The Access sTfR assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of soluble transferrin receptor (sTR) levels in human serum and plasma (heparin) using the Access Immunoassay Systems. This assay is intended as an aid in the diagnosis of Iron Deficiency Anemia (IDA), and for the differential diagnosis of IDA and Anemia of Chronic Disease (ACD).

This assay may also be used in conunction with an Access Ferritin measurement to provide a calculated sTR log ferritin index. This index is intended as an aid in the diagnosis of IDA, and for the differential diagnosis of IDA and ACD.

Device Description

Access sTfR: The sTfR assay reagent pack consists of two specific reagents: (R1a) paramagnetic particles coated with streptavidin:biotinylated soluble transferrin receptor monoclonal antibody, proteins (mouse, goat, bovine), bovine serum albumin (BSA), 0.1% sodium azide, and 0.17% ProClin 300; and (R1b) Monoclonal mouse anti-human soluble transferrin receptor alkaline phosphatase (bovine) conjugate, BSA, 0.1% sodium azide and 0.17% ProClin 300. Two assay packs containing 50 tests per pack are provided for a total of 100 assay determinations.

The Access sTfR assay is a sequential two-step immunoenzymatic ("sandwich") assay. A sample is added to a reaction vessel along with paramagnetic particles coated with anti-sTfR antibody. During incubation, the sTfR antigen in the sample binds to the immobilized anti-sTfR antibody on the solid phase. Alkaline phosphatase conjugated anti-sTfR antibody is then added and reacts with a different antigenic site on the sTfR molecule.

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

Here's a breakdown of the acceptance criteria and study information for the Access sTfR device, based on the provided FDA 510(k) summary:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Acceptance Criteria	Reported Device Performance	Meets Criteria?
Method Comparison	Slope: 0.99 – 1.01 (95% CI)	Slope: 1.00 (95% CI: 0.99 – 1.01)	Yes
	Intercept: -0.14 - 0.15 (95% CI)	Intercept: -0.016 (95% CI: -0.14 - 0.15)	Yes
	Correlation Coefficient (R): Not explicitly stated as acceptance, but comparison shows R = 1.00	Correlation Coefficient (R): 1.00	Yes (Excellent)
Imprecision	≤ 0.72 nmol/L SD at concentrations ≤ 9 nmol/L	Sample 1 (9.1 nmol/L): 0.24 nmol/L SD	Yes
	≤ 8.0% CV at concentrations > 9 nmol/L	Sample 2 (17 nmol/L): 2.6% CV < 8%	Yes
		Sample 3 (20 nmol/L): 2.4% CV < 8%	Yes
		Sample 4 (33 nmol/L): 1.8% CV < 8%	Yes
		Sample 5 (67 nmol/L): 2.0% CV < 8%	Yes
		Sample 6 (118 nmol/L): 2.2% CV < 8%	Yes
Linearity	"The assay demonstrated linearity across the measuring interval."	"The assay demonstrated linearity across the measuring interval."	Yes (Direct statement)
Detection Capability	Not explicitly stated as acceptance criteria, but listed as targets to be determined.	LoB: 0.04 nmol/L	Achieved targets
		LoD: 0.05 nmol/L	Achieved targets
		LoQ: 0.05 nmol/L (≤ 20% within-lab CV)	Achieved targets

Study Details

Sample size used for the test set and the data provenance:
- Method Comparison: N = 200 patient samples.
- Imprecision: N = 6 samples (Sample 1-6) tested in duplicate, in 2 runs/day for a minimum of 20 days (total N for each sample is 80 measurements).
- Linearity & Detection Capability: Sample sizes for these specific studies are not explicitly stated, but the studies were performed on the Dxl 9000 Access Immunoassay Analyzer.
- Data Provenance: Not specified in the provided document (e.g., country of origin, retrospective or prospective).
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This device is an in vitro diagnostic (IVD) immunoassay for the quantitative determination of soluble transferrin receptor (sTfR) levels. The performance studies (method comparison, imprecision, linearity, detection capability) do not involve human experts establishing a "ground truth" in the way an imaging AI might. Instead, the "ground truth" (or reference standard) for method comparison is the measurement from the predicate device (Access sTfR Assay on Access 2 Immunoassay System). For imprecision, linearity, and detection capability, the ground truth is established by the analytical measurement procedures themselves against defined statistical targets.
Adjudication method for the test set:
- Not applicable. As noted above, this is an IVD immunoassay, not a system requiring human adjudication of results in the traditional sense. The reference method (predicate device) serves as the comparator for the method comparison study.
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 IVD immunoassay, not an imaging AI or a device that assists human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance studies (method comparison, imprecision, linearity, detection capability) represent the standalone performance of the Access sTfR assay on the Dxl 9000 Access Immunoassay Analyzer. Its output is a quantitative sTfR value.
The type of ground truth used:
- Method Comparison: Measurements from the predicate device (Access sTfR Assay on Access 2 Immunoassay System). This serves as the reference for comparison against the new device.
- Imprecision, Linearity, Detection Capability: Analytical measurements are compared against pre-defined statistical performance targets (e.g., SD, CV, LoB, LoD, LoQ) established according to CLSI guidelines.
The sample size for the training set:
- Not applicable. This is a conventional immunoassay, not a machine learning/AI device requiring a separate "training set" in that context. The device uses established biochemical reactions and a stored calibration curve.
How the ground truth for the training set was established:
- Not applicable (see above). The device establishes its "calibration" using internal calibrators and controls to create a stored calibration curve, as is typical for immunoassays. This is distinct from machine learning model training with labeled ground truth data.

