3. Biosimilars are legally approve successive version
of innovator biopharmaceutical product which made
up by a different sponsor to following patent and
exclusive expiry of innovators product.
Biosimilars are considered as similars because of
there manufacturing complexities and structures are
similar to innovators product.
4. Interpretations of biosimilar product are followed by
three terms
SBP (Similar Biologic Product)
FOB (Follow On Biologic)
SEB (Subsequent Entry Biologics)
6. Krabeva
Brand Name : Krabeva
Generic Name : Bevacizumab
Bevacizumab is produced in a Chinese Hamster
Ovary mammalian cell expression system in a
nutrient medium containing the antibiotic gentamicin
and has a molecular weight of approximately 149
kDa.
7. Krabeva® being launched post successful
completion of phase 3 clinical trials and approved
by by BIOCON’s marketing authorization by the
Drug controller general of India (DCGI).
Routes of administration: Intravenous
it is a recombinant humanized monoclonal antibody
(Mab) used for the treatment of various types of
cancer.
9. VEGF: Vascular endothelial growth factor, a
polypeptide that is structurally related to platelet-
derived growth factor (PDGF).
While expressed in normal tissues, Tumors release
the VEGF protein in physiologically relevant levels,
causing nearby blood vessels to sprout new vessels
— a process called angiogenesis. New blood
vessels feed the growth of the tumor while providing
a "highway" for tumor cells to spread to other parts
of the body
10. VEGF also acts as a mitogen for vascular
endothelial (vessel lining) cells, stimulating these
cells to divide and multiply. VEGF: ◦ Promotes tumor
vessel Survival ◦ Promotes tumor vessel permeability
and ◦ Stimulates tumor vessel growth
VEGF:
◦ Promotes tumor vessel Survival
◦ Promotes tumor vessel permeability and
◦ Stimulates tumor vessel growth
11. Proposed effect
Potential effects on
vessel
Potential impact to
tumors
Anti-vascular
Regression of
existing tumor
vasculature
Reduction of tumor
size
Anti-angiogenesis
Inhibition of new and
recurrent
tumor vessel growth
Inhibition of tumor
growth
12. it is a therapeutic antibody that specifically binds to
the VEGF protein — a potent source of
angiogenesis.
It may block the tumor's ability to communicate with
nearby blood vessels, preventing its ability to grow
and in response retardation of metastatic tumor
growth occurs.
Specifically, Bevacizumab binds VEGF and prevents
the interaction of VEGF to its receptors (Flt-1 and
KDR) on the surface of endothelial cells.
13.
14. Abnormalities on the tumor vessel cause plasma
leakage from the vessels, creating high pressure
inside the tumor that may restrict anti cancer drug
delivery.
◦ Promotes regression of existing vessels
◦ Normalization of growing vessels
◦ Preventing vessel growth
◦ Abnormalities contributing to vessel permeability are
closed
15. Krabeva® with the first of its kind Qual check
feature, which is an innovative temperature-sensitive
packaging that include the thermo-chromic sticker
which change color irreversibly if cold chain
temperature is not maintained. It provides greater
confidence to pharmacists about quality of product
that they are gonna dispensing and will enable better
patient safety.
16. Dosage & Administration
Dosage Forms
100mg/4ml single-use vial
400mg/16ml single-use vial
Administration
Administration of this drug only by the Intravenous infusion not
intravenous push or bolus.
Do not instigate Krabeva until the 28 days period time of
surgeries, only administered after the incision of surgery has
fully healed.
Two types of infusion :
First infusion: administered over 85-90 minutes.
Subsequent infusion: if first infusion is tolerated then give
the second infusion which is timely period of over 60 minutes.
17. Contradiction
Contradictions are none
OVERDOSAGE
The highest dose were tested in humans is (20 mg/kg
4), it was associated with the headache in 9 of 16
patient & with severe headache in 3 of 16 patients.
18. Manufacturing
Bevacizumab derived from a murine monoclonal
antibody. By using hybridomas technique to
generate mice immunized with 165- residue form of
recombinant human vascular endothelial growth
factor (rhuVEGF165). The antibody later then
humanized to human IgG1.
19. Upstream process – Fermentation
Fed batch culture at a 12,000L scale using CHO cells in
suspension using serum free, low protein cell culture
growth media containing recombinant human insulin.
Downstream process – Purification
SPA: affinity column (protein A resin), binds to
bevacizumab and it removes mainly host cells protein
(CHOP) and DNA.
AEX: Anion exchange chromatography in flow through
mode, design to reduce CHO proteins, DNA, protein A,
potential viruses.
CEX : cation exchange chromatographic designed to
further reduced the residual amounts of CHO proteins,
gentamycin and aggregates in bind and elute mode
The pool is concentrated, diafiltered and further
concentrated.
26. Clinical Development
Krabeva’s bevacizumab developed for global
markets with a focus to meet the strict qualities & the
regulatory requirements to provide the highest
quality of biosimilar to patient.
It is currently in the pipeline, the phase 3 clinical
study involving 146 patients of mCRC conducted
after the approval from DGCI and regulatory
approvals of India.
27. Market Size
The market size for Bevacizumab both innovator
product and biosimilar, In India is estimated at Rs
177 Crore, according to IPSOS June MAT 2017
data.
