history of embolotherapy 1904 dawbain - inject melted wax/carotid 1930 brooks - inject muscle/int....
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History of EmbolotherapyHistory of Embolotherapy
1904 Dawbain - inject melted wax/carotid1904 Dawbain - inject melted wax/carotid
1930 Brooks - inject muscle/int. carotid1930 Brooks - inject muscle/int. carotid
1960 Lussenhop & Spence - MM spheres1960 Lussenhop & Spence - MM spheres
1971 PVA Plug1971 PVA Plug
1972 Hemorrhage controlled auto-clot1972 Hemorrhage controlled auto-clot
1974 Serbinenko -Detachable balloons1974 Serbinenko -Detachable balloons
History of EmbolotherapyHistory of Embolotherapy
White et. al. - flow directed cath w/det. Bal.White et. al. - flow directed cath w/det. Bal.
1974 Gel Foam1974 Gel Foam
1975 Wool Coil1975 Wool Coil
1981 Ethanol used kidney infarction1981 Ethanol used kidney infarction
1982 Amplatz - boiled contrast1982 Amplatz - boiled contrast
Improvements in Visualization, Catheter Improvements in Visualization, Catheter Technology, Embolic AgentsTechnology, Embolic Agents
Embolic Agent VariablesEmbolic Agent Variables
DeliveryDelivery Mechanical EffortMechanical Effort Tortuousity of VesselsTortuousity of Vessels Procedure Time - Radiation, ContrastProcedure Time - Radiation, Contrast
PlacementPlacement Flow directedFlow directed Proximal or distalProximal or distal In-vivo sizingIn-vivo sizing Reflux tendencyReflux tendency
Embolic Agent VariablesEmbolic Agent Variables
RadiopacityRadiopacity Additives tantulum, barium, et. al.Additives tantulum, barium, et. al. MRI CompatibilityMRI Compatibility
ActivationActivation ToxicityToxicity Expansion Expansion NecrosisNecrosis
Embolic Agent VariablesEmbolic Agent Variables
SizingSizing Ranges and toleranceRanges and tolerance
Inflammatory ResponseInflammatory Response Local mild or giant cell reactionLocal mild or giant cell reaction
Pain on AdministrationPain on Administration Alcohol, gelfoam, PVAAlcohol, gelfoam, PVA
Permanent or TemporaryPermanent or Temporary Auto-lysisAuto-lysis
RecanalizationRecanalization
Vessels recanalizeVessels recanalize
Embolic can “wash-out”Embolic can “wash-out”
Vessel with embolic can remodelVessel with embolic can remodel
Not important in pre-op embosNot important in pre-op embos
Timing is the key variableTiming is the key variable
Embolic Agent VariablesEmbolic Agent Variables
CostCost Total procedure cost and patient lifeTotal procedure cost and patient life
Occlusion MechanismOcclusion Mechanism MechanicalMechanical ThrombusThrombus
HemodynamicsHemodynamics Large vs. small vesselsLarge vs. small vessels High flow or slower flowHigh flow or slower flow
ParticlesParticles
Irregular shapeIrregular shape Induce an inflammatory responseInduce an inflammatory response Auto-lysisAuto-lysis Some are temporarySome are temporary Occlusion sustainabilityOcclusion sustainability ThrombogenicThrombogenic May be difficult to handleMay be difficult to handle
Mechanical DevicesMechanical Devices
CoilsCoils ThrombogenicThrombogenic Size and deliverySize and delivery PermanentPermanent
BalloonsBalloons Latex or siliconeLatex or silicone Mechanical occlusionMechanical occlusion
Liquid EmbolsLiquid Embols
Ethanol and Ethibloc are painfulEthanol and Ethibloc are painful Results can take time post Results can take time post
procedureprocedure Can be difficult to handleCan be difficult to handle Obliteration, permanentObliteration, permanent Extensive necrosis possibleExtensive necrosis possible
GluesGlues
Acrylates used but not approved Acrylates used but not approved Polymerize upon contact with Polymerize upon contact with
ionic solutionsionic solutions Some use Acetic acid or heavy water to delaySome use Acetic acid or heavy water to delay
High inflammatory responseHigh inflammatory response PermanentPermanent Experience is criticalExperience is critical Difficult to handleDifficult to handle
Embolic AgentsEmbolic Agents
Spheres Particles Mechanical Liquid Sclerosant
Embosphere PVA Coils NBCA Ethanol
