This reagent is intended for the in vitro quantitative determination of Fructosamine (glycated protein) in human serum when run on the Hitachi 704 automated chemistry analyzer. Measurements of fructosamine are used as an aid for short-term glycemic control related to diabetes management.

Device Description

Thermo DMA's fructosamine reagent is intended for the in vitro quantitative determination of Fructosamine in human serum. Under alkaline conditions, analytes with Amadori rearrangements, such as Fructosamine, have reducing activity that can be differentiated from other reducing substances. In the presence of carbonate buffer, fructosamine rearranges to the eneaminol form, which reduces Nitroblue tetrazolium (NBT) to a formazan. The absorbance at 530 nm is measured at two time points and the absorbance change is proportional to the fructosamine concentration. A 10-minute incubation is employed to allow fast reacting interfering reducing substances to react. Removal of endogenous glucose is not required due to the fact that a pH of greater than 11 is required for glucose to reduce NBT.

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Here's a breakdown of the acceptance criteria and study details for the Thermo DMA Fructosamine Assay, based on the provided text:

Thermo DMA Fructosamine Assay: Acceptance Criteria and Study Details

The provided document describes the Thermo DMA Fructosamine Assay, intended for the in vitro quantitative determination of Fructosamine in human serum. The study primarily focuses on demonstrating substantial equivalence to a predicate device (Sigma Diagnostics Fructosamine, Procedure No. 465) through method comparison and precision studies.

1. Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in a dedicated section. Instead, it presents performance data and then concludes that the device is "safe and effective" and that "No significant differences exist between the results obtained on samples analyzed utilizing the Thermo DMA Fructosamine when compared to those obtained when utilizing the predicate device in these studies."

Based on the presented data, the implicit acceptance criteria and the device's reported performance are summarized below:

Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance
Method Comparison	Strong correlation with the predicate device, with a slope close to 1, an intercept close to 0, and a high correlation coefficient.	Number of Sample Pairs: 49Range of Sample Results: 1.25 - 5.10 mmol/LMean (Sigma): 2.17Mean (Thermo DMA): 2.17Slope: 0.980Intercept: 0.039Correlation Coefficient: 0.998
Precision (Within Run)	Low Coefficient of Variation (CV%)	Level 1: Mean = 2.21 mmol/L, SD = 0.02 mmol/L, CV = 1.1% (N=20)Level 2: Mean = 3.47 mmol/L, SD = 0.04 mmol/L, CV = 1.1% (N=20)
Precision (Total Run)	Low Coefficient of Variation (CV%)	Level 1: Mean = 2.21 mmol/L, SD = 0.04 mmol/L, CV = 1.6% (N=10)Level 2: Mean = 3.42 mmol/L, SD = 0.04 mmol/L, CV = 1.2% (N=10)
Sensitivity	Ability to detect low concentrations of fructosamine.	Instrument Resolution: 0.02 mmol/L (based on A = 0.001)Serial Dilution: 0.1 mmol/L (based on control material)
Reportable Range	Ability to accurately measure fructosamine over a clinically relevant range, encompassing both normal and elevated levels.	Observed Range (asymptomatic samples): 1.6 - 2.6 mmol/L (N=31)Linearity: Demonstrated acceptable performance up to 6.0 mmol/L
Specificity (Bilirubin)	Absence of significant interference at clinically relevant bilirubin levels.	At 2.5 mmol/L fructosamine: Positive interference > 2.8 mg/dL bilirubin.At 4.1 mmol/L fructosamine: Positive interference > 13.5 mg/dL bilirubin. (Suggests interference at higher bilirubin levels, implying an implicit acceptance of lower levels/consideration for clinical context)
Specificity (Hemoglobin)	Absence of significant interference at clinically relevant hemoglobin levels.	"Hemolyzed samples are not recommended for use in this assay."At 2.5 mmol/L fructosamine: Negative interference > 83 mg/dL hemoglobin. (Indicates the need to avoid hemolyzed samples, suggesting this is a limitation rather than direct "acceptance" for hemolyzed samples)
Specificity (Ascorbic Acid)	Absence of significant interference at clinically relevant ascorbic acid levels.	At 2.5 mmol/L fructosamine: Negative interference > 4 mg/dL ascorbic acid.At 4.2 mmol/L fructosamine: Negative interference > 8 mg/dL ascorbic acid. (Suggests interference at higher ascorbic acid levels, implying an implicit acceptance of lower levels/consideration for clinical context)
Specificity (Lipemic Interference)	Absence of significant interference at clinically relevant triglyceride levels.	At 2.5 mmol/L fructosamine: Positive interference > 242 mg/dL triglycerides. (Suggests interference at higher triglyceride levels, implying an implicit acceptance of lower levels/consideration for clinical context)
Reference Ranges	Should align with established clinical reference ranges for non-diabetic and diabetic populations.	For 55 non-diabetic subjects: 1.9 - 2.9 mmol/L (95th percentile 2.7 mmol/L).For diabetic subjects: 2.1 - 5.0 mmol/L (10% of values below 2.7 mmol/L). (These are presented as external reference ranges, not directly "acceptance criteria" but used to frame the device's utility in a clinical context.)

