Reagents: For the direct, quantitative determination of low-density lipoprotein cholesterol (LDL-C) in human serum or plasma. Calibrators: For the calibration of the N-geneous™ LDL Cholesterol assay in serum or plasma. Controls: To monitor the performance of Genzyme LDL Cholesterol Reagents.

Device Description

The Genzyme N-geneous™ LDL Cholesterol Reagent is a two-reagent homogeneous method for the direct quantitative determination of low density lipoprotein cholesterol (LDL-C) in human serum and plasma. The principle of the test is based upon a unique detergent which selectively solubilizes only the non-L.DL lipoproteins, allowing them to be removed by cholesterol enzymes prior to the LDL cholesterol reaction. The LDL particles remain intact. The hydrogen peroxide produced by the reaction of the enzymes with the released cholesterol is consumed by a peroxidase reaction with 4-aminoantipyrine. yielding a colorless product. A second detergent, capable of releasing LDL cholesterol molecules, is added. The enzyme reaction with LDL cholesterol in the presence of the coupler produces color which is proportional to the amount of LDL cholesterol in the sample.

AI/ML Overview

The Genzyme N-geneous™ LDL Cholesterol Reagent is a two-reagent homogeneous method for the direct quantitative determination of low density lipoprotein cholesterol (LDL-C) in human serum and plasma. The study aimed to demonstrate substantial equivalence to existing predicate devices: Direct LDL Cholesterol Immunoseparation Reagent and β-Quantification methods.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for "substantial equivalence" are implicitly derived from the comparative performance studies against the reference methods. The device's performance metrics (slope, intercept, correlation coefficient, mean, standard deviation, mean difference, mean percent difference) were compared to those of the predicate devices. Precision was also evaluated.

Metric	Acceptance Criteria (Implied for Substantial Equivalence)	N-geneous™ LDL vs. β-Quantification (n=54)	N-geneous™ LDL vs. Direct LDL (n=92)
Comparative Studies
Slope	Close to 1.0	0.96	0.94
Intercept	Close to 0.0	3.02	4.46
Correlation Coefficient (r)	High (e.g., >0.95 for strong correlation)	0.96	0.97
Mean Difference (mg/dL)	Close to 0.0	-2.62	-2.81
Mean Percent Difference (%)	Close to 0.0	-1.9%	-2.0%
Precision Studies		Within-Run %CV	Between-Run %CV
LDL <130 mg/dL (Low)	Low %CV (e.g., <5%)	0.73%	2.27%
LDL 130-159 mg/dL (Mid)	Low %CV (e.g., <5%)	0.66%	1.95%
LDL ≥160 mg/dL (High)	Low %CV (e.g., <5%)	0.62%	1.73%

Note: The document states "These data demonstrate that the performance of the N-geneous™ LDL Cholesterol Reagents in the clinical laboratory is substantially equivalent." without explicitly stating numerical acceptance criteria. The reported performance metrics are presented to show their alignment with accepted ranges for substantial equivalence in such comparative studies.

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

Sample Size for Test Set:
- For comparison against β-Quantification: 54 serum samples.
- For comparison against Direct LDL Immunoseparation Reagent: 92 serum samples.
Data Provenance: The samples were tested at Genzyme Corporation. The country of origin of the data is implicitly the United States as Genzyme Corporation is based in Cambridge, MA. The study is retrospective in nature, as existing serum samples were used for testing.

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

Not applicable. This is an in vitro diagnostic (IVD) device for quantitative measurement. Ground truth is established by reference methods (β-Quantification and Direct LDL Cholesterol Immunoseparation Reagent), not by expert consensus or interpretation of images/clinical findings.

4. Adjudication Method for the Test Set

Not applicable. As described above, this is an IVD device where ground truth is determined by established reference methods, not by human adjudication of clinical or imaging data.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Not applicable. This is an in vitro diagnostic (IVD) device. MRMC studies are typically performed for imaging or interpretation-based diagnostic devices to assess human reader performance with and without AI assistance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, a standalone study was performed. The data presented for the N-geneous™ LDL performance and its comparison to the reference methods (β-Quantification and Direct LDL) represents the algorithm's performance without human intervention in the measurement process itself, beyond standard laboratory procedures for operating the assay.

