The Concept of Biosimilars: From Characterization to Evolution—A Narrative Review

FADI FARHAT,a,† ALFREDO TORRES,b WUNGKI PARK,b GILBERTO DE LIMA LOPES,b RAJA MUDAD,b CHUKWUEMEKA IKPEAZU,b SIMON ABI AAD
b,†

aDepartment of Hematology-Oncology, Hammoud Hospital University Medical Center, Saida, Lebanon; bDepartment of Hematology-
Oncology, University of Miami-Sylvester Comprehensive Cancer Center, Miami, Florida, USA
†Contributed equally
Disclosures of potential conflicts of interest may be found at the end of this article.

ABSTRACT

Biologic agents are currently the fastest emerging segment
of drug expenditure. Unlike chemically synthesized small molecule
drugs, biologics are more complex, medicinal products
produced by a living organism. They have become part of
the standard of care in the treatment of a large variety of diseases,
such as growth disorders, autoimmune diseases, cancer,
cardiovascular illnesses, hemophilia, and rare genetic conditions,
to name a few. Biosimilars, which are copies of biologics
that are highly similar, were introduced in the market with
an aim to offer efficacy that is not clinically different from
the originator or reference product, at lower prices. We aim
to clarify the concept of biosimilar, from definitions, history, market entry, challenges faced, and future evolution. For
that purpose, we performed a literature search on the sites of
the medicines regulatory agencies and PubMed from 1990 to
2014 with the keywords “biosimilars,” “market,” and
“regulatory.” In 2006, the first biosimilar, somatropin [rDNA
origin], was marketed and led the way for biosimilar drug
manufacturing. As a result, manufacturers have entered a
diversified competition, facing challenges in manufacturing
these complex agents, such as immunogenicity and efficiency.
Biosimilars are set to evolve differently in various markets,
namely the U.S., Japan, the European Union, and the
“pharmerging” economies. The Oncologist 2018;23:346–352

Blockage of a receptor by the Monoclonal Antibody

INTRODUCTION

The financial burden of health care and prescription medication
has been increasing tremendously all over the world, with an
estimated total cost of 1.2 trillion U.S. dollars (USD) by the end
of 2016 [1]. Biologic medicines, known simply as biologics, are
large and complex molecules, produced from or by microorganisms.
This relatively new line of pharmaceutical products represents
a significant portion of pharmaceutical product costs,
with an estimate of up to 210 billion USD (17.5%) of the total
medical spending [1].
For successful entry of a biosimilar market, the following
are needed: (a) adequate research and development capacity,
(b) specific biomanufacturing platform, (c) supporting activities
such as legal expertise and global distribution and commercialization
channels, (d) an international network of marketing sales
representatives, and (e) strong lobbying with regulatory bodies,
opinion leaders, and governments to accelerate the approval of
laws and regulations [2].
Biologics have made substantial contributions to improve
the effectiveness of treatment of many areas of disease and

they are expected to continue to do so in the future. However,
these benefits come at increasingly higher costs, which endanger
accessibility and the financial sustainability of health care.
As a result, the expiration of patents and other intellectual
property rights of biologics made it possible for biosimilars to
enter the market, which in turn increased competition among
manufacturers of biologics, contributing to billions of dollars in
savings in the health care sector [3]. In Europe, most biosimilars
are marketed with a discount of around 20%–35% versus the
price of their reference products [4]. This allows patients to
receive therapies that were difficult or impossible to be
received. For example, in countries where access to epoetins
was especially restricted (e.g., Bulgaria, the Czech Republic,
and Romania), cost savings have been estimated at 50%,
with an increase in average uptake of more than 250% for a
biosimilar [5].
Recently, many reviews have been published on biosimilars
[4, 6, 7]. In particular, Santi et al. and Vital et al. focused on the
aspects to be considered in biosimilar follicle-stimulating

hormone (FSH) and rituximab usage, respectively [6, 7]. In this
article, we aim to clarify the concept of biosimilars in all therapeutic
classes, including definitions, history, market entry, challenges
faced, and future evolution.