Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard immunoassay system for HbA1c testing, focusing on reagents, analyzer components (light absorption, scattered light, fluorescence), and performance metrics typical of analytical chemistry devices. There is no mention of AI, ML, or any computational methods beyond standard data processing for quantitative analysis.

Therapeutic

No
This device is an in vitro diagnostic (IVD) system used to measure HbA1c levels in blood, which aids in the diagnosis and monitoring of diabetes. It does not directly treat or prevent a disease, but rather provides information for diagnosis and monitoring.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the system "is used as an aid in diagnosis of diabetes mellitus" and "to identify patients who may be at risk for developing diabetes mellitus."

SaMD (Software as a Medical Device)

No

The device description clearly states it is comprised of a test kit (reagents) and an automatic immunoassay analyzer, which is a hardware component.

IVD (In Vitro Diagnostic)

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 system is used "as an aid in diagnosis of diabetes mellitus, as an aid to identify patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus." It also states it is an "in vitro diagnostics reagent system intended for quantitative determination of % hemoglobin A1c (DCCT/NGSP) in venous whole blood." This clearly indicates the device is intended for use on biological samples (venous whole blood) outside of the body to provide information for medical diagnosis and monitoring.
Device Description: The "Device Description" details a "reagent system" and an "automatic immunoassay analyzer" used for the "quantitative determination of % hemoglobin A 1c (DCCT/NGSP) in venous whole blood." This further supports its use in laboratory testing of biological samples.
In Vitro Diagnostics Reagent System: The "Intended Use" specifically labels the system as an "in vitro diagnostics reagent system."

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 monitor therapeutic measures.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Hipro® Glycosylated Hemoglobin (HbA1c) Test System comprised of the Hipro Glycosylated hemoglobin (HbA1c) test kit and the HP-AFS/1 automatic immunoassay analyzer is used as an aid in diagnosis of diabetes mellitus, as an aid to identify patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. It is an in vitro diagnostics reagent system intended for quantitative determination of % hemoglobin A1c (DCCT/NGSP) in venous whole blood.

Product codes (comma separated list FDA assigned to the subject device)

PDJ, LCP

Device Description

The Hipro® Glycosylated hemoglobin (HbA1c) test system is intended for quantitative determination of % hemoglobin A 1c (DCCT/NGSP) in venous whole blood. It is composed of Glycosylated hemoglobin (HbA1c) test kit and automatic immunoassay analyzer. Glycosylated hemoglobin (HbA1c) test kit consists of two reagents R1 and R2, which are liquid and ready to use. Reagent R1 contains glycine buffer and latex, and reagent R2 contains glycine buffer and two types of antibodies, Goat anti-mouse IgG, mouse anti-human HbAlc monoclonal antibody.

HP-AFS/1 Automatic Immunoassay Analyzer is made up of light absorption test module, scattered light test module, fluorescence test module, press components, data transmission interface and printer. And the absorption test module is made up of absorption light path unit, and lightabsorption sensor part. The scattered light test module is made up of scattered light path unit and scattered light sensor part.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Prescription Use

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Precision: Precision experiments were performed for the Glycosylated hemoglobin Test Kit based on CLSI Guideline EP5-A3 using four EDTA K2 whole blood samples with targeted HbA1c concentrations (5.2%, 6.4%, 8.0% and 12.3%), two controls (6% and 11%). Samples were analyzed on three Automatic Immunoassay Analyzer instruments using three lots of reagents. Each sample was analyzed in duplicate per run, two runs per day for 20 days. The samples were randomized in experiment.

