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 a 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.

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

The Access sTfR QC is intended for monitoring system performance of the Access sTfR assay.

Device Description

The Access sTfR reagent, calibrators, controls, and the Access Immunoassay Analyzers (Access, Access 2, Synchron LXi 725, UniCel DxC 600i, UniCel Dxl 600, and UniCel Dxl 800) comprise the Access Immunoassay Systems for the quantitative determination of soluble transferrin receptor in human serum and plasma.

Automated; Paramagnetic particles coated with mouse monoclonal antibody against sTfR. Uses the same mouse monoclonal antibodies against sTfR in the capture phase and signal phase as the predicate device.

Utilizes dioxetane-based chemiluminescent substrate; measures light production from a chemiluminescent reaction.

Calibrators are comprised of natural sTfR at 6 levels (0, 3, 10, 30, 80, and 150 nmol/L) in a buffered matrix.

QCs are human sTfR provided as a liquid at 3 levels (~10, ~25, ~90 nmol/L) in a buffered matrix.

AI/ML Overview

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1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance (Access sTfR)
Imprecision (Total precision)	≤ 8% CV for concentrations > 9 nmol/L	2.6 to 5.4% CV for samples > 9 nmol/L
Imprecision (Total precision)	< 0.72 nmol/L SD for concentrations < 9 nmol/L	0.08 to 0.38 nmol/L SD for samples < 9 nmol/L
Imprecision (Within run precision)	Not explicitly stated, but generally lower than total precision	1.6 to 5.2% CV for samples > 9 nmol/L
Imprecision (Within run precision)	Not explicitly stated, but generally lower than total precision	0.04-0.22 nmol/L SD for samples ≤ 9 nmol/L
Analytical Sensitivity (Lowest detectable level)	Not explicitly stated, but should be distinguishably non-zero	< 0.05 nmol/L
Dilution Recovery (Mean recovery)	100 ± 15%	Within 100 ± 15%
Dilution Recovery (Individual mean recovery)	At least 92% within 100 ± 20%	At least 92% within 100 ± 20%
Methods Comparison (Correlation with Predicate)	High correlation (e.g., r > 0.95 or similar)	r = 0.96 (y=0.8901X + 0.6853)
Analytical Specificity (Interference avoidance)	No significant interference from therapeutic drugs, similar compounds, or common contaminants	No significant interference from therapeutic drugs, similar compounds, bilirubin, total protein, hemoglobin, triglycerides, or rheumatoid factor (up to 850 IU/mL)
Reagent Stability (Opened)	Not explicitly stated, but ensures practical shelf-life	28 days
Calibrator Stability (Opened)	Not explicitly stated, but ensures practical shelf-life	90 days
Control Stability (Opened)	Not explicitly stated, but ensures practical shelf-life	90 days
Calibration Curve Stability	Not explicitly stated, but ensures practical shelf-life	28 days
Clinical Sensitivity (sTfR for IDA/ACD+IDA)	Optimized sensitivity with reasonable specificity	86% sensitivity at 21 nmol/L cutoff
Clinical Specificity (sTfR for IDA/ACD+IDA)	Optimized specificity with reasonable sensitivity	49.1% specificity at 21 nmol/L cutoff
Clinical Sensitivity (sTfR/log ferritin index for IDA/ACD+IDA)	Optimal sensitivity	80.7% sensitivity at 14 cutoff
Clinical Specificity (sTfR/log ferritin index for IDA/ACD+IDA)	Optimal specificity	82.5% specificity at 14 cutoff

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

Methods Comparison (Analytical Study):
- Sample Size: 271 samples
- Data Provenance: Not explicitly stated, but implies clinical samples used for comparing the new assay to the predicate. The "External Site" suggests multiple locations.
- Retrospective/Prospective: Not specified.
Clinical Studies (Clinical Trial):
- Sample Size: Not explicitly stated for the clinical trial itself, but implied to be sufficient to derive sensitivity and specificity values.
- Data Provenance: "Prospective multicenter clinical trial." This indicates data was collected forward-in-time from multiple clinical sites. The country of origin is not specified.
- Retrospective/Prospective: Prospective.

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 the clinical studies, "diagnosis of Iron Deficiency Anemia (IDA), and for the differential diagnosis of IDA and Anemia of Chronic Disease (ACD)" would typically involve clinical experts (e.g., hematologists, clinical pathologists), but the number and qualifications are not mentioned.

