AXIS-SHIELD 3-REAGENT HOMOCYSTEINE ASSAY FOR SYNCHRON

K112790 · Axis-Shield Diagnostics, Ltd. · LPS · May 7, 2012 · Clinical Chemistry

Device Facts

• Record ID: K112790
• Device Name: AXIS-SHIELD 3-REAGENT HOMOCYSTEINE ASSAY FOR SYNCHRON
• Applicant: Axis-Shield Diagnostics, Ltd.
• Product Code: LPS · Clinical Chemistry
• Decision Date: May 7, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1377
• Device Class: Class 2

Intended Use

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 Story

Quantitative enzymatic assay for total homocysteine in human serum/plasma; used on Beckman Coulter Synchron LX 20 Pro and UniCel DxC 600 systems. Input: patient serum/plasma samples. Principle: bound/dimerized homocysteine reduced to free form; reacted with serine via cystathionine beta-synthase (CBS) to form cystathionine; broken down by cystathionine beta-lyase (CBL) to form homocysteine, pyruvate, and ammonia; pyruvate converted to lactate by lactate dehydrogenase (LDH) using NADH. Output: rate of NADH conversion to NAD+ (measured at 340 nm), directly proportional to homocysteine concentration. Used in clinical laboratories by technicians/pathologists. Results assist clinicians in diagnosing/treating hyperhomocysteinemia and homocystinuria.

Clinical Evidence

Method comparison study using 100 samples across the full measuring range. Comparison of subject device on Synchron LX Pro vs. predicate on Olympus AU400: slope 1.01 (95% CI: 0.99-1.04), intercept 0.07 (95% CI: -0.30 to 0.44), r=0.997. Comparison of subject device on Unicel DxC vs. predicate on Olympus AU400: slope 0.99 (95% CI: 0.97-1.02), intercept 0.74 (95% CI: 0.30-1.11), r=0.994.

Technological Characteristics

Enzymatic cycling assay; reagents include cystathionine beta-synthase (CBS), cystathionine beta-lyase (CBL), and lactate dehydrogenase (LDH). Measures absorbance change at 340 nm. Designed for use on automated clinical chemistry analyzers (SYNCHRON and UniCel systems).

Indications for Use

Indicated for patients suspected of having hyperhomocysteinemia and homocystinuria. Contraindicated for patients on S-adenosyl-methionine therapy due to potential for falsely elevated results; caution advised for patients taking methotrexate, carbamazepine, phenytoin, nitrous oxide, anticonvulsants, or 6-azauridine triacetate.

Regulatory Classification

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.

Predicate Devices

• Axis-Shield Liquid Stable (LS) 2-part Homocysteine Reagent (k083222)

Reference Devices

• Olympus AU400

Submission Summary (Full Text)

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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:

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.

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## Description of Device:

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 (△ A340 nm).

# 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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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 [phone]. 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 [phone]. 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 [phone] or [phone] 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:

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 homocysturia.

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