ADVIA CHEMISTRY GLUCOSE OXIDASE ASSAY AND ADVIA CHEMISTRY GLUCOSE HEXOKINASE

K042015 · Bayer Healthcare, Diagnostics Division · CGA · Sep 29, 2004 · Clinical Chemistry

Device Facts

• Record ID: K042015
• Device Name: ADVIA CHEMISTRY GLUCOSE OXIDASE ASSAY AND ADVIA CHEMISTRY GLUCOSE HEXOKINASE
• Applicant: Bayer Healthcare, Diagnostics Division
• Product Code: CGA · Clinical Chemistry
• Decision Date: Sep 29, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1345
• Device Class: Class 2
• Attributes: Pediatric

Indications for Use

The Bayer ADVIA 1650 Glucose Oxidase and Glucose Hexokinase II assays are in vitro diagnostic devices for use in the quantitative determination of glucose levels in human cerebrospinal fluid (CSF), serum, plasma, and urine 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

The Bayer ADVIA Chemistry Glucose assays (Hexokinase and Oxidase) are in vitro diagnostic reagents used on the ADVIA 1650 Chemistry system. The device processes human CSF, serum, plasma, or urine samples. The Hexokinase assay uses a multi-component liquid reagent system (ATP, NAD, hexokinase, G6PDH) to catalyze glucose phosphorylation, resulting in NADH production proportional to glucose concentration. The Glucose Oxidase assay uses a single reagent (glucose oxidase, peroxidase, phenol, indicator) to produce a red-violet quinoneimine dye. Both assays measure absorbance changes via spectrophotometry. Used in clinical laboratory settings by trained personnel, the output is a quantitative glucose concentration value. This data assists clinicians in diagnosing and managing carbohydrate metabolism disorders. The device provides a diagnostic tool for monitoring glucose levels across multiple matrices.

Clinical Evidence

Bench testing only. Precision studies followed NCCLS EP5-A guidelines using CSF quality controls over 12 days (n=42-43), showing total imprecision CVs of 2.7-3.4%. Linearity was confirmed with ≤5% deviation across reportable ranges (0-700 mg/dL for Hexokinase; 0-750 mg/dL for Oxidase). Method comparison against the predicate using 55-56 patient CSF samples yielded R-values of 0.987 (Hexokinase) and 0.994 (Oxidase), with slopes of 1.026 and 0.973 respectively.

Technological Characteristics

In vitro diagnostic reagent assays for automated chemistry analyzer. Glucose Oxidase and Hexokinase II enzymatic methods. Analytical ranges: 0-750 mg/dL (Oxidase) and 0-700 mg/dL (Hexokinase).

Indications for Use

Indicated for quantitative glucose determination in human CSF, serum, plasma, and urine to diagnose and treat carbohydrate metabolism disorders, including diabetes mellitus, neonatal hypoglycemia, idiopathic hypoglycemia, and 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

• Roche Glucose Hexokinase (K953847)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
k042015

B. Purpose for Submission:
Addition of new matrix (cerebrospinal fluid)

C. Analyte:
Glucose

D. Type of Test:
Quantitative enzymatic tests

E. Applicant:
Bayer Healthcare LLC

F. Proprietary and Established Names:
Bayer ADVIA Chemistry Glucose Oxidase Assay
Bayer ADVIA Chemistry Glucose Hexokinase Assay

G. Regulatory Information:
1. Regulation section:
21 CFR §862.1345
2. Classification:
Class II
3. Product Code:
CGA and CFR
4. Panel:
Chemistry (75)

H. Intended Use:
1. Intended use(s):
Glucose hexokinase:
"The Bayer ADVIA 1650 Glucose Hexokinase II assay is an in vitro diagnostic device for use in the quantitative determination of glucose in human cerebrospinal fluid (CSF), serum, plasma (lithium heparin), and urine on the ADVIA 1650 Chemistry system. Such measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes

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mellitus, neonatal hypoglycemia, idiopathic hypoglycemia and insulin overdose.”

Glucose oxidase:
“The Bayer ADVIA 1650 Glucose Hexokinase II assay is an in vitro diagnostic device for use in the quantitative determination of glucose in human cerebrospinal fluid (CSF), serum, plasma (lithium heparin), and urine 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.”

2. Indication(s) for use:
See above.

3. Special condition for use statement(s):
For prescription use only

4. Special instrument Requirements:
Bayer ADVIA Chemistry Analyzers

I. Device Description:

Glucose hexokinase assay:
Three individual liquid components comprise the device. Reagents 1 and 2 contain buffer, sodium azide, ATP, and NAD, while the Reagent 2 Mix contains glucose-6-phosphate dehydrogenase and hexokinase in buffer. Reagent 2 Mix is added to Reagent 2 and mixed before being transferred into the R2 container on the ADVIA 1650.

