Cobert's Manual Of Drug Safety And Pharmacovigilance (Third Edition). William Gregory
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The PRAC’s primary duties include evaluation of potential signals arising from spontaneous reports and or PSURs/PBRERs, advising on risk and risk management (including regula-tory options) and monitoring regulatory actions. Their domain is largely in the post-approval area, but they do have authority for drugs under study.
The PRAC’s member contact information and declarations of interest are published on the EMA website. The PRAC includes independent experts from all EU member states in pharmacoepidemiology, clinical pharmacology, biologics, signal detection, risk communication, and vaccine vigilance. The Detailed Rules for PRAC procedures have been published (http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000537.jsp&mid=WC0b01ac058058cb18).
A yearly PRAC work plan is published during the first quarter of the year. They issue work programs in advance of their monthly meetings and publish meeting highlights and meeting minutes which usually involve safety issues on specific drugs. The meeting highlights are posted on the EMA website the day after the meeting and the minutes are published after PRAC’s about a month later (http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000537.jsp).
An analysis of the first 18 months of PRAC activities has been published and concluded positively: “Early signs, … based on process indicators such as those reported here for RMPs, ADRs, signals, PSURs and EU Pharmacovigilance Referrals, point to more systematic and proportionate risk management planning, the promotion of reporting (including from patients), greater coordination of real-time signal management, faster assessment and decision-making, and thus strengthening of the link between pharmacovigilance assessments and regulatory actions such as labelling changes to optimize safe and effective drug use.”1
Post-marketing PV EU Regulation
Four different kinds of documents exist at the EU level as follows:
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):
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