ACCU-CHEK AVIVA PLUS BLOOD GLUCOSE MONITORING SYSTEM

K101299 · Roche Diagnostics · LFR · Sep 21, 2011 · Clinical Chemistry

Device Facts

• Record ID: K101299
• Device Name: ACCU-CHEK AVIVA PLUS BLOOD GLUCOSE MONITORING SYSTEM
• Applicant: Roche Diagnostics
• Product Code: LFR · Clinical Chemistry
• Decision Date: Sep 21, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1345
• Device Class: Class 2
• Attributes: Pediatric

Indications for Use

The ACCU-CHEK Aviva Plus Blood Glucose Monitoring System is intended to be used for the quantitative measurement of glucose (sugar) in fresh capillary whole blood samples drawn from the fingertips, forearm, upper arm, or palm. The ACCU-CHEK Aviva Plus Blood Glucose Monitoring System is intended to be used by a single person and should not be shared. The ACCU-CHEK Aviva Plus Blood Glucose Monitoring System is intended for self testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid to monitor the effectiveness of diabetes control. The ACCU-CHEK Aviva Plus Blood Glucose Monitoring System should not be used for the diagnosis of or screening of diabetes or for neonatal use. Alternative site testing should be done only during steady - state times (when glucose is not changing rapidly). The ACCU-CHEK Aviva Plus Test Strips are for use with the ACCU-CHEK Aviva Blood Glucose Meter to quantitatively measure glucose (sugar) in fresh capillary whole blood samples drawn from the fingertips, forearm, upper arm, or palm.

Device Story

System measures capillary whole blood glucose; utilizes ACCU-CHEK Aviva meter and Aviva Plus test strips with modified GDH-PQQ enzyme. User applies 0.6 μL blood sample to strip; meter applies AC voltages at four frequencies to assess sample/environment, followed by DC voltage to measure glucose-proportional current. System provides hematocrit and temperature-compensated results. Intended for single-patient home use; operated by patient. Output displayed on meter; aids in diabetes management. Includes code key for calibration; supports data transmission to external devices.

Clinical Evidence

Clinical performance evaluated via user study with 195 subjects (fingertip) and 314 (palm), 155 (forearm), 156 (upper arm). Accuracy compared to hexokinase reference method. Results showed high correlation (r=0.989 for fingertip). System accuracy for glucose ≥75 mg/dL met 99.2% within ±20% for fingertip samples. Bench testing included precision, linearity, interference, hematocrit (10-65%), and altitude (up to 10,000 ft) studies.

Technological Characteristics

Disposable dry reagent test strip; electrochemical sensing; Mut. Q-GDH enzyme; PQQ coenzyme; electrochemical mediator; meter-based display; single-patient use design.

Indications for Use

Indicated for people with diabetes for self-testing of capillary whole blood glucose from fingertips, forearm, upper arm, or palm to monitor diabetes control. Contraindicated for neonates, diagnosis/screening of diabetes, and patients who are dehydrated, hypotensive, in shock, critically ill, or in a hyperosmolar state.

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

• ACCU-CHEK Aviva System (K060620 and K043474)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number:
k101299

B. Purpose for Submission:
New blood glucose monitoring system (new Aviva Plus glucose test strips with a modified GDH-PQQ methodology are intended to be used with the cleared ACCU-CHECK Aviva meter)

C. Measurand:
Capillary whole blood Glucose

D. Type of Test:
Quantitative amperometric assay, glucose dehydrogenase (mutant GDH- PQQ)

E. Applicant:
Roche Diagnostics

F. Proprietary and Established Names:
ACCU-CHEK Aviva Plus Blood Glucose Monitoring System

G. Regulatory Information:
1. Regulation section:
21 CFR §862.1345, Glucose Test System
2. Classification:
Class II
3. Product code:
NBW (System, Test, Blood Glucose, Over The Counter)
LFR (glucose dehydrogenase, glucose)

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4. Panel:
Clinical Chemistry (75)

H. Intended Use:

1. Intended use(s):
See Indications for Use below.

2. Indication(s) for use:
The ACCU-CHEK Aviva Plus Blood Glucose Monitoring System is intended to be used for the quantitative measurement of glucose (sugar) in fresh capillary whole blood samples drawn from the fingertips, forearm, upper arm, or palm. The ACCU-CHEK Aviva Plus Blood Glucose Monitoring System is intended to be used by a single person and should not be shared.

