Development and verification of pharmacovigilance documents

The DOCLINX team provides services for the development and review of pharmacovigilance documents.

We will develop for your company or conduct an expert assessment of the following documents:

• Pharmacovigilance System Master File (PSMF) — a detailed description of the pharmacovigilance system used by the marketing authorization holder for data on one or more registered medicinal products.
• Risk Management Plan — a detailed description of the risk management system.
• Periodic Safety Update Report (PSUR) — a report for presenting the benefit-risk assessment of a medicinal product by the marketing authorization holder during a specific period of time during the postauthorization phase.

Why do pharmaceutical companies need to create and maintain a pharmacovigilance system?

The objectives of pharmacovigilance are:

• prevention of adverse consequences of adverse reactions in humans that develop after the use of registered medicinal products in accordance or not in accordance with the conditions of the marketing authorization or as a result of exposure related to professional activities;
• ensuring the safe and effective use of medicinal products, in particular by providing timely information on the safety of medicines to patients, healthcare professionals, and the public.

Medicinal products in circulation are subject to monitoring of efficacy and safety in order to identify possible negative consequences of their use, individual intolerance, and to warn medical professionals against the use of such medicinal products.

Subjects involved in the circulation of medicinal products are obliged to report to the authorized executive body on side effects, adverse reactions, serious adverse reactions, unexpected adverse reactions when using medicinal products, individual intolerance, lack of efficacy of medicinal products, as well as other facts and circumstances that pose a threat to human life or health when using medicinal products and identified at all stages of the circulation of medicinal products.

For what purpose is it necessary to create and maintain a Pharmacovigilance System Master File?

The Pharmacovigilance System Master File is intended to describe the pharmacovigilance system and document its compliance with the requirements of the EAEU bodies and the legislation of member states. The Pharmacovigilance System Master File allows for proper planning and conducting of audits of the pharmacovigilance system by the marketing authorization holder, as well as inspections by authorized bodies. The Pharmacovigilance System Master File includes an overview of the marketing authorization holder's pharmacovigilance system, which allows for its overall assessment by authorized bodies at the registration and postregistration stages.

The compilation of the Pharmacovigilance System Master File and the updating of the information contained in it allow the marketing authorization holder and the qualified person for pharmacovigilance to:

• ensure that the pharmacovigilance system is implemented in accordance with the requirements of the Union bodies and the legislation of member states;
• confirm the system's compliance with current requirements;
• obtain information about system deficiencies or identify non-compliance with requirements;
• obtain information about risks or ineffectiveness in carrying out certain areas of pharmacovigilance activities.

The use of the Pharmacovigilance System Master File contributes to the optimization of the proper system management process and the improvement of the pharmacovigilance system. Requirements for the submission of a brief description of the marketing authorization holder's pharmacovigilance system, the submission of the Pharmacovigilance System Master File, as well as the chronology (sequence) of changes facilitate the planning and effective conduct of inspections by the authorized bodies of member states based on the risk assessment method.

What is the purpose of a Risk Management Plan?

The main purpose of the risk management process is to ensure the use of a medicinal product with the maximum possible benefit of using the medicinal product over the risks for each patient and for target populations as a whole. Proper planning of the risk management system should be ensured throughout the entire life cycle of the medicinal product. The risk management system should be proportionate to the identified and potential risks of using the medicinal product, as well as the need to obtain safety data at the post-registration stage.

The risk management process consists of the following interrelated and repetitive stages:

• characterization of the safety profile of the medicinal product with the identification of important identified risks, important potential risks and missing information, as well as aspects of the safety profile that require active management measures or further study (safety specification);
• planning pharmacovigilance activities to characterize risks and identify new risks, as well as increasing the overall level of knowledge about the safety profile of the medicinal product (pharmacovigilance plan);
• planning and implementation of risk minimization activities, as well as evaluating the effectiveness of these activities (risk minimization plan).

Since safety data accumulates during the post-registration phase with an increase in knowledge about the safety profile of the medicinal product, appropriate changes are made to the risk management plan.

At the stage of registration of a medicinal product, as well as at other stages of the life cycle of a medicinal product, necessary additional measures may be identified to study aspects of safety or efficacy, or additional risk minimization measures to ensure the use of the medicinal product when the benefit outweighs the risk, which should be included in the risk management plan and implemented by the marketing authorization holder.

What is the purpose of a Periodic Safety Update Report?

The Periodic Safety Update Report is a pharmacovigilance document that allows the marketing authorization holder to present an assessment of the benefit-risk ratio of a medicinal product at certain stages of the postregistration period.

The authorized bodies of the EAEU member states should evaluate the Periodic Safety Update Report to establish possible newly identified risks and their impact on the benefit-risk assessment of the medicinal product. Based on the results of the evaluation of the Periodic Safety Update Report, the authorized body of the member state determines the need for further studies of the safety or efficacy of the medicinal product, the application of certain actions regarding the registration status of the medicinal product, or making changes to its general characteristics in order to ensure its use when the benefit outweighs the risk.

The main purpose of the Periodic Safety Update Report is to present a comprehensive and critical analysis of the benefit-risk ratio of the medicinal product, taking into account all new safety data and the cumulative impact of this data on the safety or efficacy profile of the medicinal product. The Periodic Safety Update Report is a tool for post-registration assessment of the benefit-risk ratio of a medicinal product at certain stages of its life cycle.

The Periodic Safety Update Report is not intended for the immediate presentation of important safety or efficacy information, nor is it a tool for identifying new safety information. The cumulative assessment of safety and efficacy data in the Periodic Safety Update Report may lead to the identification of new aspects of the safety or efficacy profile of the medicinal product.

The marketing authorization holder must constantly evaluate and analyze the impact of new data on the benefit-risk ratio, reassess this indicator, and determine the need to optimize the benefit-risk ratio by introducing effective risk management and minimization measures when new safety information is identified for the medicinal product during its post-registration use.

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Regulatory acts

• Decision of the EEC Council dated 03.11.2016 No. 87 "On approval of the Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union"
• Federal Law of 12.04.2010 No. 61-FZ "On the Circulation of Medicinal Products"
• Order of Roszdravnadzor dated 15.02.2017 No. 1071 "On approval of the Procedure for implementing pharmacovigilance"
• Order of the Ministry of Health of Russia dated 14.11.2018 No. 777n "On approval of the Procedure for suspending the use of a medicinal product for medical use"