Topics

The proposed concepts and measures in Topic I are intended to defragment GCT research and establish a national value chain. These measures aim to promote the development and application of these therapies across all phases of life and all specialist fields. They include expanding national networking structures, interacting with political decision-makers, fostering collaboration between science, clinical practice, industry and other stakeholders, and strengthening international links.

It aims to increase the visibility of stakeholders and the network, promote interdisciplinary collaboration, provide comprehensive information on GCT activities and initiate discussions to strengthen the value chain. The objective is to position GCTs as a strategic focus of innovation policy, supported by analysis of their strengths and weaknesses along with intensive communication with different interest groups.

These efforts will be implemented in close coordination with stakeholders, under supervision by the working groups. A proposal is also made for a governance structure to oversee implementation of the National Strategy.

Certain measures will be coordinated by the National Network Office for GCTs. Milestones to measure target attainment include the establishment of a roundtable meeting of stakeholders as an official expert committee, a national GCT map, an informative website, a clinical data register, regular analyses, network meetings, professional development events, progress reports and information events for political stakeholders. In addition, communication with regulators, patients’ organizations, funding providers and other stakeholders will be systematically expanded at the national and European levels. The success of the National Strategy for GCTs will require the effective interaction of wide-ranging measures, which must be implemented step by step. There are, initially, three priority measures in Topic I: 1) establish a governance structure involving relevant stakeholders (in a bottom-up approach), 2) create a national GCT network map and 3) prepare an annual progress report on the National Strategy for GCTs.

Working Groups

Excellent training and continuous development of skills are essential for the successful development, manufacturing and clinical application of GCTs. For this reason, they are the focus of Topic II. In Germany and elsewhere, there is often a shortage of high-quality staff in different academic and non-academic fields, e.g., in manufacturing, process and methods engineering, analytics, quality control and quality assurance, as well as regarding protection of intellectual property (IP), entrepreneurship, treatment strategies and clinical translatability. As a result, by international comparison, Germany has an insufficient number of investigator-initiated trials (IITs) and start-ups, especially when compared to the USA, China and the United Kingdom.

To change this, the experts in Topic II recommend a substantial strengthening and refining of the national talent pipeline, focusing on the following key points:

• Establish and expand training and development programs for specialists in all occupational groups (i. e., academic and non-academic professionals; scientific, scientific-technical and technical professionals)
• Implement these programs at suitable locations with collaboration from academia and industry (see Topic VI, Objective 1, Measure 1)
• Develop adequate upskilling concepts, career concepts, bonus concepts and interaction concepts

To support implementation of the proposed measures and fully exploit the defined success indicators to accompany the implementation process, dedicated packages of measures have been developed with clearly defined targets, timelines and resource requirements.

The measures described in this section should provide a concept for a multi-track, modular training program for a certificate in “Gene- and Cell-based Therapies”, with proposals for implementation regarding extra-occupational, interdisciplinary Master’s and doctoral programs as well as targeted training programs. In this regard, we propose establishing national GCT education and training centers to consolidate academic, non-academic and industrial skills. Furthermore, we recommend targeted measures to create incentive and bonus systems, develop career concepts and draft interaction concepts between stakeholders involved in training and career development, e. g., academia and industry.

If these measures and their implementation strategies are enacted promptly, it should be possible to rectify the weaknesses in this area and facilitate the urgently needed translation of GCTs into medical care in Germany with lasting effect.

Working Groups

Translating knowledge into tangible impact: the technology transfer strives to apply the results of biomedical research to deliver benefits for patients, economy and society. In this context, it is essential to keep the entire translation chain in mind – from patenting new ideas to collecting essential pre-clinical data and establishing suitable production processes through to clinical proof-of-concept in a suitable patient population. This is the only way we will be able to keep pace internationally with other nations, such as the USA and China, which are leaders in GCTs. From the patients’ perspective as well, a robust transfer of knowledge in Germany and Europe is essential to provide swift access to novel therapies, create jobs and exert influence on price developments. And, of course, a successful translation of GCTs will support value creation in Germany and Europe.

To achieve this, it will be necessary to raise awareness of the requirements and opportunities of translation of GCTs and spread an understanding of the fundamentals of product development, thereby shaping technology transfer units in such a way that they can support the entire transfer process, from protection of IP to application in clinical practice. In addition to highly qualified specialists, this will require support from a central product development unit (PDU) specializing in GCTs and the targeted deployment of consultants. These would advise on specific aspects of product development, particularly in relation to production and regulatory affairs.

