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. With the advent of the administration of recombinant erythropoietin as a biologic therapy to increase red blood cell mass, an erythropoietin assay may be used also to aid in the prediction and monitoring of response to recombinant erythropoietin treatment in persons with anemias.
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.

Device Description

The Access® EPO assay consists of the reagent pack and calibrators. Other items needed to perform the assay include the Access substrate and wash buffers.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Access® EPO Assay based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

Performance Metric	Acceptance Criteria	Reported Device Performance
Precision	Total precision of ≤ 10% CV at EPO concentrations > 3 mIU/mL	Internal Data: - Precision tested at concentrations from approximately 9 to 475 mIU/mL. - Within-run imprecision ranged from 1.8% CV to 8.7% CV. - Total imprecision ranged from 2.6% CV to 8.7% CV. Conclusion: Meets the criterion; total precision values are all ≤ 10% CV.
Analytical Sensitivity	Lowest detectable level of EPO distinguishable from zero (Access EPO Calibrator S0) is ≤0.6 mIU/mL	Internal Data: - Reported as ≤0.6 mIU/mL.
Dilution Recovery (Linearity)	Sample mean recovery values for all serum and plasma samples were within the range of 100 ± 15%.	Internal Data: - Dilution recovery studies performed by diluting multiple human serum and plasma (heparin) samples at various levels with Access EPO Calibrator S0. - Sample mean recovery values were within the range of 100 ± 15%.
Methods Comparison	Acceptable agreement with predicate device (RDS Quantikine ELISA assays).	Internal Site Study: - Slope of 1.0511, intercept of -1.3595, and correlation coefficient (r) of 0.988. - N=103 with EPO concentration range of approximately 3 to 182 mIU/mL. External Site Study: - Slope of 1.1216, intercept of -2.4168, and correlation coefficient (r) of 0.995. - N=113 with EPO concentration range of approximately 3 to 193 mIU/mL.
Analytical Specificity	No significant interference from therapeutic drugs, similar compounds, or potential sample contaminants (total protein, bilirubin, hemoglobin, and triglycerides).	Internal Data: - No significant interference from therapeutic drugs or similar compounds. - No significant interference from potential sample contaminants (total protein, bilirubin, hemoglobin, and triglycerides).
Stability	EPO reagents stable for 28 days after opening; calibrators stable for 90 days after opening; calibration curve stable for 28 days.	Internal Data: - EPO reagents are stable for 28 days after opening. - Calibrators are stable for 90 days after opening. - The calibration curve is stable for 28 days.

2. Sample Sizes Used for the Test Set and the Data Provenance:

Precision: Not explicitly stated as a separate "test set" in the context of clinical samples, but the study was performed on samples with EPO concentrations ranging from 9 to 475 mIU/mL.
Dilution Recovery (Linearity): "Multiple human serum and plasma (heparin) samples." The exact number is not provided.
Methods Comparison:
- Internal Site Study: N=103
- External Site Study: N=113
Analytical Specificity: Not explicitly stated as a numerical sample size, but indicates testing for interference from "therapeutic drugs or similar compounds" and "potential sample contaminants."
Data Provenance: The studies are described as "Internal Site Study" and "External Site Study," suggesting the data comes from within Beckman Coulter's testing facilities and at least one other external laboratory. The samples were "human serum and plasma (heparin)." The country of origin is not explicitly stated, but the submission is to the FDA (USA). The studies appear to be prospective in nature, as they involve testing the performance of the new Access® EPO assay.

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

This information is not provided in the document. For an immunoassay, the "ground truth" for the test set is typically established by comparing the device's results to a well-established, often reference, method. In this case, the predicate device (RDS Quantikine ELISA) served as the reference for method comparison. The document does not describe expert adjudication for these numerical results.

4. Adjudication Method for the Test Set:

This is not applicable in the context of an immunoassay performance study focused on quantitative measurements. Adjudication methods (like 2+1, 3+1) are typically used in imaging or diagnostic accuracy studies where expert consensus is required to establish a qualitative or subjective ground truth. Here, the comparison is against an established quantitative predicate method.

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:

This information is not applicable to this device. The Access® EPO Assay is an in vitro diagnostic (IVD) immunoassay, not an AI-powered diagnostic imaging device or an AI human-in-the-loop system. Therefore, MRMC studies examining human reader performance with or without AI assistance are not relevant here.

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

Yes, the studies presented represent the standalone performance of the Access® EPO Assay. This is an automated immunoassay system; its performance metrics (precision, sensitivity, linearity, methods comparison, specificity, stability) characterize the algorithm and instrument's ability to quantitatively determine EPO levels without direct human interpretation of the assay's core output.

