A Cell Graft or a Drug? Legal and Practical Aspects of Somatic Cells Application in Graft-Versus-Host Disease Experimental Treatment: The Polish Experience

• Steroid-refractory GvHD is a field of growing interest for experimental cell therapies with mesenchymal stem/stromal cells as well as regulatory T cells.
• According to current law in European Union, human cells intended for human application can be consider either as cell grafts or as advanced therapy medicinal products (ATMP).
• There are 3 main kinds of ATMP: gene therapy medicinal products, somatic cell therapy medicinal products, and tissue engineering medicinal products.
• Cells that are expanded in vitro become an ATMP.
• ATMP, which is prepared on a nonroutine basis according to specific quality standards and used within the same Member State in a hospital under the exclusive professional responsibility of a medical practitioner to comply with an individual medical prescription for a custom-made product for an individual patient, is excluded from the scope of the EU Pharmaceutical Directive.

IntroductionAllogeneic hematopoietic stem and progenitor cell (HSPC) transplantation and organ transplantation are well-established treatments for different conditions. Graft versus host disease (GvHD) is a major complication in both methods. There has been a rapid increase in the application of nonhematopoietic somatic cells, such as mesenchymal stem cells and regulatory T cells in GvHD experimental therapy. According to current European Union (EU) law, human cells intended for human application can be considered either as cell grafts or as advanced therapy medicinal products (ATMPs).Objective, Materials and MethodsThe aim of the paper is an attempt to answer, based on GvHD experimental treatment data as well as existing EU and Polish law, whether cells cease to be cells (cell grafts) and becomes drugs (ATMPs); if yes, when; and what are the consequences of such situation both for patients as well as for physicians engaged in the treatment process in Poland.Results and DiscussionData analysis confirmed the interest in the experimental GvHD cell therapy. In the vast majority of analyzed cases the in vitro culture step in the cell preparation protocols has been foreseen. Therefore, the answer to title question was unambiguous—expanded cells are recognized in EU as ATMPs. In borderline cases, a scientific recommendation by the Committee for Advanced Therapies (CAT) of the European Medicines Agency (EMA) can play an important auxiliary role; however, it is currently neither required by Polish law nor legally binding in Poland.