The Bio-Rad VARIANT II TURBO Link Hemoglobin Alc Program is intended for the percent determination of hemoglobin A1c in human whole blood using ion-exchange high-performance liquid chromatography (HPLC).

The VARIANT II TURBO Link Hemoglobin A Ic Program is for use with the VARIANT II TURBO Link Hemoglobin Testing System interfaced with an automated sample transport system.

The Bio-Rad VARIANT II TURBO Link Hemoglobin AIc Program is Professional Use Only. Measurement of hemoglobin A Ic is effective in monitoring long-term glycemic control in individuals with diabetes mellitus.

Device Description

The VARIANT II TURBO Link Hemoglobin Testing System is the next generation Instrument VARIANT II TURBO Hemoglobin Testing System. It integrates the VARIANT II TURBO with the Sysmex HST-N (Hematology Sample Transportation)/XN-9000 TLA systems to allow management of patient sample tubes with A 1c order on the same platform. The VARIANT II TURBO Link system communicates with the Sysmex HST-N/XN-9000 TLA hardware and software in order to receive, identify, inject, and analyze samples with an A 1 c order.

The VARIANT II TURBO Link Hemoglobin Testing System is a fully automated, highthroughput hemoglobin analyzer. It consists of three modules - the VARIANT II TURBO Link Chromatographic Station (VCS), the VARIANT II TURBO Link Sampling Station (VSS), and the Reagent Reservoir Module. In addition, a personal computer (PC) is used to control the VARIANT II TURBO Link system using Clinical Data Management (CDM™) software.

AI/ML Overview

Here's an analysis of the acceptance criteria and study information for the Bio-Rad VARIANT™ II TURBO Link Hemoglobin A1c Program, based on the provided text:

Premarket Notification (510(k)) Summary: K140801

It is important to note that this 510(k) pertains to a device modification (specifically, software and firmware updates) of an already cleared device, the VARIANT™ II TURBO Link Hemoglobin A1c Program (K070819). The document explicitly states: "When compared to the predicate device, there are no changes to the performance specifications, intended or indications for use, or operating principles. Moreover, Risk Analysis and Verification/Validation testing results demonstrate that the changes do not affect product safety, effectiveness, and substantial equivalency claims." Therefore, the "acceptance criteria" for the modified device are primarily centered on demonstrating that the changes do not degrade the performance of the predicate device. The performance claims for the modified device are directly transferred from the predicate.

1. Table of Acceptance Criteria and Reported Device Performance

As this is a modification to an already cleared device and the document states "No change, claims transferred from predicate device" for performance, specific numerical acceptance criteria and reported performance for the modified device itself are not explicitly presented as a new performance study. Instead, the acceptance is based on demonstrating that the software and firmware updates do not negatively impact the performance validated for the predicate device.

The main acceptance criteria for this specific 510(k) effectively become:

The modified device (with updated software and firmware) performs as safely and effectively as the predicate device.
Risk mitigations, hazard controls, and residual risks are as safe and effective as the predicate device.
Design verification/validation tests met established acceptance criteria (which implicitly refer to the predicate's performance).

Acceptance Criteria Category	Specific Criteria (Implicitly from Predicate)	Reported Device Performance (Modified Device)
Performance Claims	Maintain all performance specifications and claims of the predicate device (K070819). The predicate device is certified by NGSP as traceable to the Diabetes Control and Complications Trial (DCCT) Reference method.	"No change, claims transferred from predicate device." The verification/validation testing demonstrated that the changes did not affect product safety, effectiveness, and substantial equivalency claims, implying that the modified device maintained the predicate's performance.
Safety and Effectiveness	Device modifications do not introduce new safety concerns or reduce effectiveness compared to the predicate device.	"Risk Analysis and Verification/Validation testing results demonstrate that the changes do not affect product safety, effectiveness, and substantial equivalency claims."
Functional Integrity	The new CDM Software version 5.2.1, new reporting units (mmol/mol HbA1c (IFCC), %HbA1c (JDS)), new printing options (Export to PDF), and updated firmware versions function as intended without adverse impact.	"The software updates include customer requested features, whereas both software and firmware include specific defect fixes... Risk Analysis and Verification/Validation testing results demonstrate that the changes do not affect product safety, effectiveness, and substantial equivalency claims." "Design verification/validation tests met established acceptance criteria."
Substantial Equivalence	Demonstrated substantial equivalence to the predicate device (K070819).	"When considering the similarities of the intended use, general features and characteristics of the assay, and use of the same technology, it can be concluded that the VARIANT II TURBO Link Hemoglobin A1c Program is substantially equivalent to the cleared and currently marketed predicate device." (This is the overall conclusion of the 510(k) submission based on the studies performed).

