The Bio-Rad Homocysteine by HPLC test is intended for the quantitative determination of total Homocysteine in human plasma or serum. The device can assist in the diagnosis and treatment of patients suspected of having hyperhomocysteinemia or homocysteinuria. For in vitro diagnostic use only.

Device Description

The Bio-Rad Homocysteine by HPLC test is based on precolumn derivatization and a 5 minute chromatography. The precolumn derivatization includes a release of the plasma/serum bound fraction of Homocysteine by a chemical reduction and subsequent fluorescent labeling with a thiolspecific dye. Reduction and derivatization require only 5 minute incubation. Separation of Homocysteine, Internal Standard and other biological thiols (Glutathione, Cysteine, Cysteinglycine) takes place on a selected Reversed Phase cartridge followed by fluorescence detection (lex = 385 nm, lem = 515 nm). Quantitative analysis is performed using the Bio Rad Clinical Data Management System (K960392).

AI/ML Overview

The Bio-Rad Homocysteine by HPLC assay establishes substantial equivalence to an existing device, the AXIS® Homocysteine Enzyme Immunoassay, to demonstrate its safety and effectiveness.

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" for the Bio-Rad Homocysteine by HPLC assay. However, it presents a comparison of its performance characteristics against the predicate device, AXIS® Homocysteine Enzyme Immunoassay, to establish substantial equivalence. The key performance indicator for proving substantial equivalence appears to be the correlation study.

Parameter	Bio-Rad Homocysteine by HPLC (Reported Performance)	AXIS® Homocysteine Enzyme Immunoassay (Predicate Performance)
Coefficient of Correlation	0.9472 (against AXIS® Homocysteine)	N/A (this is the reference for correlation)
Slope	1.023 (against AXIS® Homocysteine)	N/A
Y-Intercept	-0.542 (against AXIS® Homocysteine)	N/A
Analytes Measured/Reported	Homocysteine	Homocysteine
Basic Principle	Chromatography	Immunoassay
Derivatization	Pre-column	Enzymatic conversion to SAH
Separation Mechanism	Reverse Phase	Monoclonal Antibody
Detection Mechanism	Fluorescence	Spectrophotometric
Measurement Type	Quantitative	Quantitative
Sample Type	Serum or Plasma	Serum or Plasma
Calibrators	Single (15 - 20 µMol/L)	2, 4, 8, 15, 30, & 50 µMol/L
Reportable Range	0.5 - 100 µMol/L	2 - 50 µMol/L
Precision (Within Run Total)	Low: 8.25 µMol/L, 3.77% CV (intra), 4.40% CV (total) Mid: 19.53 µMol/L, 1.87% CV (intra), 2.60% CV (total) High: 39.96 µMol/L, 1.16% CV (intra), 2.74% CV (total)	Low: 6.1 µMol/L, 7.3% CV (intra), 9.3% CV (total) Mid: 10.3 µMol/L, 6.8% CV (intra), 8.1% CV (total) High: 21.4 µMol/L, 5.2% CV (intra), 7.1% CV (total)
Sensitivity	0.5 µMol/L	0.5 µMol/L
Expected Values (95% Conf. L.)	5.7 - 15.1 µMol/L	5 - 15 µMol/L

Acceptance Criteria (Implied): The primary acceptance criterion for substantial equivalence is an excellent correlation between the Bio-Rad Homocysteine by HPLC method and the predicate AXIS® Homocysteine Enzyme Immunoassay. The reported correlation coefficient of 0.9472 is presented as fulfilling this criterion, along with a slope close to 1.0 (1.023) and a Y-intercept close to 0 (-0.542). The other performance parameters are presented for comparative purposes to demonstrate similar performance characteristics.

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

The document mentions a "correlation study" to determine accuracy but does not specify the sample size used for this test set. The data provenance is also not explicitly stated (e.g., country of origin, retrospective or prospective).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

This information is not applicable as the "ground truth" for the test set in this context is the measurement obtained from the predicate device, the AXIS® Homocysteine Enzyme Immunoassay, not expert consensus. Therefore, no experts were used to establish ground truth in the traditional sense.

4. Adjudication Method for the Test Set:

This is not applicable. The comparison is a quantitative measurement against a predicate device, not a subjective interpretation requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and If So, What Was the Effect Size of How Much Human Readers Improve With AI vs Without AI Assistance:

This is not applicable. This device is an in-vitro diagnostic assay, not an imaging device or an AI-assisted diagnostic tool that involves human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

The study performed is effectively a standalone performance evaluation of the Bio-Rad Homocysteine by HPLC assay, comparing its results directly to the predicate device. It assesses the algorithm's (or, in this case, the assay's) performance without human interpretation or intervention in the measurement process for the purpose of the correlation study.

7. The Type of Ground Truth Used:

The ground truth used for establishing substantial equivalence is the results obtained from the legally marketed predicate device, the AXIS® Homocysteine Enzyme Immunoassay method.

8. The Sample Size for the Training Set:

This information is not applicable. The Bio-Rad Homocysteine by HPLC device is an analytical assay, not a machine learning algorithm that requires a "training set" in the conventional sense. Its method is based on established chemical and chromatographic principles.

