Marketing Authorisation Applications
In the EU, marketing authorisation of GTMPs falls under the mandatory
scope of the central authorisation procedure, through submission to, and
review by, the EMA and its committees. The CAT is responsible for the
primary evaluation of ATMP marketing authorisation applications for the
CHMP. Marketing authorisation of GTMPs requires, as for all medicinal
products, that the applicant demonstrates the quality, safety and the
efficacy in patients. The data submitted by developers of GTMPs in their
application for marketing authorisation must include a range of
information, including the way the medicine is manufactured, its effects
in laboratory studies, benefits and side effects observed in patients,
and how risks will be managed, as well as the proposed information to be
provided to patients and doctors. It is also important to ensure that
environmental risks from innovative medicines are understood and
controlled and this is discussed in the ERA. The objective of an ERA is
to identify and evaluate any potential adverse effects of the GMO,
either direct or indirect, immediate or delayed, on human health and the
environment. Importantly, the ERA should be conducted with a view to
evaluate if there is a need for risk management, and if so, the most
appropriate methods to use. Two guidelines have been issued by the EMA
on the expected content for the ERA for GTMP and/or medicinal products
containing GMOs [4,19].
At the same time, in line with the regulatory science strategy of the
Agency and to support the translation of ATMPs into patient treatments,
the EMA has recognised the need to streamline interactions with ERA
Competent authorities during the assessment of the ERA.
The improvements in this field have been made through complementing the
guidelines with detailed recommendations for dossier submissions in the
‘European Medicines Agency pre-authorisation procedural advice for users
of the centralised procedure’ [20].which provide
assistance with early planning, method development and evaluation; and
updating procedures to facilitate a consistent approach for the
assessment of the environmental risks of medicines containing GMO
[21].
The common application forms developed for the assessment of GMO aspects
in the context of clinical trials with IMPDs already adapt the technical
requirements to the characteristic of human cells genetically modified
by means of retro/lentiviral vectors or medicinal products that contain
AAV vectors. To reduce administrative burdens, the technical
requirements at the time of filing, marketing authorisation applications
are built on the same common application forms used for clinical trial
approval. The medicinal products eligible for a “specific ERA” in the
context of clinical trial applications are also eligible for this type
of ERA at marketing authorisation applications.
In addition, to deliver a contribution that is fit for purpose in view
of the sharp increase of the number of ATMPs in development and expected
marketing authorisation applications involving GMOs, the consultation
process with national competent authorities responsible for
environmental risks is now focused on the questions/aspects identified
by the rapporteur, in particular on the risk minimisation measures.