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EF: BfArM is one of the two national regulatory bodies within the portfolio of the German Federal Ministry of Health that approve drugs and medical devices in Germany; how do you work with the PEI, and what are your priorities for the coming years? 

KB: We have two regulatory agencies in Germany, with divided responsibilities, and the BfArM is responsible for chemicals, generic products, and medical devices. The Paul Ehrlich Institute (PEI) is responsible for blood and the majority of biological medicines, and especially during the pandemic, they were very important in the vaccine assessment for the European market. They have been extremely active in several areas, such as the approval at the EMA for vaccines. BfArM was during the pandemic e.g. responsible for the approval of the first therapeutics for Covid-19 and other EMA procedures.  

BfArM sees itself as an enabler in fostering innovation. We are well aware that the European system has room for improvement to become a pioneer as a lucrative location for research and development of innovative approaches in the healthcare sector. We are working to improve, taking the lessons learned into account and applying all the regulatory flexibility shown during the pandemic to the more routine cases. The new clinical trial regulation is an important milestone to provide a better and safer framework to bring innovation as safely and as fast as possible to patients in Europe.  

We have a new mandatory clinical trial information system whereby all European countries can apply for clinical trials through this new channel, which is a big advantage. We have been also working after receiving feedback to improve it in a way that is user-friendlier for every stakeholder. The digital approach makes the procedure easier. I believe it will be key in the new pharma legislation planned by the European Commission, as they are interested in fostering practicality and making processes faster and easier while avoiding duplication of the information and procedures. At BfArM, we fully support this approach; the better use of data is a key point we are working on, as well as on digital applications. BfArM has been number 1 in the world in assessing such digital health applications, the so called “DiGA”. After BfArM clears a product, it is reimbursed by the statutory health insurance companies. A new business model is growing, other countries are highly interested, and agencies are contacting us to follow our lead. We are also building our research tool (research health data lab) that will leverage specific data of German statutory health insurance companies, which will be a driver for research and fostering a closer relationship with the patients.  

EF: Does this include the work you are doing in Real4Reg, and with real-world evidence?  

KB: This is a separate topic but a field where we work. Adopting new technologies to ease the procedures and complimentary use of real-world evidence with data-driven information is crucial to improve regulatory systems. I am working with Emer Cooke, ED  of the EMA, as co-chair and partner in the DARWIN project on better data use and real-world data, controlling it, and transcribing real-world data to real-world evidence. The Real4Reg is the European approach and a planned national attempt to make our research data available to other European health data spaces. We are proud of Real4Reg's success within the European system; it is working well and growing. Last year we made a good start on DARWIN with studies organized by the Center in Rotterdam, which we are following up on in Germany to improve fieldwork evidence. There has been a lot of progress in defining the data needed to provide better results, and this is becoming clearer every day.  

EF: How do you balance your priorities working with other regulatory bodies for their improvement while remaining competitive at an international level?   

KB: BfArM is one of the leaders as Rapporteur in many procedures within the European system. We have 1300 employees with different expertise, which is significantly more than other agencies in the network; therefore, it is crucial to build a network between the regulatory agencies to share knowledge, expertise – and workload. As chair of the Heads of Medicine Agencies (HMA) management group, I am fostering a strengthened network. We have established tactical groups and implemented measures for capacity building and training of assessors in smaller agencies. The European system aims to build multinational assessment teams, with experts e.g. on the clinical side from BfArM, a preclinical expert from another agency, maybe Sweden, and quality assessment from Malta, to foster experience, knowledge, and improvement within the European system.  

EF: How do you see the role of healthcare in improving the economy? How are you collaborating with the Ministry of Economy to that end? 

