Thus, an objective comparison between reference
and a biosimilar must determine not only the
frequency of an undesirable event but also the
relative occurrences of the drug-related and non-
drug-related causes.
The RMP is the responsibility of the manufacturer
and the use of the drug must adhere to conditions
outlined in the Summary of Product Characteristics.
However, drugs are used in many locations and
under differing circumstances (for example,
medicines dispensed through a hospital pharmacy
in the inpatient setting are administered to the
patient by a healthcare professional within the
hospital, whereas medicinal products dispensed
through an outpatient or community pharmacy
in primary care are administered by the patient
at home) and it is therefore extremely difficult
to monitor all side effects that occur in all these
situations.
As a consequence, only serious adverse events
can be identified and recorded but monitoring
is very dependent on the local organisation of
pharmacovigilance. The recent introduction of
serialisation following EU directives (falsified
medicines directive; FMD) should theoretically
facilitate traceability. The EU FMD (2011/62/EU) was
adopted in 2011 and introduced new harmonised
measures to ensure that the use of medicines in the
EU is as safe as possible, and that trade in medicines
is controlled properly. 10
Safety features introduced for the packaging of
medicines include: a unique identifier (a 2D data
matrix code and human readable information) that
must be scanned at fixed points along the supply
chain; and an anti-tampering device, allowing
verification of whether the packaging of a medicine
has been compromised. However, this system
has been developed to ascertain that medicines
are genuine and not counterfeit, but not for
pharmacovigilance purposes.
The RMP required by the European Medicines
Agency for a biosimilar is expected to take into
account any identified or potential risks also
covered in the RMP of the reference product. 2,11
Therefore, implementing traceability at the level
of hospital and community pharmacies, both for
reference drugs and biosimilars, is complex. Indeed,
at present, traceability by batch is not required for
reference biologics. 12 The anticipated great increase
in the number of authorised biosimilars would
necessitate development of specific systems to trace
all batches regardless of their origin (reference or
biosimilar) but also across different brands of
a specific biosimilar.
At the community pharmacy level, all brands
14 | 2019 | hospitalpharmacyeurope.com
of a biosimilar plus the reference drug should be
available because substitution by the pharmacist
(such as for generics) is not allowed in many
countries (see key concepts chapter in this
handbook). Implementation at community levels
is therefore likely to be problematic and costly. 12,13
Questions arise regarding the availability of
the traceability data generated by hospital and
community pharmacies. 14 Whose property are
these data? Will these data be freely accessible even
though they will comprise data specific to each
biosimilar and reference?
Considering the decline in available health
resources in many countries, mainly related to
increasing costs of medicines and innovations, it is
unlikely that public funds would be made available
to help implement widespread traceability systems.
The manufacturer of a specific biosimilar might
perhaps be willing to pay to obtain traceability
data of their own product but might be unlikely
to support the expenditure required to follow
all prescriptions or switching activities. At a
community pharmacy level, the problem seems
quite unsolvable.
Conclusions
These practical, but fundamental, considerations
might impact on the implementation of biosimilars
in several countries. In contrast to biosimilars,
which are considered as new compounds,
traceability data are not required for reference drugs
more than 20 years old. Therefore in community
pharmacies, there might be a temptation to
prescribe and dispense the reference instead of
the biosimilar to avoid complicated procedures.
However, at the hospital level, financial incentives
to prescribe bisosimilars, such as those being
implemented in many countries, could help mitigate
this risk.
Healthcare professionals can improve
pharmacovigilance through a number of ways,
including:
• Recording the trade name and batch number
at all levels, including at dispensing and patient
administration.
• Ensure that trade name and batch number are
reported in case of suspected adverse events,
according to local practice and national regulations
• In primary care and community pharmacies,
the trade name and batch number of the biologic
medicine should be provided to the patient
• In any cases of switching, it is important to record
the trade name and batch number for each of the
medicines.
Furthermore, what about risk analysis and
related cost–benefit analyses? Indeed, as previously
discussed, biosimilarity is ascertained by rigid,
extensive physicochemical and biological tests,
and clinical trials. 2-4 Some of these preclinical tests
allow all the drug-related parameters implicated
in immunological tolerance to be determined. The
primary structure of the reference and biosimilar
are the same, therefore, by definition, the antigenic
properties of all particular sequences should be
identical. The level of foreign protein, and also the
level and the characteristics of aggregates that can
induce antigenic behaviour, must also lie in the
range observed for the reference, and biosimilars
and reference products should have comparable
levels of safety. Thus, to believe that the risk of
a biosimilar, which conforms to the characteristics
of the reference, inducing more or new side effects
compared with the reference, has no real meaning
from a scientific point of view.
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