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

The Access OV Monitor assay is a sandwich immunoenzymatic assay. The Access OV Monitor assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access OV Monitor assay reagent pack, Access OV Monitor assay calibrators, along with the UniCel Dxl Wash Buffer II are designed for use with the Dxl 9000 Access Immunoassay Analyzer in a clinical laboratory setting.

AI/ML Overview

The document provided is an FDA 510(k) clearance letter and a 510(k) summary for the Beckman Coulter Access OV Monitor assay. This device is an in vitro diagnostic (IVD) immunoassay for measuring CA 125 antigen levels to aid in the management of ovarian cancer patients.

The information requested pertains to the performance study design for AI/ML-based diagnostic devices, which is typically quite different from the validation of an immunoassay. Specifically, sections like "Number of experts used to establish ground truth", "Adjudication method", "Multi-Reader Multi-Case (MRMC) comparative effectiveness study", and "Effect size of how much human readers improve with AI vs without AI assistance" are relevant to AI/ML device validation studies, not typically to immunoassay validation.

An immunoassay like the Access OV Monitor is validated by demonstrating its analytical performance characteristics (e.g., precision, linearity, limits of detection) and method comparison against a predicate device, rather than by human reader studies or expert consensus on images.

Therefore, many of the requested fields are not applicable to this type of device and the information provided in the document. However, I will do my best to extract the relevant information where it exists and explicitly state when a requested criteria is not applicable.

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided FDA 510(k) summary for the Access OV Monitor assay:

Device: Access OV Monitor Immunoassay

The study primarily focuses on demonstrating the substantial equivalence of the new Access OV Monitor assay run on the Dxl 9000 Access Immunoassay Analyzer to its predicate device (Access OV Monitor assay on the Access Immunoassay System, K023597). This is achieved by comparing their analytical performance characteristics.

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document does not explicitly state "acceptance criteria" in a tabulated format for each performance metric, but rather lists the study results and implies they met predefined criteria (e.g., "met the acceptance criteria of R2 ≥ 0.90 and slope 1.00 ± 0.09"). The "acceptance criteria" column below is inferred from these statements and typical IVD validation expectations.

Performance Metric	Implied Acceptance Criteria (Inferred from text)	Reported Device Performance (Access OV Monitor on Dxl 9000)
Method Comparison
R² (Concordance)	R² ≥ 0.90	1.00
Slope	1.00 ± 0.09	0.98 (95% CI: 0.97 - 0.99)
Intercept	(Not explicitly stated numeric criterion, evaluated with CI)	-0.14 (95% CI: -0.38 - 0.13)
Imprecision (Within-Laboratory/Total %CV)	(Performance depends on concentration level; generally, lower %CV desired)	Ranged from 2.6% to 6.1% for concentrations > 15 U/mL. SD of 0.2 for concentrations ≤ 15 U/mL. (See full table in source document)
Linearity	Device should be linear across its analytical measuring interval	Linear throughout the analytical measuring interval of approximately 2.0 - 5,000 U/mL
Limit of Blank (LoB)	(Specific value to be determined and met; typically lowest possible)	0.5 U/mL
Limit of Detection (LoD)	(Specific value to be determined and met)	0.7 U/mL
Limit of Quantitation (LoQ)	(Specific value to be determined and met)	2.0 U/mL
Measuring Range	Consistent with predicate and intended use	2.0 - 5,000 U/mL (Compared to predicate's 0.5 - 5000 U/mL)
Sample Volume	(Not an "acceptance criterion" but a characteristic change)	30 uL (Predicate: 25 uL)
Substrate	(Not an "acceptance criterion" but a characteristic change)	Lumi-Phos PRO substrate (Predicate: Access Substrate)

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

Method Comparison Study: 152 samples.
Imprecision Study: 120 replicates per sample level (e.g., Sample 1, Sample 2, etc, see N column in table). "Multiple samples" tested in triplicate in 2 runs per day for a minimum of 20 days.
Data Provenance: The document does not specify the country of origin of the data or whether samples were retrospective or prospective. It is typical for immunoassay validation studies to use a mix of clinical samples (retrospective) and spiked samples.

