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62    Copyright (c) 2020 Infusion Nurses Society
Journal of Infusion Nursing
The Art and Science of Infusion Nursing
Pharmacology Report
Biosimilar Basics
Susan Kleppin, RPh, FASHP
DOI: 10.1097/NAN.0000000000000362
Author Affiliation: Chartwell Midwest Wisconsin, Middletown,
Wisconsin.
Susan Kleppin, RPh, FASHP, is the director of pharmacy for
Chartwell Midwest Wisconsin.
The author of this article has no conflicts of interest to declare.
B
rand name drugs, once approved by the US Food
and Drug Administration (FDA), have an assigned
period of time during which they can be marketed
exclusively by the manufacturer before a generic
version of the drug can be introduced into the marketplace.
These medications are chemically synthesized. Generic
medications are chemically identical to the brand name
drug. Biologics (or biological products) are generally made
from human or animal materials, and the chemical struc
tures are large and complex. Biologics include products
such as vaccines, blood and blood components, allergen
ics, somatic cells, gene therapy, tissues, and recombinant
therapeutic proteins.1  Biologics have no generic versions
because of the way they are produced.
Biologics are often very expensive and thus patient
access to them to treat illness or disease can be limited. In
an effort to make biologics more affordable, increase access,
and create more competition in the health care market,
Congress paved the way for the development and approval
of biosimilars through the passage of the Biologics Price
Competition and Innovation Act (BPCIA) of 2009. This legisla
tion authorized the FDA to implement an abbreviated regula
tory pathway for approval of biosimilars.2 It is estimated that
introduction of biosimilars could reduce the cost of biologics
by $44 billion over the next decade, although this would be
dependent on several factors.3 Like other medications, brand
name biologics are also allowed a period of exclusivity, and,
until the last decade, no biosimilars were available. The first
biosimilar was approved in 2015; the FDA has licensed addi
tional biosimilars every year.4 As of the writing of this article,
the FDA has approved 26 biosimilars, and 7 have been intro
duced into the market (Table 1).
What are biosimilars? Not identical to the brand name
biologic (often referred to as the reference product), bio
similars are copies of the complex medicines made from
biological material. They are considered "highly similar"
medicines, having the same clin
ical effect as the brand name
or reference product with no
clinically meaningful differences
in safety, purity, and potency.2
Since biosimilars are grown in
living systems with unique cell
lines, there is variability from
the reference biologic product.
It is important to understand the variation that occurs:
(1) all biologics and biosimilars are "living" molecules that
naturally vary; (2) the FDA requires extensive, state-of-the-
art analyses that compare the biosimilars to their reference
products; (3) any variations in the biosimilar must be within
the boundaries established for the reference product; and (4)
when the variations occur they are not clinically significant.5
Biosimilars are marketed in the same dosage form, strength,
and route of administration as the reference product.
The manufacturer of a biosimilar must generate data to
compare the proposed product to the reference product.
A variety of studies are conducted: (1) analytical studies
demonstrating that the biologic product is highly similar
to the reference product; (2) animal studies, including an
assessment of toxicity; and (3) a clinical study or studies
sufficient to demonstrate the safety, purity, and potency of
the biosimilar in 1 or more of the indications for which the
reference product is licensed.2
Each biosimilar that is FDA-approved will have a specific
naming standard. The name of the biologic is followed
by a suffix of 4 random letters to distinguish between
them.6 Each will also have a brand name associated with it,
assigned by the manufacturer.
Unlike generic medications, the biosimilars cannot be
automatically substituted for the reference product. The
biosimilar can only be dispensed if a prescription order is
written for that specific biosimilar. A manufacturer could
seek to prove that their biosimilar is "interchangeable" per
FDA standards. The FDA finalized its interchangeability guid
ance that addresses the requirements that need to be met
to obtain an interchangeability designation in May 2019.7
The manufacturer must have data demonstrating that the
biosimilar is expected to produce the same clinical result as
the reference product in any given patient. In addition, the
Susan Kleppin, RPh,
FASHP, Director of
Pharmacy, Chartwell
Midwest Wisconsin
Copyright (c) 2020 Infusion Nurses Society. Unauthorized reproduction of this article is prohibited.

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VOLUME 43    |    NUMBER 2    |    MARCH/APRIL 2020
journalofinfusionnursing.com    63
risk in switching between the biosimilar and the reference
product in terms of safety or decreased efficacy cannot be
any greater than using the reference product alone.7
If a manufacturer follows this guidance and can demon
strate that a biosimilar is interchangeable with its reference
product, pharmacists may be able to substitute a biosimilar
for the reference product on receipt of a prescription order.
State pharmacy laws would govern this, and laws vary from
state to state.8 Some states will require that both the pre
scriber and the patient be notified before an interchange
able biosimilar could be dispensed.8
Data in Table 1 shows that several biosimilars have been
FDA approved for 2 years or more but are not yet marketed
in the United States. The marketing of these agents has
been slowed by ongoing patent litigation.9,10 The acceler
ated approvals of biosimilars over the last 2 years demon
strates that manufacturers are interested in the biosimilar
market and that the abbreviated approval pathway is
having the desired effect. Yet the biosimilars that are being
marketed currently are not dominating the market. There
are several factors that are limiting the widespread use of
the biosimilars that are currently available. The cost of the
biosimilar products in some cases is not dramatically differ
ent from the reference product.11 Proven interchangeability
might help reduce the price of biologics, and market share
can be shifted more rapidly from one product to another.