7. The Type of Ground Truth Used:

For the quantitative performance studies, particularly the "Methods Comparison," the ground truth was effectively the results obtained from established predicate devices, specifically the R&D Systems Quantikine IVD Erythropoietin ELISA Kit. These predicate devices are themselves validated diagnostic assays.

8. The Sample Size for the Training Set:

This information is not provided in the document. For an immunoassay, a "training set" in the context of machine learning isn't directly applicable in the same way it would be for an AI algorithm. Instead, "training" for such a system typically involves:

Assay development and optimization using numerous samples.
Establishing calibration curves using specific calibrator materials.
Method validation experiments that might involve hundreds or thousands of samples over time.
The document refers to "Summary of Performance Studies" as direct validation of the assay's performance attributes rather than detailing a distinct "training set."

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

As mentioned above, the concept of a "training set" with an explicitly established ground truth (like expert consensus or pathology for AI) is not directly applicable to this type of IVD immunoassay. The development and calibration of the assay would rely on:

Reference materials/standards: The assay is standardized against the "WHO 2nd IRP 67/343" (International Reference Preparation). This serves as a fundamental "ground truth" for the quantitative measurement of EPO.
Known concentrations: During assay development, samples with known EPO concentrations (often characterized by reference methods or gravimetric methods for primary standards) would be used to build and validate the assay's response curve.
Cross-validation with existing methods: Early in development, comparison with established methods would help refine the assay's performance.

Summary

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K052223

OCT -6 2006

Applicant:	Beckman Coulter, Inc.Immunodiagnostics Development Center1000 Lake Hazeltine DriveChaska, MN 55318		Page 1 of 2Date Prepared: October 4, 2006
Contact Person:	Lynn Weist, Staff Regulatory Specialist
Trade Name:	Access® EPO Assay
Product Classificationand Code:	Device Class - IIClassification Code - GGT (EPO Assay) and JIT (Calibrators)
Predicate Devices:	K936016 - Quantikine IVD Erythropoietin ELISA Kit - R & D Systems, Inc.K983203- IMMULITE EPO - Diagnostic Products Corp.K980737 - Nichols Advantage Chemiluminescent Erythropoietin Immunoassay - NicholsInstitute DiagnosticsK992799 - Sangui Bio Tech, Inc. EPO [Erythropoietin] ELISA Kit
Device Description:	The Access® EPO assay consists of the reagent pack and calibrators. Other items neededto perform the assay include the Access substrate and wash buffers.
Intended Use:	The Access EPO assay is a paramagnetic particle, chemiluminescent immunoassay for thequantitative determination of erythropoietin levels in human serum and plasma (heparin)using the Access Immunoassay Systems. This assay is intended as an aid in the diagnosisof anemias and polycythemias. With the advent of the administration of recombinanterythropoietin as a biologic therapy to increase red blood cell mass, an erythropoietin assaymay be used also to aid in the prediction and monitoring of response to recombinanterythropoietin treatment in persons with anemias.The Access EPO calibrators are intended to calibrate the Access EPO assay for thequantitative determination of EPO levels in human serum and plasma (heparin) using theAccess Immunoassay Systems.

Comparison of Technological

Characteristics:

Attribute	Access EPO	R&D Systems	DPC	Nichols	Sangui Bio Tech
Assay Type /Format	2-sitesimultaneousimmunometric(sandwich)chemiluminescent	ELISA	2-site sequentialenzymeimmunometric(sandwich)chemiluminescent	2-site simultaneousimmunometric(sandwich)chemiluminescent	2-site simultaneousimmunometric(sandwich) assay(ELISA)
Composition	Paramagneticparticles coatedwith goat anti-mouse IgG:mouse anti-recombinanthuman EPOmonoclonalantibody, BSA,sodium azide andProClin 300.Chicken anti-recombinantmouse EPOalkaline	Microplate -polystyrenemicroplate coatedwith mousemonoclonalantibody againstrecombinanthuman EPO.Conjugate - anti-EPO polyclonal(rabbit) antibody:horseradishperoxidaseconjugate w/thimerosal as a	Solid phase -Polystyrene beadcoated with ananti-ligand derivedfrom streptavidin.Reagent - ligand-labeled murinemonoclonal anti-EPO antibody withpreservative.Alkalinephosphataseconjugated to goatpolyclonal anti-	Streptavidin coatedmagnetic particlesin a buffercontaining goat,rabbit and mousegamma globulinwith sodium azideand ProClin 300.Acridinium ester-labeled mousemonoclonalantibody to humanEPO in a bufferedprotein solution withantimicrobial	Carboxyl-terminalmouse monoclonalantibody & an affinitypurified region-restricted amino-terminal sheepantibody. Solidphase coated withavidin. Captureantibodies arecoupled with biotin.Horseradishperoxidase labeledTag antibody.

