ADVIA CHEMISTRY GLUH_3 REAGENTS

K120681 · Siemens Healthcare Diagnostics, Inc. · CFR · May 15, 2012 · Clinical Chemistry

Device Facts

• Record ID: K120681
• Device Name: ADVIA CHEMISTRY GLUH_3 REAGENTS
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: CFR · Clinical Chemistry
• Decision Date: May 15, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1345
• Device Class: Class 2
• Attributes: Pediatric

Indications for 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. For in vitro diagnostic use only. For prescription use only.

Device Story

ADVIA Chemistry Glucose Hexokinase 3 (GLUH 3) reagent is an in vitro diagnostic assay for quantitative glucose measurement. The device uses a two-component reagent system: Reagent 1 (buffer, ATP, NAD) is added to the sample to establish baseline absorbance and correct for interference; Reagent 2 is added to initiate glucose conversion via hexokinase and glucose-6-phosphate dehydrogenase enzymes. The resulting absorbance change at 340/410 nm is proportional to glucose concentration. Operated by laboratory personnel on ADVIA Chemistry systems, the assay provides quantitative results used by clinicians to diagnose and manage carbohydrate metabolism disorders. This specific submission expands the cleared plasma types to include Sodium Fluoride/Potassium Oxalate, in addition to previously cleared Li-Heparin and K-EDTA.

Clinical Evidence

No clinical studies performed. Evidence consists of analytical matrix comparison testing. 82 matched serum/plasma sample sets (56 patient, 26 spiked/diluted) were analyzed on the ADVIA 1650 Chemistry System. Linear regression yielded y = 1.011x + 0.78, r=0.999, with 95% CI for slope 1.003–1.019. All other analytical performance characteristics (precision, linearity, specificity) were previously cleared under k101854.

Technological Characteristics

Two-component liquid reagent system. Principle: Hexokinase/glucose-6-phosphate dehydrogenase enzymatic method. Analyte: Glucose. Assay range: 4-700 mg/dL. Instrumentation: ADVIA Chemistry systems. Sample types: Serum, urine, CSF, and plasma (Li-Heparin, K-EDTA, Na-Fluoride/K-Oxalate).

Indications for Use

Indicated for quantitative glucose determination in human serum, plasma, urine, and CSF to diagnose/treat 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 GLUH_3 Reagent (k101854)

Submission Summary (Full Text)

{0}

1

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k120681

B. Purpose for Submission:
Addition of another anticoagulant (sodium fluoride/potassium oxalate) as a sample type

C. Measurand:
Glucose

D. Type of Test:
Quantitative enzymatic test

E. Applicant:
Siemens Healthcare Diagnostics Inc.

F. Proprietary and Established Names:
ADVIA Chemistry Glucose Hexokinase (GLUH_3) Reagent

G. Regulatory Information:

| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| CFR – Hexokinase, Glucose | Class II | 21 CFR 862.1345
Glucose test system | 75 |

H. Intended Use:

1. Intended use(s):
See indications for use below.

2. Indication(s) for use:
For in vitro diagnostic use in the quantitative determination of glucose in human

{1}

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.

3. Special conditions for use statement(s):

For in vitro diagnostic use only. For prescription use only.

4. Special instrument requirements:

ADVIA 1650 Chemistry System

I. Device Description:

The ADVIA Chemistry Glucose Hexokinase_3 (GLUH_3) device consists of two component reagents. Reagent 1 contains buffer, ATP, and NAD. Reagent 2 contains glucose-6-phosphate dehydrogenase, hexokinase, buffer, ATP, and NAD. Reagents are ready to use and require no additional preparation. Reagents 1 and 2 contain sodium azide.

