(91 days)
Reagent: For the quantitative determination of high-density cholesterol lipoprotein cholesterol in human serum or plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus, atherosclerosis and various liver and renal diseases). For In Vitro Diagnostic Use. Calibrator: For calibration of the Ultra HDL Cholesterol assay. For In Vitro Diagnostic Use.
The new Ultra N-geneous® HDL Cholesterol Kit is a two-reagent homogeneous method for the direct quantitative determination of high density lipoprotein cholesterol (HDL-C) in human serum and plasma. The new Ultra N-geneous® HDL Cholesterol assay does not contain polyanion or divalent metal. "precipitation reagent". This new method is based on accelerating the reaction of cholesterol oxidase and dissolving HDL selectively using a specific detergent.
This document describes the validation of the Genzyme Ultra N-geneous® HDL Cholesterol Reagent and Calibrator. The device is a two-reagent homogeneous method for the direct quantitative determination of high-density lipoprotein cholesterol (HDL-C) in human serum and plasma. The validation aims to demonstrate its substantial equivalence to the current Liquid N-geneous® HDL Cholesterol Reagent method and the Centers for Disease Control (CDC) designated comparison method.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparative performance results and the NCEP goals for precision. The reported device performance is presented in comparison to the predicate devices.
Comparative Performance (Ultra N-geneous® HDL vs. Predicates)
| Performance Metric | Acceptance Criteria (Implied) | Reported Performance (vs. Liquid N-geneous® HDL) | Reported Performance (vs. Designated Comparison Method) |
|---|---|---|---|
| Slope | Close to 1.0 | 0.98 | 0.99 |
| Intercept (mg/dL) | Close to 0.0 | 3.42 | 2.81 |
| Correlation Coefficient (r) | High (e.g., >0.95) | 0.996 | 0.996 |
| Mean Difference (mg/dL) | Low (e.g., within clinical limits) | 2.3 | 2.0 |
| Mean Percent Difference | Low (e.g., within clinical limits) | 4.5 | 3.9 |
| Range (mg/dL) | - | 33.6 - 133.0 | 32.0 - 133.0 |
Precision Performance (Ultra N-geneous® HDL)
| Metric with NCEP Target | Low (<40 mg/dL) | Mid (40-59 mg/dL) | High (≥60 mg/dL) |
|---|---|---|---|
| Within-run n | 20 | 20 | 20 |
| Mean (mg/dL) | 32.9 | 50.6 | 101.4 |
| SD (mg/dL) | 0.3 | 0.2 | 0.7 |
| %CV | 0.8 | 0.5 | 0.7 |
| Between-run n | 40 | 40 | 40 |
| Mean (mg/dL) | 32.8 | 50.0 | 100.1 |
| SD (mg/dL) | 0.4 | 0.7 | 1.1 |
| %CV | 1.3 | 1.5 | 1.1 |
Physician Office Laboratory (POL) Performance (N-geneous™ HDL - Lyophilized format)
| POL Site | Correlation (vs. Genzyme ref lab) | Correlation (vs. POL's current HDL method) | NCEP CVs Achieved? | NCEP SD Achieved? |
|---|---|---|---|---|
| Site #1 | Not fully reported (Slope 1.11) | 0.97 | Yes (for CVs ≤5% at ≥42 mg/dL) | Yes (for SD ≤1.7 mg/dL at <42 mg/dL) |
| Site #2 | 0.99 | 0.99 | Yes (for CVs ≤5% at ≥42 mg/dL) | Yes (for SD ≤1.7 mg/dL at <42 mg/dL) |
| Site #3 | 0.99 (Slope 0.93) | 0.98 | Yes (for CVs ≤5% at ≥42 mg/dL) | Yes (for SD ≤1.7 mg/dL at <42 mg/dL) |
The study demonstrates that the Ultra N-geneous® HDL Cholesterol Reagent performs comparably to the predicate devices, with high correlation coefficients, low mean differences, and precision that meets NCEP goals.
2. Sample Size and Data Provenance
- Test Set for Comparative Studies:
- vs. current Liquid N-geneous® HDL: 101 serum samples.
- vs. Designated Comparison Method: 52 serum samples.
- Test Set for POL studies: 40 serum samples for each of the three POL sites.
- Provenance: The samples were "human serum and plasma." The studies were conducted at Genzyme Corporation (Cambridge, MA) and Pacific BioMetrics (Seattle, WA) for the primary comparative studies. The POL studies were conducted at three different physician office laboratories. The data appears to be prospective in the sense that specific experiments were conducted to generate this data for the submission.
3. Number of Experts and Qualifications (for Ground Truth)
- No "experts" in the traditional sense (e.g., radiologists interpreting images) were used for establishing ground truth.
- The ground truth for comparative studies was established by recognized reference methods:
- The "current Liquid N-geneous® HDL Cholesterol Reagent method."
