Tosoh Automated Glycohemoglobin Analyzer HLC-723G8
Device Facts
| Record ID | K200904 |
|---|---|
| Device Name | Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 |
| Applicant | Tosoh Bioscience, Inc. |
| Product Code | PDJ · Clinical Chemistry |
| Decision Date | Aug 5, 2021 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1373 |
| Device Class | Class 2 |
Intended Use
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is intended for in vitro diagnostic use for the measurement of % hemoglobin A1c (HbA1c) (DCCT/NGSP) and mmol/mol hemoglobin A1c (IFCC) in venous whole blood specimens using ion-exchange high-performance liquid chromatography (HPLC). This test is to be used as an aid in diagnosis of diabetes and identifying patients who may be at risk for developing diabetes, and for monitoring of long-term blood glucose control in individuals with diabetes mellitus.
Device Story
Automated HPLC system for quantitative measurement of stable HbA1c in venous whole blood. Input: whole blood samples. Operation: ion-exchange chromatography using non-porous cation exchange column; step gradient elution separates hemoglobin fractions based on ionic charge. Output: %HbA1c (NGSP) and mmol/mol (IFCC) values. Used in clinical laboratory settings; operated by trained laboratory personnel. System includes sampling unit, liquid pump, degasser, column, detector, microprocessors, and printer. Results aid clinicians in diabetes diagnosis and glucose monitoring. Device detects hemoglobin variants to ensure HbA1c result validity, though variant-specific performance is not FDA-cleared.
Clinical Evidence
Bench testing only. Precision/repeatability study (CLSI EP05-A3) across 4 concentrations (5.0-12.0%) showed total CVs ≤ 1.28%. Method comparison (CLSI EP09c) against Trinity Biotech Premier Hb9210 using 220 patient samples demonstrated strong correlation (Deming slope 1.013, intercept 0.1336). Interference studies (CLSI EP07-A2) confirmed no clinically significant interference from endogenous substances (albumin, ascorbic acid, bilirubin, lipemia, rheumatoid factor) or common hemoglobin variants (HbC, HbD, HbE, HbS, HbF, HbA2) using software v5.24.
Technological Characteristics
Automated ion-exchange HPLC system. Uses TSKgel G8 Variant HSi column. Detection via flow cell absorbance at 415nm with 500nm background correction. Measuring range 4.0-16.9% HbA1c. Traceable to DCCT/NGSP and IFCC. Connectivity via bi-directional interface. Software-controlled via smart media card. Components include sampling unit, liquid pump, degasser, detector, and printer.
Indications for Use
Indicated for in vitro diagnostic measurement of HbA1c in venous whole blood to aid in diabetes diagnosis, identify patients at risk for diabetes, and monitor long-term glycemic control in individuals with diabetes mellitus.
Regulatory Classification
Identification
A hemoglobin A1c test system is a device used to measure the percentage concentration of hemoglobin A1c in blood. Measurement of hemoglobin A1c is used as an aid in the diagnosis of diabetes mellitus and as an aid in the identification of patients at risk for developing diabetes mellitus.
Special Controls
(b) Classification. Class II (special controls). Hemoglobin A1c test systems must comply with the following special controls: 1) The device must have initial and annual standardization verification by a certifying glycohemoglobin standardization organization deemed acceptable by FDA. 2) The premarket notification submission must include performance testing to evaluate precision, accuracy, linearity and interference, including the following: i) Performance testing of device precision must, at a minimum, use blood samples with concentrations near 5.0%, 6.5%, 8.0% and 12% hemoglobin A1c. This testing must evaluate precision over a minimum of 20 days using at least 3 lots of the device and 3 instruments, as applicable. ii) Performance testing of device accuracy must include a minimum of 120 blood samples that span the measuring interval of the new device and compare results of the new device to results of the standardized test method. Results must demonstrate little or no bias versus the standardized method. iii) Total error of the new device must be evaluated using single measurements by the new device compared to results of the standardized test method, and this evaluation must demonstrate a total error less than or equal to 6%. iv) Performance testing must demonstrate that there is little to no interference from common hemoglobin variants, including Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2 and Hemoglobin S. 3) When assay interference from Hemoglobin F or interference with other hemoglobin variants with low frequency in the population is observed, a warning statement must be placed in a black box and must appear in all labeling material for these devices describing the interference and any affected populations.
*Classification.* Class II (special controls). The special controls for this device are:(1) The device must have initial and annual standardization verification by a certifying glycohemoglobin standardization organization deemed acceptable by FDA. (2) The premarket notification submission must include performance testing to evaluate precision, accuracy, linearity, and interference, including the following: (i) Performance testing of device precision must, at a minimum, use blood samples with concentrations near 5.0 percent, 6.5 percent, 8.0 percent, and 12 percent hemoglobin A1c. This testing must evaluate precision over a minimum of 20 days using at least three lots of the device and three instruments, as applicable. (ii) Performance testing of device accuracy must include a minimum of 120 blood samples that span the measuring interval of the device and compare results of the new device to results of a standardized test method. Results must demonstrate little or no bias versus the standardized method. (iii) Total error of the new device must be evaluated using single measurements by the new device compared to results of the standardized test method, and this evaluation must demonstrate a total error less than or equal to 6 percent. (iv) Performance testing must demonstrate that there is little to no interference from common hemoglobin variants, including Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2, and Hemoglobin S. (3) When assay interference from Hemoglobin F or interference with other hemoglobin variants with low frequency in the population is observed, a warning statement must be placed in a black box and must appear in all labeling material for these devices describing the interference and any affected populations.
