Waxman
Biosimilars Bill, implications for the biotech industry
On March 11, 2009, Henry
A Waxman (D-Calif.), chairman of House Committee on Energy and
Commerce; Frank Pallone (D-N J), Nathan Deal (R-Ga), and Jo
Ann Emerson (R-Mo), introduced the bipartisan “Promoting
Innovation and Access to Life-Saving Medicine Act” (H R 1427)
that is intended to give the US Food and Drug Administration (US FDA)
the authority to approve biosimilar versions of biotech drugs.
The bill provides the approval of biosimilar products that are defined
as “no clinically meaningful differences between the
biological product and the reference product” as well as
“interchangeable” biosimilars, defined as a product
that can be “switched one or more times” with the
reference product “without an expected increase in the risk
of adverse events”. The bill also provides incentives for
brand companies to develop new therapies. Specifically, similar to the
current structure for approved drugs, the bill would provide five years
of exclusivity for a novel molecular structure before any biosimilar
could be approved. The bill also provides three-year exclusivity for
certain modifications of a previously approved product (such as a new
condition of use) and a six-month pediatric exclusivity period. These
exclusivity provisions are a change in direction for Waxman, as his
biosimilar bill put forth in the 2007 Congress (H R 1038) provided no
exclusivity for brand biologic products. Finally, Waxman’s
bill also provides first biosimilar applicants with at least six-month
exclusivity period if an interchangeable biosimilar product is
approved. Senator Susan Collins (R-Maine) announced that she will
co-sponsor the senate version of the bill, expected to be introduced
soon by Senators Charles Schumer (D-N.Y.) and Sherrod Brown (D-Ohio).
The bill provides the approval of biosimilar products that are defined
as “no clinically meaningful differences between the
biological product and the reference product” as well as
“interchangeable” biosimilars, defined as a product
that can be “switched one or more times” with the
reference product “without an expected increase in the risk
of adverse events”. The bill also provides incentives for
brand companies to develop new therapies. Specifically, similar to the
current structure for approved drugs, the bill would proviKiran.gifde
five years of exclusivity for a novel molecular structure before any
biosimilar could be approved. The bill also provides three-year
exclusivity for certain modifications of a previously approved product
(such as a new condition of use) and a six-month pediatric exclusivity
period. These exclusivity provisions are a change in direction for
Waxman, as his biosimilar bill put forth in the 2007 Congress (H R
1038) provided no exclusivity for brand biologic products. Finally,
Waxman’s bill also provides first biosimilar applicants with
at least six-month exclusivity period if an interchangeable biosimilar
product is approved. Senator Susan Collins (R-Maine) announced that she
will co-sponsor the senate version of the bill, expected to be
introduced soon by Senators Charles Schumer (D-N.Y.) and Sherrod Brown
(D-Ohio).
Patent disputes addressed
The bill would establish a procedure for resolving patent disputes
before a biosimilar is approved, and would establish penalties for
failure to litigate patents in a timely manner. It also presents patent
dispute provisions similar to those proposed in H R 1038.
Under the current bill, a biosimilar applicant has discretion to send a
written request for patent information to the BLA holder. Within 60
days, the BLA holder must provide the applicant a list of all patents
relating to the approved product, including patents claiming the
biological product, formulations, and methods of using and
manufacturing the product, even if the claimed methods for
manufacturing are not used to make the reference product. The BLA
holder must update the patent list for two years after receiving the
request. At any time thereafter, the biosimilar applicant may provide
notice of the biosimilar application with respect to one or more
patents, either listed by the BLA holder or not. This notice, which the
applicant sends to the BLA holder, patent owner, and the Federal Trade
Commission (FTC), must include a detailed statement of the factual and
legal basis for applicant’s belief that the listed patents
are invalid, unenforceable, or not infringed.
Within 45 days of receiving the biosimilar applicant’s
notice, the BLA holder or patent owner may sue for patent infringement,
but only with regard to patents listed in the notice. If the BLA holder
or patent owner does not file suit within 45 days, the biosimilar
applicant may bring an action for declaratory judgment that the patents
are invalid or not infringed. If the BLA holder or patent owner sues
after 45 days, the BLA holder or patent owner is entitled to damages
only in the form of reasonable royalties in the event that a court
finds infringement by the applicant. The bill also states that if a
patent owner or licensee fails to disclose a patent in response to an
applicant’s request for patent information in a timely
manner, the patent owner or licensee may not bring an action
“under this title” for patent infringement.
