Amgen 2012 Annual Report Download - page 30

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studies and patient registries, and may engage in risk management activities such as physician education initiatives and patient
advocacy group initiatives. We may also conduct or be required by regulatory agencies to conduct further clinical trials to provide
additional information on our marketed products’ safety and efficacy. Those additional trials may include studying doses or
schedules of administration different from those used in previous studies, use in other patient populations or other stages of the
disease or use over a longer period of time. Additional trials of this nature are sometimes required by regulatory agencies as a
condition of their approval to market our products, and they might also request or require that we conduct specific studies, including
observational epidemiological studies, in order to identify or assess possible safety risks of our marketed products that are observed
or suggested by available scientific data and such trials are sometimes referred to as PMCs or PMRs. In the United States, if the
FDA becomes aware of new safety information after approval of a product, it may require us to conduct further clinical trials to
assess a known or potential serious risk. If we are required to conduct such a post-approval study, periodic status reports must be
submitted to the FDA. Failure to conduct such post-approval studies in a timely manner may result in substantial civil or criminal
penalties. Data resulting from these clinical trials may result in expansions or restrictions to the labeled indications for which our
products have already been approved and to the reimbursement provided by government and commercial payers for our products.
The FDA also has the authority to require companies to implement a REMS for a product to ensure that the benefits of the
drug outweigh the risks. The FDA may require the submission of a REMS before a product is approved or after approval based
on new safety information, including new analyses of existing safety information. In determining whether a product will require
a REMS before the product is approved, the FDA may consider a number of factors.
Each REMS is unique and varies depending on the specific factors required. While the elements of REMS may vary, all
REMS require the sponsor to submit periodic assessment reports to the FDA to demonstrate that the goals of the REMS are being
met. Failure to comply with a REMS, including submission of a required assessment or any modification to a REMS, may result
in substantial civil or criminal penalties and can result in additional limitations being placed on a product’s use and, potentially,
withdrawal of the product from the market. We currently have approved REMS for our ESAs, Prolia® and Nplate®. The FDA and
sponsor companies continue to learn how best to implement, operate and monitor the effectiveness of REMS, and the requirements
of our REMS and those of other companies may change over time. The FDA published guidance intended to limit or remove
REMS requirements for certain products. The FDA will also be looking at ways to standardize REMS programs, with the intent
to make the establishment, review and assessment of these programs less burdensome on the agency and the sponsor. The FDA
will hold a series of public meetings on REMS over the next several years and will solicit stakeholder feedback in an effort to
continue to focus and improve their risk management oversight.
Adverse events that are reported after marketing approval also can result in additional limitations being placed on a product’s
use and, potentially, withdrawal of the product from the market. The FDA has authority to mandate labeling changes to products
at any point in a product’s lifecycle based on new safety information or as part of an evolving label change to a particular class
of products.
The FDA also uses various advisory committees of external experts to assist in its mission to protect and promote the public
health and to obtain independent expert advice on scientific, technical and policy matters. The committees are generally advisory
only and FDA officials are not bound to or limited by their recommendations. We have participated in meetings of the Oncology
Drug Advisory Committee, the Cardiovascular and Renal Drug Advisory Committee and the Advisory Committee for Reproductive
Health Drugs, among others, to address certain issues related to our products, including Aranesp®, EPOGEN®, Prolia® and
XGEVA®.
FDA Approval of Biosimilars. The PPACA authorizes the FDA to approve biosimilars via a separate, abbreviated pathway.
The law establishes a period of 12 years of data exclusivity for reference products in order to preserve incentives for future
innovation and outlines statutory criteria for science-based biosimilar approval standards that take into account patient safety
considerations. Under this framework, data exclusivity protects the data in the innovator’s regulatory application by prohibiting
others, for a period of 12 years, from gaining FDA approval based in part on reliance on or reference to the innovator’s data in
their application to the FDA. The new law does not change the duration of patents granted on biologic products. In February 2012,
the FDA released three draft guidance documents as part of the implementation of the abbreviated approval pathway for biosimilars.
While the FDA guidance documents are not legally binding on the public or on the FDA, they indicate the FDA’s current thinking
on the development of biosimilars. The draft guidance documents provide insight on a range of technical, scientific and regulatory
issues. The guidance documents generally provide that, for approval, a sponsor must demonstrate that the proposed product is
“biosimilar” (a term defined by statute) to a single reference product already licensed by the FDA. In assessing biosimilarity, the
FDA indicated that it intends to use a risk-based “totality of the evidence” approach to evaluate all available data submitted by
the applicant. Generally, a biosimilar application must include a clinical study or studies sufficient to demonstrate safety, purity
and potency in one or more indications for which the reference product is licensed and the biosimilar applicant seeks approval.
The scope and magnitude of clinical data needed will depend on the extent of uncertainty about the biosimilarity of the product
as well as the frequency and severity of safety risks associated with the reference product. The FDA indicated that it is still