Biosimilar development

What is a biosimilar
A medicine which similar to biological biopharmaceutical
medicine that has already been autorized
The active substance of a biosimilar is similar to the one of
biological /biopharmaceutical reference medicine (sugars,
proteins, or nucleic acids or complex)
Used in the same dose to treat the same disease
Biosimilar in Indonesia : Kalbio, Dexa, Biofarma
Ex: EPO (Erythropoietin untuk anemia pada pasien gagal
ginjal)

Development pipeline

Exploratory

Drug
charaterization

Drug candidate
desain

Understand
the
disease
Epid data
Identity
antigen

Seed
history
Presentatio
n
Route
of
administrati
on

Preclinical
studies

Bulk
manufactur
e
Formulation
Identity
Purity
Standard
stability

Pilot scale

Safety
Toxicology
Teratology

Clinical
developme
nt

Clinical lot
cGMP
QC
QS

Regulatory
Approval

GCP
Phase I
Phase II
Phase III

Commercial
manufacturin
g

Document

Regulatory
compilance
cGMP
QC
QMS

Preparation of Biopharmaceutical

The DNA sequence and the host cell will

significantly

Develop host cell

No two master cell bank are exactly

identical

Establish cell bank

Protein production

The condition of culturing can affect the nature of the

end product

Any change in the purification process can affect the clinical product
charateristics

Purification

Storage and handling

Formulation
Analysis

Poor adherence to cold storage requirements and shaking can affect clinical
efficacy and safety
Component and process of the formulation. Can significanly affect the product
behavior in patients
Analysis has limited ability to detect all product charateristic that may affect clinical
efficacy and safety

Process in Biosimilar : Research scale

Upstrea
m

Start

Downstre
am

Analysis

Gen sequence

MCB

Harvest

Chemical/physi
cal

Vector

Fermentation

Capture

Biology

Host cells

Enzyme process

Intermediet
purification

Polishing

Process in Biosimilar : Start gene design

Sintetic gene
Conventional Gene isolation

Vector cloning
Vector expression

Mamalian
Bacteria
Yeast

Upstream : research scale

Upstrea
m

MCB

Fermentation

Sintetic gene/ conventional Gene isolation,vector

cloning, expression test
MCB characterization, MCB storage
Mammalian,yeast, bacteria : media, growth
factor
Fermentor and bio-reactor
Secondary Metabolism detector

Downstream : research scale

Downstre
am

Harvest

Capture

Centrifuge, TFF (Tangensial flow filtration), direct filtration

Microfluidic, French Press, sonicator
Chromatography system
Chromatography resin

Enzyme process

Trypsin, or protease
Conventional Gene isolation

Intermediet
purification

Chromatography system
Chromatography resin

Polishing

Chromatography system
Chromatography resin

Analysis

Analysis

Chemical/physi
cal

Biology

Primary, secondary, tertier and quartenary structure

LC-MS/MS
DLS
CD
Binding assay : ELISA or SPR
In vitro assay
Endotoxin test
Host cell DNA /protein residual
Isoelectric focusing
Western blot