K Number
K991733
Date Cleared
1999-07-13

(53 days)

Product Code
Regulation Number
862.1475
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

ACE® LDL-C Reagent is intended for use in the quantitative determination of low density lipoprotein cholesterol in human serum.
ACE® LDL-C Reagent is intended for the quantitative determination of LDL cholesterol in serum using the ACE® clinical chemistry system.
LDL-C Calibrator is intended for the calibration of the ACE® LDL-C Assay.
LDL-C Controls are intended to monitor the performance of the ACE® LDL-C Assay.
The measurement of LDL cholesterol is a factor in the pathogenesis of atherosclerosis and coronary artery disease.

Device Description

The ACE® LDL-C Reagent contains two reagents. An aliquot of serum is added to the first reagent, which contains a unique detergent that selectively solubilizes the non LDL lipoproteins. Enzymes also present in the first reagent consume the cholesterol in a non color forming reaction. The second reagent contains another detergent that releases the remaining LDL lipoproteins. The enzyme reaction with LDL cholesterol, in the presence of a chromogenic coupler, produces color that is directly proportional to the amount of LDL cholesterol in the sample.

AI/ML Overview

The ACE® LDL-C Reagent is intended for the quantitative determination of low density lipoprotein cholesterol in human serum.

Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

ParameterAcceptance Criteria (Predicate Device)Reported Device Performance (Proposed Device)
Assay Range6.6 mg/dL to 992 mg/dL3 mg/dL to 800 mg/dL
Precision - Within Run≤ 0.73 %CV≤ 2.6 %CV
Precision - Between Run≤ 2.27 %CV≤ 3.2 %CV
Correlation vs. Reference method (Ultracentrifugation) - Slope0.951.111
Correlation vs. Reference method (Ultracentrifugation) - Intercept+3.02-15.5
Correlation vs. Reference method (Ultracentrifugation) - r0.960.9747
Correlation vs. Immunoseparation method - Slope0.941.09
Correlation vs. Immunoseparation method - Intercept+4.46-17.8
Correlation vs. Immunoseparation method - r0.970.9728

Note: The acceptance criteria are implicitly derived from the performance of the predicate device (Genzyme N-geneous® LDL Cholesterol Reagent) as this is a 510(k) submission seeking substantial equivalence.

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

  • Correlation vs. Reference method (Ultracentrifugation): n = 70
  • Correlation vs. Immunoseparation method: n = 66
  • Data Provenance: Not explicitly stated, but typically for such clinical testing, the data would be laboratory-generated. The document does not specify country of origin or whether it's retrospective or prospective.

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

This information is not provided in the document. The ground truth for the correlation studies was established by widely accepted laboratory methods (Ultracentrifugation and Immunoseparation method, and Friedewald calculation), not by expert consensus in the human interpretation sense.

4. Adjudication Method for the Test Set

This is not applicable as the studies are focused on comparing quantitative measurements from different assays, not on human interpretation or diagnosis requiring adjudication.

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 applicable. This submission is for a diagnostic reagent, not an AI-assisted diagnostic device that involves human readers interpreting results.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

This is not applicable in the context of an "algorithm" as commonly used for AI. The study describes the standalone performance of the reagent (a chemical assay) by comparing its measurements to established reference methods.

7. The Type of Ground Truth Used

  • Correlation vs. Reference Method: Ultracentrifugation
  • Correlation vs. Immunoseparation Method: Immunoseparation method
  • Correlation vs. Friedewald Calculation: Friedewald calculation

These methods are well-established laboratory techniques for determining LDL-C and serve as the ground truth or reference methods for comparison.

8. The Sample Size for the Training Set

This information is not provided. As this is a chemical reagent, it does not involve a "training set" in the machine learning sense. The development of the reagent would involve method optimization, but not a distinct "training set" of patient data in the same way an AI algorithm would.

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

This is not applicable for a chemical reagent. The development process would involve analytical chemistry and biochemistry principles to formulate the reagents to achieve the desired performance characteristics.

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JUL 13 1999

K991733

510(k) PREMARKET NOTIFICATION ACF® LDL-C Reagent

SUMMARY OF SAFETY AND EFFECTIVENESS

In lieu of a 510(k) statement under 513(i) of the Act, this Summary of Safety and Effectiveness is provided as a 510(k) summary for disclosure to any other persons/companies without specific written authorization from Schiapparelli Biosystems, Inc.