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

Not Applicable. This is an immunoassay, not an AI/ML diagnostic imaging device. The "ground truth" for the performance characteristics of an immunoassay is its analytical measurements, often compared against a reference method or validated predicate, not expert consensus on images.

4. Adjudication Method for the Test Set

Not Applicable. See point 3.

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

Not Applicable. This is an immunoassay, not an AI/ML diagnostic imaging device intended to assist human readers.

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

Not Applicable. This is an immunoassay, the "performance" is the analytical output of the instrument-reagent system itself, which is inherently "standalone" in generating the quantitative result. There's no separate "algorithm" performance in the sense of an AI model.

7. The Type of Ground Truth Used

For an immunoassay, "ground truth" refers to the true concentration of the analyte, which is established through:

Reference Methods: Highly accurate and precise methods not explicitly detailed but implied by standard validation practices.
Comparative Measurements against a Predicate Device: The current study uses the predicate device (Access OV Monitor on the Access Immunoassay System) as its primary comparator to establish substantial equivalence.
Known Concentrations: For linearity and limits studies, samples are often prepared at known concentrations (e.g., by diluting a high-concentration sample).

8. The Sample Size for the Training Set

Not Applicable. This is an immunoassay, not an AI/ML device that requires a "training set" in the machine learning sense. The assay is "trained" or developed through biological and chemical methods, and its performance is characterized through analytical validation.

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

Not Applicable. See point 8.

Summary

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May 10, 2024

Beckman Coulter, Inc Kuljeet Kaur Senior Manager Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318

Re: K240479

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: February 19, 2024 Received: February 20, 2024

Dear Kuljeet Kaur:

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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Ying Mao -S

Ying Mao, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

Submission Number (if known)

K240479 Device Name

Access OV Monitor

Indications for Use (Describe)

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 lmmunoassay 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.

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21CFR807.92.

510(k) Number: K240479

Date Prepared: May 01, 2024

Submitter Name and Address:

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318

Primary Contact:

Kuljeet Kaur, Senior Regulatory Affairs Manager Email: kkaur@beckman.com Office Phone: (952) 465-1914

Alternate Contact:

Kate Oelberg, Senior Staff Quality and Regulatory Affairs Email: kmoelberg@beckman.com Phone: (612) 431-7315

Trade Name: Access OV Monitor Common Name: OV Monitor Chemiluminescence Immunoassay Classification Regulation: 21 CFR 866.6010 Classification Product Code: LTK

Predicate Device:

Access OV Monitor 510(k) Number K023597

Device Description

Intended Use

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125 antigen concentrations should be used in conjunction with other clinical methods used for monitoring ovarian cancer.

SystemAttribute/Characteristic	Predicate Access OV Monitor assay(K023597) run on the AccessImmunoassay System	Access OV Monitorassay run on the Dxl9000 AccessImmunoassayAnalyzer Instrument
Intended Use/Indications for Use	The Access OV Monitor assay is aparamagnetic particle,chemiluminescent immunoassay forthe quantitative determination of CA125 antigen levels in human serumand plasma using the AccessImmunoassay Systems. This device isindicated for use in the measurementof CA 125 antigen to aid in themanagement of ovarian cancerpatients. Serial testing for patient CA125 antigen concentrations should beused in conjunction with other clinicalmethods used for monitoring ovariancancer.	Same
Analyte Measured	CA 125	Same
Standardization	Working Calibrators	Same
Technology	chemiluminescent	Same
Format	Sandwich Immunoassay	Same
Method	Automated	Same
Calibration	Utilizes a stored calibration curve	Same
Sample Type	Serum/Plasma	Same
Stability	28 days after opening	Same
Reagent Packformulation andpackaging	Access Reagent Pack formulation andpackaging.	Same
Reagent Configurations	One Configuration:100 determinations, 2 packs, 50tests/pack	Same
Measuring Range	0.5 - 5000 U/mL	2.0 - 5,000 U/mL
Sample Volume	25 uL	30 uL
Instrument	Access Immunoassay system	Dxl 9000 AccessImmunoassay Analyzer
Substrate	Access Substrate	Lumi-Phos PROsubstrate