Some insurance companies have restricted patient
access to biosimilars because of contract provisions with
the manufacturers of the biologic reference product in
which the insurer grants formulary exclusivity to the ref
erence product in exchange for rebates.11 There is also
prescriber and patient reluctance to use biosimilars, and
this reluctance is also having an impact on the use of bio
similars. Prescribers may not have a good understanding
of the biosimilar approval process and thus have concerns
about the efficacy and safety of the products. A national
Copyright (c) 2020 Infusion Nurses Society. Unauthorized reproduction of this article is prohibited.
TABLE 1
Biosimilars Approved in the United States as of December 2019a
Biosimilar Product (Brand Name)
Manufacturer
Date Approved
Date Marketed
Filgrastim-sndz (Zarxio)
Sandoz
3/2015
9/2015
Infliximab-dyyb (Inflectra)
Celitrion/Pfizer
4/2015
11/2016
Etanercept-szzs (Erelzi)
Sandoz
8/2016
Not yet marketed
Adalimumab-atto (Amjevita)
Amgen
9/2016
Not yet marketed
Infliximab-abda (Renflexis)
Samsung/Merck
4/2017
7/2017
Adalimumab-adbm (Cyltezo)
Boehringer Ingelheim
8/2017
Not yet marketed
Bevacizumab-awwb (Mvasi)
Amgen/Allergan
9/2017
Not yet marketed
Trastuzumab-dkst (Ogivri)
Mylan
9/2017
Not yet marketed
Infliximab-qbtx (Ixifi)
Pfizer
12/2017
Not yet marketed
Epoetin alfa-epbx (Retacrit)
Pfizer
5/2018
12/2018
Pefilgrastim-jmdb (Fulphilia)
Mylan
6/2018
7/2018
Filgrastim-aafi (Nivestym)
Pfizer
7/2018
10/2018
Adalimumb-adaz (Hyrimoz)
Sandoz
10/2018
Not yet marketed
Pefligrastim-cbqv (Udenyca)
Coherus Biosciences
11/2018
1/2019
Rituximab-abbs (Truxima)
Celltrion/Teva Pharmaceuticals
11/2018
Not yet marketed
Trastuzumab-pkrb (Herzuma)
Celltrion/Teva Pharmaceuticals
12/2018
Not yet marketed
Trastuzumab-dttb (Ontruzant)
Samsung Bioepis
1/2019
Not yet marketed
Trastuzumab-qyyp (Traximera)
Pfizer
3/2019
Not yet marketed
Etanercept-ykro (Eticovo)
Amgen/Allergan
4/2019
Not yet marketed
Trastuzumab (Kanjinti)
Amgen/Allergen
6/2019
Not yet marketed
Bevacizumab-bvzr (Zirabev)
Pfizer
6/2019
Not yet marketed
Rituximab-pvvr (Ruxience)
Pfizer
7/2019
Not yet marketed
Adalimumab-bwwd (Hadlima)
Samsung/Merck
7/2019
Not yet marketed
Pegfilgrastim-bmez (Ziextenzo)
Sandoz
11/2019
Not yet marketed
Adalimumab-afzb (Abrilada)
Pfizer
11/2019
Not yet marketed
Infliximab-axxq (Avsola)
Amgen
12/2019
Not yet marketed
aData compiled from the US Food and Drug Administration website.1

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64    Copyright (c) 2020 Infusion Nurses Society
Journal of Infusion Nursing
survey of specialty physicians that have high utilization of
biologic products demonstrated that 55% of the physicians
surveyed did not believe that the biosimilars were safe
and effective.12 Similar surveys of patients have found the
same. A survey of adult patients with rheumatologic dis
ease published in 2019 showed overall patient satisfaction
with a switch to an infliximab biosimilar, but those surveyed
expressed concern regarding safety and efficacy as well.13
Nurses should educate themselves about biosimilars to be
able to respond to questions posed by patients. The FDA has
educational material on its website for health care providers
that can be accessed for more information.14 There is also
information for patients that nurses could share with patients
and use to address patient questions and concerns.15
When preparing and/or administering a biosimilar, nurses
should follow the directions provided by the manufacturer,
pharmacy, or hospital for the specific product being given. As
always, know which product you are administering. Nurses can
contribute to the postmarketing surveillance of these products
by reporting patient side effects and/or adverse reactions to
a biosimilar promptly and through the appropriate channels.
The introduction of biosimilars has the potential to
decrease treatment costs and improve access to biologics.
The education of nurses, pharmacists, and prescribers will
lead to better adoption in clinical practice. The collabo
ration of these 3 disciplines can lead to sound formulary
decision-making in hospitals, the development of biosimilar
treatment protocols, and shared responsibility in the edu
cation of patients about biosimilar use.
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answers. Updated February 6, 2018. Accessed December 10, 2019.
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Copyright (c) 2020 Infusion Nurses Society. Unauthorized reproduction of this article is prohibited.