Method Comparison: A method comparison study was performed to compare the sample results from the candidate method, Hipro® Glycosylated hemoglobin (HbA1c) test kit on the Hipro HP-AFS/1 Automatic Immunoassay analyzer, to results from the Bio-Rad Hemoglobin Testing System. This study was conducted with the EDTA K2 whole blood samples. One hundred and twenty (120) samples from the NGSP reference laboratory were used in the evaluation. These samples were measured by the NGSP reference laboratory using a Bio-Rad Hemoglobin Testing System (X axis) and by the Hipro® Glycosylated Hemoglobin (HbA1c) Test System (Y axis). All acceptance criteria for method comparison were met. The difference plots show there is good agreement between the Hipro® Glycosylated Hemoglobin (HbA 1c) Test System and the NGSP Bio-Rad Hemoglobin Testing System.

Total Error: Calculated using the results of bias estimation (%Bias) in the method comparison study and precision estimates in the precision study, at concentrations 5.2%, 6.4%, 8.0% and 12.3% near the cut-off. Formula: %TE =|%Bias| + 1.96 * %CV * (1+%Bias/100).

Linearity: One dilution series consisting of 9 levels were prepared using the EDTA K2 WB sample pools with HbA1c through mixing high and low concentrations at the upper and lower end of the measuring range. Samples were measured in triplicate and data analysis was done separately for each sample. Linear regression analysis was done according to EP6-2nd edition. Linear range: 4.3%-14% HbA1c.

Endogenous Interference: A study evaluated Lipemia, Unconjugated Bilirubin, Conjugated Bilirubin, Glucose, Rheumatoid Factor, and Total Protein for potential interference. Pooled whole blood samples with two HbA1c levels were spiked with maximum levels of interferents. An interferent was defined as significant if it caused >7% deviation of a measurement.

Drug Interference: A study evaluated 16 commonly used drugs for potential interference with the measurement of %HbA1c using EDTA K2 WB samples at 2 different HbA1c levels (approximately 6.5% and 8.5%). Each drug was added in two defined concentrations. Significant interference was defined as > ±7% deviation from the reference value. All acceptance criteria for drug interferences were met.

Cross-reactivity: Studies were performed to determine cross-reactivity with Hb A0, Carbamylated Hb, Glycated Albumin, Labile Hb A1c, Acetylated Hb, and Hb A1a+b.

Hemoglobin variants: Testing was conducted to determine if there was any significant interference with major hemoglobin variants (HbS, HbC, HbD, HbE) and HbF and HbA2. Each sample was tested twice on one Hipro HP-AFS/1 Automatic Immunoassay analyzer. Results obtained with the Hipro® Glycosylated hemoglobin (HbA1c) test kit were compared to those obtained with reference methods. Interference was observed with HbF when its concentration was > 8%.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K151321

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 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.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

September 12, 2024

Shijiazhuang Hipro Biotechnology Co., Ltd. % Hanson Chen, Official Correspondent Shenzhen Joyantech Consulting Co., Ltd. 1713A, 17th Floor, Block A Zhongguan Times Square, Liuxian Avenue, Xili Town, Nanshan District Shenzhen. Gaungdong 518000 China

Re: K220999

Trade/Device Name: Hipro Glycosylated Hemoglobin (HbA1c) Test System Regulation Number: 21 CFR 862.1373 Regulation Name: Hemoglobin A1c Test System Regulatory Class: Class II Product Code: PDJ, LCP Dated: October 13, 2023 Received: October 13, 2023

Dear Hanson Chen:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

1

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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.

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For comprehensive regulatory information about medical devices and radiation-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,

Joshua Balsam -S

Joshua M. Balsam, Ph.D. Branch Chief Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics 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) K220999

Device Name

Hipro® Glycosylated Hemoglobin (HbA1c) Test System

Indications for Use (Describe)

The Hipro® Glycosylated Hemoglobin (HbA1c) Test System comprised of the Hipro Glycosylated hemoglobin (HbA1c) test kit and the HP-AFS/1 automatic immunoassay analyzer is used as an aid in diagnosis of diabetes mellitus, as an aid to identify patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. It is an in vitro diagnostics reagent system intended for quantitative determination of % hemoglobin A1c (DCCT/NGSP) in venous whole blood.