The ACCU-CHEK Aviva Plus Blood Glucose Monitoring System is intended for self testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid to monitor the effectiveness of diabetes control. The ACCU-CHEK Aviva Plus Blood Glucose Monitoring System should not be used for the diagnosis of or screening of diabetes or for neonatal use. Alternative site testing should be done only during steady - state times (when glucose is not changing rapidly).

The ACCU-CHEK Aviva Plus Test Strips are for use with the ACCU-CHEK Aviva Blood Glucose Meter to quantitatively measure glucose (sugar) in fresh capillary whole blood samples drawn from the fingertips, forearm, upper arm, or palm.

3. Special conditions for use statement(s):
- For in vitro diagnostic use only
- Device is for over-the-counter (single patient use) only and should not be shared
- Not intended for use on neonates
- Not for the diagnosis of or screening for diabetes mellitus
- Not to be used for patients who are dehydrated, hypotensive, in shock, critically ill or in a hyperosmolar state

4. Special instrument requirements:
ACCU-CHEK Aviva Blood Glucose Meter

I. Device Description:
The ACCU-CHEK Aviva Plus Blood Glucose Monitoring System consists of:

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- ACCU-CHEK Aviva Blood Glucose Meter (cleared under k060620)
- ACCU-CHEK Aviva Plus test strips with modified GDH – PQQ technology
- Code key
- ACCU-CHEK MultiClix Lancing Device with 12 Lancets

ACCU-CHEK Aviva Control solution is required but sold separately

## J. Substantial Equivalence Information:

1. Predicate device name(s):

ACCU-CHEK Aviva

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

k060620

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Indications for Use | Same | For the quantitative measurement of glucose in fresh capillary whole blood |
| Measuring Range | 20 – 600 mg/dL | 10 – 600 mg/dL |
| Hematocrit Range | 10 – 65% | 10 – 70% |
| Detection Method | Same | Amperometry |
| Measuring Time | Same | 5 seconds |
| Sample Volume | Same | 0.6 μL |
| Capillary Sample Sites | Fingertip, forearm, upper arm, palm | Fingertip, forearm, upper arm, palm thigh, calf |
| Coding | Same | Code Key |
| Memory | Same | 500 stored results |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Enzyme | Modified Glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ) | Glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ) |
| Intended Users | Single patient use | Single patient and healthcare professional |
| Sample Type | Capillary blood only | Rx use: capillary, venous, arterial, and neonatal blood
OTC use: capillary blood only |

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

- CLSI EP7 - Interference Testing in Clinical Chemistry
- CLSI EP5 – Evaluation of Precision Performance of Quantitative Measurement Methods
- ISO15197:2003 - In vitro diagnostic test systems – Requirements for blood-glucose monitoring systems for self-testing in managing diabetes mellitus.

L. Test Principle:

When an ACCU-CHEK® Aviva Plus test strip is inserted into the ACCU-CHEK® Aviva meter, a small alternating current (AC) is applied until the application of blood causes a spike in the conductivity to be observed at the measurement and sample - sufficiency electrodes. Both are used to assure an adequate sample has been applied. The meter then applies a series of AC voltages at four frequencies and reads the AC responses. These carry information about the sample type and environmental temperature; they also allow the system to perform various internal quality checks. After the AC measures are completed, a small (DC) voltage is applied and current is observed which is proportionate to the glucose. The AC and DC information are then combined to provide a hematocrit and temperature compensated glucose result.

The enzyme on the test strip, a variant of glucose dehydrogenase, converts the glucose in the blood sample to gluconolactone. This reaction creates a harmless DC electrical current that the meter interprets for the blood glucose result. The sample and environmental conditions are also evaluated using a small AC signal.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Repeatability Precision (Within Vial)

A total of 50 individual strip vials per each of three strip lots were used for data collection. These vials were separated into 5 sets of 10 vials each and assigned to 1 of 5 venous blood samples at varying concentrations.

