Interchangeable or Interchangeability in reference to a biological product is defined as,

“biological product that maybe substituted for the reference product without the
intervention of the healthcare provider who prescribed the reference product”.

Points to considered for biosimilar interchageability:

1. An interchangeable biosimilar is expected to produce the same clinical result as the
reference in any given patient.
Under the Biologics Price Competition and Innovation Act (BPCIA), an interchangeable
biosimilar is defined as a biosimilar that is expected to produce the same clinical result as the
reference product in any given patient. It may be substituted for the reference product without
prescriber intervention, and the risk in terms of safety or efficacy of switching or alternating
between biological products is no higher than using the reference product alone.
2. The Federal Drug Administration’s (FDA) official guidance on interchangeability is still
in draft form.
The FDA released the draft guidance for biosimilar interchangeability in January 2017, and the
final guidance is yet to be released. Despite the guidance being in draft form, it is still possible
for a manufacturer to achieve an interchangeability designation for a biosimilar, though it would
be more difficult to do so. Diligent and frequent interactions between the manufacturer and the
FDA would be necessary to ensure that data requirements are met.
3. An interchangeability designation is achieved through the submission of additional data.
In order to be designated an interchangeable biosimilar, a product faces rigorous evaluation and
must meet additional requirements based on further evaluation and testing. Therefore, a
manufacturer would need to provide additional information to demonstrate that the biosimilar is
expected to produce the same clinical result as the reference product in any given patient.
Also, if a product will be administered more than once, data must prove that there is no added
safety and efficacy risk associated with switching or alternating between the biosimilar and
reference product.
4. Provider and patient confidence in biosimilars could be enhanced through the
interchangeability designation.
Many attribute the slow market uptake of biosimilars to stakeholders’ lack of familiarity and
comfort with these products. The delay in market uptake can be compared to when generics first
became available, although generic products are different in nature. Acceptance of small-
molecule generics by physicians and payers took time, despite generics being chemically
identical to the original brand-name products. The generics market has been enhanced over the
years through strategies such as automatic substitution policies within pharmacies as well as
through payer efforts. Given the fact that most biologics are covered under the medical benefit
and are administered by physicians, the degree of retail-based pharmacy-level substitution may
not prove to be as impactful as it has been for generic drugs. However, the interchangeability
designation has the potential to significantly enhance provider and patient confidence in
biosimilars, as more information about switching these particular therapies would be available as
a result of the approval process.
5. Manufacturers must assess multiple factors when considering whether to pursue
interchangeability.
A manufacturer’s decision to pursue interchangeability is multifaceted. The company must
evaluate whether the investment of capital and resources required to meet the additional data
requirements (after already having incurred significant costs to develop the biosimilar product) is
worth the value of the designation. For example, the development of additional trials and
switching studies is not something that can be accomplished overnight. Developing this clinical
program can lead to significant delays in market entry, potentially further delaying access to life-
saving therapies. Additionally, there are thoughts that “interchangeability” may not hold as much
weight for certain biosimilars, given the therapeutic category and/or site of administration. For
example, the pharmacovigilance associated with short-acting or supportive care biosimilar agents
utilized in the inpatient setting may enhance provider and patient confidence in the products
since patient responses can be monitored and measured much sooner than they can be for
disease-modifying agents.

CURRENT SCENARIO:
Australia’s Pharmaceutical Benefits Advisory Committee (PBAC) can designate biosimilars as
interchangeable, known as ‘a-flagging’.
In Australia, the payer body has the exclusive authority to determine substitution of biosimilars
at the pharmacy level. The substitution of biosimilars is recommended as its default policy
Decisions on ‘a-flagging’ are, however, made on a case-by-case basis. The PBAC has permitted
substitution (‘a-flagging’) of biosimilars of infliximab and etanercept for the treatment of
Psoriatic arthritis and Ankylosing Arthritis