[Commentary] The regulation of clinical stem cell research and applications: three dynamics of global regulatory diversification

The evolving regulatory landscape for clinical stem cell research is characterized by a conflict between the striving for international harmonization and an increasing process of global regulatory diversification. Attempts of regulatory harmonization are exemplified, for instance, by the 2016 Guidelines for Stem Cell Research and Clinical Translation by the International Society for Stem Cell Research (ISSCR 2016), the Advanced Therapy and Medicinal Products (ATMP) Regulation of the European Medicines Agency (EMA), or by the ATMP Cluster of the US Food and Drug Administration (FDA), EMA and Health Canada (Arcidiacono 2012). These processes of harmonization have evolved from a pharmaceutical model of drug development and the ideal of Evidence-Based Medicine (EBM), with the multiphase randomized controlled trial (RCT) system as methodological gold standard. In parallel to these developments, however, discontent with the use of the multi-phase trial system for the clinical validation of stem cell-based medicinal product has grown. A politics of opposition has emerged that has called for the use of alternative methods and forms of evidence, to reduce the costs of clinical testing and to increase access to non-systematically proven innovative interventions at an earlier stage. Calls for international harmonization in the stem cell field have been undermined too, by practical challenges to standardize clinical and cell processing procedures in large-scale, multi-country trials, which require a complex logistical infrastructure and significant financial resources. For academic researchers and small to mid-size biotech companies these resources are often not available (Rosemann 2014). Since industry involvement in stem cell medicine has remained at a low level, the mobilization of resources to take investigational stem cell products or therapies through rigorous multi-phase trials, remains typically a challenge. This politics of alter-standardization has taken an increasingly global form. Many impulses for regulatory change and a shift away from multi-phase trials for stem cell-based treatments, have come from Asia, especially from Japan, India, China and South Korea (Sleeboom-Faulkner et al. 2016). But opposition to EBM and the multi-phase trial system, and calls for the emerging of new models and methodologies of clinical innovation in the stem cell field has also increasingly evolved in the European Union and the USA. These clashes have resulted in three central dynamics of regulatory diversification. These developments challenge the use of multi-phase trial methodology as the central methodological instrument for therapy development in the stem cell field in many respects.