Significant changes are on the horizon for clinical trials in Germany. At the end of January 2024, the German Federal Health Ministry has presented the draft for a “Medical Research Act” (Medizinforschungsgesetz or MFG). The draft bill proposes legislative amendments in several areas that span from clinical trials, GMP issues for ATMPs up to pharmaceutical pricing and reimbursement (AMNOG) as well as administrative re-organizations of regulatory agencies and Ethics Committees.
This blog discusses the proposed changes for clinical trials with pharmaceuticals, medical devices and companion diagnostics.
The Medical Research Act is part of Germany’s new National Pharma Strategy which aims to make Germany more attractive for pharmaceutical R&D and manufacturing.
On 13 December 2023 the German Federal Government officially published a Strategy Paper (Strategiepapier) for the new Pharma Strategy. We had reported in a previous blog on this development when the Strategy Paper was not yet approved within the Government.
The discussions about a Medical Research Act were ongoing since the summer of 2023. Now, the German Government appears determined to push this forward. On 26 January 2024, the draft bill was distributed to stakeholders. The public consultation is currently ongoing and comments can be submitted by 22 February 2024. On 20 February 2024, the public hearing is scheduled.
In the following, we will summarize the proposed changes for clinical trials with pharmaceuticals, medical devices and companion diagnostics and discuss some of their background and implications.
2. Proposed changes for Clinical Trials in the Medical Research Act
With respect to clinical trials, the Medical Research Act proposes following core changes:
- Ethics Committee procedures will be reorganized and Ethics Committees will be specialized for specific indications. This will be one of the most significant and most controversial amendments. A “Federal Ethics Committee” will be established that will (initially) be in charge of clinical trials that are particularly urgent or demanding. Its competence shall encompass clinical trials with an overarching master protocol with several sub-studies, clinical trials in which new medicinal products are tested first-in-human and clinical trials with Advanced Therapy Medicinal Products (ATMPs). Further, the Ethics Committees are expected to follow binding guidelines on the application and interpretation of the Clinical Trials Regulation (EU) No. 536/2014. The German Association of Medical Ethics Committees, a non-profit association, will be charged to issue such guidelines for Ethics Committees.
- Companion Diagnostics (CDx): The procedures and competencies for clinical trials using CDx will be streamlined and simplified. Currently, the national rules for clinical trial applications for studies that investigate a medicine together with an unapproved CDx are very complicated and burdensome. Inter alia, for combined pharmaceutical/CDx-studies two separate regulatory approval applications must be submitted. A centralized or single-gate approval procedure would be a significant simplification for the industry.
- Decentralized Clinical Trials (DCTs): The proposed new act will facilitate DCTs by modifying the pharmaceutical distribution rules. The new rules would enable clinical trial sponsors to have the study drugs directly distributed to trial participants. This will require a change of the rules for the so-called special distribution channel under German pharmaceutical laws. However, the sponsor companies need to be careful from a data protection perspective as the direct shipment of investigational products to study subjects can endanger the pseudonymization and study blinding. Hence, sponsors need to consider data protection safeguards to not to jeopardize their DCTs.
- Electronic Informed Consent becomes a more practical alternative to written consent. This will also be helpful for decentralized clinical trials.
- The rules for labeling of investigational products will be amended to allow a labeling of these products in English only.
- Standard Contractual Clauses for clinical trial agreements shall be published by the German Government to accelerate the contracting process and expedite the start of clinical trials. So far, a legal obligation to use those standard contractual clauses is not envisaged in the draft bill but their purpose is to enable standardization. However, industry stakeholders are concerned that the clauses may not be flexible enough to consider the specific circumstances and requirements of the respective clinical trials.