2. Sample Size and Data Provenance

Test Set (Method Comparison): 49 sample pairs.
- Data Provenance: Not explicitly stated, but the comparison describes using a "commercially available calibrator as a reference" and "Serum samples were assayed in parallel," suggesting prospective collection for the purpose of this comparison study. The country of origin is not specified, but the submission is from the USA.
Test Set (Reportable Range/Observed Range): 31 human serum samples.
- Data Provenance: "asymptomatic with respect to fructosamine," suggesting these were normal, healthy individuals. Again, likely prospective for this study, country of origin not specified.
Test Set (Precision):
- Within Run: 20 data points for Level 1, 20 for Level 2.
- Total: 10 samples for Level 1, 10 for Level 2.
- Data Provenance: Not specified, but generally, precision studies use controls or pooled patient samples run repeatedly, likely prospective.

3. Number of Experts and Qualifications for Ground Truth for Test Set

Not Applicable. This is an in vitro diagnostic assay directly measuring a biochemical marker (fructosamine). The "ground truth" for the method comparison is the measurement obtained from the predicate device (Sigma Diagnostics Fructosamine). For sensitivity, precision, and linearity, the ground truth is derived from the known concentrations in control materials or the inherent properties of the measurement system. Expert consensus is not used to establish the "ground truth" for the quantitative values of fructosamine.

4. Adjudication Method for the Test Set

Not Applicable. As this is a quantitative chemical assay, expert adjudication in the traditional sense (e.g., for image interpretation) is not relevant. The "adjudication" is the direct comparison of quantitative results from the candidate device to the predicate device, or to known values from controls.

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

No. This type of study is typically relevant for medical imaging or subjective interpretation tasks where multiple human readers assess cases. This document describes an in vitro diagnostic assay, where the "reader" is an automated clinical chemistry analyzer (Hitachi 704). Therefore, an MRMC study is not applicable.

6. Standalone Performance (Algorithm Only)

Yes, implicitly. The entire study describes the standalone performance of the "Thermo DMA Fructosamine Assay" reagent when run on an automated analyzer. There is no human interpretation or intervention in the measurement process itself beyond loading samples and calibrators. The results presented (Method Comparison, Precision, Sensitivity, Reportable Range, Specificity) are all measures of the algorithm/reagent's performance in isolation from subjective human interpretation.

7. Type of Ground Truth Used

Comparator Device Measurements: For the method comparison study, the ground truth was essentially the quantitative results obtained from the predicate device (Sigma Diagnostics Fructosamine).
Known Concentrations/Control Material: For precision, sensitivity, and linearity, the "ground truth" was established by using control materials with known or expected fructosamine concentrations or by the inherent capability of the instrument to resolve small changes in absorbance.
Clinical Observation: For the "Reportable Range" study, 31 "asymptomatic" human serum samples were used to establish an observed normal range, implying a form of clinical ground truth for typical healthy levels.

