The Liquid Stable (LS) 2-Part Homocysteine Reagent 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

The Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent Test System includes two reagents and two calibrators.

The first reagent (Reag 1) includes Lactate dehydrogenase (LDH), Serine, nicotinamide adenine dinucleotide reduced di-sodium salt (NADH), tris [2-carboxyethyl] phosphine (TCEP) reductant, with buffers and stabilizers (Trizma Base and Trizma Hydrochloride), and preservative (Sodium Azide).

The second reagent (Reag2) includes Cystathionine beta-Synthase (CBS) and Cystathionine beta-Lvase (CBL) cvcling enzymes with preservative (sodium azide).

The Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent kit will also include two calibrators; Calibrator "0" (0 µmol/L) and Calibrator "28" (28 µmol/L).

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the Axis-Shield Liquid Stable (LS) 2-Part HOMOCYSTEINE REAGENT, based on the provided 510(k) summary:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Metric/Description	Reported Device Performance Against Predicate Device
Precision	Substantial equivalence in precision.	"The Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent assay is substantially equivalent to CATCH Incorporated Liquid Stable (LS) 2-Part Homocysteine Reagent assay in terms of precision..."
Limit of Detection (Sensitivity)	Substantial equivalence in limit of detection.	"...and limit of detection (sensitivity)..."
Specificity (Interferences)	Substantial equivalence in specificity.	"...and specificity (interferences) as demonstrated in non-clinical performance data in this 510(k) submission."
Method Comparison (Clinical Performance)	Linear regression analysis parameters (slope, intercept, r-value) and average percent bias indicating agreement with the predicate.	- Slope: 0.99 (95% Confidence interval 0.980 to 1.001) - Intercept: 0.3165 (95% Confidence interval 0.031 to 0.290) - r-value: 1.00 (95% Confidence interval 1.00 to 1.00) - Average Percent Bias: 0.01% (95% Confidence interval -0.10 to 0.07%)

Study Details

Sample Size Used for the Test Set and Data Provenance:
- Sample Size: 94 plasma specimens.
- Data Provenance: Not explicitly stated, but the submission is from Axis-Shield Diagnostics, Ltd. in the UK, suggesting potential European origin. It is a retrospective comparison study against an existing, legally marketed device.
Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- This is a quantitative diagnostic assay. The "ground truth" for the test set is established by the predicate device (CATCH Incorporated Liquid Stable (LS) 2-Part Homocysteine Reagent assay) measurements rather than expert consensus on images or clinical diagnoses. Therefore, expert involvement for ground truth establishment as in image interpretation studies is not applicable here.
Adjudication Method for the Test Set:
- Not applicable. The comparison is between two quantitative assays, not subjective interpretations requiring adjudication.
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:
- No. This is a study comparing the performance of a new quantitative laboratory assay against a predicate assay, not an AI-assisted diagnostic tool for human readers.
If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
- Yes, this is a standalone performance study. The Axis-Shield device is a reagent system for automated laboratory analysis, and its performance is evaluated directly without human interpretation in the loop impacting the result.
The Type of Ground Truth Used:
- The "ground truth" in this context is the quantitative results obtained from the legally marketed predicate device, the CATCH Incorporated Liquid Stable (LS) 2-Part Homocysteine Reagent assay. The study aims to demonstrate that the new device produces results that are substantially equivalent to this established method.
The Sample Size for the Training Set:
- Not applicable. This device is a biochemical reagent system, not a machine learning model that requires a dedicated "training set" in the computational sense. The "development" and "optimization" of the reagent would involve internal testing and validation, but not a formally segregated "training set" like in AI/ML contexts.
How the Ground Truth for the Training Set Was Established:
- Not applicable, as there is no "training set" in the conventional AI/ML sense for this type of device.

Summary

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ADMIN 3.0 Axis-Shield Liquid Stable (LS) 2-Part HOMOCYSTEINE REAGENT 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: k0832222

JUL 3 1, 2009

Submission correspondent:

Dr Claire Dora Regulatory Affairs Manager Axis-Shield Diagnostics, Ltd. The Technology Park Dundee DD2 1XA, UK

Device Name: Axis-Shield Liquid Stable (LS) 2-Part HOMOCYSTEINE REAGENT Classification Name: Urinary Homocystine (Nonquantitative) Test System Trade Name: Axis-Shield Liquid Stable (LS) 2-Part HOMOCYSTEINE REAGENT Common Name: Homocysteine Enzyme Assay Governing Regulation: 21 CFR 862.1377 Device Classification: Class II Classification Panel: Clinical Chemistry Product Code: LPS

Legally marketed device to which equivalency is claimed:

CATCH Incorporated, Liquid Stable (LS) 2-Part Homocysteine Reagent, K062808.

Intended Use of Device:

Description of Device:

The Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent Test System includes two reagents and two calibrators.

The second reagent (Reag2) includes Cystathionine beta-Synthase (CBS) and Cystathionine beta-Lvase (CBL) cvcling enzymes with preservative (sodium azide).

The Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent kit will also include two calibrators; Calibrator "0" (0 µmol/L) and Calibrator "28" (28 µmol/L).

