The Access EPO assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of erythropoietin levels in human serum and plasma (heparin) using the Access Immunoassay Systems. This assay is intended as an aid in the diagnosis of anemias and polycythemias.

Device Description

The Access EPO Calibrators are intended to calibrate the Access EPO assay for the quantitative determination of EPO levels in human serum and plasma (heparin) using the Access Immunoassay Systems.

The Access EPO assay is a two-site immunoenzymatic ("sandwich") assay. A sample is added to a reaction vessel along with the paramagnetic particles coated with mouse monoclonal anti-EPO, blocking reagent and the alkaline phosphatase conjugate. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of analyte in the sample. Analyte concentration is automatically determined from a stored calibration.

AI/ML Overview

The provided text describes the 510(k) premarket notification for the Beckman Coulter "Access EPO" assay when run on the Dxl 9000 Access Immunoassay Analyzer. This document outlines the device's technical characteristics, its intended use, and comparative studies against a predicate device. However, it does not describe an AI-powered diagnostic device or a study involving human readers and AI assistance. Instead, it describes an immunoassay for measuring erythropoietin levels. Therefore, many of the detailed points requested in your prompt (e.g., number of experts for ground truth, MRMC study, effect size of AI, standalone AI performance) are not applicable to this specific submission.

Despite this, I will extract and present the available information that aligns with your request regarding acceptance criteria and study details for this non-AI diagnostic device.

Here's the breakdown based on the provided document:

Device Name: Access EPO

Intended Use: The Access EPO assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of erythropoietin levels in human serum and plasma (heparin) using the Access Immunoassay Systems. This assay is intended as an aid in the diagnosis of anemias and polycythemias.

1. Table of Acceptance Criteria and Reported Device Performance

The document defines performance characteristics (acceptance criteria implicitly by demonstrating acceptable results) through various analytical studies.

Study Parameter	Acceptance Criteria (Implicit from demonstrated performance)	Reported Device Performance
Method Comparison	Slope close to 1, Intercept close to 0, High Correlation Coefficient (comparing new system to predicate)	N = 152 samples (141 native, 11 spiked) - Concentration Range: 0.79 - 697 mIU/mL (Access 2 values) - Slope: 0.99 (95% CI: 0.97 – 1.00) - Intercept: -0.040 (95% CI: -0.19 – 0.22) - Correlation Coefficient (R): 1.00 (Demonstrates substantial equivalence to predicate)
Imprecision (Within-Laboratory)	≤ 0.30 mIU/mL SD at concentrations ≤ 3.0 mIU/mL ≤ 10.0% CV at concentrations > 3.0 mIU/mL	Performed on four Dxl 9000 Access Immunoassay Analyzers, testing four native samples and one spiked sample. All reported within-laboratory %CVs are well below 10% for concentrations > 3.0 mIU/mL, and SDs are below 0.30 mIU/mL for concentrations ≤ 3.0 mIU/mL. - Sample 1 (2.0 mIU/L): Within-Laboratory SD 0.07, %CV 3.8 - Sample 2 (18 mIU/L): Within-Laboratory SD 0.5, %CV 3.0 - Sample 3 (105 mIU/L): Within-Laboratory SD 2.8, %CV 2.7 - Sample 4 (267 mIU/L): Within-Laboratory SD 6.3, %CV 2.4 - Sample 5 (548 mIU/L): Within-Laboratory SD 20.4, %CV 3.7
Linearity	Assay demonstrates linearity across the measuring interval.	"The assay demonstrated linearity across the measuring interval" (Specific range is 0.6-750 mIU/L, as stated in the "Measuring Range" table).
Limit of Blank (LoB)	Not explicitly stated as acceptance criteria, but claimed value is provided.	Claimed LoB for Access assay is 0.6 mIU/mL.
Limit of Detection (LoD)	Not explicitly stated as acceptance criteria, but claimed value is provided.	Claimed LoD for Access assay is 0.6 mIU/mL.
Limit of Quantitation (LoQ)	Not explicitly stated as acceptance criteria, but claimed value is provided.	Claimed LoQ for Access assay is 0.6 mIU/mL.

