The GlycoMark™ test provides quantitative measurement of 1,5-anhydroglucitol (15AG) in serum or plasma. The test is for professional use, and is indicated for the intermediate term monitoring of glycemic control in people with diabetes.

Device Description

The GlycoMark™ reagents provide for a fully automated enzymatic test for 15AG. The assay requires the two-reagent boxed set (Reagent 1 and Reagent 2) and the 15AG standard (purchased separately). A two-level control set ("Low" and "High") is also available separately.

AI/ML Overview

The provided text describes the 510(k) summary for the GlycoMark™ device. It includes nonclinical and clinical data, but it does not specify acceptance criteria for the device's performance in a traditional sense (e.g., a specific sensitivity or specificity threshold that must be met). Instead, it presents performance characteristics and clinical study results primarily for comparison with a predicate device and to demonstrate safety and effectiveness for its intended use.

However, I can extract the reported device performance and infer "acceptance" by its successful 510(k) clearance by the FDA, implying these performance characteristics were deemed adequate.

Here's a breakdown of the requested information based on the provided text:

1. A table of acceptance criteria and the reported device performance

Since explicit "acceptance criteria" are not stated as quantitative targets that the device must meet (e.g., "sensitivity must be >X%"), I will present the reported performance characteristics. The FDA's clearance (K031604) implies these performance results were acceptable for market entry.

Characteristic	Inferred Acceptance Criteria (Meeting predicate similarities & clinical relevance)	Reported Device Performance (GlycoMark™)
Analytical Sensitivity	Should be sufficient to detect clinically relevant levels of 15AG.	0.2 µg/mL (defined as mean 15AG concentration plus one standard deviation of a saline blank).
Within-Assay Precision	Comparable to predicate or clinically acceptable for monitoring. (Predicate: Intra-run %CVs less than 2%)	Between 1.28 %CV and 3.83 %CV at two levels (low 4.6 µg/mL, high 14.7 µg/mL).
Between-Assay Precision	Comparable to predicate or clinically acceptable for monitoring. (Predicate: Between-day %CVs between 3% and 4%)	Between 0.79 %CV and 3.71 %CV with two control samples and two serum pool samples (concentrations 4.7 µg/mL to 27.0 µg/mL).
Linearity	Should be linear across the expected physiological range of 15AG.	Linear up to at least 110 µg/mL 15AG.
Sample Stability	Samples should be stable under appropriate storage conditions for practical laboratory use.	Serum samples stable at room temperature or 2-8°C for up to seven days; endures up to three freeze/thaw cycles.
Interfering Substances	Should not be significantly affected by common interfering substances encountered in blood samples.	Not affected by hemoglobin up to 125 mg/dL, triglycerides up to 1153 mg/dL, and bilirubin up to 53.3 mg/dL.
Clinical Performance	Should demonstrate responsiveness to changes in glycemic control, similarly to or with advantages over existing markers, for intermediate-term monitoring.	Demonstrated significant changes vs. baseline (p<0.05, Wilcoxon signed-rank test) at Visit 2, similar to fructosamine and glucose, and earlier than A1C (which showed significant change at Visit 3). Indicated for intermediate-term monitoring of glycemic control.

2. Sample size used for the test set and the data provenance

Sample Size for Test Set (Clinical Data): 77 patients with diabetes (both Type 1 and Type 2).
Data Provenance: The study was a "prospective, longitudinal study." The text does not specify the country of origin, but given the submission is to the FDA from Tomen America, Inc. in New York, N.Y., it is highly probable the study was conducted in the USA or adhering to international standards accepted by the FDA.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The device is an assay for a biomarker (1,5-anhydroglucitol). The "ground truth" for evaluating its performance isn't typically established by expert consensus on image interpretation, but rather through comparison with other established clinical markers and the physiological changes observed in patients.

Number of Experts: Not applicable in the context of establishing a ground truth for a quantitative biomarker assay in the same way it would be for an AI diagnostic imaging device.
Qualifications of Experts: Not applicable. The "ground truth" here is the actual physiological state of glycemic control, as measured by various established biomarkers (A1C, fructosamine, glucose) and changes in patient treatment.

