ATMPs can be classified as either gene therapies, somatic cell therapies, tissue engineered products or combined ATMPs, depending on a whole host of information submitted to CAT, including active substance and key elements of manufacturing. So far, the CAT has issued over 100 recommendations for the classification of innovative medicines as ATMPs.
Manufacturers are encouraged to get their ATMPs classified free of charge to gain access to incentives, such as fee reductions for scientific advice and the certification of quality and non-clinical data of ATMPs. The classification also helps sponsors to identify the applicable regulatory framework and development path, as well as the scientific or regulatory guidance to be followed.
The reflection paper offers decision trees to help companies decide if they might qualify for such incentives and fall under one of the treatment categories. It also offers criteria distinctions between the categories of ATMPs, such as criteria distinguishing somatic cell therapy medicinal products (sCTMP) and tissue engineered products (TEPs).
sCTMP and TEPs both contain or consist of engineered cells or tissues cells or tissues, the EMA says that to be considered “engineered,” the cells have to have been manipulated during the manufacturing process so that their biological characteristics, physiological functions or structural properties have been modified to be relevant for their intended function. Examples of substantial manipulations include cell expansion (culture), genetic modification of cells, differentiation/activation with growth factors.
The EMA also offers an example of when a gene therapy medicinal product may be confused for a cell therapy medicinal product. The “borderline scenario” relates to products that are modified by adding an mRNA sequence, for example dendritic cells electroporated with mRNA in vitro and administrated to the patient to elicit a specific immune response.
“One could argue that the claimed mechanism of action is directly related to the expression of the mRNA encoded antigens to stimulate e.g. tumour specific immune responses. However, due to its relatively short half-life there may be little or no residual mRNA at the time of re-administration of the dendritic cells (DCs) to the patient. Thus, it can be claimed that…the mRNA electroporated DCs could be seen as an intermediate in the manufacturing process where the phenotype is finally altered without alteration of the genotype of the cells. Therefore, the product was considered not to comply with the definition of a gene therapy medicinal product,” the EMA concludes.
The paper also clarifies in particular:
- What is considered as a non-homologous use of cells or tissues;
- When medicines based on recombinant viral vectors are considered as vaccines against infectious disease and not as gene-therapy medicinal products; and
- Criteria for classification as combined ATMPs, including products that incorporate an active substance and one or more medical devices.
ATMP classification, along with other pre-authorisation services offered by the Agency such as Innovation Task Force briefing meetings, often constitutes the first contact between the Agency and ATMP developers. It is often used as a first step to initiate a tailored dialogue on product development plan with the Agency.
Comments on the reflection paper should be sent to firstname.lastname@example.org by Oct.31.