The 3-Reagent Homocysteine Assay for Beckman Coulter SYNCHRON® and UniCel® systems is intended for in vitro quantitative determination of total homocysteine in human serum and plasma. The device can assist in the diagnosis and treatment of patients suspected of having hyperhomocysteinemia and homocystinuria.

Device Description

Bound or dimerised homocysteine (oxidised form) is reduced to free homocysteine, which then reacts with serine catalysed by cystathionine beta-synthase (CBS) to form cystathionine. Cystathionine in turn is broken down by cystathionine beta-lyase (CBL) to form homocysteine, pyruvate and ammonia. Pyruvate is then converted by lactate dehydrogenase (LDH) to lactate with nicotinamide adenine dinucleotide (NADH) as coenzyme. The rate of NADH conversion to NAD+ is directly proportional to the concentration of homocysteine (delta A340 nm).

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the 3-Reagent Homocysteine Assay, based on the provided text:

1. Acceptance Criteria and Reported Device Performance

The submission focuses on establishing substantial equivalence to a predicate device. The acceptance criteria are implicitly defined by the performance of the predicate device (Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent) and demonstrated through method comparison metrics.

Acceptance Criteria (Implicit, based on predicate performance)	Reported Device Performance (SYNCHRON®/UniCel® vs. Olympus AU400)
Method Comparison (SYNCHRON® LX Pro Analyzer):
Close to 1.0 (95% CI) for slope	Slope: 1.01 (95% CI: 0.99 to 1.04)
Close to 0.0 (95% CI) for intercept	Intercept: 0.07 (95% CI: -0.30 to 0.44)
Close to 1.0 (95% CI) for correlation coefficient (r)	Correlation coefficient (r): 0.997 (95% CI: 0.99 to 1.00)
Method Comparison (UniCel DxC Analyzer):
Close to 1.0 (95% CI) for slope	Slope: 0.99 (95% CI: 0.97 to 1.02)
Close to 0.0 (95% CI) for intercept	Intercept: 0.74 (95% CI: 0.30 to 1.11)
Close to 1.0 (95% CI) for correlation coefficient (r)	Correlation coefficient (r): 0.994 (95% CI: 0.99 to 1.00)
Other Non-Clinical Performance:	Substantially equivalent performance
Precision (comparable to predicate)	Demonstrated to be substantially equivalent
Calibration (comparable to predicate)	Demonstrated to be substantially equivalent
Limit of Detection (comparable to predicate)	Demonstrated to be substantially equivalent
Linearity on Dilution (comparable to predicate)	Demonstrated to be substantially equivalent

2. Sample Size and Data Provenance (Test Set)

Sample Size: 100 samples
Data Provenance: The text does not explicitly state the country of origin or whether the data was retrospective or prospective. It only mentions "human serum and plasma" samples.

3. Number and Qualifications of Experts for Ground Truth (Test Set)

The concept of "experts" and "ground truth" as typically applied in AI/imaging device studies (e.g., radiologists) is not applicable to this type of chemical assay. For this device, the comparison is against a legally marketed predicate device, where the "ground truth" is essentially the established performance of that predicate using accepted laboratory methods (e.g., a "reference" assay or the predicate itself).

4. Adjudication Method (Test Set)

Not applicable. This is a quantitative chemical assay, not an interpretative task requiring human adjudication of results in the way an imaging study would. The comparison is statistical (Passing & Bablock method comparison and Pearson correlation analysis) between the new device and the predicate.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. This type of study is not relevant for a quantitative chemical assay like a homocysteine test. MRMC studies are used to assess the impact of a device on decision-making or diagnostic accuracy when human interpretation is involved.

6. Standalone (Algorithm Only) Performance Study

Yes, in a sense. The described "method comparison study" implicitly evaluates the standalone performance of the 3-Reagent Homocysteine Assay against the already established performance of the legally marketed predicate device (Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent) when run on different analyzer platforms. There is no human-in-the-loop component for these quantitative results.

7. Type of Ground Truth Used (Test Set)

The "ground truth" for the test set is the results obtained from the legally marketed predicate device (Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent) when tested on the Olympus AU400 analyzer. The study design is a method comparison, where the new device's results are compared to the predicate's results for the same samples.

8. Sample Size for the Training Set

Not applicable. This is a reagent-based assay, not a machine learning or AI algorithm that requires a "training set" in the traditional sense. The device's performance is inherent to its chemical reactions and physical characteristics.

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

Not applicable. As stated above, there is no "training set" for this type of device. The development and optimization of the reagent formulations would involve various internal validation steps (e.g., verifying chemical reactions, stability, sensitivity) rather than establishing "ground truth" through a dataset that directly trains an algorithm.