Ten runs were performed on each sample, with an n = 10 replicates collected per vial/strip lot. This resulted in a total of 100 replicates collected for each strip lot and glucose level tested. Results are summarized in the table below.

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| Level | 1 | | | 2 | | | 3 | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Lot 1 | Lot 2 | Lot 3 | Lot 1 | Lot 2 | Lot 3 | Lot 1 | Lot 2 | Lot 3 |
| Mean | 42.7 | 42.5 | 40.9 | 90.0 | 90.7 | 87.1 | 121.9 | 121.2 | 120.4 |
| SD | 2.1 | 1.5 | 1.5 | 2.9 | 3.9 | 2.8 | 4.1 | 5.5 | 4.0 |
| CV(%) | 4.8 | 3.4 | 3.6 | 3.3 | 4.3 | 3.3 | 3.3 | 4.6 | 3.3 |
| n | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
| Level | 4 | | | 5 | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Lot 1 | Lot 2 | Lot 3 | Lot 1 | Lot 2 | Lot 3 |
| Mean | 185.9 | 182.4 | 183.1 | 312.8 | 306.5 | 309.7 |
| SD | 6.3 | 6.6 | 5.4 | 10.7 | 12.9 | 10.2 |
| CV(%) | 3.4 | 3.6 | 3.0 | 3.4 | 4.2 | 3.3 |
| n | 100 | 100 | 100 | 100 | 100 | 100 |

Intermediate Precision (Day-to-Day)

Intermediate precision was assessed by analyzing three levels of commercial linearity controls. Results were collected over 10 consecutive days by two operators using three strip lots. Results are summarized in the table below.

| Level | 1 | 2 | 3 |
| --- | --- | --- | --- |
| mean | 45.1 | 118.7 | 307.4 |
| SD | 1.4 | 3.0 | 7.7 |
| CV (%) | 3.1 | 2.5 | 2.5 |
| n | 300 | 300 | 300 |

b. Linearity/assay reportable range:

Linearity was evaluated using 8 spiked whole blood samples with glucose concentrations ranging from 18 to $632\mathrm{mg / dL}$ (18, 38, 63, 81, 153, 314, 470, and $632\mathrm{mg / dL}$ ) as measured by the reference method. Per lot, each sample was measured 4 times out of 8 strip vials for a total of 32 replicates per level.

Results are summarized in the table below:

| Strip Lot | Slope | Intercept | Corr Coeff (r) | Range of recoveries |
| --- | --- | --- | --- | --- |
| 1 | 0.992 | -0.649 | 1.000 | 98 – 105% |
| 2 | 0.977 | -0.842 | 1.000 | 96 – 103% |
| 3 | 1.011 | -0.415 | 1.000 | 98 – 107% |

The claimed range of measurement for this device is 20 to $600\mathrm{mg / dL}$ glucose.

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

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The Aviva Plus system is calibrated to a hexokinase method on a laboratory analyzer. A method comparison was performed using this method as the comparative method. See Comparison studies in 2a below.

The controls recommended for the ACCU-CHEK Aviva Plus Blood Glucose Monitoring System were cleared under k043474.

The sponsor provided a protocol and acceptance criteria to verify the closed-vial stability (shelf life) and open vial stability of the test strips. The stability protocols and acceptance criteria were reviewed and found to be acceptable. The sponsor claims a closed-vial (shelf life) and open-vial stability of 18 months when stored at 36 – 86° F (2 – 30° C)

d. Detection limit:

The claimed reportable range for the system is 20 – 600 mg/dL. This range was verified by the linearity study (M.1.b) above.

e. Analytical specificity:

To assess potential interference, whole blood samples were spiked with glucose at concentrations of approximately 25, 55, 120, 350, and 500 mg/dL and split into a control sample and a test sample. Various endogenous and exogenous substances were then added to the test sample only. Concentrations tested were at least three times the upper therapeutic level (for drugs) or three times the highest expected concentration (for endogenous substances). Concentrations listed in CLSI EP7-A2 were used when available. For substances not listed in CLSI EP7-A2, other published references were consulted. Each combination of glucose concentration and interferent concentration was analyzed 16 times per strip lot using three strip lots for a total of 48 measurements per each combination of glucose and interferent. The % difference between the test sample and the control sample was calculated. The sponsor defines no significant interference as ≤ 10%.

