What is Pharmacovigilance?

WHO Definition

Pharmacovigilance (PV) is the detection, assessment, understanding and prevention of adverse effects or any other medicine-related (WHO) problem.

Mission Statement of GPV

To provide high quality science-based proactive risk management strategies and operational excellence in a fully compliant global pharmacovigilance system with the ultimate goal to safeguard patients´ well-being and thus protect the company.

Pharmacovigilance is a science contributing to the protection of patients and public health.

We need an efficient Pharmacovigilance system to...

Fulfill our manufacturer's responsibility towards patients and health care professionals.
Fulfill all regulatory reporting requirements worldwide.
Anticipate or minimize risks and to take appropriate measures accordingly.

The European Medicines Agency's (EMA) main responsibility is the protection and promotion of public and animal health, through the evaluation and supervision of medicines for human and veterinary use. But also:

The scientific evaluation of applications for EU marketing authorizations for human and veterinary medicines in the centralized procedure.
Coordinating the EU's safety-monitoring or pharmacovigilance system for medicines.
Coordinating inspections with the assessment of marketing-authorization applications.

FDA is responsible for protecting the public health by assuring:

Safety
Efficacy
Security
WHO is the directing and coordinating authority for health within the United Nations system.
Responsible for providing leadership on global health matters, shaping the health research agenda, setting norms and standards, articulating evidence-based policy options, providing technical support to countries and monitoring and assessing health trends.
The World Health Organization set up its international drug monitoring program after the thalidomide incident. Since 1978 the Program has been carried out by Uppsala Monitoring Centre (UMC) in Sweden.

Uppsala Monitoring Centre priorities are:

The safety of patients and the safe and effective use of medicines in every part of the world.
To coordinate the WHO Program for International Drug Monitoring and its more than 100 member countries.
To collect, assess and communicate information from member countries about the benefits, harms and risks of drugs and other substances used in medicine to improve patient therapy and public health worldwide.
To collaborate with member countries in the development and practice of the science of pharmacovigilance.

The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) brings together the regulatory authorities and pharmaceutical industry of EU/EEA , Japan and the US to discuss scientific and technical aspects of drug registration.

ICH Categories

Quality Guidelines Harmonization achievements in the Quality area based on Good Manufacturing Practice (GMP) risk management.
Safety Guidelines to uncover potential risks like carcinogenicity, genotoxicity and nephrotoxicity.
Efficacy Guidelines Design, conduct, safety and reporting of clinical trials.
Multidisciplinary Guidelines Cross-cutting topics which do not fit uniquely into one of the Quality, Safety and Efficacy categories. It includes the ICH medical terminology.

Local PV legislation

In each country there are legal requirements which have to be followed.
Local Pharmacovigilance personnel must be familiarized with the local requirements.
Global PV personnel must evaluate the local requirements for potential global impact (e.g. setting up reporting rules for expedited case reporting to Health Authorities, writing of aggregated safety reports).

Quality Documents are essential to ensure consistency in processes, and must be:

Clear and concise
Complete
Consistent
Controlled
Current

A BI employee must read the Quality Documents, based on global and local Curricula defining the mandatory Quality Documents per function. In many Countries/departments the Quality Documents are distributed via Learning Once Source (LOS). It is worked on a global roll out plan.

The overall quality objectives of a pharmacovigilance system are:

Complying with the legal requirements
Preventing harm from adverse reactions in humans arising from the use of authorised medicinal products
Promoting the safe and effective use of medicinal products
Contributing to the protection of patients’ and public health

Quality and Compliance

Quality Planning
Quality Adherence
Quality Control/ Assurance
Quality Improvement

The Quality System is an integral part of the pharmacovigilance system and therefore the EU-QPPV has to have the overview of the quality system.
Clear responsibilities and communication lines have to be established so that the EU-QPPV can fulfil her/his tasks.
The main function of the quality system is to monitor the implemented processes and to conduct regular quality controls.

ALSO READ: Pharmacovigilance: Questions and Answers

What has to be monitored?

