/mL), Cisplatin (2000 µq/mL), Melphalan (100 µg/mL), Acetominopehn (200 µg/mL), Aspirin (500 µg/mL), Paclitaxel (10 ng/mL), Biotin (50 ng/mL), Vitamin D2 (1 U/mL) all showed no significant interference.
Specificity (Sample Contaminants)	No significant interference (<10% change) from specified sample contaminants.	Total protein (9%), Bilirubin (20 mg/dL), Hemoglobin (1000 mg/dL), and Triglycerides (1800 mg/dL) all showed no significant interference.
Analytical Sensitivity (Lowest Detectable Level)	Distinguishable from zero.	0.2 U/mL (Calibrator S0).
Analytical Sensitivity (Claimed in Labeling)		0.5 U/mL.
Measurement Range	Accurate measurement between lower limit of detection and highest calibrator value.	Approximately 0.5 U/mL to 5,000 U/mL.
Recovery (Linearity Studies)	Average recovery within an acceptable range, with individual recoveries also acceptable.	Average recovery of 107%, with individual recoveries ranging from 100% to 118%.
Precision (Within-run Imprecision)	Coefficient of Variation (CV) within acceptable limits for various concentrations.	Ranged from 1.3% CV to 2.4% CV for concentrations from ~24 to 2962 U/mL.
Precision (Between-run Imprecision)	CV within acceptable limits.	Ranged from 3.3% CV to 6.0% CV.
Precision (Total Imprecision)	CV within acceptable limits.	Ranged from 3.9% CV to 6.0% CV.
Method Comparison
Correlation (vs. Predicate Device)	Acceptable correlation coefficient (r).	r = 0.9871 (compared to Abbott Axsym CA 125 assay).
Bias (vs. Predicate Device)	Acceptable bias (slope, intercept).	y = 1.197 + (-0.985) across the range of the Axsym assay (0 - 600 U/mL).
Clinical Performance
Clinical Sensitivity (vs. Predicate Device)	Comparable to predicate device.	84.4% (95% CI = 71.2% - 92.3%)
Clinical Specificity (vs. Predicate Device)	Comparable to predicate device.	82.5% (95% CI = 82.5% - 90.0%)
Monitoring Ovarian Cancer Patients	CA 125 concentrations obtained with the device should be comparable and parallel those of the FDA cleared predicate device.	Results from 20 female subjects with ovarian cancer (stages I to IV), monitored for 7-53 months, demonstrated comparable and paralleled CA 125 concentrations to the FDA cleared predicate device.

2. Sample Size for Test Set and Data Provenance

Specificity (Therapeutic Drugs & Sample Contaminants): The exact number of samples tested for each compound/contaminant is not specified, but the compounds themselves are listed. Each compound was tested at a specific concentration.
Analytical Sensitivity: Not explicitly stated as a separate "test set" but likely derived from a series of dilutions or measurements around the lower limit.
Recovery: 6 human serum samples.
Precision: Not explicitly stated as a separate "test set" size, but concentrations from 24 to 2962 U/mL were tested, implying multiple measurements at these levels.
Correlation: 290 samples.
Clinical Data (Sensitivity & Specificity): The total number of subjects used to calculate clinical sensitivity and specificity is not explicitly stated, but it is derived from the comparison between the Access OV Monitor and the Abbott Axsym CA 125 assays.
Clinical Data (Monitoring): 20 female subjects diagnosed with ovarian cancer (stages I to IV).
Data Provenance: The document does not explicitly state the country of origin for the data or whether the studies were retrospective or prospective, although the monitoring study for clinical data implies a prospective approach over an extended period (7 to 53 months).

3. Number of Experts for Ground Truth and Qualifications

This information is not provided in the given text. For an immunoassay, the "ground truth" is typically established by the reference measurement method itself or by clinical diagnosis, rather than by human expert interpretation of an image or a complex medical case.

4. Adjudication Method

This information is not applicable as the studies described pertain to an in vitro diagnostic immunoassay, not a device requiring interpretation or adjudication by human experts in the context of a "test set" like in radiological imaging. The "truth" for this type of device is based on analytical measurements and correlation with an existing, cleared device.

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

An MRMC study was not conducted, and therefore, the effect size of human readers improving with AI assistance is not applicable. This type of study design is typically used for imaging diagnostics where human interpretation is a critical component, not for quantitative immunoassays.

6. Standalone Performance Study

Yes, a standalone performance study was conducted. All the analytical performance studies (Specificity, Analytical Sensitivity, Recovery, Precision) and the correlation study against the Abbott Axsym CA 125 assay represent the standalone performance of the Access® OV Monitor assay. The clinical sensitivity and specificity calculations also reflect the standalone performance of the device in comparison to a predicate.

