COBAS INTEGRA GLUCOSE HK GEN 3 ASSAY

K092603 · Roche Diagnostics · CFR · Dec 4, 2009 · Clinical Chemistry

Device Facts

• Record ID: K092603
• Device Name: COBAS INTEGRA GLUCOSE HK GEN 3 ASSAY
• Applicant: Roche Diagnostics
• Product Code: CFR · Clinical Chemistry
• Decision Date: Dec 4, 2009
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 862.1345
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

In vitro test for the quantitative determination of glucose in serum, plasma, urine and cerebrospinal fluid (CSF). Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia and pancreatic islet cell tumors.

Device Story

The COBAS INTEGRA Glucose HK Gen. 3 Assay is an in vitro diagnostic reagent system used on COBAS INTEGRA systems. It utilizes an enzymatic hexokinase reference method to quantitatively measure glucose levels in serum, plasma, urine, and cerebrospinal fluid. The device is operated by laboratory professionals in clinical settings. The system processes samples to produce a quantitative glucose concentration value. Healthcare providers use these results to diagnose and monitor carbohydrate metabolism disorders, such as diabetes mellitus and various forms of hypoglycemia. The assay provides clinical utility by enabling accurate glucose assessment, which informs therapeutic decisions and patient management.

Clinical Evidence

Bench testing only. Verification and validation activities performed per design control procedures to assess impact of modified reaction timing on assay performance. Results demonstrated that predetermined acceptance criteria were met.

Technological Characteristics

Hexokinase (HK) enzymatic assay; photometric measurement. Operates on Roche COBAS INTEGRA systems. Modification: reduced reaction time post-R2 reagent addition. Wavelength, sample/reagent volumes, and calibration parameters unchanged. Software-based calculation of glucose concentration adjusted for new timing parameters.

Indications for Use

Indicated for the quantitative determination of glucose in human serum, plasma, and urine on Roche COBAS INTEGRA systems.

Regulatory Classification

Identification

A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.

Special Controls

*Classification.* Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.

Predicate Devices

• COBAS INTEGRA Glucose HK Gen. 3 Assay (K061048)

Submission Summary (Full Text)

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Glucose HK Gen. 3 Stat Assay

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| 510(k) Summary | 1092603 |
|----------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Introduction | According to the requirements of 21 CFR 807.92, the following information<br>provides sufficient detail to understand the basis for a determination of<br>substantial equivalence. |
| Submitter<br>name, address,<br>contact | Roche Diagnostics<br>9115 Hague Road<br>Indianapolis, IN 46250<br>(317) 521 - 3831 |
| | Contact Person: Kathie J. Goodwin |
| | Date Prepared: August 24th, 2009 |
| Device Name | Proprietary names: COBAS INTEGRA Glucose HK Gen. 3 Assay |
| | Common names: Glucose HK Gen. 3 |
| | Classification names: Glucose Test System |
| | Regulation Number: 21 CFR 862.1345 |
| | Product codes: CFR |
| Device<br>Description | The cassette COBAS INTEGRA Glucose HK Gen. 3 contains an in<br>vitro diagnostic reagent system intended for use on COBAS<br>INTEGRA SYSTEMS for the quantitative determination of glucose in<br>serum, plasma, urine, and cerebrospinal fluid (CSF). |
| | The test principle is an enzymatic reference method with hexokinase. |
| Intended use | In vitro test for the quantitative determination of glucose in serum, plasma,<br>urine and cerebrospinal fluid (CSF). |
| Indications for<br>Use | Glucose measurements are used in the diagnosis and treatment of<br>carbohydrate metabolism disorders including diabetes mellitus, neonatal<br>hypoglycemia, idiopathic hypoglycemia and pancreatic islet cell tumors. |

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Substantial equivalence The table below indicates the similarities between the modified COBAS INTEGRA Glucose HK Gen. 3 test and its predicate device COBAS INTEGRA Glucose HK Gen. 3, K061048.

