In finalizing the bill, Sen. Edward Kennedy (D-MA), chair of the Senate Health, Education, Labor and Pensions (HELP) Committee,
clarified that a reference product can have only one 12-year exclusivity period. Such exclusivity starts the day FDA approves
the product for market, and innovators can't add more years by developing new formulations or dosage forms, adding new indications
or conducting pediatric studies. The exclusivity applies only to a biologic that is comparable to a new chemical entity for
drugs, and not to a slightly different version of an existing treatment.
Kennedy touted the Senate compromise as a way to "encourage the innovation that leads to these new medical miracles," as well
as to ensure that they are affordable for patients. Senators Orrin Hatch (R-UT), Mike Enzi (R-Wyo), ranking Republican on
the HELP committee, and Hillary Clinton (D-NY) all signed off on the measure, making partisan changes difficult.
One reason for agreeing to 12 years exclusivity, said Clinton, is that many biotech therapies have been on the market long
enough to be eligible immediately for follow-on competition. Amgen's anemia treatment Epogen (epoetin alfa), for example,
was approved in the US in 1989, and other biotech therapies for multiple sclerosis, cancer, hepatitis C, and diabetes have
or will soon exceed the exclusivity period.
DELICATE BALANCING ACT
The Senate bill announced in June permits generics makers to file an application for a biosimilar four years after the start
of the innovator's exclusivity period, a move that triggers a multistep process designed to resolve patent issues early on.
It calls for an exchange of confidential information between the follow-on firm and the innovator on manufacturing process
and product characteristics to identify effective patents. It is not clear just how the system will work, and biotech firms
are concerned that the follow-on firm will determine which patents can be litigated, making it harder to defend patent rights.
Congress also offers a process for developing interchangeable FOBs. But to gain approval of an FOB that pharmacists can substitute
for the original product without the prescriber's okay, the follow-on maker will have to conduct clinical trials to show that
the new product can be switched with the original one without any clinical differences. The legislation offers FOB sponsors
a one-year data exclusivity award as an incentive to take that route.
The main testing and regulatory provisions of the FOB legislation reflect multiple trade-offs between the demands of innovators
and generics firms. The measure calls for at least one or more clinical studies to assess immunogenicity of a follow-on, but
gives FDA leeway to waive that requirement.
FDA may develop guidance for testing and developing FOBs, but generics firms don't have to wait for such guidance in order
to move forward with testing and applications. Such guidance could indicate that existing science does not support follow-ons
for a certain product class, but FDA could revise such a finding later on.
Follow-on applicants will start off by paying user fees on applications while FDA assesses the costs of running the program
and recommends changes in the fee structure. Along those lines, the FDA review division that approved the innovator will assess
any follow-ons—not FDA's Office of Generic Drugs. This could encourage FDA reviewers to compare proprietary brand data when
evaluating an FOB, something that innovators strongly oppose.
A provision in the Senate bill calls for the government to determine how much money the healthcare system saves from allowing
follow-on biologics to come to market. A lot of interest groups have predicted huge gains from FOBs, and it will be interesting
to see the results.
Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD 301.656.4634, firstname.lastname@example.org