Summary

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July 3, 2024

Beckman Coulter Inc. Neha Desai Staff Quality and Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318

Re: K240987

Trade/Device Name: Access sTfR Regulation Number: 21 CFR 866.5880 Regulation Name: Transferrin Immunological Test System Regulatory Class: Class II Product Code: DDG Dated: April 10, 2024 Received: April 10, 2024

Dear Neha Desai:

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

510(k) Number (if known) K240987

Device Name Access sTfR

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 K240987

Submitted Bv:

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

Primarv Contact:

Neha Desai Staff Quality and Regulatory Affairs Phone: (612) 244-9788 Email: nhdesai@beckman.com

Alternate Contact:

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

Device Name

Common Name: Access sTfR Trade Name: Access sTfR on Dxl 9000 Access Immunoassay Analyzer Classification Name: Transferrin immunological test system Classification Requlation: [21 CFR 866.5880]

Predicate Device

Device Name: Access sTfR 510(k) Numbers: K080634

Device Description

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the solid phase. Alkaline phosphatase conjugated anti-sTfR antibody is then added and reacts with a different antigenic site on the sTfR molecule.

Intended Use

The Access sTfR assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of soluble transferrin receptor (sTfR) levels in human serum and plasma (heparin) using the Access Immunoassay Systems. This assay is intended as an aid in the diagnosis of Iron Deficiency Anemia (IDA), and for the differential diagnosis of IDA and Anemia of Chronic Disease (ACD).

This assay may also be used in conjunction with an Access Ferritin measurement to provide a calculated sTfR/log ferritin index. This index is intended as an aid in the diagnosis of IDA, and for the differential diagnosis of IDA and ACD.

Parameter	Access sTfR Assay on Access 2Immunoassay System (Predicate)	Access sTfR Assay onDxl 9000 AccessImmunoassay System
Intended use	The Access sTfR assay is aparamagnetic particle, chemiluminescentimmunoassay for the quantitativedetermination of soluble transferrinreceptor (sTfR) levels in human serumand plasma (heparin) using the AccessImmunoassay Systems. The assay isintended as an aid in the diagnosis ofIron Deficiency Anemia (IDA), and for thedifferential diagnosis of IDA and Anemiaof Chronic Disease (ACD).This assay may also be used inconjunction with an Access Ferritinmeasurement to provide a calculatedsTfR/log ferritin index. This index isintended as an aid in the diagnosis ofIDA, and for the differential diagnosis ofIDA and ACD.	Same
Technology	2-site (sandwich) chemiluminescent	Same

Comparison of Technological Characteristics to the Predicate

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Parameter	Access sTfR Assay on Access 2Immunoassay System (Predicate)	Access sTfR Assay onDxl 9000 AccessImmunoassay System
Format	Chemiluminescent	Same
Calibration	Utilizes a stored multi-point calibrationcurve	Same
Sample Type	Serum and plasma (heparin)	Same
MeasuringRange	3.0 to 150 nmol/L	0.05 – 150 nmol/L
Instrument	Access Immunoassay system	Dxl 9000 AccessImmunoassay Analyzer
Substrate	Access Substrate	Lumi-Phos Pro Substrate

Standard/Guidance Document Referenced (if applicable):

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 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 Edition using Passing-Bablok regression and Pearson's correlation compared the Access 2 Immunoassay System and the Dxl 9000 Access Immunoassay Analyzer.

N	ConcentrationRange*(nmol/L)	Slope	Slope95% Cl	Intercept	Intercept95% Cl	CorrelationCoefficient R
200	0.10 - 142	1.00	0.99 – 1.01	-0.016	-0.14 - 0.15	1.00

*Range is Access 2 values

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Imprecision:

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

≤ 0.72 nmol/L SD at concentrations ≤ 9 nmol/L
• ≤ 8.0% CV at concentrations > 9 nmol/L

A study based on CLSI EP05-A3 performed on the Dxl 9000 Access Immunoassay Analyzer tested multiple samples in duplicate in 2 runs per day for a minimum of 20 days.

Concentration (nmol/L)	Repeatability (Within-run)					Between-run		Between-day		Within- Laboratory (Total)
Sample	N	Mean	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 1	80	9.1	0.15	1.6	0.10	1.1	0.15	1.7	0.24	2.6
Sample 2	80	17	0.3	1.8	0.3	1.7	0.1	0.8	0.5	2.6
Sample 3	80	20	0.4	2.0	0.0	0.01	0.3	1.3	0.5	2.4
Sample 4	80	33	0.4	1.2	0.4	1.1	0.2	0.7	0.6	1.8
Sample 5	80	67	0.7	1.1	0.4	0.6	1.1	1.6	1.4	2.0
Sample 6	80	118	1.5	1.3	1.2	1.0	1.6	1.4	2.6	2.2

Linearitv:

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

Detection Capability:

Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) studies were conducted on the Dxl 9000 Access Immunoassay Analyzer following CLSI guideline EP17-A2.

	nmol/L
Limit of Blank (LoB)	0.04
Limit of Detection (LoD)	0.05
Limit of Quantitation (LoQ)	0.05
≤ 20% within-lab CV

Substantial Equivalence Comparison Conclusion

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

§ 866.5880 Transferrin immunological test system.

(a)
Identification. A transferrin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the transferrin (an iron-binding and transporting serum protein) in serum, plasma, and other body fluids. Measurement of transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell disorders, such as iron deficiency anemia.(b)
Classification. Class II (performance standards).