Bioethics guides us in how to use the rapidly advancing power of life science and technology responsibly and ethically to the ultimate benefit of society, humans and other living beings. However, factors such as diverse cultural backgrounds have led to heated debates on divisive bioethical topics and issues arising from the explosive progress in science. In light of this situation, we feel the need to clarify our own position on bioethical approaches.
Our approach to ethical business conduct
In our work we encounter various bioethical topics and issues, including animal testing and clinical research, stem cell use, the use of genetically modified microorganisms, and the potential impact of new genome editing techniques such as CRISPR/Cas. We are strongly committed to conducting this research in an ethical manner. Patient well-being and benefit is always our number one priority, both during treatment with our drugs and when our products are distributed to academic researchers and the biopharmaceutical industry. We carefully evaluate our position on controversial topics so that we can develop frameworks and make informed decisions that meet the highest ethical standards.
How we assess bioethical topics and issues
The Bioethics Advisory Panel of Merck KGaA, Darmstadt, Germany (MBAP), co-chaired by a senior executive biomedical expert from our company and the Head of our Global Health Institute, gives clear guidance on bioethical topics and issues, which steers our actions and entrepreneurial conduct. The MBAP consists of renowned international experts in the fields of bioethics, theology, science, and law from the United States along with countries across Europe, Asia, and Africa. The panel’s composition reflects the fact that the evaluation and assessment of bioethics are strongly contingent on cultural and regional factors. The bioethical assessment of topics must be viewed holistically. The MBAP meets once yearly and also spontaneously, if required, in response to emerging urgent bioethical issues. We publish a summary of the discussions from each meeting on our internal electronic collaboration platform. Our employees can ask MBAP members for advice and are able to report concerns on ethical issues through channels such as our SpeakUp line or by reaching out to the bioethics office.
Our dedicated guidance panels for genome editing and stem cell matters operate under the overarching MBAP. These panels are responsible for the operational implementation of our stance and are empowered to make decisions about specific questions on individual projects. Formed in 2011, the Stem Cell Research Oversight Committee (SCROC) performs tasks such as verifying all internal research proposals that employ human stem cells and ensuring compliance with our ethical guidelines and any legal requirements. This also includes collaboration with external partners.
In 2019, we additionally established the Digital Ethics Board (DEB) as a sub-committee of the MBAP. Its purpose is to guide our new digital business models with a strong focus on health. One member of the DEB will join the MBAP as a digital expert.
Our commitment: Identifying topics and issues early on
As a global company, it is crucial for us to promptly identify and address new developments concerning bioethical topics and issues in order to define our own stance. Although we align all our business activities with international and national legislation, many bioethical discussions raise questions that far exceed the current scope of legislators, which is why we also seek the advice of external experts.
The birth of the first babies from genome-edited embryos in China significantly disrupted the realm of bioethics in 2019. This breach of law, ethics and academic self-regulation led to marked global criticism. Subsequent discussions emphasized the need for profound bioethical debate and meaningful governance of genome-editing research in the human germline. Statements and positions were issued by the National Academy of Sciences, the Royal Society and the German Ethics Council. This furthermore led to the creation of the World Health Organization (WHO) expert advisory committee on Developing Global Standards for Governance and Oversight of Human Genome Editing. Regulation in this research field is expected to emerge in the following years.
Bioethics Advisory Panel discussions
From November 2018 to March 2019, we held internal workshops on Artificial Intelligence (AI) ethics to create a baseline on all Advanced Machine Learning (AML) and AI projects at our company and to identify potential (bio-)ethical issues resulting from these projects. In particular, we produced eight guiding ethical aspects to evaluate projects that might be ethically problematic. This improves our ability to develop new technologies responsibly and address potential ethical issues arising from the usage of AI early on. Currently, no ethical questions or problem statements have arisen from our ongoing and planned AML and AI projects.
As a result of these workshops and of new digital health business models that we are developing, the MBAP addressed the topic of digital ethics in 2019. Since these business models involve enabling access to and exchange of patient data, core guidance and foundational ethics must be established in order to gain stakeholders’ trust, which is critical for their success. Another major topic discussed by the panel was our genome editing principle.