Predicate Devices
Reference Devices
- Trinity Biotech Ultra2
- Trinity Premier Hb9210 system
Related Devices
- K131580 — AUTOMATED GYLCOHEMOGLOBIN ANALYZER HLC-723G8 · Tosoh Bioscience, Inc. · Jan 23, 2014
- K071132 — G8 AUTOMATED HPLC ANALYZER, MODEL HLC-723 G8 · Tosoh Bioscience, Inc. · Sep 16, 2008
Submission Summary (Full Text)
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September 14, 2021
Tosoh Bioscience, Inc. Louise Musante Regulatory Compliance Consultant, Senior Regulatory Specialist 6000 Shoreline Court. Suite 101 South San Francisco, California 94080
Re: K200904
Trade/Device Name: Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 Regulation Number: 21 CFR 862.1373 Regulation Name: Hemoglobin A1c test system Regulatory Class: Class II Product Code: PDJ, LCP
Dear Louise Musante:
The Food and Drug Administration (FDA) is sending this letter to notify you of an administrative change related to your previous substantial equivalence (SE) determination letter dated August 5, 2021. Specifically, FDA is updating this SE Letter as an administrative correct a typo in the sponsor's 510(k) summary.
Please note that the 510(k) submission was not re-reviewed. For questions regarding this letter please contact Leslie Landreee, OHT7: Office of In Vitro Diagnostics and Radiological Health, (301) 796-6147, leslie.landree@fda.hhs.gov.
Sincerely.
Leslie
Landree -S
Digitally signed by Leslie
Landree -S
Date: 2021.09.14 17:43:06
-04'00'
Leslie Landree Acting Diabetes Diagnostic Devices Branch Chief OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
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August 5, 2021
Tosoh Bioscience, Inc. Louise Musante Regulatory Compliance Consultant, Senior Regulatory Specialist 6000 Shoreline Court, Suite 101 South San Francisco, California 94080
Re: K200904
Trade/Device Name: Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 Regulation Number: 21 CFR 862.1373 Regulation Name: Hemoglobin A1c test system, Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: PDJ, LCP Dated: September 25, 2020 Received: September 29, 2020
Dear Louise Musante:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. 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's 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
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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE(@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
# Marianela Perez-torres -S
Marianela Perez-Torres, Ph.D. Deputy Director OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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### Indications for Use
510(k) Number (if known) k200904
Device Name
Tosoh Automated Glycohemoglobin Analyzer HLC-723G8
Indications for Use (Describe)
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is intended for in vitro diagnostic use for the measurement of % hemoglobin A1c (HbA1c) (DCCT/NGSP) and mmol/mol hemoglobin A1c (IFCC) in venous whole blood specimens using ion-exchange high-performance liquid chromatography (HPLC). This test is an aid in diagnosis of diabetes and identifying patients who may be at risk for developing diabetes, and for monitoring of long-term blood glucose control in individuals with diabetes mellitus.
| Type of Use (Select one or both, as applicable) | |
|-------------------------------------------------|---------------------------------------------|
| X Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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### k200904 510(k) Summary Tosoh Bioscience, Inc.'s Tosoh Automated Glycohemoglobin Analyzer HLC-723G8
May 26, 2020 DATE PREPARED:
- 1. COMPANY NAME/CONTACT Tosoh Bioscience, Inc. 6000 Shoreline Court, Suite 101 South San Francisco, CA 94080
- 2. CONTACT: Louise Musante Regulatory Compliance Consultant Email: louise.musante@tosoh.com Cell Phone: (650) 242-5563
#### 3. DEVICE INFORMATION
Device Trade Name: Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 Regulation Numbers: 21 CFR Part 862.1373 and 21 CFR Part 864.7470 Regulation Names: Hemoglobin A1c test system, Glycosylated hemoglobin assay Product Code: PDJ, LCP Device Class: Class II 510(k) Review Panel: Clinical Chemistry
#### 4. PREDICATE DEVICE
Trade name: VARIANT II TURBO HbA1c Kit – 2.0 on the VARIANT II TURBO Hemoglobin Testing System
| 510(k) submitter/holder: | Bio-Rad Laboratories, Inc., |
|--------------------------|--------------------------------------------|
| | Clinical Diagnostics Group |
| | 4000 Alfred Nobel Drive Hercules, CA 94547 |
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#### 510(k) Numbers:
k122472 (monitoring claim) k142448 (diagnostic claim)
#### 5. REFERENCE DEVICES USED IN NON-CLINICAL PERFORMANCE TESTING
#### Method Comparison testing:
Trinity Biotech Premier Hb9210™ HbA1c Analyzer, by Primus Corporation DBA Trinity Biotech, k112015, Product Code LCP
#### Hemoglobin Variant Interference (HbC, HbE and HbS) testing:
Primus Model CLC 330, aka Ultra2 Affinity HbA1c Analyzer, by Primus Corporation DBA Trinity Biotech, k891235, Product Code LCP
#### Hemoglobinopathy Interference (HbF and HbA2) testing:
VARIANT II TURBO HbA1c Kit - 2.0 on the VARIANT II TURBO Hemoglobin Testing System by Bio-Rad Laboratories, Inc., k142448, Product Code LCP
#### 6. DEVICE DESCRIPTION
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is an automated High-Performance Liguid Chromatography (HPLC) system that separates and reports stable hemoglobin A1c (sA1c) percentage in venous whole blood. The operational portion of the G8 is composed of a sampling unit, liquid pump, degasser, column, detector, microprocessors, sample loader, smart media card, operation panel, and a printer.