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

The document does not explicitly provide details on a test set sample size or data provenance in the context of a new clinical or performance study for the modified device. The studies conducted were primarily an engineering verification and validation to affirm that the software and firmware changes did not degrade performance.

The studies mentioned are:

Risk Analysis (FMEA): Identified and mitigated risks associated with modifications.
Verification and Validation Testing: Evaluated the modified product against acceptance criteria to ensure safety, effectiveness, and substantial equivalence to the predicate.

Since the performance claims are transferred from the predicate device (K070819), any "test set" for performance evaluation would have been part of the original predicate's clearance. This submission indicates that existing product risk tables and customer complaints were reviewed, suggesting that real-world operational data (retrospective, ongoing) might have informed the risk analysis process.

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

This document does not describe the use of experts to establish a "ground truth" for a test set in the conventional sense of a diagnostic performance study. The focus is on demonstrating that software and firmware changes do not compromise the previously established performance.

The "ground truth" for the original HbA1c measurement performance (predicate device) is stated as being certified by the NGSP as traceable to the Diabetes Control and Complications Trial (DCCT) Reference method. This is an external, highly standardized, and internationally recognized reference method, not established by individual experts for this specific submission.

The risk analysis process involved a "trained risk assessment team," but their qualifications and exact number are not specified, nor were they establishing clinical ground truth.

4. Adjudication Method for the Test Set

No adjudication method for a test set is mentioned, as this submission focuses on verification/validation of software/firmware changes and demonstrating substantial equivalence to a predicate device, rather than a new primary diagnostic performance study requiring expert adjudication of cases.

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

No MRMC study was performed or described. This device is an automated, high-throughput hemoglobin analyzer, not a diagnostic imaging AI tool requiring human "readers" or "assistance."

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

Yes, the device (both predicate and modified) is inherently a standalone algorithm (or automated system) without human-in-the-loop performance influencing the primary measurement. It's a fully automated analyzer that performs ion-exchange high-performance liquid chromatography. The "algorithm" is integral to its operation, but it's not a separate software AI algorithm in the contemporary sense of providing diagnostic interpretations to a human. The updated software and firmware control the instrument itself.

The verification and validation "determined whether risk mitigations, hazard controls, and residual risks were as safe and effective as the predicate device," which implies standalone performance of the modified system.

7. The Type of Ground Truth Used

The "ground truth" for the overall performance of the HbA1c measurement method (which is unchanged from the predicate) is traceable to the Diabetes Control and Complications Trial (DCCT) Reference method, as certified by the NGSP (National Glycohemoglobin Standardization Program). This is a highly standardized and validated reference method for HbA1c.

8. The Sample Size for the Training Set

No training set is mentioned. This is not an AI/Machine Learning device that undergoes a "training" phase with a dataset. It's an analytical instrument.

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

Not applicable, as no training set was used.

Summary

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K140801

JUN 2 5 2014

Special 510(k) Summary – Device Modification

Introduction	This 510(k) summary is being submitted in accordance with the requirements of 21 CFR807.92 and the Safe Medical Device Act of 1990.
Submitter	Bio-Rad Laboratories, Inc.Clinical Systems Division4000 Alfred Nobel DriveHercules, CA 94545
ContactPerson	Ebony McKinniesRegulatory Affairs Representative III(510)741-6265
DateSubmitted	April 23, 2014
Device Name	VARIANT™ II TURBO Link Hemoglobin A1c Program
Classification	Glycosylated hemoglobin assay, 21 CFR 864.7470 [LCP]
PredicateDevice	Table 1: Predicate DevicerumberVARIANTIM II TURBO Link HemoglobinK07081921 CFR 864.7470 [LCP]
Intended andIndications forUse	Alc ProgramThe Bio-Rad VARIANT II TURBO Link Hemoglobin A1c Program is intended for thepercent determination of hemoglobin Alc in human whole blood using ion-exchangehigh-performance liquid chromatography (HPLC).The VARIANT II TURBO Link Hemoglobin Alc Program is for use with theVARIANT II TURBO Link Hemoglobin Testing System interfaced with an automatedsample transport system.The Bio-Rad VARIANT II TURBO Link Hemoglobin A1c Program is Professional UseOnly.Measurement of hemoglobin Alc is effective in monitoring long-term glycemic controlin individuals with diabetes mellitus.