Three compounds were found to cause significant interference:

| Compound Name | Concentration at Which Significant Interference Criteria was Seen (mg/dL) |
| --- | --- |
| Triglycerides | >1800 |
| Galactose | >15 |
| Ascorbic Acid | >3 |

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The sponsor includes the following in the limitations section of the labeling:

- Lipemic samples (triglycerides) in excess of 1800 mg/dL may produce elevated results.
- Blood concentrations of galactose >15 mg/dL will cause overestimation of blood glucose results.
- Intravenous administration of ascorbic acid which results in blood concentrations of ascorbic acid >3 mg/dL will cause overestimation of blood glucose results.

The remaining compounds tested were found to not cause significant interference, as follows:

| Compound Name | Concentration at Which No Significant Interference Criteria was Seen (mg/dL) |
| --- | --- |
| β - Carotene | 0.6 |
| 5-Fluorocytosine | 30 |
| Acarbose | 60 |
| Acetaminophen | 20 |
| Acetazolamide | 6 |
| Acetone | 60 |
| Acetylprocainamide | 15 |
| Acetylsalicylic Acid | 60 |
| Acyclovir | 5 |
| Albumin | 5000 |
| Albuterol | 25 |
| Allopurinol | 5 |
| Aminocaproic Acid | 0.08 |
| Amiodarone HCI | 5 |
| Amitriptyline HCI | 1 |
| Amoxapine | 0.1 |
| Amoxicillin | 600 |
| Ampicillin | 5.3 |
| Astemizole | 1 |
| Atropine | 1 |
| Bile Acids | 1.5 |
| Buspirone HCI | 1 |
| Caffeine | 10 |
| Compound Name | Concentration at Which No Significant Interference Criteria was Seen (mg/dL) |
| --- | --- |
| Captopril | 0.5 |
| Carbamazepine | 3 |
| Cefaclor | 200 |
| Cefadroxil | 10.5 |
| Cephalexin | 32 |
| Cephalothin Sodium | 200 |
| Cetirizin Dihydrochloride | 1 |
| Chenodeoxycholic Acid | 3 |
| Chlorothiazide | 2 |
| Chlorpropamide | 80 |
| Cholesterol | 500 |
| Cholic Acid | 2.4 |
| Cimetidine | 10 |
| Citric Acid | 30 |
| Clindamycin | 4.5 |
| Clonidine HCI | 2 |
| Conjugated Bilirubin | 15 |
| Creatinine | 30 |
| Cyclophosphamide | 37.5 |
| Desipramine HCI | 0.1 |
| Dexamethasone | 0.09 |
| Dextromethorphan HBr | 1 |
| Diclofenac | 5 |
| Dicumarol | 20 |
| Digoxin | 1 |

