The Access BR Monitor assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CA 15-3 antigen levels in human serum and plasma (heparin) using the Access Immunoassay Systems. This device is indicated for use in the measurement of CA 15-3 antigen to aid in the management of breast cancer patients. Serial testing for CA 15-3 antigen concentrations should be used in conjunction with other clinical methods for monitoring breast cancer.

Device Description

The Access BR Monitor assay, Access BR Monitor Calibrators, and the Access Immunoassay analyzers comprise the Dxl 9000 Access Immunoassay Amalyzer for the quantitative determination of CA 15-3 antigen levels in human serum and plasma (heparin) using the Dxl 9000 Access Immunoassay Analyzer.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Access BR Monitor device, based on the provided FDA document:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria	Reported Device Performance
Method Comparison	Not explicitly stated as numerical acceptance criteria for slope, intercept, or correlation coefficient, but inferred by comparison to predicate.	Comparing Dxl 9000 to Access 2: - Slope: 0.95 (95% CI: 0.94 - 0.96) - Intercept: 0.70 (95% CI: 0.31 - 1.4) - Correlation Coefficient (R): 1.00(Implied acceptance if comparable to predicate)
Imprecision (Within-Laboratory)	- SD ≤ 1.5 U/mL at concentrations ≤ 15 U/mL - CV ≤ 10.0% at concentrations ≥ 15 U/mL	Met acceptance criteria. - Sample 1 (4.2 U/mL): SD 0.1, CV 3.4% - Sample 2 (19 U/mL): CV 2.9% - Sample 3 (34 U/mL): CV 3.2% - Sample 4 (79 U/mL): CV 3.0% - Sample 5 (105 U/mL): CV 3.0% - Sample 6 (425 U/mL): CV 3.2% - Sample 7 (825 U/mL): CV 4.0%
Linearity	Not explicitly stated numerically, but stated as being linear throughout the analytical measuring interval.	Met acceptance criterion, indicating linearity throughout the analytical measuring interval (0.8 – 1,000 U/mL).
Limit of Blank (LoB)	0.4 U/mL	Met acceptance criterion. LoB estimate: 0.1 U/mL.
Limit of Detection (LoD)	0.5 U/mL	Met acceptance criterion. LoD estimate: 0.3 U/mL.
Limit of Quantitation (LoQ)	Not explicitly stated numerically, but two different LoQ definitions are provided.	- 20% CV LoQ estimate: 0.3 U/mL - LoQ at 20% within-laboratory imprecision estimate: 0.8 U/mL

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

Method Comparison: N = 163 samples.
- Data Provenance: Not specified in the provided text (e.g., country of origin, retrospective or prospective).
Imprecision:
- Sample 1, 2: N = 126
- Sample 3, 4, 5, 6, 7: N = 120
- Data Provenance: Not specified.
Linearity, LoB, LoD, LoQ: Sample sizes not explicitly stated for these specific studies, beyond the "N" for method comparison and imprecision.
- Data Provenance: Not specified.

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

There is no mention of experts or ground truth establishment for the test set in the provided document. The studies described are analytical performance studies (method comparison, imprecision, linearity, limits) of an immunoassay device, which typically compare the device's measurements against a reference method or predetermined values, not against expert consensus on clinical diagnoses.

4. Adjudication Method for the Test Set

Not applicable, as the studies are analytical performance assessments of an immunoassay, not studies involving human interpretation or adjudication of clinical cases.

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

No, an MRMC comparative effectiveness study was not done. This device is an immunoassay for measuring CA 15-3 antigen levels, not an AI-assisted diagnostic imaging or interpretation tool that would involve human readers.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done

Yes, the studies described (Method Comparison, Imprecision, Linearity, LoB, LoD, LoQ) are all examples of standalone performance evaluations of the immunoassay system. The device itself (Access BR Monitor on the Dxl 9000 Access Immunoassay Analyzer) operates as an "algorithm only" in the sense that it automates the measurement of the analyte; there is no human-in-the-loop for the measurement process itself.

7. The Type of Ground Truth Used

The "ground truth" for these analytical studies is either:

Reference method/Predicate device results: For the method comparison study, the Access 2 Immunoassay System served as the reference (predicate) for comparison.
Known concentrations/values: For studies like Imprecision, Linearity, LoB, LoD, and LoQ, calibrated samples or controls with known or expected analyte concentrations are used as the reference against which the device's measurements are assessed. The document refers to "predetermined values" or "calculated estimates" based on established statistical methods (e.g., CLSI guidelines).

8. The Sample Size for the Training Set

Not applicable. This device is an immunoassay, not a machine learning or AI model that requires a "training set." Its calibration is established through a stored calibration curve, as mentioned in the "Comparison of Technological Characteristics" table.

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

Not applicable, as there is no "training set" in the context of an AI/ML model for this immunoassay device. The "calibration curve" for the immunoassay is established using calibrators, which are materials with known concentrations of the analyte, manufactured and tested according to quality control standards.

Summary

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May 9, 2024

Beckman Coulter, Inc. Kate Oelberg Senior Staff Quality and Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318

Re: K240403

Trade/Device Name: Access BR Monitor Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: MOI Dated: February 9, 2024 Received: February 9, 2024

Dear Kate Oelberg:

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 (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"

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(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).

