Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Toward expanded patient access to gene and cell therapy products: a comparative study of the regulatory approaches in the European Union, the United States and Japan ***

Dr. Valeria Facchinetti (Abschlußjahr: 2017)

Summary
Language: English
Gene and cell therapy (GCT) products constitute a class of heterogeneous biopharmaceuticals with the potential to provide innovative treatments for a broad range of medical conditions for which conventional approaches have been proved inadequate.
Efforts have been made in many jurisdictions to establish a tailored regulatory approach in order to promote effective product development and to accelerate the practical applications of these innovative therapies, while ensuring public health protection. However, being these therapies in the frontline of a rapidly evolving field, a continuous reshaping of the regulatory framework is required to accommodate the improved scientific knowledge and technological progress.
The aim of this Master thesis is to compare the regulatory frameworks for gene and cell therapy products currently in force in the three ICH jurisdictions, namely Europe, the United States, and Japan. For this purpose, the regulatory pathways and specific requirements adopted by the different jurisdictions are analysed and discussed. Particular emphasis has been given to the strategies employed to address the challenges posed by this category of medicinal products and to the mechanisms to facilitate timely patient access to new innovative therapies. In addition, in the view of the increasingly global context of medicines development and regulation, this study includes an overview on the ongoing international initiatives to achieve regulatory harmonization/convergence in order to facilitate the global availability of safe and effective therapies in a timely manner.
The analysis of the three legal frameworks reveals a high level of regulatory convergence, along with differences and specificities. GCT products are regulated as biologics in the US, whereas in the EU and in Japan are regulated within specific regulatory frameworks. A tailored approach for regulating these products is deemed necessary in each jurisdiction, and the necessary flexibility is achieved by means of different regulatory tools. In the EU and in the US a marketing authorisation is generally granted on the base of confirmatory quality, safety and efficacy data supporting a positive benefit/risk profile. However, a flexible approach is applied and the type of evidences to be submitted is decided on a case-by-case basis in the US and in accordance with a risk-based approach in the EU.  Japan has introduced in 2014 a new two-phased approval system for regenerative medicine, consisting of a time-limited conditional approval after demonstration of safety and probable benefit, followed by a full marketing authorisation after submission of confirmatory clinical data. Licensing schemes similar to the Japanese approval system for regenerative medicine products are available also in the EU (conditional approval and adaptive pathways) and in the US (accelerated approval) as tools to expedite the development of advanced therapies and to decrease the time to marketing authorisation. Additional specific programs to provide further licensing flexibility and development support are available in all three jurisdictions, as well as mechanisms to make these therapies available to eligible patients besides participation in clinical trial and treatment with authorised products.
Although the overall regulatory approaches to evaluation of quality, safety and efficacy are based on the current ICH guidelines and present a high grade of similarity, several aspects related to the development of advanced therapies are still not fully harmonized across jurisdictions. For instance, quality requirements for biological materials and provisions related to donor screening and testing are region specific, and compliance with GCP and GMP is achieved with some local implementation differences.  The extent of GMP compliance required before entering clinical trials differs among jurisdictions, with the more restrictive requirements present in the EU.
Interestingly, despite the high level of convergence achieved by the ICH members, there is the perception among developers and other stakeholders that the European regulatory framework for these products is less flexible and presents more burdensome requirements than in other jurisdictions. This can partially be ascribed to the lack of a single global regulatory system operating in the EU in regards to several functions (e.g. regulatory oversight of clinical trials and hospital exemption and provisions regulating starting material and GMO requirements), which are regulated at national level.
In view of the global development, a prospective regulatory harmonization and convergence is deemed paramount by both the regulatory community and the industry. With this purpose, many international initiatives have been initiated to promote regulatory science at global level and to harmonize internationally recognized requirements in the advanced therapies field.
As agreed by the global regulatory community, a timely availability of safe and effective gene and cell therapies will be achieved only through the coordination of international regulatory efforts and by promoting the development of common regulatory approaches capable of efficient responses to the rapidly developing field while ensuring adequate standards.
Pages: 77, Annexes: pages: 15