Therasphere Gelfoam Balloons Hydrogel Acetic acid
Hepasphere Sotradecol
Contour SE Ethibloc
Beadblock
SpheresSpheres
CalibratedCalibrated Radio-pacity Radio-pacity Flow directedFlow directed CarrierCarrier Dry or wetDry or wet Polymer, hydrogel, glassPolymer, hydrogel, glass Mechanical occlusionMechanical occlusion
Company HistoryCompany History
Microspheres developed to purify Human Serum Microspheres developed to purify Human Serum Albumin and antibodies -1970sAlbumin and antibodies -1970s
IBF-French Biological Industries and later IBF-French Biological Industries and later Biosepra produce microspheres for drug Biosepra produce microspheres for drug purification - 1980spurification - 1980s
Microspheres used to produce albumin, insulin, Microspheres used to produce albumin, insulin, and genetically engineered human growth and genetically engineered human growth hormone - 1980shormone - 1980s
First use of microsphere as a human implant at First use of microsphere as a human implant at LRB in Paris, 1989 LRB in Paris, 1989
Early 1990s:Early 1990s:
Microspheres used to produce biotech drugs Microspheres used to produce biotech drugs such as TPA, AT3, gene therapy vaccinessuch as TPA, AT3, gene therapy vaccines
Sepracor purchases BiosepraSepracor purchases Biosepra
Company HistoryCompany History
Biosepra spins off from Sepracor, 1994Biosepra spins off from Sepracor, 1994
Biosepra, through its French distributor, obtains Biosepra, through its French distributor, obtains CE Mark for Embosphere, 1997CE Mark for Embosphere, 1997
Biosepra sells chromatography business, 1998Biosepra sells chromatography business, 1998
Biosepra purchases majority share of Biosphere Biosepra purchases majority share of Biosphere Medical SA and changes corporate name to Medical SA and changes corporate name to Biosphere Medical, 1999Biosphere Medical, 1999
BSMD files 510k, 1999BSMD files 510k, 1999
Company HistoryCompany History
Management team nucleus hired, 1999Management team nucleus hired, 1999
IDE filed for UAE clinicals, 1999IDE filed for UAE clinicals, 1999
European distribution expanded, 1999European distribution expanded, 1999
Australia and Canada approve Embosphere, 2000Australia and Canada approve Embosphere, 2000
PIPEs completed, 2000PIPEs completed, 2000
FDA clearance for Embosphere, 2000FDA clearance for Embosphere, 2000
Sales force recruited, 2000Sales force recruited, 2000
Company HistoryCompany History
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 beadsCross-linked acrylic beads• Precisely calibratedPrecisely calibrated• Micro-porousMicro-porous• Embedded with gelatinEmbedded with gelatin
• CompliantCompliant• HydrophilicHydrophilic• Non-clumpingNon-clumping• Patented and proprietaryPatented and proprietary
• Spherical Spherical • Non AggregatingNon Aggregating• Uniform occlusionUniform occlusion• Predictable penetrationPredictable penetration
• Irregular shape Irregular shape • ClumpingClumping• Non-uniform occlusion Non-uniform occlusion • More proximal occlusionMore proximal occlusion
EmbosphereEmbosphere
PVAPVA
A Precise CalibrationA Precise Calibration
PVA type 1
50-150 microns
PVA type 2
50-150 microns
Embosphere Microspheres -
Biosphere Medical
100-300 microns
Ultra-Drivalon 50-150m
Particle diameter (m)
1 10 100 1000
% (
volu
me)
0
10
20
30
Contour Emboli 45-150m
Particle diameter (m)1 10 100 1000
% (
volu
me)
0
10
20
30
Microspheres 100-300m
Particle diameter (m)1 10 100 1000
% (
volu
me)
0
10
20
30
Ultra-Drivalon 50-150m
Particle diameter (m)
1 10 100 1000
% (
volu
me)
0
10
20
30
Contour Emboli 45-150m
Particle diameter (m)1 10 100 1000
% (
volu
me)
0
10
20
30
Microspheres 100-300m
Particle diameter (m)1 10 100 1000
% (
volu
me)
0
10
20
30
U ltra-d riv alon – N ycom e d 5 0-1 5 0 m
C o nto u r em b oli - Targe t 5 0-1 5 0 m
E M B O SP HE R E - B iosp he re M e dical 1 00 -3 00 m
% V
olum
e%
Vol
ume
% V
olum
e
A Precise calibrationA Precise calibration
The only particulate embolic The only particulate embolic material you can trust !material you can trust !