Processing and reporting of Individual Case Safety Reports (ICSR)
Signal Management
Risk Management System described in the Risk Management Plan (RMP)
Preparation and reporting of Periodic Safety Reports
Implementation of safety variations and communication of safety concerns
Communicating information to patients and healthcare professionals about changes to the risk-benefit balance of products
Business continuity plans

Monitoring of processes

The Quality System covers also :
The SOP System
The document management system
PV Training
Facilities and systems
Personnel and Resources
Audit- and inspection reports

Corrective and Preventive Action

If a non compliance is detected, GPV Quality & Compliance must be informed in order to improve and correct the processing and avoid the occurrence of an error or a discrepancy and to perform:

An impact and root cause analysis to identify the underlying reason
And define corrective and preventive actions (CAPA)

Corrective Action (CA)- Action to eliminate the root cause of a detected non-compliance or other undesirable situation; to prevent the recurrence of the non-compliance

Preventive Action (PA)- Action to eliminate the root cause of a potential non-compliance or other undesirable situation; to prevent the occurrence of a non-compliance

Pharmacovigilance System Master File (PSMF)

PSMF is a detailed description of the Pharmacovigilance System used by the marketing authorisation holder with regard to one or more authorised products.

BI is legally required as MAH for medicinal products authorised in the EU to maintain and make available upon request a Pharmacovigilance System Master (PSMF) File describing the Global PV System operated by BI.

ALSO READ: Pharmacovigilance System Master File (PSMF)

Contributes to the appropriate management and improvement of the global pharmacovigilance system

PSMF Supports

Planning and conduct of Audits
Preparation of inspection
Competent authorities during Marketing Authorization procedures and post-marketing.

Documentation Management System

IDEA (International Document management and Electronic Archiving) is BI's Approach to Electronic Document Management.

IDEA for CON is the system for Quality Documents .A viewer self-training is to be done within the first days after job start (precondition for access to LOS).
IDEA for GEN is the system for filing Official Documents that are to be filed either due to regulatory requirements or business needs (record retention).
BIRDS is the Boehringer Ingelheim document management system for submission documentation to the Authorities. All submission chain activities are unified in this system. Periodic Reports are also stored here.

Training Management System

LOS (Learning One Source) system is a learning management system. It is used to administer, monitor and oversee employee training of all types, e.g. self-training of Quality Documents and other controlled documents or e-learnings.

Tasks:

Learning items based on Curricula are automatically assigned to user depending on the function, and must be completed on or before due date.
E-learnings and Quality Documents are to be confirmed per e-signature after completion.
New employees have a timeline of 42 days for completion of Quality Documents trainings as of access to LOS. For e-learnings the timeline is specified per training item.

GDSS System

GDSS is a virtual system which consists of several individual systems for Adverse Event processing and reporting.

ARISg Adverse Reaction Information System global supports the collection, evaluation, reporting and analyses of adverse event data in accordance with international regulations.

E2B E2B module supports the standardized electronic data exchange between the Marketing Authorization Holder (MAH) and the regulatory authorities as laid down in ICH –Multi-disciplinary Group 2 Expert Working Group documents. BI is an E2B gateway user.

System which allows:

Automated and manual selection of specific Individual Case Safety Reports (ICSRs) for transmission to specific recipients
Customized mapping of ICSR data from ARISg to the E2B file
Tracking of receipt and acceptance of transmitted E2B files

DSIS is the data retrieval system for GPV.

This environment includes an Ad Hoc and Standard reports environment that will retrieve data primarily from the data warehouse, and is used to address any internal/external requests for aggregated data.

Signal Detection Risk Management Therapeutic Area Physicians will receive data from Empirica on a pre-defined basis to detect signals of potential new adverse events for BI drugs. RM TA Physician will evaluate the signals, and appropriate actions will be implemented.

Detect Database

Data Entry Standards for the Entry of Suspect Drugs in Clinical Trials.
Contains all the information required for entering a clinical trial case into ARISg
The information is sorted by trial number.

Importance of Pharmacovigilance

Pharmacovigilance (PV) is one of the fundamental wings of the healthcare system and pharmaceutical companies. As per WHO, Pharmacovigilance is a branch of pharmacological science comprising the activities related to the detection, assessment, understanding, and prevention of adverse effects of the drug. Fundamentally, it is aimed to ensure guaranteed patient safety and is considered as an arm of patient care.

Pharmacovigilance is also extended to vaccines, biological, medical devices, herbal drugs, veterinary medicines, blood, and blood-related products.