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 system consists of the following components, which are 510(k) exempt and clearance is not required;
- G8 Variant Elution Buffer HSi No. 1 (S), No. 2 (S), No. 3 (S) ●
- TSKgel® G8 Variant HSi (column)
- Hemoglobin A1c Controls Levels 1 and 2 ●
- 21 CFR 862.1660, Product Code JJX o
- Hemoglobin A1c Calibrator Set
- 21 CFR 862.1150, Product Code JIT o
- Hemolysis and Wash Solution
- 21 CFR 864.8540, Product Code GGK o
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 uses ion-exchange HPLC for rapid, accurate, and precise separation of the stable form of HbA1c (sA1c) from other hemoglobin fractions. The G8 uses a non-porous cation exchange column and separates the hemoglobin
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components in the blood. Separation is achieved by utilizing differences in ionic interactions between the cation and exchange group on the column resin surface and the hemoglobin components in a step gradient elution. The hemoglobin fractions (designated as A1a. A1b. F. LA1c+, SA1c, A0, and, if present, H-V0, H-V2, H-V2 and H-V3) are subsequently removed from the column by performing a step-wise elution gradient using the varied salt concentrations in the Variant Elution Buffers HSi 1, 2 and 3. The peaks, H-V0, H-V1, H-V2 and H-V3 are typically presumptive HbAD, HbAS, HbAC and HbAE respectively.
The software compares the retention times of hemoglobin fractions in a sample to the expected "windows of retention" and labels each fraction that correctly elutes within a defined expected window of retention. The software designates a hemoglobin fraction as POX (where X is the order of the peak as it elutes from the column) if it does not match a defined window of retention. All automated processes in the G8 are controlled by internal microprocessors, using software downloaded via a smart media card.
The result report is printed and can be stored on the instrument. The data can be transmitted to a host computer through a bi-directional interface. The result report includes the sample ID, date, percentage and retention time of each fraction of hemoglobin, sA1c percentage and total A1 percentage, along with a chromatogram of the elution pattern of the hemoglobin fractions. If a sample contains a hemoglobin variant, the column elutes the fraction depending upon its charge.
#### 7. INDICATION FOR USE STATEMENT
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is intended for in vitro diagnostic use for the measurement of % hemoglobin A1c (HbA1c) (DCCT/NGSP) and mmol/mol hemoglobin A1c (IFCC) in venous whole blood specimens using ion-exchange high-performance liquid chromatography (HPLC). This test is to be used as an aid in diagnosis of diabetes and identifying patients who may be at risk for developing diabetes, and for monitoring of long-term blood glucose control in individuals with diabetes mellitus.
#### 8. INTENDED USE STATEMENTS:
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is intended for in vitro diagnostic use for the measurement of % hemoglobin A1c (HbA1c) (DCCT/NGSP) and mmol/mol hemoglobin A1c (IFCC) in venous whole blood specimens using ion-exchange high-performance liguid chromatography (HPLC). This test is to be used as an aid in diagnosis of diabetes and identifying patients who may be at risk for developing diabetes, and for monitoring of long-term blood glucose control in individuals with diabetes mellitus.
#### 9. SUBSTANTIAL EQUIVALENCE COMPARISON
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8, v5.24, is substantially equivalent to the claimed predicate device; the Bio-Rad VARIANT II TURBO HbA1c Kit – 2.0 on the VARIANT II TURBO Hemoglobin Testing System (K122472 and K142448), based on comparisons of the intended use and technological characteristics.
