DC Bead Information Brochure.pdf - Biocompatibles

Drug Delivery Embolisation System for
PRECISION TACE
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Lower systemic
doxorubicin 2,3
“DC Bead can be loaded with doxorubicin to
provide accurate dosage of the drug - making it
suitable for superselective [PRECISION] TACE. 1 ”
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Higher doxorubicin
dose in the tumour
for longer 3,4
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Consistent treatment
from a consistent
product 2

Drug Delivery Embolisation System for PRECISION TACE
Efficacy, confidence and convenience
97%
of physicians rated the
embolisation result
as good or excellent 2
“The drug eluting bead is a
promising option. Our patients have
tolerated the treatment well. 3
Dr Ronnie Poon, Queen Mary Hospital, Hong Kong”
87%
of physicians
indicated that in
their experience
PRECISION TACE
with DC Bead was
“better” than current
treatment 2 86%
of physicians
reported a reduced
incidence of sideeffects
compared
with conventional
TACE 2
“Favourable pharmacokinetic
profile should prompt a better
tolerance to treatment with reduction
”
of drug related toxicity. 4
Dr M. Varela, Barcelona Liver Cancer Clinic, Spain
“TACE with doxorubicin eluting
beads [PRECISION TACE with
DC Bead ] is well tolerated (in
neuroendocrine carcinoma).
”
5
Prof Thierry DeBaere, Institut Gustave Rousy, Villejuif, France

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Specifically designed for the controlled
loading and delivery of oncolytic drugs,
DC Bead Drug Delivery Embolisation
System brings a new level of efficacy,
confidence and convenience to trans-arterial
chemo-embolisation: PRECISION TACE.
Developed from a sulphonate-modified N-Fil
hydrogel, PRECISION TACE with DC Bead has
been proven effective in the treatment of
hepatocellular carcinoma (HCC), neuroendocrine
carcinoma and other malignant tumours. 3,4,5
PRECISION TACE with DC Bead is supported by an extensive programme of clinical trials.

PRECISION TACE
Drug Delivery Embolisation System for
Designed to improve patient outcomes
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Improved Response and Reduced Complications with
PRECISION TACE with DC Bead
Improving response
“
Objective response
was 78% at 6 months
with DC Bead (87%
at 150mg dose) with
no dose limiting
drug toxicity. 4
”
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Pharmacokinetic Profile of Systemic Doxorubicin
Lowering toxicity
“
Mean systemic
doxorubicin was 30
times lower in patients
treated with DC Bead
vs those treated with
conventional TACE. 4
”

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Consistent delivery ensuring
continued drug delivery to the
tumour over an extended period
“
The degree of variability
of Cmax in drug eluting
bead [DC Bead ] treated
patients was lower than
in those treated with
conventional TACE, with
no relationship to the
administered dose. 4
”
DC Bead loaded with
doxorubicin has been
studied in a number of
pre-clinical models
Porcine Liver 28 Days after Embolisation with
Unloaded and Doxorubicin Loaded DC Bead 2
Unloaded DC Bead - necrosis remains local to
the bead
Doxorubicin loaded DC Bead - necrosis extends
beyond location of the bead as a result of sustained
doxorubicin release over an extended period
* Necrosed Tissue
PRECISION TACE:
1 hour post treatment 8
Beads
Fibrous tissue
Viable tumour
PRECISION TACE:
14 days post treatment 8
Eluted doxorubicin from the beads
Completely necrosed liver tumour tissue

Drug Delivery Embolisation System for PRECISION TACE
Targeted embolisation combined with
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DC Bead 700-900μm
Loaded with 25mg/ml Doxorubicin
DC Bead primary embolic
characteristics allow accurate,
targeted delivery
A narrow distribution of calibrated beads
“
Catheter delivery experiments
showed that all beads were
easily deliverable without
aggregation or occlusion of the
catheter with drug loading doses
as high as 37.5mg/ml. 1
”
Before Delivery
After Delivery
“
Compressibility and rigidity is
maintained during and after
catheter delivery. 1
”
DC Bead 500-700μm loaded with 25mg/ml doxorubicin before
and after delivery through a 2.7F microcatheter. 2

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consistent drug delivery...
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An easy to use product
specifically designed to load
and elute drugs in a controlled
and reproducible profile
supported by technical data for
increased user confidence
Drug Loading
DC Bead Drug Delivery Properties
• Loads and elutes drugs relevant to clinical use
• Uniform distribution of drug throughout the
loaded beads
• Consistent local delivery to the tumour, over an
extended period
Hydrated Beads
Loaded Beads
“
Doxorubicin interacts with
DC Bead sulphonate groups. 1
”
Hydration shell
associated with
ionic groups
Bulk
(non-bound)
water
Interaction of doxorubicin
with SO-
3 groups displaces
water from the hydration
shells

...over an extended time period
For Longer 1
In Vitro Doxorubicin Elution
PRECISION TACE vs TACE 1
With DC Bead drug elution is
dependent on ion exchange and is
controlled and sustained - unlike
the rapid separation of the drug
from Lipiodol ®
“
DC Bead should enable
delivery of drug to the
tumour site over an
extended period while
minimising systemic release
of doxorubicin and reducing
the side effects associated
with conventional TACE. 1
”
• The elution half life of doxorubicin from DC Bead
ranged from 6-72 days, depending on bead size
Doxorubicin (25mg) in Saline (2.5ml)
+ Lipiodol ® (2.5ml)
White areas are
unassociated Lipiodol ®
droplets
• Doxorubicin was lost from Lipiodol ® within 4 hours
• The oily phase of Lipiodol ® did not associate with
doxorubicin
• Lipiodol ® does not help carry doxorubicin to the
tumour bed

