The Raichem HDL-Cholesterol Direct Reagent is intended for the quantitative determination of HDL-Cholesterol in serum or plasma. The Raichem HDL-Cholesterol Calibrator is intended to be used for the calibration of the Raichem HDL-Cholesterol Direct assay.

Device Description

The Raichem HDL-Cholesterol Direct test is based upon two sets of reaction sequences. In the first set of reactions Chylomicrons. VLDL selectively react with cholesterol esterase and are then eliminated from the reaction scheme. The addition of the second reagent causes the reaction of HDL-Cholesterol with cholesterol esterase and the subsequent production of color. The resultant increase in absorbance is directly proportional to the concentration of HDL-Cholesterol in the sample. The Raichem HDL-Cholesterol Calibrator is a serum calibrator used for the calibration of the Raichem HDL-Cholesterol Direct assay.

AI/ML Overview

Acceptance Criteria and Device Performance Study for Raichem HDL-Cholesterol Direct Reagent

1. Table of Acceptance Criteria and Reported Device Performance

This device is an in-vitro diagnostic (IVD) reagent for determining HDL-Cholesterol levels. The acceptance criteria are based on performance characteristics relevant to an IVD, such as precision, linearity, and comparison with a reference method.

Acceptance Criteria Category	Specific Acceptance Criteria	Reported Device Performance	Comments
Precision	Within-Run CV% for various HDL-C levels		Meets NCCLS EP5-T2 guidelines.
	- For HDL-C ~33 mg/dL	CV% = 0.8%
	- For HDL-C ~51 mg/dL	CV% = 0.6%
	Total CV% for various HDL-C levels
	- For HDL-C ~33 mg/dL	CV% = 2.7%
	- For HDL-C ~51 mg/dL	CV% = 2.6%
Calibrator Standardization	Traceable to National Institute of Standards Standard Reference Material (1951a); Meets CRMLN "HDL Cholesterol Method Evaluation Protocol for Manufacturers" requirements.	Confirmed by ultracentrifugation, traceable to NIST SRM 1951a. Procedures meet CRMLN August 1995 requirements.
Lower Detection Limit	Not explicitly stated as an "acceptance criterion" but determined as a performance characteristic.	Determined to be 1 mg/dL
Linearity	Not explicitly stated as an "acceptance criterion" but determined as a performance characteristic.	1 to 150 mg/dL
Comparison to CDC Designated Reference Method	Correlation Coefficient (r) to CDC method	r = 0.987	Strong correlation, indicating good agreement.
	Regression Equation to CDC method	$y = 0.9488x + 2.0$	Slope close to 1, intercept close to 0; indicates good accuracy.
Comparison to Predicate Device (Raichem HDL-Cholesterol Reagent - dextran sulfate method)	Correlation Coefficient (r) to predicate device	r = 0.988	Strong correlation, indicating substantial equivalence.
	Regression Equation to predicate device	$y = 1.011x + 0.192$	Slope close to 1, intercept close to 0; indicates good agreement.

2. Sample Size and Data Provenance

Test Set (Precision): 48 runs over 24 days. The specific number of distinct patient samples used for precision is not explicitly stated, but typically multiple aliquots from a few representative samples would be run repeatedly. The provenance of these samples (e.g., country of origin) is not mentioned. Likely prospective data collected for the study.
Test Set (Comparison Testing - CDC Method): 47 sample pairs. The provenance is not mentioned. Likely prospective data collected for the study.
Test Set (Comparison Testing - Predicate Device): 48 sample pairs. The provenance is not mentioned. Likely prospective data collected for the study.

3. Number of Experts and Qualifications for Ground Truth

For an in-vitro diagnostic device like the Raichem HDL-Cholesterol Direct Reagent, ground truth is established by a reference method rather than expert interpretation of images or clinical assessments.

