N-GENEOUS HDL CHOLESTEROL KIT/CHOLESTEROL CALIBRATOR by GENZYME CORP.

for the quantitative determination of high density lipoprotein (HDL) cholesterol in human serum or plasma. For in vitro diagnostic use. For the calibration of N-geneous HDL Cholesterol ass in serum or plasma. For in vitro diagnostic use.

Device Description

The Genzyme N-geneous™ HDL Cholesterol Kit is an in vitro diagnostic product cleared (FDA Reference No. K962186) for use in the clinical laboratory for the quantitative determination of high density lipoprotein cholesterol in human serum or plasma. The first reagent contains a mixture of polymers and polyanions that bind to the surface of low-density lipoproteins (LDL), very low-density lipoproteins (VLDL) and chylomicrons. These complexed lipoproteins are stabilized, even in the presence of detergent which is added as part of the second reagent, together with the remaining components of a cholesterol reagent. HDL particles, on the other hand, are not stabilized by the polymers and polyanions and become solubilized by the detergent. Consequently, only the HDL cholesterol is subject to cholesterol measurement.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Genzyme N-geneous™ HDL Cholesterol Reagent Kit, based on the provided 510(k) Premarket Notification:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the NCEP (National Cholesterol Education Program) goals for precision. No explicit numerical targets for correlation coefficients are provided, but the reported values demonstrate substantial equivalence.

Acceptance Criteria (NCEP Goals for POL sites using N-geneous™ Kit)	Reported Device Performance (N-geneous™ Kit in POL)
CVs ≤6% at ≥42 mg/dL HDL cholesterol	Achieved ≤6%
SD ≤2.5 mg/dL at <42 mg/dL HDL cholesterol	Achieved ≤2.5 mg/dL
Comparative Performance Studies:
Correlation vs. Reference Lab:
Correlation Coefficient (r)	Site #1: 0.99, Site #2: 0.99, Site #3: 0.99
Correlation vs. Traditional PTA Method:
Correlation Coefficient (r)	Site #1: 0.97, Site #2: 0.99, Site #3: 0.98

Note on Acceptance Criteria: While the NCEP goals are explicitly stated for precision, the acceptance criteria for correlation are implied by the statement "These data demonstrate that the performance... is substantially equivalent." The high correlation coefficients (0.97-0.99) are presented as evidence of this equivalence.

Study Details

Sample Size used for the test set and the data provenance:
- Sample Size: 40 serum samples.
- Data Provenance: The samples were "split samples" analyzed at three Physician's Office Laboratories (POLs) and Genzyme (reference lab). This indicates prospective collection relative to the study's comparison phase, but the original source/country of the patient samples is not specified.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is not applicable as the "ground truth" for the comparative performance study was established by a reference laboratory (Genzyme) using the same N-geneous™ HDL Cholesterol Kit, or by the POLs using their traditional Sodium Phosphotungstate MgCl2 method (PTA). No human experts were explicitly used for ground truth establishment in this context. The reference methods themselves serve as the comparative standard.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. The study involved direct comparison of quantitative results from different testing sites/methods, not interpretive adjudication of results.
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:
- Not applicable. This is an in vitro diagnostic device for chemical analysis (HDL cholesterol), not an imaging device requiring human readers or AI assistance in interpretation.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, the performance characteristics (precision, and correlation against a reference method/site) were assessed for the N-geneous™ HDL Cholesterol Kit itself, which is a reagent kit used on clinical chemistry analyzers. This constitutes a standalone chemical assay performance assessment without a human interpretive "loop" altering the analytical result. The study focused on the performance of the kit in different laboratory settings.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Reference Method/Site Comparison:
  - For the comparison between POLs and the reference laboratory (Genzyme), the results from Genzyme using the N-geneous™ HDL Cholesterol Kit served as the reference standard.
  - For the comparison between the N-geneous™ HDL Cholesterol Kit and existing methods at the POLs, the "ground truth" were the results obtained by the POLs using their respective Sodium Phosphotungstate MgCl2 method (PTA). This is a comparison against an established, conventional method.
- Precision: The NCEP goals for precision served as the benchmark. The "true" HDL cholesterol levels in the serum pools (low, mid, high) were determined by the assay itself.
The sample size for the training set:
- Not applicable. This is an in vitro diagnostic device, not an AI or machine learning algorithm that requires a separate training set. The development of the reagents and assay methodology would involve internal R&D, but the submission describes validation studies, not AI model training.
How the ground truth for the training set was established:
- Not applicable, as there is no training set mentioned in the context of this 510(k) submission.