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| Diltiazem | 20 |
| --- | --- |
| Diphenhydramine HCI | 1 |
| Dipyrone | 11 |
| Disopyramide | 5 |
| DL Dopa | 2.8 |
| DL-Tyrosine | 24 |
| DL-β-Hydroxybutyric Acid | 100 |
| D-Mannitol | 600 |
| D-Mannose | 10 |
| D-Norpropoxyphene Maleate | 1 |
| Dopamine HCI | 1.5 |
| Doxazosin Mesylate | 1 |
| Doxycycline Hyclate | 3 |
| D-Penicillamine | 2.4 |
| D-Sorbitol | 70 |
| EDTA Calcium Disodium Salt | 180 |
| Enalapril | 8 |
| Ephedrine | 1 |
| Equilin | 15 |
| Erythromycin | 60 |
| Estradiol | 0.1 |
| Estrone | 1 |
| Ethanol | 350 |
| Ethosuximide | 25 |
| Ethyl Acetoacetate | 20 |
| Ethylene Glycol | 5 |
| Famotidine | 0.6 |
| Felodipine | 5 |
| Fenofibrate | 5 |
| Fenoprofen | 20 |
| Flecainide Acetate | 1 |
| Fluoxetine HCI | 12 |
| Flurbiprofen | 5 |
| Fructose | 250 |
| Furosemide | 6 |
| Galactose-1-phosphate | 5 |
| Gamma Globulins | 3000 |
| Gemfibrozil | 15 |
| Gentamicin Sulfate | 3.6 |
| Gentisic Acid | 50 |
| Glimepiride | 1 |
| Glipizide | 8 |
| Glucosamine | 450 |
| Glybenclamide | 1.5 |
| --- | --- |
| Glycerol | 10 |
| Hemoglobin | 500 |
| Heparin Lithium | 8000 U/dL |
| Heparin Sodium | 8000 U/dL |
| Humulin N | 20 U/dL |
| Humulin R | 20 U/dL |
| Hydrochlorothiazide | 0.61 |
| Hydrocortisone | 1 |
| Hydroxychloroquine Sulfate | 4 |
| Ibandronic Acid | 0.5 |
| Ibuprofen | 40 |
| Indomethacin | 5 |
| Isoniazid | 5 |
| Kanamycin | 6 |
| Lactic Acid | 100 |
| Lactose | 10 |
| L-Cysteine | 5 |
| L-Cystine | 50 |
| Lecithin | 500 |
| L-Glutathione, oxidized | 183.9 |
| L-Glutathione, reduced | 12.3 |
| Lidocaine | 1.2 |
| Lisinopril | 1 |
| lodoacetate | 35 |
| Loratadine | 1 |
| Lovastatin | 0.4 |
| L-Phenylalanine | 50 |
| L-Thyroxine | 5 |
| Magnesium Sulfate | 26 |
| Metaproterenol | 1.81 |
| Metformin | 50 |
| Methyl Dopa | 2.5 |
| Methylhydroxy progesterone | 50 |
| Metoclopramide HCI | 0.13 |
| Metoprolol Tartrate | 0.7 |
| Mexiletine HCI | 1 |
| Misoprostol | 0.8 |
| Nadolol | 2 |
| Naproxen | 100 |
| Neostigmine Bromide | 0.2 |
| Neostigmine Methyl Sulfate | 0.2 |

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| Nicotine | 2 |
| --- | --- |
| Nifedipine | 40 |
| Nitrofurantoin | 4 |
| Nordoxepin HCI | 5 |
| Normethyl-(±)-verapamil HCI | 1 |
| Nortriptyline HCI | 0.3 |
| Oleic Acid | 35 |
| Omeprazole | 0.52 |
| Oxalic Acid | 20 |
| Palmitic Acid | 150 |
| Penicillin G | 15 |
| Phenelzine Sulfate | 0.5 |
| Phenytoin | 10 |
| Pindolol | 0.5 |
| Pioglitazone | 5 |
| Piroxicam | 10 |
| Polysorbate 80 | 24 |
| Potassium Chloride | 50 |
| Pralidoxime Iodide (PAM) | 25 |
| Primidone | 5 |
| Probenecid | 60 |
| Procainamide HCI | 10 |
| Propranolol HCI | 1 |
| Pseudoephedrine | 1 |
| Pyridoxine HCI (Vitamin B6 HCl) | 3 |
| Pyruvic acid | 4 |
| Quinine Sulfate | 4.8 |
| Ramipril | 3.58 |
| Ranitidine HCI | 20 |
| Repaglinide | 5 |
| Rifampicin | 8 |
| Rosiglitazone | 5 |
| Salicylic Acid | 60 |
| Sodium Bicarbonate | 336 |
| Stearic Acid | 15 |
| Streptomycin Sulfate | 15 |
| Sucrose | 500 |
| Terfenadine | 25 |
| Tetracycline HCI | 10 |
| Theophylline | 25 |
| Thioridazine HCI | 4 |
| Tobramycin | 3.6 |
| Tolazamide | 200 |
| Tolbutamide | 100 |
| --- | --- |
| Trazodone HCI | 2 |
| Triamterene | 6 |
| Trimethoprim | 6 |
| Unconjugated Bilirubin | 40 |
| Urea | 600 |
| Uric Acid | 40 |
| Valproic Acid | 50 |
| Vancomycin HCI | 20 |
| Verapamil HCI | 1 |
| Vitamin B12 | 1 |
| Vitamin E | 20 |
| Voluven | 800 |
| Warfarin | 10 |
| Xylitol | 200 |
| Xylose | 100 |
| Zenapax (Daclizumab) | 10 |

