Focus on Biosimilars
What are Biosimilars?
Defining the new category and exploring physicians’
attitudes about biosimilars in the marketplace
A growing number of biosimilars are making their
way through the drug pipeline, bringing with them
the promise of effective drugs at more affordable
prices. However, many health-care providers do not
know what this class of drugs is and how the agents
are approved, developed, and prescribed.
In a recent survey of 1,201 U.S. physicians
across multiple specialties, most respondents did
not understand the definition of a biologic or the
concepts of “extrapolation” and “interchangeability.” 1
For instance, just 69.3 percent of hematologists and
oncologists correctly identified which drugs used in
their specialty were considered biologics (the refer-
ence products for biosimilars).
“The results of this survey highlight a significant
need for evidence-based education about biosimilars
for physicians across specialties,” concluded lead author
Hillel Cohen, from Sandoz, Inc., which specializes
in the development of biosimilar products, and
co-authors. “Although the vast majority of physicians
have heard about biosimilars, their knowledge of the
fundamentals was low.”
Biosimilars are a complex drug category. Their
distinctive elements influence how the drugs
are manufactured, reproduced, and prescribed
to treat patients. Contrary to popular miscon-
ception, they are not simply generic versions of
medications. One reason for the lack of awareness
about biosimilars is their relative novelty in the
U.S.; the first biosimilar was approved in the U.S.
in 2015, but in Europe, Australia, Japan, and other
countries, they have been safely used in clinical
practice for more than five years.
Drug Administration (FDA).
How the products are developed
and how they enter the market-
place is a bit more complicated.
But what are biologics? These
drugs are developed from living
organisms, whether human, ani-
mal, or microorganism cells. 2 They
cannot be made through synthetic
chemical processes, unlike tradition-
al medications. Biologic products also
are distinctive because they can be made
of sugars, proteins, nucleic acids, or com-
plex combinations of these substances, or they
may be living entities such as cells and tissues. 3
“These products are grown in living systems
and usually in cells,” explained Gary H. Lyman,
MD, MPH, professo r of medicine at the University
of Washington and co-director of the Hutchinson
Institute for Cancer Outcomes Research at the Fred
Hutchinson Cancer Research Center in Seattle,
Washington. “We can clone the gene and ensure that
the protein that is produced has the same amino
acid sequence, but there are many other structural
and functional differences that can emerge when
you go from the original biologic to a biosimilar.”
Generics Versus Biosimilars
Although each drug class carries distinctive charac-
teristics, generic and biosimilar medications share the
same goal: to provide patients with less-costly treat-
ment options that offer the same clinical benefits as
more expensive brand-name or biologic medications.
“There are many ... structural and
functional differences that can
emerge when you go from the
original biologic to a biosimilar.”
—GARY H. LYMAN, MD, MPH
ASH Clinical News spoke with hematologists,
oncologists, and pharmacists about the state of
biosimilars, gaps in knowledge about their devel-
opment, and perceptions about their safety and
efficacy.
Defining the Category
In the simplest terms, a biosimilar is a biologic prod-
uct that is similar (but not identical) to a biologic
product already approved by the U.S. Food and
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ASH Clinical News
“Generic products are simple molecules, while
biosimilars are large proteins or macromolecules,
so they are different in their structure and how they
are produced,” Brandon Shank, PharmD, MPH,
a clinical pharmacy specialist at the University of
Texas MD Anderson Cancer Center in Texas, told
ASH Clinical News.
The divergence starts with the manufacturing
process. Generic products are identical cop-
ies of branded drugs; they can be reproduced
easily by assessment of the pharmacokinetics
and dynamics of an FDA-approved drug and
production of a similar chemical formulation
that uses the same active ingredients. Gener-
ics are also approved with the same strength,
indication, form, and route of administration as
branded products, and they must be manufac-
tured under the same strict standards.
Unlike generics, biologics are not identical cop-
ies of their reference products. Instead, the FDA
mandates that there are “no clinically meaningful
differences in terms of safety and effectiveness from
the reference product,” as well as only minor differ-
ences in the clinically inactive components. 2
“Depending on which drug is being reworked,
the manufacturing process can be really compli-
cated,” Dr. Shank said, adding that, due to their
makeup, biosimilars may need to be grown in a live
model or need a specific enzymatic reaction with
a protein and bacteria. Companies that are accus-
tomed to making generic products would need to
vastly alter their facilities to be able to effectively
manufacture biosimilar products.
Receiving Approval
Biosimilars face different regulatory hurdles than
biologic products or generic drugs. The approval of
biosimilars is outlined in the Biologics Price Com-
petition and Innovation Act of 2009. 4 The legisla-
tion accelerates biosimilar approvals by creating an
abbreviated approval pathway that requires a less
substantial data package submission.
Approval of a traditional oncology biologic
requires submission of a biologic license application
and a standard approval process that includes lab
work and analytics.
Most of the traditional approval deliberations
are “heavily weighted on pivotal clinical trials
December 2017