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

Method Comparison Test Set: 152 samples (141 native, 11 spiked).
Imprecision Test Set: 5 samples (4 native, 1 spiked), tested in duplicate in 2 runs per day for 20 days on each of four analyzers (total 80 replicates per sample).
Data Provenance: The document does not specify the country of origin for the samples or if they were retrospective or prospective. Given it's a 510(k) submission for a laboratory diagnostic, the samples are typically human biological samples collected for validation purposes.

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

Not applicable. This is not an image-based AI diagnostic device requiring expert adjudication of images. The "ground truth" for an immunoassay is typically established through reference methods or analysis of sample characteristics (e.g., known concentrations for spiked samples, or comparison to a cleared predicate device for native samples).

4. Adjudication Method for the Test Set

Not applicable, as it's an immunoassay for quantitative determination of erythropoietin, not a subjective interpretation task that would require adjudication.

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 device is an automated immunoassay system, not an AI-assisted diagnostic tool that involves human readers.

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

Not applicable in the context of an "algorithm only" AI performance. The performance described here is the "standalone" performance of the immunoassay system (Dxl 9000 Access Immunoassay Analyzer with Access EPO assay reagents).

7. The Type of Ground Truth Used

The ground truth for this device's performance evaluation is established through:

Comparison to a Predicate Device: For the method comparison study, the predicate device (Access EPO Assay on Access 2 Immunoassay System) served as the reference for native samples.
Known Concentrations: For imprecision and linearity studies, samples of known or targeted concentrations (including spiked samples) are used.
Reference Standards/Materials: Implied for establishing accurate concentrations for LoB, LoD, and LoQ.

8. The Sample Size for the Training Set

Not applicable. This is an immunoassay, not a machine learning model that requires a "training set" in the conventional sense of AI development. The "training" of the instrument involves calibration using specific calibrators provided with the assay.

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

Not applicable as there is no "training set" for an AI model. The "calibration" of the immunoassay is done using Access EPO Calibrators, which are intended to calibrate the assay. The ground truth for these calibrators would be established by the manufacturer through rigorous analytical methods to assign their precise concentrations.

Summary

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April 22, 2024

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

Re: K240182

Trade/Device Name: Access EPO Regulation Number: 21 CFR 864.7250 Regulation Name: Erythropoietin Assay Regulatory Class: Class II Product Code: GGT Dated: January 22, 2024 Received: January 23, 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 (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"

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K240182 - Kate Oelberg

(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 QS 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) 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, Min Wu

Min Wu, 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

510(k) Number (if known) K240182

Device Name Access EPO

Indications for Use (Describe)

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 K240182

Submitted Bv:

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

Primarv Contact:

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

Alternate Contact:

Kuljeet Kaur Senior Manager, Regulatory Affairs Phone: (952) 368-7816 Email: kkaur@beckman.com

Device Name

Common Name: Access EPO Trade Name: Access EPO Reagent on Dxl 9000 Access Immunoassay Analyzer Classification Name: Ervthropoietin assay Classification Requlation: [21 CFR 864.7250]

Predicate Device

Device Name: Access EPO 510(k) Numbers: K052223

Device Description

The Access EPO Calibrators are intended to calibrate the Access EPO assay for the quantitative determination of EPO levels in human serum and plasma (heparin) using the Access Immunoassay Systems.

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After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of analyte in the sample. Analyte concentration is automatically determined from a stored calibration.

