275infliximab or CT-P13 [ 48 , 49 ]. Another infliximabELISAhas been developed that
could quantify CT-P13 equally well as with reference infliximab [ 49 ]. An additional
problem that may arise from interchangeability is the challenge that is introduced in
monitoring long-term safety for the biosimilar separate from the originator drug.
This issue has been addressed by the consideration of a unique suffix for each newly
approved biosimilar, and for CT-P13, the FDA designated it as infliximab-dnnp.
Low incidence adverse drug reactions (ADRs) may require large numbers of
patients followed for years to determine risk. In Europe the EMA mandated a risk
management plan of biosimilar infliximab which includes two patient registries
with a total targeted enrollment of 6200 patients in both RA and IBD, with a special
focus on serious infections including TB, and is planned to have final submission of
data in 2026 [ 50 ].
Changesin manufacturing may occur and increase product robustness and phys-
iochemical properties, by the deliberate introduction of new technology or alterna-
tive raw materials, or change in production scale or sites to meet changes in market
demand [ 51 ]. These changes are not uncommon, and there have been at least 36
post- approval changes for Remicade and 21 for Humira [ 52 ]. The FDA and EMA
have rigorous-defined mechanisms to detect meaningful changes in the pre- and
post- change product [ 53 , 54 ]. For example, for the multiple changes made between
2003 and 2013 in a total of 544 batches for reference adalimumab, comparability
exercises revealed a very high level of consistency in multiple parameters including
glycan mapping, TNF binding and affinity, and neutralization of TNF.
In summary, key issues that will impact on the legitimacy of interchangeability
must address disease-specific design of switch studies, efficacy, and long-term dura-
tion of follow-up after switches, serial measurement of drug trough levels and ADAs
at appropriately determined time points, and accountability forpossible divergence
of biosimilarity over time. These variables have not all been definitively proven to
be identical between diseases. Caution must be exercised in considering the issues
of extrapolation and interchangeability beyond presumed short-term and unknown
long-term cost savings.
Gastroenterologist Concerns: Reintroduction of Biosimilars
In order to prevent confusion regarding adverse eventsdue to originator versus a
newly introduced biosimilar,the World Health Organization (WHO) mandated new
drug naming in accordance with the international nonproprietary names [ 55 ]. The
FDA recently published a draft guidance summary regarding the nonproprietary
naming of biosimilar agents to avoid confusion and inadvertent assumption of inter-
changeability due to the biosimilar and reference product having the same proper
name, which relates to the chemical structures and pharmacologic features of the
product. Currently, the FDA is recommending biosimilars have a core name shared
among the related products and a distinguishing suffix consisting of four lowercase
letters added to the core name to provide clarification for prescribers, pharmacists,
15 Biosimilars in Inflammatory Bowel Disease 2017: State of the Science