The Roche UNIMATE HDL Direct reagent is an in vitro diagnostic device intended for use in clinical and physician's office laboratories (POL) on COBAS MIRA systems for the quantitative determination of High Density Lipoprotein Cholesterol (HDL CHOL) in serum.

Device Description

The Roche UNIMATE HDL Direct reagent is an in vitro diagnostic test for the quantitative determination of High Density Lipoprotein Cholesterol (HDL CHOL) in serum. UNIMATE HDL Direct is intended for use in clinical and physician's office laboratories (POL) on COBAS MIRA systems. Determination of HDL cholesterol is useful for early detection of an increased risk of atherosclerosis. The principle of the Roche UNIMATE HDL Direct reagent is based on the absorbance of synthetic polymers and polyanions to the surface of lipoproteins. LDL, VLDL, and chylomicrons are transformed into a detergent-resistant form, whereas HDL is not. Combined actions of polymers, polyanions and detergent solubilizes cholesterol from HDL, but not from LDL, VLDL, and chylomicrons. Solubilized cholesterol is oxidized by the sequential enzymatic action of cholesterol esterase and cholesterol oxidase. The H,O, produced in this reaction is reacted with chromogens to form a colored dye. The increase in absorbance at 550 nm is directly proportional to the HDL cholesterol concentration of the sample.

AI/ML Overview

The document describes the Roche UNIMATE HDL Direct reagent, an in vitro diagnostic test for the quantitative determination of High Density Lipoprotein Cholesterol (HDL CHOL) in serum, specifically for use in physician's office laboratories (POLs).

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a single consolidated table. However, it implicitly uses the National Cholesterol Education Program (NCEP) goals for precision as an acceptance criterion for within-run and total precision, and correlation coefficients for agreement between methods.

Acceptance Criterion (Implicit)	Reported Device Performance
Correlation (Roche UNIMATE HDL Direct POL vs. RDS Reference)	Across three POL sites: Site #1: r = 0.990; Site #2: r = 0.994; Site #3: r = 0.991 (all indicating strong correlation). Linear Regression also provided, showing minimal bias.
Correlation (POL Usual Method vs. UNIMATE HDL Direct)	Across three POL sites: Site #1: r = 0.965; Site #2: r = 0.986; Site #3: r = 0.944 (all indicating strong correlation, though slightly lower than internal comparison). Linear Regression also provided.
Within-run Precision	Performed on three serum pools and Roche N and P controls. Not explicitly stated in tabular form, but the text indicates: "Each POL site achieved the NCEP goals of CVs ≤ 6% at ≥ 42 mg/dL, and SDs of ≤ 2.50 mg/dL at < 42 mg/dL when using the UNIMATE HDL Direct reagent."
Total Precision	Determined by duplicate determinations twice a day over five days (20 determinations). Not explicitly stated in tabular form, but the text indicates: "Each POL site achieved the NCEP goals of CVs ≤ 6% at ≥ 42 mg/dL, and SDs of ≤ 2.50 mg/dL at < 42 mg/dL when using the UNIMATE HDL Direct reagent."
Traceability to National Reference System for Cholesterol	Documented by performing a direct comparison with the cholesterol reference method using fresh human specimens that cover the NCEP medical decision points. (No specific performance metrics are provided in this summary, just the statement that it was documented).

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

Sample Size for Test Set:
- Site #1: 50 split samples
- Site #2: 59 split samples
- Site #3: 65 split samples
Data Provenance: The data was collected from three different physician office laboratories (POLs). These were "split samples," meaning aliquots of each sample were also tested in-house at Roche Diagnostics Systems' (RDS) laboratory to establish a reference site. This suggests the data is prospective, as it was collected specifically for this study. The country of origin is not explicitly stated, but given the sponsor's location (New Jersey, USA) and FDA submission, it's highly likely to be USA.

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

The concept of "experts" establishing ground truth in the traditional sense (e.g., radiologists interpreting images) is not directly applicable here. The "ground truth" or reference in this context is established by:

Roche Diagnostics Systems' (RDS) laboratory using the Roche UNIMATE HDL Direct reagent, serving as a reference for comparison with POL results. The qualifications of the personnel performing these tests are not specified, but it's assumed they are skilled laboratory technicians following standardized protocols.
The POL's "usual method" for HDL cholesterol determination served as another comparator, representing current practice.

