LANDSCAPE
Evolving landscape of biosimilars
current and future
Since 2006, approximately 50 biosimilars have been authorised by the European Medicines Agency
and continuing pressure on healthcare budgets is expected to force a change in attitude towards
these drugs
Irene Krämer PhD
Pharmacy Department,
University Medical Center,
Johannes Gutenberg-
University, Mainz,
Germany
The European biosimilar market is the most
mature in the world. The first guidance on
biosimilars was issued by a European authority, the
European Medicines Agency (EMA), and subsequently,
many health authorities, including the World Health
Organization, implemented specific regulations for
the approval of biosimilars. Today most countries
have specific regulations for the approval procedure
of the follow-on products of recombinant biologics
when the reference products come off patent.
Expiry of the patent protection and competition
by biosimilars usually favours the reduction of
prices for the reference product and biosimilars.
The economic benefit of biosimilars depends on
the specifics of the individual healthcare system,
especially regarding the pricing and reimbursement
structures. While the rates of discount generally
amount to 90% for generics, they are expected
to amount to less than 50% for biosimilars. The
development process for biosimilars is expensive
and takes a long time because of the mandatory
clinical programme required by the regulatory
authorities. In addition, the contribution of
analytical studies to cost and time must not be
underestimated. It takes up to eight years to bring
a biosimilar to market, and development costs range
from US$100–250 million (about 50-times that to
launch a conventional generic). 1
Since the very beginning of the biosimilar era,
European hospital pharmacists engaged in the
field of biosimilars. At first, we had to learn that
biosimilars represent a new entity of medicinal
products according to the licensing procedure of the
EMA. Very soon, hospital pharmacists embraced the
topic and set guidelines and conditions for the use
of biosimilars in hospital patients. In 2005, a special
interest group of pharmacists published a checklist
to aid hospital pharmacists in the evaluation of
biosimilars. 2 At that time, most of the biosimilars
coming to the market were hormones and cytokines.
While this so-called first generation of biosimilars
was established, another, and much more complex,
class of biologics – monoclonal antibodies (mAbs)
and their derivatives (for example, fusion proteins,
receptors, incomplete antibodies) – continued
to revolutionise the treatment of patients with
oncological diseases, autoimmune diseases, asthma,
wet macular degeneration, and others.
Of note, hospital pharmacists gradually became
more familiar with the subject and a panel of
experts (authors) reviewed the 31 previously drawn
evaluation criteria for biosmilars 2 and produced
a shortlist of ten criteria relevant for clinicians,
pharmacists and clinical practice. 3 These included:
how long the drug had been on the market;
18 | 2019 | hospitalpharmacyeurope.com
number of registered indications; serious and
mild adverse events and their frequency; differing
contraindications; and precautions or warnings
compared with the reference compound, among
others. The publication also suggested a decision
matrix system to enable physicians and pharmacists
to give their own weight to these criteria. This
decision matrix system was designed to support
objective decision-making and rational selection
of biosimilars by Pharmacy and Therapeutics
committees in hospitals. While a general selection
matrix can be regarded as an important step
forward, additional, more refined selection matrices
for specific groups of biosimilars are necessary and
their implementation requires expert knowledge.
Various parameters of biosimilars should be assessed
specifically at product level and on a case-by-case
basis. Moreover, additional efforts for registries/
Phase IV studies and potential additional costs
arising for stock keeping and administration should
be considered. The varying consequences deriving
from initiating treatment with a biosimilar for naïve
patients or switching experienced patients from
the reference to a biosimilar, as well as multiple
switches between the reference and one or more
biosimilars, are not described in the current decision
matrix system.
Additional studies and more experience will make
us more confident about the therapeutic equivalence
in extrapolated indications, potential safety issues,
multiple switching, naming and traceability, as well
as the economic impact of biosimilars. Meanwhile
formulary management of biosimilars and the
good prescribing, distribution and administration
practices will remain a challenge. In the hospital,
local guidelines for prescribing, substitution,
switching and pharmacovigilance have to be
developed in an appropriate and pragmatic manner.
Useful information can be found in the European
Public Assessment Reports (EPARs) and various
position statements of associations of healthcare
professionals. Post-marketing pharmacovigilance
is mandatory to determine the benefit–risk profile
of biologics and biosimilars throughout their life
cycle. Different post-marketing commitments
for different biosimilars of the same reference
product can be required. Especially in the case of
switching, patients should be monitored closely for
adverse drug reactions, and reporting by hospital
pharmacists should be encouraged.
Approved biosimilars
Since 2006, about 50 biosimilar products across 15
different biological classes have been approved by the
EMA (Table 1). 4 In 2017 and 2018, biosimilar products