Masterarbeit

Regulatory requirements regardings cell-based medicinal products for human and veterinary use in Germany and Europe - a comparison ***

Dr. Johanna Kuhlmann-Gottke (2014)

Advanced therapy medicinal products (ATMPs) form a new and innovative class of medicines in the EU which are regulated by Regulation (EC) No 1394/2007 on ATMPs. There are three types of ATMPs defined in the legislation: gene therapy products, somatic cell therapy products (sCTMPs) and tissue engineered products (TEPs). Both sCTMPs and TEPs are referred to as “cell-based medicinal products” (CBMPs).
The aim of this Master thesis is to compare the regulatory situation for human cell-based medicinal products with that for veterinary CBMPs in Germany and Europe. For this purpose, the current regulatory pathways for CBMPs (i.e. sCTMPs and TEPs) for human and veterinary use are analysed and discussed, and the need for a new regulatory framework for veterinary cell-based therapies is reviewed, based on the current practice.
There is no doubt that the complexity and diversity of CBMPs necessitated a dedicated human regulatory framework. However, the level of success with human CBMPs has not met the expectations of the pre-ATMP era. With a view to the future, the adaptive licensing approach for innovative new medicines for the treatment of diseases with high unmet medical need might become increasingly important, as it aims to maximize the positive effect of new treatments on public health by balancing timely access for patients with the need to gain knowledge on their benefits and risks. In this context, the German implementation of the Hospital Exemption (HE) clause for ATMPs manufactured on a non-routine basis must be considered as adaptive licensing approach on a national level.
With respect to CBMPs for veterinary use, there is currently no legislative framework in place, neither in Germany nor in a European context. However, requests for MUMS classification and for regulatory and scientific advice for veterinary CBMPs are increasing.
The existing minor-use-minor-species (MUMS) / limited market policy at Community level is rather inadequate for the regulatory challenges associated with CBMPs. The specificity and complexity of cell-based products requires a specific regulatory approach. There is a definite need for clear and reliable legal provisions as well as defined responsibilities and competences for such veterinary CBMPs, both on the European and on the national German level, as shown by presented case studies.
At present, decisions with respect to legal classification and marketing authorisation (MA) obligation are taken on a case-by-case basis, including the risk that, in the long term, those uncertainties might deter developing companies and non-commercial entities and thus impede therapeutic innovation in the veterinary field. To prevent this development, legal definitions and competences corresponding to those in the human legislation should be issued as soon as possible, as well as data requirements for MA applications for those new products. Such an approach aiming at a regulatory framework for veterinary innovative therapies should, in any case, be harmonised among the different European NCAs and the EMA.
There is currently no need for a legal framework equivalent to the human ATMP legislation. A “leaner” solution would be more appropriate for the veterinary field. Here, the German implementation of the HE clause might serve as a model for a regulatory approach to make the product available on the basis of a limited dataset within an authorised setting and to subsequently use the data collected under the HE in order to grant a “full” MA.
Pages: 62, Annexes: -