#### Substantial equivalence -

#### comparison

| Feature | COBAS INTEGRA Glucose Gen. 3<br>Assay<br>Serum/Plasma Application | Predicate Device: COBAS<br>INTEGRA Glucose Gen. 3 Assay<br>Serum/Plasma Application<br>(K061048) |
|--------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------|
| Intended Use | In vitro test for the quantitative<br>determination of glucose in serum,<br>plasma, urine, and cerebrospinal fluid<br>(CSF) on COBAS INTEGRA<br>systems. | Same |
| Assay Protocol | Enzymatic reference method with<br>Hexokinase | Same |
| Sample Type | Serum<br>Plasma: Li-heparin, K2-EDTA, K3-<br>EDTA and fluoride plasma | Same |
| Calibrator | Calibrator f.a.s. | Same |
| Calibration<br>Frequency | Each lot and as required following<br>quality control procedures | Same |
| Controls | Precinorm U or Precinorm U Plus<br>And<br>Precipath U or Precipath U Plus | Same |
| Reagent Stability | Shelf life at 2 to 8°C<br>Integra 400/400 Plus: On-board in use<br>at 10-15°C for 8 weeks<br>Integra 800: On-board in use at 8°C<br>for 8 weeks | Same |
| Measuring<br>Range | Regular Applications:<br>4.32 - 720 mg/dL<br>Stat Applications:<br>4.32 - 541 mg/dL | Regular Applications:<br>2.16 - 720 mg/dL |

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Substantial equivalence –

comparison

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| comparison<br>Feature | COBAS INTEGRA Glucose Gen. 3 Assay<br>Serum/Plasma Application | | | Predicate Device: COBAS INTEGRA Glucose Gen. 3 Assay<br>Serum/Plasma Application (K061048) | | |
|--------------------------|----------------------------------------------------------------------|--------------|--------|--------------------------------------------------------------------------------------------|--------------|--------|
| Precision - Serum/Plasma | Serum – Regular Application:<br>Repeatability (Within-Run Precision) | | | Serum:<br>Within-Run Precision | | |
| | Sample | Mean (mg/dL) | CV (%) | Sample | Mean (mg/dL) | CV (%) |
| | HS1 | 64.3 | 0.69 | Level I | 80.7 | 0.41 |
| | HS2 | 120 | 0.78 | Level II | 225 | 0.47 |
| | HS3 | 665 | 0.70 | | | |
| | PNU | 90.8 | 0.58 | | | |
| | PPU | 247 | 0.59 | | | |
| | Intermediate (Between Run Precision) | | | Between Run | | |
| | Sample | Mean (mg/dL) | CV (%) | Sample | Mean (mg/dL) | CV (%) |
| | HS1 | 64.3 | 1.26 | Level I | 80.0 | 1.09 |
| | HS2 | 120 | 1.41 | Level II | 225 | 0.90 |
| | HS3 | 665 | 1.32 | | | |
| | PNU | 90.8 | 1.24 | | | |
| | PPU | 247 | 1.21 | | | |
| | Serum - Stat Application:<br>Repeatability (Within-Run Precision) | | | | | |
| | Sample | Mean (mg/dL) | CV (%) | | | |
| | HS1 | 64.7 | 0.61 | | | |
| | HS2 | 121 | 0.69 | | | |
| | HS3 | 487 | 0.74 | | | |
| | PNU | 91.4 | 0.58 | | | |
| | PPU | 249 | 0.57 | | | |
| | Intermediate (Between Run Precision) | | | | | |
| | Sample | Mean (mg/dL) | CV (%) | | | |
| | HS1 | 64.7 | 1.08 | | | |
| | HS2 | 121 | 1.40 | | | |
| | HS3 | 487 | 1.10 | | | |
| | PNU | 91.4 | 1.15 | | | |
| | PPU | 249 | 1.07 | | | |

