The VARIANT™ II ß-thalassemia Program is intended for the separation and area percent determinations of hemoglobins A2 and F and as an aid in the identification of abnormal hemoglobins in whole blood using ion-exchange high performance liquid chromatography (HPLC).

The VARIANT™ II ß-thalassemia Program is intended for use only with the Bio-Rad VARIANT™ II Hemoglobin Testing System

For in vitro diagnostic use only.

Device Description

The VARIANT™ II is a fully automated HPLC system which can be used to separate and determine area percentages for hemoglobins A, and F and to provide qualitative determinations of abnormal hemoglobins.

The VARIANTM II B-thalassemia Short Program utilizes principles of ion exchange high performance liquid chromatography(HPLC). The samples are automatically mixed and diluted on the VARIANT™ II Sampling Station(VSS) and injected into the analytical cartridge. This is a change from the unmodified program(VARIANT) where samples had to be mixed and diluted manually before being placed on the instrument. The VARIANT™ II chromatographic station(VCS) dual pumps deliver a programmed buffer gradient of increasing ionic strength to the cartridge, where the HbA, F are separated based on their ionic interactions with the cartridge material. The separated HbA. F then pass through the flow cell of the filter photometer, where changes in the absorbance at 415 nm are measured. An additional filter at 690 nm corrects the background absorbance. The VARIANT™ II Clinical Data Management(CDM) software performs reduction of raw data collected from each analysis. One level calibration is used for the adjustment of the calculated HbAyF values. A patient sample report and a chromatogram are generated by CDM for each sample. Minor differences in the separation efficiency of individual analytical cartridges are corrected by the use of the Hemoglobin A /F Calibrator.

AI/ML Overview

The provided text does not contain detailed acceptance criteria or a specific study that outlines numerical performance metrics for the device, beyond a general statement that "Testing met all acceptance criteria" and demonstrated "excellent concordance between the two methods."

Therefore, much of the requested information cannot be extracted from the given document.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Not explicitly stated in numerical terms.	"Testing met all acceptance criteria." "excellent concordance between the two methods [VARIANT and VARIANT II B-thalassemia programs]."

2. Sample size used for the test set and the data provenance

The document does not specify the sample size for the test set or the data provenance (e.g., country of origin, retrospective or prospective).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document does not mention the use of experts to establish ground truth or their qualifications. Given the nature of the device (HPLC for hemoglobin analysis), it is likely that a reference method or clinical samples with known diagnoses served as the ground truth.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

The document does not describe any adjudication method.

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. The device is an automated HPLC system for hemoglobin analysis, not an AI-assisted diagnostic imaging or interpretation tool for human readers.

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

Yes, the device (VARIANT™ II β-thalassemia Program) is an automated system for chemical analysis, implying standalone performance. The document describes it as "a fully automated HPLC system which can be used to separate and determine area percentages for hemoglobins A, and F and to provide qualitative determinations of abnormal hemoglobins."

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The document does not explicitly state the type of ground truth used. However, given that it compares the "VARIANT™ II β-thalassemia Program" with the "unmodified program (VARIANT)," it is highly probable that the ground truth was established by:

Reference methods: Confirmed analysis from established, highly accurate methods for hemoglobin quantification and identification.
Clinical samples with confirmed diagnoses: Samples from patients with known β-thalassemia or other hemoglobinopathies.

The term "concordance between the two methods" suggests a comparison against the existing VARIANT system, which would serve as a de facto reference in this context for evaluating the modified device.

8. The sample size for the training set

The document does not specify a training set or its size. As this is a 510(k) submission for a device modification (primarily automating sample preparation), it's more likely that the validation focused on performance equivalence rather than machine learning algorithm training.

9. How the ground truth for the training set was established

Not applicable, as a training set is not mentioned in the context of the device's development or evaluation in this document.