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Principle of the Assay

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 dehvdrogenase (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 (Δ A340 nm).

Reduction: Dimerised homocysteine, mixed disulfide, and protein-bound forms of HCY in the sample are reduced to form free HCY by the use of tris [2-carboxyethy]] phosphine (TCEP).

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HCY-SS-HCY (dimerised homocysteine)
R1-SS-HCY (R1 = thiol residue)	------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Protein-SS-HCY

Enzymatic Conversion: Free HCY is converted to cystathionine by the use of cystathionine beta-synthase and excess serine. The cystathionine is then broken down to homocysteine, pyruvate and ammonia. Pyruvate is converted to lactate via lactate dehydrogenase with NADH as coenzyme. The rate of NADH conversion to NAD+ (Δ A340 nm) is directly proportional to the concentration of homocysteine.

Image /page/1/Figure/5 description: This image shows a diagram of the metabolic pathway involving homocysteine, serine, cystathionine, pyruvate, and ammonia. The conversion of homocysteine and serine to cystathionine is catalyzed by cystathionine beta-synthase (CBS). Cystathionine is then converted back to homocysteine, pyruvate, and ammonia by cystathionine beta-lyase (CBL). The conversion of NADH to NAD+ is measured at 340 nm.

Axis-Shield Liquid Stable (LS) 2-Part HOMOCYSTEINE Reagent 510(k) Premarket notification submission ADMIN 3.0 510(k) Summary FINAL v2.0

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Comparison of Technological Characteristics:

The Axis-Shield Liguid Stable (LS) 2-Part Homocysteine Reagent and CATCH Incorporated Liquid Stable (LS) 2-Part Homocysteine Reagent are both two reagent clinical chemistry enzymatic assays for the quantitative determination of total homocysteine in human serum and plasma. The reagent and calibrator formulations and the assay methodology of the Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent assay are essentially equivalent to the CATCH Incorporated Liquid Stable (LS) 2-Part Homocysteine Reagent assay. The idifference between the assays is the Stable (LS) 2-Part Homocysteine Reagent assay contains 0.748 KU/L Cystathionine beta-Synthase, whereas the CATCH Incorporated Liquid Stable (LS) 2-Part Homocysteine Reagent contains >20 KU/L Cystathionine beta-Synthase.

Summary of Non-Clinical Performance:

The Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent assay is substantially equivalent to CATCH Incorporated Liquid Stable (LS) 2-Part Homocysteine Reagent assay in terms of precision, limit of detection (sensitivity) and specificity (interferences) as demonstrated in non-clinical performance data in this 510(k) submission.

Summary of Clinical Performance:

The Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent assay demonstrated substantially equivalent performance to the CATCH Incorporated Liquid Stable (LS) 2-Part Homocysteine Reagent assay indicated by a method comparison study.

Passing-Bablok linear regression method comparison was performed on 94 plasma specimens in the range of 6.5 to 49.0 umol/L homocysteine. The Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent assay versus the CATCH Incorporated Liguid Stable (LS) 2-Part Homocysteine Reagent gave a slope of 0.99% (95% Confidence interval 01980 to 1:001) and an intercept of 03165 (95% Confidence interval 01031 (0 0.290). The Axis-Shield Liquid Stable (LS) 2-Part Homocysteine Reagent assay versus CATCH Incorporated Liquid Stable (LS) 2-Part Homocysteine Reagent gave an r value of 1.00 (95% Confidence interval 1.00 to 1.00). The average percent bias exhibited by Axis-Shield Liquid Stable 2-Part Homocysteine Reagent versus CATCH Incorporated Liquid Stable 2-Part Homocysteine Reagent in this study was 0.01% (95% Confidence interval of the average percent bias is =0.10 to 0.07%).

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Image /page/3/Picture/0 description: The image shows a partial view of a seal or emblem. The emblem includes a stylized graphic of three overlapping, curved lines, possibly representing waves or a stylized design element. To the left of the graphic, there is text arranged in a circular pattern, which appears to be part of the emblem's official name or title. The text is oriented vertically and follows the curve of the circle.

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

Axis-Shield Diagnostics Ltd. c/o Dr. Claire Dora The Technology Park Dundee, Scotland United Kingdom DD2 1XA

JUL 3 1 2009

Re: K083222

Trade/Device Name: Axis-Shield Liquid Stable (LS) 2-Part HOMOCYSTEINE REAGENT Regulation Number: 21 CFR § 862.1377 Regulation Name: Urinary Homocysteine (Nonquantitative) Test System Regulatory Class: Class II Product Code: LPS, JIT Dated: June 11, 2009 Received: June 16, 2009

Dear Dr. Claire Dora:

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 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); medical device reporting of medical devicerelated adverse events) (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/MedicalDevices/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 yours,

G.C.H.

Courtney C. Harper, Ph.D. Acting Director Division of Chemistry and Toxicology 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): K083222

Device Name: Axis-Shield Liquid Stable (LS) 2-Part HOMOCYSTEINE REAGENT

For in vitro diagnostic use.

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)

signature

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

510(k) K083222

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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.