ESMA as a Residual Lawmaker: The Political Economy and Constitutionality of ESMA’s Product Intervention Measures on Complex Financial Products

This article proposes that product intervention constitutes a form of residual lawmaking by ESMA that allows it to tackle aspects of investor protection not addressed by EU incomplete financial laws. Whilst product intervention may bring about certain advantages and may contribute to mitigating regulatory arbitrage problems, it constitutes a highly intrusive regulatory mechanism that raises important questions concerning: (a) ESMA’s rationale and motivations for its use; (b) its compliance with the EU constitutional framework; and (c) its adequacy for the regulation of complex financial products. This article addresses these questions through an analysis of the rationale and consequences of ESMA’s product intervention measures on binary options and contracts for differences of May 2018–July 2019, and of recent reforms of ESMA’s powers. It offers three main contributions to the existing literature. First, it contributes to the literature on administrative discretion and agencies’ rulemaking through an analysis of the political economy of ESMA’s deployment of product intervention powers and, also, of what this reveals about the relationships between ESMA and the EU Institutions, on the one side, and ESMA and National Competent Authorities, on the other. Second, it contributes to the literature on the constitutionality of EU agencies through an examination of the compliance of ESMA’s product intervention measures with EU constitutional law and requirements. Third, it examines whether product intervention constitutes an adequate mechanism to address problems pertaining to investor protection in complex financial products markets and, in doing so, it contributes to the scholarly discussion on complex financial products’ regulation.

Clinical Trials and Machine Learning: Regulatory Approach Review

: Machine Learning, a fast-growing technology, is an application of Artificial Intelligence that has significantly contributed to drug discovery and clinical development. In the last few years, the number of clinical applications based on Machine Learning has constantly been growing. Moreover, it is now also impacting National Competent Authorities during the assessment of most recently submitted Clinical Trials that are designed, managed, or generating data deriving from the use of Machine Learning or Artificial Intelligence technologies. We review current information available on the regulatory approach to Clinical Trials and Machine Learning. We also provide inputs for further reasoning and potential indications, including six actionable proposals for regulators to proactively drive the upcoming evolution of Clinical Trials within a strong regulatory framework, focusing on patient safety, health protection, and fostering immediate access to effective treatments.

Regulatory Perspectives of Pyrrolizidine Alkaloid Contamination in Herbal Medicinal Products

The toxicity of plants containing certain pyrrolizidine alkaloids has long been recognized in grazing animals and humans. Genotoxicity and carcinogenicity data from in vitro and in vivo (animal) studies were published over the last few decades for some of the 1,2-unsaturated pyrrolizidine alkaloids, leading to regulatory action on herbal medicinal products with pyrrolizidine alkaloid-containing plants more than 30 years ago. In recent years, it has become evident that in addition to herbal medicinal products containing pyrrolizidine alkaloid-containing plants, these products may also contain pyrrolizidine alkaloids without actually including pyrrolizidine alkaloid-containing plants. This is explained by contamination by accessory herbs (weeds). The national competent authorities of the European member states and the European Medicines Agency, in this case, the Committee on Herbal Medicinal Products, reacted to these findings by setting limits for all herbal medicinal products. This review article will briefly discuss the data leading to the establishment of thresholds and the regulatory developments and consequences, as well as the current discussions and research in this area.

Analysis of Medical Device Alerts Issued by the Portuguese Medicines Agency: Scoping the Purpose of New Regulatory Recommendations