Bio-Rad Laboratories, Inc. VARIANT™ II TURBO Link Hemoglobin A1c Program Special 510(k) – Device Modification

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Description of The VARIANT II TURBO Link Hemoglobin Testing System is the next generation Instrument VARIANT II TURBO Hemoglobin Testing System. It integrates the VARIANT II TURBO with the Sysmex HST-N (Hematology Sample Transportation)/XN-9000 TLA systems to allow management of patient sample tubes with A 1c order on the same platform. The VARIANT II TURBO Link system communicates with the Sysmex HST-N/XN-9000 TLA hardware and software in order to receive, identify, inject, and analyze samples with an A 1 c order.

The VARIANT II TURBO Link Hemoglobin Testing System is a fully automated, highthroughput hemoglobin analyzer. It consists of three modules - the VARIANT II TURBO Link Chromatographic Station (VCS), the VARIANT II TURBO Link Sampling Station (VSS), and the Reagent Reservoir Module. In addition, a personal computer (PC) is used to control the VARIANT II TURBO Link system using Clinical Data Management (CDM™) software.

Table 2: FDA-cleared assays for use on the VARIANT II TURBO Link Hemoglobin Testing System with CDM Software

VARIANT IITURBO LinkAssay	AssayPart No.	Component Names and Part Nos.	Explanation of Test
VARIANT IITURBO LinkHemoglobinA1c Program	270-2716	The assay contains the following components Whole Blood Primer, 270-0352, 270-0351, 270-0352 Elution Buffer A, 270-2717 Elution Buffer B, 270-2718 Wash/Diluent Solution, 270-2729 CD-ROM, 270-2719 Cartridge Set, 270-22724 Sample Vials, 270-2149 Calibrator/Diluent Set Additional Required/Available components: Wash/Diluent Solution Set, 270-2730 Elution Buffer A Set Prefilters, 270-2713 Stainless Steel Prefilter Adapters, 270-2465 Microvial Adapters, 270-2720, 270-2721	The VARIANT II TURBO LinkHemoglobin A1c Program is awell established method ofmeasuring the level ofHemoglobin A1c in red bloodcells. Therapy for diabetesrequires the long-termmaintenance of a blood glucoselevel as close as possible tonormal levels to minimize therisk of long-term vascularconsequences.

The following table shows the similarities and differences between the predicate and Comparison to Predicate modified device. Device

Table 3: VARIANT II TURBO Link Hemoglobin A1c Program

Feature	Predicate:	Modified device
	Bio-Rad VARIANT TM II TURBOLink Hemoglobin A1c ProgramK070819	Bio-Rad VARIANT TM II TURBO LinkHemoglobin A1c ProgramK140801
Similarities
Technology	Ion-exchange high performance liquid chromatography
Sample type	Anticoagulated whole blood (EDTA)

Bio-Rad Laboratories, Inc.

VARIANT™ II TURBO Link Hemoglobin A1c Program Special 510(k) - Device Modification

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Feature	Predicate:Bio-Rad VARIANT TM II TURBOLink Hemoglobin A1c ProgramK070819	Modified device:Bio-Rad VARIANTTM II TURBO LinkHemoglobin A1c ProgramK140801
Calibrator	Human anticoagulated whole blood treated with EDTA
Certification	Certified by the NGSP as traceable to the Diabetes Control and Complications Trial(DCCT) Reference method.
Instrument Control	Windows Operating System with Proprietary Assay Software
Kit configuration	1600 Tests: Whole Blood Primer (6 vials), Elution Buffer A (1 each), Elution BufferB (1 each), Calibrator/Diluent Set (1 each), CD-ROM (1 each), Cartridge Set (1 each),Sample vials – package of 100 (2 each), Wash/Diluent Solution (1 each).
Chemistry	Cation Exchange Matrix
Safety Standards forElectrical Equipmentfor IVD Use	BS EN 61010 Certified
ElectromagneticCompatibility	BS EN 61326 Certified
Intended Use	The Bio-Rad VARIANT II TURBO Link Hemoglobin A1c Program is intended forthe percent determination of hemoglobin A1c in human whole blood using ion-exchange high-performance liquid chromatography (HPLC).The VARIANT II TURBO Link Hemoglobin A1c Program is for use with theVARIANT II TURBO Link Hemoglobin Testing System interfaced with an automatedsample transport system.The Bio-Rad VARIANT II TURBO Link Hemoglobin A1c Program is forProfessional Use Only.
Performance Claims	No change, claims transferred from predicate device.
Differences
CDM Software	CDM Software version 4.1	CDM Software version 5.2.1
Reporting Units	%HbA1c (NGSP)	% HbA1c (NGSP), mmol/mol HbA1c(IFCC), or %HbA1c (JDS)
Printing Options	Export text file to external printer	External printer and Export to PDF options
VARIANT II TURBOLink Testing SystemFirmware	EPROMVCS 41.507VSS 51.505VSS PUMP4.50	EPROM &n FLASH N/A HST FLASHVCS 42.507VSS 52.815VSS Pump5.0 XN 9000 FLASHVTCS 42.507VTSS 52.815VTSS PUMP5.00 Automated SamplingStation Sysmex HST Trackline Sysmex HST or Sysmex XN-9000Trackline Historical DatabaseReview N/A Archive Viewer – this tool does not allowtransmission to an LIS, and is not intended