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#### Table 1 – Comparison Table of Subject Device to Predicate Device
| Attributes | Tosoh Automated<br>Glycohemoglobin<br>Analyzer HLC-723G8,<br>v5.24<br>(Subject Device) | VARIANT II TURBO HbA1c<br>Kit - 2.0 on the VARIANT<br>II TURBO Hemoglobin<br>Testing System<br>(K142448) | VARIANT II TURBO HbA1c<br>Kit - 2.0 on VARIANT II<br>TURBO Hemoglobin<br>Testing System<br>(K122472) | Differences | Differences<br>raise any<br>additional<br>safety<br>issues? |
|------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------|-------------------------------------------------------------|
| General Information | | | | | |
| Regulation # | 21 CFR 862.1373<br>21 CFR 864.7470<br>21 CFR 862.1150 | 21 CFR 862.1373 | 21 CFR 864.7470 | Same | N/A |
| Regulation<br>Name | Hemoglobin A1c Test<br>System<br>Glycosylated<br>Hemoglobin Assay<br>Calibrator | Hemoglobin A1c test<br>system | Glycosylated Hemoglobin<br>Assay | Same | N/A |
| Regulatory Class | Class II | Class II | Class II | Same | N/A |
| Product Code | PDJ, LCP, JIS | PDJ | LCP | Same | N/A |
| Indications for<br>Use | The Tosoh Automated<br>Glycohemoglobin Analyzer<br>HLC-723G8 is intended for<br>in vitro diagnostic use for<br>the measurement of %<br>hemoglobin A1c (HbA1c)<br>(DCCT/NGSP) and<br>mmol/mol hemoglobin<br>A1c (IFCC) in venous whole<br>blood specimens using<br>ion-exchange high-<br>performance liquid<br>chromatography (HPLC).<br>This test is to be used as<br>an aid in diagnosis of<br>diabetes and identifying<br>patients who may be at<br>risk for developing<br>diabetes, and for<br>monitoring of long-term<br>blood glucose control in<br>individuals with diabetes<br>mellitus. | The VARIANT II TURBO<br>HbA1c Kit - 2.0 is intended<br>for the quantitative<br>determination of<br>hemoglobin A1c (IFCC<br>mmol/mol and NGSP %) in<br>human whole blood using<br>ion-exchange high-<br>performance liquid<br>chromatography (HPLC) on<br>the VARIANT™ II TURBO<br>Hemoglobin Testing<br>System and VARIANT II<br>TURBO Link Hemoglobin<br>Testing System.<br>This test is to be used as<br>an aid in diagnosis of<br>diabetes and as an aid in<br>identifying patients who<br>may be at risk for<br>developing diabetes.<br>The VARIANT™ II TURBO<br>HbA1c Kit – 2.0 is intended<br>for Professional Use Only.<br>The Hemoglobin Capillary<br>Collection System (HCCS)<br>is intended for the<br>collection of human whole<br>blood for the percentage | The Bio-Rad VARIANT II<br>TURBO HbA1c Kit - 2.0 is<br>intended for the<br>quantitative<br>determination of<br>hemoglobin A1c in human<br>whole blood using ion-<br>exchange high<br>performance liquid<br>chromatography (HPLC) on<br>the VARIANT II TURBO<br>Hemoglobin Testing<br>System. Measurement of<br>hemoglobin A1c is<br>effective in monitoring<br>long-term glycemic control<br>in individuals with<br>diabetes mellitus. The Bio-<br>Rad VARIANT II TURBO<br>HbA1c Kit - 2.0 is intended<br>for Professional Use Only. | Different | No |
| Attributes | Tosoh Automated<br>Glycohemoglobin<br>Analyzer HLC-723G8,<br>v5.24<br>(Subject Device) | VARIANT II TURBO HbA1c<br>Kit - 2.0 on the VARIANT<br>II TURBO Hemoglobin<br>Testing System<br>(K142448) | VARIANT II TURBO HbA1c<br>Kit - 2.0 on VARIANT II<br>TURBO Hemoglobin<br>Testing System<br>(K122472) | Differences | Differences<br>raise any<br>additional<br>safety<br>issues? |
| | | determination of<br>hemoglobin A1c using Bio-<br>Rad HPLC methods. | | | |
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#### Table 2 – Comparison Table of Technological Characteristics: Subject Device to Predicate Device
| Attributes | Tosoh Automated<br>Glycohemoglobin<br>Analyzer HLC-723G8,<br>v5.24<br>(Subject Device) | Bio-Rad VARIANT II<br>TURBO HbA1c Kit - 2.0 on<br>the VARIANT II TURBO<br>Hemoglobin Testing<br>System<br>(K142448) | VARIANT II TURBO<br>HbA1c Kit - 2.0 on<br>VARIANT II TURBO<br>Hemoglobin Testing<br>System<br>(K122472) | Differences | Differences<br>raise any<br>additional<br>safety<br>issues? |
|---------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------|-------------------------------------------------------------|
| Product Specifications | | | | | |
| Instrument<br>Platform | Automated<br>Glycohemoglobin Analyzer<br>HLC-723G8 | VARIANT™ II TURBO<br>Hemoglobin Testing<br>System and VARIANT™ II<br>TURBO Link Hemoglobin<br>Testing System | VARIANT™ II TURBO<br>Hemoglobin Testing<br>System and VARIANT™ II<br>TURBO Link Hemoglobin<br>Testing System | Different | No |
| Detection<br>Method | Analyte passes through a<br>flow cell where changes in<br>absorbance are measure<br>at 415nm and recorded as<br>a digital chromatogram.<br><br>An additional filter at<br>500nm corrects for<br>background absorbance. | Analyte passes through a<br>flow cell where changes in<br>absorbance are measure<br>at 415nm and recorded as<br>a digital chromatogram.<br><br>An additional filter at<br>690nm corrects for<br>background absorbance. | Analyte passes through a<br>flow cell where changes in<br>absorbance are measure<br>at 415nm and recorded as<br>a digital chromatogram.<br><br>An additional filter at<br>690nm corrects for<br>background absorbance. | Different | No |
| Assay Principle | Ion-exchange HPLC | Ion-exchange HPLC | Ion-exchange HPLC | Same | N/A |