Comparison of Technological Characteristics to the Predicate (Assay)

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Standard/Guidance Document Referenced (if applicable):

CLSI EP05-A3: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Third Edition

CLSI EP06-2nd Edition-: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach: Approved Guideline

CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition

CLSI EP09c: Measurement Procedure Comparison and Bias Estimation Using Patient Samples- Third Edition

Summary of Studies:

Method Comparison: A method comparison study was performed to compare the Access OV Monitor assay on the Dxl 9000 Access Immunoassay Analyzer to the predicate device. A total of one hundred fifty-two (152) samples falling within the measuring range of the Access OV Monitor assay were evaluated. The results of the within range method comparison study met the acceptance criteria of R2 ≥ 0.90 and slope 1.00 ± 0.09.

N	ConcentrationRange*(U/mL)	Slope	Slope95% CI	Intercept	Intercept95% CI	R2
152	2.4 - 5001	0.98	0.97 - 0.99	-0.14	-0.38 - 0.13	1.00

*Range is Access 2 values

Imprecision: A study based on CLSI EP05-A3 performed on the Dxl 9000 Access Immunoassay Analyzer tested multiple samples in triplicate in 2 runs per day for a minimum of 20 days. On the Dxl 9000 Access Immunoassav Analyzer, the within-laboratory (total) % CV ranged from 2.6% to 6.1%, for OV Monitor concentrations > 15 U/mL and the within-laboratory SD of 0.2 for a sample concentration ≤ 15 U/mL was observed.

Concentration (U/mL)		Repeatability(Within-run)		Between-run		Between-day		Within-Laboratory(Total)
Sample	N	Mean	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 1	120	5.5	0.1	1.7	0.1	1.6	0.2	3.4	0.2	4.1
Sample 2	120	54	1.6	2.9	0.0	0.0	1.2	2.2	2.0	3.6
Sample 3	120	89	1.5	1.6	1.7	1.9	1.2	1.3	2.5	2.8
Sample 4	120	524	9.4	1.8	5.8	1.1	8.7	1.7	14.0	2.7
Sample 5	120	1578	30.0	1.9	17.8	1.1	20.8	1.3	40.6	2.6
Sample 6	120	2837	94.9	3.3	23.3	0.8	131.2	4.6	163.7	5.8
Sample 7	120	3632	101.6	2.8	52.9	1.5	162.4	4.5	198.7	5.5
Sample 8	120	4489	128.1	2.9	28.4	0.6	239.4	5.3	273.0	6.1

Linearity: A verification study was performed to evaluate the linearity of the Access OV Monitor assay on the Dxl 9000 Access Immunoassay Analyzer based on CLSI EP06-Ed2. The Access

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OV Monitor assay is linear on the Dxl 9000 Access Immunoassay Analyzer throughout the analytical measuring interval of approximately 2.0 - 5,000 U/mL.

Limit of Blank (LoB): The LoB for Access OV Monitor assay is 0.5 U/mL on Dxl 9000 Access Immunoassay Analyzer.

Limit of Detection (LoD): The LoD estimate for the Access OV Monitor assay is 0.7 U/mL on Dxl 9000 Access Immunoassay Analyzer.

Limit of Quantitation (LoQ): The maximum LoQ determined for the Access OV Monitor assay is 2.0 U/mL on Dxl 9000 Access Immunoassay Analyzer.

Substantial Equivalence Comparison Conclusion

Beckman Coulter's Access OV Monitor assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to OV Monitor assay on the Access Immunoassay System (K023597) as demonstrated through the information and data provided in this submission. The performance testing presented in this submission provides evidence that the device is safe and effective in its intended use.

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.