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# Hematocrit study:

The effect of different hematocrit levels was evaluated using venous whole blood samples with hematocrit levels of 10 – 65% (10,15, 20, 25, 30, 43, 50, 55, 60, and 65%) spiked with glucose to achieve target concentrations of 25, 55, 120, 350, and 500 mg/dL. Three strip lots were evaluated, and there were 30 measurements for each combination of strip lot, glucose concentration, and hematocrit level tested. The results demonstrated that the ACCU-CHEK Aviva Plus Blood Glucose Monitoring System produces accurate results over the claimed hematocrit range of 10 – 65%.

f. Assay cut-off:

Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:

# System Accuracy:

To assess system accuracy, the ACCU-CHEK Aviva Plus Blood Glucose Monitoring System was compared to a hexokinase – based reference method. All of the samples were capillary fingersticks collected by a trained technician. Additional blood from the same fingerstick was collected for the reference measurement.

If native samples could not be collected for glucose concentrations <50 mg/dL or >400 mg/dL, then samples could be collected into a Lithium heparin anticoagulant tube and allowed to age in order to achieve a glucose concentration <50 mg/dL or spiked with glucose to achieve a glucose concentration >400 mg/dL.

Five samples were allowed to glycolyze to achieve a concentration less than 50 mg/dL and four samples were spiked to achieve a concentration greater than 400 mg/dL.

Linear regression based on single glucose measurements produced the following:

| Lot | n | Range of values mg/dL | Slope | Slope 95% CI | Intercept | Intercept 95% CI | r | Std. Error |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 10
0 | 20-529 | 1.026 | (1.001, 1.051) | -3.1 | (-8.4, 2.2) | 0.992 | 14.6 |
| 2 | 10
0 | 22-511 | 1.042 | (1.017, 1.067) | -3.7 | (-8.8, 1.4) | 0.993 | 14 |
| 3 | 10
0 | 19-542 | 1.018 | (0.993, 1.043) | -2.4 | (-7.6, 2.8) | 0.992 | 14.6 |

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System accuracy results for glucose concentration $< 75\mathrm{mg / dL}$

| Strip Lot | Within ±5 mg/dL | Within ± 10mg/dL | Within ± 15mg/dL |
| --- | --- | --- | --- |
| 1 | 15/16 (93.8%) | 16/16 (100%) | 16/16 (100%) |
| 2 | 14/16 (87.5%) | 16/16 (100%) | 16/16 (100%) |
| 3 | 12/16 (75%) | 16/16 (100%) | 16/16 (100%) |
| Combined | 41/48 (85.4%) | 48/48 (100%) | 48/48 (100%) |

System accuracy results for glucose concentration $\geq 75\mathrm{mg / dL}$

| Strip Lot | Within ±5% | Within ± 10% | Within ± 15% | Within ±20 % |
| --- | --- | --- | --- | --- |
| 1 | 53/84 (63.1%) | 74/84 (88.1%) | 82/84 (97.6%) | 84/84 (100%) |
| 2 | 44/84 (52.4%) | 73/84 (86.9%) | 81/84 (96.4%) | 83/84 (98.8%) |
| 3 | 50/84 (59.5%) | 75/84 (89.3%) | 83/84 (98.8%) | 83/84 (98.8%) |
| Combined | 147/252 (58.3%) | 222/252 (88.1%) | 246/252 (97.6%) | 250/252 (99.2%) |

b. Matrix comparison:

Not applicable. Fresh capillary whole blood is the only acceptable matrix.

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):

User results with capillary blood from the fingertip

A user performance study was performed to compare the lay user self-test results to the hexokinase reference method. The study was performed in 2 clinical sites with samples from 195 subjects using three lots of test strips. Each subject was asked to read the English version of the First Time Guide and Owner's Booklet, which will be provided to users when the device is marketed. Subjects were not allowed to practice testing with controls or blood prior to performing their own fingerstick blood glucose test.