| Specimen Types | Human Venous Whole<br>Blood | Human Venous Whole<br>Blood | Human Venous Whole<br>Blood | Same | N/A |
| Methodology | Dilutes whole blood<br>specimen with Hemolysis<br>& Wash Solution, and then<br>injects a small volume of<br>this specimen onto the<br>TSKgel G8 Variant HSi<br>column. | Dilutes whole blood<br>specimen and then injects<br>a small volume of this<br>specimen onto the<br>analytical cartridge. | Dilutes whole blood<br>specimen and then injects<br>a small volume of this<br>specimen onto the<br>analytical cartridge. | Same | N/A |
| Attributes | Tosoh Automated<br>Glycohemoglobin<br>Analyzer HLC-723G8,<br>v5.24<br>(Subject Device) | Bio-Rad VARIANT II<br>TURBO HbA1c Kit - 2.0 on<br>the VARIANT II TURBO<br>Hemoglobin Testing<br>System<br>(K142448) | VARIANT II TURBO<br>HbA1c Kit - 2.0 on<br>VARIANT II TURBO<br>Hemoglobin Testing<br>System<br>(K122472) | Differences | Differences<br>raise any<br>additional<br>safety<br>issues? |
| Performance Specifications | | | | | |
| Measuring<br>Range | 4.0 to 16.9% HbA1c<br>(NGSP) | 3.4 to 20.6% HbA1c<br>(NGSP) | 3.4 to 20.6% HbA1c<br>(NGSP) | Different | No |
| Traceability and<br>Standardization | Traceable to the Diabetes<br>Control and Complications<br>Trial (DCCT) reference<br>method and IFCC.<br>Certified via the National<br>Glycohemoglobin<br>Standardization Program<br>(NGSP) | Traceable to the Diabetes<br>Control and Complications<br>Trial (DCCT) reference<br>method and IFCC.<br>Certified via the National<br>Glycohemoglobin<br>Standardization Program<br>(NGSP) | Traceable to the Diabetes<br>Control and Complications<br>Trial (DCCT) reference<br>method and IFCC.<br>Certified via the National<br>Glycohemoglobin<br>Standardization Program<br>(NGSP) | Same | N/A |
| Matrix | K2-EDTA and K3-EDTA<br>Venous Whole Blood | K2-EDTA, K3-EDTA,<br>Capillary blood in<br>Hemoglobin Capillary<br>Collection System (HCCS) | K2-EDTA, K3-EDTA,<br>Capillary blood in<br>Hemoglobin Capillary<br>Collection System (HCCS) | Same | N/A |
| Hemoglobin<br>Variant<br>Interference | Accurate and reportable<br>HbA1c% results in the<br>presence of HbC (39%),<br>HbD (39.5%), HbS (39%).<br>Non-clinically significant<br>interference is defined as<br><= 6% relative difference<br>in the results from a<br>comparative method at<br>6% or 9% HbA1c.<br><br>Accurate HbA1c% in the<br>presence of HbF up to<br>25%. Non-clinically<br>significant interference is<br>defined as = 6% relative<br difference in the results<br>from a comparative<br>method at 6% or 9%<br>HbA1c.<br><br>Accurate HbA1c% in the<br>presence of HbA2 up to<br>12%. Non-clinically<br>significant interference is<br>defined as = 6% relative<br difference in the results<br>from a comparative | Accurate and reportable<br>HbA1c% results in the<br>presence of HbC, HbD,<br>HbS. Non-clinically<br>significant interference<br>defined as ±7% from the<br>control.<br><br>Accurate HbA1c% in the<br>presence of HbF up to<br>25%.<br><br>Accurate HbA1c% in the<br>presence of HbA2 up to<br>10%. | Accurate and reportable<br>HbA1c% results in the<br>presence of HbC, HbD,<br>HbS. Non-clinically<br>significant interference<br>defined as ±7% from the<br>control.<br><br>Accurate HbA1c% in the<br>presence of HbF up to<br>25%.<br><br>Accurate HbA1c% in the<br>presence of HbA2 up to<br>10%. | Different | No |
| Attributes | Tosoh Automated<br>Glycohemoglobin<br>Analyzer HLC-723G8,<br>v5.24<br>(Subject Device) | Bio-Rad VARIANT II<br>TURBO HbA1c Kit - 2.0 on<br>the VARIANT II TURBO<br>Hemoglobin Testing<br>System<br>(K142448) | VARIANT II TURBO<br>HbA1c Kit - 2.0 on<br>VARIANT II TURBO<br>Hemoglobin Testing<br>System<br>(K122472) | Differences | Differences<br>raise any<br>additional<br>safety<br>issues? |
| | method at 6% or 9%<br>HbA1c. | | | | |
| | Accurate and reportable<br>HbA1c% results in the<br>presence of 26% HbE.<br>Non-clinically significant<br>interference is defined as<br><= 6% relative difference<br>in the results from a<br>comparative method at<br>6% or 9% HbA1c. | Accurate and reportable<br>HbA1c% results in the<br>presence of HbE. Non-<br>clinically significant<br>interference defined as<br>±7% from the control. | Accurate and reportable<br>HbA1c% results in the<br>presence of HbE. Non-<br>clinically significant<br>interference defined as<br>±7% from the control. | Different | No |
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#### 10. SUMMARY OF TECHNOLOGICAL DIFFERENCES
#### Indications for Use:
The predicate device is cleared separately for the monitoring claim (K122472) and diagnostic claim (K142448). Tosoh seeks clearance for both the monitoring and diagnostic claim combined in this pre-market submission by combining the claims sought and obtained separately for previously cleared Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 submissions; k071132 for the long-term monitoring of people diagnosed with diabetes under 21 CFR 864.7470 as well as the same analyzer cleared in k131580 as a diagnostic HbA1c device under 21 CFR 862.1373. As both clearances are for the same device, with incremental changes, the combination of "Indications for Use" does not raise any additional safety or efficacy questions for the subject device.
