History of Embolotherapy

1904 Dawbain - inject melted wax/carotid
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1930 Brooks - inject muscle/int. carotid
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1960 Lussenhop & Spence - MM spheres
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1971 PVA Plug
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1972 Hemorrhage controlled auto-clot
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1974 Serbinenko -Detachable balloons
History of Embolotherapy

White et. al. - flow directed cath w/det. Bal.
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1974 Gel Foam
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1975 Wool Coil
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1981 Ethanol used kidney infarction
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1982 Amplatz - boiled contrast
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Improvements in Visualization, Catheter
Technology, Embolic Agents
Embolic Agent Variables
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Delivery
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Mechanical Effort
Tortuousity of Vessels
Procedure Time - Radiation, Contrast
Placement
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Flow directed
Proximal or distal
In-vivo sizing
Reflux tendency
Embolic Agent Variables
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Radiopacity
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Additives tantulum, barium, et. al.
MRI Compatibility
Activation
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Toxicity
Expansion
Necrosis
Embolic Agent Variables
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Sizing
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Inflammatory Response
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Local mild or giant cell reaction
Pain on Administration
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Ranges and tolerance
Alcohol, gelfoam, PVA
Permanent or Temporary

Auto-lysis
Recanalization

Vessels recanalize

Embolic can “wash-out”
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Vessel with embolic can remodel
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Not important in pre-op embos

Timing is the key variable
Embolic Agent Variables
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Cost
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Occlusion Mechanism
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Total procedure cost and patient life
Mechanical
Thrombus
Hemodynamics
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Large vs. small vessels
High flow or slower flow
Particles
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Irregular shape
Induce an inflammatory response
Auto-lysis
Some are temporary
Occlusion sustainability
Thrombogenic
May be difficult to handle
Mechanical Devices
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Coils
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Thrombogenic
Size and delivery
Permanent
Balloons
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Latex or silicone
Mechanical occlusion
Liquid Embols
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Ethanol and Ethibloc are painful
Results can take time post procedure
Can be difficult to handle
Obliteration, permanent
Extensive necrosis possible
Glues
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Acrylates used but not approved
Polymerize upon contact with ionic
solutions
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Some use Acetic acid or heavy water to delay
High inflammatory response
Permanent
Experience is critical
Difficult to handle
Embolic Agents
Sclerosant
Spheres
Particles Mechanical Liquid
Embosphere
PVA
Coils
NBCA
Therasphere
Gelfoam
Balloons
Hydrogel Acetic acid
Ethanol
Hepasphere
Sotradecol
Contour SE
Ethibloc
Beadblock
Spheres
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Calibrated
Radio-pacity
Flow directed
Carrier
Dry or wet
Polymer, hydrogel, glass
Mechanical occlusion
Company History

Microspheres developed to purify Human Serum
Albumin and antibodies -1970s

IBF-French Biological Industries and later
Biosepra produce microspheres for drug
purification - 1980s

Microspheres used to produce albumin, insulin,
and genetically engineered human growth
hormone - 1980s
Company History

First use of microsphere as a human implant at
LRB in Paris, 1989

Early 1990s:

Microspheres used to produce biotech drugs
such as TPA, AT3, gene therapy vaccines

Sepracor purchases Biosepra
Company History

Biosepra spins off from Sepracor, 1994
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Biosepra, through its French distributor, obtains
CE Mark for Embosphere, 1997
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Biosepra sells chromatography business, 1998
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Biosepra purchases majority share of Biosphere
Medical SA and changes corporate name to
Biosphere Medical, 1999

BSMD files 510k, 1999
Company History

Management team nucleus hired, 1999
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IDE filed for UAE clinicals, 1999
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European distribution expanded, 1999
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Australia and Canada approve Embosphere, 2000
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PIPEs completed, 2000
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FDA clearance for Embosphere, 2000

