ST AIA-PACK HbA1c is designed for In Vitro Diagnostic Use Only for the quantitative measurement for percent concentration of Hemoglobin A1c (HbA1c) in EDTA whole blood on Tosoh AIA System Analyzer. HbA1c measurement is used in the management and treatment of diabetes.

Device Description

The ST AIA-PACK HbA1c is an enzyme immunoassay which, after pretreatment, is performed entirely in ST AIA-PACK HbA1c test cups. The whole blood sample must first be pretreated prior to immunocomplex formation between HbA1c and sheep anti-HbA1c polyclonal antibody. Sample pretreatment is performed to achieve complete hemolysis of erythrocytes and to expose carbohydrate part of HbA1c in the whole blood sample using ST AIA-PACK HbA1c PRETREATMENT SOLUTION (40 °C, 20 minutes). HbA1c present in the pretreated test sample is captured on the magnetic beads along with hemoglobin and bound with enzyme-labeled sheep anti-HbA1c polyclonal antibody in the AIA-PACK test cup. The beads are washed to remove the unbound materials and are then incubated with a fluorogenic substrate, 4-methylumbelliferyl phosphate (4MUP). The amount of enzyme-labeled polyclonal antibody that binds to the beads is directly proportional to the HbA1c concentration in the test sample. A standard curve using a range of known standard percent concentrations aligned to NGSP % is constructed and unknown HbA1c percent concentrations are calculated using this curve.

AI/ML Overview

Here's an analysis of the acceptance criteria and the study data provided for the ST AIA-PACK HbA1c device:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the studies performed and the comparison to the predicate device. Based on the provided text, the key performance characteristics evaluated and their results are:

Acceptance Criteria (Implied)	Device Performance (ST AIA-PACK HbA1c)
Correlation with Predicate Device
Slope (Deming Regression)	1.027 (95% CI: 1.006 to 1.047)
Intercept (Deming Regression)	-0.168 (95% CI: -0.326 to -0.011)
Correlation Coefficient (R)	0.99
Bias	0.025
Recovery	-4.9% to 2.2% (within a measuring range of 3-14% HbA1c)
Within-Run Precision (CV%)	1.1% to 1.9%
Total Precision (CV%)	1.9% to 4.0%
Assay Range	3.0 to 14%
Cross-reactivity with HbF	>10% (comparable to predicate's 15%)
Cross-reactivity with HbS	1 out of 5 variant HbS specimens was outside +/- 10% recovery (Predicate had "NO" cross-reactivity)

Note on Acceptance Criteria: The document implies that these performance metrics, particularly the correlation and precision values, were considered acceptable as part of demonstrating substantial equivalence to the predicate device. Specific numerical acceptance ranges for each metric are not explicitly stated in the provided text as "acceptance criteria." However, the strong correlation (R=0.99), small bias, and reported precision values are generally considered indicative of acceptable performance for diagnostic devices. The deviations in HbS cross-reactivity are noted, but the conclusion of substantial equivalence suggests it was deemed acceptable in the overall context.

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

Correlation Study (Test Set): 126 patient specimens.
Precision Study (Test Set): Three levels of unaltered EDTA whole blood specimens. Each level was assayed with 2 replicates, 2 times a day for 20 non-consecutive days, resulting in 40 runs and 80 determinants per specimen level.
Recovery Study (Test Set): The exact number of samples for the recovery study is not explicitly stated, but it involved "high sample and low sample" with similar hemoglobin concentrations.
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It refers to "patient specimens" and "unaltered Human EDTA Whole Blood Specimen," suggesting human samples.

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

The provided text describes analytical performance studies (correlation, recovery, precision) comparing the device to a predicate device or evaluating its inherent performance characteristics. There is no mention of "experts" in the traditional sense (e.g., radiologists interpreting images) for establishing ground truth in this context.

For this type of in vitro diagnostic device, the "ground truth" for comparative effectiveness is established by the reference method (the predicate device, Tosoh Automated Glycohemoglobin Analyzer HLC-723G7, which uses an HPLC method) or by the inherent properties of the samples themselves when evaluating precision and recovery. The predicate device's HbA1c values are used as the reference for the correlation study.