4. Adjudication method for the test set

Not applicable for a quantitative biomarker assay. Adjudication methods like "2+1" are typically used in studies involving human interpretation (e.g., radiology reads) where discrepancies need to be resolved. The clinical study tracked changes in biomarker levels over time.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This device is a standalone assay, not an AI-assisted diagnostic tool for human readers.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the GlycoMark™ device is a standalone in vitro diagnostic (IVD) assay. Its performance characteristics (analytical sensitivity, precision, linearity, stability, interference) and clinical correlation were evaluated as an automated enzymatic test without human interpretation as part of the measurement process. The results are quantitative measurements of 15AG.

7. The type of ground truth used

The "ground truth" in the clinical study was the physiological state of glycemic control, as evidenced by:

Changes in A1C levels (a long-term glycemic control marker, used as a reference).
Changes in fructosamine levels (an intermediate-term glycemic control marker).
Changes in glucose levels.
The initiation or modification of antihyperglycemic treatments in patients with suboptimal glycemic control.

The GlycoMark™'s performance was assessed by its ability to reflect changes in this physiological state, and its responsiveness compared to parallel measurements of A1C, fructosamine, and glucose.

8. The sample size for the training set

Not applicable. This is an IVD assay, not a machine learning model that requires a training set in that sense. The "development" and "optimization" of the assay chemistry would involve laboratory experimentation rather than a data training set.

9. How the ground truth for the training set was established

Not applicable, as it is not an AI/ML model with a discrete training set.

Summary

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Image /page/0/Picture/0 description: The image shows the date SEP 22 2003. The text is in a bold, sans-serif font. The date is likely extracted from a document or photograph.

TOMEN

TOMEN AMERICA INC

1285 AVENUE OF THE AMERICA NEW YORK, N.Y. 10019-6028

TELEPHONE (212) 397-4600 FACSIMILE (212) 582-2007

510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is K031604.

807.92 (a)(1): Name:	Tomen America, Inc.
Address:	1285 Avenue of the AmericasNew York, NY 10019
Phone:	(212) 397-4600
FAX:	(212) 582-2007
Contact:	Mr. Shuhei Kato

807.92 (a)(2): Device name- trade name and common name, and classification

Trade name:	GlycoMark™
Common Name:	1,5-anhydroglucitol (15AG) Assay

Classification: Assay, Glycosylated Hemoglobin; 21 CFR 864.7470

807.92 (a)(3): Identification of the legally marketed predicate device

GlycoMark™ is substantially equivalent to existing A1C assays, namely the Tina-Quant A1C Assay, K934070 (Roche Diagnostics Corporation, Indianapolis, IN). Both assay systems are indicated for use by people with diabetes to monitor glycemic control.

807.92 (a)(4): Device Description

Page 1 of 4

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807.92 (a)(5): Intended Use

807.92 (a)(6): Technological Similarities and Differences to the Predicate

Similarities / Differences Between GlycoMark™™ and A1C Assays
CHARACTERISTIC	GlycoMark™™	Tina-Quant A1CK934070
Intended Use	Quantitativemeasurement of15AG in serum orplasma	Quantitative measurement of thepercent of glycated hemoglobin inwhole blood
Indications for Use	Indicated for theintermediate termmonitoring ofglycemic control inpeople with diabetes	Used in the management andtreatment of diabetes, for monitoringlong term glycemic control
Risk to Patient	Not a critical analyte- reflects glucosemonitoring over time	Not a critical analyte - reflects glucosemonitoring over time
Sample	Serum or plasma	Whole blood
Sample Preparation	Standard processingfor serum or plasma	Prepare hemolysate with hemolyzingreagent
Calibration	Parameters andcalibration factorsprovided byinstrumentationcompany	Parameters and calibration factorsprovided by instrumentation company
Methodology	Colorimetric assay;sample plus theaddition of Reagent 1(pretreatment) andReagent 2 (colorreagent)	Turbidimetric inhibition immunoassayfor hemolyzed whole blood
Detection Method/Throughput	System adapted forhigh-throughput,laboratory analyzers,e.g., Hitachi 917	System adapted for high-throughput,laboratory analyzers, e.g., Hitachi 917
Testing Environment	Professional use	Professional use
Precision	Intra-run %CVsbetween 1% and 4%,between-day %CVsbetween 1% and 4%	Intra-run %CVs less than 2%,between-day %CVs between 3% and4%

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807.92 (b)(1): Brief Description of Nonclinical Data

Evaluations were performed for analytical sensitivity, within-assay precision, between-assay precision, linearity, sample stability, and interfering substances. Those resulting data are summarized below.