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Linear regression analysis results based on single glucose measurements are summarized below:

| n | Range of values mg/dL | Slope | Slope 95% CI | Intercept | Intercept 95% CI | r | Std. Error |
| --- | --- | --- | --- | --- | --- | --- | --- |
| 195 | 41-472 | 0.969 | (.949, .989) | 2.3 | (-1.3, 5.9) | 0.989 | 11.6 |

System accuracy results for glucose concentration $< 75\mathrm{mg / dL}$

| Within ±5 mg/dL | Within ±10mg/dL | Within ±15mg/dL |
| --- | --- | --- |
| 23/29 (79.3%) | 29/29 (100%) | 29/29 (100%) |

System accuracy results for glucose concentration $>75\mathrm{mg / dL}$

| Within ±5% | Within ±10% | Within ±15% | Within ±20% |
| --- | --- | --- | --- |
| 94/166 (56.6%) | 152/166 (91.6%) | 164/166 (98.8%) | 165/166 (99.4%) |

User results with capillary blood from alternate sites

A user performance study was performed to compare the lay user self-test results to the hexokinase reference method. The study was performed in 2 clinical sites. For samples collected from the palm, 153 subjects collected capillary blood from the thenar site and 161 subjects collected blood from the hypothenar site. No significant difference was seen between the thenar and hypothenar sites, and they were combined for a total of 314 measurements from the palm. Forearm samples were collected by 155 subjects and upper arm samples were collected by 156 subjects. Each subject was asked to read the English version of the First Time Guide and Owner's Booklet, which will be provided to users when the device is marketed. Subjects were not allowed to practice testing with controls or blood prior to performing their own fingerstick blood glucose test.

Linear regression analysis based on single glucose measurements are summarized below:

| Alternate Site | n | Range of values mg/dL | Slope | Slope 95% CI | Intercept | Intercept 95% CI | r | Std. Error |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Palm | 314 | 60-439 | 0.983 | (0.963, 1.003) | 0.1 | (-2.9, 3.1) | 0.984 | 11.6 |
| Forearm | 155 | 61-381 | 1.004 | (0.967, 1.041) | -1.9 | (-8.1, 4.3) | 0.975 | 16.3 |
| Upper Arm | 156 | 61-381 | 0.929 | (0.896, 0.962) | 8.4 | (2.8, 14) | 0.976 | 14.8 |

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System accuracy results for glucose concentration $< 75\mathrm{mg / dL}$

| Alternative Site | Within ±5 mg/dL | Within ± 10mg/dL | Within ±15mg/dL |
| --- | --- | --- | --- |
| Palm | 8/11 (73%) | 11/11 (100%) | 11/11 (100%) |
| Forearm | 3/6 (50%) | 5/6 (83%) | 6/6 (100%) |
| Upper Arm | 4/6 (67%) | 5/6 (83%) | 6/6 (100%) |

System accuracy results for glucose concentration $\geq 75\mathrm{mg / dL}$

| Alternate Site | Within ±5% | Within ± 10% | Within ± 15% | Within ± 20% |
| --- | --- | --- | --- | --- |
| Palm | 158/303 (52%) | 242/303 (80%) | 280/303 (92%) | 299/303 (99%) |
| Forearm | 64/149 (43%) | 104/149 (70%) | 136/149 (91%) | 147/149 (99%) |
| Upper Arm | 66/150 (44%) | 109/150 (73%) | 135/150 (90%) | 146/150 (97%) |

# 4. Clinical cut-off:

Not applicable.

# 5. Expected values/Reference range:

The sponsor states the following in their labeling:

# Expected Values

The normal fasting glucose level for an adult without diabetes is below $100\mathrm{mg / dl}^{1,2}$ . Two hours after meals, the normal blood glucose level for a non-diabetic adult is less than $140\mathrm{mg / dl}^2$ . For people with diabetes: please consult your healthcare professional for the blood glucose level appropriate for you. You should treat your low or high blood glucose as recommended by your healthcare professional.

