Following European regulation 1394/2007, mesenchymal stromal cell (MSCs) have become an advanced therapy medicinal product (ATMP) that must be produced following the good manufacturing practice (GMP) standards. We describe the upgrade of our existing clinical-grade MSC manufacturing process to obtain GMP certification. Staff organization, premises/equipment qualification and monitoring, raw materials management, starting materials, technical manufacturing processes, quality controls, and the release, thawing and infusion were substantially reorganized. Numerous studies have been carried out to validate cultures and demonstrate the short-term stability of fresh or thawed products, as well their stability during long-term storage. Detailed results of media simulation tests, validation runs and early MSC batches are presented. We also report the validation of a new variant of the process aiming to prepare fresh MSCs for the treatment of specific lesions of Crohn’s disease by local injection. In conclusion, we have successfully ensured the adaptation of our clinical-grade MSC production process to the GMP requirements. The GMP manufacturing of MSC products is feasible in the academic setting for a limited number of batches with a significant cost increase, but moving to large-scale production necessary for phase III trials would require the involvement of industrial partners.

With this analysis we would like to raise some issues that emerge as a result of recent evolutions in the burgeoning field of human cells, tissues, and cellular and tissue-based product (HCT/P) transplantation, and this in the light of the current EU regulatory framework. This paper is intended as an open letter addressed to the EU policy makers, who will be charged with the review and revision of the current legislation. We propose some urgent corrections or additions to cope with the rapid advances in biomedical science, an extensive commercialization of HCT/Ps, and the growing expectation of the general public regarding the ethical use of altruistically donated cells and tissues. Without a sound wake-up call, the diverging interests of this newly established ‘healthcare’ industry and the wellbeing of humanity will likely lead to totally unacceptable situations, like some of which we are reporting here.

Blood, tissue and cell establishments (BTCs) stand out in the management of donor selection, procurement and processing of all types of substances of human origin (SoHO). In the last decades, the framework created around BTCs, including hospitals and national health system networks, and their links to research, development and innovation organizations and agencies have spurred their involvement in the study of groundbreaking advanced therapy medicinal products (ATMP). To further improve strategic synergies in the development of ATMPs, it will be required to promote intra- and inter-European collaborations by creating an international network involving BTCs and major stakeholders (i.e., research organizations, hospitals, universities, patient associations, public agencies). This vision is already shared with the European Blood Alliance, the association of non-profit blood establishments, with 26 member states throughout the European Union and European Free Trade Association states. Herein we present and analyze the "BTC for ATMP Development And Manufacture" (BADAM) model, an ethically responsible business model based on the values and missions of BTCs and their commitment to health equity, patient access and education (based on voluntary donation of SoHO to address unmet clinical needs, while contributing to training professionals and scientific literacy of our Society).

The late 1980s saw the emergence of experimental therapies based on human cell and tissue products (HCTPs) within academic and hospital settings, several of them wound healing related. In 2008, the European Commission introduced the Regulation on advanced therapy medicinal products (ATMPs), defining many of these HCTPs as ATMPs, and more specifically as somatic cell therapy medicinal products (sCTMPs) or tissue‐engineered products (TEPs). In 2013, we predicted that the ATMP regulation would adversely impact Member States' health care systems and would threaten the sustainability of many HCTPs provided by public health institutions. To assess the current ATMP state of play and investigate whether these predictions ultimately came true, we consulted relevant scientific and trade literature and official competent authority reports and surveyed the former Belgian HCTP producers. We found that the ATMP Regulation produced 19 authorised ATMPs, with 16 of them (84.2%) belonging to the gene therapy medicinal product (GTMP) class and only 3 HCTPs (15.8%), 2 TEPs and 1 sCTMP. List prices varied according to the ATMP class, with public health insurances struggling to reimburse ATMPs, especially the exuberantly priced GTMPs. This led to marketing authorization withdrawals, and crowd funding approaches and lotteries to determine who would receive lifesaving treatments. A hospital exemption (HE) scheme was enacted to protect ATMPs not intended for commercial exploitation. Whilst limited financial resources generally hampered HE utilisation by public actors, stringent regulatory policies made it virtually impossible in Belgium, resulting in meaningful HCTPs no longer being available to surgeons and their patients.