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 (QS) 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

Form Approved: OMB No. 0910-0120 Expiration Date: 07/31/2026 See PRA Statement below.

Submission Number (if known)

K240403 Device Name

Access BR Monitor

Indications for Use (Describe)

The Access BR Monitor assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CA 15-3 antigen levels in human serum and plasma (heparin) using the Access Immunoasay Systems. This device is indicated for use in the measurement of CA 15-3 antigen to aid in the management of breast cancer patients. Serial testing for CA 15-3 antigen concentrations should be used in conjunction with other clinical methods for monitoring breast 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 21 CFR 807.92.

510(k) Number: K240403

Date Prepared: April 29, 2024

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

Primary Contact:

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

Alternate Contact:

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

Device Name:

Common Name: Immunoassay for the determination of CA 15-3 antigen Trade Name: Access BR Monitor Reagents Classification Name: Tumor-associated antigen immunological test system Classification Regulation: (21 CFR 866.6010)

Predicate Device: Device Name: Access BR Monitor 510(k) Numbers: K072612, K033036

Device Description

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Intended Use

Parameter	Access BR Monitor on Access 2Immunoassay System Predicate -K072612	Access BR Monitor on Dxl9000 Access ImmunoassayAnalyzer
Intended use	The Access BR Monitor assay is aparamagnetic particle,chemiluminescent immunoassay forthe quantitative determination of CA15-3 antigen levels in human serumand plasma (heparin) using the AccessImmunoassay Systems. This device isindicated for use in the measurementof CA 15-3 antigen to aid in themanagement of breast cancer patients.Serial testing for CA 15-3 antigenconcentrations should be used inconjunction with other clinical methodsfor monitoring breast cancer.	Same
AnalyteMeasured	CA 15-3 antigen levels in humanserum and plasma (heparin)	Same
Technology	Two-site immunoenzymatic("sandwich") assay	Same
Format	Chemiluminescent	Same
Method	Automated	Same
Calibration	Utilizes a stored calibration curve	Same
Measuring Range	0.5 – 1,000 U/mL	0.8 - 1,000 U/mL
Substrate	Access Substrate	Lumi-Phos PRO Substrate
Instrument	Access 2 Immunoassay system;	Dxl 9000 Access ImmunoassayAnalyzer

Comparison of Technological Characteristics to the Predicate

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Standard/Guidance Document Referenced (if applicable):

These standards can be copied or found from requlatory submission reports:

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 3rd Edition: Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Third Edition

Summary of Studies

Method Comparison: A study based on CLSI EP09c, 3rd Edition20 using Passing-Bablok regression and Pearson's correlation compared the Access 2 Immunoassay System and the Dxl 9000 Access Immunoassay Analyzer.

N	ConcentrationRange*(U/mL)	Slope	Slope95% Cl	Intercept	Intercept95% Cl	CorrelationCoefficient R
163	0.55 - 990	0.95	0.94 - 0.96	0.70	0.31 - 1.4	1.00

*Range is Access 2 values

Imprecision: The within-laboratory imprecision is ≤ 1.5 U/mL SD at concentrations ≤ 15 U/mL and ≤ 10.0% CV at concentrations ≥ 15 u/mL. The results met the acceptance criteria and indicated that the imprecision of the Access BR Monitor assay is acceptable on Dxl 9000 Access Immunoassay Analyzer.

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	126	4.2	0.1	2.0	0.1	2.8	0.0001	0.0	0.1	3.4
Sample 2	126	19	0.3	1.6	0.4	2.0	0.2	1.2	0.5	2.9
Sample 3	120	34	0.8	2.2	0.6	1.7	0.6	1.6	1.1	3.2
Sample 4	120	79	1.8	2.3	1.5	2.0	0.0	0.0	2.4	3.0
Sample 5	120	105	1.9	1.8	2.4	2.3	0.0	0.0	3.1	3.0
Sample 6	120	425	9.2	2.2	9.8	2.3	0.0	0.0	13.4	3.2
Sample 7	120	825	26.3	3.2	19.9	2.4	1.8	0.2	33.0	4.0

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Linearity: The results of this study met the acceptance criterion, indicating that the Access BR Monitor assay is linear on the Dxl 9000 Access Immunoassay Analyzer throughout the analytical measuring interval (0.8 – 1,000 U/mL).

Limit of Blank (LoB): The LoB estimate for BR Monitor was determined to be 0.1 U/mL on Dxl 9000 Immunoassay Analyzer. The results of this study demonstrate that the BR Monitor assay met the acceptance criteria of 0.4 U/mL on Dxl 9000 Access Immunoassay Analyzer.

Limit of Detection (LoD): The LoD estimate for the BR Monitor assay is 0.3 U/mL on Dxl 9000 Immunoassay Analyzer. The results of this study demonstrate that the BR Monitor assay met the acceptance criteria of 0.5 U/mL on Dxl 9000 Access Immunoassay Analyzer.

Limit of Quantitation (LoQ): The results provided demonstrate the 20% CV LoQ estimate for the BR Monitor assay to be 0.3 U/mL. The results provided demonstrate the LoQ at 20% within-laboratory imprecision estimate of the BR Monitor assay to be 0.8 U/mL on the Dxl 9000 Immunoassay Analyzer.

Conclusion: Beckman Coulter's Access BR Monitor on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to the Access BR Monitor on the Access 2 Immunoassay System 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.