#### Instrument Platform:
The subject device and predicate device are both automated High-Performance Liquid Chromatography (HPLC) systems that separate and report hemoglobin A1c percentage in venous whole blood. Aside for the sample volume requirement (3μL of whole blood and 80μL of diluted samples for the subject device and 50μL of venous whole blood and diluted samples for the predicate device), both systems use software algorithms to measure HbA1c concentrations, in the presence of variants. The difference in instrument platform does not raise any additional safety or efficacy questions for the subject device.
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#### Detection Method:
The subject device allows the analyte to pass through a flow cell where changes in absorbance are measure at 415nm and recorded as a digital chromatogram. An additional filter at 500nm corrects for background absorbance. The predicated device uses the same absorbance wavelength to detect and record the sample as a digital chromatogram. The additional filter, however, uses a wavelength of 690nm, correcting for background absorbance. The difference in background wavelength subtraction does not raise any additional safety or efficacy questions for the subject device.
#### Measuring Range:
The subject device has a measuring range of 4.0 to 16.9% HbA1c (NGSP), whereas the predicate device has a measuring range of 3.4 to 20.6% HbA1c (NGSP). The difference in measuring range does not raise any additional safety or efficacy questions for the subject device.
#### 11. SUMMARY OF NON-CLINICAL PERFORMANCE TESTING
Non-clinical performance tests were conducted to support the substantial equivalence determination of this 510(k) submission. No clinical performance tests were conducted to support the substantial equivalence determination of this 510(k) submission. The non-clinical performance tests and summary of results are as follows;
#### a) Precision/Repeatability
The precision repeatability study was performed in compliance with CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition, to verify whether or not the previously established claim of imprecision at ≤ 2% was affected by the software modification to version 5.24 of the Tosoh Automated Glycohemoglobin Analyzer HLC723-G8. Four concentrations of HbA1c% in K2EDTA venous whole blood were tested. The concentrations were approximately 5.0%, 6.5%, 8.0% and 12.0%. A total of seven-hundred and twenty measurements per concentration were measured using the study design: three analyzers over twenty non-consecutive days with three reagent lots. Specimens were run in duplicate, two times per day for a total of seven-hundred and twenty unique results per concentration.
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| HbA1c%<br>(Target)<br>Mean | Repeatability | | Between Run | | Between Day | | Between Lot | | Between<br>Instruments | | Total | |
|---------------------------------------------------------------|---------------|--------|-------------|--------|-------------|--------|-------------|--------|------------------------|--------|--------|--------|
| | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| Sample1<br>[5%]<br>5.46% | 0.0188 | 0.35 | 0.0132 | 0.24 | 0.0266 | 0.49 | 0.0291 | 0.53 | 0.0272 | 0.50 | 0.0532 | 0.97 |
| Sample2<br>[6.5%]<br>6.38% | 0.0212 | 0.33 | 0.0084 | 0.13 | 0.0288 | 0.45 | 0.0280 | 0.44 | 0.0478 | 0.75 | 0.0665 | 1.04 |
| Sample3<br>[8%]<br>7.60% | 0.0199 | 0.26 | 0.0146 | 0.19 | 0.0386 | 0.51 | 0.0441 | 0.58 | 0.0737 | 0.97 | 0.0973 | 1.28 |
| Sample4<br>[12%]<br>11.91% | 0.0277 | 0.23 | 0.0167 | 0.14 | 0.0666 | 0.56 | 0.0684 | 0.57 | 0.0239 | 0.20 | 0.1036 | 0.87 |
| *: Negative variance component's values have been set to '0'. | | | | | | | | | | | | |
#### Table 3 - Summary of Precision Analysis of All Analyzers Combined
*: Negative variance component's values have been set to '0'.
