Pharmacovigilance does not begin only when a medicinal product is placed on the market, nor is it limited to collecting and reporting suspected adverse reactions. It is a continuous activity that accompanies a medicinal product throughout its life cycle, contributing to the progressive understanding of its safety profile and the maintenance of a favourable benefit-risk balance.

A properly structured pharmacovigilance system enables organisations to gather information from different sources, identify new risks, meet regulatory requirements and implement timely measures to protect patients.

Before placing the product on the market

During clinical development, the available safety information is limited by the number of trial participants, the duration of exposure and the characteristics of the population studied.

At this stage, it is important to:

   - Identify important identified and potential risks;

   - Recognise gaps in the available information;

   - Define the necessary pharmacovigilance activities;

   - Plan additional measures to characterise or minimise risks;

   - Prepare the safety documentation required for the Marketing Authorisation Application.

The Risk Management Plan — RMP — is a central instrument for describing the medicinal product’s safety profile and defining the strategy for monitoring and minimising risks.

Preparing for product launch

Before a medicinal product is placed on the market, the pharmacovigilance system should be fully operational.

Preparations should include:

   - Clear allocation of responsibilities;

   - Appointment of the applicable pharmacovigilance responsible persons;

   - Establishment of procedures and communication channels;

   - Implementation of a contact line for receiving safety information;

   - Execution of pharmacovigilance agreements with partners;

   - Training of teams that may receive safety information;

   - Preparation of processes for case management, literature monitoring, signal management and reconciliations;

   - Establishment of business continuity arrangements.

These preparations are essential to ensure that relevant information is identified, forwarded, assessed and reported within the applicable timelines.

After placing the product on the market

Use of a medicinal product by a broader and more diverse population generates information that was not available during clinical development.

Following product launch, monitoring includes information from various sources, such as:

   - Spontaneous reports from healthcare professionals and patients;

   - Scientific and medical literature;

   - Clinical and non-interventional studies;

   - Patient support programmes;

   - Product quality complaints with a potential safety impact;

   - Medical information enquiries;

   - Regulatory authorities;

   - Commercial partners and distributors;

   - Databases and other surveillance systems.

The integrated analysis of these sources supports the identification of changes in the medicinal product’s safety profile.

Safety case management

Individual case safety report management involves more than recording an adverse reaction. Each case should be evaluated regarding its validity, seriousness, expectedness and the quality of the available information.

The process may include:

   - Receipt and triage of information;

   - Verification of the minimum validity criteria;

   - Medical coding;

   - Clinical assessment;

   - Follow-up for additional information;

   - Duplicate detection;

   - Quality control;

   - Submission to authorities and communication to partners;

   - Follow-up and archiving of documentation.

Consistent and timely case management is essential to ensure data quality and compliance with regulatory obligations.

Literature monitoring

Scientific literature is an important source of safety information. Monitoring should identify publications that may contain individual cases, new risks, changes in the frequency or severity of known risks and other information relevant to the benefit-risk balance.

The search strategy should be documented, reproducible and adapted to the active substances, medicinal products and territories covered.

Signal management

A safety signal is information suggesting a new potential association, or a new aspect of a known association, between a medicinal product and an event.

Signal management includes several stages:

   - Detection;

   - Validation;

   - Confirmation;

   - Analysis and prioritisation;

   - Assessment;

   - Recommendation of actions;

   - Documentation and follow-up.

A signal does not necessarily represent a confirmed risk. It indicates that the available information should be investigated to determine whether further action is required.

Periodic benefit-risk evaluation

The safety profile of a medicinal product should be reviewed periodically and whenever relevant new information becomes available.

Periodic safety reports — PSURs/PBRERs — provide an integrated evaluation of new safety data, exposure to the medicinal product, identified signals and the overall benefit-risk balance.

This evaluation may result in:

   - Updates to the product information;

   - Introduction of new warnings or precautions;

   - Implementation of additional risk-minimisation measures;

   - Performance of additional studies;

   - Updates to the RMP;

   - Targeted communication to healthcare professionals or patients.

System quality and oversight

Outsourcing pharmacovigilance activities does not remove the responsibilities of the Marketing Authorisation Holder. Appropriate oversight mechanisms must therefore be maintained.

These mechanisms may include:

   - Documented procedures;

   - Agreements with clearly defined responsibilities and timelines;

   - Performance indicators;

   - Periodic reconciliations;

   - Management of deviations and corrective and preventive actions;

   - Initial and continuous training;

   - Change control;

   - Risk-based audits;

   - Business continuity arrangements;

   - Periodic system review.

An effective quality system demonstrates that pharmacovigilance activities are performed consistently, remain traceable and comply with the applicable requirements.

An integrated approach to pharmacovigilance

Pharmacovigilance requires scientific knowledge, regulatory experience, robust processes and the ability to adapt. Integrating these capabilities makes it possible to transform information from different sources into decisions that support the safe and effective use of medicinal products.

Zemir Pharma Consulting provides support across different pharmacovigilance areas, from individual activities to integrated system management. Our services include QPPV and local contact services, case management, literature monitoring, signal management, PSUR/PBRER and RMP preparation, agreements, training, audits and inspection readiness.

Do you need support implementing, maintaining or strengthening your pharmacovigilance system? Contact Zemir Pharma Consulting to discuss a solution adapted to your portfolio and regulatory responsibilities.