Introduction: Medical devices are healthcare technologies with a significantly growing market worldwide. This study aims to analyze medical device alerts issued by the Portuguese Medicines Agency, INFARMED, I.P. during 2017, as well as to identify the respective regulatory actions and to suggest additional recommendations.Material and Methods: All alerts on medical device alerts publicly available in the website of INFARMED, I.P. were identified and analyzed, including actions taken. Additionally, reports on medical devices from the Portuguese national competent authorities were compared with reports from other European Union member states such as Germany.Results: A total of 32 safety alerts were identified: 18 (56%) related with devices without identified records of commercialization in Portugal, six (19%) related with devices voluntarily withdrawn from the market, such as counterfeit products, and eight (25%) categorized as ‘other’. In both Portugal and Germany, 0.28 and 4.53 reports of national competent authorities per million inhabitants were identified, respectively. Diverse regulatory actions were taken, such as six compulsory indications to not acquire or use devices.Discussion: Considering that the European Union is an open market where citizens should have equal access to medical devices, the Portuguese system of medical device safety alerts seems to be functioning normally. The identified safety alerts seemed relevant, with Portugal registering a proportionally slightly lower number of alerts when compared with higher sales volume markets, which may be explained by an underreporting of this type of problems. Further studies are needed to confirm these preliminary results, although the development of databases comprising data on patients using medical devices is recommended in order to generate automatic email and text message alerts.Conclusion: A limited number of safety alerts on medical devices was identified in Portugal, with few reported cases of counterfeit or falsified devices. The Portuguese Medicines Agency contributes to the citizens’ access to quality medical devices, by issuing safety alerts, recommendations and mandatory market withdrawals for unsuitable or unsafe medical devices.

Adverse Drug Reaction Reporting by Patients in 12 European Countries

Patients who report suspected adverse drug reactions (ADRs) help minimize drug safety risks and bolster the pharmacovigilance system. The aim of this study was to examine the contribution of patients to pharmacovigilance and compare the tools used to promote patient reporting in European countries that implemented this reporting type in 2012–2013. A web-based questionnaire was sent to the national competent authorities (NCAs) of the European countries. The received answers were systematized and compared using statistical analysis. The performed statistical analysis demonstrated that changes in the number of received ADR reports increased significantly in each country during the analyzed period. These changes were significantly different in Ireland and Finland from those in the other reviewed countries. The common source of information on direct patient reporting was the country’s NCA website. Other sources used were social media pages, leaflets, and posters. This is the first study on patient reporting schemes implemented after the significant reform of the European regulatory system for pharmacovigilance. However, some countries did not actively promote their patient reporting schemes. Our findings indicate that countries with minimal experience in pharmacovigilance systems that include direct patient reporting should organize comprehensive campaigns on ADR reporting.

Medicine Shortages: From Assumption to Evidence to Action - A Proposal for Using the FMD Data Repositories for Shortages Monitoring

Medicine shortages may negatively impact patient care and the patient experience. Shortages should be a priority of industry, supply chain stakeholders and national competent authorities, and deserve more than empathy or “lip-service” but serious engagement and action. Under the overarching principle that without correct measurements in place there cannot be any improvement in overall performance (1), stakeholders in the pharmaceutical supply chain, notably pharmaceutical manufacturers have made the call for all relevant sources of information to be used in order to provide additional intelligence about the root causes and drivers of shortages, including the identification of bottlenecks in the supply chain. This paper outlines a proposal for using the data stored in the interoperable network of national repositories being set up in the context of the Falsified Medicines Directive (Directive 2011/62/EU) and its Delegated Regulation 2016/161/EU on safety features for providing additional intelligence in monitoring shortages. The paper analyses the potential feasibility and readiness of using this data for monitoring shortages as well as the strengths and weaknesses of the approach. We explore also what are some of the other complementary data sources that could be analyzed in conjunction with the data in the repository system to sharpen the overall analysis. Lastly, we provide a theoretical but concrete use case for using the abovementioned data for better informing decisions to prevent and mitigate shortages. In doing so, we explain the interlink between patient needs at country level, demand from economic actors, intra-EU parallel trade and manufacturer-imposed supply quotas and propose a mechanism for collaboration between national competent authorities and supply chain stakeholders for early detection and action to prevent medicine shortages from occurring.