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Substantial equivalence –

| Feature | COBAS INTEGRA Glucose Gen. 3 Assay<br>Serum/Plasma Application | | | Predicate Device: COBAS INTEGRA Glucose Gen. 3 Assay<br>Serum/Plasma Application (K061048) | | |
|-------------------|----------------------------------------------------------------------|--------------|--------|--------------------------------------------------------------------------------------------|--------------|--------|
| Precision - Urine | Urine – Regular Application:<br>Repeatability (Within-Run Precision) | | | Urine:<br>Within-Run Precision | | |
| | Sample | Mean (mg/dL) | CV (%) | Sample | Mean (mg/dL) | CV (%) |
| | HS1 | 8.65 | 2.28 | Level I | 15.0 | 1.35 |
| | HS2 | 17.3 | 1.05 | Level II | 43.6 | 0.64 |
| | HS3 | 672 | 0.53 | | | |
| | PNU | 90.8 | 0.58 | | | |
| | PPU | 247 | 0.59 | | | |
| | Intermediate (Between Run Precision) | | | Between Run | | |
| | Sample | Mean (mg/dL) | CV (%) | Sample | Mean (mg/dL) | CV (%) |
| | HS1 | 8.65 | 2.83 | Level I | 15.1 | 0.75 |
| | HS2 | 17.3 | 1.37 | Level II | 43.8 | 0.83 |
| | HS3 | 672 | 1.01 | | | |
| | PNU | 90.8 | 1.24 | | | |
| | PPU | 247 | 1.21 | | | |
| | Serum - Stat Application:<br>Repeatability (Within-Run Precision) | | | | | |
| | Sample | Mean (mg/dL) | CV (%) | | | |
| | HS1 | 8.58 | 2.71 | | | |
| | HS2 | 17.4 | 1.16 | | | |
| | HS3 | 476 | 0.64 | | | |
| | PNU | 91.4 | 0.58 | | | |
| | PPU | 249 | 0.57 | | | |
| | Intermediate (Between Run Precision) | | | | | |
| | Sample | Mean (mg/dL) | CV (%) | | | |
| | HS1 | 8.58 | 3.20 | | | |
| | HS2 | 17.4 | 1.65 | | | |
| | HS3 | 476 | 1.09 | | | |
| | PNU | 91.4 | 1.15 | | | |
| | PPU | 249 | 1.07 | | | |

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·

Substantial
equivalence –
comparison

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squares
comparison

| Feature | COBAS INTEGRA Glucose Gen. 3 Assay<br>Serum/Plasma Application | | | Predicate Device: COBAS INTEGRA Glucose Gen. 3 Assay<br>Serum/Plasma Application<br>(K061048) | | |
|---------------------------|------------------------------------------------------------------------------------------------|-----------------|--------|-----------------------------------------------------------------------------------------------|-----------------|--------|
| Precision - CSF | CSF - Regular Application:<br>Repeatability (Within-Run Precision) | | | CSF - Regular Application:<br>Within-Run Precision | | |
| | Sample | Mean<br>(mg/dL) | CV (%) | Sample | Mean<br>(mg/dL) | CV (%) |
| | Level I | 57.7 | 1.13 | Level I | 57.7 | 1.13 |
| | Level II | 168 | 1.49 | Level II | 168 | 1.49 |
| | CSF - STAT Application:<br>Repeatability (Within-Run Precision) | | | | | |
| | Sample | Mean<br>(mg/dL) | CV (%) | | | |
| | CSF 1 | 39.6 | 0.63 | | | |
| | CSF 2 | 283 | 0.39 | | | |
| | CSF 3 | 517 | 0.51 | | | |
| | PNU Plus | 92.4 | 0.53 | | | |
| | PPU Plus | 240 | 0.43 | | | |
| Analytical<br>Sensitivity | Lower Limits of Measurement:<br>Limit of Blank = 2.16 mg/dL<br>Limit of Detection = 4.32 mg/dL | | | Lower Detection Limit:<br>2.16 mg/dL | | |

