ADVIA CHEMISTRY GLUCOSE HEXOKINASE_3 (GLUH_3) REAGENT, MODELS REF 05001429

K101854 · Siemens Healthcare Diagnostics · CFR · Mar 7, 2011 · Clinical Chemistry

Device Facts

• Record ID: K101854
• Device Name: ADVIA CHEMISTRY GLUCOSE HEXOKINASE_3 (GLUH_3) REAGENT, MODELS REF 05001429
• Applicant: Siemens Healthcare Diagnostics
• Product Code: CFR · Clinical Chemistry
• Decision Date: Mar 7, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1345
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

For in vitro diagnostic use in the quantitative determination of glucose in human serum, plasma, urine, and cerebrospinal fluid (CSF) on the ADVIA 1650 Chemistry System. Such measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and insulin overdose.

Device Story

ADVIA Chemistry Glucose Hexokinase_3 (GLUH_3) is a two-component enzymatic reagent system for the ADVIA 1650 Chemistry System. It measures glucose in human serum, plasma (Li-heparin, K-EDTA), urine, and CSF. Principle: Hexokinase phosphorylates glucose with ATP; glucose-6-phosphate dehydrogenase oxidizes the product, reducing NAD to NADH. The system measures NADH absorbance at 340/410 nm as an endpoint reaction. The difference in absorbance between Reagent 1 (buffer, ATP, NAD) and Reagent 2 (enzymes, buffer, ATP, NAD) is proportional to glucose concentration. Used in clinical laboratories by trained personnel. Output is a quantitative glucose concentration (mg/dL). Results assist clinicians in diagnosing and managing carbohydrate metabolism disorders. The device includes automated dilution for samples exceeding the upper reportable range.

Clinical Evidence

Bench testing only. Precision studies (N=80 per serum/urine control, N=40 per CSF control) showed CVs ranging from 0.3% to 2.4%. Linearity confirmed across 3-833 mg/dL range. Method comparison against predicate (N=51-113 samples per matrix) showed high correlation (r=1.000) and slopes near 1.0. Matrix comparison for K-EDTA and Li-Heparin plasma confirmed equivalence. No clinical data required.

Technological Characteristics

Two-component liquid reagent containing hexokinase, glucose-6-phosphate dehydrogenase, ATP, NAD, and sodium azide. Photometric detection at 340/410 nm. Operates on ADVIA 1650 Chemistry System. Traceable to NIST SRM 965a. Storage: 2-8°C; 18-month shelf life; 60-day on-board stability. Standards: CLSI EP5-A2 (precision), CLSI EP17-A (LoD/LoB).

Indications for Use

Indicated for quantitative glucose measurement in human serum, plasma, urine, and CSF for diagnosis and treatment of carbohydrate metabolism disorders (diabetes mellitus, neonatal/idiopathic hypoglycemia, insulin overdose).

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

• ADVIA Chemistry Glucose Hexokinase II reagent (k042015)

Submission Summary (Full Text)

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# MAR - 7 2011

#### 510(k) Summary of Safety and Effectiveness for the

#### ADVIA® 1650 Chemistry Glucose Hexokinase 3 (GLUH 3) method

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.

A. 510(k) Number:

B. Date of Preparation: July 26, 2010

#### C. Proprietary and Established Names:

ADVIA® 1650 Chemistry Glucose Hexokinase 3 (GLUH 3) reagent

# D. Applicant:

Siemens Healthcare Diagnostics Inc., 511 Benedict Ave, Tarrytown, NY 10591

Kira Gordon, Sr. Regulatory Affairs Specialist

Office: [phone] Fax: [phone]

# E. Regulatory Information:

ADVIA 1650 Chemistry Glucose Hexokinase 3 Reagent

- 1. Regulation section: 21 CFR & 862.1345 Glucose test system.
- 2. Classification: Class II
- 3. Product Code: CFR. Hexokinase, Glucose
- 4. Panel: Clinical Chemistry

#### F. Predicate Device:

ADVIA 1650 Chemistry Glucose Hexokinase 3 reagent is substantially equivalent to the ADVIA Chemistry Glucose Hexokinase II reagent cleared under k042015

#### G. Device Description:

The ADVIA 1650 Chemistry Glucose Hexokinase 3 (GLUH 3) method uses a twocomponent reagent. Sample is added to Reagent 1, which contains the buffer, ATP, and NAD. Absorbance readings of the sample in Reagent 1 are taken and are used to correct for interfering substances in the sample. Reagent 2 is added, which initiates the conversion of glucose and the development of absorbance at 340/410 nm. The difference between the absorbance in Reagent 1 and Reagent 2 is proportional to the glucose concentration.

