The document describes an implantable continuous glucose monitor consisting of a subcutaneous sensor and external monitor. The sensor uses fluorescent glucose sensing technology powered by RF from the monitor to continuously monitor glucose levels for up to 1 year. The monitor alerts the user to hypo- and hyperglycemic events in advance via an LCD screen and alarm. The device aims to provide a better solution for managing diabetes than existing intermittent fingerstick monitors by eliminating pain and providing continuous, real-time glucose data to help regulate insulin levels.

1. IMPLANTABLE CONTINUOUS GLUCOSE MONITOR
Team #2: John Lac La, Katherine Moore, Shravya Nadig
May 15, 2015
Submitted in partial fulfillment of course requirement for:
BME 272: Biomedical Device Design and Principles
Spring 2015
Prof. Evgenia Mandrusov

2. Table of Contents
I. Abstract …………………………………………………………………………………………... 2
II. Device Description (Mechanism of action) ……………………………………………………… 2
A. Disclaimer: where the device idea came from ……………………………………………2
B. Intellectual Property Statement …………………………………………………………. 2
C. Background ……………………………………………………………………………… 2
D. Sensor ……………………………………………………………………………………. 3
E. Monitor ………………………………………………………………………………….. 4
III. Market Need Assessment ………………………………………………………………………… 5
A. Market Size ……………………………………………………………………………… 5
B. Market Dynamics ………………………………………………………………………... 5
C. Market Need …………………………………………………………………………….. 6
D. Willingness to Pay ………………………………………………………………………. 6
E. Target Market …………………………………………………………………………… 7
IV. Regulatory Strategy ……………………………………………………………………………… 7
A. Device classification …………………………………………………………………….. 7
B. Target geographies ………………………………………………………………………. 7
V. Specifications …………………………………………………………………………………….. 8
VI. Sterilization method …………………………………………………………………………….. 10
VII. Verification/Validation test plan ………………………………………………………………... 11
VIII. Failure Mode and Effects Analysis (FMEA) ………………………………………………….... 12
A. FMEA Table ………………………………………………………………………….... 12
B. MAUDE database review / analysis ………………………………………………...…. 14
IX. Instructions for Use (IFU) ……………………………………………………………………..... 16
X. Post market surveillance plan …………………………………………………………………... 25
XI. Appendix A: References ………………………………………………………………………... 26
XII. Appendix B: Key Regulatory Documents ……………………………………………………… 27
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3. I. Abstract
To address the market need of a better method for patients to manage diabetes mellitus,
Longevity Glucometrics, Inc. has developed a continuous implantable glucose monitor (CIGM)
to replace existing intermittent blood glucose monitors (“fingersticks”) that require patients to
provide a small blood sample throughout the day.
Some advantages of the CIGM over existing intermittent fingerstick systems include:
● Real time data is provided to the patient continuously
○ Important for patients who are prone to hyper- or hypoglycemia, which can
present a real danger to their life.
● Elimination of pain from having to draw blood
● A history of blood glucose levels that can be analyzed by physicians
● Smart system that can warn the patient of dangerous blood glucose levels
II. Device Description
A. Disclaimer: This device was inspired by the Dexcom G4 Platinum CBGM. The sensor is
based on a sensor currently being developed by Senseonics, Incorporated (formerly Sensors for
Medicine and Science, Inc.).The Senseonics Continuous Glucose Monitoring System is being
designed to be the first fully implantable continuous glucose monitoring system that is highly
accurate and stable throughout its long sensor life.
B. Intellectual Property Statement: This device and the associated technology is patented
by Senseonics Inc.
C. Background
Type I diabetes is an autoimmune disorder in which the patient’s body destroys the
insulin producing beta cells of the pancreas [1]. Without insulin, blood glucose levels increase.
High glucose levels, or hyperglycemia, can result in diabetic ketoacidosis and coma [1]. Over
time, elevated glucose levels result in heart disease, kidney failure, and damage to the eyes [1].
To treat type I diabetes, patients inject themselves with artificial insulin. However, blood
glucose levels can fluctuate throughout the day depending on diet and activity level [1]. In order
to inject the correct dosage, patients must monitor their blood glucose levels. Injecting too large
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4. a dose of insulin can result in depressed glucose levels, or hypoglycemia [2]. Possible effects of
hypoglycemia include coma, brain damage, stroke, and even death [1].
The current standard method of monitoring blood glucose levels is through the use of
intermittent blood glucose monitor [1]. These devices require patients to draw and analyze small
amounts of blood throughout the day [1]. For Type I diabetics, these devices often do not provide
a complete history of daily blood glucose levels, leading to cycle of slightly elevated and then
depressed blood glucose levels throughout the day [2]. Continuous blood glucose monitoring
(CBGM) has been shown to reduce mean glycaemia (the occurrence of hyper- and hypoglycemic
events) in Type I diabetics [2]. CBGM provides a detailed history blood glucose levels, and can
even predict the occurrence of hyper- and hypoglycemic events, allowing patients to regulate
their glucose levels before they become dangerous [2].
