Translating Academic Drug Discovery Into Clinical Development: A Survey of the Awareness of Regulatory Support and Requirements Among Stakeholders in Europe.

Important discoveries by academic drug developers hold the promise of bringing innovative treatments that address unmet medical needs to the market. However, the drug development process has proved to be challenging and demanding for academic researchers, and regulatory challenges are an important barrier to implementing academic findings in clinical practice. European regulators offer varying degrees of support services to help drug developers meet regulatory standards and requirements. "Strengthening Training of Academia in Regulatory Sciences and Supporting Regulatory Scientific Advice" (STARS) is a European Commission-funded consortium aiming to strengthen the training of academics in regulatory science and requirements. Here, we report the results of four surveys that investigated the awareness and utilization of support tools offered by European regulators and identified the regulatory challenges and support needs of researchers. The surveys targeted four main European stakeholders in academic medicines research: academic research groups (706 respondents), academic research centers (99), funding organizations (49), and regulators (22). The results show that while European regulators provide various regulatory support tools, less than half of the responding academic researchers were aware of these tools and many experienced challenges in reaching a sufficient level of regulatory knowledge. There was a general lack of understanding of the regulatory environment that was aggravated by poor communication between stakeholders. The results of this study form a foundation for an improved European medicines regulatory network, in which regulatory challenges faced by academia are tackled.

[Digital health applications (DiGA): assessment of reimbursability by means of the "DiGA Fast Track" procedure at the Federal Institute for Drugs and Medical Devices (BfArM)]. / Digitale Gesundheitsanwendungen (DiGA): Bewertung der Erstattungsfähigkeit mittels DiGA-Fast-Track-Verfahrens im Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM).

With the Digital Health Care Act (DVG), the legislator has made it possible for digital health applications (DiGA) to be included in standard care and reimbursement in accordance with the Fifth Book of the German Social Code (SGB V). The prerequisite for the "app on prescription" is a listing in the DiGA directory after a positive evaluation procedure at the Federal Institute for Drugs and Medical Devices (BfArM). In addition to comprehensive quality and safety parameters, the manufacturers must also prove a positive healthcare effect.With the DiGA directory, the BfArM has been offering addressee-oriented comprehensive transparency on DiGA and their properties since October 2020. The article explains the path to the app on prescription from the support and advisory services offered by the BfArM to the evaluation procedure (DiGA Fast Track) and the evaluation criteria to the contents of the directory. It can be seen that there is great interest in the Fast Track procedure. The evidence of positive healthcare effects, i.e. an actual added value for patients, is balanced and at an appropriate level with predominantly randomised controlled trial evidence. The fact that the procedure can also be associated with challenges for the applicants, e.g. to adequately address deficiencies in the legally prescribed assessment period, is indicated by the numbers of withdrawn applications in relation to the listed DiGA. The BfArM is in close exchange with all parties involved regarding this new procedure. The conclusion of this article shows which considerations and potentials result from this for further development from the point of view of the BfArM.

[Digitization of the healthcare system: the BfArM's contribution to the development of potential]. / Beitrag des BfArM zur Potenzialentfaltung der Digitalisierung im Gesundheitswesen ­ digital readiness@BfArM.

Digitalization is a clear megatrend of our time, also in the health sector, which is currently experiencing enormous acceleration due to the COVID-19 pandemic in addition to paving the way due to changes in the legal framework. Looking to the future, this trend will contribute to further digitalization and the merging of individual digital products, including medicinal products and medical devices, into a digital ecosystem. This will be supported by ever-shorter development cycles and technological progress. Digitization will not only strengthen patient sovereignty, but also enable more patient-centered medicine; artificial intelligence will improve and accelerate diagnoses and will contribute to a better understanding of disease patterns and underlying mechanisms or causes.In order to continue to enable innovations in the future, to focus on emerging trends, and, above all, to further improve patient safety, the BfArM is contributing in many places to transforming the opportunities associated with digitalization into possibilities - without losing sight of the risks. The following is an overview of how, for example, the expansion of the Research Data Center, activities addressing interoperability, research projects using artificial intelligence, (inter-)national cooperation, the utilization and inclusion of "Real World Data" in our benefit/risk assessments, and the evaluation of digital health and digital care applications among other activities of the BfArM contribute to "digital readiness" in Germany and Europe.

[Support for innovation at the BfArM-experiences from the consultations on digital health applications (DiGA)]. / Innovationsunterstützung im BfArM ­ Erfahrungen aus den Beratungen zu digitalen Gesundheitsanwendungen (DiGA).

Since May 2020, manufacturers have been able to submit an application to the Federal Institute for Drugs and Medical Devices (BfArM) for the inclusion of a digital health application (DiGA) in the directory pursuant to section 139e of the German Social Code Book V. This new application procedure is based on specific requirements and assessment parameters for which a large number of procedural and scientific questions arise on the side of the manufacturers.In order to meet this need, the BfArM has specifically expanded its established information and advisory services for these new questions. This article describes in detail what these are in relation to DiGA, where the corresponding information and documents can be found and what distinguishes them in each case. Furthermore, with a view to the counselling interviews conducted between May 2020 and April 2021, their influence on the outcome of the respective application procedure for inclusion in the DiGA directory is analysed. This confirms that the early discussion of parameters relevant to the evaluation and the consideration of the advisory recommendations correlate with a positive evaluation result. For the DiGA listed in the directory, 80% of the manufacturers had previously received advice from the BfArM. The rate of withdrawn or rejected applications, on the other hand, was significantly higher if manufacturers had not previously sought advice from the BfArM in advance compared to manufacturers who discussed key aspects (63% vs. 35%). Overall, all sides benefit from the early, intensive exchange - in the end especially the patients through introduction of DiGA into standard healthcare due to higher application quality without delay.

Strengthening regulatory science in academia: STARS, an EU initiative to bridge the translational gap.

Truly disruptive medicine innovation and new treatment paradigms tend to start in non-commercial research institutions. However, the lack of mutual understanding between medicine developers and regulators when it comes to medicine development significantly delays or even prevents the access of patients to these innovations. Here, we outline what regulatory-related barriers hamper the translational development of novel products or new treatment paradigms initiated in academia, and propose key steps towards improved regulatory dialogue among academia, funding bodies and regulatory authorities. Moreover, we briefly describe how the STARS (Strengthening Training of Academia in Regulatory Science) project aims to reach out to medicine innovators in academia to bridge the regulatory knowledge gap and enhance this dialogue to facilitate the implementation of academic research findings in clinical practice.