Submitter

Schiapparelli Biosystems, Inc. 368 Passaic Avenue Fairfield, NJ 07004 Phone: (973) 882-8630

Contact Person

Steven Dalessio Manager, Quality Assurance/Regulatory Affairs Phone: (973) 882-8630

Device Names

Proprietary Name:ACE® LDL-C ReagentLDL-C CalibratorLDL-C Controls
Common Name:Homogeneous assay for low density lipoprotein cholesterol
Classification Name:Low density lipoprotein cholesterol testCalibrator, PrimaryLow density lipoprotein cholesterol control
Predicate Device:Genzyme N-geneous® LDL Cholesterol Reagent[510(k) Number K971573]Genzyme N-geneous® LDL Cholesterol CalibratorGenzyme LDL Control Set

Device Description

The ACE® LDL-C Reagent contains two reagents. An aliquot of serum is added to the first reagent, which contains a unique detergent that selectively solubilizes the non LDL lipoproteins. Enzymes also present in the first reagent consume the cholesterol in a non color forming reaction. The second reagent contains another detergent that releases the remaining LDL lipoproteins. The enzyme reaction with LDL cholesterol, in the presence of a chromogenic coupler, produces color that is directly proportional to the amount of LDL cholesterol in the sample.

Intended Use of the Device

ACE® LDL-C Reagent is intended for use in the quantitative determination of low density lipoprotein cholesterol in human serum.

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510(k) PREMARKET NOTIFICATION ACE® LDL-C Reagent

SUMMARY OF SAFETY AND EFFECTIVENESS

COMPARATIVE FEATURES OF PREDICATE AND PROPOSED DEVICES

PARAMETERPREDICATE DEVICEPROPOSED DEVICE
Trade NameGenzyme N-geneous® LDL CholesterolReagentACE® LDL-C Reagent
Reference No.K971573TBD
AnalyteLDL cholesterolLDL cholesterol
Intended UseQuantitative determination ofLDL cholesterolQuantitative determination ofLDL cholesterol
MethodologyHomogeneous, DirectHomogeneous, Direct
ReagentsReagent 1VolumeLiquid; Detergent, Enzymes300 µLLiquid; Detergent, Enzymes300 µL
Reagent 2VolumeLiquid; Detergent, Chromogenic coupler100 µLLiquid; Detergent, Chromogenic coupler100 µL
SpecimenTypeVolumeSerum and plasma3 µLSerum3 µL
Assay SystemReagent 1 + SampleReagent 2TemperatureIncubate 300 sec and ReadRead at 300 sec37 °CIncubate 300 sec and ReadRead at 300 sec37 °C
Detection MethodTypeWavelength, nmSpectrophotometricBichromatic: 546/660SpectrophotometricBichromatic: 544/692

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510(k) PREMARKET NOTIFICATION ACE® LDL-C Reagent

SUMMARY OF SAFETY AND EFFECTIVENESS

PERFORMANCE ASSESSMENT

Non-clinical test results submitted in the premarket notification include within-run and between-run precision and method correlation. Following is a data summary.

PARAMETERPREDICATE DEVICEPROPOSED DEVICE
Performance SummaryAssay RangePrecisionWithin RunBetween Run6.6 mg/dL to 992 mg/dL≤ 0.73 %CV≤ 2.27 %CV3 mg/dL to 800 mg/dL≤ 2.6 %CV≤ 3.2 %CV
Correlation vsReference method (Ultracentrifugation)Hitachi 911
Slope0.951.111
Intercept+3.02-15.5
r0.960.9747
n5470
Correlation vsImmunoseparation methodFriedewald calculation
Slope0.941.09
Intercept+4.46-17.8
r0.970.9728
n9266

Based on these data, the Schiapparelli Biosystems ACE® LDL-C Reagent is substantially equivalent to the predicate device Genzyme N-geneous® LDL Cholesterol Reagent. On this basis, the reagent is determined to be safe and effective for its intended use. Performance details are included in the reagent product labeling.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around it. Inside the circle is an abstract symbol resembling a stylized caduceus or a representation of the human form.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 13 1999

Mr. Steven Dalessio Manager, Ouality Assurance/Regulatory Affairs Schiapparelli Biosystems, Inc. 368 Passaic Avenue Fairfield. New Jersey 07004

Re: K991733

Trade Name: ACE® LDL-C Reagent Regulatory Class: I reserved (Product codes: MRR, JJX) II (Product code: JIS) Dated: May 20, 1999 Received: May 21, 1999

Dear Mr. Dalessio:

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 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). 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 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 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 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/dsma/dsmamain.html".

Sincerely yours,

Steven Autman

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

510(k) Number (if known): K991733

ACE® LDL-C Reagent Device Name:

Indications For Use:

ACE® LDL-C Reagent is intended for the quantitative determination of LDL cholesterol in serum using the ACE® clinical chemistry system.

LDL-C Calibrator is intended for the calibration of the ACE® LDL-C Assay.

LDL-C Controls are intended to monitor the performance of the ACE® LDL-C
Assav Assay.

The measurement of LDL cholesterol is a factor in the pathogenesis of
atherosclerosis and coronary artery disease atherosclerosis and coronary artery disease.

Jean looper

(Division Sign-Off) Division of Clinical Laboratory Devices 11,2 510(k) Number.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

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OR

Over-The-Counter Use

(Optional Format 1-2-96)

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§ 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.