HemosIL Homocysteine is an automated latex enhanced immunoassay for the quantitative determination of total L-homocysteine in human citrated plasma on IL Coagulation Systems. Homocysteine (Hcy) values can assist in the diagnosis and treatment of patients suspected of having hyperhomocysteinemia or homocystinuria.

HemosIL Homocysteine Controls are assayed quality controls intended to monitor the accuracy and precision of HemosIL Homocysteine on IL Coagulation Systems.

For in vitro diagnostic use.

Device Description

HemosIL Homocysteine Controls are assayed quality controls intended to monitor the accuracy and precision of HemosIL Homocysteine on IL Coagulation Systems.

Hey levels in patient plasma are measured automatically on IL Coagulation Systems in three stages:

Reduction of mixed disulfides and protein-bound forms of Hcy present in the plasma samples to free Hcy.
Enzymatic conversion of free Hcy to S-adenosyl-L-homocysteine (SAH) by the SAH hydrolase (SAHH) in the presence of an excess of adenosine.
Competitive agglutination reaction between anti-SAH and SAH / conjugate.

The degree of agglutination is inversely proportional to the concentration of total Hev in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the HemosIL Homocysteine and HemosIL Homocysteine Controls, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Metric (Implicit)	Acceptance Criteria (Implicit)	Reported Device Performance
Method Comparison	Correlation with predicate device (Abbott IMx Homocysteine)	Strong correlation (e.g., r > 0.95 or similar range)	ACL Advance: Slope: 0.8292, Intercept: 0.3503, r: 0.9915 (for 76 paired samples with Hcy levels 4.2 to 56.7 umol/L)
Precision	Within-run Coefficient of Variation (CV%)	Low CV% (typically < 10% for clinical assays, often < 5% for high precision)	ACL TOP: Hcy Control Level 1: 2.0%, Hcy Control Level 2: 1.5%, Hcy Plasma Sample: 2.9% ACL ELITE/ELITE PRO/8/9/10000: Hcy Control Level 1: 2.3%, Hcy Control Level 2: 4.3%, Hcy Plasma Sample: 2.6% ACL Futura/ACL Advance: Hcy Control Level 1: 3.5%, Hcy Control Level 2: 2.6%, Hcy Plasma Sample: 3.5%
Precision	Total Coefficient of Variation (CV%)	Low CV% (typically < 10% for clinical assays, often < 5% for high precision)	ACL TOP: Hcy Control Level 1: 4.8%, Hcy Control Level 2: 3.5%, Hcy Plasma Sample: 5.5% ACL ELITE/ELITE PRO/8/9/10000: Hcy Control Level 1: 5.1%, Hcy Control Level 2: 6.2%, Hcy Plasma Sample: 5.9% ACL Futura/ACL Advance: Hcy Control Level 1: 6.0%, Hcy Control Level 2: 3.5%, Hcy Plasma Sample: 5.6%
Substantial Equivalence	Equivalence in performance and intended use to predicate device	Demonstrated (via method comparison and precision data)	Stated: "HemosIL Homocysteine is substantially equivalent to the commercially available predicate device (Abbott IMx Homocysteine) in performance and intended use."

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

Sample Size for Test Set (Method Comparison): 76 paired sodium citrate and EDTA patient plasma samples.
Data Provenance: Not explicitly stated regarding country of origin. The samples are patient plasma samples, implying a clinical setting. It is a retrospective study as it's a "method comparison study evaluating 76 paired... samples," suggesting pre-collected samples.

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

This information is not provided in the document. For in vitro diagnostic assays like this, the "ground truth" is typically the result from a recognized reference method or a legally marketed predicate device, rather than expert consensus on interpretation.

4. Adjudication Method for the Test Set

This information is not applicable/provided as the study describes a quantitative laboratory assay comparison, not a diagnostic imaging or subjective interpretation task requiring adjudication. The comparison is directly between numerical results from two different assay methods.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic interpretation tasks (e.g., radiology reads) where different readers evaluate cases. The HemosIL Homocysteine assay is an automated, quantitative lab test, not subject to individual "reader" variability in the same way.

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

Yes, this entire study represents standalone performance. The HemosIL Homocysteine is an automated device designed to quantify homocysteine levels directly. The performance metrics (method comparison and precision) are inherent to the device's ability to produce accurate and precise measurements autonomously. There is no human-in-the-loop component for the measurement itself.

7. The Type of Ground Truth Used

The "ground truth" for the method comparison study was the results obtained from the predicate device, Abbott IMx Homocysteine. This is a common approach for demonstrating substantial equivalence for new IVD devices. The precision studies use defined control levels and patient plasma samples, with the mean values serving as a reference for assessing reproducibility.

8. The Sample Size for the Training Set

This information is not applicable/provided. The HemosIL Homocysteine is an immunoassay, not a machine learning or AI-driven device in the sense that it requires a "training set" to learn. Its performance is based on the chemical and enzymatic reactions described.

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

This information is not applicable as there is no "training set" in the context of this immunoassay device.

Summary

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Ka61598

510(k) Summary HemosIL Homocysteine and HemosIL Homocysteine Controls

Submitted by:

Instrumentation Laboratory Co. 113 Hartwell Avenue Lexington, MA 02421

Contact Information:

Carol Marble, Regulatory Affairs Director Phone: 781-861-4467 Fax: 781-861-4207 cmarble@qa.ilww.com E-mail:

Summary Prepared:

June 7, 2006

Section 5

Device Trade Name:

HemosIL Homocysteine HemosIL Homocysteine Controls

Regulatory Information:

862.1377	Urinary homocysteine (nonquantitative) test system
LPS		Class II
862.1660	Single (specified) analyte controls (assayed and unassayed)
JJX		Class I

Identification of Predicate Device:

K992858 Abbott IMx Homocysteine

Device Intended Use and Description:

HemosIL Homocysteine Controls are assayed quality controls intended to monitor the accuracy and precision of HemosIL Homocysteine on IL Coagulation Systems.

Hey levels in patient plasma are measured automatically on IL Coagulation Systems in three stages:

1. Reduction of mixed disulfides and protein-bound forms of Hcy present in the plasma samples to free Hcy.
1. Enzymatic conversion of free Hcy to S-adenosyl-L-homocysteine (SAH) by the SAH hydrolase (SAHH) in the presence of an excess of adenosine.
1. Competitive agglutination reaction between anti-SAH and SAH / conjugate.

The degree of agglutination is inversely proportional to the concentration of total Hev in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates.

HemosIL Homocysteine Kit and Controls 510(k)

Page 1 of 2

SEP 2 2 2006

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510(k) Summary HemosIL Homocysteine and HemosIL Homocysteine Controls

Statement of Technological Characteristics of the Device Compared to Predicate Device:

HemosIL Homocysteine is substantially equivalent to the commercially available predicate device (Abbott IMx Homocysteine) in performance and intended use.

Summary of Performance Data:

Method Comparison

In a method comparison study evaluating 76 paired sodium citrate and EDTA patient plasma samples with homocysteine levels ranging from 4.2 to 56.7 umol/L, the correlation statistics for HemosIL Homocysteine (sodium citrate plasma) versus the predicate device (EDTA plasma) are shown below:

IL System	Slope	Intercept	r
ACL Advance	0.8292	0.3503	0.9915

Precision

Within run and total precision assessed over multiple runs using two control levels and a plasma sample gave the following results:

ACL TOP	Mean (µmol/L)	CV% (Within run)	CV% (Total)
Hcy Control Level 1	11.4	2.0	4.8
Hcy Control Level 2	22.4	1.5	3.5
Hcy Plasma Sample	8.1	2.9	5.5
ACL ELITE/ELITE PRO/8/9/10000	Mean (µmol/L)	CV% (Within run)	CV% (Total)
Hcy Control Level 1	12.3	2.3	5.1
Hcy Control Level 2	22.8	4.3	6.2
Hcy Plasma Sample	8.4	2.6	5.9
ACL Futura/ACL Advance	Mean (µmol/L)	CV% (Within run)	CV% (Total)
Hcy Control Level 1	10.5	3.5	6.0
Hcy Control Level 2	21.1	2.6	3.5
Hcy Plasma Sample	7.9	3.5	5.6

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Image /page/2/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with three stripes forming its body and wings. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Carol Marble Instrumentation Laboratory Company 113 Hartwell Ave. Lexington MA 02421

SEP 2 2 2006

Re: K061598

Trade/Device Name: Hemosit Homocysteine and HemosIL Homocysteine Controls Regulation Number: 21 CFR 862.1377 Regulation Name: Urinary homocystine (non-quantitative) test system Regulatory Class: Class II Product Code: LPS, JJX Dated: August 21, 2006 Received: August 22, 2006

Dear Ms. Marble:

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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled; "Misbranding by reference to premarket wotification" (21 CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Alberto Gutierrez

Alberto Gutierrez, Ph.D. 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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Indications for Use Statement

510(k) Number (if known): Kob 1598

Device Name:

HemosIL Homocysteine and HemosIL Homocysteine Controls

Indications for Use:

HemosIL Homocysteine Controls are assayed quality controls intended to monitor the accuracy and precision of HemosIL Homocysteine on IL Coagulation Systems.

For in vitro diagnostic use.

V Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 807 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)

Carol C. Benson
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

K06 1598

HemosIL Homocysteine Kit and Controls 510(k)

Page 1 of 1

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.