FDA laid out its basic approach for biosimilar development in three draft guidance documents published in February 2012, and a CDER/Center for Biologics Evaluation and Research (CBER) Biosimilar Implementation Committee is weighing comments and further changes. Drug-review staff members are talking to manufacturers about biosimilar development options, as seen in 47 requests for pre-investigational new drug (IND) meetings on proposed biosimilars to 11 reference products, as of early October. 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. This advisory program is highly work-intensive for FDA, because each meeting with a sponsor entails at least four internal sessions and consultation with CDER and CBER biosimilar review committees to ensure that staff advice is consistent across divisions.
Amidst all the discussion, the agency still awaits its first official 351(k) biosimilar application, as authorized by the Biologics Price Competition and Innovation Act (BPCI), which was enacted through the Affordable Care Act of 2010. Teva Pharmaceuticals recently received FDA approval for its version of Amgen's Neupogen (filgrastim), but opted for a biological license application (BLA) instead of the new route. This approach gives Teva 12-years exclusivity for its product and avoids the complex patent dispute resolution process established by BPCI.
In addition to technical and scientific challenges, a number of legal and regulatory issues will determine the development path for a new biosimilar. A convoluted process for addressing exclusivity and patent rights presents a clear challenge, and there is considerable debate over biosimilar names and product codes. The size and shape of clinical studies remains uncertain, along with questions about non-US comparators and bridging studies. Interchangeability is the ultimate goal for most biosimilars manufacturers, but FDA indicates that such a designation may require more extensive test data. All sides anticipate lawsuits, citizens' petitions, and other legal battles to resolve these and other controversies.