D. Sensor
Intermittent blood glucose monitors consist of a test strip and a sensor [1]. The test strip
contains glucose oxidase, an enzyme that oxidizes glucose to hydrogen peroxide [2]. This
reactions is then detected by the sensor, and the amount of hydrogen peroxide produced reflects
blood glucose levels [2]. Existing continuous blood glucose monitors utilize the same enzymatic
reaction to monitor blood glucose levels [3]. However, the enzyme is moisture and heat
sensitive, degrading quickly in the body [3]. As a result, existing implantable continuous blood
glucose monitors such as the Dexcom G4 have a lifespan of approximately 7 days [3]. These
sensors require the patient to frequently remove and implant the sensor to obtain accurate results
[3].
The implantable CBGM developed by Longevity Glucometrics has a lifespan of 1 year
[3]. This is because the Longevity sensor monitors blood glucose using a micro-fluorimeter, not
an enzymatic reaction [3]. The sensor consists of a LED excitation source, an integrated
photodiode, and a ferrite antenna, encased in a biocompatible polymer (Figure 1) [4, 5]. The
surface of the sensor is coated in a glucose sensitive hydrogel [5]. The LED excites the hydrogel,
and the hydrogel fluoresces in the presence of glucose [4, 5]. The photodiode measures the
degree of fluorescence and the degree of fluorescence indicates blood glucose level [5]. The
ferrite antenna communicates blood glucose measurements to the external monitor and powers
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5. the micro-fluorimeter via RF [5]. As no chemical reaction occurs and the hydrogel is stable in
interstitial fluid, the Longevity Glucometrics sensor is able to provide accurate results for up to 1
year [4].
Figure 1. Components of the implantable blood glucose sensor. Image is of the Senseonics
device [4, 5].
E. Monitor
The external monitor consists of a computer, an RF transmitter, and a LCD screen. The
RF transmitter powers and communicates with the implanted sensor [5]. The computer interprets
the fluorescence measurement and converts it into a blood glucose measurement. This data is
then stored by the monitor where it can be viewed by the user via the LCD screen, or
downloaded for further analysis. The monitor is programmed to predict and alert the user of
hyper- or hypoglycemic events 15 minutes in advance [2].
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6. III. Market Needs Assessment
A. Market Size
There are 29.1 million people with diabetes in the United States, of these, 2.5 million have Type
I diabetes [2]. Every year, 13,000 children in the United States are diagnosed with Type I
diabetes [1]. The United States has some of the highest rates of Type I diabetes in the world
(Figure 2).
Figure 2. Global incidence of Type I diabetes [6].
B. Market Dynamics
The number of diabetics is expected to reach 366 million globally by 2030 [5]. As the
number of diabetics in the United States continues to increase, the diabetes care market is
expected to grow to $16 million by 2017 [7]. The United States healthcare system spends on
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7. average $11,000 per diabetic per year [6]. Globally, diabetes care accounts for 11% of all
healthcare expenditures [6].
In 2012, the
market for continuous
blood glucose monitors
grew by 20% [7].
Worldwide, CBGM
account for only 0.6% of
the diabetes care market
(Figure 3), however
recent advancements in
CBG monitoring is
expected to increase
market share for CBG
monitors, especially in
the United States [8].
Figure 3. Diabetes Treatment Worldwide Market, 2010 [8]
C. Market Need
Market research has shown that patients desire a long-term, implantable continuous blood
glucose monitor [7]. All products on the market currently have an average lifespan of 7 days [3].
The Longevity Glucometrics sensor has a lifespan of 1 year [4].
D. Willingness to Pay
Insurance payers would pay for a CBG monitor that lowers mean glycemia [2]. Reducing
the occurrence of hyper- and hypoglycemic events would reduce diabetes care cost for insurance
payers and patients. Reducing mean glycemia would also reduce the patient’s risk of developing
heart disease, stroke, kidney failure, ulcers, and glaucoma [1], further reducing the health care
costs associated with Type I diabetes.
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8. E. Target Market
Our target market will be Type I diabetics in the United States. Type I diabetics would
benefit the most from continuous blood glucose monitoring [2]. Additionally, Type I diabetes is
a chronic, incurable condition that develops during childhood [1]. As such, Type I diabetics
require daily blood glucose monitoring throughout their entire lives [1]. The choice of target
geography was based on the high incidence of Type I diabetes in the United States (Figure 2) and
early adoption of CBG monitors in the United States [8]. At a later date, Longevity Glucometrics
may expand into Australian, Canadian, and European markets.
IV. Regulatory Strategy
A. Device Classification
Our initial target geography is the United States. Medical devices in the United States are
regulated by the FDA. According to the FDA, glucose test systems, such as the Longevity
Glucometrics sensor, are Class II medical devices [9]. In order to market our device we would
have to file a 510(k) and receive FDA clearance. Our predicate devices would be the Dexcom G4
Platinum implantable glucose monitor and the Medtronic CGM [2,3]. In order to obtain FDA
clearance to market our device, we would have to demonstrate our sensor is substantially
equivalent to existing implantable CBG monitors [9]. As a Class II device, our product would be
subject to both general controls and special controls, such as postmarket surveillance [9].
At a later date, if we decide to expand into European markets, we must obtain a CE Mark
prior to selling our device. According to the EU Medical Device Directive, our product is a long-
term, implantable, active medical device [10]. As such it is a Class IIb device and Longevity
Glucometrics must conform with Annexes II-VI in order to affix and CE Mark and market our
device in Europe [10].
