Regulation in the European Union
Product development, the regulatory approval
process, and safety monitoring of medicinal products and their manufacturers in the European Union proceed in much the same manner
as they do in the United States. Therefore, many of the issues discussed above apply similarly in the context of the European Union.
In addition, drugs are subject to the extensive price and reimbursement regulations of the various European Union Member States.
As is the case in the United States, the
various phases of pre-clinical and clinical research in the European Union are subject to significant regulatory controls. The
Clinical Trials Directive 2001/20/EC, as amended (and which will be replaced from the end of May 2019 or later by Regulation (EU)
No 536/2014) provides a system for the approval of clinical studies in the European Union via implementation through national legislation
of the Member States. Under this system, approval must be obtained from the competent national authorities of the European Union
Member States in which the clinical trial is to be conducted. Furthermore, a clinical trial may only be started after a competent
ethics committee has issued a favorable opinion on the clinical trial application, which must be supported by an investigational
medicinal product dossier with supporting information prescribed by the Clinical Trials Directive and corresponding national laws
of the Member States and further detailed in applicable guidance documents. A clinical trial may only be undertaken if provision
has been made for insurance or indemnity to cover the liability of the investigator or sponsor. In certain countries, the sponsor
of a clinical trial has a strict (faultless) liability for any (direct or indirect) damage suffered by trial subjects. The sponsor
of a clinical trial, or its legal representative, must be based in the European Economic Area. European regulators and ethics committees
also require the submission of adverse event reports during a study and a copy of the final study report.
Marketing approvals under the European
Union regulatory system may be obtained through a centralized or decentralized procedure. The centralized procedure results in
the grant of a single marketing authorization that is valid for all (currently 28) European Union Member States and three EFTA
members (Norway, Iceland, Liechtenstein).
Pursuant to Regulation (EC) No. 726/2004,
as amended, the centralized procedure is mandatory for drugs developed by means of specified biotechnological processes, advanced
therapy medicinal products, drugs for human use containing a new active substance for which the therapeutic indication is the treatment
of specified diseases, including but not limited to acquired immune deficiency syndrome, neurodegenerative disorders, auto-immune
diseases and other immune dysfunctions, as well as drugs designated as orphan drugs. The CHMP also has the discretion to permit
other products to use the centralized procedure if it considers them sufficiently innovative or they contain a new active substance.
In the marketing authorization application,
or MAA, the applicant has to properly and sufficiently demonstrate the quality, safety and efficacy of the drug. Under the centralized
approval procedure, the CHMP, possibly in conjunction with other committees, is responsible for drawing up the opinion of the EMA
on any matter concerning the admissibility of the files submitted in accordance with the centralized procedure, such as an opinion
on the granting, variation, suspension or revocation of a marketing authorization, and pharmacovigilance.
The CHMP and other committees are also
responsible for providing guidelines and have published numerous guidelines that may apply to our product candidates. These guidelines
provide additional guidance on the factors that the EMA will consider in relation to the development and evaluation of drug products
and may include, among other things, the pre-clinical studies required in specific cases; and the manufacturing and control information
that should be submitted in a MAA; and post-approval measures required to monitor patients and evaluate the long term efficacy
and potential adverse reactions. Although these guidelines are not legally binding, we believe that our compliance with them is
likely necessary to gain approval for any of our product candidates.