This document provides an overview of biosimilars including their definition, categories, development principles, and regulatory approval process. Biosimilars are biological products that are highly similar to an existing approved biologic reference product. They are developed through a stepwise comparative process to demonstrate similarity in terms of safety, purity and potency. Some key points covered include: - Biosimilars are large protein therapeutics derived from living organisms unlike traditional small molecule drugs. - They include categories like hormones, monoclonal antibodies, and recombinant proteins. - Their development follows principles of extensive characterization studies comparing them to the reference product. - In India, biosimilars require approval through the regulatory pathway overseen by authorities

1. BIOSIMILARS
SAFETY AND EFFICACY
Presented by:
Vinay Kumar Gautam
17PPM2688
Semester 1
Credit Presentation-1
NIPER (Mohali)

2. Flow of Presentation
• What is Biologics Agent ?
• Biologics Are Large, Protein-Based Therapeutics That Vary in Size and
Complexity
• What is biosimilars
• Definition of biosimilars
• Category of Biosimilars
• Merits /Demerits
• Uses of biosimilars
• Principles for development of Biosimilars
• Regulatory pathway for approval of Biosimilars in India
• Biosimilar development is comparative and progresses in a step-wise
manner
• Concerns with a biosimilars
• How Safety and efficacy of biosimilars can be increase
• conclusion

3. What is Biologics Agent ?
•Biologic agents are made up of or derived from,
proteins
•Rather than being chemically synthesized, they are
produced from living organism, like yeast and
bacteria.
•One of the oldest and most well-known biologic
product, insulin is made by bacteria.

4. Biologics Are Large, Protein-Based
Therapeutics That Vary in Size and
Complexity
Increasing Complexity1. Aspirin (acetylsalicylic acid) prescribing information, Bayer.
2. Insulin product information, Sigma-Aldrich. www.sigmaaldrich.com/content/dam/sigma-
aldrich/docs/Sigma/Product_Information_Sheet/2/i6634pis.pdf. Accessed February 6, 2017.
3. Online Mendelian Inheritance in Man.
www.omim.org/entry/139250?search=human%20growth%20hormone&highlight=hormone%20growth%20human. Accessed Feburary 6, 2017.
4. Chennamsetty N, et al. mAbs. 2009;1:580-582

5. What is Biosimilars ?
The concept of a “similar biological medicinal product” was adopted in
EU pharmaceutical legislation in 2004 and came into effect in 2005. The
first biosimilar i.e. Omnitrope® medicine was approved by the European
Commission in 2006.
Biosimilars are biological products that are the replica of their innovator
biopharmaceuticals. These are developed after patent expiration of
innovator biopharmaceuticals and are submitted for separate marketing
approval. In view of the structural and manufacturing complexities of
biopharmaceuticals, biosimilars should not be considered as “biological
generics.”
As the name suggests, biosimilars are similar to
a particular biologic, they are not the same.

6. Definition of Biosimilars
SBP (Similar Biologic Product)
A biotherapeutic product which is similar in terms
of quality, safety and efficacy to an already
licensed reference biotherapeutic product.
FOB (Follow-on-biologic)
A biological product that is highly similar to U.S.
licensed reference biologic product with no
clinically meaningfully differences in terms of
safety, purity, potency.

7. BIOSIMILARS also called
 Similar biologic-India
 follow on products -United States
 Bio-comparables –Mexico
 Subsequent entry biological (SEB)-Canada
Based on the above definitions, three determinants in
definition of biosimilars product:
• It should be a biologic product
• Reference product should be an already licensed
biologic product
• Demonstration of high similarity in safety,
quality & efficacy is necessary

8. Category of Biosimilars
Category Active substance Biosimilars Uses
Human growth
hormone
Somatotropin Omnitrope
Growth hormone
deficiency
Recombinant product
Epoetin
Epoetin alfa
HEXAL
To treat anaemia
Recombinant product
Filgrastim Biograstim
To prevent infections
after chemotherapy
Monoclonal antibody
Infliximab Inflectra
To treat chronic
inflammatory diseases.
Hormones
Follitropin Alfa Bemfola
To treat fertility
problem in females
Hormones
Insulin Glargine Abasaglar
To treat
hyperglycaemia
Recombinant protein
Etanercept Benepali
To treat rheumatic
disorder