Beckman Coulter, Inc. Abbreviated 510k: Access® EPO Assay and Calibrators
Response to FDA Request for Information (Verbal October 3, 2006) October 4, 2006

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510(k) Summary

Comparison of Technological Characteristics: (continued)

Attribute	Access EPO	R&D Systems	DPC	Nichols	Sangui Bio Tech
Composition(continued)	phosphatase(bovine) conjugate,BSA, sodium azideand ProClin 300.TRIS saline buffercontaining BSA,proteins (chicken,bovine, mouse),sodium azide andProClin 300	preservative.	EPO antibody inbuffer, withpreservative.	agents. Biotinlabeled mousemonoclonal antibodyto human EPO in abuffered proteinsolution, withsodium azide andProClin 300.	agents.
MeasuringRange /ReportableRange	0.6 - 750 mlU/mL	0-200 mIU/mL	0-200 mlU/mL	5-700 mU/mL	Unknown
Standardization	WHO 2nd IRP67/343	WHO 2nd IRP67/343	WHO 2nd IRP67/343	WHO 1st IS 87/684	Unknown

Summary of Performance Studies:

Precision: The assay exhibits total precision of ≤ 10% CV at EPO concentrations > Assay precision was tested at concentrations from approximately 9 to 475 3mlU/mL. mIU/mL. The within-run imprecision ranged from 1.8% CV to 8.7% CV. Total imprecision ranged from 2.6% CV to 8.7% CV.

Analytical Sensitivity: The lowest detectable level of EPO distinguishable from zero (Access EPO Calibrator S0) is ≤0.6 mIU/mL.

Dilution Recovery (Linearity); Dilution recovery studies were performed by diluting multiple human serum and plasma (heparin) samples at various levels with Access EPO Calibrator Sample mean recovery values for all serum and plasma samples, were within the SO. range of 100 ± 15%.

Methods Comparison: Internal and external site comparison studies run with both the Access EPO and RDS Quantikine ELISA assays demonstrated acceptable agreement and the following statistical data.

Internal Site Study: Slope of 1.0511, intercept of -1.3595, and correlation coefficient (r) of 0.988. For this study N=103 with an EPO concentration range of approximately 3 to 182 mIU/mL.

External Site Study: Slope of 1.1216, intercept of -2.4168, and correlation coefficient (r) of 0.995. For this study N=113 with an EPO concentration range of approximately 3 to 193 mIU/mL.

Analytical Specificity: There was no significant interference from therapeutic drugs or similar compounds in the Access EPO assay. In addition, there was no significant interference from potential sample contaminants (total protein, bilirubin, hemoglobin, and triglycerides).

Stability: EPO reagents are stable for 28 days after opening and calibrators are stable for 90 days after opening. The calibration curve is stable for 28 days.

Conclusion:

The EPO Assay and EPO Calibrators on the Access Immunoassay Systems is substantially equivalent to the predicates for the measurement of EPO in human serum and plasma.

CONFIDENTIAL

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle with its wings spread, symbolizing protection and care. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle emblem.

Public Health Service

Food and Druq Administration 2098 Gaither Road Rockville MD 20850

Ms. Lynn Weist Staff Regulatory Specialist Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318

K052223 Re:

Trade/Device Name: Access® EPO Assay Regulation Number: 21 CFR & 864.7250 Regulation Name: Erythropoietin Assay Regulatory Class: II Product Code: GGT, JIT Dated: August 30, 2006 Received: August 31, 2006

Dear Ms. Weist:

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.

OCT - 6 2006

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 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.

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Page 2 –

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 (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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 (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

lobat Z. Beckerf

Robert L. Becker, Jr., MD, PAD Director Division of Immunology and Hematology 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): K052223

Device Name: Access® EPO Assay

Indications for Use:

Access® EPO assay is a paramagnetic particle, The 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. With the advent of the administration of recombinant erythropoietin as a biologic therapy to increase red blood cell mass, an erythropoietin assay may be used also to aid in the prediction and monitoring of response to recombinant erythropoietin treatment in persons with anemias.

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.

Robert Zietzke
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K052223

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR Over-The-Counter Use ________________________________________________________________________________________________________________________________________________ (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Beckman Coulter, Inc. Abbreviated 510k: Access® EPO Assay and Calibrators Response to FDA Request for Information, dated September 16, 2005 August 30, 2006

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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).”