B. Target Geographies: United States. Later: Canada, Australia, and Europe
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9. V. Specifications
Specification Rationale Input Method Output
Performance /
Functional
1. Sensor lifespan - 1
Year
Reduces number of
implants needed
during patient's
lifetime
Device has a 1-year
lifespan when used in a
relevant clinical model
Accelerated life
span testing
Estimate: 1
year,
2 months, 1
week
2. Sensor size:
0.5cm by 2cm
cylinder
Small size so implant
is not noticeable
when implanted
under the skin.
Cylinder should measure
0.5cm +/- 0.05cm by 2
cm +/- 0.05cm
Mitutoyo Digital
Caliper
0.53cm by
2.08cm
3. Sensor monitors
glucose by
fluorescent glucose
chemistry
No chemical reaction
required so device is
longer lasting and
more accurate
Fluorescent glucose
indicating polymer in
sensor responds to
changing glucose levels
Laboratory
Testing
Polymer
passed test
4. Light emitting
diode in sensor
powered by RF from
the monitor
Capable of powering
diode for 1 year.
Sensor powered for 1
year in accelerated
clinical model
Accelerated life
span testing
Sensor
passed test
Biocompatibility
1. Monitor sounds
an alarm in event of
hypo- and
hyperglycemia
Alerts patients of
dangerous blood
glucose levels
Monitor sounds 80 dB
(+/- 10 dB) alarm with
alternating 2400/2850 Hz
tones when hypo- or
hyperglycemia is
detected
Sonopan sound
level meter tester 80.5 Decibels
2. Sensor is fully
subcutaneous
No wires through the
skin means faster
healing time
Sensor implantation
results in healing time of
2 (+/- 0.5) days in
relevant human pre-
clinical model
Clinical tissue
testing 2.3 days
3. Sensor must be
biocompatible
Implanted sensor
must not cause
immunological
response from host
Must pass
biocompatibility tests per
ISO 10933 for blood
implant device, > 30 days
Cytotoxicity,
Sensitization,
Irritation
Reactivity,
systemic toxicity,
subchronic
toxicity,
genotoxicity,
implantation, and
hemotoxicity
testing
Implant
passed
all tests
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10. 4. Sensor must be
sterile
Sensor must not
cause infection after
being implanted
Perform sterilization per
ISO 11737-2:2009
American
Sterilizer Model L
22
Passed
sterilization
test
5. Armband receiver
monitor must be
biocompatible
Receiver monitor
must not irritate
patient's skin
Must pass
biocompatibility tests per
ISO 10933 for skin
surface contact device, <
24 hours
Cytotoxicity,
sensitization, and
Irritation
or intracutaneous
reactivity testing
Device
passed
all tests
Human Factors
1. Monitor has an
LCD screen
Patients can easily
see current and
predicted blood
glucose levels
Monitor has 1 built-in
LCD screen measuring 3
cm (+/-0.5cm) by 7 cm
(+/- 0.5cm)
Mitutoyo Digital
Caliper
3.24cm by
7.15cm
2. Small monitor
Comfortable to wear
all day. Easily hidden
under clothing
Monitor should measure
5 cm +/-0.5cm by 10 cm
+/- 0.5cm
Mitutoyo Digital
Caliper
5.23cm by
10.19cm
3. Monitor worn
with adjustable
adhesive band
Monitor can be worn
on arm or waist
Bands available in
multiple sizes (3-6 in, 7-
10 in, 11-15 in, 20-30 in,
31-40 in, 41-50 in )
Mitutoyo Digital
Caliper
All bands
within spec
4. Band is textured,
non-slip material
Monitor can be worn
without moving
Band should move less
than 1 (+/- 0.5) cm in any
direction in 24 hours
(LCD model)
Mitutoyo Digital
Caliper
Averaged
1.19cm
5. Monitor is
programmable
Patients can calibrate
monitor to correctly
detect hypo- and
hyperglycemia
Monitor has 3 labeled
buttons ( +, -, menu) and
a mini-USB port
Mitutoyo Digital
Caliper Passed
Labeling and
Packaging
1. Sensor to be
labeled as sterile
Sensor must be
sterile since it will be
implanted into
patient
Label must measure 1in
by 2in (+/- 0.1 in)
Mitutoyo Digital
Caliper
1.05 in by
2.06 in
2. Monitor to be
labeled as nonsterile
Monitor will be used
outside the body and
does not require
sterility
Label must measure 1in
by 2in (+/- 0.1 in)
Mitutoyo Digital
Caliper
1.04 in by
2.09 in
1. Sensor to be
protected by cushion
container
To protect the sensor
from physical
damage during
storage and transport
Cushion container must
be at least 1 inch thick on
all sides (+/- 0.10 in)
Mitutoyo Digital
Caliper 1.05 in thick
Environmental
1. LCD to be legible User must be able to Must be legible between Konica Minolta Passed
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11. in normal room
lighting
read the screen easily
in normal room
lighting
320 - 500 Lux (+/- 32
Lux)
luminance meter
2. LCD to be legible
in full daylight
User must be able to
read the screen easily
outdoors
Must be legible between
10,000 - 25,000 Lux (+/-
1000 Lux)
Konica Minolta
luminance meter Passed
3. LCD to be legible
in dim daylight
User must be able to
read the screen easily
in overcast outdoor
lighting
Must be legible at 1,000
Lux (+/- 100 Lux)
Konica Minolta
luminance meter Passed
4. Monitor must
function at high and
low temperatures
User might be in very
cold or very hot
environments
Device must function in
30F and 100F (+/- 10
degrees) for 1 hour each
Konica Minolta
luminance meter Passed
Safety
Receiver monitor
must be water
resistant
To resist sweat and
light rain in case user
is caught in the rain
for a short time
Device must function in 4
inches of water for 1 hour
Tub of deionized
water Passed
Receiver monitor
must use low power
battery
In the event of
serious electrical
short, user will not be
severely shocked
Power source must not
exceed 5 volts (+/- 50
mV) and 2.3 amps (+/-
100 mA)
Fluke digital
multimeter
(DMM)
5.12 V, 2.35
A
VI. Sterilization Method
To ensure complete sterilization of the glucose sensor, without negatively impacting the
specialized glucose-sensitive hydrogel polymer, a combination of a specially designed universal
homogeneous ultraviolet irradiation is employed [11].
