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.