COVID-19 CHALLENGES TO THE CHILD ABDUCTION PROCEEDINGS

While creating a new notion of everyday life, the COVID-19 pandemic also affects the resolution of cross-border family disputes, including the international child abduction cases. The return of an abducted child to the country of his or her habitual residence is challenged by travel restrictions, international border closures, quarantine measures, but also by closed courts or cancelled hearings. Those new circumstances that befell the whole world underline two issues considering child abduction proceedings. The first one considers access to justice in terms of a mere possibility of the applicant to initiate the return proceeding and, where the procedure is initiated, in terms of the manner of conducting the procedure. The legislation requires a quick initiation and a summary resolution of child abduction proceedings, which is crucial to ensuring the best interests and well-being of a child. This includes the obligation of the court to hear both the child and the applicant. Secondly, it is to be expected that COVID-19 will be used as a reason for child abduction and increasingly as justification for issuing non-return orders seen as a “grave risk” to the child under Article 13(1)(b) of the Child Abduction Convention. By analysing court practice from the beginning of the pandemic in March 2020 to March 2021, the research will investigate how the pandemic has affected child abduction proceedings in Croatia. Available national practice of other contracting states will also be examined. The aim of the research is to evaluate whether there were obstacles in accessing the national competent authorities and courts during the COVID-19 pandemic, and in which manner the courts conducted the proceedings and interpreted the existence of the pandemic in the context of the grave risk of harm exception. The analyses of Croatian and other national practices will be used to gain an overall insight into the effectiveness of the emerging guidance and suggest their possible broadening in COVID-19 circumstances or any other future crises.

Activities of the Eurasian Economic Commission as the Main Regulatory Body of the Eurasian Economic Union

Introduction. One of the most important aspects of the functioning of modern regional international integration organizations is the activity of their executive and regulatory bodies in cooperation with national competent authorities. This is especially relevant in the process of the functioning of the Eurasian Economic Union and the development of the legal order of this integration association. Purpose. The purpose of the study is to study and analyze the most important aspects of the activities of the Eurasian economic Commission in the context of interaction with national regulatory authorities. Methodology. The study used both General scientific methods of cognition - analysis, synthesis, induction, deduction, comparison, and private law methods (formal legal, technical-legal, and the method of legal analogy). Results. The article reveals the specifics of the legal status of the Eurasian Economic Commission as the main regulatory body of the Eurasian Economic Union, its specificity in the context of a set of supranational powers, largely due to which the integration processes within the Union are developing. Conclusion. The conclusions made as a result of the study can be used in relation to the improvement and development of the legal systems of international organizations of regional integration with the participation of the Russian Federation, in particular, the Eurasian Economic Union, as well as the process of interaction of national government bodies with the Eurasian Economic Commission.

Responsibilities of the Marketing Authorisation Holders in Respect of GMP Compliance (Review)

Introduction. The article is focused on differences in quality assurance-related obligations and responsibilities between Marketing Authorisation Holders (MAHs) and manufacturing authorisation holder (manufacturers) in pharmaceutical industry. In case of outsourcing and technical agreements there is a need to differentiate responsibilities related to quality assurance between the above mentioned categories.Text. The guidelines for the pharmaceutical sector of the European Union (EU) provide guidance on the responsibilities of the MAHs in relation to the GMP rules, which are scattered throughout the various chapters of the GMP and its appendices. In addition, certain provisions on this topic are contained in the EU directives. With this in mind the European Medicines Agency (EMA) issued in January 2020 a draft Reflection paper on Good manufacturing practice and Marketing Authorisation Holders. The draft clarifies that while certain activities of an MAH may be delegated to the manufacturer, MAH retains ultimate responsibility for the performance of a medicinal product, its safety, quality and efficacy. The important obligation of MAH in this context is to facilitate GMP compliance by establishing a robust two-way communication system with national competent authorities, manufacturing sites, Qualified Persons (QPs) certifying batches before release, and other interested parties. The MAH ought to communicate to manufacturing personnel, normally through QPs, production processes and related quality control procedures, including subsequent variations, described in registration dossiers.Conclusion. A general one conclusion: in view of rapid developments in the EU GMP Guide, the Eurasian Economic Union GMP requirements ought to be updated. In respect of specific responsibilities of MAH pertaining to GMP compliance the EMA draft Reflection paper merits attention as a guidance regarding separation of obligations and responsibilities between MAH and personnel of manufacturing sights.