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)

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510(k) Summary	K220999
1. Contact Details
1.1 Applicant information
Applicant Name	Shijiazhuang Hipro Biotechnology Co., Ltd.
Address	No. 3 Building, Block C Fang Yi Science Park, No. 365 Huai'an East
Road, Hi-tech Zone, Shijiazhuang, 050000 Hebei, P.R. China
Phone No.	+86-311-83855889
Contact person	Bruce
Date Prepared	Sep 12, 2024
Website	http://www.hiprochina.com/

1.2 Submission Correspondent

Image: Logo	Shenzhen Joyantech Consulting Co., Ltd
卓远天成	1713A, 17th Floor, Block A, Zhongguan Times Square, Liuxian
Avenue, Xili Town, Nanshan District, Shenzhen, Guangdong,
518000, China
Phone No.	+86-755-86069197
Contact person	Hanson Chen
Contact person's e-mail	hanson@cefda.com
Website	http://www.cefda.com

2. Device information

Trade name	Hipro® Glycosylated Hemoglobin (HbA1c) Test System
Model	/
Classification	II
Classification name	Hemoglobin A1c Test System
Product code	PDJ, LCP
Regulation No.	862.1373

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3. Legally Marketed Predicate Device

Trade Name	D-100™ HbA1c
510(k) Number	K151321
Product Code	PDJ, LCP
Manufacturer	Bio-Rad Laboratories, Inc.

4. Device Description

The Hipro® Glycosylated hemoglobin (HbA1c) test system is intended for quantitative determination of % hemoglobin A 1c (DCCT/NGSP) in venous whole blood. It is composed of Glycosylated hemoglobin (HbA1c) test kit and automatic immunoassay analyzer. Glycosylated hemoglobin (HbA1c) test kit consists of two reagents R1 and R2, which are liquid and ready to use. Reagent R1 contains glycine buffer and latex, and reagent R2 contains glycine buffer and two types of antibodies, Goat anti-mouse IgG, mouse anti-human HbAlc monoclonal antibody.

HP-AFS/1 Automatic Immunoassay Analyzer is made up of light absorption test module, scattered light test module, fluorescence test module, press components, data transmission interface and printer. And the absorption test module is made up of absorption light path unit, and lightabsorption sensor part. The scattered light test module is made up of scattered light path unit and scattered light sensor part.

న్. Intended Use/Indication for Use

The Hipro® Glycosylated Hemoglobin (HbA1c) Test System comprised of the Hipro Glycosylated hemoglobin (HbA1c) test kit and the HP-AFS/1 automatic immunoassay analyzer is used as an aid in diagnosis of diabetes mellitus, as an aid to identify patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. It is an in vitro diagnostics reagent system intended for quantitative determination of % hemoglobin A 1c (DCCT/NGSP) in venous whole blood.