KB:  We belong to the German Ministry of Health, and over the recent weeks and months, there have been shortages, a difficult situation to which we must find solutions. Germany was the "pharmacy of the world" for decades; we have lost that position, but the healthcare industry is still extremely important in the country. We continuously interact with all stakeholders, learned societies and ministries, pharma representatives, and associations on a national and European level. We need more diversification; many pharmaceutical products are produced only in a few facilities. During the pandemic, in the plant in Northern Italy where Propofol was manufactured, the product was close to being unavailable, but we solved the situation. The lessons learned from that experience are now in place. Last December, the Ministry moved with the cornerstone paper to improve the situation for generics and products for children and adolescents, which we welcomed. We are helping the Ministry by providing all the information we have. At BfArM, we have an advisory board to mitigate shortages, which was very effective last year regarding the lack of e.g. Tamoxifen in Germany. We also did the same for Amoxicillin and antipyretics for children. We are using innovation and AI techniques, implementing a risk management system to prevent better similar situations in the future. We are applying machine learning techniques and programs to be faster and have earlier warnings, leaving the purely reactive modus, and giving us more time for the management of new situations. Our first pilots are promising. In many instances, the state of affairs is more dynamic with digital health applications. Our innovation office receives many requests for scientific advice, our books for the decentralized procedures and scientific advice are full, and I believe we are going in the right direction. The pandemic showed the fragility of the supply chain and an overdependence on APIs from Asia, which was damaging, and an important lesson learned. The representatives of the BPI, VFA, and the BAH all agree we need more innovation and more money in the German system, it is part of the ongoing discussions, and we are doing our part. We must find the right balance: be more agile while maintaining the efficacy and safety of medicines and medical devices. We must be as flexible as possible but keep efficacy and safety as well. 

EF: Coronavirus has affected the frameworks of approval procedures; how do you see this evolving, considering you have AI, machine learning, and digital initiatives such as online technical and clinical trial information systems?  

KB: We will not return to a pre-pandemic scenario; the new environment will simplify procedural issues, streamline approaches to avoid duplication of work, and have a more agile system in the future, backed by good data. Clinical trials are more complex, and we must support initiatives that allow for digital assessments. There will be more and more remote work in clinical trials, and we will have to find here a balance, too. I am very optimistic about the changes and data quality, which I believe is necessary. Our regulatory work will change in the future, and we must be open-minded and enablers of the new way of working –a new statistical approach with complementary real-world evidence and data will be the new normal. There is a high internal validity for applications of clinical trials, but when it comes to patients, the external validity is lower. Bringing clinical trials and real-world data together will improve –particularly external validity- and reflect positively on patients' everyday treatment. The solid framework will enhance the safety and agility of introducing innovation. We already know that within the next five to ten years, 50% of the market will be cancer treatment and associated applications. We have strategically increased our experts in oncology and other fields and trained people from different areas to be oncology experts. 

EF: What therapeutic areas are bringing exciting innovation into Germany?  

KB: We will see more dynamics in digital health applications; digital tools will help to better monitor and understand the many chronic disorders. The new digital tools will help find better biomarkers, help real-world data define future indications better, and increase and improve individualized patient care, which will be a huge topic moving forward.  Recently CHMP at EMA approved two new cancer drugs for a histology-agnostic indication, and BfArM participated in the assessment. We will see more and more of such development, particularly in oncology. It is 18 years since we have had a mandatory approach in oncology products for centralized marketing authorisation. In the first six years, 24 new products were approved, 48 in the second six years, and  76 new oncology products, medicine, and cancer treatments in the last six. This trend will continue over the next years. There will be individualized therapies for many chronic disorders like diabetes, and the digital applications will monitor chronic diseases much better, training the patients to be more aware of their condition and care for themselves. Especially in cases such as hypertension and diabetes, there will be major improvements. We will see a more connected digitalized health ecosystem. 

EF: How do you rate technology adoption in Germany for these DIGA products? 

KB: I have been in touch with some health insurance leaders, and they see the growth potential, which can also be seen in the increasing rate of prescriptions. Of course, there is some criticism and fear that it is too costly, whereas others are very positive. We have feedback that patients using the applications are satisfied, and physicians prescribe them. We are going to learned societies and medical associations to discuss the pros and cons of using such applications and people's fears about using them. There is still much work to be done to improve the situation, indeed. We will support further interaction between all stakeholders, and the DiGA directory with all relevant information on a DiGA will increase trust in this digital application. 

EF: How would you like BfArM to be remembered after your tenure? 

KB: BfArM should be remembered not just as a regulator but as an enabler, not only a gatekeeper but an entity that fosters innovation and takes the regulatory system to the next stages.  

March 2023