Pharmacovigilance 8th Sem Book Pdf

[Francesca Cruiz]

TheEU pharmacovigilance system is one of the most advanced and comprehensive in the world and represents a robust and transparent instrument to ensure a high level of public health protection throughout the EU. It provides a system for monitoring the safety of medicines on the European market through prevention, detection and assessment of adverse reactions to medicines, including those due to medication errors and overdose. In addition, patients can report adverse drug reactions directly to the competent authorities.

The legal framework of pharmacovigilance for medicines marketed within the EU is provided for in Regulation (EC) No 726/2004 with respect to EU authorised medicinal products and in Directive 2001/83/EC with respect to nationally authorised medicinal products (including those authorised through the mutual recognition and decentralised systems).

In addition, Commission Implementing Regulation (EU) No 520/2012 outlines the practical details to be respected by marketing authorisation holders, national competent authorities and the EMA and Commission Commission Delegated Regulation (EU) No 357/2014 on post-authorisation efficacy studies specifies the situations in which such studies may be required.

The Black Symbol identifies medicinal products that are subject to additional monitoring. The black symbol allows patients and healthcare professionals to identify these products, and the accompanying text encourages them to report unexpected adverse reactions through national reporting systems.

In 2019, the Commission published a report on the experience of monitoring the safety of certain medicines. The report, which is based on experience reported by EMA and national authorities, gives an overview of the experience between 2013-2016 for medicines that included a black triangle in their product information and are being monitored particularly closely, generally because there is less information available about them.

Before a medicine is authorised for use, evidence of its safety and efficacy is limited to the results from clinical trials, where patients are selected carefully and followed up very closely under controlled conditions. This means that at the time of a medicine's authorisation, it has been tested in a relatively small number of selected patients for a limited length of time.

EU law therefore requires each marketing authorisation holder, national competent authority and EMA to operate a pharmacovigilance system. The overall EU pharmacovigilance system operates through cooperation between the EU Member States, EMA and the European Commission. In some Member States, regional centres are in place under the coordination of the national competent authority.

EMA coordinates pharmacovigilance in the EU and operates services and processes in line with EU legislation. The EMA pharmacovigilance system manual describes how EMA performs, monitors and reports on its pharmacovigilance duties for human medicines:

EMA's Pharmacovigilance Risk Assessment Committee (PRAC) is responsible for assessing and monitoring the safety of human medicines. It is made up of experts in medicines safety from regulatory authorities in Member States, plus scientific experts and representatives of patients and healthcare professionals nominated by the European Commission.

The Agency is responsible for developing and maintaining EudraVigilance, a system for managing and analysing information on suspected adverse reactions to medicines authorised in the European Economic Area (EEA).

EudraVigilance is a single repository for reports of suspected adverse reactions seen in healthcare practice and clinical trials. It is used by Member states, the Agency and industry.

The pharmacovigilance plan for COVID-19 vaccines sets out how EMA and the national competent authorities in the EU Member States identify and evaluate any new information that arises promptly, including any safety signals that are relevant for the benefit-risk balance of these vaccines:

Also know as the PRAC impact strategy, it aims to shift the focus of pharmacovigilance towards the activities and regulatory tools that are most relevant to patients and make the greatest difference in daily healthcare.

The PRAC has published a checklist with criteria to prioritise collaborative impact research for identifying and selecting safety topics discussed at the PRAC which require the generation of data to monitor the impact of regulatory interventions:

Follow the journey of a medicine for human use assessed by EMA in this interactive timeline. It explains all stages from initial research to patient access, including how EMA supports medicine development, assesses the benefits and risks and monitors the safety of medicines.

Information received from patients and healthcare providers via pharmacovigilance agreements, as well as other sources such as the medical literature, plays a critical role in providing the data necessary for pharmacovigilance to take place. In order to market or to test a pharmaceutical product in most countries, adverse event data received by the license holder (usually a pharmaceutical company) must be submitted to the local drug regulatory authority. (See Adverse event reporting below.)

