This document provides an overview of biosimilars including their advantages and disadvantages. It discusses regulatory guidelines for biosimilar approval in India, challenges in biosimilar development and production, and recently approved biosimilars. The conclusion recognizes biosimilars as an important part of the pharmaceutical ecosystem but one that faces barriers to adoption such as questions of interchangeability and not having approval for all reference product indications. It recommends overcoming challenges to biosimilar market access.

1. BIOSIMILARS
Z E H V A K H A N
M . S C . ( C L I N I C A L R E S E A R C H )
C T C R , S C L S
J A M I A H A M D A R D

2. CONTENT:
 INTRODUCTION
• ADVANTAGES OF BIOSIMILARS
• DISADVANTAGES OF BIOSIMILARS
 GUIDELINES ON SIMILAR BIOLOGICS
• DATA REQUIREMENTS
 BIOSIMILARS IN INDIA
 CHALLENGES IN PRODUCING BIOSIMILARS
 RECENTLY APPROVED BIOSIMILARS
 CONCLUSION
 REFERENCES

3. INTRODUCTION:
A biosimilar product is a biologic product that is approved based on
demonstrating that it is highly similar to an FDA‐approved biologic
product(reference product)
there are no clinically meaningful differences between the
biological and the reference product in terms of the safety,
purity, and potency of the product
Reference and biosimilar products are:
• Large and generally complex molecules
• Produced from living organisms
• Carefully monitored to ensure consistent quality

4. • Various Biosimilar terminologies used by different regulatory
bodies:
Regulatory bodies Terminology used for Biosimilar
US-FDA Follow on Biologics
WHO Similar Bio therapeutic Product
CDSCO Similar Biologics
The European Medicines Agency (Europe) Biosimilar
The National Health
Surveillance Agency or ANVISA(Brazil)
Follow on Biologics
The Health Products and Food
Branch (HPFB)(Canada)
Subsequent Entry Biologics
The Pharmaceuticals and Medical Devices
Agency (Japan)
Follow on Biologics

5. Contd.
While biosimilars are similar to their reference biological product, they
are not generic equivalents

6. SMALL-MOLECULE DRUG LARGE BIOLOGIC
• Small-molecule drugs are smaller and less complex than biologics
and are chemically synthesized
• Conversely, biologics are larger and more complex and are created
from living cells
Contd.

7. ADVANTAGES OF BIOSIMILARS:
• Expand Treatment Options for Complex Diseases
• Substantial Cost Savings on Expensive Therapies
• FDA-Approved, Safe and Effective Treatments
DISADVATAGES OF BIOSIMILARS:
• Biosimilars are not as much of stable as chemical based
pharmaceuticals
• The cost of development will be importantly higher than for chemical
based generics

8. Guidelines on Similar Biologic:
Regulatory Requirements for Marketing Authorization in India
• The “Guidelines on Similar Biologic” prepared by CDSCO and the
Department of Biotechnology (DBT) lay down the regulatory pathway
for a Biologic claiming to be Similar to an already authorized Reference
Biologic
• The guidelines address the regulatory pathway regarding:
o Manufacturing process
o Safety
o Efficacy
o Quality

9. Contd.
•These guidelines also address the pre‐market regulatory requirements
including:
o Comparability exercise for quality
o Preclinical and clinical studies
o Post market regulatory requirements
•The similar biologics are regulated as per the:
o Drugs and Cosmetics Act, 1940
o The Drugs and Cosmetics Rules, 1945

10. Contd.
o Rules for the manufacture, use, import, export and storage of
hazardous microorganisms/ genetically engineered organisms or cells,
1989 notified under the Environment (Protection) Act, 1986
• Various applicable guidelines are as follows:
o Recombinant DNA Safety Guidelines, 1990
o Guidelines for generating preclinical and clinical data for rDNA
vaccines, diagnostics and other biologicals, 1999
o CDSCO guidance for industry, 2008
o Guidelines and Handbook for Institutional Biosafety Committees
(IBSCs), 2011

11. DATA REQUIREMENT:
Analytical and quality characterization data:
o Comparability according to critical quality attributes of product
including physicochemical properties, biological activity,
immunological properties, functional assays, purity, contamination,
strength, and content
Non-clinical studies:
o In vitro studies: e. g. cell-based bioassay
o In vivo studies: PD activity, immunogenicity, at least one repeat dose
toxicity study, local tolerance
Safety pharmacology, reproductive toxicity, mutagenicity, and carcinogenicity
studies are not required unless warranted by repeat dose toxicity studies

12. Contd.
Clinical studies:
• Phase I: Comparative PK and PD studies; PK/PD relationship may be
evaluated (PD evaluation can also be done as part of Phase III study)
• Phase III: Comparative efficacy and safety/immunogenicity study are
essential
o Equivalence design study is preferred
o Non-inferiority design needs to be justified
• Safety and efficacy CT can be waived off if comparable quality, non-
clinical and clinical PK-PD data with post-marketing risk management
plan is provided
• Post-marketing: Safety and immunogenicity data must be submitted

