(486 days)
No
The description details standard HPLC technology and software logic based on comparing retention times to predefined windows, not AI/ML. There is no mention of learning, training data, or adaptive algorithms.
No.
This device is an in vitro diagnostic (IVD) device used to measure HbA1c in blood specimens to aid in the diagnosis and monitoring of diabetes. It does not provide therapy or treatment.
Yes
The device is intended for "in vitro diagnostic use for the measurement of % hemoglobin A1c (HbA1c)..." and "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." These statements directly indicate its purpose as a diagnostic tool.
No
The device description clearly outlines numerous hardware components including a sampling unit, liquid pump, degasser, column, detector, microprocessors, sample loader, smart media card, operation panel, and a printer. While software is used to control these components and process data, the device is fundamentally a hardware system.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is "intended for in vitro diagnostic use".
- Specimen Type: It measures % hemoglobin A1c (HbA1c) in "venous whole blood specimens", which are biological specimens taken from the human body.
- Purpose: The test is described 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." This clearly indicates a medical purpose for diagnosing and monitoring a disease.
- Technology: The device uses ion-exchange high-performance liquid chromatography (HPLC) to analyze components of the blood, which is a common technique used in in vitro diagnostics.
All of these points align with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or concerning a congenital abnormality, or to determine the compatibility of a potential recipient with a potential donor, or to monitor therapeutic measures.
N/A
Intended Use / Indications for 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 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.
Product codes (comma separated list FDA assigned to the subject device)
PDJ, LCP
Device Description
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is an automated High-Performance Liquid 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
- Hemoglobin A1c Calibrator Set
- Hemolysis and Wash Solution
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 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.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Non-clinical performance tests were conducted to support the substantial equivalence determination. No clinical performance tests were conducted.
-
Precision/Repeatability:
- Study in compliance with CLSI EP05-A3.
- Verified imprecision at ≤ 2% after software modification.
- Four concentrations of HbA1c% in K2EDTA venous whole blood were tested: approximately 5.0%, 6.5%, 8.0%, and 12.0%.
- 720 measurements per concentration were measured using 3 analyzers over 20 non-consecutive days with 3 reagent lots. Specimens were run in duplicate, two times per day.
- Key Results (Total SD and CV):
- Sample 1 [5%] (Mean 5.46%): SD 0.0532, CV 0.97%
- Sample 2 [6.5%] (Mean 6.38%): SD 0.0665, CV 1.04%
- Sample 3 [8%] (Mean 7.60%): SD 0.0973, CV 1.28%
- Sample 4 [12%] (Mean 11.91%): SD 0.1036, CV 0.87%
-
Method Comparison:
- Study in compliance with CLSI EP09c.
- Conducted at two separate sites: Tosoh G8 v5.24 Analyzer (moderate complexity clinical lab) and Trinity Biotech Premier Hb9210™ HbA1c Analyzer (NGSP SRL).
- 220 K₂EDTA venous whole blood specimens spanning the G8 v5.24 measuring range (4.0-16.9%) were tested in duplicate on both analyzers.
- Key Results (Deming Regression):
- y-Intercept: 0.1336 (95% CI: -0.0331 to 0.3005)
- Slope: 1.013 (95% CI: 0.9894 to 1.036)
- Key Results (Passing-Bablok):
- y-Intercept: 0.0720 (95% CI: -0.0472 to -0.1819)
- Slope: 1.021 (95% CI: 1.007 to 1.037)
- Bias Results (Deming):
- 5.0% Decision Level: Bias 0.1979 (4.0% Bias)
- 6.5% Decision Level: Bias 0.2172 (3.3% Bias)
- 8.0% Decision Level: Bias 0.2366 (3.0% Bias)
- 12.0% Decision Level: Bias 0.2884 (2.4% Bias)
- Total Error Estimation (Deming):
- HbA1c Level 5%: 5.99%TE´*
- HbA1c Level 6.5%: 5.41%TE´*
- HbA1c Level 8%: 5.59%TE´*
- HbA1c Level 12%: 4.15%TE´*
-
Matrix Comparison:
- Data supports the use of K2-EDTA and K3-EDTA blood collection tubes interchangeably.
-
Traceability and Expected Values (calibrators):
- Traceable to DCCT and IFCC.
- Certified via NGSP (certification expires yearly, check ngsp.org).
- IFCC units (mmol/mol) calculated using Master Equation: NGSP (%) = [0.09148 x IFCC (mmol/mol)] + 2.152.
-
Linearity and Detection Limit:
- Previously established under 510(k) K071132.
- Reportable range: 4.0 to 16.9% HbA1c.
-
Analytical Specificity:
- i. Endogenous Interfering Substances:
- Study in compliance with CLSI EP07-A2. Significant interference defined as percent recovery ± 5% of 100% recovery.
- Tested substances: Albumin (up to 5000 mg/dL), Ascorbic Acid (up to 25 mg/dL), Bilirubin C (up to 21 mg/dL), Bilirubin F (up to 18 mg/dL), Lipemia (up to 1000 mg/dL), Rheumatoid Factor (up to 550 IU/mL).