| Item | Candidate Device:
Hipro® Glycosylated Hemoglobin
(HbA1c) Test System | Predicate Device:
D-100™ HbA1c
(K151321) |
|-----------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Regulation
number | 862.1373 | 862.1373 |
| Classification | II | II |
| Product Code | PDJ, LCP | PDJ, LCP |
| Item | Candidate Device:
Hipro® Glycosylated Hemoglobin
(HbA1c) Test System | Predicate Device:
D-100™ HbA1c
(K151321) |
| Intended
use/Indication
s for use | The Hipro® Glycosylated
Hemoglobin (HbA1c) Test System
comprised of the Hipro
Glycosylated hemoglobin
(HbA1c) test kit and the HP-AFS/1
automatic immunoassay analyzer is
used as an aid in diagnosis of
diabetes mellitus, as an aid to
identify patients who may be at risk
for developing diabetes mellitus,
and for the monitoring of long-term
blood glucose control in individuals
with diabetes mellitus. It is an in
vitro diagnostics reagent system
intended for quantitative
determination of % hemoglobin
Alc (DCCT/NGSP) in venous
whole blood. | The D-100™ HbA1c test 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 D-100
Hemoglobin Testing System.
Hemoglobin A1c measurements are used
as an aid in diagnosis of diabetes
mellitus, as an aid to identify patients
who may be at risk for developing
diabetes mellitus, and for the monitoring
of long-term blood glucose control in
individuals with diabetes mellitus.
The D-100™ HbA1c test is intended for
Professional Use Only. |
| Methodology | Nephelometry Immunoassay
Method | Ion-exchange HPLC |
| Testing
Environment | Prescription use | Prescription use |
| Specimen
type | Human Whole blood | Human Whole blood |
| Matrices | K2-EDTA | K2-EDTA
K3-EDTA
Potassium Oxalate/Sodium
Fluoride, Sodium Citrate,
Sodium Heparin, Lithium
Heparin |
| Reporting
Units | % HbA1c NGSP/DCCT | % HbA1c NGSP/DCCT and mmol/mol
IFCC |
| Measurement
range | 4.3-14% HbA1c | 3.5-20 % HbA1c
15-195 mmol/mol HbA1c |
| Item | Candidate Device:
Hipro® Glycosylated Hemoglobin
(HbA1c) Test System | Predicate Device:
D-100™ HbA1c
(K151321) |
| Reagent
Stability | 2-8°C for 12 months | On-board stability for the D-100 HbA1c
calibrator pack and reagents
demonstrated 90 days stability on the D-
100 Hemoglobin Testing System. |
| Traceability | The assigned HbA1c value of the
Glycosylated hemoglobin (HbA1c)
test kit is certified with the National
Glycohemoglobin
Standardization Program (NGSP). | The D-100 HbA1c test standardization is
traceable to the International Federation
of Clinical Chemistry (IFCC) reference
calibrators. The D-100 HbA1c assay is
NGSP certified. |

Substantial Equivalence Comparison 6.

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7. Non-clinical Performance Evaluation

The assigned HbA 1c values of the Automatic Immunoassay Analyzer (Model: HP-AFS/1) is certified with the National Glycohemoglobin Standardization Program (NGSP). See NGSP website for current certification at http://www.ngsp.org.

The following performance data were provided in support of the substantial equivalence determination.

7.1 Precision

Precision experiments were performed for the Glycosylated hemoglobin Test Kit based on CLSI Guideline EP5-A3 using four EDTA K2 whole blood samples with targeted HbA1c concentrations (5.2%, 6.4%, 8.0% and 12.3%), two controls (6% and 11%).Samples were analyzed on three Automatic Immunoassay Analyzer instruments using three lots of reagents. Each sample was analyzed in duplicate per run, two runs per day for 20 days. The samples were randomized in experiment. The results are shown below:

	Repeatability		Between run		Between day		Between lot		Total
Sample	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
5.2%	0.107	2.0%	0.032	0.6%	0.000	0.0%	0.000	0.0%	0.111	2.1%
6.4%	0.179	2.8%	0.000	0.0%	0.000	0.0%	0.029	0.5%	0.182	2.8%
8.0%	0.162	2.0%	0.000	0.0%	0.000	0.0%	0.020	0.2%	0.163	2.0%
12.3%	0.145	1.2%	0.051	0.4%	0.000	0.0%	0.017	0.1%	0.155	1.2%

Analyzer 1 precision:

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6%	0.176	2.9%	0.000	0.0%	0.000	0.0%	0.020	0.3%	0.177	2.9%
11%	0.189	1.7%	0.000	0.0%	0.000	0.0%	0.038	0.3%	0.193	1.8%

Analyzer 2 precision:

Sample	Repeatability		Between run		Between day		Between lot		Total
	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
5.2%	0.109	2.1%	0.000	0.0%	0.014	0.3%	0.000	0.0%	0.110	2.1%
6.4%	0.171	2.7%	0.000	0.0%	0.013	0.2%	0.000	0.0%	0.170	2.7%
8.0%	0.145	1.8%	0.000	0.0%	0.036	0.4%	0.000	0.0%	0.150	1.9%
12.3%	0.181	1.4%	0.026	0.2%	0.000	0.0%	0.000	0.0%	0.183	1.5%
6%	0.177	2.9%	0.000	0.0%	0.020	0.3%	0.027	0.5%	0.180	3.0%
11%	0.176	1.6%	0.000	0.0%	0.056	0.5%	0.000	0.0%	0.185	1.7%

	Analyzer 3 precision:

Sample	Repeatability		Between run		Between day		Between lot		Total
	SD	%CV	SD	%CV	SD	%CV	SD	%CV	SD	%CV
5.2%	0.093	1.8%	0.000	0.0%	0.011	0.2%	0.000	0.0%	0.094	1.8%
6.4%	0.163	2.6%	0.000	0.0%	0.033	0.5%	0.000	0.0%	0.166	2.6%
8.0%	0.243	3.0%	0.000	0.0%	0.000	0.0%	0.022	0.3%	0.244	3.0%
12.3%	0.145	1.2%	0.000	0.0%	0.063	0.5%	0.050	0.4%	0.166	1.3%
6%	0.192	3.2%	0.000	0.0%	0.000	0.0%	0.000	0.0%	0.192	3.2%
11%	0.147	1.3%	0.000	0.0%	0.039	0.4%	0.036	0.3%	0.156	1.4%

All analyzers precision:

| Sample | Mean
% | Repeatability
SD | Repeatability
%CV | Between run
SD | Between run
%CV | Between day
SD | Between day
%CV | Between lot
SD | Between lot
%CV | Between analyzer
SD | Between analyzer
%CV | Total
SD | Total
%CV |
|--------|-----------|---------------------|----------------------|-------------------|--------------------|-------------------|--------------------|-------------------|--------------------|------------------------|-------------------------|-------------|--------------|
| 5.2% | 5.23 | 0.103 | 2.0% | 0.014 | 0.3% | 0.000 | 0.0% | 0.000 | 0.0% | 0.010 | 0.2% | 0.103 | 2.0% |
| 6.4% | 6.34 | 0.171 | 2.7% | 0.000 | 0.0% | 0.000 | 0.0% | 0.011 | 0.2% | 0.061 | 1.0% | 0.171 | 2.7% |

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8.0%	8.03	0.188	2.3%	0.000	0.0%	0.000	0.0%	0.016	0.2%	0.031	0.4%	0.191	2.4%
12.3%	12.53	0.158	1.3%	0.011	0.1%	0.030	0.2%	0.028	0.2%	0.093	0.7%	0.188	1.5%
6%	6.04	0.182	3.0%	0.000	0.0%	0.000	0.0%	0.018	0.3%	0.006	0.1%	0.183	3.0%
11%	11.03	0.172	1.6%	0.000	0.0%	0.031	0.3%	0.030	0.3%	0.000	0.0%	0.177	1.6%

7.2 Method Comparison

A method comparison study was performed to compare the sample results from the candidate method, Hipro® Glycosylated hemoglobin (HbA1c) test kit on the Hipro HP-AFS/1 Automatic Immunoassay analyzer, to results from the Bio-Rad Hemoglobin Testing System. This study was conducted with the EDTA K2 whole blood samples.

One hundred and twenty (120) samples from the NGSP reference laboratory were used in the evaluation. These samples were measured by the NGSP reference laboratory using a Bio-Rad Hemoglobin Testing System (X axis) and by the Hipro® Glycosylated Hemoglobin (HbA1c) Test System (Y axis).

All acceptance criteria for method comparison were met. The difference plots show there is good agreement between the Hipro® Glycosylated Hemoglobin (HbA 1c) Test System and the NGSP Bio-Rad Hemoglobin Testing System.

