PAID ADVERTISEMENT
Approving Biosimilars in the
United States: The Food and Drug
Administration (FDA) Perspective
The Biologics Price Competition and Innovation (BPCI) Act
was signed into law as part of the Affordable Care Act in
2010, amending the Public Health Service (PHS) Act and
facilitating the creation of an abbreviated, or tailored,
licensure pathway for biological products shown to be
“biosimilar” to or “interchangeable” with an FDA-licensed
biological product.1 This abbreviated pathway, which is made
possible by utilizing knowledge from the reference products
and the European Medicines Agency experience, which
approved its first biosimilar in 2006, is intended to eliminate
unnecessary (and, therefore, unethical) testing of biosimilars
in animals and humans.2
TOTALITY OF EVIDENCE: WHAT DOES IT MEAN?
FDA guidance represents a paradigm shift in the way
biosimilars are evaluated. The biosimilar approval pathway
that the FDA has outlined builds on the knowledge gained
from the reference biologic, and is based on a “Totality of
Evidence” Approach.3
The “Totality of Evidence” Approach4
When a manufacturer decides to submit a product for
review as a biosimilar, a 351(k) biologics license application
is submitted, which must include information demonstrating
biosimilarity, such as1:
• Analytical studies that demonstrate that the biological
product is “highly similar” to the reference product
(only minor differences in clinically inactive components
are permitted)
• Animal studies (including assessment of toxicity)
• Clinical studies, including the assessment of immunogenicity
and pharmacokinetics (PK) or pharmacodynamics (PD),
that sufficiently demonstrate safety, purity and potency in
one or more appropriate conditions of use for which the
reference product is licensed and for which licensure is
sought for the biosimilar product
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Clinical Knowledge
Human PK and PD
Structural and Functional Characterization
The goal of this stepwise approach is to establish the
totality of the evidence that supports the demonstration of
biosimilarity.3 This pathway also takes into account the lack
of scientific benefit in repeating the entire development
program of the reference product.2 Establishing a high degree
of similarity at the molecular level with a robust foundation
of analytical characterization reduces the need for extensive
animal and clinical testing, compared with that required for a
new originator biologic.3
First Biosimilar
Approved11:
1. Scientific Considerations5
2. Quality Considerations6
3. Questions and Answers7
Draft Guidance
Clinical
Pharmacology
Data on
Biosimilarity9
The first approved
biosimilar is filgrastim,
currently referred
to as filgrastim-sndz
until the FDA
clarifies how to
“name” biosimilars.
Draft Guidance
on Biosimilars:
FEBRUARY
MAY
MARCH
MAY
Draft Guidance
on Biosimilars:
2011
Animal Studies
Clinical Immunogenicity
The FDA Has Developed Guidance for the Regulatory Approval of Biosimilars
2010
Clinical
Studies
2013
2014
Additonal Questions
and Answers14
2015
MARCH
MARCH
SEPTEMBER
APRIL
BPCI Act Passed
as Part of the
Affordable Care Act
Draft Guidance
on Formal Meetings
With FDA and
Sponsors (procedural) 8
FDA Announces
“Purple Book”10:
Final Guidance on
Biosimilars:
Lists biological products,
including FDA licensed biosimilar
and interchangeable biological
products. It enables users to see
whether a licensed biologic is
biosimilar to, or interchangeable
with, a reference biologic.
1. Scientific Considerations 3
2. Quality Considerations12
3. Questions and Answers13