7. Type of Ground Truth Used

The ground truth was established by two recognized reference methods for LDL cholesterol measurement:

β-Quantification
Direct LDL Cholesterol Immunoseparation Reagent

These methods serve as the "true" values against which the new device's performance is compared for quantitative accuracy.

8. Sample Size for the Training Set

The document does not explicitly mention a separate "training set" or "training phase" in the context of machine learning. For traditional IVD assays, development involves method optimization and validation, often using characterized samples. However, no specific sample size for a "training set" (as understood in AI/ML contexts) is provided, suggesting this is a traditional assay validation.

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

Not explicitly stated. For traditional IVD development, ground truth for initial development/optimization would typically be established using various characterized samples, potentially measured by existing reference methods or other well-established laboratory techniques to ensure the reagent formulation and assay parameters yield accurate results. However, no details on this initial phase are provided in this summary. The provided performance data relates to the validation against established reference methods.

Summary

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K911573

510(k) PREMARKET NOTIFICATION

Genzyme Corporation One Kendall Square Cambridge, MA 02139

June 18, 1997

Reagent and C

510(k) Summary Of Safety and Effectiveness Information Upon Which An Equivalence Determination Could be Made

Trade or Proprietary Name:	Genzyme N-geneous™ LDL Cholesterol ReagentGenzyme N-geneous™ LDL Cholesterol CalibratorGenzyme LDL Control Set
Common or Usual Name:	Homogeneous assay for low density lipoprotein cholesterol
Classification Name:	Low density lipoprotein cholesterol testCalibrator, PrimaryLow density lipoprotein control
Manufacturer:	Genzyme DiagnosticsOne Kendall SquareCambridge, MA 02139-1562
Contact Person:	Nancy E. Isaac, Associate Director, Regulatory Affairs (617) 374-7431 orBeth A. Crowley, Regulatory Affairs Associate (617) 252-7669

The use of the Genzyme N-geneous™ LDL Cholesterol Reagents in the clinical laboratory setting is substantially equivalent to the Direct LDL Cholesterol Immunoseparation Reagent and the B-Quantification methods.

The principle of the test is based upon a unique detergent which selectively solubilizes only the non-L.DL lipoproteins, allowing them to be removed by cholesterol enzymes prior to the LDL cholesterol reaction. The LDL particles remain intact. The hydrogen peroxide produced by the reaction of the enzymes with the released cholesterol is consumed by a peroxidase reaction with 4-aminoantipyrine. yielding a colorless product. A second detergent, capable of releasing LDL cholesterol molecules, is added. The enzyme reaction with LDL cholesterol in the presence of the coupler produces color which is proportional to the amount of LDL cholesterol in the sample.

Comparative performance studies were conducted using the N-geneous™ LDL Cholesterol Reagents and two reference methods: Direct LDL Cholesterol Immunoseparation Reagent and 3-Quantification.

ﺎ ﻓﻲ ﺍﻟﻤﺴﺎﺣﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍ

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K971573

510(k) PREMARKET NOTIFICATION

Ninety-two serum samples, with LDL values between 68.1 and 214.5 mg/dL, were tested at Genzyme Corporation using the N-geneous™ LDL and the Direct LDL methods. Of these 92 samples, 54 were tested with the ß-Quantification reference method.

N-geneous™ LDL	vs.β-Quantification(n = 54)	vs.Direct LDL(n = 92)
Slope	0.96	0.94
Intercept	3.02	4.46
Correlation Coefficient (r)	0.96	0.97
Mean (mg/dL)	Ng: 122.5βQ: 125.1	Ng: 120.0Dir: 122.8
Standard Deviation (mg/dL)	Ng: 30.7βQ: 30.9	Ng: 30.5Dir: 31.6
Mean Difference	-2.62	-2.81
Mean Percent Difference	-1.9%	-2.0%

Precision studies were conducted using the N-geneous™ LDL Cholesterol Reagents. Both within-run and between-run studies were performed using frozen serum pools at three target levels of LDL cholesterol as determined by the National Cholesterol Education Program (NCEP): <130 mg/dL (low); 130-159 mg/dL (mid); and ≥160 mg/dL (high).