Transfer activities performed by individual people, academic institutions and universities should be considered equally in their performance assessments. It also appears necessary to offer employment prospects for research assistants who possess specific knowledge essential for the translation of a product to clinical application until they can move to a spin off. To make spin-offs and start-ups an attractive prospect for founders and venture capital providers, standardized licensing conditions should be created (drawing on international standards, such as the University Spinout Investment Terms (USIT) Guide) and access to publicly funded infrastructure facilitated. Transparent distribution of eventual revenues – taking account of inventors, the institute or hospital where the invention was made and a fund for future transfer projects at these institutions – is an important motivational factor. We have therefore formulated four specific targets regarding technology transfer, and defined measures designed to achieve them:

1. Improve the framework conditions for early identification and utilization of innovative potential of scientific results

2. Ensure comprehensive consultancy and assessment of transfer projects, incorporating the entire development process for an investigational medicinal product (IMP), from production to use in patient care

3. Facilitate efforts to exploit the social and/or economic potential of scientific results

4. Establish recognition of transfer activities and transfer successes as part of individual researchers’ and institutions’ scientific reputation

Working Groups

It is both possible and necessary to improve the regulatory framework to bolster innovative capabilities and strengths in Germany and in Europe. The following core elements have been identified and utilized to develop specific measure:

• Defragment the regulatory environment for GCTs by concentrating procedures and responsibilities, including for manufacturing authorizations, at the Paul-Ehrlich-Institut (PEI) and strengthen the PEI with additional resources

• Improve EU legislation on clinical trials (EU Clinical Trials Regulation (CTR) – Regulation (EU) No 536/2014) and improve coordination of processes for medical devices and in vitro diagnostics

• Protect, preserve and expand academic research and innovation opportunities to drive GCT developments by:

  • redefining some medication-related terminology and regulatory procedures in the field of GCTs

  • simplifying authorization procedures for frequently used processes and starting materials in the form of master file systems

  • introducing the sandbox approach as a space for innovation

• Establish a central GCT-GMP and regulatory affairs committee as a communication platform to continue the work of the National Strategy, taking the National Advisory Committee on Blood (Arbeitskreis Blut) as a model

Working Groups

The quality and safety requirements for pharmaceutical products for use on humans represent fundamental standards that apply to clinical samples as well as approved and marketed products. In the transition from laboratory testing to clinical practice, GCTs are subject to intensive product and process development in accordance with applicable guidelines on GMP. After reviewing compliance with all GMP guidelines, the responsible authority will issue a product-specific and time-limited manufacturing authorization. Given the expenditure to fulfill the various property, staffing, time, regulatory, monitoring and administrative requirements, establishing and consistently maintaining GMP infrastructure entails significant costs. This expenditure and the lack of qualified GMP professionals to operate in-house GMP infrastructure for research and development are usually prohibitive for academic institutions and start-ups with single GCT projects. In Germany, utilizing other academic and non-academic GMP contract manufacturers for innovative GCTs in the early clinical stages is only possible in limited cases, and even then, remains both time-consuming and expensive. In other European countries, and in particular outside of Europe, streamlined statutory provisions facilitate the implementation of early clinical studies. The lack of comparable regulations in Germany puts the country at a disadvantage and is a significant contributor to the loss of domestic value creation in this area. Against this backdrop, we believe there is an urgent need to improve quality standards, establish and expand GMP production capacity in Germany and optimize translational processes by streamlining structures and accelerating procedures. To achieve this in a prompt, targeted manner with due regard for the dynamics of GCT developments, we recommend four objectives:

• Promote the establishment and expansion of qualified GMP infrastructure in line with demand, for starting materials and for complex GCT products

• Secure the necessary staffing capacity and expertise for GCT manufacturing and quality control

• Increase the efficiency and speed of manufacturing processes

• Pursue development and risk-based streamlining of framework conditions

As a priority, we suggest these measures :

1. Create a central GCT-GMP and regulatory affairs committee comprising all relevant stakeholders (incl. the Federal Ministry of Health (BMG), the PEI, science and industry, etc.) to analyze and continuously drive forward progress towards the objectives in this topic in a timely, needs-based manner

2. Provide targeted and sufficient financial resources from the federal government, state governments and other funding providers to establish, expand and operate GMP infrastructure in line with demand, including a production facility for critical starting materials for GCTs

Working Groups

It is essential that ideas are recognized and supported to drive forward the development of GCTs in Germany. This happens via research and development: the driver of innovation for GCT products. They initiate the translation of pre-clinical developments into clinical trials, which ensure that the products are made available in standard healthcare. However, improvements in Germany’s research and development infrastructure are urgently required to meet the challenges in the field of GCTs. It will be necessary to establish decentralized hubs that are accessible to the scientific community across Germany. In addition, the expansion of production capacities – and access to these capacities – should be expedited to reduce the costs of clinical studies and ensure availability. Establishing incubators for start-ups and biotech companies should promote innovation, while expanding test facilities should ensure both the efficacy and the safety of these innovations. Above all, intensive collaboration between all stakeholders involved in the development and manufacture of GCT products should accelerate clinical studies initiated by scientific institutions.

Identifying future topics and providing specific support requires the equal involvement of all relevant stakeholders and the development of interdisciplinary visions. In this context, implementing novel and agile funding formats and establishing new collaboration models between industry and academia will be essential. This can facilitate the swift and sufficiently funded translation of results from basic research into early clinical studies, thereby positioning Germany as an innovation leader in the field of GCTs.