4. Adjudication Method for the Test Set

Not applicable. As described in point 3, this is an analytical device comparison, not a study involving human interpretation with adjudication.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. This type of study (MRMC, human readers with/without AI assistance) is typically performed for imaging diagnostics or other devices where human interpretation is a primary component of diagnosis. The ST AIA-PACK HbA1c is an in vitro diagnostic assay, and its performance is evaluated analytically, not through human reader performance.

6. Standalone (Algorithm Only Without Human-in-the-Loop) Performance

Yes, the studies reported (correlation, recovery, precision) represent the standalone performance of the ST AIA-PACK HbA1c device. It's an automated assay system; therefore, the reported performance metrics reflect the algorithm's and instrument's capabilities without human intervention influencing the measurement process itself.

7. Type of Ground Truth Used

Correlation Study: The ground truth was established by the predicate device, the Tosoh Automated Glycohemoglobin Analyzer HLC-723G7, which uses an HPLC method for HbA1c measurement. This is a recognized reference method.
Recovery Study: The ground truth for expected values was based on the prepared concentrations of high and low samples.
Precision Study: The ground truth for the mean HbA1c values was derived from the measurements of unaltered EDTA whole blood specimens themselves using the device over multiple runs, reflecting the inherent variability of the assay.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set." This device is an enzyme immunoassay with a predefined chemical and instrumental methodology, not a machine learning or AI model that typically requires a separate training set. Its calibration uses a "ST AIA-PACK HbA1c CALIBRATOR SET" (6 points aligned to IFCC and NGSP), which serves a similar function to training in establishing the measurement curve but is not a "training set" in the machine learning sense.

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

As noted above, there isn't a "training set" in the machine learning context. The calibration curve for the assay is established using the ST AIA-PACK HbA1c CALIBRATOR SET. These calibrators are described as "6 point aligned to IFCC and NGSP," meaning their HbA1c values are traceable to internationally recognized standards (International Federation of Clinical Chemistry and Laboratory Medicine) and reference methods (National Glycohemoglobin Standardization Program). This ensures the accuracy and standardization of the assay's measurements.

Summary

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AUG 27 2010

Section 5

510(K) Summary

从100304

HbAlc

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K100304

Tosoh Bioscience, Inc.

	510k Summary	AUG 27 2010
Tosoh ST AIA-PACK HbA1c
Date:	August 20, 2010
Submitter:	Tosoh Bioscience, Inc.3600 Gantz RoadGrove City, OH 43123
Contact Person:	Judith K. OgdenDirector, New Business and Technical DevelopmentTosoh Bioscience, Inc.6000 Shoreline Court, Suite 101,South San Francisco, CA 94080Phone: (650) 636-8112
Device Name:	ST AIA-PACK HbA1c
Classification Name:	Class IILCP21 CFR 864.7470 Glycosylated Hemoglobin Assay
Predicate Device:	K011434Tosoh Automated Glycohemoglobin AnalyzerHLC-723G7Manufactured by Tosoh Corporation.

HbAlc

. :

Section 5

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510(k) Summary

ST AIA-PACK HbA1c

According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.

Device Description:

The following products are required to use the Tosoh AIA-PACK HbA1c.

ST AIA-PACK HbA1c CALIBRATOR SET ST AIA-PACK HbA1c PRETREATMENT SOLUTION AIA-PACK HbA1c CONTROL SET

Device Intended Use:

HbAlc

Section 5

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Substantial Equivalence:

Similarities between ST AIA-PACK HbA1c and Tosoh Automated Glycohemoglobin Analyzer HLC-723G7

Specifications	ST AIA-PACK HbA1c	Tosoh AutomatedGlycohemoglobinAnalyzer HLC-723G7K011434
Intended Use	ST AIA-PACK HbA1c is designedfor In Vitro Diagnostic Use Only forthe quantitative measurement forpercent concentration ofHemoglobin A1c (HbA1c) in EDTAwhole blood on Tosoh AIA SystemAnalyzer. HbA1c measurement isused in the management andtreatment of diabetes.	Tosoh AutomatedGlycohemoglobinAnalyzer HLC-723G7K011434
Sample Type	EDTA whole blood	EDTA whole blood
Assay Range	3.0 to 14%	3.0 to 18.4%
Reference Range	3.8 to 6.0% for persons withoutdiabetes	4.2 to 5.8%
Calibrator Set	ST AIA-PACK HbA1c Calibrator Set 6point aligned to IFCC and NGSP	Hemoglobin A1c CalibratorSet 2 point aligned to IFCCand NGSP K011434
Cross reactivity to Hbvariants HbC, HbD	NO	NO