Abbreviations: CV = coefficient of variation, SD = standard deviation
| HbA1c%<br>(Target)<br>Mean | Repeatability | | Between Run | | Between Day | | Between Lot | | Total | |
|----------------------------|---------------|--------|-------------|--------|-------------|--------|-------------|--------|--------|--------|
| | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| Sample1<br>[5%] 5.43% | 0.0178 | 0.33 | 0.0146 | 0.27 | 0.0230 | 0.42 | 0.0145 | 0.27 | 0.0356 | 0.66 |
| Sample2<br>[6.5%] 6.32% | 0.0204 | 0.32 | 0.0109 | 0.17 | 0.0252 | 0.40 | 0.0061 | 0.10 | 0.0348 | 0.55 |
| Sample3<br>[8%] 7.51% | 0.0218 | 0.29 | 0.0204 | 0.27 | 0.0276 | 0.37 | 0.0203 | 0.27 | 0.0454 | 0.60 |
| Sample4<br>[12%]<br>11.89% | 0.0288 | 0.24 | 0.0254 | 0.21 | 0.0509 | 0.43 | 0.0154 | 0.13 | 0.0656 | 0.55 |
#### Table 4 - Summary of Precision Analysis for Analyzer 1 (SN 14736306)
*: Negative variance component's values have been set to '0'.
Abbreviations: CV = coefficient of variation, SD = standard deviation
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| Table 5 - Summary of Precision Analysis for Analyzer 2 (SN 14927602) | | | | | |
|----------------------------------------------------------------------|---------------|-------------|-------------|-------------|-------|
| HbA1c% (Target) | Repeatability | Between Run | Between Day | Between Lot | Total |
### Section 5 - 510(k) Summary or 510(k) Statement
| (Target)<br>Mean | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
|---------------------------------------------------------------|--------|--------|--------|--------|--------|--------|--------|--------|--------|--------|
| Sample1<br>[5%] 5.48% | 0.0202 | 0.37 | 0.0151 | 0.28 | 0.0204 | 0.37 | 0.0402 | 0.73 | 0.0517 | 0.94 |
| Sample2<br>[6.5%] 6.41% | 0.0231 | 0.36 | 0.0* | 0.0* | 0.0199 | 0.31 | 0.0480 | 0.75 | 0.0569 | 0.89 |
| Sample3<br>[8%] 7.64% | 0.0217 | 0.28 | 0.0141 | 0.18 | 0.0278 | 0.36 | 0.0720 | 0.94 | 0.0814 | 1.07 |
| Sample4<br>[12%] 11.93% | 0.0266 | 0.22 | 0.0146 | 0.12 | 0.0558 | 0.47 | 0.1228 | 1.03 | 0.1383 | 1.16 |
| *: Negative variance component's values have been set to '0'. | | | | | | | | | | |
Abbreviations: CV = coefficient of variation, SD = standard deviation
| `Mean`<br>HbA1c | `Repeatability` | | `Between Run` | | `Between Day` | | `Between Lot` | | `Total` | |
|--------------------------------------------------------------|-----------------|--------|---------------|--------|---------------|--------|---------------|--------|---------|--------|
| | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| Sample1<br>[5%] 5.47% | 0.0184 | 0.34 | 0.0092 | 0.17 | 0.0317 | 0.58 | 0.0312 | 0.57 | 0.0489 | 0.89 |
| Sample2<br>[6.5%]6.40% | 0.0201 | 0.31 | 0.0099 | 0.15 | 0.0292 | 0.46 | 0.0300 | 0.47 | 0.0475 | 0.74 |
| Sample3<br>[8%]7.64% | 0.0156 | 0.20 | 0.0050 | 0.06 | 0.0395 | 0.52 | 0.0475 | 0.62 | 0.0640 | 0.84 |
| Sample4<br>[12%]11.90% | 0.0277 | 0.23 | 0.0* | 0.0* | 0.0602 | 0.51 | 0.0678 | 0.57 | 0.0948 | 0.80 |
| *: Negative variance component's values have been set to '0' | | | | | | | | | | |
#### Table 6 - Summary of Precision Analysis for Analyzer 3 (SN 12521504)
## b) Method Comparison
The method comparison study was performed in compliance to CLSI EP09c: Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition. The study was conducted at two separate sites with the candidate device; Tosoh G8 v5.24 Analyzer, located at a moderate complexity clinical laboratory and the comparator device; Trinity Biotech Premier Hb9210™ HbA1c Analyzer, located at an NGSP SRL. Two Hundred and Twenty (220) K₂EDTA venous whole blood specimens with HbA1c concentrations that span the G8 v5.24 measuring range (4.0-16.9%) were tested in duplicate on both analyzers.
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| Target A1c<br>Concentration (%) | No. of<br>Specimens | Percent of Total<br>Samples |
|---------------------------------|---------------------|-----------------------------|
| <5% | 4 | 1.8% |
| 5.0 - 6.0% | 30 | 13.6% |
| 6.0 - 6.5% | 25 | 11.4% |
| 6.5 - 7.0% | 33 | 15.0% |
| 7.0 - 8.0% | 38 | 17.3% |
| 8.0 - 9.0% | 18 | 8.2% |
| >9.0% | 72 | 32.7% |
| Total | 220 | 100% |
#### Table 7 - Sample Distribution Across HbA1c Concentration Range
Table 8 - Summary of Method Comparison Results
| | y-Intercept | 95% CI | Slope | 95% CI |
|----------------|-------------|--------------------|-------|-----------------|
| Deming | 0.1336 | -0.0331 to 0.3005 | 1.013 | 0.9894 to 1.036 |
| Passing-Bablok | 0.0720 | -0.0472 to -0.1819 | 1.021 | 1.007 to 1.037 |
Figure 1 - Method Comparison Deming Regression Analysis of G8 v5.24 vs NGSP SRL (Trinity Premier)
Image /page/14/Figure/7 description: This scatter plot compares two different measurement methods, G8 v5.24 and Premier. The x-axis represents the Premier measurements, while the y-axis represents the G8 v5.24 measurements. The plot includes a Deming fit line, represented by the equation y = -0.1336 + 1.013x, along with a 95% confidence interval (CI) indicated by dashed lines. The data points are clustered tightly around the Deming fit line, suggesting a strong correlation between the two measurement methods.