Within-Run	Low(<130 mg/dL)	Mid(130-159 mg/dL)	High(≥160 mg/dL)
n	20	20	20
Sample Range (mg/dL)	97.1 - 99.6	144.9 - 148.7	207.0 - 211.5
Mean (mg/dL)	98.1	146.5	209.8
SD (mg/dL)	0.72	0.96	1.31
%CV	0.73%	0.66%	0.62%

Between-Run	Low(<130 mg/dL)	Mid(130-159 mg/dL)	High(≥160 mg/dL)
n	40	40	40
Sample Range (mg/dL)	93.0 - 101.9	137.5 - 148.6	199.3 - 213.9
Mean (mg/dL)	98.1	142.7	207.3
SD (mg/dL)	2.2	2.8	3.6
%CV	2.27%	1.95%	1.73%

These data demonstrate that the performance of the N-geneous™ LDL Cholesterol Reagents in the clinical laboratory is substantially equivalent to the performance of the Direct LDL Cholesterol Immunoseparation Reagent and the ß-Quantification methods.

In lieu of a 510(k) statement under 513(i) of the Act, this information is provided as a 510(k) summary for disclosure to any other persons/companies without the specific written authorization from Genzyme Corporation.

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Image /page/2/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle or bird-like figure with three curved lines representing its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the bird-like figure.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 18 1997

Nancy E. Isaac Associate Director, Requlatory Affairs Genzyme Corporation One Kendall Square Cambridge, Massachusetts 02139

駅e: K971573 N-geneous™ LDL Cholesterol Reagent/Cholesterol Calibrator Genzyme LDL Cholesterol Control Set Regulatory Class: I & II Product Code: LBR, JIS, JIS, JIX Dated: April 29, 1997 Received: April 30, 1997

Dear Ms. Isaac:

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 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 Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP 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 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 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/dsmamain.html".

Sincerely yours,
Steven Sitman

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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Image /page/4/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo features a stylized eagle or bird design, with three curved lines forming the body and wings. The logo is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 18 1997

Nancy E. Isaac Associate Director, Regulatory Affairs Genzyme Corporation -------One Kendall Square Cambridge, Massachusetts 02139

K971573 駅e: N-geneous™ LDL Cholesterol Reagent/Cholesterol Calibrator Genzyme LDL Cholesterol Control Set Regulatory Class: I & II Product Code: LBR, JIS, JIS, JIX Dated: April 29, 1997 April 30, 1997 Received:

Dear Ms. Isaac:

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 requlations 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 Good Manufacturing Practice for Medical Devices: General (GMP) requlation (21 CFR Part 820) and that, through periodic GMP inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in Please note: this response to your the Federal Register. 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

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.

તેમ 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 qeneral 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

Genzyme Corporation One Kendall Square Cambridge, MA 02139-1562 252-7500 Telephone (617)

510(k) Number (if known):

N-geneous™ LDL Cholesterol Reagent Device Name: N-geneous™ LDL Cholesterol Calibrator Genzyme LDL Cholesterol Control Set 参

Indications For Use:

Reagents:

For the direct, quantitative determination of low-density lipoprotein cholesterol (LDL-C) in human serum or plasma.

Calibrators:

For the calibration of the N-geneous™ LDL Cholesterol assay in serum or plasma.

Controls:

To monitor the performance of Genzyme LDL Cholesterol Reagents.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)
Division of Cinical Laboratory Devices
510(k) Nurnber k 971537

న Prescription Use (Per 21 CFR 801.109)

ರ್ಯ

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

(Optional Format 1-2-96)

Sk-19

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.