- The process for Radiation Protection Approvals for clinical trials that use ionizing radiation will be significantly revised. This is another area where the Medical Research Act includes a really fundamental reform. Currently, this approval process under the German radiation protection laws with the separate agency BfS is reported to slow down clinical trials. In the future, this process and its timelines shall be linked with the general clinical trial approval procedure. The deadlines for Radiation Protection Approval and related procedures will be shortened in favor of trial sponsors. Additionally, a Single-Gate Approach for all procedures is envisages. This means that the same electronic submission portal will be used for the procedure under radiation protection law as for the procedure under medicinal product or medical device law.
- Reorganizing BfArM and PEI: Germany is the only EU member state that has two different regulatory agencies (BfArM and PEI) in charge of approving clinical trials and marketing authorizations. While BfArM is responsible for “classical” synthetic medicinal products, PEI oversees inter alia vaccines, blood products and ATMPs. BfArM and PEI have similarly split competencies for the approval of clinical trials with medical devices and CDx. It is fair to say that the allocation of tasks and roles between the German federal agencies is quite complex – and we have not yet mentioned the competencies and roles of the authorities in the 16 German states… The Medical Research Act aims to reorganize the competencies between BfArM and PEI and to ensure a more intensive coordination and procedural improvements. Based on comments from stakeholders, there are also concerns that the practical implementation of such a reorganization of the agencies may cause difficulties and brain-drain. It will indeed be interesting to see how this will work from a logistical perspective since BfArM and PEI are approx. 175 kilometres away from each other.
- ATMP and GMP: The new act aims to harmonize the situation in Germany around the interpretation of GMP guidelines for Advanced Therapy Medicinal Products (ATMPs). Due to Germany’s federal structure with 16 states and the independence of the state authorities, there are regularly inconsistencies in the interpretation especially of the ATMP laws and GMP/GCP guidelines. Under the new Medical Research Act, there will be official interpretation recommendations by the competent federal authority on these ATMP GMP guidelines. The state authorities will be entitled to ask the federal authority for clarification of the interpretation GMP guidelines for ATMPs.
3. Next Steps of the Reform
The draft Medical Research Act shows that the German Ministry of Health is already well advanced in its deliberations on how to implement the German Government’s new National Pharma Strategy. Although this is still a ministerial draft, it is clear that the reform will not just lead to minor legal amendments but rather significant changes for the national clinical trial laws.
These changes to the clinical trial laws will impact pharmaceuticals, medical devices and in-vitro diagnostics, among these especially companion diagnostics.
Many of the proposed changes will indeed be helpful for companies and researchers as they will in fact reduce regulatory burden and bureaucracy. In so doing, the Medical Research Act could make Germany more attractive for clinical trials in the longer term.
However, at the same time, many of the proposed legislative changes are also quite controversial and there will be pushback by different stakeholders. As with other draft laws, there will likely be changes to this one as well. Like a famous German politician once said, “no law leaves the Parliament in the same shape as it entered the Parliament”.
It is not yet clear when the Medical Research Act will be submitted to the Parliament for the next steps of the formal legislative procedure. However, given the advanced stage of drafting and the upcoming hearings on this draft, we expect that an official draft bill will be submitted to the German Parliament (Bundestag) shortly in the next months. In any case, the legislative process would have to be completed this year in order to meet the timeline set out in the present draft where some provisions shall enter into force on 1 January 2025.
As to next steps, on 20 February 2024, already next week, there will already be an oral hearing about this draft bill with stakeholders. All relevant stakeholders and interest groups now have time to submit comments until 22 February 2024. It is a bit unusual that the hearing will take place before the stakeholder comments are collected. It is, however, an indication that industry should be prepared for a rather fast legislative procedure.
This blog has focused on the proposed changes in the Medical Research Act that will affect clinical trials. However, the draft bill will also enact new laws that will impact other legal areas like drug pricing or manufacturing incentives. Given these broad implications of the proposed Medical Research Act, pharmaceutical, medical devices and diagnostics companies as well as other life sciences industry stakeholders should closely monitor the next steps of this legal reform.
The Life Sciences Team of Covington & Burling LLP in Frankfurt (Germany) will keep you posted about the next developments.