13. Contd.
Extrapolation to other indication:
o May be possible if the same Mechanism of Action/receptors for
indications (with similar safety, efficacy, preclinical and quality data)
Reference product requirements:
o Reference biologic should be licensed in India and should be
innovator product
o If reference biologic is not marketed in India, then it should be
licensed and widely marketed for four years post approval in
innovator jurisdiction in a country with the well-established
regulatory framework
o In case no medicine or only palliative therapy is available or in the
case of national healthcare emergency, this year of 4 years may be
reduced or waived

14. • Proposal of Regulatory and Approval Pathway for
Biosimilars

16. BIOSIMILARS IN INDIA:
SUCCESS TO DATE
• India’s first biosimilar, a vaccine for hepatitis B, was marketed and
approved in 2000, according to the global Generics and Biosimilar
Initiative; more than a decade before the US FDA approved its
first biosimilar
• Approximately 70 biosimilar products have been approved in
India and, more than 25 have been developed in India since 2000
• The Indian Government has made approvals in the country
consistent with regulations elsewhere to make it easier for Indian
companies to gain approval in other jurisdictions
• In 2012, India’s Central Drugs Standard Control Organisation
published regulatory guidelines for biosimilars, with revised
guidance added in 2016

17. Top Biosimilar Products in USA
Top Biosimilar Products in India

18. Contd.
•Four of India’s largest pharmaceutical companies are:
o Dr. Reddy’s Laboratories
o Cipla
o Lupin
o Aurobindo
•With a larger slice of India’s pharmaceutical sector embracing biosimilar
development in the coming years, it would not be surprising to see the
country build as strong a position in biosimilars as it has in the generics
space

19. CHALLANGES IN PRODUCING
BIOSIMILARS:
• Despite successful development and marketing of biosimilars in
India, R&D department continue to face challenges in developing
biosimilars as they are much more complex and expensive to create
• Pharmaceutical companies in India primarily focused on the
development and production of generics need to adapt their R&D
manufacturing processes since they are producing more than simply
a copy
• Their manufacturing needs to be managed through a highly
controlled processes and manufacturing environment which requires
significant investment in order to alleviate the risk of even minor
variations introducing unacceptable changes to product quality

20. RECENTLY APPROVED BIOSIMILRS:
S.No. Biosimilar Reference Product Company FDA Approval
1 Avsola
(infliximab-axxq)
Remicade Amgen Inc. December 6, 2019
2 Abrilada
(adalimumab-afzb)
Humira Pfizer Inc. November 15, 2019
3 Ziextenzo
(pegfilgrastim-bmez)
Neulasta Sandoz Inc. November 4, 2019
4 Hadlima
(adalimumab-bwwd)
Humira Samsung Bioepis Co., Ltd. July 23, 2019
5 Ruxience
(rituximab-pvvr)
Rituxan Pfizer Inc. July 23, 2019
6 Zirabev
(bevacizumab-bvzr)
Avastin Pfizer Inc. June 27, 2019
7 Kanjinti
(trastuzumab-anns)
Herceptin Amgen Inc. June 13, 2019

21. CONCLUSION:
Biosimilar are expected to become a progressively important part of
the pharmaceutical Ecosystem
Manufacturers continue to face barriers to adoption, including:
o Questions of interchangeability
o A typical lack of approval for all the reference biologic’s
indications
o The need for biosimilar manufacturers to negotiate with payers
o The challenge of overcoming unique patent dynamics
o And innovators’ established positions within the physician
community

22. Recommendations for overcoming
challenges to market access

23. REFERENCES:
• https://www.pfizerbiosimilars.com/characteristics-of-biosimilars,
Accessed on 21 January, 2019
• https://www.mckesson.com/resources/biosimilars/, Accessed on 21
January, 2019
• https://www.pharmaceutical-technology.com/features/expanding-
generics-biosimilars-in-india/, Accessed on 21 January, 2019
• Meenakshi K. Chauhan et al, Regulatory guidelines for approval of
biosimilars in India, Europe, Brazil and China: A comprehensive
overview, International Journal of Pharmacy and Pharmaceutical
Sciences Vol 8, Issue 10, 2016
• http://cdsco.nic.in/writereaddata/Proposed%20Guidelines%20for%20Si
milar%20Biologic%202016.pdf, Accessed on 22 January, 2019

24. Contd.
• https://bioprocessintl.com/manufacturing/biosimilars/opportunities-
challenges-biosimilar-development/, Accessed on 26 January, 2019
• Pooja Paul et al, Current scenario of biosimilar, The Pharma
Innovation Journal 2018; 7(7): 188-193
• https://www.fda.gov/downloads/Training/ClinicalInvestigatorTraining
Course/UCM378510.pdf, Accessed on 27 January, 2019
• https://www.drugs.com/medical-answers/many-biosimilars-
approved-united-states-3463281/

25. THANK YOU