J. Substantial Equivalence Information:

1. Predicate device name(s):

ADVIA Chemistry GLUH_3 reagent

2. Predicate 510(k) number(s):

k101854

3. Comparison with predicate:

| Reagent Similarities and Differences | | |
| --- | --- | --- |
| Item | Candidate device: ADVIA Chemistry GLUH_3 Reagent | Predicate Device: ADVIA Chemistry GLUH_3 Reagent |
| Intended Use and indications for use | For in vitro diagnostic use in the quantitative determination of glucose in human serum, plasma, urine and CSF on the ADVIA Chemistry systems. Such measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal | Same |

{2}

| | hypoglycemia, idiopathic hypoglycemia, and insulin overdose. | |
| --- | --- | --- |
| Sample type | Serum, Urine, CSF, plasma (lithium heparin, potassium EDTA, and sodium fluoride/potassium oxalate) | Serum, Urine, CSF, plasma (lithium heparin, and potassium EDTA) |
| Reagent storage | 2 – 8 °C | Same |
| Test Methodology | Enzymatic method based on use of hexokinase and glucose-6-phosphate dehydrogenase enzymes. | Same |
| Measurement Range | 4-700 mg/dL | Same |

K. Standard/Guidance Document Referenced (if applicable):

None were referenced.

L. Test Principle:

This enzymatic method is based on the method by Slein using hexokinase and glucose-6-phosphate dehydrogenase enzymes. The ADVIA Chemistry Glucose Hexokinase_3 (GLUH_3) method is a two-component 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 reaction. Glucose is phosphorylated by adenosine triphosphate (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. The absorbance of NADH is measured as an endpoint reaction at 340/410 nm. The difference between the absorbance in Reagent 1 and Reagent 2 is proportional to the glucose concentration.

M. Performance Characteristics (if/when applicable):

The ADVIA Chemistry Glucose Hexokinase (GLUH_3) Reagent was previously 510(k) cleared under k101854. The only change to the device in the current submission is the addition of an additional anticoagulant, sodium fluoride/potassium oxalate. Additional testing was performed and submitted to demonstrate that the performance of sodium fluoride/potassium oxalate samples is substantially equivalent to the originally cleared device. All other performance data was previously reviewed under 510(k) number k101854, which is referenced below.

1. Analytical performance:

a. Precision/Reproducibility:

{3}

Previously cleared, see k101854

b. Linearity/assay reportable range:

Previously cleared, see k101854

The claimed measuring range of the device is from 4-700 mg/dL.

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

Previously cleared, see k101854

d. Detection limit:

Previously cleared, see k101854

e. Analytical specificity:

Previously cleared, see k101854

f. Assay cut-off:

Previously cleared, see k101854

2. Comparison studies:

a. Method comparison with predicate device:

Previously cleared, see k101854

b. Matrix comparison:

Eighty two matched serum plasma sample sets were compared with the device. Serum and plasma sample sets were each collected from the same patient. The plasma was collected in the anticoagulant being evaluated. The samples consisted of 56 unaltered patient samples and 26 samples that were either spiked with glucose or diluted in order to cover the complete measuring range of the device. Samples ranged in concentration from 5 – 691 mg/dL. Each sample was measured n=1 on the Siemens ADVIA 1650 Chemistry System. Linear regression was performed with the following results: y = 1.011x + 0.78 with r=0.999. The 95% confidence intervals were 1.003 – 1.019 for the slope and -1.18 to 2.73 for the y-intercept.

Urine and CSF samples are not derived from whole blood and are not directly comparable to serum and plasma samples so they were not tested in this evaluation.

4

{4}

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 following table lists the reference ranges for this assay

5

{5}

| Sample Type | | Reference Range |
| --- | --- | --- |
| Serum/Plasma | Adult: | 74–106 mg/dL (4.1–5.9 mmol/L) |
| | Newborn 1 day: | 40–60 mg/dL (2.2–3.3 mmol/L) |
| | Newborn > 1 day: | 50–80 mg/dL (2.8–4.4 mmol/L) |
| | Child: | 60–100 mg/dL (3.3–5.6 mmol/L) |
| Urine | | < 0.5 g/day |
| | | (2.78 mmol/day) |
| CSF | Adult: | 40–70 mg/dL (2.2–3.9 mmol/L) |
| | Infant/Child: | 60–80 mg/dL (3.3–4.4 mmol/L) |

Wu AHB. Tietz Clinical Guide to Laboratory Tests. 4th ed. St. Louis, MO: WB Saunders Company; 2006:444-450.

# N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

# O. Conclusion:

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