4. Adjudication Method for the Test Set:

No explicit adjudication method (like 2+1, 3+1) is mentioned for the test set. The study compares results from:

POLs using Roche UNIMATE HDL Direct vs. RDS reference lab using Roche UNIMATE HDL Direct.
POLs using their usual methodology vs. POLs using Roche UNIMATE HDL Direct.

This is a direct comparison study between methods rather than an adjudication process to determine a single "truth."

5. 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:

This is not an MRMC comparative effectiveness study in the context of human readers/interpreters and AI. This study evaluates an in vitro diagnostic reagent (a chemical test) and its performance compared to other methods and a reference laboratory. Therefore, the concept of "human readers improving with AI" is not relevant here.

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

The Roche UNIMATE HDL Direct reagent is an automated chemical assay designed for use on COBAS MIRA systems. It operates in a standalone manner in that once the sample is loaded and the instrument is running, the determination of HDL cholesterol concentration is performed by the reagent and instrumentation without direct human intervention in the result generation process for that specific test run. The results are then read and interpreted by laboratory personnel. So, yes, it performs as a standalone assay in its operation.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.):

The "ground truth" for the test set is established by two primary mechanisms:

Reference Laboratory Results: The results obtained by Roche Diagnostics Systems' (RDS) laboratory using the Roche UNIMATE HDL Direct reagent served as a highly controlled and standardized reference for evaluating the performance of the POL sites using the same reagent.
National Reference System for Cholesterol: For the broader context of method traceability, the device was compared directly to the cholesterol "reference method" (though not detailed here) that is traceable to the National Reference System for Cholesterol and covers NCEP medical decision points. This implies an established and validated reference standard for cholesterol measurement.

8. The Sample Size for the Training Set:

The document does not specify a separate "training set" or its size. This is a performance study for an in vitro diagnostic reagent, not a machine learning algorithm that typically requires training data. The study describes experiments to validate the reagent's performance in different settings.

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

As there is no "training set" in the context of a machine learning algorithm, this question is not applicable. The performance studies involved comparing the device's results against established methods and a reference laboratory to demonstrate substantial equivalence, not to "train" the device.

Summary

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K973369 510(k) Summary

ROCHE UNIMATE HDL DIRECT REAGENT

In accordance with the Safe Medical Devices Act of 1990, a 510(k) summary is provided as outlined in 21 CFR 807.92.

I. Identification of 510(k) Sponsor:

Roche Diagnostic Systems, Inc. a subsidiary of Hoffmann-La Roche, Inc. Branchburg Township 1080 U.S. Highway 202 Somerville, New Jersey 08876-3771

510(k) Submission dated September 5, 1997

James W. Haynes Contact: Regulatory Affairs Associate Phone: (908) 253-7569 Fax: (908) 253-7547

II. Device Name:

The device name, including both the trade/proprietary name and the classification name are provided in the table below.

Proprietary Name	Classification Name	Product Code	Regulation Number
Roche UNIMATE HDL Direct reagent(with POL claim)	Cholesterol test system	CHH	862.1175

Table 1

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Identification of the legally marketed device to which the 510(k) sponsor claims III. equivalence:

The following table identifies the legally marketed device to which Roche Diagnostic Systems, Inc. claims equivalence.

Proprietary Name	Predicate Product Name	K number	Date of substantial equivalence
Roche UNIMATE HDLDirect reagent(with POL claim)	Roche UNIMATE HDL Directreagent	K971902	6/16/97

Table 2

IV. Description of the Device/Statement of Intended Use:

Low HDL levels are recognized as a strong and common risk factor for atherosclerotic Coronary Artery Disease (CAD). Therefore, determination of HDL cholesterol is routinely offered as part of a lipid profile. Usually VLDL and LDL are selectively precipitated from serum or plasma samples followed by determination of cholesterol in the HDL - containing supernatant. These techniques require a centrifugation step to remove the precipitated lipoproteins and thus cannot be fully automated. UNIMATE HDL Direct, however, allows for the direct specific determination of HDL cholesterol in the presence of LDL, VLDL and chylomicrons without any sample pretreatment, therefore, lending itself to automated routine analysis.

