The safety of patients who are treated with our medicines is our absolute priority. Our pharmaceutical products need to be effective in treating the respective disease while also posing as little risk as possible to patients. That is why we consistently monitor risks and any adverse effects that may arise, and take the necessary actions to minimize them. The benefits of our drugs must always outweigh the risks for patients.
Our approach to ensuring patient safety
Through rigorous benefit-risk management, we ensure that the benefits of our drugs always outweigh the risks for patients. Every new medicine passes a series of precisely defined development stages. Before any drug is given to humans, 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 what dosage. This 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 drug when used in humans. During clinical development, we diligently use all collected data to continuously evaluate the drug’s benefit-risk profile. If we consider the drug’s benefit-risk profile to be positive, we then submit an application for marketing authorization to the regulatory authorities.
After a drug is launched, the number of patients being treated with it increases significantly. In certain circumstances, rare adverse and severe effects that go undetected during clinical development may occur, which is why we continually monitor and manage the positive benefit-risk profiles after market launch. Pharmacovigilance is the process of continuously monitoring a drug to detect and assess signals as part of signal management activities. The aim is to track the adverse effects in an effort to take appropriate action to minimize and communicate the risks in a transparent way. We always provide physicians and patients with the latest information on the safety of all our marketed drugs. This applies to the entire life cycle of a product, ranging from development, market launch and commercialization to expiration of the marketing authorization.
For new products, educational materials are developed for patients and healthcare providers to communicate the 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 content of the materials and their distribution, and describe the results from the effectiveness analysis in our periodic safety reports and risk management plans, which we submit to health authorities for evaluation.
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, patient support programs, and articles published in medical and scientific journals, and furthermore reassesses the benefit-risk profile on an ongoing basis.
Our experts make sure all information on the risks and adverse effects of our medicines is properly documented, tracked and reported to the respective health authorities in accordance with regulatory requirements. The Global Patient Safety unit analyzes all data and uses this as required to reassess the benefit-risk profile. We then inform regulatory authorities, physicians and patients about new risks, additional risk mitigation measures and potential changes in the benefit-risk balance.
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. It endorses 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
We follow international guidance and standard procedures such as the International Conference of Harmonization (ICH) guidelines and the Good Pharmacovigilance Practices (GVP) established by the European Medicines Agency (EMA). In addition, we adhere to all statutory pharmacovigilance regulations in those countries where we market our products, and we constantly work to incorporate all required changes in our Group-wide standards and processes. In 2018, for instance, we harmonized the processing of personal data worldwide according to new European legislation on data privacy.
In November 2017, the EMA implemented a new process for EudraVigilance to monitor the safety of medicines. This newly established approach provides marketing authorization holders with access to data on suspected adverse effects, requiring them to monitor the EudraVigilance data for safety signals and to report these to health authorities. In response to these new requirements and to the new data transmission format stipulated by ICH guideline E2B (R3), we upgraded our Global Safety Database to ensure the technical capabilities needed to support the coordinated exchange of individual case safety reports.
In 2018, we assessed new country-specific regulatory requirements and implemented necessary changes in order to fulfill them. Examples include the Chinese Food and Drug Administration, the new India Pharmacovigilance Guidance for Marketing Authorization for post-marketing safety reporting and the new Canadian requirements for safety signal notification.
In addition to adhering to guidelines and regulations, we have introduced a Benefit-Risk guide to our Global Patient Safety unit, which builds on the results of a joint initiative that we are involved in between the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA). These results helped us in compiling the documentation for the marketing authorization of cladribine and avelumab.
Collecting information and checking processes
Our self-developed mobile app, named agReporter, is used to report any adverse effects arising from the use of our products. Although initially intended for use by field nurses and our sales representatives, in 2018 we introduced an interface designed for non-medically trained users, thus making patient feedback the core of our efforts to consistently collect adverse effects data. In 2018, the app became available in a total of eight languages, with a Chinese version currently in the works.
In 2018, we introduced a new pharmacovigilance intelligence process to improve internal data analysis and informational output from our various sources. We have developed new capabilities in the following areas:
- advanced benefit-risk management
- big data analytics
- advanced signal detection technology
- pilot processes in patient-centric adverse effects collection
Supervising drug safety
Regulatory authorities conduct periodic inspections to verify that we are complying both with statutory requirements and 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 EMA. In 2018, four pharmacovigilance inspections were conducted in Japan, Slovakia, Slovenia, and Turkey. Every inspection has confirmed the proper functioning of our pharmacovigilance system.
Furthermore, we perform audits to ensure that all our departments and subsidiaries involved in pharmacovigilance consistently meet all requirements across the globe. In 2018, we conducted a total of 37 audits and found no significant deviations in our pharmacovigilance system from these requirements. We also audit vendors and licensing partners involved in pharmacovigilance, which help us hone our pharmacovigilance processes so that they surpass statutory requirements.
Innovative signal detection
In 2018, we successfully launched a new methodology and technical system for analyzing and managing large amounts of data from around the world, such as scientific studies and news about side effects. Through this new tool for signal detection, named Empirica, we intend to become more efficient and proactive and improve risk management. It helps us to comply with regulatory timelines for safety signals and other safety-related factors and will ensure that all signal data, documentation and decisions are captured in one place. This allows easy access to and analysis of our data as well as cross-functional collaboration between Global Patient Safety and other internal and external stakeholders. Furthermore, we established a new signal detection process that allows us to detect signals directly from the EudraVigilance Data Analysis System (EVDAS) and enables us to comply with any new requirements set by health authorities.
Up-to-date labeling and product information
Our product information explains to physicians and patients how to properly use the respective drug and allows for an informed decision on the treatment. In accordance with statutory regulations, the package insert contains all relevant information such as indication and ingredients, as well as 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.
As necessary, we review and update all product information documents such as package inserts, ensuring that our medicinal products contain the latest information on safety, efficacy and pharmaceutical formulation. 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 producing training compliance reports and performing regular audits.
Our training is delivered via a global-learning platform. All of our 20,000-plus Biopharma employees receive basic pharmacovigilance training once a year that covers the procedure for reporting adverse effects from our products. Other training courses keep employees up to date on their professional expertise as well as internal standard operating procedures and other relevant requirements. This ensures adherence to Good Pharmacovigilance Practice (GVP) requirements.
Sharing expertise with other countries
We endeavor to transfer our drug safety expertise around the world, especially in countries where health workers need to build their pharmacovigilance expertise. In 2018, we organized a workshop for 96 students from the School of Medicine of the National University in Guatemala, as reporting of adverse drug reactions is often not sufficiently represented in the curricula of medical students. The participants were already examining patients and prescribing drugs on a daily basis, so they considered the workshop to be relevant and applicable in their daily routine.
We also assist Latin American health authorities in implementing electronic reporting processes for adverse effects. Following a pilot project in Ecuador that ended in April 2018, we are supporting the implementation of electronic reporting in Argentina, El Salvador and Peru. Health authorities in Mexico and Brazil are also moving towards adopting this technology. This program makes us one of the first companies to participate in global electronic reporting.
Our activities in providing health for all include involvement in piloting a social business healthcare platform in Kenya named CURAFA. As part of this project, in 2018 we provided training to two pharmacies on pharmacovigilance awareness and safety reporting procedures, and introduced our agReporter app to the people working there.
Launched in late 2017, we are continuing the “Afrika kommt!” project in an effort to educate trainees from Africa on the safe use of pharmaceutical products. The ultimate goal is for them to eventually take what they have learned and implement it in their home countries.