Ultimately, pharmacovigilance is concerned with identifying the hazards associated with pharmaceutical products and with minimizing the risk of any harm that may come to patients. Companies must conduct a comprehensive drug safety and pharmacovigilance audit to assess their compliance with worldwide laws, regulations, and guidance.[4]

Pharmacovigilance has its own unique terminology that is important to understand. Most of the following terms are used within this article and are peculiar to drug safety, although some are used by other disciplines within the pharmaceutical sciences as well.

The activity that is most commonly associated with pharmacovigilance (PV), and which consumes a significant number of resources for drug regulatory authorities (or similar government agencies) and drug safety departments in pharmaceutical companies, is that of adverse event reporting. Adverse event (AE) reporting involves the receipt, triage, data entry, assessment, distribution, reporting (if appropriate), and archiving of AE data and documentation. The source of AE reports may include: spontaneous reports from healthcare professionals or patients (or other intermediaries); solicited reports from patient support programs; reports from clinical or post-marketing studies; reports from literature sources; reports from the media (including social media and websites); and reports reported to drug regulatory authorities themselves. For pharmaceutical companies, AE reporting is a regulatory requirement in most countries. AE reporting also provides data to these companies and drug regulatory authorities that play a key role in assessing the risk-benefit profile of a given drug. The following are several facets of AE reporting:

One of the fundamental principles of adverse event reporting is the determination of what constitutes an individual case safety report. During the triage phase of a potential adverse event report, it is important to determine if the "four elements" of a valid individual case safety report are present: (1) an identifiable patient, (2) an identifiable reporter, (3) a suspect drug, and (4) an adverse event.

If one or more of these four elements is missing, the case is not a valid individual case safety report. Although there are no exceptions to this rule there may be circumstances that may require a judgment call. For example, the term "identifiable" may not always be clear-cut. If a physician reports that he/she has a patient X taking drug Y who experienced Z (an AE), but refuses to provide any specifics about patient X, the report is still a valid case even though the patient is not specifically identified. This is because the reporter has first-hand information about the patient and is identifiable (i.e. a real person) to the physician. Identifiability is important so as not only to prevent duplicate reporting of the same case, but also to permit follow-up for additional information.

The concept of identifiability also applies to the other three elements. Although uncommon, it is not unheard of for fictitious adverse event "cases" to be reported to a company by an anonymous individual (or on behalf of an anonymous patient, disgruntled employee, or former employee) trying to damage the company's reputation or a company's product. In these and all other situations, the source of the report should be ascertained (if possible). But anonymous reporting is also important, as whistle blower protection is not granted in all countries. In general, the drug must also be specifically named. Note that in different countries and regions of the world, drugs are sold under various tradenames. In addition, there are a large number of generics which may be mistaken for the trade product. Finally, there is the problem of counterfeit drugs producing adverse events. If at all possible, it is best to try to obtain the sample which induced the adverse event, and send it to either the European Medicines Agency, FDA or other government agency responsible for investigating AE reports.

If a reporter can't recall the name of the drug they were taking when they experienced an adverse event, this would not be a valid case. This concept also applies to adverse events. If a patient states that they experienced "symptoms", but cannot be more specific, such a report might technically be considered valid, but will be of very limited value to the pharmacovigilance department of the company or to drug regulatory authorities.[6]

Adverse event coding is the process by which information from an AE reporter, called the "verbatim", is coded using standardized terminology from a medical coding dictionary, such as MedDRA (the most commonly used medical coding dictionary). The purpose of medical coding is to convert adverse event information into terminology that can be readily identified and analyzed. For instance, Patient 1 may report that they had experienced "a very bad headache that felt like their head was being hit by a hammer" [Verbatim 1] when taking Drug X. Or, Patient 2 may report that they had experienced a "slight, throbbing headache that occurred daily at about two in the afternoon" [Verbatim 2] while taking Drug Y. Neither Verbatim 1 nor Verbatim 2 will exactly match a code in the MedDRA coding dictionary. However, both quotes describe different manifestations of a headache. As a result, in this example both quotes would be coded as PT Headache (PT = Preferred Term in MedDRA).[8]

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