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

This information is not applicable for the reasons stated in point 8.

Summary

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Image /page/0/Picture/0 description: The image shows the logo for Bio-Rad Laboratories. The logo is in a rounded rectangle shape with the words "BIO-RAD" in bold, white letters against a black background. The letters are slightly stylized, giving the logo a modern and recognizable appearance.

Bio-Rad Laboratories Diagnostics Group 4000 Alfred Nobel Drive Hercules, California 94547 Telephone: 510 724 - 7000 Fax: 510 741-5824

DEC 2 1 1999

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:993107___

Submitter:	Bio-Rad LaboratoriesDiagnostics Group4000 Alfred Nobel DriveHercules, California 94547Phone: (510) 741-6263FAX: (510) 741-6471
Contact Person:	Patricia M. KlimleyRegulatory Affairs Consultant
Date of Summary Preparation:	September 16, 1999 and November 29, 1999
Device Name:	Bio-Rad Homocysteine by HPLC
Classification Name:	Urinary homocysteine (non-quantitative) test system
Predicate Device:	Axis® Homocysteine Enzyme ImmunoassayAxis® Biochemicals, ASAOslo, NorwayK980907
Statement of Intended Use:	The Bio-Rad Homocysteine by HPLC test is intendedfor the quantitative determination of totalHomocysteine in human plasma or serum.For in vitro diagnostic use only.

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Description of Device

Testing To Establish Substantial Equivalence

To establish substantial equivalence to an existing device, and thus establish the safety and effectiveness, the Bio-Rad Homocysteine by HPLC is compared to the AXIS® Homocysteine Enzyme Immunoassay (K980907). A review of the intended use of each system shows them to be the same, in that, both methods are intended for the quantitative measurement of homocysteine.

Parameter	Bio-Rad Homocysteine byHPLC	AXIS®HomocysteineEnzyme Immunoassay
Analytes Measured/Reported	Homocysteine	Homocysteine
Basic Principle	Chromatography	Immunoassay
Derivatization	Pre-column	Enzymatic conversion toSAH
Separation Mechanism	Reverse Phase	Monoclonal Antibody
Detection Mechanism	Fluorescence	Spectrophotometric
Measurement Type	Quantitative	Quantitative
Sample Type	Serum or Plasma	Serum or Plasma
Calibrators	Single ( 15 - 20 µMol/L)	2, 4, 8, 15, 30, & 50 µMol/L
Reportable Range	0.5 - 100 µMol/L	2 - 50 µMol/L
Precision	µMol/L: Within Run Total Low 8.25 3.77% 4.40% Mid 19.53 1.87% 2.60% High 39.96 1.16% 2.74%		µMol/L: Within Run Total Low 6.1 7.3% 9.3% Mid 10.3 6.8% 8.1% High 21.4 5.2% 7.1%
Sensitivity	0.5 µMol/L	0.5 µMol/L
Expected Values (95%Confidence Limit)	5.7 - 15.1 µMol/L	5 - 15 µMol/L

Technical Characteristics Compared to Predicate

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A correlation study to determine accuracy of the Bio-Rad Laboratories Homocysteine by HPLC assay was done against the AXIS® Homocysteine Enzyme Immunoassay method. The coefficient of correlation was 0.9472, the slope was 1.023, and the Y-Intercept was -0.542.

When considering an excellent correlation between the AXIS® Homocysteine Enzyme Immunoassay and the Bio-Rad Laboratories Homocysteine by HPLC method, it can be concluded that the Bio-Rad Laboratories Homocysteine by HPLC assay is substantially equivalent to the AXIS® Homocysteine Enzyme Immunoassay method, which has been 510K cleared. Based on the establishment of substantial equivalence, the safety and effectiveness of the Bio-Rad Laboratories Homocysteine by HPLC assay is confirmed.

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Image /page/3/Picture/1 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 image of an eagle with its wings spread, facing to the left. The eagle is composed of three thick, curved lines that suggest the shape of the bird.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 2 1 1999

Ms. Patricia M. Klimley Regulatory Affairs Consultant Bio-Rad Laboratories, Inc. Diagnostics Group 4000 Alfred Nobel Drive Hercules, California 94547

K993107 Re:

Trade Name: Homocysteine by HPLC Regulatory Class: II Product Code: LPS. JIT Dated: November 29 Received: November 30

Dear Ms. Klimley

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), 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 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The 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 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D, M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Statement of Indications for Use

510(k) Number:

Device Name:

Indications for Use:

K993107

Bio-Rad Homocysteine by HPLC

The Bio-Rad Homocysteine by HPLC test is intended for the quantitative determination of total Homocysteine in human plasma or serum.

The device can assist in the diagnosis and treatment of patients suspected of having hyperhomocysteinemia or homocysteinuria.

For in vitro diagnostic use only.

Jean Corce
(Division Sign-Off)

Division of Clir.ice La ratory Device 510(k) Number

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescriptive Use
(Per 21 CFR 801.109)

OR Over-The-Counter Use _

Bio-Rad Homocysteine by HPLC 3

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.