The table below summarizes the bias between the Hipro Glycosylated Hemoglobin (HbA1c) Test System and the NGSP's Bio-Rad Hemoglobin Testing System.

| | Hipro Glycosylated Hemoglobin (HbA1c) Test
System |
|--------------------------------|------------------------------------------------------|
| Mean bias vs. NGSP Bio-
Rad | -0.0148 |
| Mean bias at lower 95% CI | -0.0470 |
| Mean bias at upper 95% CI | 0.0174 |

Bias at Concentration Data Summary

Concentration	Bias	% Bias
5.23%	-0.0262	-0.5%
6.34%	-0.0163	-0.26%
8.03%	-0.0012	-0.02%
12.53%	0.0388	0.31%

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7.3 Total Error

Using the results of bias estimation (%Bias) in the method comparison study and precision estimates in the precision study, the Total Error (TE) at the following concentrations (5.2%, 6.4%, 8.0% and 12.3%) near the cut-off was calculated as follows:

%TE =|%Bias| + 1.96 * %CV * (1+%Bias/100)

The results are presented in the tables below.

Concentration	%Bias	CV%	%TE
5.23%	0.5%	2.0	4.4
6.34%	0.26%	2.7	5.5
8.03%	0.02%	2.4	4.7
12.53%	0.31%	1.5	3.3

7.4 Linearity

One dilution series consisting of 9 levels were prepared using the EDTA K2 WB sample pools with HbA1c through mixing high and low concentrations at the upper and lower end of the measuring range. Samples were measured in triplicate and data analysis was done separately for each sample. Linear regression analysis was done according to EP6-2nd edition. Study result is provided in the table below.

| Analyte | Low End of
Linear Range (%) | High End of
Linear Range (%) | Slope | Intercept | R |
|---------|--------------------------------|---------------------------------|--------|-----------|-------|
| HbA1c | 4.3 | 14 | 1.0225 | -0.1524 | 0.999 |

7.5 Endogenous Interference

A study evaluated several endogenous substances for potential interference with the measure of % HbA1c. The following five endogenous substances were evaluated:

Pooled whole blood samples with two HbA1c levels, one near the medical decision level and one above it, were spiked with the maximum level of the above five interferents in separate preparations resulting in 10 spiked samples. Another pool, without interferent, was equally prepared. A 10-level dilution series was then created for each of the 10 spiked samples by using the interferent free pool as the diluting reagent.

The experiment was performed with one reagent lot, one Hipro HP-AFS/1 Automatic Immunoassay analyzer, and in a single run from the same calibration. The ten dilution series were

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tested ten-fold for % HbA1c using the EDTA K2 WB sample only.

The mean of the ten replicates was determined and compared to the result from the reference sample (no interfering substance). The comparison was evaluated as a percent deviation. An interferent will be significant if it causes >7% deviation of a measurement in terms of % HbA1c.

Interferent	Highest Tested Concentration without Significant Interference
Lipemia	600mg/dL
Unconjugated Bilirubin	60mg/dL
Conjugated Bilirubin	60mg/dL
Glucose	9000mg/dL
Rheumatoid Factor	100IU/mL
Total Protein	15g/dL

7.8 Drug Interference

A study evaluated several drugs for potential interference with the measurement of %HbA1c using the EDTA K2 WB sample. The following drugs were studied:

| Potential Interferent | Highest Tested Concentration without
Significant Interference |
|-----------------------|------------------------------------------------------------------|
| N-Acetylcysteine | 166mg/dL |
| Ampicillin-Na | 100mg/dL |
| Ascorbic acid | 30mg/dL |
| Cefoxitin | 250mg/dL |
| Heparin | 5000 U/L |
| Levodopa | 2mg/dL |
| Methyldopa | 2mg/dL |
| Metronidazole | 20mg/dL |
| Doxycycline | 5mg/dL |
| Acetylsalicylic acid | 100mg/dL |
| Rifampicin | 6mg/dL |
| Cyclosporin | 1.66mg/dL |
| Phenylbutazone | 40mg/dL |
| Acetaminophen | 20mg/dL |
| Ibuprofen | 50mg/dL |
| Theophylline | 10mg/dL |

