Another PCMA idea is to speed new "biogenerics" to market by reducing the 12-year exclusivity for innovator biologics and
accelerating FDA efforts to establish an approval pathway for biosimilars. Here FDA officials are hard at work mapping out
an innovative "weight of evidence" approach for testing and developing biosimilar products. It relies on extensive comparative
analysis and functional studies upfront to shape the size and scope of further testing, a policy that represents "a paradigm
shift" in how FDA documents drug safety and efficacy, observed Janet Woodcock, director of the Center for Drug Evaluation
and Research (CDER), at a Drug Information Association (DIA) September conference.
Uncovering "Bad Ads"
FDA laid out this concept for biosimilar development in three draft guidances published in February 2012, and a CDER/CBER
biosimilar implementation committee is weighing comments and further changes. Meanwhile, manufacturers are seeking advice
from FDA about biosimilar development options, as seen, as of early October, in 47 requests for pre-IND meetings on proposed
biosimilars to 11 reference products. Agency staffers have held 30 meetings, and 12 INDs have been filed for possible biosimilars,
some involving new development programs and some building on data from products already licensed in Europe. Biosimilar review
committees in the agency's centers for drugs and biologics are vetting sponsor queries and agency answers to ensure that staff
advice is consistent across divisions.
Despite all the discussion, FDA still awaits its first official 351(k) biosimilar application, as authorized by the Biologics
Price Competition and Innovation Act (BPCI) in the Affordable Care Act of 2010. Teva Pharmaceuticals recently received FDA
approval of its version of Amgen's Neupogen (filgrastim), but opted for a biological license application (BLA) instead of
taking the new route. This approach gives Teva 12-years of exclusivity for its product and avoids the complex and untested
patent dispute resolution process established by BPCI.
In addition to technical and scientific challenges, a number of legal and regulatory issues will shape the development path
for a new biosimilar. Besides the convoluted process for addressing exclusivity and patent rights, there is considerable debate
over biosimilar names and product codes, which are key to market acceptance of the new products. The size and shape of clinical
studies remains uncertain, along with questions about non-US comparators and bridging studies. Interchangeability is still
the ultimate goal for most biosimilar makers, but such a designation may require more extensive test data. All sides anticipate
lawsuits and citizens' petitions that will take years to resolve, in addition to other controversies.
Despite these uncertainties, the first step for manufacturers is to develop a clear analytical plan for demonstrating biosimilarity
of a follow-on to a reference product, advised Steve Kozlowski, director of CDER's Office of Biotechnology Products (OBP).
He observed that manufacturing and product analysis are usually at the "low end of the totem pole" in drug development, but
for biosimilars, structural and functional characterization provides a foundation for determining the scope of pre-clinical
and clinical studies. Advances in manufacturing science, moreover, may support comparative assessment using a fingerprint-like
analysis or "super characterization" approach.
FDA is trying to be flexible, Kozlowski emphasized, noting that different formulations and alternative delivery devices or
container closure systems may be acceptable. While FDA expects that sponsors will have to conduct at least one immunogenicity
study, Koslowski says that "the door is open," to the concept that "added studies may not be necessary."
Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at