Our pharmaceutical products must be safe. 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.
Benefit versus risk
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 risk-benefit profile. Only if the medicine has a positive risk-benefit profile do we submit an application for marketing authorization to the regulatory authorities.
After market launch, the number of patients being treated with the drug increases significantly. In certain circumstances, rare adverse effects may occur that went undetected during clinical development, which is why we continually monitor and update the risk-benefit profiles even after market launch.
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.
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.
Our Global Drug Safety unit is responsible for pharmacovigilance; it continually collects current safety data from a wide variety of sources across the globe, to include clinical studies, spontaneous reports on adverse effects, and articles published in medical and scientific journals. Our experts ensure that all information on the potential risks and adverse effects of our medicines is properly documented, tracked and, if necessary, reported to the respective regulatory authorities. Global Drug Safety analyzes all data and, as required, uses this to reassess the risk-benefit profile. We then inform the regulatory authorities, physicians and patients about potential risks and changes in the risk-benefit balance.
We always adhere to all statutory pharmacovigilance regulations in force in those countries where we market our products and continuously work to incorporate requirement changes in our Group-wide standards and processes.
Regulatory authorities also conduct regular inspections to verify that we are complying with statutory requirements and our own internal drug safety standards.
Furthermore, we perform our own audits to ensure that all our departments, subsidiaries, vendors, and licensing partners involved in pharmacovigilance are meeting all requirements across the globe at all times.
Medical Safety and Ethics Board
Our Medical Safety and Ethics Board (MSEB) oversees the safety and risk-benefit evaluations of our drugs throughout clinical development and commercialization. As required, it will initiate appropriate measures to minimize risk, such as package insert updates. Our Chief Medical Officer (CMO) is the chairman of the MSEB, which also consists of senior physicians, scientists and experts from our company. Throughout a drug's entire life cycle, the MSEB reviews and assesses all relevant medical, ethical and safety issues. Furthermore, its tasks include the release of new investigational products for first-in-human use after conducting a thorough risk-benefit analysis based on all preclinical examination results.
The package insert informs physicians and patients how to properly use the respective drug. In accordance with the statutory regulations, the insert contains all relevant information such as ingredients and dosage, storage, mode of action, instructions for use, warnings, precautions, and adverse effects. Should the medicine contain ingredients that impact the environment, the package insert may also contain information on the proper disposal of the product.
As necessary, we review and update all package inserts, ensuring that they contain the latest information about our drugs. The leaflets also reflect changes initiated by the MSEB, such as new warnings.
In accordance with statutory requirements, all modifications to the inserts are submitted to the respective regulatory authorities for approval.
Strict quality assurance
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 the 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.
Reliable distribution processes
We want our pharmaceutical products to be readily available to physicians and patients and always arrive on time. Therefore, our distribution process 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).
All employees involved in the safety and quality of pharmaceutical products, or in planning, conducting and monitoring clinical studies, are trained according to our global training standards. These standards stipulate how we conduct and document training at all our sites. We verify compliance with these requirements by performing regular audits.
In this way, employees are kept up-to-date at all times. This includes their professional expertise as well as adherence to GCP, GDP, internal standard operating procedures, and other relevant requirements. We provide our training via a global e-learning platform on our intranet.
Joint recommendations for improved risk-benefit profiles
To optimize the risk-benefit balance of our pharmaceutical products, we work closely with other companies and public-sector organizations such as health authorities and academic institutions. We are involved in PROTECT, a research project run by the Innovative Medicines Initiative (IMI), which is a joint undertaking between the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA). PROTECT aims to further develop tools and methods used in evaluating the risks and benefits of drugs. IMI project teams, in which we have taken on a leading role, have established a framework to help accomplish the initiative's mission. Building on this, we have introduced a Benefit-Risk Guide to our Drug Safety unit and have been using this guide as a source of improvement since 2015. We last made use of its recommendations when compiling the documentation for marketing authorization for our cladribine tablets.
No critical observations in pharmacovigilance inspections
In Germany, there are two pharmaceutical regulatory agencies: the German Federal Institute for Drugs and Medical Devices (BfArM) and the Paul Ehrlich Institute (the German Federal Institute for Vaccines and Biomedicines). Both agencies conducted pharmacovigilance inspections on our company in February 2015 on behalf of the European Medicines Agency.
Furthermore, pharmacovigilance inspections were conducted by the respective national authorities in Australia, Austria, Colombia, Ghana, Japan, Spain, Croatia, and the United States in 2015 and 2016.
All inspections have continually confirmed the proper functioning of our Pharmacovigilance system.
Sharing expertise with other countries
We also pass on our drug safety expertise to other countries, especially those in which health workers (such as health agencies, physicians and nurses) still lack the necessary knowledge regarding pharmacovigilance. In 2016, for instance, we supported training events and conferences in Peru, China and Ivory Coast.
At our third Africa Luminary conference, held in Ivory Coast in October 2016, government representatives from Liberia, Uganda, the Central African Republic, Nigeria, and Kenya came together with more than 250 medical professionals as well as our own experts. The theme of the conference was “Unlocking the Pharmacovigilance Power in Africa”. Here, we provided information on monitoring the safety of drugs for cardiovascular diseases, thyroid disorders, diabetes, and infertility.
In China, too, we shared our knowledge. In partnership with the China Food and Drug Administration (CFDA), we conducted several training seminars for pharmacovigilance experts from the local Chinese pharmaceutical industry. At these seminars, we not only informed participants of the local drug safety requirements, but also about key global regulations and recommendations. Moreover, in Peru we participated in workshops on collaboration between pharmaceutical manufacturers and health authorities.