ACCUCOLOR HIGH CALIBRATOR (A3089) by SIGMA DIAGNOSTICS, INC.

Sigma Diagnostics ACCUCOLOR™ High Calibrator is for use with the Sigma Diagnostics ACCUCOLOR™ Antithrombin III (AT-III) to determine the plasma level of antithrombin III (a substance which acts with the anticoagulant heparin to prevent coagulation). This determination is used to monitor the administration of heparin in the treatment of thrombosis. The determination may also be used in the diagnosis of thrombophilia (a congenital deficiency of antithrombin III).

Device Description

This product is designed for use with Accucolor Antithrombin III Assay Kit (CRS117A). The normal range of plasma Antithrombin III (AT-III) has been reported from 79-125% in Plasma 1-234 A normal population range determined at Sigma Diagnostics (n=70) was 83-119% (mean 101.1+9.8). This product provides a reference material with an assigned value slightly above the normal range.

AI/ML Overview

This 510(k) summary primarily focuses on establishing substantial equivalence for the "Accucolor High Calibrator" to a previously marketed device, "Sigma Product A7432." The document does not describe a full performance study with acceptance criteria in the typical sense for a new diagnostic device. Instead, it relies on demonstrating that the new calibrator is equivalent to an existing, cleared calibrator.

Here's an analysis based on the provided text, addressing the requested points where information is available:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implied)	Reported Device Performance
Functional Equivalence: Used for calibration of ATIII assays.	"Both products [Accucolor High Calibrator (A3089) and Sigma Product A7432] are used for the calibration of ATIII assays."
Value Assignment Traceability: Assigned values using a secondary standard traceable to a WHO International Reference Preparation for Antithrombin III.	"Both products have values assigned using a secondary standard, which was assigned from a traceable WHO International Reference Preparation for Antithrombin III."
Safety - Communicable Disease Screening: Human source material found negative for HbsAg, HCV, HIV-1, and HIV-2 by approved test methods.	"The human source material from which this product was found negative for HbsAg and for antibodies against HCV, HIV-1, and HIV-2 by approved test methods."
Proper Use/Handling: Clear instructions for handling and disposal.	"The 'Precautions' section of the data sheet instructs the user in handling and disposal of this product and directs the user to sources of additional information on the product."
Consistency with Normal Range: Provides a reference material with an assigned value slightly above the normal AT-III range.	"The normal range of plasma Antithrombin III (AT-III) has been reported from 79-125% in Plasma (citations provided). A normal population range determined at Sigma Diagnostics (n=70) was 83-119% (mean 101.1+9.8). This product provides a reference material with an assigned value slightly above the normal range." (This is a design feature rather than a specific performance metric of the calibrator itself showing it meets a "normal range" criterion, but it shows it fulfills its intended role by being positioned above the normal range for calibration purposes).

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

Test Set: Not applicable in the context of a de novo performance study for the calibrator. The primary "study" is a demonstration of substantial equivalence.
Normal Population Range Determination: A normal population range was determined at Sigma Diagnostics using n=70 samples. The provenance of this data (e.g., country of origin, retrospective/prospective) is not specified, but it was performed "at Sigma Diagnostics." This appears to be a historical determination of a reference range, not a test set for the calibrator.

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

Not applicable. There isn't a "test set" in the sense of clinical samples being evaluated by experts to establish ground truth for the calibrator's performance. The calibrator itself is part of the measurement system's ground truth by providing a known standard.
The ground truth for the value assignment of both the new and predicate calibrators relies on traceability to a "WHO International Reference Preparation for Antithrombin III," which implies an internationally recognized standard.

4. Adjudication Method for the Test Set

Not applicable. No expert adjudication process for a test set is described.

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

Not applicable. This is not an AI/imaging device.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Not applicable. This is an in vitro diagnostic calibrator, not an algorithm. Its performance is intrinsic to its chemical properties and assigned value.

7. The Type of Ground Truth Used

The ground truth for the assigned value of the calibrators (both the new and predicate) is established through traceability to a WHO International Reference Preparation for Antithrombin III. This is an internationally recognized reference standard.
For the normal population range mentioned, the ground truth was derived from a study of n=70 individuals, defining a normal range (83-119% with a mean of 101.1+9.8).

8. The Sample Size for the Training Set

Not applicable. There is no training set in the sense of a machine learning algorithm.

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

Not applicable. There is no training set. The "ground truth" for the calibrator's value is established by its manufacturing process and traceability to an international reference standard.

Summary

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1113274

510(k) NOTIFICATION Sigma Diagnostics Inc. ACCUCOLOR™ High Calibrator

OCT 37 1997

ATTACHMENT 1

Summary of Safety and Effectiveness

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Summary of Safety and Effectiveness Accucolor High Calibrator. Product No. A3089

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The safety and effectiveness of the Sigma Accucolor High Calibrator (A3089) has been demonstrated by its substantial equivalence to Sigma Product A7432. Both products are used for the calibration of ATIII assays. Both products have values assigned using a secondary standard, which was assigned from a traceable WHO International Reference Preparation for Antithrombin III.

The human source material from which this product was found negative for HbsAg and for antibodies against HCV, HIV-1, and HIV-2 by approved test methods. The "Precautions"section of the data sheet instructs the user in handling and disposal of this product and directs the user to sources of additional information on the product.

Odegard O. Lie M. Ablidgaard U. Heparin Cofactor Activity Measured with an 1. Amidolytic Method. 1975 Thrombosis Research 6:287-294.
1. Rosenberg R, Bauer K. The Heparin-Antithrombin System: A Natural Anticoagulant Mechanism. In Hemostasis and Thrombosis; Basic Principles and Clinical Practice, Colman R, Hirsh J, Marder V, and Salzman E. Eds. Third Edition, 1994 pp 837-860. Lippincott Co., Philadelphia, PA. USA.
1. Bick R. Clinical Relevance of Antithrombin III. 1982 Seminars in Thrombosis and Hemostasis 8:276-287.
1. Demers C, Henderson P, Blajchman M, Wells M, Mitchell L, Johnston M, Ofosu F, Fernandez-Rachubinski F, Andrew M, Hirsh J, Ginsberg J. An Antithrombin III Assay Based on Factor Xa Inhibition Provides a More Reliable Test to Identify Congenital Antithrombin III Deficiency Than an Assay Based on Thrombin Inhibition. 1993 Thrombosis and Haemostasis 69:231-235.

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Image /page/2/Picture/2 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized abstract design resembling an eagle or bird in flight. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular pattern around the bird symbol. The text is in all capital letters and is evenly spaced around the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 3 1 1997

William Gilbert, Ph.D. Manager, Scientific Affairs Sigma Diagnostics Inc. 545 South Ewinq Avenue St. Louis, Missouri 63103

Re : K973274 ACCUCOLOR™ High Calibrator Requlatory Class: II Product Code: GIZ, JBQ Dated: October 2, 1997 Received: October 3, 1997

Dear Dr. Gilbert:

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 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 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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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/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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510(k) Number (if known):

Device Name: _Sigma Diagnostics ACCUCOLOR™ High Calibrator

Indications For Use:

(PLÉASE 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 Clinical Laboratory Devices
510(k) Number

Prescription Use
(Per 21 CFR 801.109) /

Over-The-Counter Use

Regulation Number and Section

§ 864.5425 Multipurpose system for in vitro coagulation studies.

(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.