Steps of sterilization:
• 300 seconds of ultraviolet radiation exposure
• 3 days inclusion compound of hydrogen peroxide with tenside in urea
• 0.15 % effective hydrogen peroxide concentration
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12. VII. Verification/Validation Test Plan
The Verification and Validation stage is the pinnacle of the design activity. The working
of the design is tested in this stage. Verification involves comparison of the data input to the data
output. Validation ensures that the device meets the clinical requirements, is safe in use and does
what it is supposed to do. This requires the device to meet the ISO 13485 standards.
● Verification: Design outputs satisfy input requirements
○ Biocompatibility
■ Sensor (implant exposed to blood & tissue for >30 days)
● Tests to be performed (per ISO 10933)
○ Cytotoxicity, sensitization, irritation or intracutaneous reactivity,
systemic toxicity (acute), subchronic toxicity (subacute toxicity),
genotoxicity, implantation, hemocompatibility
■ Armband Receiver Monitor (exposed to surface of undamaged skin for < 24
hours at a time)
● Tests to be performed (per ISO 10933)
○ Cytotoxicity, sensitization, irritation or intracutaneous reactivity
○ Packaging (sterility, robustness)
■ Sensor Implant
● Perform accelerated life testing
● Perform impact testing
● Perform temperature stress testing
■ Armband Receiver Monitor
● Perform impact testing
● Perform humidity and temperature testing
○ Device Performance Bench tests
■ Sensor Implant
● Perform in-vitro testing
■ Armband Receiver Monitor
● Perform cyclic loading test (armband)
● Perform impact testing
● Perform humidity and temperature testing
○ Shelf life
■ Perform accelerated life testing (both components)
● Validation: Design specification meet user needs
○ Simulated Use
■ Perform controlled usability test (clinical environment)
○ Safety and Efficacy Animal studies
■ Perform controlled usability test (clinical environment)
■ Animal studies not necessary
○ Comparative device studies
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13. ■ Study existing non-medical armband-worn devices for user experience
information
VIII. Failure Mode and Effects Analysis (FMEA)
A. FMEA Table
Abbreviation Meaning
S Severity
O Occurrence
RPI Risk Potential Index (S*O)
RRM Risk Reduction Measure
RR Residual Risk
A Is the risk acceptable (Yes/No)?
Part
Potential
Failure Mode Potential Harm S
Causes of
Failure O RPI
Current
Control
Measure RRM RR A
Implant
Device is not
biocompatible
Local
inflammatory
response 3
Improper
prior testing
on the body 2 6
Bio-
compatibility
Testing N/A 6 Y
Implant
Device is not
hemocompatib
le
Blood clots form
around implant 3
Platelet
adhesion to
the implant
surface 5 15
Hemo-
compatibility
Testing
Changed
surface
coating of
implant 4 Y
Armband
Device is not
biocompatible
Localized rash,
skin irritation 1
Material of
the band
acts as
irritant 3 3
Irritation or
Intracutaneou
s Reactivity
Testing N/A 3 Y
Implant
Device is not
sterile
Infection and
potential sepsis 4
Inadequate
sterilization 1 4
Implantation
Testing N/A 4 Y
Receiver
Monitor
Device is not
biocompatible
Localized rash,
skin irritation 2
Skin-irritating
coating used 2 4
Sensitization
and Irritation
Test N/A 4 Y
RF signal
Interference
with RF signal
Blood glucose is
not continuously
monitored 3
Inadequate
EMF
shielding 3 9
Benchtop RF /
EMF testing
Added
shielding
material 2 Y
Implant
LED
breaks/stops
emitting light
Blood glucose is
not monitored 4
Unreliable
LED (long
term) 1 4
Benchtop
burn-in testing N/A 4 Y
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14. Indicating
polymer
Polymer is
degraded by
oxidative
reactions
Polymer does not
fluoresce in the
presence of
glucose.
Blood glucose is
not monitored. 4
Inadequate
testing of
Polymer 1 4
Laboratory
polymer
testing N/A 4 Y
LCD
screen on
monitor
LCD screen
does not
function
Patient cannot
read blood
glucose
measurements 3
Low quality
screen 2 6
Benchtop
testing N/A 6 Y
Armband
Armband does
not stay in
place or slips
RF signal does
not reach implant
so LED is not
powered.