Summary

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KU279d

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.

Submission correspondent:

Karen Hill Requlatory Affairs Manager Axis-Shield Diagnostics Ltd. The Technology Park Dundee DD2 1XA. Scotland, UK

Device Name: 3-Reagent Homocysteine Assay for SYNCHRON® and UniCel®

Reagents:

Classification Name: Urinary Homocystine (Nonquantitative) Test System Trade Name: 3-Reagent Homocysteine Assay for SYNCHRON® and UniCel® Common Name: Homocysteine Enzyme Assay Governing Regulation: 862.1377 Device Classification: Class II Classification Panel: Clinical Chemistry Product Code: LPS

Legally marketed device to which equivalency is claimed:

Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent (K083222)

Intended Use of Device:

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Description of Device:

Comparison of Technological Characteristics:

The 3-Reagent Homocysteine Assay for SYNCHRON® and UniCel® and the Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent are both enzymatic assays for the quantitative determination of total homocysteine in human serum and plasma. The calibrator formulations are identical and although both assays use the same cycling enzyme assay technology, the number or reagents and reagent formulations are different.

Summary of Non-Clinical Performance:

The 3-Reagent Homocysteine Assay for SYNCHRON® and UniCel® is substantially equivalent to the Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent in terms of precision, calibration, limit of detection and linearity on dilution as demonstrated in non-clinical performance data in this 510(k) submission.

Summary of Clinical Performance:

The 3-Reagent Homocysteine Assay for SYNCHRON® and UniCel® demonstrated substantially equivalent performance to the Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent as indicated by a method comparison study, in which a Passing & Bablock method comparison and a Pearson correlation analysis was conducted using 100 samples covering the full measuring range of the assay.

The 3-Reagent Homocysteine Assay for SYNCHRON® and UniCel® on the Synchron. LX Pro analyzer demonstrated substantially equivalent performance to the Axis-Shield

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Liquid Stable (LS) 2-Part Homocysteine Reagent on the Olympus AU400 analyser as indicated by a slope of 1.01 (95% Cl: 0.99 to 1.04), an intercept of 0.07 (95% Cl: -0.30 to 0.44) and a correlation coefficient (r) of 0.997 (95% CI: 0.99 to 1.00).

The 3-Reagent Homocysteine Assay for SYNCHRON® and UniCel® on the Unicel DxC analyzer demonstrated substantially equivalent performance to the Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent on the Olympus AU400 analyser as indicated by a slope of 0.99 (95% Cl: 0.97 to 1.02), an intercept of 0.74 (95% Cl: 0.30 to 1.11) and a correlation coefficient (r) of 0.994 (95% CI: 0.99 to 1.00).

Axis-Shield 3-Reagent Homocysteine Assay for Synchron 510(k) Premarket notification submission ADMIN 3.0 510(k) Summary Final Rev 3.0 2012-04-18

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Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles three overlapping abstract shapes, often interpreted as human figures or flowing elements.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

Axis-Shield Diagnostics Ltd. c/o Karen Hill Regulatory Manager The Technology Park Luna Place Dundee, UK, DD2 1XA, UK

MAY - 7 2012

K112790 Re:

Trade/Device Name: 3-Reagent Homocysteine Assay for Synchron® and Unicel® Regulation Number: 21 CFR § 862.1377 Regulation Name: Urinary Homocysteine (Nonquantitative) Test System Regulatory Class: Class II Product Code: LPS Dated: March 30, 2012 Received: April 3, 2012

Dear Karen Hill:

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 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 r reaso oe ac nove a determination that your device complies with other requirements of the Act that I Dr. I has made sond regulations administered by other Federal agencies. You must comply or any I detail claracts and enterests, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-607), laboling (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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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 (301) 796-5450. 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 (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical

Devices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance ...

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) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm

Sincerely vours.

V.
George H. Liggins, Ph.D.

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indication for Use

510(k) Number (if known):

KII2790 Device Name:

3-Reagent Homocysteine Assay for SYNCHRON® and Unicel®

Indication For Use:

Prescription Use _ X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Ruta Clima

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K112790

Regulation Number and Section

§ 862.1377 Urinary homocystine (nonquantitative) test system.

(a)
Identification. A urinary homocystine (nonquantitative) test system is a device intended to identify homocystine (an analogue of the amino acid cystine) in urine. The identification of urinary homocystine is used in the diagnosis and treatment of homocystinuria (homosystine in urine), a heritable metabolic disorder which may cause mental retardation.(b)
Classification. Class II.