ES 1
00/3
00ES
300
/500
ES 5
00/7
00ES
700
/900
0
100
200
300
400
500
600
Ves
sel d
iam
eter
(µ
)
PVA
150
/250
PVA
250
/400
PVA
400
/600
PVA
600
/100
00
100
200300
400
500
600
700
800
Competitive Advantage Competitive Advantage
“Controlled Vessel Targeting”
Embolization efficiencyEmbolization efficiency
ES
100/
300
ES
300/
500
ES
500/
700
ES
700/
900
PVA
150
/250
PVA
250
/400
PVA
400
/600
PVA
600
/100
00
2.5
5
7.5
10
12.5
15
17.5
20
22.5
Num
ber
of p
arti
cles
PVA
Embosphere
Perfectly sphericalPerfectly spherical
A direct correlation between the A direct correlation between the size of the vesselssize of the vessels
andand
the size of embolic !the size of embolic !
Inert biocompatible materialInert biocompatible material
Cross-linked acrylic bead impregnated Cross-linked acrylic bead impregnated with gelatinwith gelatin Chromatography media Chromatography media Cell-culturing history Cell-culturing history
Acute and chronic animal testing Acute and chronic animal testing Strong safety profileStrong safety profile
Six year implantSix year implant Complete mechanical occlusionComplete mechanical occlusion Inert material Inert material Remains unchanged over timeRemains unchanged over time
6 year implant
PVA DegradationPVA Degradation
Chronic inflammatory response
Histology slides courtesy of Dr. Alex Laurent, Hopital Lariboisiere, Paris
Non-uniform occlusion
LLong-term tolerance - Facial AVMong-term tolerance - Facial AVM
1 year
Female patientFemale patient. 25 yrs.. 25 yrs. 1989 sept Embolization with ES 500-700 & 1989 sept Embolization with ES 500-700 &
700-900700-900 1990 march1990 march Surgery Surgery 6M6M 1990 oct 1990 oct SurgerySurgery 1Y1Y 1993 feb 1993 feb SurgerySurgery 1995 oct 1995 oct Surgery Surgery 6Y6Y
6 years
6 years
Long term Long term tolerance tolerance
Facial AVM Facial AVM
Male patient, 31 yo, lip AVM1988 Embolization PVA1990 dec Embolization ES 800-10001992 nov Surgery (23 M)
23 Months
*
*
*
ES
ESES
PVA particle
23 Months* = Macrophages
BiocompatibilityBiocompatibility
PermanentPermanent
DurableDurable
CompleteComplete
MechanicalMechanical
OcclusionOcclusion
Compressible and HydrophilicCompressible and Hydrophilic
Elastic shape and hydrophilic surface prevent aggregation within the catheter, simplifying handling and promoting accurate delivery to the target vessel.
Compressible and HydrophilicCompressible and Hydrophilic
Assume 33% compression
gets backin roundshape
Embosphere and 3F CathetersEmbosphere and 3F Catheters
Brand I.D. Embosphere size in m
Micro Ferret .018 300-500
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 exclusiveproperties of their manufacturers.Here above information is purely given as indications.
A unique ease of useA unique ease of use
A superior catheter patencyA superior catheter patency
Compressible and HydrophilicCompressible and Hydrophilic
Summary of Competitive AdvantagesSummary of Competitive Advantages
Embosphere (ES) PVA ES Advantage
Spherical shape, Narrow size range
Irregular shape, wide range of sizes
Targeted and 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
Key Features & BenefitsKey Features & Benefits
FeaturesFeatures RoundRound CalibratedCalibrated InertInert CompressibleCompressible HydrophilicHydrophilic
BenefitsBenefits Complete lumen fillingComplete lumen filling Control and targetingControl and targeting BiocompatibleBiocompatible Catheter patencyCatheter patency Easy to injectEasy to inject
Platform technologyPlatform technology
The proven embolicThe proven embolic
Embosphere® microspheres:First generation of calibrated microspheres
The new Gold StandardThe new Gold Standard
EmboGold™ microspheres:User-friendly stained calibrated microspheres
Embosphere® microspheres
From right to left
40-120µm100-300µm300-500µm500-700µm700-900µm900-1200µm
Embosphere® microspheres
Calibrated microspheres available in1ml or 2ml
sizes Product codes
40-120µm 110GH 120GH100-300µm 210GH 220GH300-500µm 410GH 420GH500-700µm 610GH 620GH700-900µm 810GH 820GH900-1200µm 1010GH 1020GH
EmboGold™ microspheres
New pre-filled syringe under peel-off blister tray
Calibrated microspheresStained with Gold
100-300µm 300-500µm500-700µm 700-900µm900-1200µm
EmboGold™ microspheres
VisibilityConvenience
Performance
Stained calibrated microspheres available in PFS1ml or 2ml
sizes Product codes
100-300µm S210EG S220EG300-500µm S410EG S420EG500-700µm S610EG S620EG700-900µm S810EG S820EG900-1200µm S1010EG S1020EG