The present slide focuses on the applications and different uses of biosimilars along with the basic difference in between biosimilars and bioequivalence.

1. BIOSIMILARS
Definition: A biosimilar (also known as follow on biologic or subsequent entry biologic) is a
biologic medical product that is almost an identical copy of an original product that is
manufactured by a different company. Biosimilars are approved version of original innovators
product and can be manufactured when the original product patent expires. Reference to the
original product is an integral component of the approval.
OR
Legally approved subsequent versions of innovator biopharmaceutical
product made by a different sponsor following patent and exclusivity expiry of the innovator
product. Because of structural and manufacturing complexities these are biological products are
considered as similar, but not generic equivalents of innovator biopharmaceuticals.
Unlike with generic drugs of the more common small molecule type,
biologics generally exhibit high molecular complexity and may be quite sensitive to changes in
manufacturing processes. Despite that heterogeneity all biopharmaceuticals including biosimilars
must maintain consistent quality and clinical performance throughout their lifestyle. Overall it is
harder to ascertain fungibility between generics and innovators among biologics than it is among
totally synthesized and semi-synthesized drugs. That is why the name biosimilar was coined to
differentiate them from small molecule generics.
According to USFDA, EMA analytical studies demonstrate that the biological product is highly
similar to the reference product despite minor differences is clinically inactive components,
animal studies. They are sufficient to demonstrate safety, purity and potency in one or more
appropriate conditions of use for which the reference product is licensed and intended to be used
and for which licensure is sought for the biological product.
Nomenclature: The WHO and USFDA have been working for years on the non-proprietary
naming of biosimilars. In August 2015 the FDA published a draft guideline on the topic. In brief
the guideline cells for the assignment a four character alphabetic suffix to the non-proprietary
name of the original product to distinguish between innovators drugs and their biosimilars. The
WHO INN system cells this suffix a biologic modifier.
Interpretation of Biosimilars product:
 SBP(SimilarBiologic Product): WHO---- Similar to an already licensed reference
biotherapeutic product in terms of quality, safety and 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 entersthe
marketsubsequent to a version previously authorized in Canada with demonstrated
similarity to a reference biologic drug.

2. Basedon different definitions there are three determinants for a compound to be a
biosimilar. They are:
1. It should be a biologic product.
2. The reference product should be an already licensed biologic product.
3. The demonstration of high similarity in safety, quality and efficacy is necessary.
Similarity should be demonstrated using a set of comprehensive exercise at
quality, clinical level and non- clinical level.
Difference between generic and biologicals:
 Heavier:Unlike structurally well defined, low molecular weight chemical drugs
biosimilars are high molecular weight compounds with complex three dimensional
structure. e.g Mol. Wt. of Aspirin is 180 Da whereas for interferon-β it is 19000 Da.
 Larger: Typical biologics are 100-1000 times larger than small molecule chemical drug.
 Difficult to define structure : Small molecule drugs are easy to reproduce and specify by
mass spectroscopy and other techniques whereas for larger molecules( biosimilars) lack
of appropriate investigative tools to define structure of large protein.
 Manufacturers of biosimilars don’t have access to manufacturing process of innovator
products unlike generics.
Concerns with the use of biosimilars:
 Efficacy issues: Differences between the bioactivity of the biosimilars and their
innovative product.e.g. 11 epotin Alfa products from 4 different countries have shown
significant diversions from specification for in-vivo bioavailability by 71-226%.
 Safety issues: Concerns regarding immunogenicity has been observed where increase
in cases of pure red cell alpha associated with specific formulation of epotin-α.
 Pharmacovigilance: Due to limited clinical database at the time of approval. Also
vigorous pharmacovigilance is required where immunogenicity is an unique case.
 Naming and labelling: Generic adaptation of chemical medicines is assigned to the
same name as they are identical copies of the reference product. Biosimilars require
unique INNs as this would facilitate prescribing and dispensing ofbiopharmaceuticals
and precise pharmacovigilance.
Applications of Biosimilars: There are 25 approved biosimilars by the USA till date
and the most recent biosimilar approval was Abrilada on November 2019.
I. First application is insulin glargine for the treatment of diabetes mellitus.
II. Six applications are for the neutropenia treatment pefilgastrin and three for breast
cancer treatment Trastuzumab.
III. Currently 7 biosimilars have been approved by the USFDA for use in Crohn’s
disease ulcerative colitis and colorectal cancer. Other biologics are involved in
gastroentreologic diseases for which there are no FDA approved biosimilars.

3. Global Scenario :In 2010 sales of biologicals reached 100 billion dollar worldwide with the
12 biologics generating 30 billion dollar. Global market for biosimilars was 311 million dollar in
2010 and expected to increase to 2 billion – 2.5 billion dollar in 2015.
Indian scenario:One of the leading contributors in the world of biosimilar market because of
cost effective manufacturing, highly skilled, reasonably priced workforce and huge market.
Some of the biosimilars approved in India are :
 Epotin alfa--- Epofit in August 2005 by Intas biopharmaceuticals.
 Darbopoetin alfa ----- Cresp in August 2010 by Dr. Reddy’s Laboratories
 Reteplase ---- Mirel in 2009 by Reliance Life Sciences.
Others are : Avastin ----- Mvasi, Zibrabev
Enbrel------ Erelzi / Eticovo
Herceptin ----- Ogivri / Hercuma