Other topics included new developments in the Stem Cell Research Oversight Committee and the Global Health Institute.
Digital Ethics Board
As a result of the MBAP discussions on digital ethics in 2019, we decided to create the Digital Ethics Board (DEB) to deal with all ethical questions resulting from our Digital (Health) Businesses, especially from the intended joint venture Syntropy (with Palantir). The DEB is designed as a sub-board of the MBAP, and its chair will join the MBAP as a digital expert. The DEB will consist of world-leading experts in digital health business models as well as experts in ethics and medicine. The first step will be to develop a Digital Code of Ethics to address questions and scenarios that may arise from our new Digital Businesses. The DEB will play a pivotal role in ensuring that we develop new technologies responsibly and address potential ethical issues arising from the usage of digital health technologies early on. We strive to be the “ethical digital health company”, adhering to the highest ethical standards in crucial areas such as patient data handling.
Biotechnology and genetic engineering
We utilize genetically modified organisms (GMOs) in our research and development work and have been manufacturing biotech products using GMOs since the 1980s. Without this technology, the major medical advances of past years would not have been possible.
Our most important research hubs for medical biotechnology are Darmstadt (Germany), Boston (Massachusetts, USA), Beijing (China), and Tokyo (Japan). Major biotech production sites are located in Martillac (France), Aubonne (Switzerland) and Corsier-sur-Vevey (Switzerland), which is one of the largest biopharmaceutical production sites in Europe.
Across our Group, we manufacture our biotech products in accordance with the highest standards, and all our biotech activities are subject to strict statutory regulations worldwide. Compliance with these regulations is monitored by our biological safety officers. We continuously track regulatory changes that relate to biotech products and adapt our processes accordingly, thus ensuring we adhere to all statutory requirements.
Using genome-editing techniques
We are a leading supplier of technologies such as CRISPR/Cas9, which can be used to target and modify specific genes, a process known as genome editing. CRISPR/Cas9 opens up new possibilities in genetic engineering research that could bring about major advances in the treatment of serious diseases or in “green genetic engineering”, which is the use of genome editing techniques in plant cultivation. Statutes in different countries allow for a varying degree of latitude in applying this technique.
Our Genome Editing Technology Principle provides a mandatory ethical and operational framework for our employees, setting clear operational boundaries for us both as a supplier of custom targeted nucleases and genetically modified cell lines, and as a user of genome editing technologies for scientific research. This principle includes background information on the topic and explains our stance on genome editing.
Following the critical debate surrounding the announcement that a Chinese researcher’s work had led to the birth of the first babies from genome-edited embryos, global discussions emphasized the need for profound bioethical debate and meaningful governance of genome-editing research in the human germline. The topic was presented in detail by the Taiwanese member of the MBAP, and potential regulatory consequences were discussed by the panel, including the implications for our company as a provider and user of this technology. Our Principle on Genome Editing, published in 2017, addresses the subject of human germline editing, taking a strict stance against it.
Bioethical views on germline editing (GE) have been evolving for years in academic and societal discussions. Once the safety profile of the use of GE on embryos has been made fully accessible through clinical studies, and once the benefits significantly outweigh the risks, there may be cases where the use of GE on embryos could be ethically acceptable. Even the German Ethics Council took a similar position. One example of this cystic fibrosis, a monogenetic disease.
Considering the progress in genome editing and evolving ethical views, such as the German Ethics Council’s perspective, the MBAP agreed that we needed to update our Genome Editing Principle. Sections on background information, the wording on germline genome editing, and the section on artificial gametes subsequently underwent minor revisions. Our statement on human germline editing is as follows:
“Merck KGaA, Darmstadt, Germany does not support the use of genome editing in human embryos and clinical applications of germline interventions in humans in accordance with the German Embryo Protection Act. Our company recognizes that there may be value of responsibly conducted related research.”
Stem cell research
We currently neither participate in clinical programs that utilize human embryonic stem cells or cloned human cells for the treatment of diseases, nor do we pursue such approaches ourselves. We do, however, use human embryonic stem cells in our research and offer our customers several select stem cell lines. Thus, our Stem Cell Principle ensures compliance with our ethical approach. All projects are reviewed and approved by the SCROC before any stem cells are used for research purposes. We only use cell lines approved by the United States National Institute of Health (NIH) and allowed under the German Embryo Protection Act and the German Stem Cell Law.
