The safety of patients treated with our medicines is a critical priority. That is why we consistently monitor risks and adverse effects as they arise, and take the necessary action to minimize them. Through rigorous benefit-risk assessments, we ensure that the benefits of our drugs always outweigh the risks for patients.
Our approach to ensuring patient safety
Our pharmaceutical products need to be effective in treating the respective disease while also posing as little risk as possible to patients. To ensure their safety, every new medicine passes a series of precisely defined development stages. Prior to using a drug in humans, we first 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 what dose. This also helps us determine the dose that humans can safely tolerate. Only once this is complete do we perform clinical studies to investigate the safety and efficacy of the drug when used in humans. During clinical development, we diligently use all collected data to continuously evaluate the drug's benefit-risk profile. We only submit an application for marketing authorization to the regulatory authorities if the medicine has a positive benefit-risk profile.
Continual monitoring
After a drug is launched, the number of patients being treated with it increases significantly. In certain circumstances, rare adverse effects that go undetected during clinical development may occur, which is why we continually monitor and update the benefit-risk profiles even after market launch. For new products approved in 2017, we introduced educational materials for patients and healthcare providers on potential risks.
Pharmacovigilance is the process of continuously monitoring a drug to detect, assess and understand adverse effects in an effort to take appropriate action to minimize risk.
We always provide physicians and patients with the latest information on the safety of our drugs. This applies to the entire life cycle of a product, ranging from development, market launch and commercialization to expiration of the marketing authorization.
How we monitor patient safety
Our Global Patient Safety unit is responsible for pharmacovigilance; it continually collects current safety data from a wide variety of sources across the globe, including clinical studies, spontaneous reports on adverse effects, and articles published in medical and scientific journals. In 2017 we launched a new methodology and technical system providing effective, state-of-the-art capabilities for signal detection and management using data collected worldwide and big data analytics.
Our experts ensure that all information on the potential risks and adverse effects of our medicines is properly documented, tracked and reported to the respective health authorities in accordance with regulatory requirements. Global Patient Safety analyzes all data and uses this as required to reassess the benefit-risk profile. We then inform regulatory authorities, physicians and patients about potential risks and changes in the benefit-risk balance.
To meet the growing demands of our innovative R&D pipeline, Global Patient Safety underwent a strategic reorganization and specialization process in 2017. This resulted in two dedicated units specializing in the co-development and benefit-risk management of our investigational pipeline products, and in the global pharmacovigilance of our broad portfolio of products marketed worldwide. This specialization has already created new capabilities in advanced benefit-risk management, big data analytics, advanced signal detection technology, and pilot processes in patient-centric adverse effects collection.
Our Product Quality unit (MBQ) processes quality complaints relating to our products. When quality defects may have an impact on patient safety or lead to adverse effects, Global Patient Safety gets involved.
Our Medical Safety and Ethics Board
Our Medical Safety and Ethics Board (MSEB) oversees the safety and benefit-risk evaluations of our drugs throughout clinical development and commercialization. As required, it initiates appropriate measures to minimize risk, such as package insert updates. This board is chaired by our Chief Medical Officer (CMO) and consists of experienced physicians, scientists and experts from our company. Throughout a drug's entire life cycle, the MSEB reviews and assesses important medical safety risks and benefit-risk issues, and reviews ethical issues if necessary.
Our commitment: Guidelines and statutory requirements
To evaluate benefits and risks, we have introduced a Benefit-Risk Guide to our Global Patient Safety unit. This manual builds on the results of a joint initiative of the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA) in which we are involved. We benefited from the recommendations when compiling the documentation for marketing authorization of the drug cladribine. Subsequently we made use of these learnings for the documentation required for the marketing authorization of avelumab.
In producing pharmaceuticals, quality assurance is a key aspect. The Current Good Manufacturing Practice (CGMP) regulations ensure that pharmaceuticals meet the standards set for identity, purity, potency, and safety. Compliance with these regulations is mandatory for pharmaceutical companies and is closely monitored by health authorities. As a pharmaceutical manufacturer, we have appropriately trained employees, as well as suitable facilities, processes and procedures in order to meet all requirements.
