THERMO DMA FRUCTOSAMINE ASSAY, MODEL 7500-135/235

K012525 · Thermo Dma, Inc. · LCP · Oct 4, 2001 · Hematology

Device Facts

• Record ID: K012525
• Device Name: THERMO DMA FRUCTOSAMINE ASSAY, MODEL 7500-135/235
• Applicant: Thermo Dma, Inc.
• Product Code: LCP · Hematology
• Decision Date: Oct 4, 2001
• Decision: SESE
• Submission Type: Abbreviated
• Regulation: 21 CFR 864.7470
• Device Class: Class 2

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.

Device Story

Thermo DMA Fructosamine Assay is an in vitro diagnostic reagent for quantitative determination of fructosamine in human serum. Used on Hitachi 704 automated clinical chemistry analyzer. Principle: alkaline conditions cause fructosamine to rearrange to eneaminol form, reducing Nitroblue tetrazolium (NBT) to formazan. Absorbance measured at 530 nm at two time points; absorbance change proportional to fructosamine concentration. 10-minute incubation allows fast-reacting interfering substances to react; high pH (>11) prevents glucose interference. Operated by laboratory technicians in clinical settings. Output provides index of average glycemic state over previous weeks, aiding clinicians in diabetes management and short-term glycemic control decisions.

Clinical Evidence

Bench testing only. Method comparison study (n=49) on Hitachi 704 analyzer showed correlation coefficient of 0.998, slope 0.980, intercept 0.039. Precision studies (within-run CV 1.1%, total CV 1.2-1.6%) and linearity (up to 6.0 mmol/L) demonstrated acceptable performance. Sensitivity is 0.02 mmol/L. Interference studies evaluated bilirubin, hemoglobin, ascorbic acid, and triglycerides.

Technological Characteristics

In vitro diagnostic reagent; colorimetric assay. Principle: NBT reduction to formazan in carbonate buffer (pH >11). Form factor: liquid reagent for automated clinical chemistry analyzers (Hitachi 704). Measurement: absorbance at 530 nm. No specific materials of construction or connectivity specified.

Indications for Use

Indicated for the quantitative determination of fructosamine in human serum to aid in short-term glycemic control monitoring for diabetic patients. No specific age or gender contraindications provided.

Regulatory Classification

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.

Predicate Devices

• Sigma Diagnostics Fructosamine (Procedure No. 465)

Submission Summary (Full Text)

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K0/2525

# OCT = 4 2001

# Thermo DMA

845 Avenue G East Arlington, TX 76011-7709

[phone] Fax: [phone] 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.
- 2. 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)

- 3. 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.
- 4. 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
- 2. 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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. 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 [phone] or [phone] 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 [phone]

# 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) |