Benefit-risk management for medicinal products and medical devices
Patient safety is Bayer’s top priority. HealthCare continuously assesses the medical benefit-risk balance of its medicinal products and medical devices throughout their entire product life cycle. The efficacy, safety and tolerability of pharmaceuticals and their behavior in the body are studied in Phases I-III of preclinical and clinical development. The documentation submitted to the regulatory authorities contains the results of these studies and comprehensive information on the product’s benefit-risk assessment. Marketing authorization is only granted for a product if it satisfies the safety requirements of the health and regulatory authorities.
Following registration, HealthCare continues to compile safety-relevant information in an internal pharmacovigilance Pharmacovigilance is defined as the science of, and activities related to, the identification, assessment, comprehension and prevention of side effects or other problems associated with pharmaceutical products. database. This information is continuously evaluated and the risk-benefit balance regularly assessed by medical experts in the Global Pharmacovigilance Department. In this process, Bayer works closely with the responsible regulatory and supervisory authorities at the international and national levels. These include the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and Germany’s Federal Institute for Drugs and Medical Devices (BfArM).
Additional safety-relevant information is also compiled using Post-Authorization Safety Studies (PASS) conducted after approval. Protocols and summaries of PASS results are entered into the PAS registry in compliance with E.U. pharmacovigilance legislation.
Online annex: 3-8.1-1:limited assurance
HealthCare has a global pharmaceutical monitoring system in which experts from various disciplines work together in functional safety management teams (SMTs). These teams jointly evaluate the available benefit and safety data and other relevant product information so as to identify potential safety concerns at an early stage or detect possible changes in the benefit-risk ratio. In addition to internally compiled safety data from clinical trials, post-marketing studies and ad hoc information on adverse side effects, the company’s experts conduct assessments using external databases and the information contained in scientific publications. SMTs produce detailed safety risk management plans. These plans are updated as soon as relevant new benefit-risk data become available. Implementation of risk mitigation activities is coordinated by local SMTs in the country organizations. All processes are documented, regularly updated and integrated into a quality management system.
Should risks be identified during this assessment, Bayer immediately undertakes suitable steps to safeguard the health of patients – such as updating product information for patients and physicians. Further elements of risk mitigation programs can include targeted information, e.g. patient education brochures and training measures for medical specialists, as well as direct communication with medical experts (Direct Healthcare Professional Communication, DHPC) and even product withdrawals if necessary. These measures are coordinated with the competent authorities.
HealthCare’s quality and risk management functions also make further contributions to increased safety. We examine external and internal quality assurance requirements for our products through systematic internal audits – not just in research and development, but also in production. These audits also cover institutes sub-contracted by us and our suppliers. More information on our quality management can be found in Chapter 7.2 “Production.”
In line with the statutory requirements, strict safety and quality standards also apply to animal health products. Within the scope of the approval / authorization procedures, Animal Health also carries out studies in order to ensure the quality, efficacy and safety of its products.
Analysis of residues of pharmaceuticals in the environment
Active pharmaceutical ingredients can enter the environment, either through human or livestock excreta, improper disposal of unused medicines or during the production process. HealthCare carries out ecotoxicological investigations of the environmental behavior of residues and degradation products to assess the potential environmental impact of our pharmaceutical products. In accordance with applicable law regarding human and veterinary pharmaceuticals, an environmental risk assessment takes place for all active ingredients for which the company is targeting an approval procedure in Europe or the United States. Here it must be examined whether significant risks may arise for the environment when the pharmaceuticals are used as instructed.
Based on currently available information derived from measurements carried out by authorities and scientific institutes, the existing concentrations of individual active pharmaceutical ingredients from human or veterinary medicines in drinking water do not have any adverse effects on human health. This subject is dealt with in particular by a WHO report on pharmaceuticals in drinking water published in 2012 that comes to the conclusion that traceable effects on human health through the current extent of exposure via drinking water are highly improbable. This estimation corresponds with the studies by national authorities and institutes known to us.
In the production of our pharmaceuticals, internal company wastewater threshold values ensure that no risk to the environment results from the release of traces of active ingredients in wastewater from production sites. All HealthCare production sites worldwide are evaluated with regard to these threshold values. Site-specific measures aimed at a further reduction are taken should it not be possible to observe these standards over the long term. This includes substance-specific measures such as filtration, evaporation, oxidation, incineration or biological clarification in wastewater treatment plants.
Online annex: 3-8.1-2:limited assurance
Within the scope of our product stewardship, we actively participate in research projects aimed at further studying pharmaceutical residues in the environment and introducing targeted measures to prevent them.
Since 2015, we have coordinated the “Intelligence-led Assessment of Pharmaceuticals in the Environment” project in Europe, which seeks new ways to improve environmental risk assessment. To this end, information from toxicological studies, pharmacological modes of action and computer-based models are analyzed with the goal of developing models and methods for determining possible environmental risks of pharmaceutical substances in early development stages and prioritizing for further environmental assessment existing substances that previously have not been evaluated.
Bayer was represented on the Scientific Advisory Board of noPILLS, an E.U.-sponsored cooperation project completed in 2015 and involving several European countries with the goal of reducing pharmaceutical residues in water. The project demonstrated that a reduction in pharmaceutical residues in water can only be achieved through cooperation between numerous parties. Educating consumers on the correct disposal of pharmaceuticals, improving wastewater treatment technology and the collection of excreta in connection with certain medicines proved to be effective approaches for achieving this objective.
In Germany, HealthCare participates in the “Risk Management of Emerging Compounds and Pathogens in the Water Cycle” initiative sponsored by the German Ministry for Education and Research. HealthCare is a member of the steering committee. The “SAUBER+” project, which is part of this initiative, deals with the study of wastewater from health care industry facilities that is contaminated with active pharmaceutical ingredients and disease pathogens. Here it was determined that these emissions are not higher on average than those from private households. The reduction of pharmaceutical emissions generally depends on the individual active ingredients and should pursue a holistic approach. HealthCare was a member of the Stakeholder Advisory Board of that project, which was concluded in 2015.