# References:

$^{1}$ American Diabetes Association: Diagnosis and Classification of Diabetes Mellitus (Position Statement). Diabetes Care 34 (Supp. 1) S66, 2011

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2Tietz Fundamentals of Clinical Chemistry, 6th Edition, Edited by Burtis CA and Ashwood ED, W. B. Saunders Co., Philadelphia, PA, 2008, p. 849

## N. Instrument Name:

ACCU-CHEK Aviva Blood Glucose Meter

## O. System Descriptions:

1. **Modes of Operation:**

Each test strip is single use and requires a sample volume of 0.6 uL.

Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device?

☑ Yes ☐ X or No

Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission?

☑ Yes ☐ X or No

2. **Software:**

FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:

☐ Yes ☐ X or No

3. **Specimen Identification:**

There is no sample identification function with this device. Samples are applied directly to the test strip as they are collected.

4. **Specimen Sampling and Handling:**

This device is intended to be used with capillary whole blood from the finger, palm, forearm, and upper arm only. The whole blood sample is applied directly to the test strip by capillary action.

5. **Calibration:**

The meter is coded by the user by inserting a code key. The labeling instructs the user to leave the code key in the meter until a new box of test strips is opened and to change the

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code key each time a new box of test strips is opened.

6. Quality Control:

Controls are not included in the ACCU-CHEK Aviva Plus Blood Glucose Monitoring System starter kit, but the labeling explains how users can obtain two levels of controls. The labeling also provides recommendations on when to test control materials. The meter can recognize a control solution automatically and control results are not stored in memory. An acceptable range for each control level is printed on the test strip vial label. If the control values fall outside these ranges, the user is referred to a troubleshooting chart which includes information on how to contact the Customer Care Service Center.

P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:

1. Infection Control studies: The ACCU-CHEK Aviva Plus Blood Glucose Monitoring System is intended for single-patient use only. Disinfection efficacy studies were performed on the materials comprising the meter and lancing device by an outside commercial testing facility demonstrating complete inactivation of hepatitis B virus (HBV) with the chosen disinfectant, Super Sani-Wipes (EPA Registration Number 9480-4). Robustness studies were also performed by the sponsor demonstrating that there was no change in performance or external materials for the meter and lancing device after 260 cleanings and 260 disinfection steps with Super Sani-Wipes. The robustness studies were designed to simulate 5 years of single-patient use. Labeling was reviewed for adequate instructions for the validated cleaning and disinfection procedures.

2. A usability study was performed to assess the readability of the labeling by recruiting untrained lay users who were provided with the test kit containing labeling for the US market. These lay users also completed a questionnaire regarding the clarity of the instructions and the ease of use of the device. The majority of the users responded that they understood the instructions and were able to successfully operate the device.

3. Flesch-Kincaid readability assessment was conducted for the meter user's manual and test strip package insert and were found to be 7.5 and 8.2, respectively.

4. The Customer Care Service Center is available 24/7, 365 days a year. The toll free phone number is 1-800-858-8072.

5. The sponsor claims an operating condition range of $14 - 40^{\circ}\mathrm{C}$ and $10 - 80\%$ relative humidity. Combinations of the claimed temperature and humidity operating conditions were evaluated by measuring whole blood samples at target glucose concentrations of 70, 120, and $250~\mathrm{mg/dL}$ and comparing the meter results to a reference method. The results demonstrated that the system produces accurate results over the claimed range of operating conditions.

6. To evaluate the effects of altitude, glycolyzed venous blood samples from three donors were spiked to glucose concentrations of approximately 40, 90, and $400\mathrm{mg/dL}$ and tested

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in a glove box chamber set to simulate atmospheric conditions at 10,000 feet. Three lots of glucose strips were tested in six runs with three replicates per run. This resulted in a total of 18 replicates for each combination of strip lot, glucose level, and donor and a total of 54 replicates overall. These studies demonstrated that altitudes up to 10,000 feet have no significant effect on blood glucose measurements

7. Electromagnetic Compatibility (EMC) testing was performed and found to be adequate in k043474. The Aviva meter in this submission is identical to the one reviewed in k043474.

Q. Proposed Labeling:

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

R. Conclusion:

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

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