One of the most important provisions in ACA for manufacturers is the Biologics Price Competition and Innovation Act (BPCI),
which authorizes FDA to establish an abbreviated framework for approving "highly similar" versions of licensed biological
products. FDA launched the lengthy process of implementing this measure by holding a two-day public hearing last month to
discuss the views of manufacturers, academics, pharmacy groups, and patient advocates on how to develop relevant processes
and policies. Most of the 50-some speakers at the meeting agreed that follow-on biologics have to be safe and effective and
of high quality, and that some clinical trials may be needed to document comparability of these complex large molecules. Patient
advocates urged speedy FDA action to bring needed therapies to patients at affordable prices, but also backed thorough product
assessment to ensure comparability to reference products.
Innovator firms, as expected, proposed a high bar for follow-on biologics, with extensive product characterization, comparative
clinical trials, post-market studies, pharmacovigilance requirements, and dim prospects for achieving interchangeability.
Pharmaceutical and biotechnology manufacturers also want biosimilars to be very distinct from innovator drugs, with unique
names and codes and labeling that admittedly will limit prescribing. "Biosimilars will be similar, but not the same," stated
PhRMA associate vice-president Marie Vodicka.
Follow-on biologics advocates agreed that some preclinical and clinical testing is warranted, but that study requests should
not be excessive or arbitrary. Interchangeability should be possible, although it may involve additional testing, and follow-ons
should be able to adopt the same names and codes as innovators to ease prescribing, dispensing, and postmarket monitoring.
Scientists noted that new technology can better characterize biologics, making some in vivo testing unnecessary—and thus avoiding the ethical issues raised by requiring sponsors to conduct redundant animal and human
FDA has to set user fees for follow-on biologics applications, and pharmaceutical companies want sponsors to fully cover the
agency's advisory and review activities, including postmarketing surveillance. Generic-drug manufacturers are looking for
moderate fees linked to metrics that will expedite approvals and not "create a barrier for entry for biogenerics," stated
Mylan Vice-President Rasmus Rojkjaer, representing the Generic Pharmaceutical Association (GPhA) at the hearing.
Generic-drug makers are unhappy that the BPCI provides 12 years of data exclusivity for innovator biologics, and they're livid
over the prospect of an additional exclusivity period—or patent "evergreening"—for "next generation" therapies. BIO Executive
Vice-President Sara Radcliffe claimed that additional exclusivity for structurally modified products is critical to preserving
incentives for innovation. FDA has the difficult task of determining when changes in a product's safety, purity, or potency
make it sufficiently distinct to warrant additional exclusivity.
The new law broadened the definition of "biologic" to include certain proteins such as insulin and human growth hormone that
have been regulated for years as drugs. Now generic versions of these products may require more extensive testing to come
to market, once FDA sorts out which proteins and polypeptides should be considered biologics, and which are chemically synthesized
and thus remain drugs.
Another contentious topic is whether sponsors of follow-on biologics can reduce the scope of clinical testing by extrapolating
data from one study to additional populations or indications. Extrapolation of results across indications may be appropriate
when the product's mechanism of action is well-understood, explained Parexel principal consultant Bruce Babbitt. But Jim Shehan,
vice-president of Novo Nordisk (Princeton, NJ), urged caution is using this approach unless "scientifically justified." The
use of foreign clinical data also came up at the hearing, along with discussion of whether a biotech therapy approved in Europe,
but not in the US, can serve as the reference product for FDA approval of a biosimilar.
Rachel Behrman, director of the Office of Medical Policy in the Center for Drug Evaluation and Research (CDER), chaired the
meeting and will be weighing these statements and additional comments filed with the agency through Dec. 31, 2010, in developing
agency proposals. John Jenkins, director of CDER's Office of New Drugs (OND), chairs FDA's Biosimilars Review Committee that
will coordinate advice to sponsors on developing biosimilars and the review of resulting applications. Jenkins has appointed
Leah Christl as acting OND associate director for biosimilars to oversee policy implementation and relevant training of OND
FDA is expected to issue guidance on many of the key issues discussed, even though sponsors can submit follow-on biologics
applications before then. Many experts supported more formal guidance to ensure transparency and predictability for biosimilar
development, while some advocated for a flexible and case-by-case approach to weighing test requirements for these products.
The challenge for FDA will be to do both.
Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634, firstname.lastname@example.org