Summary

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K99川27

JUN 1 0 1999

Special 510(k): Device Modification Summary

Submitter:	Bio-Rad Laboratories, Inc.4000 Alfred Nobel Drive,Hercules, California 94547Phone: (510) 741-6188FAX: (510) 741-6471
Contact Person:	Juliet CarraraRegulatory Affairs/Quality Assurance Manager
Date of Summary Preparation:	March 29, 1999
Device Name:	VARIANT™ II β-thalassemia
Classification Name:	Class II, 81JPD Hemoglobin A₂ Quantitation
Unmodified Device:	VARIANT™ β-thalassemiaK924122Bio-Rad LaboratoriesHercules, CA 94547
Statement of Intended Use:	The VARIANT™ II β-thalassemia Program isintended for the separation and area percentdeterminations of hemoglobins A2 and F and as anaid in the identification of abnormal hemoglobins inwhole blood using ion-exchange high performanceliquid chromatography (HPLC).
	The VARIANT™ II β-thalassemia Program isintended for use only with the Bio-RadVARIANT™ II Hemoglobin Testing System
	For in vitro diagnostic use only.

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Description of Device

Technical Characteristics Compared to Unmodified Device

The main difference between the VARIANT™ and VARIANT™ II involves the patient sample preparation. In VARIANT™ II the preparation is automated, in VARIANT™ the preparation is manual.

Technical Characteristic	VARIANT I	VARIANT II
Sample Preparation:Calibrator and controls	Manual Preparation.	Manual Preparation
Sample Preparation:Patient Samples	Manual Preparation.	Automatic Preparation
Run SET UP	Run sequence is programmedmanually.	Run sequence read from barcodes.

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TechnicalCharacteristic	VARIANT	VARIANT II
STAT Samples	Available.	Not Available.
Analyte Identification	Analyte peaks are labelled.	Analyte peaks are labelled.
Calibration	Calibration response factors are used to adjust observed values.	Calibration response factors are used to adjust observed values.
Data Retrieval	Chromatograms are not stored in the database.	Chromatograms are stored in the database.
Reanalysis	Not available	Available
Sample Identification	Manual identification	Barcode identification
Summary Report	Not available	Available

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Performance Characteristics

Testing described in Section F of this submission focuses on performance characteristics of VARIANT™ II ß-Thal Short. Testing met all acceptance criteria.

When considering the similarities of the intended use, characteristics of the two VARIANT ß-thalassemia programs, the use of the same technology, and the excellent concordance between the two methods, it can be concluded that the VARIANT and the VARIANT II B-thalassemia programs are substantially equivalent. Based on the establishment of substantial equivalence, the safety and effectiveness of the VARIANT II ß-thalassemia program is confirmed.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the top half of the circle. Inside the circle is a stylized image of an eagle with its wings spread, depicted with three curved lines.

JUN 1 0 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Juliet Carrara Regulatory Affairs and Quality Assurance Manager Bio-Rad Laboratories, Inc. 4000 Alfred Nobel Drive Hercules, California 94547

Re: K991127

Trade Name: VARIANT™ II ß-thalassemia Short Program Regulatory Class: II Product Code: JPD Dated: May 28, 1999 Received: June 3, 1999

Dear Ms. Carrara:

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 Putman

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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Statement of Indications for Use

510(k) Number:

K991127

Device Name:

Indications for Use:

Bio-Rad VARIANT™ II ß-thalassemia

The VARIANT™ II ß-thalassemia Program is intended for use only with the Bio-Rad VARIANT™ II Hemoglobin Testing System

For in vitro diagnostic use only.

	(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE
	Concurrence of CDRH, Office of Device Evaluation (ODE)

	(Division Sign-Off)Division of Clinical Laboratory Devices510(k) Number K991127
Prescriptive Use		OR over-the-counter Use
	(Per 21 CFR 801.109)

Regulation Number and Section

§ 864.7400 Hemoglobin A

2 assay.(a)
Identification. A hemoglobin A2 assay is a device used to determine the hemoglobin A2 content of human blood. The measurement of hemoglobin A2 is used in the diagnosis of the thalassemias (hereditary hemolytic anemias characterized by decreased synthesis of one or more types of hemoglobin polypeptide chains).(b)
Classification. Class II (performance standards).