Blood glucose is
not monitored. 4
Slippery
material
used 3 12
Usability
testing
(simulated
use)
Added
rubber
grip strips
to reduce
band
movement
once
secured 3 Y
Speaker
Does not emit
alarm at
specified
volume
Patient may not
be alerted of
hyper- and
hypoglycemic
condition. 5
Low quality
component 2 10
Benchtop
testing
Changed
vendors 5 Y
mini-USB
port
USB port does
not function
Doctor cannot
download data
from device.
Blood glucose
history is
unknown. 3
Poor
connection to
main board 2 6
Benchtop
testing N/A 6 Y
Implant
Device does
not remain in
original
implant site
Patient will not
know where to
reposition the
armband.
Blood glucose is
not monitored 4
Implant
device shape
is too
aerodynamic 1 4
Implantation
Testing N/A 4 Y
Receiver
Monitor
Battery meter
fails to warn
user of low
battery
None. User must
replace with new
batteries. 1
Software
coding bug 3 3
Software
Engineering
(testing) N/A 3 Y
Receiver
Software
Software
miscalculates
glucose level
readings
Blood glucose
level is reported
incorrectly to the
user 4
Software
runtime
errors 2 8
Software
Engineering
(testing)
Algorithm
validated
by
multiple
teams 4 Y
Receiver
Software
USB software
update fails
None. User must
try again or send
device in for
service 1
ROM /
chipset stops
responding 2 2
Software and
Hardware
benchtop
testing N/A 4 Y
Armband
Armband
breaks due to
cyclic fatigue
Blood glucose
monitoring stops
and user must
replace 2
Weak
armband
material
used 3 6
Fatigue stress
testing
(cyclical)
Changed
to a
stronger
material 2 Y
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15. armband. User
can use
alternative
method to check
blood
glucose levels in
the meanwhile.
Severity Levels (Severity)
Rating Severity Description
5 Catastrophic Results in patient death or poses immediate threat to life
4 Critical Results in emergency medical care (e.g. rushed to E.R.)
3 Serious Results in professional medical intervention
2 Minor
Results in temporary injury not requiring professional
intervention
1 Negligible Does not cause injury, results in user inconvenience
Probability Levels (Occurrence)
Rating Description Probability Range
5 Frequent > 10^-3
4 Probable < 10^-3 and > 10^-4
3 Occasional < 10^-4 and > 10^-5
2 Remote < 10^-5 and > 10^-6
1 Improbable < 10^-6
B. MAUDE Database Review / Analysis
The Manufacturer and User Device Experience (MAUDE) database was created, and
maintained, by the FDA. The primary goal of this database is to maintain a record of complaints
relating to any particular medical device that is regulated by the FDA. While not strictly
mandated to do so, it is in good practice for medical device manufacturing companies to monitor
the MAUDE database after releasing a medical device. This will allow the manufacturer to
monitor any problems that arise and also gather feedback on how the device may be improved in
the future. Ideally, the manufacturer will use incident reports from the MAUDE database to
update and refine the FMEA with the ultimate goal of improve the device over time.
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16. At the time of writing, the FDA has not approved any continuous implantable glucose
monitor device. Consequently, the MAUDE database does not contain any pertinent information
for the team to evaluate. The team did, however, find incident reports from a device that is
similar enough for consideration. The Dexcom G4 Platinum continuous glucose monitor has an
implantable sensor which connects to an external monitor via electrodes through the skin. This
particular device has complaints about intermittent inaccuracies, sensor breakage after
implantation, and hardware failure. The team took these complaints into consideration and
modified the FMEA to either include these potential failure modes or increase their frequency.
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17. IX. Instructions For Use
Instructions for Use
“Longevity Glucometrics”
Implantable Continuous Glucose Sensor
Table of Contents
1.0 Device Description
2.0 How Supplied
3.0 Indications
4.0 Contraindications
5.0 Warnings
6.0 Precautions
6.1 Sensor Packaging and Handling - Precautions
6.2 Sensor Placement - Precautions
6.3 Sensor Removal - Precautions
6.4 Monitor Device - Precautions
6.5 Armband - Precautions
7.0 Potential Adverse Events
8.0 Summary of Clinical Information
8.1 Clinical Study - Abstract
9.0 Directions for Use
9.1 Implant Site Evaluation
9.2 Implant Site Preparation
9.3 Sensor Implantation Procedure
9.4 Sensor Removal Procedure
9.5 Transmitter Positioning
9.6 Armband Adjustment
9.7 Starting a Sensor Session
9.8 Sensor Calibration
10.0 Patents and Trademarks
1.0 DEVICE DESCRIPTION
A small sensor that measures glucose levels just underneath the skin
Transmitter that is fastened on top of the sensor and sends data wirelesslessly to the receiver.
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18. 1. Small Sensor that measures glucose levels just underneath the skin.
a. The sensor is comprised of a micro-fluorometer enclosed in a clear, biocompatible
polymer shell.
2. Transmitter that is fastened on top of the sensor and sends data wirelessly to the receiver.
a. The transmitter is a small, external, rechargeable device that attaches to an
armband and is worn directly over the sensor.
3. Receiver that displays your glucose trends in vivid colors so you can easily see when it’s
high, low or within range.
a. The receiver is a LCD color display that shows current blood glucose levels. The
receiver also records blood glucose levels, allowing the patient to view their blood
glucose history, and their doctor to download and analyze the data.
