Amgen 2011 Annual Report Download - page 43

clinical trials to investigate the safety and efficacy of our product candidates in a large number of patients who
have the disease or condition under study. The time and expense required for us to perform this clinical testing is
substantial and may vary by product. For example, the clinical trials for the BLA for Prolia®/XGEVA®were
large and required substantial time and resources to recruit patients and significant expense to execute.
Historically, our products have required smaller, shorter trials. Foreign studies performed under an IND must
meet the same requirements that apply to U.S. studies. The FDA will accept a foreign clinical study not
conducted under an IND only if the study is well-designed, well-conducted, performed by qualified investigators,
and conforms to good clinical practice. Phase 1, 2 and 3 testing may not be completed successfully within any
specified time period, if at all. (See Item 1A. Risk Factors — We may not be able to develop commercial
products.) The FDA monitors the progress of each trial conducted under an IND and may, at its discretion,
re-evaluate, alter, suspend, or terminate the testing based on the data accumulated to that point and the FDA’s
risk/benefit assessment with regard to the patients enrolled in the trial. (See Item 1A. Risk Factors — We must
conduct clinical trials in humans before we can commercialize and sell any of our product candidates or existing
products for new indications.)
Applications. The results of preclinical and clinical trials are submitted to the FDA in the form of a BLA for
biologic products subject to the Public Health Service Act or an NDA for drugs subject to the approval
provisions of the FDCA. The submission of the application is no guarantee that the FDA will find it complete
and accept it for filing. If an application is accepted for filing, following the FDA’s review, the FDA may grant
marketing approval, request additional information, or deny the application if it determines that the application
does not provide an adequate basis for approval. We cannot take any action to market any new drug or biologic
product in the United States until our appropriate marketing application has been approved by the FDA.
Post-approval Phase. After we have obtained approval to market our products, we monitor adverse events
from the use of our products and report such events to regulatory agencies, along with information from post
marketing surveillance or studies. We may utilize other research approaches to learn or confirm information
about our marketed products, including observational 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 different
doses or schedules of administration that were 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, under the Food and Drug
Administration Amendments Act of 2007 (the FDAAA), 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 FDAAA also gave the FDA authority to require companies to implement a REMS for a product to
ensure that the benefits of the drugs outweigh the risks. While risk management activities and programs are not
new, with FDAAA the FDA gained new authority to implement specific risk management requirements and new
enforcement power to ensure that the goals of the REMS are being met. The FDA began to implement REMS in
2008. 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 including:
• estimated size of the population likely to use the product;
• seriousness of the condition treated and expected benefits of the product;
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