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#### Table 9 - Method Comparison Bias Results – Passing Bablok
| Decision Level | Bias | % Bias |
|----------------|--------|--------|
| 5.0% | 0.1753 | 3.5% |
| 6.5% | 0.2068 | 3.2% |
| 8.0% | 0.2383 | 3.0% |
| 12.0% | 0.3224 | 2.7% |
#### Table 10 - Method Comparison Bias Results - Deming
| Decision Level | Bias | % Bias |
|----------------|--------|--------|
| 5.0% | 0.1979 | 4.0% |
| 6.5% | 0.2172 | 3.3% |
| 8.0% | 0.2366 | 3.0% |
| 12.0% | 0.2884 | 2.4% |
#### Table 11 - Total Error Estimation
| Total Error [%] | | | | | |
|------------------------------------------------------------------|----------------|-------|--------|-------|----------|
| | Passing Bablok | | Deming | | |
| HbA1c Level | `%TE´* | %Bias | `%TE´* | %Bias | %CVTotal |
| Sample1 [5%] | 5.48 | 3.5 | 5.99 | 4.0 | 0.974054 |
| Sample2 [6.5%] | 5.31 | 3.2 | 5.41 | 3.3 | 1.042108 |
| Sample3 [8%] | 5.59 | 3.0 | 5.59 | 3.0 | 1.281173 |
| Sample4 [12%] | 4.45 | 2.7 | 4.15 | 2.4 | 0.870450 |
| *: Calculated as: $` %Bias + 1.96 x %CVTotal x (1+ %Bias/100)´$ | | | | | |
#### c) Matrix Comparison
The data supports the use of K2-EDTA and K3-EDTA blood collection tubes, as they show no clinical or statistical difference and thus may be used interchangeably for testing HbA1c on the G8 HPLC Analyzer.
#### d) Traceability and Expected Values (calibrators)
The assigned HbA1c values of the Tosoh Automated Glycohemoglobin Analyzer are certified with The National Glycohemoglobin Standardization Program (NGSP). The NGSP certification expires in one year. See NGSP website for current certification at http://www.ngsp.org.
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The final reportable result is traceable to both the International Federation of Clinical Chemistry (IFCC) and the Diabetes Control and Complications Trial (DCCT). The International Federation of Clinical Chemistry (IFCC) units of mmol/mol are calculated using the Master Equation NGSP (%) = [0.09148 x IFCC (mmol/mol)] + 2.152. HbA1c results are provided to the customers using two different units: NGSP equivalent units (%) and IFCC equivalent units (mmol/mol).
Calibrators (Tosoh A1c Calibrator Set) and Controls (Canterbury Scientific Hemoglobin A1c Control) are recommended for use with this device. The calibrators and controls were previously cleared under 510(k) k071132 and k021484, respectively.
- e) Linearity and Detection Limit
Linearity and Detection Limit was previously established for this assay under 510(k) k071132. The reportable range for this device is 4.0 to 16.9% HbA1c.
- f) Analytical Specificity
- i. Endogenous Interfering Substances
The endogenous interference study was performed in compliance to CLSI EP07-A2. Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition. Significant interference was defined as percent recovery ± 5% of the expected 100% recovery. Interference studies were conducted on known concentrations of HbA1c%. Specimens were spiked with increasing amounts of the interfering substance.
| Potential Interfering<br>Substance | Range Tested | HbA1c% Concentrations | Concentration with No<br>Interference |
|------------------------------------|-------------------|-----------------------|---------------------------------------|
| Albumin | 500 to 5000 mg/dL | 6.6 and 14.7 | 5000 mg/dL |
| Ascorbic Acid | 3.0 to 25 mg/dL | 6.4 and 10.8 | 25 mg/dL |
| Bilirubin C | 2.0 to 21 mg/dL | 6.5 and 14.3 | 21 mg/dL |
| Bilirubin F | 2.0 to 18 mg/dL | 6.5 and 14.3 | 18 mg/dL |
| Lipemia | 1 to 1000 mg/dL | 6.4 and 14.1 | 1000 mg/dL |
| Rheumatoid Factor | 110 to 550 IU/mL | 6.3 and 12.6 | 550IU/mL |
Table 12 - Endogenous Interfering Substances Tested
- ii. Drug Interference
The exogenous drug interference study was performed under clearance of k071132. Acetylsalicylic Acid was tested because it does form acetylated hemoglobin, which may interfere with the %HbA1c when measured by HPLC. Acetaldehyde was tested because it can form aldehyde hemoglobin, which can cause an increase in the…