The principle of the Roche UNIMATE HDL Direct reagent is based on the absorbance of synthetic polymers and polyanions to the surface of lipoproteins. LDL, VLDL, and chylomicrons are transformed into a detergent-resistant form, whereas HDL is not. Combined actions of polymers, polyanions and detergent solubilizes cholesterol from HDL, but not from LDL, VLDL, and chylomicrons. Solubilized cholesterol is oxidized by the sequential enzymatic action of cholesterol esterase and cholesterol oxidase. The H,O, produced in this reaction is reacted with chromogens to form a colored dye. The increase in absorbance at 550 nm is directly proportional to the HDL cholesterol concentration of the sample.

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Summary of the technological characteristics of the new device in comparison to V. those of the predicate.

The Roche UNIMATE HDL reagent was previously cleared on June 16, 1997 (K971902) for use in clinical laboratories. The proposed labeling for the Roche UNIMATE HDL reagent has been modified to include the use of this product in physician office laboratories.

In addition, Roche has documented traceability to the National Reference System for Cholesterol by performing a direct comparison with the cholesterol reference method using fresh human specimens that cover the National Cholesterol Education Program (NCEP) medical decision points.

VI. Brief discussion of the clinical and nonclinical tests relied on for a determination of substantial equivalence:

Comparative performance studies were performed at three different physician office laboratories (POLs) on a minimum of 50 split samples provided by each laboratory. Aliquots of each sample were also tested in-house at Roche Diagnostics Systems' (RDS) laboratory to establish a reference site for comparative purposes. The study utilized COBAS MIRA Systems in use at each of the POLs. The results obtained for each sample at each POL site were compared to results using the POL's usual method and to Roche UNIMATE HDL Direct reagent's results.

The sample results obtained at the POL user sites for the UNIMATE HDL Direct studies were compared to the RDS reference laboratory UNIMATE HDL Direct sample results and gave the following results:

Parameter	Site #1	Site #2	Site #3
n =	50	59	65
Correlation	r = 0.990	r = 0.994	r = 0.991
Linear Regression	y = 1.03x - 0.03 mmol/L(-1.0 mg/dL)	y = 1.06x - 0.07 mmol/L(-2.5 mg/dL)	y = 0.97X - 0.03 mmol/L(-1.2 mg/dL)

Table 3

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The sample results obtained at the POL user sites for their usual methodologies were compared to the POL user sites UNIMATE HDL Direct sample results and gave the following correlations for each independent study:

ableT0	At
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Parameter	Site #1	Site #2	Site #3
n =	50	59	65
Correlation	r = 0.965	r = 0.986	r = 0.944
Linear Regression	y = 0.86x + 0.12 mmol/L(4.7 mg/dL)	y = 0.99x + 0.0 mmol/L(0.0 mg/dL)	y = 1.07x - 0.16 mmol/L(-6.1 mg/dL)

Within-run testing of 20 replicates was performed on three serum pools and, on Roche N and Roche P controls. Total precision was determined by performing duplicate determinations twice a day over five days for a total of 20 determinations at each POL site. Each POL site achieved the NCEP goals of CVs ≤ 6% at ≥ 42 mg/dL, and SDs of ≤ 2.50 mg/dL at < 42 mg/dL when using the UNIMATE HDL Direct reagent.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 21 1997

James W. Haynes Requlatory Affairs Associate Roche Diagnostics Systems 1080 U.S. Highway 202 Somerville, New Jersey 08876-3771

Re : K973369 Roche UNIMATE HDL Direct Reagent Regulatory Class: II Product Code: LBR, JIS Dated: September 5, 1997 ··· Received: September 8, 1997

Dear Mr. Haynes:

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 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 The general controls provisions of the Act 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 Requlations, 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 Druq Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in requlatory In addition, FDA may publish further announcements action. concerning your device in the Federal Reqister. 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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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 leqally 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 requlation (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 requlation 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/dsmamain.html".

sincerely yours,
Steven Litman

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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Page 1 of 1

510(k) Number (if known)

Roche UNIMATE HDL Direct reagent Device Name:

Indications for Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)
Division of Clinical Laboratory vices
510(k) Number. k9733/9

Prescription Use, (Per 21 CFR 801.109)

ﻤﺎ ﻳﻌﺘ

Over-The-Counter Use (Optional Format 1-2-96)

Regulation Number and Section

§ 862.1475 Lipoprotein test system.

(a)
Identification. A lipoprotein test system is a device intended to measure lipoprotein in serum and plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.