- No interference found at highest tested concentrations.
- ii. Drug Interference:
- Previously performed under K071132 for Acetylsalicylic Acid and Acetaldehyde.
- FDA confirmed that Levodopa, Methyldopa, Acetaminophen, and Ibuprofen do not interfere with HPLC technology, so additional interference data for these drugs was not needed.
- iii. Cross Reactivity with Hemoglobin Derivatives:
- Tested with ~6.5% and ~8% HbA1c.
- No interference from: Acetylated Hb (up to 50 mg/dL), Carbamylated Hb (up to 25 mg/dL), Aldehyde Hb (up to 25 mg/dL), Labile HbA1c (up to 1000 mg/dL).
- iv. Hemoglobin Variant Interference:
- Study in compliance with CLSI EPO7-A2. Software version 5.24 modified to reduce interference. Non-clinically significant interference defined as
- i. Endogenous Interfering Substances:
§ 862.1373 Hemoglobin A1c test system.
(a)
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.(b)
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.
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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
2
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:
-
- COMPANY NAME/CONTACT Tosoh Bioscience, Inc. 6000 Shoreline Court, Suite 101 South San Francisco, CA 94080
-
- 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
Glycohemoglobin
Analyzer HLC-723G8,
v5.24
(Subject Device) | VARIANT II TURBO HbA1c
Kit - 2.0 on the VARIANT
II TURBO Hemoglobin
Testing System
(K142448) | VARIANT II TURBO HbA1c
Kit - 2.0 on VARIANT II
TURBO Hemoglobin
Testing System
(K122472) | Differences | Differences
raise any
additional
safety
issues? |
|------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------|-------------------------------------------------------------|
| General Information | | | | | |
| Regulation # | 21 CFR 862.1373
21 CFR 864.7470
21 CFR 862.1150 | 21 CFR 862.1373 | 21 CFR 864.7470 | Same | N/A |
| Regulation
Name | Hemoglobin A1c Test
System
Glycosylated
Hemoglobin Assay
Calibrator | Hemoglobin A1c test
system | Glycosylated Hemoglobin
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
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. | The VARIANT II TURBO
HbA1c Kit - 2.0 is intended
for the quantitative
determination of
hemoglobin A1c (IFCC
mmol/mol and NGSP %) in
human whole blood using
ion-exchange high-
performance liquid
chromatography (HPLC) on
the VARIANT™ II TURBO
Hemoglobin Testing
System and VARIANT II
TURBO Link Hemoglobin
Testing System.
This test is to be used as
an aid in diagnosis of
diabetes and as an aid in
identifying patients who
may be at risk for
developing diabetes.
The VARIANT™ II TURBO
HbA1c Kit – 2.0 is intended
for Professional Use Only.
The Hemoglobin Capillary
Collection System (HCCS)
is intended for the
collection of human whole
blood for the percentage | The Bio-Rad VARIANT II
TURBO HbA1c Kit - 2.0 is
intended for the
quantitative
determination of
hemoglobin A1c in human
whole blood using ion-
exchange high
performance liquid
chromatography (HPLC) on
the VARIANT II TURBO
Hemoglobin Testing
System. Measurement of
hemoglobin A1c is
effective in monitoring
long-term glycemic control
in individuals with
diabetes mellitus. The Bio-
Rad VARIANT II TURBO
HbA1c Kit - 2.0 is intended
for Professional Use Only. | Different | No |
| Attributes | Tosoh Automated
Glycohemoglobin
Analyzer HLC-723G8,
v5.24
(Subject Device) | VARIANT II TURBO HbA1c
Kit - 2.0 on the VARIANT
II TURBO Hemoglobin
Testing System
(K142448) | VARIANT II TURBO HbA1c
Kit - 2.0 on VARIANT II
TURBO Hemoglobin
Testing System
(K122472) | Differences | Differences
raise any
additional
safety
issues? |
| | | determination of
hemoglobin A1c using Bio-
Rad HPLC methods. | | | |
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Image /page/8/Picture/0 description: The image shows the logo for Tosoh Bioscience. The logo consists of a red cross-like symbol with a white square in the center, along with the text "TOSOH BIOSCIENCE" in bold black letters. Below the cross symbol, the text "TOSOH" is written in a smaller font size.
Table 2 – Comparison Table of Technological Characteristics: Subject Device to Predicate Device
| Attributes | Tosoh Automated
Glycohemoglobin
Analyzer HLC-723G8,
v5.24
(Subject Device) | Bio-Rad VARIANT II
TURBO HbA1c Kit - 2.0 on
the VARIANT II TURBO
Hemoglobin Testing
System
(K142448) | VARIANT II TURBO
HbA1c Kit - 2.0 on
VARIANT II TURBO
Hemoglobin Testing
System
(K122472) | Differences | Differences
raise any
additional
safety
issues? |
|---------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------|-------------------------------------------------------------|
| Product Specifications | | | | | |
| Instrument
Platform | Automated
Glycohemoglobin Analyzer
HLC-723G8 | VARIANT™ II TURBO
Hemoglobin Testing
System and VARIANT™ II
TURBO Link Hemoglobin
Testing System | VARIANT™ II TURBO
Hemoglobin Testing
System and VARIANT™ II
TURBO Link Hemoglobin
Testing System | Different | No |
| Detection
Method | Analyte passes 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. | Analyte passes through a
flow cell where changes in
absorbance are measure
at 415nm and recorded as
a digital chromatogram.