For Comparison to the CDC Designated Comparison Method: The ground truth for this comparison was established by the "CDC Designated Comparison Method," which is performed by a laboratory that is part of the Cholesterol Reference Method Laboratory Network (CRMLN). This method is standardized to the CDC reference method for HDL-Cholesterol. No individual "experts" are identified, but rather the accredited laboratory and its reference method serve as the gold standard.
For Calibrator Standardization: The ground truth for the calibrator value is established by ultracentrifugation and is traceable to the National Institute of Standards Standard Reference Material (1951a). This also relies on established measurement techniques and certified reference materials, not individual experts.

4. Adjudication Method

Not applicable. For IVD devices, ground truth is typically established by reference methods or certified materials, not through adjudication of expert opinions.

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

Not applicable. This is an in-vitro diagnostic reagent, not an AI-assisted diagnostic tool that involves human readers interpreting cases.

6. Standalone Performance

Yes, the studies conducted represent the standalone performance of the algorithm (reagent in this case) as it measures HDL-Cholesterol concentrations directly from serum or plasma samples. The reported precision, linearity, lower detection limit, and comparison with reference methods are all measures of the device's standalone performance.

7. Type of Ground Truth Used

The type of ground truth used is:

Reference Method/Standard:
- For comparison testing, the "CDC Designated Comparison Method" (standardized to the CDC reference method for HDL-Cholesterol) served as the gold standard.
- For calibrator standardization, ultracentrifugation, traceable to the National Institute of Standards Standard Reference Material (1951a), was used.

8. Sample Size for the Training Set

Not applicable. This device is an in-vitro diagnostic reagent, not a machine learning or AI algorithm that requires a "training set" in the conventional sense. Its performance is based on chemical reactions and analytical validation, not statistical learning from data.

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

Not applicable, as there is no "training set" for this type of device. The scientific principles and validation of the chemical reactions, along with the standardization of the calibrator against established reference methods, dictate its performance.

Summary

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510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is:

1. Submitter's Name/Contact Person

Melissa Saner/Technical Marketing Manager

Address

Raichem Division of Hemagen Diagnostics, Inc. # 2022395 Formerly: Reagents Applications, Inc. 8225 Mercury Court San Diego, CA 92129 Phone: 619-569-8009 extension 111 Fax: 619-569-6208 Email: msaner@raichem.com

Date Prepared

August 4, 1998

2. Device Name

Trade Name:	Raichem HDL-Cholesterol Direct Reagent
Common Name:	High density (HDL) cholesterol test
Classification Name:	Lipoprotein test system
Device Classification:	I
Regulation Number:	21 CFR 862.1475
Panel:	Chemistry (75)
Product Code:	LBS
Trade Name:	HDL-Cholesterol Calibrator
Common Name:	HDL-Cholesterol Calibrator
Classification Name:	Calibrator, Primary
Device Classification:	II
Regulation Number:	21 CFR 862.1150
Panel:	Chemistry (75)
Product Code:	JIS

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3. Predicate Device

CDC Designated Comparison Method: Cholesterol Reference Method Laboratory Network

Raichem HDL-Cholesterol Reagent: 510(k) Docket No. K830207A Boehringer Mannheim Direct HDL-Cholesterol: 510(k) Docket No. K963213 Boehringer Mannheim C.f.a.s. HDL-C (Calibrator); 510(k) Docket No. K963213 Raichem Serum Calibrator (Ortho Automated Reference Serum Assayed -Marketed by Chiron Diagnostics): No 510(k) Docket Number Assigned (Pre Medical Device Amendments of 1976) (Medical Device Listing Document No. A 268140)

4. Description of Device

5. Intended Use of Device

6. Substantial Equivalence

A. Technological Characteristics

Proposed Device

The Raichem HDL-Cholesterol Reagent involves the direct selective reaction of HDL-1. Cholesterol utilizing surfactants and MgCl2 in a specific buffered environment.
1. The Raichem HDL-Cholesterol Calibrator is a serum calibrator used for the calibration of the Raichem HDL-Cholesterol Direct assay.