Differences between ST AIA-PACK HbA1c and Tosoh Automated Glycohemoglobin Analyzer HLC-723G7

Specifications	ST AIA-PACK HbA1c	Tosoh AutomatedGlycohemoglobinAnalyzer HLC-723G7K011434
Methodology	Immuno Enzymometric Assay(IEMA) using fluorescence detection	HPLC Method
Assay time	38 minutes (10 min. incubation and20 min. pretreatment)	2.2 minutes.
Cross reactivity withHbF	>10% of HbF	15%
Cross reactivity withHbS	1 out 5 variant HbS specimens wasoutside the criteria of +/- 10%recovery.	NO

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Comparative Analysis (Correlation)

The correlation for ST AIA-PACK HbA1c was determined based on guidance from CLSI Protocol EP9-A2.

The correlation study between Tosoh Automated Glycohemoglobin Analyzer HLC-723G7 (HPLC method) NGSP % (x) and ST AIA-PACK HbA1c NGSP % (y) was carried out using 126 patient specimens.

	Regression Analysis
	Deming	Regular
Slope:	1.027 (1.006 to 1.047)	1.020 (1.000 to 1.040)
Intercept:	-0.168 (-0.326 to -0.011)	-0.120 (-0.277 to -0.037)
	95% Confidence Intervals are shown in parentheses
Corr Coef (R):	0.99
Bias:	0.025
Points (Plotted/Total):	126/126
Result Ranges:	3.0 to 13.9% (AIA-1800); 2.8 to 14.6% (G7)

Recovery

A recovery study was performed for ST AIA-PACK HbA1c to support the measuring range of 3-14%* based on guidance from CLSI Protocol EP6-A. The maximum recovery was 2.2% and the minimum recovery was -4.9%.

Image /page/4/Figure/8 description: The image shows a scatter plot titled "Recovery". The x-axis is labeled "Expected value (%)", and the y-axis is labeled "Measured value (%)". A linear trendline is plotted through the data, and the equation of the line is y = 1.024x - 0.104, with an R-squared value of 0.999.

*: HbA1c (NGSP %)

Note: High sample and low sample have the same hemoglobin concentration (approximately 14 g/dL).

Section 5

HbA1c

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Precision

The precision for ST AIA-PACK HBA1c was determined based on guidance from CLSI Protocol EP5-A2.

Precision was assessed by assaying three levels of unaltered EDTA whole blood specimens. Estimates of total and within-run precision were obtained from measurements of 2 replicates in a single run, 2 times a day for 20 non-consecutive days. This equaled to a total of 40 runs and 80 determinants.

Within Run Precision

Specimen	Reagent Set # 1			Reagent Set # 2			Reagent Set # 3
	Mean(%)*	PooledSD (%)*	CV(%)	Mean(%)*	PooledSD (%)*	CV(%)	Mean(%)*	PooledSD (%)*	CV(%)
HWB-1**	5.3	0.096	1.8	5.5	0.099	1.8	5.5	0.090	1.6
HWB-2**	8.1	0.093	1.1	8.2	0.137	1.7	8.2	0.122	1.5
HWB-3**	13.1	0.244	1.9	13.0	0.192	1.5	13.0	0.204	1.6

Within-run precision was determined to be from 1.1 to 1.9%

*(%): HbA1c (NGSP%), ** HWB: Unaltered Human EDTA Whole Blood Specimen.

