Amgen 2012 Annual Report Download - page 31

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evaluating a number of relevant issues, and additional guidance documents are expected to be released, including guidance on the
criteria for interchangeability (which the FDA has indicated would be a “higher standard” than biosimilarity).
FDA Regulation of Product Marketing and Promotion. The FDA closely reviews and regulates the marketing and promotion
of products. We are required to obtain the FDA approval before marketing or promoting a product as a treatment for a particular
indication. Our product promotion for approved product indications must comply with the statutory standards of the FDCA, and
the FDA’s implementing regulations and standards. The FDA’s review of marketing and promotional activities encompasses, but
is not limited to, direct-to-consumer advertising, healthcare provider-directed advertising and promotion, sales representative
communications to healthcare professionals, promotional programming and promotional activities involving the Internet. The
FDA may also review industry-sponsored scientific and educational activities. The FDA may take enforcement action against a
company for promoting unapproved uses of a product or for other violations of its advertising and labeling laws and regulations.
Enforcement action may include product seizures, injunctions, civil or criminal penalties or regulatory letters, which may require
corrective advertising or other corrective communications to healthcare professionals. Failure to comply with the FDA’s regulations
also can result in adverse publicity or increased scrutiny of company activities by the U.S. Congress or other legislators.
FDA Regulation of Manufacturing Standards. The FDA regulates and inspects equipment, facilities, laboratories and
processes used in the manufacturing and testing of products prior to providing approval to market products. If after receiving
approval from the FDA, we make a material change in manufacturing equipment, location or process, additional regulatory review
may be required. We also must adhere to current Good Manufacturing Practice regulations and product-specific regulations enforced
by the FDA through its facilities inspection program. The FDA also conducts regular, periodic visits to re-inspect our equipment,
facilities, laboratories and processes following an initial approval. If, as a result of those inspections, the FDA determines that our
equipment, facilities, laboratories or processes do not comply with applicable FDA regulations and conditions of product approval,
the FDA may seek civil, criminal or administrative sanctions and/or remedies against us, including suspension of our manufacturing
operations. Such issues may also delay the approval of new products undergoing FDA review.
Regulation of Combination Products. When our products are used with medical devices, they may be considered combination
products, which are defined by the FDA to include products comprised of two or more regulated components or parts (e.g., a
biologic and a device). When regulated independently, biologics and devices each have their own regulatory requirements. However,
the regulatory requirements for a combination product comprised of a biologic administered with a delivery device are more
complex, as in addition to the individual regulatory requirements for each component, additional combination product regulatory
requirements may apply. We expect that in the future a number of our pipeline products may meet this definition and be evaluated
for regulatory approval under this framework. In addition, due to regional differences in regulation structures and systems outside
the United States, the definition and regulatory requirements for combination products may differ significantly depending on the
region.
New Innovation Provisions Available to Regulatory Agencies Reviewing Drug Applications. In the United States, the FDA
may grant accelerated approval status to products that treat serious or life-threatening illnesses and that provide meaningful
therapeutic benefits to patients over existing treatments. Under accelerated approval regulations, the FDA may approve a product
based on a surrogate endpoint that is reasonably likely to predict clinical benefit or based on an effect on a clinical endpoint other
than survival or irreversible morbidity. The sponsor/marketing applicant will then be required to conduct additional, post-approval
confirmatory trials to verify and describe clinical benefit, and the product may have certain post-marketing restrictions as necessary
to assure safe use. The FDA is also given greater flexibility to withdraw approval granted under accelerated approval, if it is
warranted. Additional legislation has been approved in 2012 that could further expand the FDA's authority. For example, the FDA
may consider ways to more greatly use the accelerated approval pathway for rare or very rare diseases, and a new review designation
was created to help foster the innovation of promising new therapies with the potential to shorten the timeframe for conducting
pivotal trials and speed up patient access to the approved product.
In Europe, the preexisting conditional approval pathway provides for the European Medicines Agency (EMA) to apply
greater flexibility in terms of their benefit/risk evaluation in order to promote innovation. While no plans to revise or add to this
statutory provision have been announced, there are on-going discussions at the EMA to consider so-called “adaptive licensing”.
It is not clear at this stage whether such proposals will result in meaningful changes to the EU regulatory approval pathway.
Approval and Post-Approval Regulation Outside the United States. In the EU countries, Switzerland, Canada and Australia,
regulatory requirements and approval processes are similar in principle to those in the United States. Additionally, depending on
the type of drug for which approval is sought, there are currently two potential tracks for marketing approval in the EU, including
a centralized procedure. In the centralized procedure, which is required of all products derived from biotechnology, a company
submits a single marketing authorization application to the EMA which conducts a thorough evaluation, drawing from its scientific
resources across Europe. If the drug product is proven to fulfill the requirements for quality, safety and efficacy, the CHMP adopts
a positive opinion, which is transmitted to the EC for final approval of the marketing authorization. While the EC generally follows
the CHMP's opinion, it is not bound to do so. In the EU, biosimilars have been approved under a sub-pathway of the centralized
procedure since 2006. The pathway allows sponsors of a biosimilar to seek and obtain regulatory approval based in part on the