An additional filter at
690nm corrects for
background absorbance. | Analyte passes through a
flow cell where changes in
absorbance are measure
at 415nm and recorded as
a digital chromatogram.
An additional filter at
690nm corrects for
background absorbance. | Different | No |
| Assay Principle | Ion-exchange HPLC | Ion-exchange HPLC | Ion-exchange HPLC | Same | N/A |
| Specimen Types | Human Venous Whole
Blood | Human Venous Whole
Blood | Human Venous Whole
Blood | Same | N/A |
| Methodology | Dilutes whole blood
specimen with Hemolysis
& Wash Solution, and then
injects a small volume of
this specimen onto the
TSKgel G8 Variant HSi
column. | Dilutes whole blood
specimen and then injects
a small volume of this
specimen onto the
analytical cartridge. | Dilutes whole blood
specimen and then injects
a small volume of this
specimen onto the
analytical cartridge. | Same | N/A |
| Attributes | Tosoh Automated
Glycohemoglobin
Analyzer HLC-723G8,
v5.24
(Subject Device) | Bio-Rad VARIANT II
TURBO HbA1c Kit - 2.0 on
the VARIANT II TURBO
Hemoglobin Testing
System
(K142448) | VARIANT II TURBO
HbA1c Kit - 2.0 on
VARIANT II TURBO
Hemoglobin Testing
System
(K122472) | Differences | Differences
raise any
additional
safety
issues? |
| Performance Specifications | | | | | |
| Measuring
Range | 4.0 to 16.9% HbA1c
(NGSP) | 3.4 to 20.6% HbA1c
(NGSP) | 3.4 to 20.6% HbA1c
(NGSP) | Different | No |
| Traceability and
Standardization | Traceable to the Diabetes
Control and Complications
Trial (DCCT) reference
method and IFCC.
Certified via the National
Glycohemoglobin
Standardization Program
(NGSP) | Traceable to the Diabetes
Control and Complications
Trial (DCCT) reference
method and IFCC.
Certified via the National
Glycohemoglobin
Standardization Program
(NGSP) | Traceable to the Diabetes
Control and Complications
Trial (DCCT) reference
method and IFCC.
Certified via the National
Glycohemoglobin
Standardization Program
(NGSP) | Same | N/A |
| Matrix | K2-EDTA and K3-EDTA
Venous Whole Blood | K2-EDTA, K3-EDTA,
Capillary blood in
Hemoglobin Capillary
Collection System (HCCS) | K2-EDTA, K3-EDTA,
Capillary blood in
Hemoglobin Capillary
Collection System (HCCS) | Same | N/A |
| Hemoglobin
Variant
Interference | Accurate and reportable
HbA1c% results in the
presence of HbC (39%),
HbD (39.5%), HbS (39%).
Non-clinically significant
interference is defined as
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
Substance | Range Tested | HbA1c% Concentrations | Concentration with No
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 LA1c fraction.
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With HPLC, the red cells are lysed and eluted across the column for separation of the hemoglobin fractions. Research of the FDA website and others show no contraindication of Levodopa. Methyldopa. Acetaminophen and Ibuprofen when used by pre-diabetic or diabetic patients, and the drugs do not interfere with the HPLC technology as they might during an antigen/antibody reaction. FDA stated that based on the technology of the device, it has been shown that the additional substances do not appear to interfere with this type of device; therefore, the additional interference data on these drugs was not needed.
-
iii. Cross Reactivity with Hemoglobin Derivatives
A cross-reactivity study was performed with potential interferences from Acetylated hemoglobin (Hb), Carbamylated Hb, Aldehyde Hb, and Labile HbA1c with HbA1c values of ~6.5% and ~8% HbA1c. The following results were concluded as not interfering with the assay. -
Acetylated Hb up to 50 mg/dL
-
Carbamylated Hb up to 25 mg/dL ●
-
. Aldehyde Hb up to 25 mg/dL
-
Labile HbA1c up to 1000 mg/dL
iv. Hemoglobin Variant Interference
The hemoglobin variant interference study was performed in compliance to CLSI EPO7-A2, Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition. Interference when measuring %HbA1c in clinical specimens due to certain levels of Hb variants (HbC, HbD, HbE, and HbS) and hemoglobinopathies (HbA2 and HbF) is wellknown. To reduce possible interference and to enhance the performance of the G8 in the presence of these variants and hemoglobinopathies, Tosoh modified the software algorithms. The modified software, version 5.24, reduces interference when measuring %HbA1c.
An interference study was performed to identify the level of Hb variants and hemoglobinopathies likely to cause interference, thus verifying that the G8 software modification (version 5.24) did reduce measurement interference of %HbA1c under these conditions. Non-clinically significant interference was defined as