Sales force recruited, 2000
Embosphere® Microspheres are precisely calibrated,
spherical, hydrophilic, micro-porous beads made of
a cross-linked acrylic co-polymer which is then
cross-linked with gelatin.
• Cross-linked acrylic beads
• Precisely calibrated
• Micro-porous
• Embedded with gelatin
• Compliant
• Hydrophilic
• Non-clumping
• Patented and proprietary
Embosphere
PVA
• Spherical
• Non Aggregating
• Uniform occlusion
• Predictable penetration
• Irregular shape
• Clumping
• Non-uniform occlusion
• More proximal occlusion
A Precise Calibration
% (volume)
50-150 microns
% Volume
Ultra-Drivalon 50-150m
Ultra-drivalon – Nycomed
50-150
PVA type
1 m
30
20
10
0
1
10
100
Particle diameter (m)
1000
1
10
100
Particle diameter (m)
1000
1
10
100
Particle diameter (m)
1000
- TargetContour Emboli 45-150m
% Volume
Contour emboli
PVA type
2
50-150 m
50-150 microns
% (volume)
30
20
10
0
30
% (volume)
% Volume
Embosphere
Microspheres
- Medical
EMBOSPHERE
- Biosphere
Microspheres
100-300m
100-300
m
Biosphere
Medical
100-300 microns
20
10
0
A Precise calibration
The only particulate embolic
material you can trust !
Competitive Advantage
Vessel diameter (µ)
“Controlled Vessel Targeting”
600
500
400
300
200
100
0
800
700
600
500
400
300
200
100
0
Embolization efficiency
Number of particles
22.5
20
17.5
15
12.5
10
7.5
5
2.5
0
Embosphere
PVA
Perfectly spherical
A direct correlation between the
size of the vessels
and
the size of embolic !
Inert biocompatible material

Cross-linked acrylic bead impregnated
with gelatin



Acute and chronic animal testing

6 year implant

Chromatography media
Cell-culturing history
Strong safety profile
Six year implant



Complete mechanical occlusion
Inert material
Remains unchanged over time
PVA Degradation
Non-uniform occlusion
Chronic inflammatory response
Histology slides courtesy of Dr. Alex Laurent, Hopital Lariboisiere, Paris
Long-term tolerance - Facial AVM





Female patient. 25 yrs.
1989 sept Embolization with ES 500-700 &
700-900
1990 march
Surgery
6M
1990 oct
Surgery
1Y
1993 feb
Surgery
1995 oct
Surgery
6Y
6 years
1 year
6 years
Long term tolerance
Facial AVM
Male patient, 31 yo, lip AVM
1988 Embolization PVA
1990 dec Embolization ES 800-1000
1992 nov Surgery (23 M)
23 Months
*
PVA particle
ES
ES
*
ES
*
23 Months
* = Macrophages
Biocompatibility
Permanent
Durable
Complete
Mechanical
Occlusion
Compressible and Hydrophilic
Elastic shape and hydrophilic surface prevent
aggregation within the catheter, simplifying handling
and promoting accurate delivery to the target vessel.
Compressible and Hydrophilic
Assume
33%
compression
gets back
in round
shape
Embosphere and 3F Catheters
Brand
I.D.
Micro Ferret
.018
Embosphere size
in m
300-500
Rapid Transit
.021
500-700
Turbo Tracker
.021
500-700
Renegade
.021
500-700
GT Leggiero
.023
500-700
Tracker 325
.024
700-900
Slip Cath
.025
700-900
SP Cath
.025
700-900
Mass Transit
.027
700-900
Trademarks and product names are exclusive
properties of their manufacturers.
Here above information is purely given as indications.
Compressible and Hydrophilic
A unique ease of use
A superior catheter patency
Summary of Competitive Advantages
Embosphere (ES)
PVA
Spherical shape,
Narrow size range
Irregular shape,
Targeted and
wide range of sizes controlled
Complete, permanent
occlusion
Elastic structure
Non-elastic
structure
Microcatheters
Non-fragmentation
Minimizes untargeted
tissue necrosis
Hydrophilic/
Charged surface
Non-hydrophilic/
Non-charged
No clumping
Ease of use
No migration
ES Advantage
Key Features & Benefits

Features

Benefits

Round
Calibrated
Inert
Compressible
Hydrophilic

Complete lumen filling
Control and targeting
Biocompatible
Catheter patency
Easy to inject


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Platform technology
The proven embolic
Embosphere® microspheres:
First generation of calibrated microspheres
The new Gold Standard
EmboGold™ microspheres:
User-friendly stained calibrated microspheres
Embosphere® microspheres
From right to left
40-120µm
100-300µm
300-500µm
500-700µm
700-900µm
900-1200µm
Embosphere® microspheres
Calibrated microspheres available in
1ml or
2ml
sizes
Product codes
40-120µm
100-300µm
300-500µm
500-700µm
700-900µm
900-1200µm
110GH
210GH
410GH
610GH
810GH
1010GH
120GH
220GH
420GH
620GH
820GH
1020GH
EmboGold™ microspheres
New pre-filled syringe
under peel-off blister tray
Calibrated microspheres
Stained with Gold
100-300µm 300-500µm
500-700µm 700-900µm
900-1200µm
EmboGold™ microspheres
Visibility
Convenience
Performance
Stained calibrated microspheres available in PFS
1ml or
2ml
sizes
Product codes
100-300µm
300-500µm
500-700µm
700-900µm
900-1200µm
S210EG
S410EG
S610EG
S810EG
S1010EG
S220EG
S420EG
S620EG
S820EG
S1020EG