Disclaimer
The device was inspired by a Dexcom developed product called “Dexcom CGM” which has
similar design and functionality as our device. The image is of the Sensonics device continuous
glucose monitor.
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19. 2.0 HOW SUPPLIED
Sterile:Sensor only. Sterilized with ethylene oxide gas. Non-pyrogenic.
Contents: One (1) Implantable Continuous Glucose Sensor
One (1) Monitor Device
One (1) Armband attachment
Storage: Store at room temperature only.
3.0 INDICATIONS
The Longevity Glucometrics Continuous Implantable Glucose Monitor (CIGM) is indicated to
provide continuous, real time, blood glucose levels for patients currently living with diabetes and
must otherwise use an external glucose monitor on a daily basis.
4.0 CONTRAINDICATIONS
The Longevity Glucometrics CIGM is contraindicated for use with:
❖ Patients that have not been diagnosed with diabetes mellitus
❖ Patients who do not use an external blood glucose monitor on a regular basis
❖ Patients who are hypersensitive to boronic acid-based compounds
❖ Patients who cannot receive antiplatelet or anticoagulation therapy
5.0 WARNINGS
❖ The sensor device is intended for single-use only. Do not reuse. Do not resterilize. Do not
use if the package is opened or damaged.
❖ Use the sensor device before the “Use By” date as specified on the device package label.
Store in a cool, dark, and dry location.
❖ Do not use if package is not fully intact or if there exists other reasons to suspect that the
sterility of the sensor device has been compromised.
❖ Administer appropriate antiplatelet therapy before and after implantation of the sensor
device.
❖ Do not over-tighten armband on patient’s arm. Tighten only enough to prevent the
monitor from freely moving away from target site.
❖ Use only the type of batteries specified on the label in the battery compartment of the
monitor. Do not substitute with a different type of batteries. Do not connect monitor to an
external power source.
❖ Do not use near strong radio frequency (RF) signals that have the ability to interfere with
the Bluetooth signal.
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20. 6.0 PRECAUTIONS
❖ The implantable continuous glucose sensor device should only be used by surgeons and
physicians that are trained in subcutaneous surgical techniques and trained to implant this
device.
➢ The long-term safety and effectiveness of the sensor device has not been
established beyond two years.
➢ The safety and effectiveness of the implantable continuous glucose sensor device
has not been established in patients who:
■ are less than 18 years old
■ are pregnant or lactating
■ have known hypersensitivity to rubber compounds (material used to make
the majority of the armband)
6.1 SENSOR PACKAGING & HANDLING - PRECAUTIONS
❖ Do not use sensor if the packaging is not fully intact or shows other signs of failure or
external tampering.
❖ Do not use if device packaging is physically damaged
❖ Handle the device with care.
❖ Only handle device outside it’s packaging when ready to implant the device into patient.
❖ Avoid unnecessary handling of the sensor device to avoid / reduce risk of damage.
6.2 SENSOR PLACEMENT - PRECAUTIONS
❖ Do not place sensor device more than 1.0 cm (+/- 0.25 cm) below the outer epidermis to
ensure a strong signal to the monitor device.
❖ Use caution if placing sensor device in a crevice between two tissue systems (e.g.
overlapping muscle fibers) as the sensor could seep into the crevice and become too deep
to signal the monitor device.
❖ The sensor device may be repositioned, after initial deployment, so long as it is handled
with care.
❖ The sensor device should be placed so that the body of the device runs parallel to the host
tissue (such as muscle fiber) to minimize longitudinal strain.
6.3 SENSOR REMOVAL - PRECAUTIONS
❖ Do not make incision more than 2.0 cm away from the sensor to ensure the sensor can be
reached from the incision site.
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21. ❖ If sensor is accessible but resistance is felt during removal, surrounding tissue may need
to be incised to free the sensor.
❖ Keep sensor level and stable during removal to avoid movement and potential migration
of the sensor during removal.
6.4 MONITOR DEVICE - PRECAUTIONS
❖ Check battery connectors for corrosion before inserting new batteries. Do not insert
batteries if corrosion is found.
❖ Ensure that the battery door is fully closed before use. The body of the monitor is
designed to be water resistant (from sweat, light rain, etc.) but this feature cannot
function if the battery door is not fully sealed.
❖ Change out depleted batteries promptly, do not leave them in the device for a prolonged
period of time.
❖ Read the battery label and use only specified battery type (i.e. size, type, and voltage). Do
not connect monitor to an external power source.
6.5 ARMBAND - PRECAUTIONS
❖ Do not use armband if any part of the band is torn or beginning to break apart.
❖ Do not expose armband to temperatures above 120°F.
❖ Ensure the patient does not experience hyper reactivity to rubber compounds.
❖ Tighten the armband only enough to secure the monitor. Do not over tighten.