Intended Use

Parameter	Access EPO Assay on Access 2Immunoassay System (Predicate)	Access EPO Assay on Dxl 9000Access Immunoassay System
Intended use	The Access EPO assay is aparamagnetic particle, chemiluminescentimmunoassay for the quantitativedetermination of erythropoietin levels inhuman serum and plasma (heparin) usingthe Access Immunoassay Systems. Thisassay is intended as an aid in thediagnosis of anemias and polycythemias.	Same
Technology	2-site (sandwich) chemiluminescent	Same
Format	Chemiluminescent	Same
Calibration	Utilizes a stored multi-point calibrationcurveCalibrators are provided at six levels –zero and approximately 5, 25, 125, 375and 750 mIU/mL	Same
Sample Type	Serum and plasma (heparin)	Same
MeasuringRange	0.6-750 mIU/L	Same
Instrument	Access Immunoassay system	Dxl 9000 Access ImmunoassayAnalyzer
Substrate	Access Substrate	Lumi-Phos Pro Substrate

Comparison of Technological Characteristics to the Predicate

Standard/Guidance Document Referenced (if applicable):

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These standards can be copied or found from regulatory 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 30 Edition: Measurement Procedure Comparison and Bias Estimation Using Patient Samples: Third Edition

Summary of Studies

Method Comparison:

A study based on CLSI EP09c, 3rd Edition using Passing-Bablok regression and Pearson's correlation tested 141 native and 11 spiked samples across three Access 2 Immunoassay Systems and three Dxl 9000 Access Immunoassay Analyzers.

N	ConcentrationRange*(mIU/mL)	Slope	Slope95% CI	Intercept	Intercept95% CI	CorrelationCoefficientR
152	0.79 - 697	0.99	0.97 – 1.00	-0.040	(-0.19) - 0.22	1.00

*Range is Access 2 values

Imprecision: The assay was designed to have within-laboratory imprecision as listed below:

≤ 0.30 mIU/mL SD at concentrations ≤ 3.0 mIU/mL
≤ 10.0% CV at concentrations > 3.0 mlU/mL

A study based on CLSI EP05-A3performed on each of four Dxl 9000 Access Immunoassay Analyzers tested four native samples and one spiked sample in duplicate in 2 runs per day for 20 days.

Concentration (mIU/L)		Repeatability(Within-run)		Between-run		Between-day		Within-Laboratory
Sample	N	Mean	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 1	80	2.0	0.05	2.3	0.02	1.0	0.06	2.8	0.07	3.8
Sample 2	80	18	0.2	1.2	0.1	0.5	0.5	2.7	0.5	3.0
Sample 3	80	105	2.2	2.2	1.0	1.0	1.4	1.4	2.8	2.7
Sample 4	80	267	4.9	1.8	1.2	0.4	3.8	1.4	6.3	2.4
Sample 5	80	548	9.3	1.7	0.0	0.003	18.1	3.3	20.4	3.7

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Linearity: A study based on CLSI EP06-Ed2 performed on the Dxl 9000 Access Immunoassay Analyzer determined the assay demonstrated linearity across the measuring interval.

Limit of Blank (LoB): The claimed LoB for Access assay is 0.6 mIU/mL on Dxl 9000 Access Immunoassay Analyzer.

Limit of Detection (LoD): The claimed LoD for Access assay is 0.6 mIU/mL on Dxl 9000 Access Immunoassay Analyzer.

Limit of Quantitation (LoQ): The claimed LoQ for Access assay is 0.6 mlU/mL on Dxl 9000 Access Immunoassay Analyzer.

Substantial Equivalence Comparison Conclusion

Beckman Coulter's Access EPO Assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to the Access EPO Assay 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

§ 864.7250 Erythropoietin assay.

(a)
Identification. A erythropoietin assay is a device that measures the concentration of erythropoietin (an enzyme that regulates the production of red blood cells) in serum or urine. This assay provides diagnostic information for the evaluation of erythrocytosis (increased total red cell mass) and anemia.(b)
Classification. Class II. The special control for this device is FDA's “Document for Special Controls for Erythropoietin Assay Premarket Notification (510(k)s).”