- The "Center for Disease Control (CDC) designated comparison method (DCM)."
- The HDL reference method (ultracentrifugation, chemical precipitation, and Abell-Kendall) for samples with triglyceride levels >400 mg/dL.
- The qualifications of the personnel performing these reference methods are not explicitly stated but are presumed to be standard for clinical laboratory professionals following established protocols.
4. Adjudication Method
- Not applicable. This study involves quantitative measurements against reference methods, not subjective interpretation requiring adjudication among experts.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC comparative effectiveness study was done. This is a comparison of an in-vitro diagnostic device's analytical performance against predicate methods, not a study involving human readers or interpretation of results for diagnostic decisions where AI assistance might be beneficial.
6. Standalone Performance
- Yes, a standalone performance study was done. The comparative performance studies (vs. Liquid N-geneous® HDL and vs. DCM), as well as the precision studies, assess the performance of the Ultra N-geneous® HDL Cholesterol Reagent as a standalone algorithm (or assay). The results reported (slope, intercept, correlation, mean difference, %CV, SD) are all measures of the device's inherent analytical performance.
7. Type of Ground Truth Used
- The ground truth used was analytical reference methods:
- The existing "Liquid N-geneous® HDL Cholesterol Reagent method."
- The "Center for Disease Control (CDC) designated comparison method (DCM)."
- For specific cases (triglycerides >400 mg/dL), the "HDL reference method (ultracentrifugation, chemical precipitation, and Abell-Kendall)" was used.
- These are established laboratory methods considered to provide accurate measurements of HDL cholesterol.
8. Sample Size for the Training Set
- Not applicable. This document describes the validation of an in-vitro diagnostic reagent, not an AI/machine learning model that requires a "training set." The reagent's performance is based on chemical reactions and optical detection, not learned patterns from data.
9. How the Ground Truth for the Training Set Was Established
- Not applicable. As stated above, there is no "training set" in the context of this device.
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Genzyme Corp rati n One Kendall Square Cambridge, MA 02139
JUL 2 5 2002
Ultra N-geneous® HDL Cholesterol R ag nt and Calibrator April 24, 2002
ATTACHMENT 1
K02/3/6
510(k) Summary Of Safety and Effectiveness Information Upon Which An Equivalence Determination Could be Made
| Trade or Proprietary Name: | Genzyme Ultra N-geneous® HDL Cholesterol Reagentand Calibrator |
|---|---|
| Common or Usual Name: | Homogeneous assay for high density lipoproteincholesterol |
| Classification Name: | High density lipoprotein cholesterol test |
| Manufacturer: | Genzyme DiagnosticsOne Kendall SquareCambridge, MA 02139-1562 |
| Contact Person: | Robert Yocher Vice President, Regulatory Affairs (617) 374-7275 orBarbara Pizza, Manager Regulatory Associate (617) 252-7953 |
The use of the new Ultra Genzyme N-geneous® HDL Cholesterol in clinical and physician's office laboratory settings is substantially equivalent to the current Liquid N-geneous® HDL Cholesterol Reagent method (I). The new Ultra N-geneous® HDL Cholesterol Kit is a two-reagent homogeneous method for the direct quantitative determination of high density lipoprotein cholesterol (HDL-C) in human serum and plasma.
The new Ultra N-geneous® HDL Cholesterol assay does not contain polyanion or divalent metal. "precipitation reagent". This new method is based on accelerating the reaction of cholesterol oxidase and dissolving HDL selectively using a specific detergent. The users use the reagent in the same manner as the current Liquid N-geneous® HDL Cholesterol Reagent.
Comparative performance studies were conducted using the Ultra N-geneous® HDL Cholesterol Reagent compared to (1) the reference method: the Center for Disease Control (CDC) designated comparison method (DCM) and (2) the current Liquid N-geneous® HDL Cholesterol Reagent method (1). When samples contained triglyceride levels >400 mg/dL. the HDL reference method (ultracentrifuqation, chemical precipitation and Abell-Kendall) was performed.
One-hundred and one serum samples, with HDL values between 33.6 and 133.0 mg/dL, were tested at Genzyme Corporation using the Ultra N-geneous® HDL Reagent on the Hitachi 911 Analyzer, the predicate Liquid N-geneous® HDL Cholestero! Reagent method on the Hitachi 911 analyzer. Fiftytwo serum samples with HDL values between 32.0 -- 133.0 mg/dL were tested using the Ultra N-
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geneous® HDL Reagent on the Hitachi 911 Analyzer and at Pacific BioMetrics (Seattle, WA) using the Designated Comparison Method for samples with triglyceride levels ≤400 mg/dL.