The software updates include customer requested features, whereas both software and Description of firmware include specific defect fixes. When compared to the predicate device, there Change are no changes to the performance specifications, intended or indications for use, or operating principles. Moreover, Risk Analysis and Verification/Validation testing results demonstrate that the changes do not affect product safety, effectiveness, and substantial equivalency claims.

Bio-Rad Laboratories, Inc. VARIANT™ II TURBO Link Hemoglobin A1c Program Special 510(k) - Device Modification

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Risk Management Process for Device Modifications

In accordance with ISO 14971:2012, and internal risk management processes and procedures a defined risk analysis was used to identify, mitigate, or eliminate potential risks associated with the device modifications. For each identified risk, a Failure Mode and Effects Analysis (FMEA) was conducted. This was performed in a systematic manner by a trained risk assessment team until consensus was reached that an adequate analysis had been performed. The risk evaluation for the device software and firmware modifications included the following tasks:

Reviewed modifications and design inputs to identify potential risks and ■ hazards:
Reviewed existing product risk tables and customer complaints to identify potential risks and hazards:
. Considered requirements of IEC 62304:2009, Software Design and Development processes and plan to identify potential risks and hazards;
Identified and implemented risk mitigations and hazard controls through software, hardware, and labeling for misuse and use scenarios;
트 Updated existing FMEA and Hazard Analysis tables with newly identified risks, software defects, residual risks, mitigations and hazard controls:
Evaluated modified product using established verification and validation processes, plans and protocols with appropriate acceptance criteria that determined whether risk mitigations, hazard controls, and residual risks were as safe and effective as the predicate device;
I Conducted a comprehensive risk management review and wrote a Risk Management Report that summarized all risk activities and deemed the modified product safe, effective, and comparable to the predicate device.

Design verification/validation tests met established acceptance criteria.

Conclusion

When considering the similarities of the intended use, general features and characteristics of the assay, and use of the same technology, it can be concluded that the VARIANT II TURBO Link Hemoglobin A1c Program is substantially equivalent to the cleared and currently marketed predicate device.

Bio-Rad Laboratories. Inc. VARIANT™ II TURBO Link Hemoglobin A1c Program Special 510(k) - Device Modification

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Image /page/4/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized graphic of an eagle or bird-like figure with three wing-like shapes. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the graphic.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Canirol Center - WO66-G609 Silver Spring, MD 20993-0002

BIO-RAD LABORATORIES, INC. EBONY MCKINNIES REGULATORY AFFAIRS REPRESENTATIVE III 4000 ALFRED NOBEL DR. HERCULES CA 94547

June 25, 2014

Re: K140801

Trade/Device Name: VARIANT™ II TURBO Link Hemoglobin A Ic Program Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: II Product Code: LCP Dated: May 23, 2014 Received: May 27, 2014

Dear Ms. McKinnies:

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. Ilsting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading,

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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 is 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803): good manufacturing practice requirements as set forth in the quality systems (OS) 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-Ms. McKinnies

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.lda.gov/MedicalDevices/Safety/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Katherine Serrano -S

For : Courtney H. Lias

Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.

510(k) Number (if known) K 140801

Device Name

VARIANT™ II TURBO Link Hemoglobin A Ic Program

Indications for Use (Describe)

The VARIANT II TURBO Link Hemoglobin A Ic Program is for use with the VARIANT II TURBO Link Hemoglobin Testing System interfaced with an automated sample transport system.

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

PLEASE DO NOT WRITE BELOW THIS LINE -- CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Stayce Beck -S

Regulation Number and Section

§ 864.7470 Glycosylated hemoglobin assay.

(a)
Identification. A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.(b)
Classification. Class II (performance standards).