Call to action: Harmonization of pharmacovigilance regulations for post-marketing pregnancy and breastfeeding safety studies.

Globally, more than 200 million women become pregnant each year, most of whom receive medications despite limited information on their safe use during pregnancy. The paucity of drug safety data on pregnant and breastfeeding women stems from the routine exclusion of this population from clinical trials due to scientific, ethical, regulatory and legal concerns. Consequently, at the time of initial drug approval, there may be scant safety data to inform the drug benefit-risk balance to the mother, foetus or infant. Although momentum is growing to include this underrepresented population in clinical trials, most information on drug exposure outcomes comes from data collected in the postmarketing setting. Regulatory guidance and legislation on medication use in pregnancy and breastfeeding were reviewed globally by the TransCelerate IGR PV Pregnancy and Breastfeeding Team. The International Conference of Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) standards and Council for International Organizations of Medical Sciences guidelines served as benchmarks for national safety regulations and guidance. The landscape assessment identified a lack of harmonization of global regulations on research in pregnant and breastfeeding women and a lack of specific regulations on this topic in the majority of the territories included in the assessment. This article focuses on the ambiguities and lack of harmonization in global regulations on postmarketing pregnancy and breastfeeding safety studies. There is currently no ICH standard to guide these types of safety studies and, in most regions reviewed, there are no clear regulations or guidance on when and how to conduct them. While a challenging undertaking, greater clarity and harmonization would facilitate more timely completion of postmarketing pregnancy safety studies that would ultimately generate the critical data needed to optimize benefit-risk decisions for women who may conceive, as well as pregnant and breastfeeding women.

Regulations Governing Medicines for Maternal and Neonatal Health: A Landscape Assessment.

Limited evidence related to the safety or efficacy of medicines in pregnancy and during breastfeeding is available to inform patients and healthcare professionals. Understanding the current regulatory landscape in the clinical trial and postmarketing settings is critical to facilitate the development of applicable processes and tools for studying medicine use during pregnancy and breastfeeding and comply with health authority expectations. This review summarizes key findings from a landscape assessment of regulations, guidelines, and guidance on the use of medicines in pregnancy and breastfeeding issued by health authorities in various territories (including the Americas, Europe, Africa, and Asia Pacific) and outlines relevant initiatives undertaken by health authorities, academic institutions, industry consortia, and public-private organizations. While global pharmacovigilance legislation regarding medication use during pregnancy and breastfeeding exists and continues to evolve, the landscape assessment revealed that there is a lack of global legislative harmonization in both the clinical trial and postmarketing surveillance settings and regulatory gaps still exist in many countries/regions. Despite ongoing efforts from health authorities and public and private organizations, intensive efforts for legislation harmonization and stakeholder collaboration are required to improve the current environment of medication safety in pregnancy and breastfeeding.

Core Data Elements for Pregnancy Pharmacovigilance Studies Using Primary Source Data Collection Methods: Recommendations from the IMI ConcePTION Project.

INTRODUCTION AND OBJECTIVE: The risks and benefits of medication use in pregnancy are typically established through post-marketing observational studies. As there is currently no standardised or systematic approach to the post-marketing assessment of medication safety in pregnancy, data generated through pregnancy pharmacovigilance (PregPV) research can be heterogenous and difficult to interpret. The aim of this article is to describe the development of a reference framework of core data elements (CDEs) for collection in primary source PregPV studies that can be used to standardise data collection procedures and, thereby, improve data harmonisation and evidence synthesis capabilities. METHODS: This CDE reference framework was developed within the Innovative Medicines Initiative (IMI) ConcePTION project by experts in pharmacovigilance, pharmacoepidemiology, medical statistics, risk-benefit communication, clinical teratology, reproductive toxicology, genetics, obstetrics, paediatrics, and child psychology. The framework was produced through a scoping review of data collection systems used by established PregPV datasets, followed by extensive discussion and debate around the value, definition, and derivation of each data item identified from these systems. RESULTS: The finalised listing of CDEs comprises 98 individual data elements, arranged into 14 tables of related fields. These data elements are openly available on the European Network of Teratology Information Services (ENTIS) website ( http://www.entis-org.eu/cde ). DISCUSSION: With this set of recommendations, we aim to standardise PregPV primary source data collection processes to improve the speed at which high-quality evidence-based statements can be provided about the safety of medication use in pregnancy.

The evolution of pharmacovigilance ecosystems: Does Moore's law invite the use of Occam's razor?

AIMS: Moore's law predicts the doubling of complexity of integrated circuits every 2 years; Kryder's corollary assumes a doubling of data storage every 13 months. With the increasing volume of legislation, pharmacovigilance systems today are inherently complex, and the emphasis has shifted from reactive (responding to emerging risks) to planned, active, risk-proportionate approaches operating throughout the life cycle of medicines. METHODS: Exploration of the drivers for increasing complexity of pharmacovigilance systems, focusing on regulatory environment, data management and evaluation. RESULTS: Evaluation of postmarketing data plays an increasingly important role in pharmacovigilance. There is great interest on the part of all stakeholders in optimizing the use of these data. Innovative approaches, including pharmacogenetics and passive measures (sensors), will lead to increased complexity and volumes of data and inevitably to an increase in the volume of case reports. There is a multiplicity of regulations and guidelines on how to manage these data, with an inherent lack of harmonization. CONCLUSION: We summarize the current characterization of safety data types, sources and the classification of these data. Using this benchmark, we discuss the future requirements of an effective pharmacovigilance ecosystem, keeping the principle of parsimony in mind. In this complex, continuously and rapidly changing environment, there is a need for a return to simplicity and pragmatism. The application of Occam's razor could help to support the rapid provision of new, affordable medicines with a positive benefit to risk profile.