The safety of patients treated with our medicines is our top priority. Our medicinal products must be effective in treating the respective disease while posing the lowest possible risk to patients. That is why we aim to continuously monitor any risks or adverse effects that may arise and take the necessary actions to minimize them.
Our approach to ensuring patient safety
Through a rigorous benefit-risk management process, we help to ensure that the benefits of our medicinal products always outweigh the risks for patients. Every new medicine goes through a series of precisely defined development stages. Before any medicinal product is administered to human subjects, we conduct extensive preclinical testing both in vitro and in vivo. Through toxicological testing, we determine whether an active pharmaceutical ingredient is toxic to living organisms and, if so, at which dosage. This testing also helps us determine the dose that humans can safely tolerate. Only when this is complete do we perform human clinical studies to investigate the safety and efficacy of the medicinal product. During clinical development, we diligently use all the collected data to continuously evaluate the medicinal product’s benefit-risk profile. If we consider the medicinal product’s benefit-risk profile to be positive, we then submit an application for marketing authorization to the relevant regulatory authorities.
Continual monitoring of product safety risk profiles
Once we launch a new medicinal product, the number of patients being treated with the product increases significantly. In rare circumstances, there may be adverse and potentially serious effects that were not detected during clinical development, which is why we continuously monitor risks and assess the benefit-risk profiles of the products after their market launch. Pharmacovigilance includes the process of monitoring a medicinal product on an ongoing basis to detect and assess safety signals as part of signal management activities. Our pharmacovigilance system and our pharmacovigilance business continuity management help to ensure continuous monitoring of adverse effects, allowing us to proactively and transparently minimize and communicate any risks. Emergency response procedures for business continuity are managed in accordance with global and local business continuity plans, tested in regular, defined intervals or with mock scenarios. In addition, we provide healthcare professionals and patients with the latest information on the safety of our marketed medicinal products. The scope of continuous safety monitoring covers the entire life cycle of a product, ranging from development, market launch and commercialization to the expiration or cancellation of its marketing authorization.
We continuously monitor our service objectives through our pharmacovigilance quality strategy and annual quality plan. We also regularly monitor our performance and compliance through the internal and external reporting of key performance indicators. These include making timely submissions of high-quality documents to health authorities, along with assessments to support the safety monitoring of products throughout their life cycles.
The capabilities we have developed and strengthened in this area include:
- Advanced benefit-risk management
- Safety data analytics in support of benefit-risk strategy implementation (taking into account and integrating real-world data)
- Advanced signal detection methodology
- Reporter-oriented methods for collecting adverse effects (such as via mobile app)
- Comprehensive evaluation of identified adverse effects by the company in the context of the products’ known benefit-risk profiles and ensuring medicinal product information and labels reflect any relevant changes
Based on regulatory approval conditions for newly approved medicinal products, we develop and update educational materials for patients and healthcare providers in accordance with the requirement to communicate any known and potential risks and ways to minimize them. We assess the effectiveness of these materials in close collaboration with our Benefit-Risk Action Team. If required, we adjust the contents of the materials and their distribution and describe the results from the effectiveness analysis in our periodic safety reports and risk management plans. We then submit these to the relevant health authorities for evaluation and approval.
By 2025, we aim to deliver product specific safety and benefit-risk strategies to support the execution of all key priority programs in line with internal and external stakeholders’ expectations. These strategies will enable us to understand in greater detail the benefit-risk profiles at each stage of product development and post-marketing. During the reporting year, we worked toward achieving this goal by providing high-level safety and benefit-risk contributions for development programs with priority in oncology, neurology and immunology. Our contributions include for example, safety planning where all safety issues are properly defined with their corresponding strategy. And additionally, ongoing or planned safety investigations are also structured along with risk minimization measures. Additionally, we supported new partnering and in-licensing opportunities with medical safety strategies and outputs and ensured professional contract management for exchanging safety data. We also worked to develop a better understanding of Global Patient Safety’s tasks and interactions during early development. Our initiatives included the scope extension of the Benefit-Risk Action Team to early development phases, and the respective enhancement of the Benefit-Risk Strategy Document to enable early, evidence-based safety decisions.
Roles and responsibilities
Our Global Patient Safety unit is responsible for drug safety. It continuously collects current safety data from a wide variety of sources across the globe, including clinical studies, early access programs, spontaneous reports on adverse effects, patient support programs, and articles published in medical and scientific journals. Our vision is to embed a deep knowledge of safety into early decision-making as we evolve to practice predictive safety.
Our experts help to ensure that all information on the risks and adverse effects of our medical products are properly documented, tracked and reported to the respective health authorities in accordance with regulatory requirements. Our Global Patient Safety unit analyzes all data and reassesses the benefit-risk profile based on these data, where required. We then inform regulatory authorities, healthcare professionals and patients about new risks, additional risk mitigation measures and potential changes in the benefit-risk profile. We convey this information through stipulated regulatory reports, safety communications (as applicable) and corresponding product label updates.