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# Substantial
equivalence –

| comparison | | |
|---------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------|
| Feature | COBAS INTEGRA Glucose Gen. 3<br>Assay<br>Serum/Plasma Application | Predicate Device: COBAS<br>INTEGRA Glucose Gen. 3 Assay<br>Serum/Plasma Application<br>(K061048) |
| Limitations -<br>Interference | Icterus - No significant interference up to<br>an I index of 60 (approximate<br>concentration of conjugated and<br>unconjugated bilirubin: 60 mg/dL or<br>1026 umol/L)* | Same |
| | Hemolysis - No significant interference<br>up to an H index of 1200 (approximate<br>hemoglobin concentration: 1200 mg/dL<br>or 744 umol/L)* | Same |
| | Lipemia – No significant interference up<br>to an L index of 1900. There is a poor<br>correlation between the L index<br>(corresponds to turbidity) and the<br>triglyceride concentration.* | Same |
| | Other - In very rare cases gammopathy,<br>in particular type IgM (Waldenstrom's<br>macroglobulinemia), may cause<br>unreliable results. | Same |
| | Drugs - No interference was found at<br>therapeutic concentrations using common<br>drug panels. | Not Specified |
| | *measured at a glucose concentrations of<br>approximately 63.07 mg/dL and 297.33<br>mg/dL | |
| comparison<br>Feature | COBAS INTEGRA Glucose Gen. 3<br>Assay<br>Serum/Plasma Application | Predicate Device: COBAS<br>INTEGRA Glucose Gen. 3 Assay<br>Serum/Plasma Application<br>(K061048) |
| Expected Values | Plasma<br>Fasting: 74 - 109 mg/dL<br>(Per Thomas L. Blutglucose. In: Thomas L,<br>ed. Labor und Diagnose, 6th ed.<br>Frankfurt/Main: TH-Books, 2005:193-199.) | Plasma<br>Fasting: 70 - 115 mg/dL<br>(Per Thomas L, ed. Labor und Diagnose, 4th<br>ed. Marburg: Die medizinische<br>Verlagsgesellschaft 1992.) |
| | Urine<br>1st morning: 6 - 20 mg/dL<br>24-h urine: 6 - 17 mg/dL<br>(average of 1350 mL urine/24 h) | Same |
| | acc. to Tietz:<br>Serum,Plasma<br>Adults: 74 - 106 mg/dL<br>60-90 years: 82 - 115 mg/dL<br>>90 years: 75 - 121 mg/dL<br>Children: 60 - 100 mg/dL<br>Neonates (1 day): 40 - 60 mg/dL<br>Neonates (>1 day): 50 - 80 mg/dL | Same |
| | Urine<br>24-h urine: <0.5 g/24 h<br>Random Urine: 1 - 15 mg/dL<br>CSF<br>Children: 60 - 80 mg/dL<br>Adults: 40 - 70 mg/dL | Same |
| Method<br>Comparison -<br>Serum | Glucose values for human serum samples obtained on a COBAS INTEGRA 800 analyzer<br>with the COBAS INTEGRA Glucose HK Gen. 3 reagent were compared to those determined<br>on the same analyzer with the same reagent, but with the Stat application.<br>n=79 | |
| | Passing Bablok<br>y=0.997x + 0.033 mmol/L<br>$ \tau = 0.999 $<br>SD (md 95) = 0.067 | Linear Regression<br>y=0.997x + 0.032 mmol/L<br>r=1.00<br>Sy.x = 0.032 |
| Feature | COBAS INTEGRA Glucose Gen. 3<br>Assay<br>Serum/Plasma Application | Predicate Device: COBAS<br>INTEGRA Glucose Gen. 3 Assay<br>Serum/Plasma Application<br>(K061048) |
| Method<br>Comparison -<br>Urine | Glucose values for human urine samples obtained on a COBAS INTEGRA 800 analyzer<br>with the COBAS INTEGRA Glucose HK Gen. 3 reagent were compared to those determined<br>on the same analyzer with the same reagent, but with the Stat application.<br>n=50 | |
| | Passing Bablok<br>$y=1.00x + 0.002$ mmol/L<br>$\tau = 0.996$<br>SD (md 95) = 0.082 | Linear Regression<br>$y=1.00x +0.003$ mmol/L<br>r=1.00<br>Sy,x = 0.041 |

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# Substantial
equivalence –
comparison

equivalence.

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# Substantial
equivalence –

1 :

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Image /page/8/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circular pattern around the eagle. The logo is black and white.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

DEC 4, 2009

Roche Diagnostics c/o Kathie J Goodwin · Regulatory Affairs Consultant 9115 Hague Road, Po Box 50416 Indianapolis, IN 46250

Re: k092603

Trade/Device Name: Cobas Integra Glucose Hk Gen 3 Assay Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose test system. Regulatory Class: II Product Code: CFR Dated: November 3, 2009 Received: November 5, 2009

Dear: Ms. Goodwin:

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. Ilsting 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); 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).

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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 [phone]. 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 [phone]. 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 [phone] or ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

CFC

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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## Indications for Use Form

510(k) Number (if known): Kog 3603

Device Name: COBAS INTEGRA Glucose HK Gen. 3 Assay

Indications for Use:

In vitro test for the quantitative determination of glucose in serum, plasma, urine and cerebrospinal fluid (CSF).

Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia and pancreatic islet cell tumors.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

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

510(k) K092603

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