4. Adjudication Method for the Test Set

This information is not provided in the document. For clinical diagnoses used as ground truth, an adjudication process (e.g., consensus by multiple experts) is often used, but it's not detailed here.

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

There was no MRMC comparative effectiveness study described. This device is an in vitro diagnostic (IVD) assay for measuring a biomarker (sTfR), not an AI-powered image analysis or diagnostic aid that would assist human readers in interpreting images or other complex data. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply to this specific device.

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

Yes, the studies described are for the device's standalone performance as an in vitro diagnostic assay. The "Access sTfR reagents, calibrators, controls, and the Access Immunoassay Analyzers" perform the quantitative determination of sTfR levels. There isn't a human-in-the-loop component in the actual measurement and result generation of the sTfR value itself. The clinical interpretation of that sTfR result (and sTfR/log ferritin index) is then performed by a clinician.

7. The Type of Ground Truth Used

Analytical Studies (Methods Comparison): The ground truth for method comparison was values obtained from the predicate device (Quantikine® IVD® sTfR ELISA). This is a common approach for demonstrating substantial equivalence for quantitative assays.
Clinical Studies: The ground truth for the clinical study was the diagnosis of Iron Deficiency Anemia (IDA) and Anemia of Chronic Disease (ACD). This would typically be established through a combination of clinical assessment, laboratory tests (beyond just sTfR), and potentially bone marrow biopsy or response to iron therapy, which constitutes outcomes data or expert consensus-based clinical diagnosis. The document does not specify the exact methods for defining IDA and ACD beyond the general diagnoses.

8. The Sample Size for the Training Set

The document does not explicitly describe a "training set" in the context of an algorithm or machine learning model. This is an immunoassay (laboratory test), not a software/AI device that typically undergoes separate training and test phases.

The "analytical studies" and "clinical studies" described serve as validation studies for the device's performance, much like a traditional device's verification and validation.
There's no mention of a development phase where a model would be "trained" on a specific dataset.

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

As there is no explicit "training set" mentioned in the context of typical machine learning, this question is not applicable. The development and optimization of the immunoassay reagents and protocols are based on scientific principles of immunology and chemistry, rather than an algorithmic training process on ground truth data.

Summary

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AUG 1 1 2008

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.

The assigned 510(k) number is: K080634

Submitter's Name and Address

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: 952-368-1271 Fax: (952) 368-7610 Contact: Lynn Weist

Date Prepared: June 5, 2008

Device Names

Proprietary Name: sTfR, sTfR Calibrators, and sTfR QC on the Access® Immunoassay Systems
Common Name: Immunological test for soluble transferrin receptor

Classification Name: Transferrin Immunological Test

Predicate Device

Quantikine® IVD® sTfR ELISA R & D Systems, Inc. 614 McKinley Place N.E. Minneapolis, MN 55413

510(k) Number: K970718

Device Description

Beckman Coulter, Inc. Confidential

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Access sTfR OIVD 510(k) Submission: 510(k) Summary

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 lmmunoassay 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).

The Access sTfR QC is intended for monitoring system performance of the Access sTfR assay.

Comparison of Technological Characteristics

Attribute	Quantikine IVD sTfR ELISA	Access sTfR
IntendedUse (Assay)	For the quantitativedetermination of solubletransferrin receptor.	For the quantitativedetermination of solubletransferrin receptor. Mayalso be used in conjunctionwith a ferritin measurement toprovide a calculated sTfR/logferritin index.
AssayFormat	Two site, sandwich assay;Enzyme linkedimmunosorbent assay(ELISA)	Two site, sandwich assay;Sequential two-stepimmunoenzymaticchemiluminescentimmunoassay

Beckman Coulter, Inc. Confidential

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Access sTfR
OIVD 510(k) Submission: 510(k) Summary

Attribute	Quantikine IVD sTfR ELISA	Access sTfR
Test System	Manual; Polystyrene microplate coated with mouse monoclonal antibody against sTfR	Automated; Paramagnetic particles coated with mouse monoclonal antibody against sTfR. Uses the same mouse monoclonal antibodies against sTfR in the capture phase and signal phase as the predicate device.
Detection System	Chromogenic reaction	Utilizes dioxetane-based chemiluminescent substrate; measures light production from a chemiluminescent reaction.
Calibrators	Calibrators are comprised of purified plasma sTfR at 6 levels (0, 3, 7, 20, 40, and 80 nmol/L)	Calibrators are comprised of natural sTfR at 6 levels (0, 3, 10, 30, 80, and 150 nmol/L) in a buffered matrix.
Controls	QCs are provided as lyophilized human sTfR at 3 levels (~7.5, ~20, ~50 nmol/L) in a buffered matrix.	QCs are human sTfR provided as a liquid at 3 levels (~10, ~25, ~90 nmol/L) in a buffered matrix.

