Читать книгу Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition) - William Gregory - Страница 110

Four different kinds of documents exist at the EU level as follows:

Regulations: These are mandatory requirements and are applicable in all EU countries as written. They are translated exactly into national languages but cannot be altered. They are usually high-level documents.

Directives: These, too, are mandatory requirements as well, but can vary in each EU country depending on the local translation/adaptation. Often the member states have up to three years to put these directives into effect as national legislation.

Guidances/Practices/Decisions: These are also mandatory requirements. They are more focused on a specific topic or theme. Note that in the US, the term guidance or guideline represents FDA’s current thinking on a topic but, unlike the EU, they are not mandatory.

Recommendation/Opinion: These are not mandatory and are usually more general documents (e.g., healthcare policy, providing priorities).

The previous legally-binding document covering post-authorization PV was called EudraLex Volume 9A. It covered all EU PV Regulations. It was amended in 2010 and since then thousands of pages of documents have been issued to update the EU PV Regulation. This new legislation aims to rationalize, simplify and improve workflow, to stop useless tasks, to be more consistent, to focus on risks, to improve transparency to all stakeholders, to help ensure that commitments made are actually done and to involve patients and the public.

It is impossible to provide here an exhaustive list of these numerous documents. Here is list of the key ones (see http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000258.jsp&mid=WC0b01ac05800241de):

Regulations (EU) Nos. 1235/2010 and 1027/2012

Directives 2010/84/EU and 2012/26/EU

Good Vigilance Practices (GVP)

Note 1: Modules XI, XII, XIII and XIV have been cancelled. Their content has been incorporated into other documents.

Note 2: These are living documents. They are periodically updated, submitted to PV stakeholders (including the pharmaceutical industry) for comments/proposals, validated, and then published.

These documents require the EMA, the member states, and others to set up systems to handle the collection, verification, exchange, and presentation of adverse reaction reports within the European Union but also to identify safety signals and manage risks.

Table 1. EU Good Pharmacovigilance Practice (GVP) Modules and Annexes.

The roles and responsibilities of the MAH are spelled out and require that an appropriate system of PV is put in place by the MAH. All information regarding the benefit–risk profile must be promptly and fully sent to the competent authorities. And most critically, it describes the role of the EU Qualified Person for Pharmacovigilance (EU QPPV), to be appointed by the MAH and to be continuously (24/7) available for safety matters. In brief, the QPPV establishes and maintains the PV system, has an overview of all the products and safety issues pending, and makes sure all safety functions are handled properly. The QPPV’s roles are discussed in detail elsewhere in this manual. The QPPV must ensure that all suspected ADRs are collected, collated, reported, and accessible within the EU. The MAH must prepare, update, and have available a “Pharmacovigilance System Master File” (PSMF). Requirements for risk management systems, expedited reporting, PSURs/PBRERs, special situations, databases, documentation, company post-marketing safety studies, quality assurance/control and regulatory matters are also addressed (Regulations and Directives). These topics are covered in detail in this manual in the individual chapters.

Specific obligations for member states’ national health agencies are similar to what is required for pharmaceutical industry; how PV is to be done, handling of ICSRs, PSURs/PBRERs, signal detection, medication errors, benefit–risk analyses, communication, data exchange, crisis management plans relating to safety matters, inspections, rapid-alert and non-urgent information communication system, how referrals to the EMA are to be done.

The Practices Annexes to the Modules include a glossary, abbreviations, terminology, references to guidelines and templates for the EU Risk Management Plan, the PSUR/PBRER sections, and distribution requirements for reporting to competent authorities.

In summary, this is a complete and well-prepared set of documents that shapes a consistent PV System at the EU level. The documents are rich in explanations and background and anyone in the field of PV, whether in the EU or elsewhere, should read and be familiar with these documents. Many of the principles and procedures are used throughout the rest of the world as they are based on the common seminal antecedent documents of PV, namely, the Council for International Organizations of Medical Sciences (CIOMS) and ICH documents.