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Total precision

Specimen	Reagent Set # 1			Reagent Set # 2			Reagent Set # 3
	Mean(%)*	PooledSD (%)*	CV(%)	Mean(%)*	PooledSD (%)*	CV(%)	Mean(%)*	PooledSD (%)*	CV(%)
HWB-1**	5.3	0.175	3.3	5.5	0.120	2.2	5.5	0.109	2.0
HWB-2**	8.1	0.256	3.2	8.2	0.161	1.9	8.2	0.158	1.9
HWB-3**	13.1	0.528	4.0	13.0	0.314	2.4	13.0	0.310	2.4

Total precision was determined to be from 1.9 to 4.0%

*(%): HbAlc (NGSP%), ** HWB: Unaltered Human EDTA Whole Blood Specimen.

Limit of Detection (LoD) and Limit of Quantitation (LoQ):

This section is not applicable.

Standards:

Number	FDARecognitionNumber	Revision	Title
C28-A3NCCLS	7-202	09/08/09	How to Define and Determine ReferenceIntervals in the Clinical Laboratory; ApprovedGuideline - Second Edition
EP5-A2NCCLS	7-110	8/20/04	Evaluation of Precision Performance ofQuantitative Measurement Methods;Approved Guideline-Second Edition
EP6-ANCCLS	7-193	4/1/03	Evaluation of the Linearity of QuantitativeMeasurement Procedures; A StatisticalApproach; Approved Guideline
EP9-A2NCCLS	7-92	9/20/02	Method Comparison and Bias EstimationUsing Patient Samples; Approved Guideline -Second Edition

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K 100 304

Tosoh Bioscience, Inc.

Conclusion:

The Tosoh Bioscience, Inc. ST AIA-PACK HbA1c ASSAY is substantially equivalent to the Tosoh Automated Glycohemoglobin Analyzer HLC-723G7 (K011434), for the quantitative measurement of HbA1c in EDTA whole blood samples.

HbAlc

Section S

8 of 8

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/8/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three stripes forming its body and wings. The eagle faces right and is positioned within a circle. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the upper half of the circle.

Tosch Bioscience, Inc. c/o Ms. Judy Ogden 6000 Shoreline Court, Suite 101 South San Francisco, CA 94080

Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

AUG 2 7 2010

Re: K100304

Trade/Device Name: Tosoh ST AIA-PACK HbA1c Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP, JIT, JJY Dated: August 5, 2010 Received: August 6, 2010

Dear Ms. Ogden:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 requirements, including, but not limited to: registration and listing (21) CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market. :

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Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Courtney C. Harper, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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K100304

510(k) Number (if known):

Device Name:

Indication For Use:

K106304

Tosoh ST AIA-PACK HbA1c

ST AIA-PACK HbA1c is designed for IN VITRO DIAGNOSTIC USE ONLY for the quantitative measurement for percent concentration of Hemoglobin Alc (HbA1c) in EDTA whole blood on Tosoh AIA System Analyzer. HbA1c measurement is used in the management and treatment of diabetes.

Prescription Use 2 (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

Doug Rheinben.

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

100304

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510(k) Number (if known):

K100304

Device Name:

Indication For Use:

The ST AIA-PACK HbA1c CALIBRATOR SET is intended for IN VITRO DIAGNOSTIC USE ONLY for the calibration of ST AIA-PACK HbA1c Assay.

Tosoh ST AIA-PACK HbA1c Calibrator Set

Prescription Use _____________________________________________________________________________________________________________________________________________________________ く (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE, CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

Doug Thenken

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

K100304

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510(k) Number (if known):

K100304

Device Name:

Indication For Use:

The AIA-PACK HbA1c CONTROL SET is intended for IN VITRO DIAGNOSTIC USE ONLY for performing quality control procedures with the ST AIA-PACK HbA1c Assay.

Tosoh ST AIA-PACK HbAlc Control Set

Prescription Use _ V (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Doug Rheinheim

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

K100 304

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510(k) Number (if known):

K100304

Device Name:

Tosoh ST AIA-PACK HbAlc Pretreatment Solution

Indication For Use: .

The ST AIA-PACK HbA1c PRETREATMENT SOLUTION is intended for IN VITRO DIAGNOSTIC USE ONLY for the pretreatment of the patient samples or AIA-PACK HbA1c CONTROL SET for the ST AIA-PACK HbA1c assay.

Prescription Use __ V (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

Doug Rheinheim

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

K100304

Regulation Number and Section

§ 864.7470 Glycosylated hemoglobin assay.

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