7. Type of Ground Truth Used

Analytical Performance (Specificity, Analytical Sensitivity, Recovery, Precision): The ground truth was established through reference analytical methods and standards (e.g., spectrophotometry for total protein, known concentrations of therapeutic drugs, calibrated reference materials).
Correlation: The ground truth was based on the quantitative results obtained from the Abbott Axsym CA 125 assay, which served as the predicate device.
Clinical Data (Sensitivity & Specificity): The ground truth for disease status (ovarian cancer) would have been established by clinical diagnosis, possibly confirmed by pathology or other definitive medical diagnoses. The specific method for determining "true positive" and "true negative" cases is not detailed but would align with clinical standards.
Clinical Data (Monitoring): The ground truth for monitoring effectiveness was implicitly established by comparing the CA 125 concentration trends to clinical outcomes and the trends observed with the FDA-cleared predicate device against the known disease progression of the 20 ovarian cancer patients.

8. Sample Size for Training Set

This information is not provided in the document. For an in vitro diagnostic assay like this, "training set" typically refers to studies performed during the development and optimization phase, rather than a distinct, formally reported dataset as seen in machine learning applications.

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

As the concept of a formal "training set" for this type of immunoassay is not explicitly mentioned or detailed, the method for establishing its ground truth is not provided. However, during the development of such an assay, internal studies would use well-characterized samples (e.g., spiked samples, clinical samples with known CA 125 levels from reference methods, samples from patients with confirmed clinical status) to optimize reagents, calibrate signals, and establish initial operating parameters.

Summary

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DEC 1 1 2002

510(k) Summary K023597

Intended Use

Summary of Studies

Specificity: There was no significant interference from therapeutic drugs or similar compounds using the Access OV Monitor. The following compounds were tested: doxorubicin at 100 µg/mL, amthopterin at 500 μg/mL, carboplatin at 1000 μg/mL, cyclophosphamide at 1000 μg/mL, 5-fluorouracil at 1000 µg/mL, cisplatin at 2000 µq/mL, melphalan at 100 µg/mL, acetominopehn at 200 µg/mL, aspirin at 500 µg/mL, paclitaxel at 10 ng/mL, biotin at 50 ng/mL and vitamin D2 at 1 U/mL.

In addition, there was no significant interference (<10% change) from potential sample contaminants (total protein at 9%, bilirubin at 20 mg/dL. hemoglobin at 1000 mg/dL, and triglycerides at 1800 mg/dL).

Analytical Sensitivity: The lowest detectable level of CA 125 antigen distinguishable from zero (Access® OV Monitor Calibrator S0) is 0.2 U/mL. An analytical sensitivity of 0.5 U/mL will be claimed in the labeling. Samples can be accurately measured between the lower limit of detection and the highest calibrator value (approximately 0.5 U/mL and 5,000 U/mL).

Recovery: Linearity studies performed by diluting 6 human serum samples at various levels with Access® OV Monitor Zero Calibrator provided an average recovery of 107%, with individual recoveries ranging from 100% to 118%.

Precision: Within-run assay imprecision was tested for concentrations from approximately 24 to 2962 U/mL. The within run imprecision ranged from 1.3% CV to 2.4% CV. Between-run assay imprecision ranged from 3.3% CV to 6.0% CV. Total imprecision ranged from 3.9% CV to 6.0% CV.

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Correlation: A comparison of OV Monitor values from 290 samples, ranging from approximately 0 to 600 U/mL, run with both the Access® OV Monitor immunoassay and the Abbott Axsym CA 125 assay demonstrated an acceptable correlation coefficient of: r = 0.9871; and a bias with a slope of y = 1.197 + (-0.985) across the range of the Axsym assay (approximately 0 - 600 U/mL).

Clinical Data: The data generated demonstrates comparable clinical sensitivity and clinical specificity for the Access OV Monitor and the Abbott Axsym CA 125 assays. The clinical sensitivity and specificity were calculated at: Sensitivity = 84.4% (95% confidence interval = 71.2% -92.3%); Specificity = 82.5% (95% confidence interval = 82.5% - 90.0%).

Results from 20 female subjects who where diagnosed with ovarian cancer (stages I to IV) and who were monitored (7 months to 53 months) over the course of disease demonstrate that CA 125 concentration obtained with the Access OV Monitor assay were comparable and paralleled those results obtained with the FDA cleared predicate device.

Conclusion

The data generated demonstrates acceptable non-clinical (laboratory) performance, and good correlation between the Access OV Monitor assay and the Abbott Axsym CA 125 assay. Clinical sensitivity and clinical specificity for the Access OV Monitor and the Abbott Axsym CA 125 assays were found to be substantially equivalent.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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198 Gaither Road

Ms. Mara Caler Regulatory Affairs Beckman Coulter, Inc. 4300 N. Harbor Blvd Fullerton, CA 92835

Re:

K023597 Trade/Device Name: Access® OV Monitor Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: LTK Dated: November 25, 2002 Received: November 27, 2002

Dear Ms. Caler:

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 (OS) 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Page. 1 of 1

510(k) Number (K023597):

Device Name: Access® OV Monitor

Indications For Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

S. Plewes for S. Bautista

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number

Prescription Use
(Per 21 CFR 801.109)

Over-The Counter Use

(Optional Format 1-2-96)

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.