Beckman Coulter, Inc.

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Summary of Analytical Studies

Imprecision: Access sTfR exhibits total precision ≤ 8% at concentrations greater than 9 nmol/L, and total SD < 0.72 nmol/L at concentrations < 9 nmol/L. Assay precision was tested at concentrations from approximately 1 to 140 nmol/L. Within run precision ranged from 1.6 to 5.2% CV for samples > 9 nmol/L, and SD 0.04-0.22 nmol/L for samples with concentrations ≤ 9 nmol/L. Total precision ranged from 2.6 to 5.4% CV for samples > 9 nmol/L, and SD 0.08-0.38 nmol/L for samples with concentrations ≤ 9 nmol/L.

Analytical Sensitivity: The lowest detectable level of soluble transferrin receptor distinguishable from zero (Access sTfR Calibrator S0) is <0.05nmol/L.

Dilution Recovery (Linearity): Dilution recovery studies were performed by diluting multiple serum and plasma (heparin) samples at various levels with Access sTfR Calibrator S0 and Wash Buffer II. Sample mean recovery values for all serum and plasma samples were within the range 100±15%. with at least 92% of individual mean recovery values within the range of 100±20%.

Methods Comparison (External Site):

A comparison of sTfR values from 271 samples, ranging from approximately 10-80 nmol/L, run with both the Access sTfR assay and the R&D Systems Quantikine IVD sTfR ELISA demonstrated acceptable correlation with the following statistical data: y=0.8901X + 0.6853. r=0.96

Analytical Specificity: There was no significant interference from therapeutic drugs or similar compounds in the Access sTfR assay. In addition, there was no significant interference from potential sample contaminants (bilirubin, total protein, hemoglobin, and triglycerides) or from rheumatoid factor at concentrations up to 850 IU/mL.

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

Summary of Clinical Studies

A prospective multicenter clinical trial was conducted to test the effectiveness of Access sTfR and the sTfR/log ferritin index in differentiation of iron deficiency anemia (IDA) and anemia of chronic disease (ACD).

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sTfR: Sensitivity is optimized (detection of 86% of patients with IDA or ACD + IDA with 49.1% specificity) by using a cutoff of 21nmol/L, and this is the recommended cutoff. sTfR values greater than or equal to 21 nmol/L are predictive of iron deficiency anemia.

sTfR/log ferritin index: Optimal sensitivity and specificity (detection of 80.7% of patients with IDA or ACD + IDA with 82.5 % specificity) are obtained using a cutoff of 14 (using nmol/L for sTfR in sTfR Index calculations), and this is the recommended cutoff. sTfR Index values greater than or equal to 14 are predictive of iron deficiency anemia.

Conclusion

Access sTfR, sTfR Calibrators, and sTfR QC on the Access Immunoassay Systems is substantially equivalent to R & D Systems Quantikine IVD sTfR ELISA for the measurement of soluble transferrin receptor in serum or plasma.

Beckman Coulter, Inc. Confidential

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Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 11 2008

Beckman Coulter, Inc. c/o Ms Lynn Weist Staff Regulatory Affairs Specialist 1000 Lake Hazeltine Drive Chaska, MN 55318-1084

Re: K080634

Trade/Device Name: Access® sTfR, Access® sTfR Calibrators and Access® sTfR OC Regulation Number: 21 CFR 866.5880 Regulation Name: Transferrin immunological test system Regulatory Class: Class II Product Code: DDG, JIT, JJX Dated: July 29, 2008 Received: July 30, 2008

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.

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 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.

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); 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

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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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

ia m Chen

Maria M. Chan, Ph.D. Acting Division Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

510(k) Number (if known): K080634

Device Name: Access® sTfR, Access® sTfR Calibrators, Access® sTfR QC

Indications For Use:

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.

The Access sTfR QC is intended for monitoring system performance of the Access sTfR assay.

Prescription Use × (Part 21 CFR 801 Subpart D)

AND/OR

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

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

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

Maria McChan

Division Sign-Off

Page 1 of 1

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K080634

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).