Our Healthcare Quality unit processes quality complaints related to our products. Whenever quality defects could have an impact on patient safety or lead to adverse effects, Global Patient Safety becomes involved.
Our Global Patient Safety unit hosts a Pharmacovigilance Intelligence Council that focuses on changes in pharmacovigilance legislation and their impacts on our global and local pharmacovigilance systems. This council enables us to make strategic decisions and govern changes in pharmacovigilance requirements, which fosters our target to ensure continuous compliance with regulatory requirements.
Our Medical Safety and Ethics Board
Our Medical Safety and Ethics Board (MSEB) is the governance board that oversees the safety and benefit-risk assessments of our medicinal products throughout their clinical development and commercialization. This internal board is chaired by our Chief Medical Officer and comprises experienced physicians, scientists and experts from our company. Throughout a medicinal product’s entire life cycle, the MSEB reviews and assesses important medical safety risks and benefit-risk issues and endorses appropriate measures to minimize risks, such as updates to product information. The MSEB also assess human-related bioethical matters as appropriate and is accountable for the use of our medicinal products in early and post-study access.
The cross-functional Benefit-Risk Action Team is responsible for signal management, benefit-risk assessment, risk management and all topics related to product safety and the benefit-risk profile of our medicinal products. Recommendations from the Benefit-Risk Action Team are endorsed by the Pharmacovigilance Advisory Board, chaired by the head of Global Patient Safety. Important issues may be submitted to the MSEB for final assessment and endorsement.
Our commitment: Guidelines and statutory requirements
We rigorously aim to follow international guidance and standard procedures. These include the International Council for Harmonisation (ICH) guidelines, the Good Pharmacovigilance Practices (GVP) established by the European Medicines Agency (EMA), Title 21 of the Code of Federal Regulations governed by the U.S. Food and Drug Administration (FDA), and other pharmacovigilance regulations issued by national health authorities. We also aim to comply with relevant new statutory pharmacovigilance regulations in the countries where we market our products.
Inspections and audits for drug safety monitoring
Regulatory authorities conduct periodic inspections to verify that we comply with statutory requirements as well as our own internal pharmacovigilance standards. We follow up on the findings of health authority inspections and take necessary actions to ensure the ongoing compliance of our pharmacovigilance system. In 2023, we had five pharmacovigilance inspections (2022: four).
We also perform audits to our systems and processes to ensure that all our units and subsidiaries involved in pharmacovigilance consistently meet all global requirements. In 2023, we conducted a total of seven pharmacovigilance audits (2022: 19) and found no significant deviations in our pharmacovigilance systems from these requirements and standards. We also conducted twelve external audits at our vendors and licensing partners involved in pharmacovigilance, helping us to improve our pharmacovigilance processes and to comply with regulatory requirements.
Applying our proactive safety strategy to benefit-risk assessments
Regarding product safety risk assessments, we have successfully implemented in the past years an improved benefit-risk management strategy to become a more proactive and benefit-risk-focused organization. This strategy firmly establishes the concepts and principles for conducting benefit-risk assessments at each stage of product development and post-marketing. In addition, our Benefit-Risk Action Team co-leadership model, created in 2022, enables us to understand in even greater detail the benefit-risk profiles of our products and enable early decision-making within our organization to protect patient safety. Ultimately, we aim to provide the right medicine to the right patient at the right time.
Product safety assessment and emergency response procedures
We use a product prioritization tool that objectively scores the safety profile of our products, forming the basis of our product prioritization strategy. The tool ranks our products into high-, medium- or low-risk categories, defining our approach for benefit-risk activities and product safety surveillance. Our actions include individual case safety report management, signal and risk management, our benefit-risk strategy and aggregate safety reporting. These measures ensure the efficient management of safety risks of our medicinal products throughout their life cycles.
If our safety risk assessments identify any emerging safety issues, safety observations that require urgent safety measures or other new safety information that could impact the benefit-risk balance of the medicinal product (e.g. product recall as part of crisis management), we promptly notify health authorities via the respective emergency response procedures. These steps include seeking health authority approval for further actions and communicating the information to relevant healthcare professionals. In addition, we promptly share this information with our business partners and clinical trial investigators, enabling them to take proper actions where the medicinal product concerned is used.
Innovative safety signal detection
Through our tools for safety signal detection, we analyze and manage large volumes of global data, such as scientific studies and information about adverse events in connection with our medicinal products. These tools ensure we retain adequate oversight and comply with regulatory timelines for safety signals and other safety-related factors. They also enable us to archive all signal data, documentation and decisions in a unified repository, which facilitates easy data access and analysis as well as cross-functional collaboration between our Global Patient Safety unit and other internal and external stakeholders.