The efficient use of financial resources, as exemplified by international examples (the BioCanRx network, Canada; the Oncode Institute, the Netherlands; Catapult and the Medical Research Council (MRC), United Kingdom), could support this.

Considering the challenges and potential in the field of GCTs, the implementation of GMP-light procedures for phase I/II clinical studies should be advanced to strengthen Germany as a location for research. Furthermore, there will be a need to realistically assess the necessity for animal experiments, expedite respective authorization procedures and increasingly promote alternative methods to ensure Germany’s competitive position internationally, while also meeting ethical standards. Introducing performance indicators is essential to promote transparency and efficiency in authorization procedures for GCTs. Ethics committees must be optimized and made more efficient by harmonizing standards and introducing specialist bodies with the aim of expediting authorization procedures.

Involving patients into research processes at an early stage is essential to give due consideration to their needs and perspectives, as well as to integrate this information into the design of research projects and clinical studies.

Specific education and training programs, grants and career-support measures in biomedical research, combined with topics such as spin-offs and translation/transfer, should encourage specialists to move to Germany and remain here. Modifications to existing education and training systems and specialized study programs can help to meet the increased demand for GCT specialists.

Working Groups

Early access to high-quality care with GCTs can improve the quality of life and health of the most critically ill patients. In some cases, it could even present the first and only treatment options. Challenges involved for early access to GCTs include securing approval for these new medicinal products and applying them in practice-. This require amendments to existing provisions and possibly the creation of new structures and instruments, if necessary. The following are key measures in this context:

1. Giving patients swift access to specialist care in terms of diagnosis, both to facilitate the start of treatment and to monitor the success of GCT during treatment.

   1. Develop and implement education and advanced training programs to ensure optimal access to GCTs and support continuous advancements in diagnostics

   2. Establish interdisciplinary therapy decision boards as the gold standard in GCT diagnostics.

   3. Develop nationally standardized qualification criteria, standards and reference datasets for corresponding GCT access and ongoing diagnostics.

2. Enhance the flexibility of reimbursement and care models for GCTs while reinforcing Germany’s position as a leading location for research and treatment. This includes promoting an innovation-friendly environment with high-quality patient care via efficient, state-of-the-art therapies by amending the Act on the Reform of the Market for Medicinal Products (AMNOG) and adapting care remuneration structures.

   1. Regarding therapeutic developments in the field of GCTs, it is important to allow for the necessary flexibility in the AMNOG process in terms of benefit assessments and price-setting to uphold access to, and the availability of, these vital therapies for patients

   2. At the level of patient care, ensuring appropriate quality assurance measures in diagnostics and treatment for patients is a priority and requires an amendment of remuneration models

3. Providing high-quality, safe and efficient treatment for patients with innovative therapies by establishing interdisciplinary GCT treatment facilities. In this context, it will be important to establish a close structural interaction between research and healthcare, streamline qualification and certification processes for treatment facilities and streamline contract design processes between treatment facilities and manufacturers. Efficient referral and communication between treatment providers must also be ensured.

4. Optimizing and establishing the data landscape to ensure the versatile availability of treatment data in research and long-term data tracking, regarding aspects such as the efficacy and side-effects of GCTs. In this context, the recording and documentation of post-marketing data should be standardized, with a target set to maintain a method-specific national GCT register.

Working Groups

The developments in the field of GCTs continues to be dynamic with particularly high needs regarding engagement with different target groups and stakeholders in society – both today and for the foreseeable future. We have therefore defined the following objectives for Topic VIII:

• Inform society about GCTs by providing reliable, target group-specific information

• Support/advise decision-makers by strengthening engagement with politics as well as initiating/maintaining an open-ended humanistic/social discourse

• Implement targeted measures to promote the potential benefits of GCTs through intensified involvement and participation of research funding organizations, foundations and parts of civil society willing to donate

Achieving these targets will require a lasting governance structure from the National Strategy and should attract widespread public attention using visible and credible ambassadors. The following measures and resources will therefore be required in the short to medium term:

• Establishment of a central communication platform with an online presence to provide information for different relevant target groups. Target group-specific services should be compiled and created for the general public, as well as specific offers for media/journalists, patients and patients’ organizations, medical expert associations, pupils, students and teachers. All should be available via a single platform.

• Regular reports should be made in relevant committees (i. e., science, health, economy) to support long-term engagement with political stakeholders and the provision of information for parliamentarians (at federal and state levels). As part of a discourse with wider society, an open-ended humanistic discussion should be promoted and reviewed with all stakeholders in society.

• Appropriate research funding organizations, foundations and supportive private individuals should be identified, provided with specific information material to organize high-profile public events that will encourage donation to raise additional funding.

The measures listed here interlink synergistically and are based on the stakeholders in this topic interacting closely with the National Network Office. Implementing these measures will require personnel at the National Network Office (information/political engagement/ social discourse), project funding for short-term agency contracts (research, graphics, events) and networking funding to help stakeholders in the GCT network interact with the specified groups in society. We estimate annual funding requirements in the six-digit euro-range, depending on the intensity of these interactions

Working Groups