Glucose oxidase assay:
This assay consists of a single, ready-to-use reagent containing buffer, phenol, indicator, sodium azide, glucose oxidase, and peroxidase.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Roche Glucose Hexokinase

2. Predicate K number(s):
K953847

3. Comparison with predicate:
Glucose hexokinase:
The predicate and the proposed assay have in common: the same intended use, the same reaction methodology and test principle, the same matrices (serum, plasma, urine, or CSF), storage conditions, and both are provided in a single

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system-specific vial of ready-to-use liquid. They differ in their manufacturer and in the instrument system they are used on.

**Glucose oxidase:**
The predicate and the proposed assay have in common the same intended use and the same matrices (serum, plasma, urine, or CSF). They differ in manufacturer, reaction methodology and test principle, and test format.

**K. Standard/Guidance Document Referenced (if applicable):**
The sponsor referenced NCCLS EP5-A for precision studies.

**L. Test Principle:**
Both assays are based on enzymatic reactions that are measured by changes in absorbance on a spectrophotometer.

**Glucose hexokinase:**
Glucose is phosphorylated by ATP in the presence of hexokinase. The glucose-6-phosphate that forms is oxidized in the presence of glucose-6-phosphate dehydrogenase causing the reduction of NAD to NADH. Thus the concentration glucose is directly proportional to the NADH concentration. The assay is read at 340 nm.

**Glucose oxidase:**
Glucose is oxidized in the presence of glucose oxidase. The resulting hydrogen peroxide reacts under catalysis of peroxidase with phenol and 4-aminophenazone to form a red-violet quinoneimine dye as an indicator.

**M. Performance Characteristics (if/when applicable):**

1. **Analytical performance:**
Analytical performance in plasma, serum, and urine were established in the predicate submissions (k011963 and k991576).

**a. Precision/Reproducibility:**
CSF precision studies were based on NCCLS EP5-A guidelines; over 12 days, two runs per day, with two levels of commercially available CSF quality controls tested in duplicate.

Precision of Bayer Glucose Hexokinase II Assay (CSF)

| | | Assayed Value (mg/dL) | Within Run | | Total Imprecision | |
| --- | --- | --- | --- | --- | --- | --- |
| Level | n= | | Std Dev | % CV | Std Dev | % CV |
| 1 | 43 | 37 | 0.6 | 1.7 | 1.2 | 3.1 |
| 2 | 43 | 60 | 0.7 | 1.2 | 1.6 | 2.7 |

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## Precision of Bayer Glucose Oxidase Assay (CSF)

| | | Assayed Value (mg/dL) | Within Run | | Total Imprecision | |
| --- | --- | --- | --- | --- | --- | --- |
| Level | n= | | Std Dev | % CV | Std Dev | % CV |
| 1 | 42 | 34 | 0.4 | 1.1 | 1.2 | 3.4 |
| 2 | 42 | 58 | 0.6 | 1.0 | 1.8 | 3.1 |

### b. Linearity/assay reportable range:

A high glucose CSF sample was diluted with saline to yield a series of dilutions that were used to test the linearity of both assays. The mean of three readings was used to calculate the recovery. Both assays had ≤5% deviation from the calculated value. This study supports the linear range claims for both assays: Glucose Hexokinase II 0-700 mg/dL, and Glucose oxidase 0-750 mg/dL.

### c. Traceability, Stability, Expected values (controls, calibrators, or method):

Stability was established in the predicate submissions.

### d. Detection limit:

Detection limits were established in the predicate submissions.

### e. Analytical specificity:

Analytical specificity was established in the predicate submissions.

### f. Assay cut-off:

Not applicable.

## 2. Comparison studies:

### a. Method comparison with predicate device:

Values obtained from patient CSF samples tested on an ADVIA 1650 analyzer were compared to the values obtained with the predicate assay on the predicate’s system.

## Method Comparison of Glucose Assays in CSF Matrix: Bayer Assays versus the Predicate

| | Hexokinase II | Oxidase |
| --- | --- | --- |
| Slope | 1.026 | 0.973 |
| Intercept | 1.25 | 4.47 |
| R value | 0.987 | 0.994 |
| N | 55 | 56 |
| Range | 39 – 214 mg/dL | 37 – 530 mg/dL |

### b. Matrix comparison:

Not applicable.

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3. Clinical studies:
a. Clinical sensitivity: Not applicable.
b. Clinical specificity: Not applicable.
c. Other clinical supportive data (when a and b are not applicable): Not applicable.

4. Clinical cut-off: Not applicable.

5. Expected values/Reference range: The expected values (Tietz, 3rd Edition) for these assay methods depend on the matrix:
Plasma/Serum: 74 to 106 mg/dL (normal population)
Urine: <0.5 g/day
CSF: 60-80 mg/dL pediatric, 40-70 mg/dL adults

N. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision.