Biosimilars are biotherapeutic products that are similar to already approved reference biologics in terms of quality, safety and efficacy. They are developed to be highly similar but not identical to existing biologics. Regulatory agencies like EMA and FDA require extensive analytical, non-clinical and clinical studies including pharmacokinetic, immunogenicity and clinical efficacy trials to establish biosimilarity. While biosimilars could increase access and lower costs, issues related to efficacy, safety, substitution and labeling need to be addressed to ensure patient safety and appropriate use.

1. BIOSIMILARS
DR. SAHIL KUMAR

2. BACKGROUND
•Technology + Biology
•Biopharmaceutical drugs/
Biologic(al) medical product/
Biological/
Biologic.
•Biopharmacology

3. • Preventive
• Therapeutic
• Diagnostic

6. BIOSIMILARS: INTRODUCTION
•A biotherapeutic product similar in quality, safety and
efficacy to an already licensed reference biotherapeutic
product. (WHO, Guideline for Similar Biotherapeutic Products, 2013)
•A Similar Biologic product is that which is similar in terms
of quality, safety and efficacy to an approved reference
biological product. (CDSCO, Guidelines on Similar Biologics, 2016)
•Biological medicine developed to be highly similar and
clinically equivalent to existing biological medicine.(EMA, 2012)
•A biological product highly similar to an FDA-approved
biological product and has no clinically meaningful
differences in safety and effectiveness . (FDA, 2017)

7. The Synonyms…
•Follow-on Biologics (FoBs)
•Follow-on Protein
•Follow-on Biologic Similar Biomedicines
•Subsequent entry biologicals
•SBMP (Similar Biological Medicinal Product)
Biosimilars are not (Bio)generics.

8. How are they manufactured?
1. Develop host cell
2. Establish a cell bank.
No two master cell banks are exactly alike.
3. Protein production
4. Purification
5. Analysis
6. Formulation
7. Storage and handling

10. FACTS AND FIGURES
•>500 million patients helped. (Karpusas M et al. Cell Mol Life
Sci1998;54:1203–1216).
•Biopharmaceuticals - fastest growing segments of
pharmaceutical industry (≈50% of the market).
•Global biosimilars market - $1.3 billion (2013) → $35
billion (2020) (Pharmaceutical Technology. 2015).
•Patent for original products is going to expire.
•418 new biopharmaceuticals being developed.
•↑ healthcare services, hopefully “price war” will ↓
expenditures.

11. [Calo-Fernández B, Martínez-Hurtado J (December 2012). "Biosimilars: Company Strategies to Capture Value
from the Biologics Market". Pharmaceuticals. 5 (12): 1393–1408]

12. 32%
51%
17%
Recombinant non-
glycosylated proteins
Recombinant
glycosylated proteins
Recombinant peptides

13. Examples

14. REGULATORY FRAMEWORK

15. THE EUROPEAN SCENARIO
 First recommendation in 2005; Revision in 2015.
 Europe forerunner in biosimilar legal framework
and regulations.
 EMA guideline 2015 recommends a stepwise
conduct of non-clinical and clinical studies.
 Non-clinical: binding capability, signal transduction
& potentially relevant differences compared.

16. Before approval, EMA requires studies which should
include:
a) Pharmacokinetic and Pharmacodynamic studies,
b) Clinical trials of appropriate patient populations,
c) Choice of clinical endpoints in efficacy trials,
d) Evaluation of the immunogenicity of the biosimilar,
e) Pharmacovigilance studies
aimed at extrapolating safety and efficacy of the new
biosimilar with respect to the already authorized
branded medicinal product.

18. THE US SCENARIO

19. INDIAN SCENARIO
•Regulatory bodies- Deptt. of Biotech. (DBT), & the CDSCO
– under the MoHFW.
•15th Aug 2016: “Guidelines on Similar Biologics:
Regulatory Requirements for Marketing Authorization
in India”
Salient features –
•If reference biologic not marketed in India, can be licensed
in other specific countries.
•Post-marketing : >200 patients; completed within 2 years.

20. •If immunogenicity evaluated in clinical studies, not
mandatory to carry out in post-marketing studies.
•If pre-approval studies >100 pts; no. of pts for safety data
can be reduced.

21. ISSUES WITH BIOSIMILARS
1) Efficacy: Difference b/w bioactivity of biosimilars and
reference products.

22. 2) Safety:
•Concerns regarding immunogenicity.
•Consequences: ↓ or ↑ of efficacy, neutralization of a
native protein & general immune effects (allergy,
anaphylaxis, serum sickness).
•Eg. Pure Red Cell Aplasia (PCRA) by Epoetin α.
•Prone for batch to batch variation. Need for continuous
robust pharmacovigilance monitoring to ensure the
traceability of the products.

23. 3) Substitution:
•↓ safety of therapy, causes therapeutic failure.
•Can confound pharmacovigilance.
•Should be made with physician’s consent.
4) Labeling:
•Labels should be different.
•A summary of product characteristics should be
transparent and clear.
•Reference products should be defined.
•Substitution advice should be provided.

24. CHALLENGES
Higher development cost.
Same company may market 2nd Generation agents.
Less stable.
Traceability.
Nomenclature.

25. CONCLUDING REMARK

26. THANK YOU
“The process
is the
product.”