United states securities and exchange commission

Table of Contents
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In the E.U., there is detailed legislation on 
pharmacovigilance and extensive guidance on good 
pharmacovigilance practices.
Regardless of the approval process employed, 
various parties share responsibilities for the 
monitoring, detection and evaluation of adverse 
events post-approval, including national authorities, 
the EMA, the EC and the marketing authorization 
holder. The EMA’s PRAC is responsible for assessing 
and monitoring the safety of human medicines and 
makes recommendations on product safety issues.
In some regions, it is possible to receive an 
“accelerated” review whereby the national regulatory 
authority will commit to truncated review timelines for 
products that meet specific medical needs.
Good Manufacturing Practices
Regulatory agencies regulate and inspect 
equipment, facilities and processes used in the 
manufacturing and testing of pharmaceutical and 
biologic products prior to approving a product. If, after 
receiving approval from regulatory agencies, a 
company makes a material change in manufacturing 
equipment, location or process, additional regulatory 
review and approval may be required. We also must 
adhere to current Good Manufacturing Practices 
(cGMP) and product-specific regulations enforced by 
regulatory agencies following product approval. The 
FDA, the EMA and other regulatory agencies also 
conduct periodic visits to re-inspect equipment, 
facilities and processes following the initial approval 
of a product. If, as a result of these inspections, it is 
determined that our equipment, facilities or processes 
do not comply with applicable regulations and 
conditions of product approval, regulatory agencies 
may seek civil, criminal or administrative sanctions or 
remedies against us, including significant financial 
penalties and the suspension of our manufacturing 
operations.
Good Clinical Practices
The FDA, the EMA and other regulatory agencies 
promulgate regulations and standards for designing, 
conducting, monitoring, auditing and reporting the 
results of clinical trials to ensure that the data and 
results are accurate and that the rights and welfare of 
trial participants are adequately protected (commonly 
referred to as current Good Clinical Practices (cGCP)). 
Regulatory agencies enforce cGCP through periodic 
inspections of trial sponsors, principal investigators 
and trial sites, contract research organizations (CROs) 
and institutional review boards. If our studies fail to 
comply with applicable cGCP guidelines, the clinical 
data generated in our clinical trials may be deemed 
unreliable and relevant regulatory agencies may 
require us to perform additional clinical trials before 
approving our marketing applications. Noncompliance 
can also result in civil or criminal sanctions. We rely 
on third parties, including CROs, to carry out many of 
our clinical trial-related activities. Failure of such third 
parties to comply with cGCP can likewise result in 
rejection of our clinical trial data or other sanctions.
In April 2014, the EC adopted a new Clinical Trial 
Regulation, which was effective in June 2014 but is 
not expected to apply until the second half of 2019. 
The regulation harmonizes the procedures for 
assessment and governance of clinical trials 
throughout the E.U. and will require that information 
on the authorization, conduct and results of each 
clinical trial conducted in the E.U. be publicly 
available.
Approval of Biosimilars 
The Patient Protection and Affordable Care Act 
(PPACA) amended the Public Health Service Act 
(PHSA) to authorize the FDA to approve biological 
products, referred to as biosimilars or follow-on 
biologics that are shown to be highly similar to 
previously approved biological products based upon 
potentially abbreviated data packages. The biosimilar 
must show it has no clinically meaningful differences 
in terms of safety and effectiveness from the 
reference product, and only minor differences in 
clinically inactive components are allowable in 
biosimilars products. The approval pathway for 
biosimilars does, however, grant a biologics 
manufacturer a 12-year period of exclusivity from the 
date of approval of its biological product before 
biosimilar competition can be introduced. There is 
uncertainty, however, as the approval framework for 
biosimilars originally was enacted as part of the 
PPACA. In 2017 there were, and there are likely to 
continue to be, federal legislative and administrative 
efforts to repeal, substantially modify or invalidate 
some or all of the provisions of the PPACA. If the 
PPACA is repealed, substantially modified or 
invalidated, it is unclear what, if any, impact such 
action would have on biosimilar regulation.
A biosimilars approval pathway has been in place 
in the E.U. since 2003. The EMA has issued a 
number of scientific and product specific biosimilar 
guidelines, including requirements for approving 
biosimilars containing monoclonal antibodies. In the 
E.U., biosimilars are generally approved under the 
centralized procedure. The approval pathway allows 
sponsors of a biosimilar to seek and obtain regulatory 
approval based in part on reliance on the clinical trial 
data of an innovator product to which the biosimilar 
has been demonstrated, through comprehensive 
comparability studies, to be “similar”. In many cases, 
this allows biosimilars to be brought to market 
without conducting the full complement of clinical 
trials typically required for novel biologic drugs.

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