8. Sample Size for the Training Set

The document does not mention a separate "training set". This type of assay (a chemical reagent kit) does not involve machine learning or AI models that typically require a distinct training set. The "training" for the assay would be the development and optimization of the chemical reactions and parameters by Thermo DMA, which precedes the validation studies described here.

9. How Ground Truth for Training Set was Established

Not Applicable. As there is no explicitly mentioned "training set" in the context of machine learning, the concept of establishing ground truth for it is not relevant to this submission. The development of the assay's methodology (e.g., optimal pH, incubation times, reagent concentrations) would have involved internal R&D, likely using chemically defined standards and characterized patient samples to ensure the reaction proceeds as intended and produces accurate results, but this is distinct from a "training set" for an AI algorithm.

Summary

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K0/2525

OCT = 4 2001

Thermo DMA

845 Avenue G East Arlington, TX 76011-7709

(817) 607-1700 Fax: (817) 649-2461 www.thermodma.com

510 (k) Summary

This Summary of Safety and Effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Submitter: Thermo DMA, Inc.

Address: 845 Avenue G East Arlington, Texas 76011

Contact Person: Thomas Dollar, Manager of Regulatory Affairs

The assigned 510 (k) number is K012525

Product Code: LCP, Assay, Glycosylated Hemoglobin

Device Name: Thermo DMA Fructosamine Assay

Device Class: II

Predicate Device: Sigma Diagnostics Fructosamine (Procedure No. 465)

Description and Intended Use: Thermo DMA's fructosamine reagent is intended for the in vitro quantitative determination of Fructosamine in human serum.

Clinical Significance 2,5:

In monitoring diabetic patients there may be a need for assays that are more sensitive than glycated hemoglobin to shorter-term alterations in average blood glucose levels. Fructosamine is reported to serve as an index to the average glycemic state during the previous several weeks. Therefore the test may represent a useful aid for short-term glycemic control related to diabetes management.

Methodology 1-4 :

Under alkaline conditions, analytes with Amadori rearrangements, such as Fructosamine, have reducing activity that can be differentiated from other reducing substances. In the presence of carbonate buffer, fructosamine rearranges to the eneaminol form, which reduces Nitroblue tetrazolium (NBT) to a formazan. The absorbance at 530 nm is measured at two time points and the absorbance change is proportional to the fructosamine concentration. A 10-minute incubation is employed to allow fast reacting interfering reducing substances to react. Removal of endogenous glucose is not required due to the fact that a pH of greater than 11 is required for glucose to reduce NBT.

Date of Preparation October 03, 2001

A Thermo Electron business

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Mothod Comparison: Comparison studies were carried out on a Hitachi 704 automated clinical chemistry analyzer using a commercially available calibrator as a reference. Serum samples were assayed in parallel and the results compared by the least regression method. The following statistics were obtained:

Number of Sample Pairs: 49 Range of Sample Results: 1.25 - 5.10 mmo1/L Mean of Results (Sigma) : 2.17 Mean of Results (Thermo DMA): 2.17 Slope: 0.980 Intercept: 0.039 Correlation Coefficient: 0.998

Precision:

Within Run
	Level 1	Level 2
Number of Data Points	20	20
Mean (mmol/L)	2.21	3.47
SD (mmol/L)	0.02	0.04
CV (%)	1.1%	1.1%
Total
	Level 1	Level 2
Number of Samples	10	10
Mean (mmol/L)	2.21	3.42
SD (mmol/L)	0.04	0.04
CV (%)	1.6%	1.2%

Sensitivity: Based on an instrument resolution of A = 0.001, the Thermo DMA Fructosamine reagent assay has a sensitivity of 0.02 mmol/L. Sensitivity studies based on serial dilutions of control material yield a sensitivity of 0.1 mmol/L.

Reportable Range: A study of 31 human serum samples, asymtomatic with respect to Pruccosamine provided an observed range of 1.6 - 2.6 mmol/L. Linearity studies conducted by Thermo DMA demonstrated acceptable performance up to 6.0 mmol/L.

