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 aim at 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 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 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.
As part of our R&D Strategy 2023, we achieved our objective of developing and implementing proactive benefit-risk management, process optimization, automation, and pharmacovigilance oversight. Furthermore, we continue monitoring 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 (KPIs).
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
- User-friendly methods for collecting adverse effects
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 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 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.
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, which fosters our target to ensure 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. 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 furthermore reviews human-related ethical issues as appropriate.
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 Global Patient Safety unit. Important issues may be submitted to the MSEB for final assessment.
Our commitment: Guidelines and statutory requirements
Our aim is to 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. Furthermore, we aim at complying with all 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 2022, we had four pharmacovigilance inspections.
Furthermore, we perform audits to ensure that all our units and subsidiaries involved in pharmacovigilance consistently meet all global requirements. In 2022, we conducted a total of 19 pharmacovigilance audits and found no significant deviations in our pharmacovigilance systems from these requirements and standards. We also conducted 16 external audits at our vendors and licensing partners involved in pharmacovigilance, helping us improve our pharmacovigilance processes and comply with regulatory requirements.
Applying our proactive safety strategy to benefit-risk assessments
With regard to product safety risk assessments, we have implemented an improved benefit-risk management strategy in order to become a proactive and benefit-risk-focused organization. In this context, we developed in 2021 the concepts and principles for conducting benefit-risk assessments at each stage of product development and post-marketing. Along with the implementation of the redesigned benefit-risk strategy, the new Benefit Risk Action Team co-leadership model was rolled out in 2022. This redesigned approach will enable us to understand in even greater detail the benefit-risk profiles of our products, enabling early decision-making within the organization to protect patient safety. Ultimately, the aim is to be able to provide the right medicine to the right patient at the right time.
Product safety assessment and emergency response procedures
A product prioritization tool as a means to objectively score the safety profile of our products has been used as a basis to define our product prioritization strategy. The scores categorize our products as being either high-, medium- or low-risk and subsequently defining our approach for benefit-risk activities and product safety surveillance. These include individual case safety report management, signal management and management of emerging safety issues, risk management, safety communication, our new benefit-risk strategy and aggregate safety reporting. This ensures the efficient management of safety risks of our medicinal products throughout their lifecycles.
If our safety risk assessments identify any emerging safety issues, safety observations that require urgent safety measures, or other new safety information that potentially impacts the benefit-risk balance of the product, 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 amounts of global data, such as scientific studies and news about adverse events. 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 2022, there were no significant 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 24,000 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 us to ensure adherence to pharmacovigilance requirements.
Enhancing patient safety and sharing expertise with other countries
We exchange experience and share our expertise by contributing to initiatives hosted by various non-profit organizations, for example, the TransCelerate Biopharma. As an active member of 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.
Reporting side effects via app
In line with our goal to enhance patient safety, we implemented a user-friendly mobile and web application in 2017 for use by 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. In the reporting year 2022 we continued to further rolled-out the application, which is now available in 14 different languages, used in more than 50 countries.
Pharmacovigilance in Access to Health
We strive to continue expanding pharmacovigilance expertise worldwide, especially 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 help establish the national pharmacovigilance system via various initiatives. These include the good pharmacovigilance practice guideline that was published in August 2022.
In 2022, we continued to raise awareness for Patient Safety Day via our affiliates in several countries, including Australia, China, Hong Kong, India, Indonesia, Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam.
In other initiatives, we contributed to the review of draft guidance documents for clinical trials and provided feedback to the health authorities in China. We also participated in the review and feedback of draft regulations for good pharmacovigilance practice before its rollout by the Eurasian Economic Union. In addition, we collaborated with the health authority in Chile to test and provide feedback about the new Integrated Vigilance System.
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 risk-benefit assessment, 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.