Major battle looms
The Waxman bill has broad support from varied groups, including the
Generic Pharmaceutical Association (GPhA), which
“applauded” the introduction of the bill; Consumers
Union, American Association of Retired Persons (AARP), National
Organization for Rare Disorders, Coalition for a Competitive
Pharmaceutical Market, General Motors, Express Scripts, Inc., National
Business Group on Health, American Federation of Labor and Congress of
Industrial Organizations(AFL-CIO), and Service Employees International
Union (SEIU). However, the Biotechnology Industry Organization (BIO)
described the Waxman bill as “filled with
potholes,” and has previously stated its position that a
14-year exclusivity period is necessary to provide adequate protections
for continued research and development of novel biologic products.
Other competing bills
Representative Anna Eshoo (D-Calif.) and House Committee on Energy and
Commerce ranking member Joe Barton (R-Texas) are
expected to reintroduce the legislation, the “Pathway for
Biosimilars Act” (PBA), that would award brand companies 12
years of protection from generic competition and an additional two
years of protection for an approved new indication, which is a
“significant improvement” over other marketed
products. The PBA also would provide six-month exclusivity for study in
pediatric populations. The PBA does permit FDA to determine
interchangeable products, and would grant at least two years of
exclusivity for the first approved interchangeable biosimilar product.
The PBA places requirements on FDA to issue proposed guidance documents
for public review, issuance of final guidance prior to waiving clinical
trials for immunogenicity of any biosimilar, prior to the approval of
any interchangeable biosimilar; and initiate a proceeding for issuance
of a guidance with respect to a product class prior to accepting a
biosimilar application for review. Further, such application may not be
approved until such final guidance is completed. Publication of such
guidance would likely have the effect of slowing the submission and
review process of biosimilars.
The PBA differs from the current Waxman bill in several respects as it
relates to patent dispute provisions. For example, in the PBA, relevant
patents include those having claims directed to the biosimilar product,
material used in the product manufacture or methods of treatment, but
not methods of manufacturing the product. In addition, the biosimilar
applicant does not have discretion to act under the PBA, but instead
must provide the bond ledger account (BLA) holder a copy of the
biosimilar application and product and production information. Within
60 days of receiving the application and information, the BLA holder
must provide the applicant a list of relevant patents. The PBA also
requires FDA to publish a notice within 30 days of accepting a
biosimilar application. Any time after FDA publishes its notice, a
third party patentee may provide notice to the biosimilar applicant
identifying at least one patent. Within 30 days of receiving that
notice, the biosimilar applicant also must send the patentee a copy of
the patent application and product or production information. Within 90
days thereafter, the patentee must provide a list of relevant patents
to the applicant. The BLA holder or patentee must explain in writing
why a listed patent would be infringed. Within 45 days of receiving the
list, the biosimilar applicant must send a written statement regarding
each listed patent that either states that the applicant will not
market until after the patent expires, or provides an explanation why
the patent would not be infringed, or is invalid or unenforceable.
Within 60 days of receiving the patent list the BLA holder or patentee
may sue for patent infringement.
Also in contrast with the Waxman bill, the biosimilar applicant may
only bring a declaratory judgment action on the date that is either
three-year before the 12-year exclusivity period for the brand company
or 120 days after the submission of explanation by the applicant.
A look ahead
Given the broad disagreement on major components of the bill between
both industry and congressional members, negotiation and compromise
will still be necessary in order to pass this complex legislation. With
other pressing issues before the House Committee on Energy and
Commerce, including universal health care and climate change, it
remains to be seen when this bill will gain the full attention of the
committee. In addition, H R 1427 was referred to the House Committee on
the judiciary, so there is more than one committee playing a role. On
the senate side, compromise on a bill will be essential, as procedural
hurdles in the senate ensure that passage will require 60 votes. Thus,
although there appears to be a consensus that biosimilar legislation
will pass this congressional session, this is simply the first, albeit
important, step in the process. Obama administration has voiced support
for biosimilar legislation, and as a candidate, Obama supported shorter
exclusivity periods for branded biologics than those proposed by BIO,
but has yet to weigh in on specifics involving the bills.
Narayanan Suresh and
Nayantara Som with inputs from Jahanara Parveen and Shalini Gupta