To determine the analytical sensitivity, twenty-one replicates of a saline reagent blank were analyzed as unknowns in one assay run. The analytical sensitivity is estimated to be 0.2 µg/ml, and this is defined as the mean 15AG concentration plus one standard deviation.

Within-assay precision, when evaluated at two levels of 15AG (low- 4.6 ug/mL) and high- 14.7 ug/mL), ranged from 1.28 %CV to 3.83 %CV. Between assay precision, when evaluated with two control samples and two serum pool samples (concentrations from 4.7 ug/mL to 27.0 ug/mL) ranged from 0.79 %CV to 3.71 %CV.

Results from linearity studies demonstrated that the GlycoMark™ test is linear up to at least 110 ug/mL 15AG. Results from sample stability studies demonstrated that serum samples may be stored at room temperature or at 2-8° C for up to seven days prior to analysis, and may endure up to three freeze/thaw cycles prior to analysis.

Results from interference testing showed that the GlycoMark™ test is not affected by hemoglobin up to 125 mg/dL (in the case of hemolyzed samples), triglycerides up to 1153 mg/dL (in the case of lipemic samples), and bilirubin up to 53.3 mg/dL (in the case of icteric samples).

807.92 (b)(2): Brief Description of Clinical Data

A prospective, longitudinal study was performed with 77 patients with diabetes (both type 1 and type 2). The patients exhibited suboptimal glycemic control (A1C level greater than or equal to 7%) at study entry, and these patients were monitored for eight weeks following initiation or modification of antihyperglycemic treatments. Measurements for GlycoMark, A1C, fructosamine, and glucose were performed every two weeks for the first four weeks (Visits 1-3) and then at Week 8 (Visit 4).

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The figure presents the mean values for each marker by visit. An asterisk (*) denotes significant changes vs. baseline values (p<0.05, Wilcoxon signed-rank test). Significant changes vs. baseline appeared at Visit 2 for GlycoMarkTM, fructosamine, and glucose; whereas a significant change did not appear until Visit 3 for A1C.

Image /page/3/Figure/1 description: This figure shows four different plots of data. The x-axis is labeled "Visit" and ranges from 0 to 5. The y-axis on the left is labeled "ug/ml 15AG or HbA1C (%)" and ranges from 0 to 10. The y-axis on the right is labeled "umol/L Fructosamine or mg/dL Glucose" and ranges from 150 to 450. The four plots are labeled "Glycomark", "A1C", "Fructosamine", and "Glucose".

807.92 (b)(3): Conclusions from Nonclinical and Clinical Testing

Nonclinical and clinical testing was performed for the GlycoMark™ assay. The assay was shown to be safe and effective for its intended use, and was substantially equivalent to other intermediate and long term markers of glycemia.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES" arranged in a circular pattern around the symbol. The logo is black and white.

SEP 2 2 2003

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Erika B. Ammirati RAC, MT(ASCP) Regulatory Consultant Tomen America, Inc. 1285 Avenue of the Americas New York, NY 10019-6028

K031604 Trade/Device Name: GlycoMarkTM Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: NOZ: JIS; JJX Dated: August 29, 2003 Received: September 2, 2003

Dear Ms. Ammirati:

Re:

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 either class II (Special Controls) or class III (PMA), 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); and good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820).

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Page 2 -

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.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Autman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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STATEMENT OF INTENDED USE

510(K) Number (if known): K031604

Device Name: GlycoMark™

Indications for Use:

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(PLEASE DO NOT WRITE BELOW THIS LINE- CONTINUE ON ANOTHER PAGE AS NEEDED)

Prescription Use(Per 21 CFR 801.109)✓	OR	Over -the-Counter Use __
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Division Sign-Off
for Ican Cooper

Office of In Vitro Diagnostic Device
Evaluation and SafetyKO3

1604

510(k).

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).