Kevin Blake

European Medicines Agency review of post‐authorisation studies with implications for the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance

A review of post‐authorisation studies requested in 2007 by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) was undertaken to determine compliance and the need for research capacity in the European Union (EU), with implications for the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP).

Proactively managing the risk of marketed drugs: experience with the EMA Pharmacovigilance Risk Assessment Committee.

Proactively managing the risk of marketed drugs: experience with the EMA Pharmacovigilance Risk Assessment Committee

Increasing scientific standards, independence and transparency in post‐authorisation studies: the role of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance

The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP), an initiative coordinated by the European Medicines Agency, aims to build capacity for and increase trust in post‐authorisation studies to further support medicine decision making.

Drug-induced PML: a global agenda for a global challenge.

The occurrence of severe adverse events such as progressive multifocal leukoencephalopathy (PML) has the potential to limit the benefits of highly efficacious medicines being developed to fulfill unmet clinical needs across therapeutic areas. Following an Expert meeting in London in July 2011 (http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/09/WC500111562.pdf), a research agenda, highlighting methodological, clinical, and communication elements, to mitigate the risk and improve the management of drug‐induced PML has been agreed upon.

Physiologically based pharmacokinetic modeling in regulatory decision‐making at the European Medicines Agency

Physiologically based pharmacokinetic (PBPK) modeling is a valuable tool in drug development and regulatory assessment, as it offers the opportunity to simulate the pharmacokinetics of a compound, with a mechanistic understanding, in a variety of populations and situations. This work reviews the use and impact of such modeling in selected regulatory procedures submitted to the European Medicines Agency (EMA) before the end of 2015, together with its subsequent reflection in public documents relating to the assessment of these procedures. It is apparent that the reference to PBPK modeling in regulatory public documents underrepresents its use. A positive trend over time of the number of PBPK models submitted is shown, and in a number of cases the results of these may impact the decision‐making process or lead to recommendations in the product labeling. These results confirm the need for regulatory guidance in this field, which is currently under development by the EMA.

Registries in European post-marketing surveillance: a retrospective analysis of centrally approved products, 2005-2013

Regulatory agencies and other stakeholders increasingly rely on data collected through registries to support their decision‐making. Data from registries are a cornerstone of post‐marketing surveillance for monitoring the use of medicines in clinical practice. This study was aimed at gaining further insight into the European Medicines Agencys (EMA) requests for new registries and registry studies using existing registries and to review the experience gained in their conduct.

The European Medicines Agency's use of prioritised independent research for best evidence in regulatory action on diclofenac

In the European Union (EU), the conclusions of the scientific committees of the European Medicines Agency (EMA) underpin regulatory decisions on medicines. In July 2012, EU legislation established the Pharmacovigilance Risk Assessment Committee (PRAC), and regulatory decisions on pharmacovigilance concerns now rely on PRAC’s assessment. As for other committees, including the Committee for Human Medicinal Products (CHMP), work is ongoing to constantly drive up the quality of opinions including further development of approaches to benefit–risk methodology.1 Central to benefit–risk assessment is basing PRAC recommendations on the scientific evaluation of best-evidence incorporating available information from all sources including analyses of data by pharmaceutical companies, academics and regulatory agencies, the literature (including prepublication manuscripts) and reports from healthcare professionals and patients. However, in line with regulators expanding their role to be not only gatekeepers but also enablers of development,2 this involves not just assessing data but also stimulating research questions and generating new data in an ‘evidence-decision’ strategy that subsequently supports regulatory decision making. The EMA’s European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP)3 and the Pharmacoepidemiological Research onOutcomes of Therapeutics by a EuropeanConsortium4 (PROTECT) programmes are examples of applying the strategy to develop infrastructure and methodologies for pharmacoepidemiological research. The EMA’s approach may also be seen in the context of a global sea-change in the science of medicines regulation.5 The core strategy is outlined in Figure 1. The present commentary relates to the June 2013 PRAC recommendation on medicines for systemic use containing the active substance diclofenac6 as an illustrative example of this evidence–decision strategy. In this particular example, the cycle, starting in 2006, stimulated research by independent, academic, third parties to generate new knowledge following the identification of a regulatory research question. These data were subsequently put in the context of all relevant and available evidence in a review that started in 2012 and that resulted in decisive and informed regulatory actions in 2013.

Promoting Safe Early Clinical Research of Novel Drug Candidates: A European Union Regulatory Perspective

The European Medicines Agency (EMA) revises its guideline on minimizing risk in first‐in‐human trials to reflect changing practice and in light of a recent tragic incident.

Geographical variation in reporting Interstitial Lung Disease as an adverse drug reaction: findings from an European Medicines Agency analysis of reports in EudraVigilance

Clinically, interstitial lung disease (ILD) is a heterogeneous group of over 150 respiratory disorders. In the context of its signal evaluation work, the European Medicines Agencys (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has seen geographic clustering of case reports of ILD from Japan. To explore this further, EudraVigilance (EV), the EMAs database of adverse drug reactions (ADRs), was analysed. The results have been used to inform on implications for pharmacovigilance including signal detection and evaluation activities.

Overview of the European Medicines Agency's Development of Product‐Specific Bioequivalence Guidelines

The European Medicines Agencys (EMA) product‐specific bioequivalence guidelines outline harmonized regulatory requirements for studies to demonstrate bioequivalence for products that may have particular needs due to their pharmacokinetics, in addition to those outlined in general guidance. As such they are potentially very useful to the pharmaceutical industry in the development of generic medicinal products and to regulatory authorities for harmonized decision‐making. Since their introduction in 2013, EMA product‐specific bioequivalence guidelines continue to increase in number, and as of June 2017, encompass a number of different pharmacotherapeutic groups and pharmaceutical forms. This article further elucidates the processes involved for stakeholders and reviews the Agencys experience with the development of these guidelines, including the scientific issues witnessed with their advancement. A comparison with the United States Food and Drug Administration approach to similar guidelines is also provided.