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# H. Intended Use:

For in vitro diagnostic use in the quantitative determination of glucose in human serum, plasma, urine and CSF on the ADVIA 1650 Chemistry system. Such measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and insulin overdose

# I. Substantial Equivalence Information:

The new device (Glucose Hexokinase 3 reagent) and the predicate device (Glucose Hexokinase II reagent) were compared. A comparison of the important features between the new device and the predicate device is provided in the following table:

| Item | Device | Predicate |
|-----------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Analyte | Glucose | Same |
| Intended Use | For <i>in vitro</i> diagnostic use in the<br>quantitative determination of glucose in<br>human serum, plasma, urine and CSF on<br>the ADVIA 1650 Chemistry system.<br>Such measurements are used in the<br>diagnosis and treatment of carbohydrate<br>metabolism disorders including diabetes<br>mellitus, neonatal hypoglycemia,<br>idiopathic hypoglycemia, and insulin<br>overdose | Same |
| Sample type | human serum, plasma, urine and CSF<br>(plasma - Li Heparin and K EDTA) | human serum, plasma, urine and CSF<br>(plasma – Li Heparin) |
| Instrument to<br>be used | ADVIA 1650 Chemistry | ADVIA 1650 Chemistry |
| Method<br>Principle | based on the method by Slein using<br>hexokinase and glucose-6-phosphate<br>dehydrogenase enzymes. | Same |
| Calibrators | Siemens Healthcare Diagnostics<br>Chemistry Calibrator REF 09784096 | Same |
| Reportable<br>range | 4 -700 mg/dL | 0 -700 mg/dL |
| Traceability | Standard reference material 965a from<br>NIST | Same |
| Format | Liquid | Concentrate |
| Reagents | Two: R1 and R2 | Three: R1, R2 and R2 mix |
| Interfering<br>Substances * | Bilirubin-NSI to 30 mg/dL at glucose<br>level of 54 mg/dL<br>Hemoglobin-NSI up to 1000 mg/dL at<br>glucose level of 52 mg/dL<br>Lipemia (Intralipid)-NSI to 1000 mg/dL | Bilirubin-NSI to 25 mg/dL at glucose<br>level of 80 mg/dL<br>Hemoglobin-NSI up to 500 mg/dL at<br>glucose level of 80 mg/dL<br>Lipemia (Intralipid)-NSI to 500 mg/dL<br>at glucose level of 80 mg/dL |
| | | |
| Precision<br>(total) | 0.8% at 87 mg/dL (serum)<br>0.7% at 297 mg/dL (serum)<br>1.1% at 49 mg/dL (urine)<br>1.9% at 301 mg/dL (urine)<br>1.0% at 56 mg/dL (CSF)<br>0.8% at 97 mg/dL (CSF) | 2.2% at 74.7 mg/dL (serum)<br>2.0% at 247.6 mg/dL (serum)<br>4.1% at 45.8 mg/dL (urine)<br>3.6% at 266.7 mg/dL (urine)<br>3.1% at 36.9 mg/dL (CSF)<br>2.7% at 60.2 mg/dL (CSF) |
| Accuracy /<br>Correlation | Serum:<br>$Y = 1.001x + 0.3$ ; N=99 r=1.000 (vs.<br>ADVIA 1650 (ADVIA GLUH reagent)<br><br>Plasma (Li-Heparin):<br>$Y = 1.001x + 0.2$ , N=88; r=1.000<br><br>Plasma (K-EDTA)<br>$Y = 1.002x - 0.0$ , N=87; r=1.000<br><br>CSF:<br>$Y = 1.005x - 0.1$ , N=113; r=1.000<br><br>Urine:<br>$Y = 0.989x - 0.3$ , N=51; r=1.000 | Serum:<br>$Y = 1.02x - 1.84$ ; N=194 r=0.998 (vs.<br>ADVIA 1650 (ADVIA glucose-single<br>reagent formulation))<br><br>Plasma (Li Heparin):<br>$Y = 1.00x - 0.09$ , N=35; r=1.000<br><br>CSF:<br>$Y = 1.03x - 1.25$ , N=55; r=0.987<br><br>Urine:<br>$Y = 0.97x - 7.44$ , N=99; r=0.999 |

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* NSI = No Significant Interference. A percentage effect > 10% is considered significant interference.

# J. Conclusion:

Comparative testing of the ADVIA 1650 Chemistry Glucose Hexokinase_3 reagent demonstrates substantially equivalent performance to the ADVIA Chemistry Glucosc Hexokinasc II reagent cleared under K042015.

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

HAR 0 7 2011

Siemens Healthcare Diagnostics, Inc. c/o Kira Gordon Senior Regulatory Affairs Specialist 511 Benedict Avenue. Tarrytown, NY. 10591. USA

Re: k101854

Trade/Device Name: ADVIA Chemistry Glucose Hexokinase (GLUH_3) Reagent Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose Test System Regulatory Class: Class II Product Code: CFR Dated: February 23, 2011 Received: February 24, 2011

Dear Ms. Gordon

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 (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 [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/Resourcesfor You/Industry/default.htm.

Sincerely yours.

CA

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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# Indication for Use

KIDI854 510(k) Number (if known):

Device Name:

ADVIA® Chemistry GLUH_3 Reagent

Indication For Use:

For in vitro diagnostic use in the quantitative determination of glucose in human serum, plasma, urine and CSF on the ADVIA 1650 Chemistry system. Such measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and insulin overdose.

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)

Carol C. Benett

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K101854