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The Pharmacovigilance System Master File (PSMF) is a detailed description of all aspects related to how a pharmaceutical company is conducting pharmacovigilance. The purpose of the PSMF is first to provide the QPPV with a constantly updated oversight of the Pharmacovigilance System and in addition to ensure that all regulatory and company requirements are met. It is also a tool for planning and for conduct of internal audits of the separate components of the pharmacovigilance system. Lastly it is a tool for the competent authorities to get an overview of how the pharmacovigilance system works in a company that holds a marketing authorization in EU. This is for instance needed for the competent authorities when they are planning and conducting inspections. It is important to understand that while the PSMF is an essential tool for the QPPV in conducting the legal obligation to maintain oversight with a marketing authorization holder – it is the responsibility of the marketing authorization holder to ensure that the information provided in the PSMF i correct at all times. The information in the PSMF spans a great variety of information from procedures, policies, guidelines, staff training and compliance to IT systems structure and validation. The term Pharmacovigilance System Master File was introduced first in the 2010 revision of the 2001/83/EC European Union Directive identified as 2010/84/EU as well as Regulation 1235/2010 which jointly govern pharmacovigilance activities in the EU. In Regulation 1235/2010, Article 1(28e) the PSMF is defined as: “Pharmacovigilance system master file: A detailed description of the pharmacovigilance system used by the marketing authorization holder with respect to one or more authorized medicinal products.” It is the intention to have only one PSMF in a company, but there can be situations where two or more may be appropriate. Splitting the PSMF up in several separate PSMFs can be relevant if the company sells products of very different nature like for instance both pharma-products and vaccines. Normally it is much simpler to have only one PSMF. When setting up a PSMF it is important to go through the list of items that have to be included in detail and note where the information will come from and who is responsible for maintenance as a regulatory agency can request access to an updated version with short notice (max 7 days). You have to ensure that all components are continuously updated at predefined intervals. When an agency request the information there won’t be time to start updating it has to be ready pretty much immediately.

The SPOR system is delivering quality data management services for substances, products, organizations and referential (SPOR) to power EU regulatory activities. The four SPOR data management services are: Substance Management Services (SMS) Product Management Services (PMS) Organization Management Services (OMS)

A safety signal for which assessments have been completed. The decision and rationale for closing a signal should be documented. If further evidence becomes available, the signal can be re-assessed.

All relevant safety information contained in the CCDS prepared by the MAH / pharmaceutical company and which the MAH requires to be listed in all countries where the company markets the product, except when the local regulatory authority specifically requires a modification. It is the reference information by which listed and unlisted events are determined for the purpose of periodic reporting for marketed products.

An independent section of the Investigator’s Brochure (IB), identical in structure to the Company Core Safety Information (CCSI), that contains a summary of all relevant safety information that is described in more detail within the main body of the IB. It is the reference safety document that determines whether an adverse drug reaction is expected or unexpected in the pre-market phase.

DMEs are serious and rare medical events that are often causally associated with drugs across multiple pharmacological / therapeutic classes. Therefore, evenasmall number of reports of suchanevent can trigger a signal and requiresspecial attention.The list is defined by the European Medicines Agency and the most recent list can be found here https://www.ema.europa.eu/documents/other/designated-medical-event-dme-list_en.xlsx

A compilation of the clinical and nonclinical data on the investigational product(s), which is relevant to the study of the investigational product(s) in human subjects.

A signal that requires continued monitoring until sufficient evidence becomes available to either confirm or refute the signal. The decision and rationale to justify closing the signal should be documented.

An undesirable outcome for which there is sufficient scientific evidence that it is caused by the medicinal product.Examples of identified risks include: an adverse reaction adequately demonstrated in non-clinical studies and confirmed by clinical data; an adverse reaction observed in well-designed clinical trials or epidemiological studies for which the magnitude of difference , compared with the comparator group (placebo or active substance or unexposed group)suggests a causal relationship; an adverse reaction suggested by a number of well-documented spontaneous reports where causality is strongly supported by temporal relationship and biological plausibility such as anaphylactic reactions or application site reactions

An undesirable outcome for which there is scientific evidence to suggest the possibility of a causal relationship with the medicinal product, but there is currently insufficient evidence to conclude that the association is causal. Examples of potential risks include: non-clinical safety concerns that have not been observed or resolved in clinical studies; adverse events observed in clinical trials or epidemiological studies for which the magnitude of difference, compared with the comparator group (placebo or active substance or unexposed group)raises suspicion of, but is not substantial enough to conclusively determine a causal relationship; a signal arising from a spontaneous reporting system; an event which is known to be associated with other products of the same class or which could be expected to occur based on the properties of the medicinal product.

A set of activities performed to determine whether there are new risks associated with an active substance or medicinal product, or whether known risks have changed, as well as any related recommendations, decisions, communications and tracking. These activities are based on an examination of individual case safety reports (ICSRs), aggregated data from active surveillance systems or studies, scientific literature information or other data sources.

A plan that describes the method(s) for signal assessment, including data sources, search criteria (and where applicable, the specific MedDRA terms or Standardized MedDRA Queries), and analytical approaches.

A living document which describes the Signal Strategy of a product, including which sources are reviewed, at which periodicity, as well as the rationale and focus of review.The Signal Strategy is updated throughout the life cycle of the product to ensure the most suitable Signal Strategy is applied at all times to monitor the product safety profile.

The process of looking for and / or identifying signals using data from any source.

Any information that arises from one or multiple sources (including observations and experiments), which suggests a new potentially causal association or a new aspect of a known association between an intervention and an event or set of events

The process of further evaluating a validated signal taking into account all available evidence, to determine whether there are new risks causally associated with the active substance or medicinal product or whether known risks have changed.

A safety issue considered by a MAH / pharmaceutical company to require urgent attention by the Competent Authority (CA) because of the potential major impact on the risk-benefit profile of the medicinal product and / or on patient or public health, and the potential need for prompt regulatory action and communication to patients and healthcare professionals.

A detailed description of the risk management system, including.

a) an identification or characterization of the safety profile of the medicinal product(s) concerned,

b) an indication of how to characterize further the safety profile of the medicinal product(s) concerned,

c) a documentation of measures to prevent or minimize the risks associated with the medicinal product, including an assessment of the effectiveness of those interventions, and

d) a documentation of post-authorization obligations that have been imposed as a condition of the marketing authorization.