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The 16 commonly used drugs listed above were added to native patient samples and examined for potential effect on % HbA1c determination. Drug interference testing was performed with EDTA K2 WB samples at 2 different HbA1c levels. The two different HbA1c concentrations will be approximately 6.5% and 8.5% HbA1c. Each drug was added in two defined concentrations with concentration 1 being several times (typically 5 times) the maximum daily dosage and concentration 2 being the maximum daily dosage level. Samples were measured in ten-fold using the Hipro® Glycosvlated Hemoglobin (HbA1c) Test System. The median value was compared to the reference value (HbA1c sample with no drug added) and the deviation from the reference was calculated.

Significant interference is defined as > ±7% deviation from the reference value observed. All acceptance criteria for drug interferences were met.

7.9 Cross-reactivity

Studies were performed to determine if the Hipro® Glycosylated hemoglobin (HbA 1c) test kit demonstrates cross-reactivity with any of the following hemoglobin fractions and glycated albumin.

Hb A0	Carbamylated Hb	Glycated Albumin
Labile Hb A1c	Acetylated Hb	Hb A1a+b

7.10 Hemoglobin variants

Hemoglobin variant testing was conducted to determine if there was any significant interference with any of the major hemoglobin variants and the Hipro® Glycosylated hemoglobin (HbA I c) test kit. Hemoglobin variants are structurally altered hemoglobin molecules with at least one amino acid exchange compared to the normal beta chain of hemoglobin. These changes are caused by mutations in the coding region of the globin genes which encode the protein part of hemoglobin. The most common hemoglobin variants are HbS, HbC, HbD and HbE. Moreover, in some conditions, the fetal hemoglobin HbF is elevated. Also, the erythrocytes of some patients (e.g. beta thalassemia minor) contain elevated levels of HbA2. Therefore, it is crucial to ensure accurate HbA1c results from patients who are carriers of these variants.

| Hemoglobin
Variant | Number of
Samples | Variant Concentration
Range (%) | Range of%HbA1c
Concentration |
|-----------------------|----------------------|------------------------------------|---------------------------------|
| HbC | 20 | 25 - 66.6% | 4.7-9.7 |
| HbD | 20 | 12.9 - 41.1% | 5.2-10.2 |
| HbE | 20 | 13.8 - 30.5% | 5.1-12.2 |
| HbF | 20 | 1.3 - 40.5% | 4.4-8.4 |

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HbS	20	16.8 - 76.9%	5.1-9.4
HbA2	20	3.1 - 6.4%	4.7-9.7

Each sample was tested twice on one Hipro HP-AFS/1 Automatic Immunoassay analyzer. Results obtained with the Hipro® Glycosylated hemoglobin (HbA1c) test kit on the Hipro HP-AFS/1 Automatic Immunoassay analyzer will be compared to those obtained with the reference methods. Results are summarized in the table below.

Hb Variant	~6.5 % HbA1c		~9.0% HbA1c
	Average	Range (%)	Average	Range (%)
HbC	-0.17	-3.77~3.77	2.27	-1.15~4.11
HbD	1.67	-1.79~5.08	2.10	1.16~3.03
HbE	1.58	-1.67~5.36	1.38	0.00~4.17
HbF	Interference was observed when the concentration of HbF is > 8%.
HbS	1.69	-3.08~6.15	1.20	1.08~1.35
HbA2	1.57	-1.79~5.00	-0.51	-1.02~0.00

8. Clinical testing

Not applicable.

1. Other information (such as required by FDA guidance/Test)
  Not applicable.

Conclusions Drawn from Non-Clinical and Clinical Tests

The Hipro® Glycosylated Hemoglobin (HbA1c) Test System is substantially equivalent to the legally marketed predicate device Bio-Rad D-100™ HbA1c (K151321).