9. • The development of biosimilars allows for wider and, as
important, earlier access to these agents because of their
lower cost and consequently greater affordability.
• Patent of original product is going to expire and
therefore opportunity for generic versions of
biopharmaceutical is very large.
• Lower cost is expected not only to improve cost-efficacy
ratios, but also to improve drug access.
Merits of Biosimilars

10. • Biosimilars are less stable than chemical based
pharmaceuticals.
• The cost of development will be significantly
higher than for chemical-based generics
• The required capital investment in property,
plant, and equipment and the costs of
manufacturing will be much higher for
biosimilars than for generic drugs
Dmerits of Biosimilars

11. Uses of biosimilars
• Blood conditions: leuko/neutro/pancytopenias
• Cancers: Colon & Breast Ca or NHL
• Immune system disorders: Rheumatoid
arthritis, Psoriasis & Crohn’s disease
• Neurological disorders: Multiple Sclerosis

12. Principles for development of Biosimilars
 Developed through sequential process
 To demonstrate the similarity by extensive characterization studies
revealing molecular & quality attributes with regard to Reference
Biologic (RB)
 The extent of testing of the Similar Biologic (SB) is less than RB
 Ensure that the product meets acceptable levels of safety, efficacy &
quality to ensure public health
 In case Reference biologic used for more than one indication→ efficacy
& safety of similar biologic has to be justified or if necessary
demonstrated separately for each of the claimed indications
 Justification will depend on:
• Clinical experience
• Available literature data
• Whether or not the same mechanism of action is involved in specific
indication

13. Ranbaxy Launched Indias first Biosimilar
of Infliximab – Infimab Dec 01201
4
Clinical effectiveness of
Infimab coupled with
cost effective pricing will
enable more number of
patients to get access to
biologic treatment in
india.

14. Regulatory pathway for approval of Biosimilars
in India
Rushvi P, Charmy K, Nirav C, Narendra C (2016) Biosimilars: an Emerging Market Opportunities in India. Pharmaceut
Reg Affairs 5: 165. doi:10.4172/2167-7689.1000165

15. Biosimilar development is comparative
and progresses in a step-wise manner
from: [Biosimilar medicines: better access. better health. [online]. 2016 Apr [cited 2017 Nov 07]; Available from:
http://www.medicinesforeurope.com/wp-content/uploads/2016/04/Medicines-
forEurope_BIOSIMILARS_INT_web.pdf]

16. Concerns with
Biosimilars
• The two biosimilar products have different origin.
• The two biosimilars may have same therapeutic effect.
• They may have different side effect and toxicology.
Hence Biosimilars require thorough testing.
Similarity between a biosimilar and its reference
biotherapeutic product should be evaluated in all
respects (quality, safety and efficacy).

17. How Safety and efficacy of biosimilars
can be increase
1. By making robust regulatory framework to
protect patients’ safety
The EU has a well-established system for monitoring,
reporting, assessing and preventing adverse drug
reactions for all medicines, including all biological
medicines. Authorities continuously evaluate the
benefit-risk balance of all medicines and take
necessary regulatory action (e.g. introducing new
warnings in the product information or restricting
use) to safeguard public health.

18. 2. By making Same safety monitoring for all
biological medicines
Safety monitoring of biosimilars follows the same
requirements that apply to all biological medicines.
There is no specific requirement just for biosimilars.
3. By making plan to manage risks always in place
Companies applying for marketing authorisation in the
EU must submit a risk management plan (RMP) for each
new medicine, including biological medicines. The RMP,
which is tailored for each product, includes a
pharmacovigilance plan and risk minimisation measures
to identify, characterise and minimise a medicine’s
important risks.
The RMP of a biosimilar is based on knowledge and
experience gained with the reference medicine.

19. 4. By conducting Post marketing surveillance
and pharmacovigilance: critical elements in
monitoring biosimilar safety
Post-marketing studies allow monitoring of known risks
and also permit detection of rare adverse drug reactions
that emerge only when large numbers of patients have
been treated for a long period.
The goal of pharmacovigilance is to promptly identify and
evaluate safety signals so that risks can be appropriately
managed

20. 5. Collecting spontaneous adverse drug reactions and
submitting PSURs
As for all medicines, companies marketing biosimilars must
collect all reports of suspected adverse drug reactions and
submit periodic safety update reports (PSURs) to regulators.
Regulatory authorities review reports for any signal
suggestive of a possible unwanted effect. If a signal is
suspected, it is evaluated by EMA’s scientific committees,
which will determine if any action is needed.
6. Additional monitoring and black triangle
The black triangle symbol identifies medicines under
additional monitoring. It is displayed in the SmPC and
package leaflet together with the sentence:

21. 7. Formulation and Packaging also influence the
Safety
The FDA and EMA allow sponsors to demonstrate
biosimilarity, even if there are formulation differences
relative to the reference product, but the manufacturer
must provide data demonstrating that the differences
are not clinically meaningful.
Example
one e.g. of a difference that has been accepted by the
EMA is the increased level of phosphorylated high
mannose-type structures in a biosimilar epoetinalfa
compared with the reference product.

22. 8. Immunogenicity
Immunogenicity is always studied for biological
medicines. This is because of the intrinsic ability of
proteins and other biological medicines to cause an
unwanted immune response, which, in rare cases,
could cause a serious adverse reaction (e.g.
anaphylaxis or delayed hypersensitivity) or reduced
efficacy.Because they are complex molecules synthesized in
living systems, mAbs (as well as other biologics) and
their biosimilar counterparts are potentially
immunogenic. Currently, it is not possible to develop an
exact copy of a biologic or to duplicate the
manufacturing process of the reference biologic, so it is
essential that a biosimilar be assessed for its
immunogenic potential in comparison with its reference
biologic.

24. Conclusion
Biopharmaceuticals are an important component of the treatment
armamentarium for a range of various diseases. Biosimilars are
biologics that are highly similar but not identical to their reference
products. Biosimilars may have the potential to increase patient access
to potentially valuable therapies at a lower cost. The goal of a biosimilar
development program is not to replicate the efficacy and safety profile
of a given reference biologic, but to demonstrate that the biosimilar and
the reference biologic product are “highly similar” in terms of
analytical, nonclinical, and clinical data based on the totality of
available evidence. Therefore the safety and efficacy parameter are
major concern towards biosimilars.

25. References
1. Biosimilar medicines: better access. better health. [online]. 2016 Apr
[cited 2017 Nov 07]; Available from:
http://www.medicinesforeurope.com/wpcontent/uploads/2016/04/Medic
ines-forEurope_BIOSIMILARS_INT_web.pdf
2. Biosimilars in the EU: Information guide for healthcare professionals.
[online]. 2017 Apr 27 [cited 2017 Nov 05]; Available
from:http://www.ema.europa.eu/docs/en_GB/document_library/Leaflet/2
017/05/ WC500226648.pdf
3. Biosimilars: A safe & effective option for patients. [online]. 2017 May
[cited 2017 Nov 06]; Available from
http://biosimilarscouncil.org/wpcontent/uploads/2017/06/Biosimilars-
Fact-Sheet_FINAL_5-31-17.pdf
4. Clinical Pharmacology Data to Support a Demonstration of Biosimilarity
to a Reference Product. [online]. 2016 Dec [cited 2017 Nov 05];
Available from:
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinf
or mation/guidances/ucm397017.pdf
5. Generics and biosimilars initiative. Building trust in cost-effective
treatments. [online]. 2015 Nov 11 [cited 2017 Nov 08]; Available from:
http://www.gabionline.net/Biosimilars/General/Biologicals-patent-
expiries

26. 6. Generics and biosimilars initiative. Building trust in cost-effective
treatments. [online]. 2015 Nov 11 [cited 2017 Nov 08]; Available from:
7. http://www.gabionline.net/Biosimilars/General/Biologicals-patent-
expiriesSchellekens H. Biosimilar therapeutics—what do we need to
consider?. NDT Plus 2009;2[Suppl 1]:i29
7. Weise M, Bielsky M-C, de Smet K, et al. Biosimilars:what clinicians should
know. Blood 2012;120:5111–7.
8. Wang J, Chow S-C. On the regulatory approval pathway of biosimilar
products. Pharmaceuticals 2012;5:353–68.
9. Casadevall N, Edwards IR, Felix T, et al. Pharmacovigilance and
biosimilars: considerations, needs and challenges. Expert Opin Biol Ther
2013;13:1039–47.
10. Choy E, Jacobs IA. Biosimilar Safety Considerations in Clinical Practice.
Semin Oncol 2014;41:S3 EMA:Guideline on good pharmacovigilance
practices (GVP):Product- or Population-Specific Considerations II:
Biological medicinal products

27. Thank you