7.0 POTENTIAL ADVERSE EVENTS
❖ Abrupt sensor malfunction
❖ Allergic reaction to fluorescence boronic acid glucose indicator
❖ Allergic skin reaction to rubber compound of armband
❖ Bleeding complications from anticoagulant or antiplatelet medication
❖ Bruising at implant site due to localized thrombosis around sensor device
❖ Death
❖ Hematoma or hemorrhagic event at the site of the implant
❖ Hypertension / Hypotension
❖ Infection, local or systemic, including bacteremia or septicemia
❖ Movement of sensor device requiring surgical intervention
❖ Pain at implant site
❖ Swelling at implant site
8.0 SUMMARY OF CLINICAL INFORMATION
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22. For brevity, only certain important aspects of the clinical trial has been included in this
document. The full clinical study can be found in its original source:
M. Mortellaro and A. DeHennis, "Performance characterization of anabiotic and fluorescence-
based continuous glucose monitoring system in patients with type 1 diabetes," Biosensors and
Bioelectronics, vol. 61, pp. 227-231, 2014.
8.1 Clinical Study - Abstract
A continuous glucose monitoring (CGM) system consisting of a wireless, subcutaneously
implantable glucose sensor and a body-worn transmitter is described and clinical performance
over a 28 day implant period in 12 type 1 diabetic patients is reported. The implantable sensor is
constructed of a fluorescent, boronic-acid based glucose indicating polymer coated onto a
miniaturized, polymer-encased optical detection system. The external transmitter wirelessly
communicates with and powers the sensor and contains Bluetooth capability for interfacing with
a Smartphone application. The accuracy of 19 implanted sensors were evaluated over 28 days
during 6in-clinic sessions by comparing the CGM glucose values to venous blood glucose
measurements taken every 15min. Mean absolute relative difference (MARD) for all sensors was
11.670.7% ,and Clarke error grid analysis showed that 99% of paired data points were in the
combined A and B zones.
9.0 DIRECTIONS FOR USE
A sensor, transmitter, and receiver are required to use the Longevity Glucometrics Continuous
Implantable Glucose Monitoring system. A blood glucose meter and testing strips are also
required for calibration. The blood glucose meter and testing strips are not provided in the
Longevity Glucometrics Continuous Implantable Glucose Monitor packaging.
Before You Start
● Make sure the correct transmitter ID has been entered into the receiver.
● Check the expiration date on the sensor package label. Insert sensor on or before the end
of the expiration date calendar day.
● Follow the blood glucose meters manufacturer’s instructions to make sure the meter is
providing accurate blood glucose values for calibration.
● Carefully remove the device from its protective packaging using standard aseptic
technique and inspect for damage.
○ Do not use if sensor is cracked or otherwise visibly damaged.
○ If it is suspected the sterility of the device has been compromised, the device
should not be used.
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23. 9.1 Implant Site Evaluation
The implantation site must be the contralateral upper arm.
1. Identify the patient’s non-dominant hand. The sensor will be implanted in the non-
dominant arm.
2. Choose an insertion site that is flat and free from where rubbing may occur.
3.
Precautions
● Avoid inserting the sensor in areas that are likely to be bumped, pushed or compressed.
● Avoid inserting the sensor in areas with scarring, tattoos, or irritation. Insertion in these
area might affect sensor performance.
Water Damage
If device falls in water, first pat the outside cover until it dries. After that open the reservoir
compartment and check the compartment and reservoir for water. If wet, dry it completely within
10 minutes of exposure to water. Exposure to liquids, including water or insulin can corrode the
mechanism.
9.2 Implant Site Preparation
1. If necessary, shave hair from implant site.
2. Disinfect implant site with iodine, alcohol, or chlorhexidine gluconate.
3. Apply lidocaine to implant site to provide local anesthesia.
9.3 Sensor Implantation Procedure
1. Make a small incision (~ 0.8 cm - 1.0 cm) in the contralateral upper arm.
2. Insert the sensor subcutaneously via the incision.
3. Close the wound with two 5-0 nylon sutures.
Precautions
● Do not place sensor device more than 1.0 cm (+/- 0.25 cm) below the outer epidermis to
ensure a strong signal to the monitor device.
● Use caution if placing sensor device in a crevice between two tissue systems (e.g.
overlapping muscle fibers) as the sensor could seep into the crevice and become too deep
to signal the monitor device.
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24. ● The sensor device may be repositioned, after initial deployment, so long as it is handled
with care.
● The sensor device should be placed so that the body of the device runs parallel to the host
tissue (such as muscle fiber) to minimize longitudinal strain.
9.4 Sensor Removal Procedure
1. If necessary, shave hair from implant site.
2. Disinfect implant site with iodine, alcohol, or chlorhexidine gluconate.
3. Apply lidocaine to implant site to provide local anesthesia.
4. Make a small incision (~ 0.8 cm - 1.0 cm) in the contralateral upper arm.
5. Insert the sensor subcutaneously via the incision.
6. Close the wound with two 5-0 nylon sutures.
9.5 Transmitter Positioning
1. Attach the transmitter to the armband using the provided holder.
2. Attach the armband to the the upper arm.
3. Position the transmitter so it is centered directly over the implantation site.
9.6 Armband Adjustment
1. Tighten the adjustable strap of the armband until the armband remains in place without
slipping down the arm.
2. Have the patient run in place for 5 minutes.
3. If the armband has moved, reposition the armband so the transmitter is centered directly
over the implantation site. Tighten armband slightly (~ 2 cm).
4. Repeat steps 2 and 3 until the armband remains stationary with the transmitter centered
directly over the implantation site, after 5 minutes of running.