Predicate Device

1. The Designated Comparison Method is performed by a laboratory that is part of the Cholesterol Reference Method Laboratory Network. This method is standardized to the CDC reference method for HDL-Cholesterol.
1. The Raichem HDL-Cholesterol Reagent involves the precipitation of VLDL and LDL utilizing dextran sulfate (500,000 MW) and magnesium sulfate.
ന് The Boehringer Mannheim Direct HDL-Cholesterol is a homogenous assay involving the selective reaction of HDL-Cholesterol utilizing PEG and sulfated cyclodextrin.
1. The Raichem Serum Calibrator (Ortho Automated Reference Serum) is a device purchased from Chiron Diagnostics by Raichem. This device is a serum calibrator used for the calibration of clinical chemistry assays.

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Page 3 510(k) Summary HDL-Cholesterol Direct

B. Performance Data

Precision

Precision studies were performed in 48 runs over a period of 24 days following the NCCLS EP5-T2 Tentative Guideline.

	Total		Within Run
Mean (mg/dL)	SD	CV %	SD	CV %
33.1	0.89	2.7	0.26	0.8
51.21	1.35	2.6	0.32	0.6

Standardization of the Calibrator

The value for the calibrator is established by ultracentrifugation. It is traceable to the National Institute of Standards Standard Reference Material (1951a). The procedures used to assign the value to this calibrator material meet the requirements of the "HDL Cholesterol Method Evaluation Protocol for Manufacturers" of the U.S. National Reference System for Cholesterol, CRMLN (Cholesterol Reference Method Laboratory Network), August 1995.

Lower Detection Limit

The lower detection limit for the proposed device was determined to be 1 mg/dL.

Linearity

1 to 150 mg/dL

Comparison Testing

Comparison of Raichem HDL-Cholesterol Direct Reagent (y) with the CDC HDL-1. Cholesterol designated comparison method (x). Testing was performed in accordance with NCCLS EP9-A Approved Guideline. The Raichem HDL-Cholesterol Direct assay was performed using the Raichem Serum Calibrator (Ortho Automated Reference Serum) on the Hitachi 717.

Number of sample pairs (n):	47
Range of results (mg/dL):	24 – 70
Correlation Coefficient:	0.987
Regression Equation:	$y = 0.9488x + 2.0$

1. Comparison of Raichem HDL-Cholesterol Direct Reagent (y) with Raichem HDL-Cholesterol Reagent (500,000 MW dextran sulfate) (x), following the NCCLS EP9-A Approved Guideline.

Number of sample pairs (n):	48
Range of results (mg/dL):	23.0 - 77.1
Correlation Coefficient:	0.988
Regression Equation:	$y = 1.011x + 0.192$

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Image /page/3/Picture/1 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features a stylized representation of an eagle or bird-like figure with three curved lines forming its body and wings. The seal is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.

SEP 2 1 1998

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Melissa Saner Technical Marketing Manager Raichem 8225 Mercury Court San Diego, California 92111-1203

K982767 Re : HDL-Cholesterol Direct Reagent and Calibrator Regulatory Class: I & II Product Code: JIX, LBS Dated: August 4, 1998 Received: August 6, 1998

Dear Ms. Saner:

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, Druq, 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 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 Requlation (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 regulatory action. In addition, FDA may publish further announcements 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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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.qov/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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HDL-Cholesterol Calibrator Device Name:

Indication(s) For Use

This calibrator is intended to be used for the calibration of the Raichem HDL-Cholesterol Direct assay.

HDL-Cholesterol Direct Reagent Device Name:

Indication(s) For Use

This reagent is intended to be used for the quantitative determination of HDL-Cholesterol in human serum or plasma.

(PLEASE DO NOT WRITE BELOW THIS LINE)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109) OR

Over-The-Counter-Use_

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K982767

Regulation Number and Section

§ 862.1150 Calibrator.

(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.