Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 107

In 2001, an EU-wide central database, called the Eudra-Vigilance System, was created (http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000679.jsp). This database serves as a repository and “clearinghouse” to ensure that all appropriate cases are available to the appropriate member states. It is used to capture SAEs as Individual Case Safety Reports (ICSRs) both pre- and post-authorization as well as spontaneous non-serious AEs. It has been designed to manage and analyze information on suspected adverse reactions to medicines which have been authorized or are being studied in clinical trials in the European Economic Area (EEA).

The EMA operates the system. This allows for a single European database accessible to the member states’ HAs. Individual cases (ICSRs) must now be reported electronically from both public and private PV organizations (using the gateway or the web reporting application).

The pharmaceutical industry can only access detailed, proprietary data for medicines for which they hold a marketing authorization. This restriction is in place to remain in compliance with EU personal data protection and privacy legislation. They can, of course, access the high level summary information available to the general public on all medications in EudraVigilance (http://www.adrreports.eu/en/index.html). Simple queries can deliver online summary tables or figures depending on the selected criteria.

The European pharmacovigilance issues tracking tool (EPITT) is a database developed by EMA for the communication of pharmacovigilance and risk-management issues between the Agency and Member States. It provides access to documents related to the safety of products/substances authorized in the EEA. The EPITT provides the functionalities for national regulatory authorities in the EEA and EMA to track signals at EU level. It is not available to the public or the pharmaceutical industry.

Other computerized systems have been developed by the EMA:

EudraVigilance Medicinal Products Dictionary (XEVMPD), also known as the Article 57 database. This is the EU drug dictionary.

SIAMED II is the Agency’s product information and application tracking system.

The European Clinical Trials Database (EudraCT) is the EU’s electronic database of clinical trials. It contains information submitted by sponsors and informs users about ongoing clinical trials in all EEA countries, enabling an overview of multi-state trials.

The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) databases. These databases contain independent (from pharma companies) post-authorization studies focusing on safety and on benefit–risk, using available expertise and research experience across Europe.

Studies database is the E-Register of Studies (EU Post-authorization Studies (PAS) register) aims to provide a publicly accessible resource for the registration of pharmacoepidemiological and pharmacovigilance studies.

PSUR/PBRER repository is a single, central platform for PSURs/PBRERs and related documents to be used by all regulatory authorities and pharmaceutical companies in the EU. The use of the PSUR Repository is mandatory for all PSUR/PBRER submissions as of June 2016.

In addition to the EMA, each European country has its own national health authority (HA) or authorities that handle drug safety. They are often called “competent authorities (CA)” in EU regulatory jargon. The EU is still evolving and the Lisbon Treaty (2005) and other subsequent treaties have altered some of the basic structures and functions of the EU governing bodies. The EU remains still a work in progress. The interplay between the central authority (primarily in Brussels but with various agencies scattered throughout the EU, such as the EMA in London/Amsterdam and the European Central Bank in Frankfurt, Germany) and the individual countries is dynamic and often changing. Note also that the EMA does not have jurisdiction over food. The European Food Safety Authority in Parma, Italy handles those matters.

As noted, for drug safety, some functions are primarily centralized in the EMA and some remain in each member state. Some national authorities are very large and powerful and exert strong influence over smaller member states. This division and, in many cases, duplication of labor, as well as the multitude of languages involved in the EU, produce a challenge for safety reporting both for the pharmaceutical industry and for the member states themselves. Most of the work in drug safety is done at the international level in English, but, obviously, at the local level the national languages are still used. The comparison with other countries, particularly the US, where the drug safety function is clearly centralized, is striking. The closest analogy would be if each of the 50 states in the US had its own mini-FDA and used languages other than English. With the UK leaving the EU, there remain only two countries that have English as a native, national language: Malta and Eire (Ireland). There has been some talk of now using more French and German. “A voir”. “Bleibt abzuwarten”. We shall see.

In terms of pharmacovigilance, the EMA has largely harmonized along the lines of ICH. They have codified the pre-marketing requirements in a document known as Regulation (EU) No. 536/2014 of the European Parliament and of the Council of 16 April 2014 and the post-marketing requirements in Regulation (EU) Nos. 1235/2010 and 1027/2012. Each is discussed in detail below. Nonetheless, there are still differences, particularly for clinical trial pharmacovigilance, from country to country.

With the regulation updated in 2010, a major effort has been made for an accurate communication and transparency. Numerous tools and publications have been set up to comply with this commitment including the EMA web portal, the publishing of committee meetings’ agendas and minutes, ad hoc newsletters such as “What’s new in Pharmacovigilance QPPV Updates”, public hearings, etc.).

For more information on the EMA, see the following websites:

EMA website (http://www.ema.europa.eu/ema/);

EMA PV System Manual (http://www.ema.europa.eu/docs/en_GB/document_library/Other/2014/07/WC500170226.pdf);

Eudravigilance (https://eudravigilance.ema.europa.eu/);

PV Q&A web page (http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/q_and_a/q_and_a_detail_000135.jsp&mid=WC0b01ac058066e97a -).