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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.