certain molecules. In some cases, a study completed in healthy
volunteers is more informative and sensitive than in patients.
Second, the FDA acknowledged that a non-US licensed product
may be used for comparison in a PK and, if applicable, PD study
as long as adequate data are presented to scientifically justify
that use along with an acceptable bridge to the US licensed reference product. Third, the FDA established four levels of similarity with the need for additional, phase III type data diminished
as a higher level of similarity is achieved.
The FDA’s approval of enoxaparin, a complex, low-molecular
weight heparin (LMWH), in July 2010 demonstrates its evolving thinking in terms of the body of data needed to determine
similarity across molecules. While not a biologic, enoxaparin
is complex enough in structure that the European Medicines
Agency (EMA) requires clinical trials for generic approval. The
FDA took a robust approach weighted on scientific analysis
of the molecule. In a Q&A about generic enoxaparin the FDA
stated that there is no scientific need to perform additional clinical studies to demonstrate equivalence of clinical effectiveness
and safety of generic enoxaparin to Lovenox. Although the EMA
Guideline requires clinical studies to demonstrate comparable
effectiveness to a similar LMWH, FDA notes that its approach is
more sensitive to differences between two enoxaparin products
than the clinical studies recommended in the EMA guideline.
The same may hold true for a biosimilar depending on the data
package and level of similarity as laid out in Exhibit B. The FDA
also created the purple book in September this year. The purple
book will contain lists of all licensed biosimilar and interchangeable biological products and will act as a reference once approvals are made in the US. While these initial guidances provide
a solid framework for development, there are still numerous
questions that remain unanswered, including the naming structure, specifics around coding in the buy-and-bill space as well
as clinical data requirements for interchangeability. The FDA is
expected to continue to release updated guidances to address
these and other issues in the coming year.
The World Health Organization (WHO) has put a proposal
together to address one of these controversial topics, naming.
WHO is responsible for ensuring there is a single name acceptable worldwide for each approved active pharmaceutical substance, known as an international nonproprietary name (INN).
The July proposal includes a voluntary global naming scheme
for all biologics including biosimilars that would involve a 4 letter code attached to the INN known as a biological qualifier.
While the US is moving towards a more concrete pathway
to biosimilar approval and usage, biosimilars are not new to
Specialty pharmaceuticals are growing in proportion of total
pharmaceutical spend in the United States as well as in cost
to the patient and healthcare system at an unsustainable rate.
The Biologics Price Competition and Innovation Act (BPCIA)
of 2009 was enacted as part of the Patient Protection and
Affordable Care Act on March 23, 2010, to alleviate some of
those pressures. It amended the Public Health Services Act to
include an abbreviated pathway in section 351(k) for biological
products shown to be biosimilar to or interchangeable with an
FDA licensed reference product. The BPCIA opened the door
for biosimilar versions of already approved biologics where
“generic” competition didn’t exist prior. Two years after the
enactment of the BPCIA, the FDA issued its first draft guidance
on biosimilars in February 2012, which laid out a framework for
approval, providing direction for biosimilar development.
MORE FDA CLARITY
The FDA continues to clarify biosimilar guidelines. The most
recent draft guidance providing additional details was published
on May 2014 and included three very interesting clarifications.
First, the FDA stated the usefulness of a pharmacokinetics (PK)
and pharmacodynamics (PD) study done in healthy subjects for
■ By Sarfaraz K. Niazi, Ph.D., Founding Chairman and CEO, Therapeutic Proteins International
As biosimilars grow in importance - competition heats up.
The Biosimilars Market
■ 20 NOV/DEC 2014 | PHARMACEUTICAL PROCESSING
■ PHARMPRO. COM