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easy preparation
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DC Bead has been designed to offer
improved operator safety and easy preparation
and handling
To give required dose of drug
50mg 100mg 150mg
Doxorubicin vials (50mg) 1 2 3
DC Bead vials 1 2 2
Doxorubicin solution per DC Bead vial (ml) 2 2 3
STEP 1
Reconstitute each 50mg
doxorubicin vial with 2ml of
sterile water for injection.
Mix well to obtain a clear
solution.
“ DC Bead loading can be performed
easily - a one step TACE procedure that
avoids the use of caustic and unstable
chemotherapy mixtures. 1
”
STEP 3
Using a syringe and needle add
the reconstituted doxorubicin
solution directly to the vial(s) of
DC Bead .
STEP 4
Agitate the DC Bead /
doxorubicin solution gently to
encourage mixing then allow to
stand until the beads are red and
the solution is almost colourless.
STEP 2
Remove as much saline as
possible from DC Bead vial(s)
using a syringe with a small
gauge needle.
Pierce bung with a second
needle to eliminate vacuum.
STEP 5
DC Bead loading time is
dependent on bead size.
If a filter needle is not
STEP 6
available, place
flattened tip of needle
against side of vial to
prevent beads being
drawn up the needle.
Transfer the loaded beads into a
10ml syringe. Add an equal
volume of non-ionic contrast
media and mix gently (a 3-way
connector and second syringe
can be used).

Drug Delivery Embolisation System for
PRECISION TACE
Biocompatibles is a world technology leader in the development of Combination Products - medical devices combined with an active pharmaceutical agent to provide
targeted and controlled delivery of the drug. A leader in the development of drug elution technology, Biocompatibles was one of the first companies to develop a drug eluting
coronary stent. The company licenses drug elution technology to leading medical device manufacturers worldwide. The company focuses on developing Combination
Products to treat cancer, benign tumours and cardiovascular disease.
Working to rigorous external and internal quality standards, all Biocompatibles' laboratories and procedures are ISO 9001 approved and comply with GLP. Where possible,
product testing is carried out to ICH standards. Internal standards regarding data published by the company include the following:
• Data will be presented in a clear and unambiguous manner.
• Terminology used will be clearly defined:
Compatibility: The drug-bead combination is considered compatible if the two can be combined with no irreversible interaction over a period typically required for loading and
delivery of the combination. This is demonstrated by post-elution evaluation to determine that the properties of the drug and bead are the same as prior to loading and delivery.
Stability: Stability refers to the long-term interaction between the drug and the bead, and the combination can be considered stable if there is no notable degradation of the
bead or drug once stored under specified conditions over a specified period, typically 1-7 days.
• Where data have been generated inside the company, the methodology or monograph used will be summarised.
If you would like further information on any of the methodology used, please contact us and we will arrange for one of our research scientists to speak to you.
• Where data have been generated outside the company, full reference to the source will be given.
Summarised below are the sources of data provided in this piece.
References
1. Lewis, A.L., Gonzalez, V., Lloyd A.W., et al. DC Bead : In Vitro Characterization of a Drug-delivery Device for Transarterial Chemoembolization. JVIR 17:335-342 (2006).
2. Data on file. Biocompatibles UK Ltd.
3. Poon, R., Treatment of Asian Patients with Hepatocellular Carcinoma (HCC) using doxorubicin Eluting Bead Embolization (PRECISION ASIA STUDY). Presentation at
CIRSE 2004.
4. Varela, M., Real, M., et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads reduces the systemic availability of doxorubicin. A pharmacokinetic
assessment. Poster presentation. AASLD 2005.
5. Coenegrachts, K., DeBaere, T., et al. TransArterial ChemoEmbolization (TACE) of Neuroendocrine Hepatic Metastases Using Drug-Eluting Beads. Presentation RSNA 2005.
6. Llovet, J.M., Real, M.I., Montaña X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular
carcinoma: a randomised controlled trial. Lancet 2002; 359:1734-1739.
7. Lammer, J. Clinical Experience with Drug Eluting Bead (DC Bead ) for Chemoembolisation of Unresectable Hepatocellular Carcinoma. Presentation at CIRSE 2005.
8. Hong, K., Khwaja, A., Liapi, E., Torbenson, M.S., Georgiades, C.S., and Geschwind, J.F.H. New Intra-arterial Drug Delivery System for the Treatment of Liver Cancer:
Preclinical Assessment in a Rabbit Model of Liver Cancer. Clin Cancer Res 2006;12(8), 2006
DC Bead is a trademark of Biocompatibles UK Ltd
Lipiodol ® is a registered trademark of Guerbet S.A., France
Manufactured by Biocompatibles UK Ltd, Chapman House,
Farnham Business Park, Weydon Lane, Farnham, Surrey,
GU9 8QL, UK. www.biocompatibles.com
EC548 © 2006 Biocompatibles UK Ltd