| vs. current Liquid N-geneous® HDL(n = 101) | vs. DesignatedComparison Method(n = 52) | |
|---|---|---|
| Slope | 0.98 | 0.99 |
| Intercept (mg/dL) | 3.42 | 2.81 |
| Correlation Coefficient (r) | 0.996 | 0.996 |
| Mean (mg/dL) | 56.4 | 58.3 |
| Standard Deviation (mg/dL) | 13.6 | 15.5 |
| Mean Difference (mg/dL) | 2.3 | 2.0 |
| Mean Percent Difference | 4.5 | 3.9 |
| Range (m/gdL) | 33.6 - 133.0 | 32.0 - 133.0 |
Precision studies were conducted using the Ultra N-geneous® HDL Cholesterol Test Kit. Both withinrun 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): <40 mg/dL (low); 40-59 mg/dL (mid); and ≥60 mg/dL (high).
| Low<40 mg/dL) | Mid(40-59 mg/dL) | High | |
|---|---|---|---|
| 20 | 20 | (≥60 mg/dL)20 | |
| Sample Range (mg/dL) | 32.4 - 33.5 | 50.1 - 50.9 | 99.4 - 102.4 |
| Mean (mg/dL) | 32.9 | 50.6 | 101.4 |
| SD (mg/dL) | 0.3 | 0.2 | 0.7 |
| %CV | 0.8 | 0.5 | 0.7 |
| Low(<40 mg/dL) | Mid(40-59 mg/dL) | High(≥60 mg/dL) | |
|---|---|---|---|
| n | 40 | 40 | 40 |
| Sample Range (mg/dL) | 31.6 - 33.5 | 48.4 - 51.1 | 97.6 - 102.2 |
| Mean (mg/dL) | 32.8 | 50.0 | 100.1 |
| SD (mg/dL) | 0.4 | 0.7 | 1.1 |
| %CV | 1.3 | 1.5 | 1.1 |
In separate comparative performance studies, three physician office laboratories (POL) analyzed separate sets of 40 serum samples using the lyophilized format of Genzyme's 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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| Parameter | Site #1 | Site #2 | Site #3 |
|---|---|---|---|
| Slobe | 0.93 | ||
| Intercept (mg/dL) | 111 | 5.90 | |
| Correlation Coefficient (r) | 0.99 | 0.99 |
In the same study, the three POL sites compared their Genzyme N-geneous™ HDL Cholesterol Reagent Kit results to their respective current HDL methods for each of these 40 patient samples. The correlation coefficient for these comparisons were:
| Parameter | Site #1 | Site #2 | Site #3 |
|---|---|---|---|
| Slope | 0.88 | ||
| Intercept (ma/dL. | 2.90 | ||
| Correlation Coefficient (r) | J.97 | 0.99 | 0.98 |
Precision studies were conducted using the lyophilized 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): <40 mg/dL (low); 40-59 mg/dL (mid); and ≥60 mg/dL (high). It was determined that each POL site achieved the NCEP goals of CVs ≤5% at ≥42 mg/dL., and ≤1.7 mg/dL SD at <42 mg/dL, when using the Genzyme N-geneous™ HDL Cholesterol Kit.
These data demonstrate that the performance of the Ultra N-geneous® HDL Cholesterol Reagent in both the clinical and physician office laboratories is substantially equivalent to the performance of the Liquid N-geneous® HDL Cholesterol Reagent and CDC Designated Comparison 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/3/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of two main elements: text arranged in a circular fashion and a stylized symbol. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" and is arranged around the upper half of the circle. The symbol is a stylized representation of a human figure, with three overlapping profiles facing to the right.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. Robert Yocher Vice President Regulatory Affairs Genzyme Corporation One Kendall Square Cambridge, MA 02139-1562
Re: K021316
Trade/Device Name: Ultra HDL Cholesterol Regulation Number: 21 CFR 862.1475 Regulation Name: Lipoprotein test system Regulatory Class: Class II Product Code: LBS; JIS Dated: July 8, 2002 Received: July 9, 2002
Dear Mr. Yocher:
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. Iisting 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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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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.
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" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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/dsmaldsmamain.html".
Sincerely yours,
Steven Butman
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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Genzyme Corporation One Kendall Square Cambridge, MA 02139
CONFIDENTIAL
Ultra N-geneous® HDL Cholesterol Reference No. K021316 July 8, 2002
. . . .
. . .
Page 1 of 1
510(k) NUMBER (if known): K021316
DEVICE NAME: _________________________________________________________________________________________________________________________________________________________________
INDICATIONS FOR USE:
Reagent:
For the quantitative determination of high-density cholesterol lipoprotein cholesterol in human serum or plasma. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus, atherosclerosis and various liver and renal diseases).
For In Vitro Diagnostic Use
&
an Cooge
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K021316
Calibrator:
For calibration of the Ultra HDL Cholesterol assay. For In Vitro Diagnostic Use
(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)
OR
Over-The-Counter-Use (Optional Format 1-2-96)
§ 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.