PAID ADVERTISEMENT
Biologics, Biosimilars and
the United States: An Overview
BIOSIMILARS VERSUS BIOLOGICS:
WHAT’S THE DIFFERENCE?
The first biosimilar has been approved in the United States,
paving the way for many others that are certain to follow.
According to the US Food and Drug Administration (FDA),
biosimilars are defined as biological products that are highly
similar to an FDA-approved biological product (also called the
reference product), with no clinically meaningful differences
in safety and effectiveness. Only minor differences in clinically
inactive components are permitted.1 This definition is closely
aligned with that of the European Medicines Agency (EMA)
and the World Health Organization (WHO).2,3
Biological products, or biologics, vary widely and can comprise
a complex combination of proteins, nucleic acids and posttranslational elements such as sugars, or they may be living
entities such as cells and tissues. For the purposes of
this discussion, we are focused on recombinant therapeutic
proteins. Biologics are isolated from a variety of natural
sources—human, animal or microorganism—and are produced
using biotechnology and/or other innovative technologies.4
DEVELOPMENT AND GROWTH OF BIOSIMILARS
IN THE UNITED STATES
Biologics have been revolutionary in the treatment of many
diseases, including cancer, multiple sclerosis and chronic
kidney disease. However, relative to the number of patients
treated, biologics account for a disproportionate amount
of healthcare resources and continue to outpace overall
pharmaceutical spending growth. In 2002, biologics had
global sales of $46 billion in US dollars, and this figure is
expected to reach $221 billion by 2017.5 In 2010, eight of
the 10 highest-expenditure drugs were biologics, accounting
for $8 billion in Medicare Part B spending.6 Conversely,
biosimilars have been predicted to lead to a $250 billion
reduction in US spending on biologic drugs for the years
2014 to 2024.7
Global Biologics Sales, 2002-20175
$169
$106
$46
$221
billion
billion
billion
billion
2002
2007
2012
2017
(projected)
Biologics continue to outpace overall spending growth
and are expected to represent 19% to 20% of global
market value by 2017.5
Drug Development Comparison8
Smallmolecule
Generic
$1-5 million
Originator
Biologic
$375 million ($1.33 billion*)
Biosimilar
$100-200 million
Time in years: 0
2
4
6
8
10
12
14
*If discovery and development costs of failed products are included.
PATHWAYS FOR DRUG APPROVAL:
BIOSIMILARS BREAKING NEW GROUND
Generics and small-molecule drugs
Small-molecule drugs, such as aspirin, and their accompanying
generics are approved via the Food, Drug, and Cosmetic Act
(FDCA). For decades, new small-molecule drugs have been
regulated and controlled with the New Drug Application (NDA)
process.9 FDA approval is based on demonstration of safety
and efficacy. Generics must demonstrate bioequivalence for
FDA approval and are approved via an abbreviated new drug
application (ANDA) process established by the Hatch-Waxman
Amendments enacted in 1984.10
Biologics
Although biologics must also prove safety and efficacy to
obtain FDA approval, the pathway is regulated differently
through the biologics license application (BLA), or Section
351(a) of the Public Health Service Act, rather than an NDA.
Both the FDA’s Center for Drug Evaluation and Research
(CDER) and Center for Biologics Evaluation and Research
(CBER) are responsible for regulation of therapeutic biological
products. A biologics license is issued if the biological product,
the manufacturing process and the manufacturing facilities
meet the requirements to ensure the continued safety, purity
and potency of the biological product.11
Biosimilars
The abbreviated, or tailored, licensure pathway for biological
products shown to be “biosimilar” to or “interchangeable”
with an FDA-licensed biological product became possible
when the Biologics Price Competition and Innovation (BPCI)
Act was signed into law as part of the Affordable Care
Act in 2010.1 Proposed biosimilars must scientifically
demonstrate that there are no clinically meaningful
differences from the reference biological product in
terms و