We want our pharmaceutical products to be readily available to physicians and patients and always arrive on time. For this to happen, our distribution processes must function reliably all over the world. By continually auditing our distribution network, we ensure that both our subsidiaries as well as our partners and contractors adhere to our quality and safety requirements. All distribution activities must comply fully with Good Distribution Practices (GDP).
Meeting statutory requirements
We always adhere to all statutory pharmacovigilance regulations in force in those countries where we market our products and are continuously working to incorporate requirement changes in our Group-wide standards and processes. In 2017, for instance, we upgraded our safety database and the associated reporting processes to meet the new requirements of the European Medicines Agency (EMA).
Collecting information and checking processes
In March 2017 we rolled out agReporter, a mobile app for reporting adverse effects from the use of our products. This tool was initially intended for use by field nurses and our sales representatives. Furthermore, we plan to add a patient-friendly interface to the app, thereby putting patients center stage in our efforts to consistently collect adverse effects data.
Supervising drug safety
Regulatory authorities conduct regular inspections to verify that we are complying both with statutory requirements as well as our own internal standards for drug safety. In Germany, these are handled by the German Federal Institute for Drugs and Medical Devices (BfArM) and the Paul Ehrlich Institute (the German Federal Institute for Vaccines and Biomedicines (PEI)) on behalf of the European Medicines Agency. In 2017 pharmacovigilance inspections were conducted in Canada, Colombia, France, Japan, and Switzerland. All inspections have continually confirmed the proper functioning of our Pharmacovigilance system.
Furthermore, we perform our own audits to ensure that all our departments, subsidiaries, vendors, and licensing partners involved in pharmacovigilance consistently meet all requirements across the globe. In 2017, we found no significant deviations from these requirements. Such audits help us hone our pharmacovigilance processes so that they surpass statutory requirements.
Labeling of products
Package inserts inform physicians and patients on how to properly use the respective drug. In accordance with statutory regulations, the insert contains all relevant information such as ingredients and dosage, storage, mode of action, instructions for use, warnings, precautions, and possible adverse effects. Should the medicine contain ingredients that may impact the environment, the package insert may also contain information on the proper disposal of the product.
We review and update all package inserts as necessary, ensuring that they contain the latest information about our medicinal products. These leaflets also reflect changes initiated by our MSEB, such as new warnings. In accordance with statutory requirements, all modifications to the inserts are submitted to the respective regulatory authorities for approval.
Internal and external training
All employees involved in the safety and quality of pharmaceutical products are trained according to our global training standards. We verify compliance with these requirements by performing regular audits. In addition, all our Biopharma employees receive basic pharmacovigilance training once a year that covers how to report adverse effects from our products.
Through such training, all employees are kept consistently up-to-date. This includes their professional expertise and training on internal standard operating procedures and other relevant requirements. In this way, we ensure adherence to Good Pharmacovigilance Practice (GVP) requirements. We provide our training via a global e-learning platform.
In 2017 we initiated a pharmacovigilance campaign in Mexico to raise awareness for adverse effect reporting. This effort is targeted at both patients and health workers (such as health authorities, physicians and nurses) along with our own Marketing & Sales people. To ensure the campaign’s success, we offered a special training program for our Marketing & Sales staff, who also receive additional informational material every two months. Moreover, we are conducting a poster campaign to make health sector employees more aware of the importance of reporting adverse effects.
Sharing expertise with other countries
We also work to transfer our drug safety expertise to other countries, especially those where health workers still lack the necessary knowledge regarding pharmacovigilance. In November 2017 we launched the “Africa kommt!” project in an effort to educate trainees from Africa on the safe use of pharmaceutical products, with the ultimate goal of them subsequently implementing the educational content in their home countries.