The safety of patients treated with our medicines is our top priority. Our pharmaceutical products must be effective in treating the respective disease while posing the lowest possible risk to patients. That is why we 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 clinical studies to investigate the safety and efficacy of the medicinal product when used in humans. During clinical development, we diligently use all the collected data to continuously evaluate the medical product’s benefit-risk profile. If we consider the medical product’s benefit-risk profile to be positive, we then submit an application for marketing authorization to the relevant regulatory authorities.
Continual monitoring
Once we launch a new medicinal product, the number of patients being treated with it 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 and manage the benefit-risk profiles after its market release. Pharmacovigilance includes the process of monitoring a medical product on an ongoing basis to detect and assess safety signals as part of signal management activities. Continuous monitoring of adverse effects allows us to proactively and transparently minimize and communicate any risks. In addition, we always provide healthcare professionals and patients with the latest information on the safety of all our marketed medicinal products. The scope of continuous safety monitoring includes the entire life cycle of a product, ranging from development, market launch and commercialization to expiration of the marketing authorization.
Capabilities that we have developed and strengthened in this area include:
- Advanced benefit-risk management
- Big Data analytics (using real-world data)
- Advanced signal detection methodology
- Patient-centric adverse effects collection methods, such as our agReporter app
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.
Roles and responsibilities
Our Global Patient Safety unit is responsible for pharmacovigilance. 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 experts help to ensure all information on the risks and adverse effects of our medical products is 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.
In order to implement our R&D Strategy 2023, our Global Patient Safety unit is on a journey of transformation. Our vision is to embed a deep knowledge of safety into early decision-making as we evolve to practice predictive safety. In 2021 we continued to refine our approach to benefit-risk assessments. For example, we applied a scoring system based on safety aspects and used it to determine the prioritization levels of our products. We also redesigned our pharmacovigilance processes using a business process management model that ensures cross-functional alignment between our corporate functions. We expect to complete the implementation of these processes in 2022.
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 its impacts on our global and local pharmacovigilance systems. This initiative enables us to make strategic decisions and govern changes in pharmacovigilance requirements, ensuring continuous compliance with regulatory requirements.
Our Medical Safety and Ethics Board
Our Medical Safety and Ethics Board (MSEB) oversees the safety and benefit-risk assessments of our medicinal products throughout their clinical development and commercialization. It endorses appropriate measures to minimize risks, such as updates to product information. This 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 reviews human-related ethical matters as appropriate.
Within the Global Patient Safety unit, the 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 Global Patient Safety unit. Important issues may be submitted to the MSEB for final assessment.
Our commitment: Guidelines and statutory requirements
We follow international guidance and standard procedures, such as the International Council for Harmonisation (ICH) guidelines and the Good Pharmacovigilance Practices (GVP) established by the European Medicines Agency (EMA) and national health authorities. In addition, we comply with and implement all new statutory pharmacovigilance regulations in the countries where we market our products.
Monitoring drug safety
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 2021, we had eight pharmacovigilance inspections.
Furthermore, we perform audits to ensure that all our units and subsidiaries involved in pharmacovigilance consistently meet all global requirements. In 2021, we conducted a total of 18 pharmacovigilance audits and found no significant deviations in our pharmacovigilance systems from these requirements and standards. We also audit our vendors and licensing partners involved in pharmacovigilance, which helps us improve our pharmacovigilance processes and comply with regulatory requirements. In light of the ongoing Covid-19 pandemic, we had to adjust our audit plan and methods by postponing several audits and conducting others remotely.
Redefining our approach to benefit-risk assessments
We have developed an improved benefit-risk strategy to help us transform from a reactive and compliance-driven organization into a proactive and benefit-risk-focused organization. By truly understanding the benefit-risk profiles of our products, we can enable early decision-making within the organization to protect the safety of patients. Ultimately, the aim is to be able to provide the right medicine to the right patient at the right time. As part of this initiative, we have also developed the concepts and principles for conducting benefit-risk assessments at each stage of product development and post-marketing.
We have concluded the pilot phase of our new benefit-risk strategy and are now following up with incremental implementation by the end of 2022.
Assessing the safety of our products
We have redesigned our pharmacovigilance processes, including elements that make up our Patient Safety product prioritization strategy. A product prioritization tool as a means to objectively score the safety-profile of our products has been used as a basis to define the product prioritization strategy. The scores categorize our products into a high-, medium- or low-risk category, thereby impacting the methodology for benefit-risk activities. These include individual case safety report (ICSR) management, signal management, our new benefit-risk strategy, and aggregate safety reporting. The new processes ensure the safety of our medicinal products throughout their lifecycles and enable us to focus our resources and expertise on high-priority assets. The drafts of these redesigned processes will be reviewed and finalized by the end of 2022.
Innovative safety signal detection
Through our tool for safety signal detection, we analyze and manage large amounts of global data, such as scientific studies and news about adverse effects. This tool helps us comply with regulatory timelines for safety signals and other safety-related factors and ensures that all signal data, documentation and decisions are captured in one place. It also enables easy access to and analysis of our data as well as cross-functional collaboration between the 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 all product information documents, such as package leaflets, to ensure our medicinal products contain the latest information on safety, efficacy and pharmaceutical formulation. In accordance with regulatory requirements, we submit all modifications to our leaflets to the respective regulatory authorities for approval. In 2021, there were no 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 the required experience and knowledge to carry out their activities. We manage our training via a global learning platform and verify compliance with training our requirements by producing training completion reports.
All our approximately 23,000 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 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 ensure adherence to pharmacovigilance requirements.
Enhancing patient safety and sharing expertise with other countries
Reporting side effects with the agReporter app
In line with our goal to enhance patient safety, in 2020 we implemented a user-friendly mobile and web application called agReporter. The application was created for use by field nurses, sales representatives, healthcare professionals, pharmacists as well as non-medically trained users to report any suspected side effects or adverse events arising from the use of our medicinal products. Our application continues to reach more users through ongoing promotion and is now being used in approximately 50 countries in 14 different languages.
Pharmacovigilance in Access to Health
We endeavor to continue expanding pharmacovigilance expertise worldwide, especially in countries where healthcare workers need to build their pharmacovigilance expertise.
We want 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.
In 2021, we took part in several projects to improve patient safety in low- and middle-income countries. For example, we collaborated with the health authorities of Cameroon to discuss and align good pharmacovigilance practice needs and actions in the country, resulting in an agreement to set up new guidelines. An initial draft was proposed to the relevant health authorities in April 2021.
Off-label use
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 may wish to administer a product to a patient suffering from a 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 and be factually balanced, clearly stating that it applies to unapproved use. In addition, we do not permit our employees to give any recommendations regarding individual patient care or treatment.