Summary

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510(k) PREMARKET NOTIFICATION

-geneous™ HDL Cholesterol
Reagent Kit
March 28, 1997

ATTACHMENT 1

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

Trade or Proprietary Name:	Genzyme N-geneous™ HDL Cholesterol Kit
Common or Usual Name:	Homogeneous assay for high density lipoprotein cholesterol
Classification Name:	High density lipoprotein cholesterol test
Manufacturer:	Genzyme DiagnosticsOne Kendall SquareCambridge, MA 02139-1562
Contact Person:	Nancy E. Isaac, Associate Director, Regulatory Affairs (617) 374-7431 or

The use of the Genzyme N-geneous™ HDL Cholesterol Kit in the physician's office laboratory setting is substantially equivalent to the N-geneous™ HDL Cholesterol Kit when used in a clinical laboratory. The Genzyme N-geneous™ HDL Cholesterol Kit is an in vitro diagnostic product cleared (FDA Reference No. K962186) for use in the clinical laboratory for the quantitative determination of high density lipoprotein cholesterol in human serum or plasma. The present clinical laboratory setting is

Beth A. Crowlev, Requlatory Associate (617) 252-7669.

In both user settings, the Genzyme N-geneous™ HDL Cholesterol Kit is a homogenous assay applicable to clinical chemistry analyzers that can accomodate two-reagent systems and does not require any off-line sample pretreatment or centrifugation steps.

being expanded to include physician office laboratories.

The first reagent contains a mixture of polymers and polyanions that bind to the surface of low-density lipoproteins (LDL), very low-density lipoproteins (VLDL) and chylomicrons. These complexed lipoproteins are stabilized, even in the presence of detergent which is added as part of the second reagent, together with the remaining components of a cholesterol reagent. HDL particles, on the other hand, are not stabilized by the polymers and polyanions and become solubilized by the detergent. Consequently, only the HDL cholesterol is subject to cholesterol measurement.

In comparative performance studies, three physician office laboratories (POL) analyzed 40 serum samples using the N-geneous™ HDL Cholesterol Reagent Kit. Split samples from the same 40 specimens were also analyzed at Genzyme, which acted as the reference laboratory. The correlation coefficient between the reference testing site and the POL testing sites for this study were:

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K971190

510(k) PREMARKET NOTIFICATION

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In the same study, the three POL sites compared their Genzyme N-geneous™ HDL Cholesterol Reagent Kit results to their respective current Sodium Phosphotungstate MgCly method (PTA) for each of these 40 patient samples. The correlation coefficient for these comparisons were:

Parameter	Site #1	Site #2	Site #3
Slope	0.88	1.05	0.77
Intercept (mg/dL)	2.90	-1.32	11.1
Correlation Coefficient (r)	0.97	0.99	0.98

Precision studies were conducted using the N-geneous™ HDL Cholesterol Test Kit. Both within-run and between-run studies were performed using frozen serum pools at three target levels of HDL cholesterol as determined by the National Cholesterol Education Program (NCEP): <35 mg/dL (low); 35-60 mg/dL (mid); and >60 mg/dL (high). It was determined that each POL site achieved the NCEP goals of CVs ≤6% at ≥42 mg/dL, and ≤2.5 mg/dL SD at <42 mg/dL, when using the Genzyme N-geneous™ HDL Cholesterol Kit.

These data demonstrate that the performance of the N-geneous™ HDL Cholesterol Kit in a physician's office laboratory is substantially equivalent to performance of the N-geneous™ HDL Cholesterol Kit in a clinical laboratory setting. Furthermore, these data demonstrate that the performance of the N-geneous™ HDL Cholesterol Kit in a physician's office laboratory is substantially equivalent to the performance of the Sodium Phosphotungstate MgCl2 method performed in their laboratory.

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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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 16 397

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

K971190 N-geneous™ HDL Cholesterol Kit/Cholesterol Calibrator Requlatory Class: I & II Product Code: LBS, JIS March 28, 1997 Dated: March 31, 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, qood 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 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 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 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 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 Bitman

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 I of_

510(k) Number (if known):__New__Filed_3/28/97

pevice Name:_N-geneous HDL Cholesterol Kit and N-geneous HDL Cholesterol Calibrator Indications For Use:.. . .

for the quantitative determination of high density lipoprotein (HDL) cholesterol in human serum or plasma.

For in vitro diagnostic use.

参

For the calibration of N-geneous HDL Cholesterol ass in serum or plasma. Y

For in vitro diagnostic use.

Division of Clinical Laboratory Devices
510(k) Number: K971790

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

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.