9.7 Starting a Sensor Session
1. Press the POWER button to turn on the receiver.
2. Press the HOME button to reach main menu.
3. Press the DOWN button to select Start Sensor. The sensor start-up process will begin.
4. Check the receiver 10 minutes after starting the sensor start-up process to make sure the
transmitter, receiver, and sensor are all communicating.
5. After sensor start-up is completed, the sensor must first be calibrated before use.
9.8 Sensor Calibration
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25. 1. Using a correctly calibrated intermittent blood glucose monitor, take a blood glucose
reading.
2. Download the sensor measurements from the transmitter.
3. Follow the on screen instructions to calibrate the sensor using the receiver until the sensor
measurements exactly match the finger-stick measurements.
10.0 PATENTS AND TRADEMARKS
This product and/or its use is covered by one or more of the following United States patents:
8,648,356. Other U.S. patents pending. Other foreign patents pending.
Longevity Glucometrics is the registered trademark of Longevity Glucometrics, Inc. and all
rights are reserved.
Caution: Federal law (USA) restricts this device to sale by or on the order of a physician.
Longevity Glucometrics, Inc.
1 Washington Square
San Jose, California 95192
Tel: (408) 555-1234 | Fax: (408) 555-4321
do not resterilize for single use only provided nonsterile sterilized by
radiation
prescription use only use by date see instructions manufacturer
batch code lot number date of manufacture professional use
caution keep dry storage temperature keep out of sunlight
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26. X. Post-market Surveillance Plan
It is important for medical devices to have an active postmarket surveillance, not just to
capture complaints, but also acquire information about the device on its performance after it has
hit the market. The operations to be carried out in this section can be summarized as:
● Clinical Literature to be reviewed by a clinical lead
● Marketing information to be reviewed by a manager
● Quality related information to be collected from the technical knowledge base
For this device, the following steps are carried out:
1. Post-market clinical follow-up study
a. Explore long-term effects of repeated sensor removal & implantation
2. Customer Complaint Monitoring
a. Establish a customer complaint hotline for doctors
b. Online form for patients to submit complaints.
c. Monitor MAUDE database for complaints about similar devices
d. Complaints are recorded and classified based on severity & frequency of
occurrence
e. Complaints with risk index >6 will be investigated
3. Revised FMEA
a. Customer complaint data : Used to update and revise the FMEA
b. FMEA : Updated once a year
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27. XI. Appendix A: References
[1] Dealing with Type 1 Diabetes in Children. (n.d.). Retrieved April 24, 2015, from
http://www.diabeticcareservices.com/diabetes-education/type-1-diabetes
[2] Klonoff, D. C. (2007). The Benefits of Implanted Glucose Sensors. Journal of Diabetes
Science and Technology (Online), 1(6), 797–800.
[3] Dexcom. Dexcom G4 Continuous Blood Glucose Monitor IFU. (2013). Retrieved April 30,
2015 from http://www.dexcom.com/sites/dexcom.com/files/dexcom-g4/docs/dexcomG4-
UsersGuide-English-mmol24hr.pdf
[4] Senseonics Inc. Product. (2012, February 9). Retrieved April 24, 2015, from
http://senseonics.com/product
[5] Mortellaro, M., & DeHennis, A. (2014). Performance characterization of an abiotic and
fluorescent-based continuous glucose monitoring system in patients with type 1 diabetes.
Biosensors and Bioelectronics, 61(0), 227-231. doi:http://dx.doi.org/10.1016/j.bios.2014.05.022
[6] International Diabetes Care Foundation. IDF Diabetes Atlas Third Edition. (2006). Retrieved
May 13, 2015 from
http://www.diapedia.org/img_cache/markdown_lightbox_5e28f279007ed217a717fc7df1b3e1163
eea248c-0104c.jpg
[7] US Diabetes Care Device Market to Grow Moderately - Millennium Research Group, Inc
(MRG). (n.d.). Retrieved April 24, 2015, from http://mrg.net/News-and-Events/Press-
Releases/Diabetes-Care-Devices-011513.aspx
[8] MedMarket Diligence, LLC; Report #D510, "Diabetes Management: Products, Technologies,
Markets and Opportunities Worldwide 2009-2018."
[9] FDA Medical Devices, 21 CFR 862.1345 (2014)
[10] COUNCIL DIRECTIVE 93/42/EEC of 14 June 1993 Concerning medical devices amended
2007
[11] J. W. H. V. S. M. A. P. von Woedtke, "Sterilization of enzyme glucose sensors: problems
and concepts," Biosens Bioelectron, vol. 17, no. 5, pp. 373-82, 2002.
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28. XII. Appendix B: Regulatory Documents and Databases
1. U.S. Food and Drug Administration (FDA)
2. Medical Device Directive (MDD)
a. 93/42/EEC
3. Manufacturer and User Device Experience (MAUDE) database
4. Code of Federal Regulations (CFR)
a. 21 CFR 800-1050 (devices)
b. 21 CFR 801 (Labelling)
c. 21 CFR 807 (510k)
d. 21 CFR 812 (IDE - investigational device exemption)
e. 21 CFR 814 (PMA - premarket approval)
f. 21 CFR 820 (Quality System Regulations)
5. International Organization for Standardization (ISO)
a. ISO 13485 (Medical Devices Quality Management Systems)
b. ISO 14971 (Risk Management for Medical Devices)
c. ISO 10993 (Biological Evaluation Series)
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