Up-to-date labeling and product information
Our product information explains to healthcare professionals and patients how to correctly use the respective product and make informed treatment decisions. In accordance with statutory regulations, the package leaflet contains all relevant information such as indication(s) and ingredients as well as dosage, storage, mode of action, instructions for use, warnings, precautions, and possible adverse effects. In addition, should the medicine contain ingredients that could impact the environment, the package leaflet may also contain information about how to dispose of the product correctly. We review and update product information documents, such as package leaflets, thereby, we want to ensure our medicinal products contain the latest information on safety, efficacy and pharmaceutical formulation. In accordance with regulatory requirements, we submit modifications to our leaflets to the respective regulatory authorities for approval. In 2023, there were no reportable incidents of non-compliance with regulations concerning the labeling of our medicinal products.
Internal and external training
Our pharmacovigilance experts are regularly trained so that they gain and maintain the required experience and knowledge to carry out their activities. We manage our training via a global learning platform and verify compliance with our training requirements by producing training completion reports.
Our approximately 25,000 internal and external Healthcare employees receive basic pharmacovigilance training once a year that covers the procedure for reporting adverse effects or special circumstances associated with the use of our medicinal products. In addition, other training courses keep employees up-to-date with respect to their professional expertise as well as internal standard operating procedures and other relevant requirements. These continuing education and training efforts help us to ensure adherence to pharmacovigilance requirements.
Enhancing patient safety and sharing expertise with other countries
We share our experiences and expertise and engage in dialogues about pharmacovigilance with health authorities by contributing to initiatives hosted by non-profit organizations and industry associations. We actively participate in expert committees and industry groups worldwide, such as the European Federation of Pharmaceutical Industries and Associations (EFPIA), the Pharmaceutical Research and Manufacturers of America (PhRMA), the Kenyan Association of Pharmaceutical Industry (KAPI), the Association des Laboratoires Pharmaceutiques Innovants (ALPI) in Algeria. We also network with health authorities to improve the safety of our medicinal products and promote the topic of pharmacovigilance.
For example, as an active member of the non-profit organization TransCelerate, we have directly contributed to initiatives such as intelligent automation opportunities in pharmacovigilance, pharmacovigilance agreements optimization and the interpretation of guidance documents and regulations. We also maintain a long-term partnership and regular dialogues with the health authority in Kenya via KAPI and we have contributed in 2023 to the work of the ALPI to help the Algerian health authority refine pharmacovigilance guideline.
Reporting side effects via app
Since 2017 we have been offering a reporter-oriented method, a mobile and web application. It allows field forces, sales representatives, healthcare professionals, pharmacists and non-medically trained users to report any suspected side effects or adverse events arising from the use of our medicinal products. Since 2023, the application has been available in 14 languages in over 70 countries.
Campaigns for patient safety
We celebrate Patient Safety Day via our affiliates worldwide to raise awareness about this vital topic. In 2023, we organized various online and on-site events with affiliates in all continents and jointly celebrated Patient Safety Day with other companies in India and Kenya.
Pharmacovigilance in Access to Health
We strive to continue expanding pharmacovigilance expertise worldwide, particularly in countries where healthcare workers need to build this expertise.
We continue our efforts to increase the contribution of pharmacovigilance in our Access to Health strategy. The key aspects of this strategy include fostering pharmacovigilance initiatives in safety data-sharing with health authorities and sustainably building pharmacovigilance capacity with reputable partners in underserved countries. For example, we have maintained a stable partnership with the Tunisian health authority over many years to actively establish the national pharmacovigilance system through various initiatives. In 2023, we sponsored or partnered with health authorities in Tunisia and Morocco to support their pharmacovigilance congresses. We also included patient safety in our rollout of trainings to 28 pharmacy students in Saudi Arabia, and around 350 pharmacy students in Egypt. We launched an initiative to raise awareness about thyroid treatments in Indonesia.
Access to approved medication for unapproved uses
We may receive inquiries about the therapeutic use of our products beyond the marketing authorization, also referred to as off-label use. For example, while each medicine is authorized for use in specific indications, a physician, based on an individual benefit-risk assessment, may wish to administer a product to a patient suffering from a serious disease for which it is not approved.
We promote our medicines strictly within the scope of their specific marketing approval. Any medical-scientific information about the use of our products beyond their existing marketing authorization is provided by qualified medical personnel in response to unsolicited inquiries. The information shared must be backed by scientific evidence, factually balanced and clearly state that it applies to unapproved use. To maintain compliance, we have implemented a standard to govern these requests. We also do not permit our employees to give any recommendations regarding individual patient care or treatment.