Specificity: Interference studies conducted by Thermo DMA determined the following;

1. Bilirubin interference At a fructosamine level of 2.5 mmol/L a positive interference was observed at bilirubin levels greater than 2.8 mg/dL. At a fructosamine level of 4.1 mmol/L a positive interference was observed at bilirubin levels greater than 13.5 mg/dL.
1. Hemoglobin interference Hemolyzed samples are not recommended for use in this assay. At a fructosamine level of 2.5 mmol/L a negative interference was observed at hemoglobin levels greater than 83 mg/dL.

Date of Preparation October 03, 2001

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Specificity: + (continued)

1. Ascorbic acid interference At a fructosamine level of 2.5 mmol/L a negative interference was observed at ascorbic acid levels greater than 4 mg/dL. At a fructosamine level of 4.2 mmol/L a negative interference was observed at ascorbic acid levels greater than 8 ma/dL.
1. Lipemic interference At a fructosamine level of 2.5 mmol/L a positive interference is observed at Triglyceride levels greater than 242 mg/dL.

Reference Ranges: Some overlap occurs between ranges for healthy and diabetic individuals. Jury and Dunn reported a range of 1.9 - 2.9 mmol/L for 55 nondiabetic subjects, with the 95th percentile being 2.7 mmol/L. A range of 2.1 -5.0 mmol/L, meanwhile was found for a group of diabetic subjects with 10% of the values being below 2.7 mmol/I.

Conclusion: Analysis of the comparative measurements presented in the 510 (k) submission for this reagent, together with linearity and precision data collected in data presented demonstrates the Thermo DMA Fructosamine assay is safe and effective. No significant differences exist between the results obtained on samples analyzed utilizing the Thermo DMA Fructosamine when compared to those obtained when utilizing the predicate device in these studies .

References:

1. Howe JEA, Browning MCK, Fraser CG: Assay of serum fructosamine that minimizes standardization and matrix problems: Use to assess components of biological variation. Clin Chem 33:269, 1987
1. Armbruster DA: Fructosamine: Structure, analysis and clinical usefulness. Clin Chem 33:2153, 1987
Lloyd D. Maroles J. Simple colorimetry of glycated serum protein in a centrifugal analyzer. Clin 3. Chem 30:1686, 1984
Jury DR, Dunn PH: Laboratory assessment of a commercial kit for measuring fructosamine in বঁ serum. Clin Chem 33:158, 1987
Johnson RN, Metcalf PA, Baker JR: Fructosamine: A new approach to the estimation of serum ર્ગ glycosylprotein. An index of diabetic control. Clin Chem Acta 127:87, 1982

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract image of an eagle with three human profiles incorporated into its design.

Mr. Thomas Dollar Manager of Regulatory Affairs Thermo DMA 845 Avenue G East Arlington, TX 76011-7709

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT - 4 2001

K012525 Re:

Trade/Device Name: Thermo DMA Fructosamine Assay Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP Dated: July 31, 2001 Received: August 6, 2001

Dear Mr. Dollar:

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. Iisting 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 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807): labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed needicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 1 additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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/cdrb/dsma/dsmamain.html".

Sincerely yours,

Steven Autman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Image /page/5/Picture/0 description: The image shows the words "Thermo DMA" in a bold, sans-serif font. The word "Thermo" is on the left, and "DMA" is on the right. The letters are black, and the background is white. The image appears to be a logo or title.

A Thermo Electron business 845 Avenue G East Arlington, Texas 76011-7709 USA Telephone 817/607-1700

INDICATIONS FOR USE STATEMENT

510(k) Number (if known): K012525

Device Name: Thermo DMA Fructosamine Assay

Indications For Use: This reagent is intended for the in vitro quantitative determination of Fructosamine (glycated protein) in human serum when run on the Hitachi 704 automated chemistry analyzer. Measurements of fructosamine are used as an aid for short-term glycemic control related to diabetes management.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

	Kesia Alexander for Jean Cooper
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number	K012525

	OR
Prescription Use		Over-The-Counter Use
(Per 21 CFR 801.109)		(Optional Format 1-2-96)

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).