The document discusses the development of biosimilars as a cost-effective alternative to biologics, which are sophisticated and expensive drugs derived from living organisms. It defines biosimilars as similar biological products that demonstrate quality, safety, and efficacy comparable to reference biologics but are not chemically identical. The regulatory framework for their approval includes stringent guidelines and requires extensive studies to ensure safety and effectiveness, particularly in terms of immunogenicity and pharmacokinetics.

5. Biotechnology has led to the development of more and more
Biologics. But the process is complex and expensive.
Developing a cheaper yet equally efficacious and safe
biological product has become a necessity. This has led to the
development of Biosimilars.

7. What is a Biosimilar?

8. Term By Definition
SBP (Similar Biologic
Product)
WHO Similar to an already licensed reference
biotherapeutic product in terms of
quality, safety & efficacy
FOB
(Follow-On Biologic)
US-
FDA
Highly similar to the reference product
without clinically meaningful differences
in safety, purity and potency
SEB
(Subsequent Entry
Biologic)
Canada Drug that enters the market subsequent
to a version previously authorized in
Canada with demonstrated similarity to
a reference biologic drug

10. Recombinant Non-glycosylated
Proteins
• Insulin
• Human Growth Hormones
• Granulocyte Colony-
stimulating Factor (G-CSF)
• Interferons
Recombinant Glycosylated
Proteins
• Erythropoietin
• Monoclonal Antibodies
• Follitropin
Recombinant Peptides
• Glucagon
• PTH

11. • Biovac B (Hepatitis B vaccine) - India.2000
• Omnitrope (Somatropin) – EMA.2006
• Zarixo (Filgastrim) USFDA.2015

12. Drug Number
Filgastrim 6
Peg-filgastrim 4
Erythropoietin 4
Insulin Glargine 4
Interferon α 2b 4
Rituximab 3
Darbepoetin 3
Teriperatide (PTH) 3

13. Structural and
manufacturing complexities
Different
companies,
different
processes
Manufacturing
process of
Innovator
molecule -
undisclosed
Mimic the activity and safety of
the original biologic.
They are not chemically identical.
They are not necessarily produced
in the same way.
“Represent a different means to a similar end.”

14. Biosimilar Generic
Source Living organisms Chemical synthesis
Size Large molecule Small molecule
Structure Complex, heterogeneous Well defined
Manufacturing process Difficult Relatively simple
Stability Unstable, sensitive to
external conditions
Stable
Immunogenicity Immunogenic Mostly non-immunogenic
Bio-equivalence with reference product No Yes
Interchangeable with Reference product No Yes
Cost High Low

15. Insulin Glargine
Lantus Sanofi Rs. 2714
Basalog Biocon Rs. 1380
Rituximab
MabThera Roche Rs. 16,ooo
Reditux Dr. Reddy’s Lab Rs. 9999

16.  Sequential process
 Demonstrate the similarity with regard to Reference
Biologic (RB)
 By extensive characterization studies revealing molecular
& quality attributes
 Ensuring that the product meets acceptable levels of
safety, efficacy & quality to affirm public health

17. Phase I
followed
by Phase
III trials
Non-
clinical and
Toxicology
Studies
Drug
Substance
Production
Clone
Selection
Reverse
Genetics
ACCESSTHE REFERENCE PRODUCT AT EVERY STEP

18. The approach established for generic medicines is not
suitable for development, evaluation and licensing of
similar biotherapeutic products (SBPs), since
biotherapeutics consist of relatively large and complex
proteins that are difficult to characterise.
April 2010, the Expert Committee
on Biological Standardization
(ECBS) established written
standards.

19. ‘Guidelines on Similar Biological Medicinal Products’, October 2005.
Amended version came into effect on 30 April 2015.

21. 26 March, 2016
Central Drugs Standard Control Organisation (CDSCO),
Ministry of Health and Family Welfare, Government of India,
announced the release of proposed revised guidance for
‘similar biologics' in India.

22. • Drugs and Cosmetics Act, 1940
• Drugs and Cosmetics Rules, 1945
• Rules for manufacture, use, import, export and storage
of hazardous micro-organisms/genetically engineered
organisms or cells, 1989
• Environment (Protection) Act, 1986

24. CDSCO
GEAC
RCGM
IBSC
• Biosafety on‐site
• Initial review of
applications to be
recommended to RCGM.
• Authorizing conduct of
research
• Exchange of genetically
engineered cell banks for
research and
development
• Review of data up to
preclinical evaluation
• Review of applications
and approval of activities
where final drug product
contains genetically
Modified organisms/
living modified
organisms.
• Approval of clinical trials
as well as new drugs.
• Clinical trial approval
• Permission for import of
drugs for clinical trial
• Export of clinical samples
for biochemical and
immunological analysis
• Permission for marketing
and manufacturing

25. Product Development
Animal Study
Clinical Trial
Licensing
Marketing
P
R
O
C
E
S
S

42. Structural and functional
comparability of similar
biologic and reference
biologic can be characterized
to a high degree of
confidence by
physicochemical and in vitro
techniques
The similar biologic is
comparable to reference
biologic in all preclinical
evaluations conducted

43. PK / PD study has demonstrated comparability and has preferentially
been done in an in-patient setting with safety measurement
(including immunogenicity) for adequate period justified by the
applicant and efficacy/PD measurements
A comprehensive post-marketing risk management plan has been
presented that will gather additional safety data with a specific
emphasis on gathering immunogenicity data

44. Single arm study in at least 100 evaluable
subjects