In 2019, the SCROC started developing a new Informed Consent Form for the use of induced pluripotent stem cells (iPSCs). iPSCs are identical to embryonic cells and can generate any type of cell in the human body. They are used in many research projects, but, in most cases, do not require specific approval by the SCROC. The SCROC also decided to support the generation of organoids derived from adult stem cells under the precondition that stem cells derived from fetal tissue should be avoided.
To date, we have not supported research aimed at producing artificial gametes. Any support on our part would have to comply with the German Embryo Protection Act and our Fertility Principle.
The topic of producing artificial gametes will be revisited by the SCROC in order to follow up on ongoing developments.
We develop treatments for infertility and seek to improve the success rate of in vitro fertilization, so we are frequently confronted with various related bioethical issues. Our legislative point of reference for these issues is the German Embryo Protection Act, and we are guided by our Fertility Principle, which was developed based on input from the MBAP.
Biosampling and biobanking
Biological samples obtained from patients within clinical studies are indispensable to the development of new precision treatments and advanced diagnostic methods. We handle these samples in a responsible and ethical manner, in compliance with all regulatory requirements and according to the consent given by patients for the use of their samples. This may include the permission to use biospecimens for further medical research beyond the clinical study through an optional consent. Since 2017, we have had standard operating procedures and a policy in place that define our principles and processes for human biosample management during and after clinical studies.
Biological samples, including tissue and body fluids, are stored in biorepositories together with the corresponding encrypted patient and specimen data.
We discover and develop innovative medicines that meet patient needs. In doing so, we adhere to all relevant statutory and regulatory requirements, as well as scientific and ethical standards. For clinical studies, these standards particularly include the Declaration of Helsinki, in which the World Medical Association formulated ethical principles for medical research involving human subjects, and the Good Clinical Practice (GCP) of the International Council for Harmonisation (ICH). More details can be found under Clinical studies.
We endeavor to drive scientific and medical progress, often doing so in close collaboration with medical professionals. We regularly receive inquiries about the off-label use of our products, such as indications for which the drug was not originally approved. While each medicine is authorized for specific indications, cases do arise in which a physician wishes to prescribe a drug to treat a disease for which it is not approved. Such applications can benefit patients. However, to use a drug in this way, solid evidence must exist showing that it can be effective and safe in the treatment of the specific disease.
Our principles for disseminating information regarding the off-label use of our products are set out in corresponding policies that apply Group-wide. In 2018, we included a statement regarding requests on off-label use in the new compliance policy concerning interactions with patients. We only market our medicines within the scope of the drug’s marketing approval; we never share information on off-label use for commercial ends but provide such information to healthcare professionals for medical purposes only and only upon direct, unsolicited request. The information must be backed by scientific evidence and factually balanced. Our employees are not permitted to make any sort of treatment recommendations for individual patients.
Parliamentary discussion on genome-editing
In May 2019, we hosted a Dialogue on Ethics of Genome Editing for German policymakers in the form of a parliamentary breakfast discussion. It was attended by 45 political stakeholders, including elected state officials, members of the German federal parliament, and other high-profile German politicians. Participants engaged in an open debate on the ethics of genome-editing one day after the publication of the German Ethics Council’s new position paper on germ cell genome-editing.
Panel discussion on ethical implications of new technologies in the health sector
In November 2019, in collaboration with the Brussels Representation of the State of Hesse, we hosted a panel discussion (representing academia, the European Parliament and Commission, and our company) on ethical implications of new technologies in the health sector, addressing ethical questions on both digital health and genome editing technology. It was attended by 100 European political stakeholders, including elected officials, Members of the European Parliament (including a vice president), representatives from various governmental and non-governmental organizations, and representatives from the pharmaceutical and biotech industries, all of whom engaged in an open debate with the panelists.
At both events, the Bioethics Advisory Panel’s recent work had a significant impact on the respective discussions, which in turn generated valuable input for the continuation of the debate.