General Pharmacy

Pharmacovigilance: A Worldwide Master Key for Drug Safety

Monitoring
Jeetu G, Anusha G1
Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka,
1
Institute of Professional Studies College of Pharmacy, Gwalior, Madhya Pradesh, India

Address for correspondence: Mr. Jeetu Gangil; E-mail: [email protected]

ABSTRACT

Pharmacovigilance is like a sunshade to describe the processes for monitoring and evaluating ADRs and it
is a key component of effective drug regulation systems, clinical practice and public health programmes. The
number of Adverse Drug Reactions (ADRs) reported resulted in an increase in the volume of data handled, and
to understand the pharmacovigilance, a high level of expertise is required to rapidly detect drug risks as well
as to defend the product against an inappropriate removal. The current global network of pharmacovigilance
centers, coordinated by the Uppsala Monitoring Centre, would be strengthened by an independent system of
review. This would consider litigious and important drug safety issues that have the potential to affect public
health adversely beyond national boundaries. Recently, pharmacovigilance has been confined, mainly to
detect adverse drug events that were previously either unknown or poorly understood. Pharmacovigilance is
an important and integral part of clinical research and these days it is growing in many countries. Today many
pharmacovigilance centers are working for drug safety monitoring in this global pitch, however, at the turn of
the millennium pharmacovigilance faces major challenges in aspect of better safety and monitoring of drugs. In
this review we will discuss about drug safety, worldwide pharmacovigilance centers and their role, benefits and
challenges of pharmacovigilance and its future consideration in healthcare sectors.

Key words: Drug safety, erice declaration, pharmacovigilance

DOI: 10.4103/0975-1483.66802

INTRODUCTION of illness, disability and even death. In some countries,

adverse drug reactions (ADRs) rank among the top 10
Drug safety and pharmacovigilance remains a dynamic leading causes of mortality. In order to prevent or to
clinical and scientific discipline. Pharmacovigilance is reduce harm to patients and thus improve public health,
defined by the World Health Organization (WHO) as ‘the mechanisms for evaluating and monitoring the safety of
science and activities relating to the detection, assessment, medicines in clinical use are vital.[1] Pharmacovigilance
understanding and prevention of adverse effects or any programs in the next 10 years, describe in brief the potential
other drug-related problem’;[1] it plays a vital role in ensuring implications of such trends on the evolution of the science.
that doctors, together with the patient, have enough These days pharmacovigilance is facing lots of challenges
information to make a decision when it comes to choosing to develop better health care systems in this global pitch.
a drug for treatment.[2] However, despite all their benefits, Major challenges are globalization, web-based sales and
evidence continues to get those bigger adverse reactions to information, broader safety concerns, public health versus
medicines which are common, yet often preventable, cause pharmaceutical industry economic growth, monitoring of

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established products, developing and emerging countries, The National Pharmacovigilance Centers: National Centers have
attitudes and perceptions to benefit and harm, outcomes played a significant role in increasing public awareness of
and impact.[3] drug safety. This development is partly attributable to the
fact that many national and regional centers are housed
HISTORICAL PERSPECTIVES OF WHO - DRUG within hospitals, medical schools or poison and drug
SAFETY MONITORING information centers, rather than within the confines of
a drug regulatory authority. Major centers in developed
In 2002, more than 65 countries have their own countries have established active surveillance programmes
pharmacovigilance centers. Membership of the WHO using record linkage and prescription event monitoring
for International Drug Monitoring is coordinated by systems (PEM) to collect epidemiological information
the WHO Collaborating Centre for International Drug on adverse reactions to specific drugs. Such systems have
Monitoring, known as the Uppsala Monitoring Centre already been implemented in New Zealand, the United
(UMC). Pharmacovigilance is now firmly based on sound Kingdom, Sweden and the United States of America. The
scientific principles and is integral to effective clinical entire cost of a pharmacovigilance system, compared with
practice. The discipline needs to develop further to meet the national expenditure on medicines or the cost of ADRs
public expectations and the demands of modern public to the nation is very small indeed.[9,10]
health. The Sixteenth World Health Assembly adopted a
resolution (WHA 16.36)[5] that reaffirmed the need for early Hospitals and Academia: A number of medical institutions
action in regard to rapid dissemination of information on have developed adverse reaction and medication error close
adverse drug reactions and led later to creation of the WHO watch systems in their clinics, wards and emergency rooms.
Pilot Research Project for International Drug Monitoring. Case-control studies and other pharmacoepidemiological
The purpose of this was to develop a system, applicable methods have increasingly been used to estimate the harm
internationally, for detecting previously unknown or poorly associated with medicines once they have been marketed.
understood adverse effects of medicines.[6] Academic centers of pharmacology and pharmacy have
played an important role through teaching, training,
WORLDWIDE SOLDIERS OF
research, policy development, clinical research, ethics
PHARMACOVIGILANCE
committees (institutional review boards) and the clinical
services they provide.[11-13]
A complex and vital relationship exists between wide ranges
of partners in the practice of drug safety monitoring. These Health Professionals: Originally physicians were the only
partners must jointly anticipate, understand and respond professionals invited to report as judging whether disease
to the continually increasing demands and expectations of or medicine causes a certain symptom by exercising the
the public, health administrators, policy officials, politicians skill of differential diagnosis. Today, different categories
and health professionals. of health professionals will observe different kinds of drug
related problems.[14,15]
The Quality Assurance and Safety: The team is a part of the
Department of Essential Drugs and Medicines Policy, Patients: Only a patient knows the actual benefit and
within the WHO Health Technology and Pharmaceuticals harm of a medicine taken. Direct patient participation
cluster. The purpose of the department is to help save lives in the reporting of drug related problems will increase
and improve health by closing the huge gap between the the efficiency of the pharmacovigilance system and
potential that essential drugs have to offer and the reality compensate for some of the shortcomings of systems
that for millions of people, particularly the poor and based on reports from health professionals only.
disadvantaged, medicines are unavailable, unaffordable,
unsafe or improperly used.[7] PHARMACOVIGILANCE IN DRUG REGULATION

The Uppsala Monitoring Centre: The principal function of the Pharmacovigilance programs made strong by links with
Uppsala Monitoring Centre is to manage the international regulators. Regulators understand that pharmacovigilance
database of ADR reports received from National Centers. [8] plays a specialized and pivotal role in ensuring ongoing
The UMC has established standardized reporting by safety of medicinal products.
all National Centers and has facilitated communication
between countries to promote rapid identification of Clinical trial regulation: In recent years there has been a
signals. substantial increase in the number of clinical trials in

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 Pharmacovigilance: A worldwide master key for drug safety monitoring

developed and developing countries. In their approval PHARMACOVIGILANCE AND INTERNATIONAL

of clinical trials, regulatory bodies look at safety and HEALTH
efficacy of new products under investigation. Safety
monitoring of medicines in common use should be an The current global network of pharmacovigilance centers
integral part of clinical practice. Education and training is coordinated by the Uppsala Monitoring Centre, would
of health professionals in medicine safety, exchange of be strengthened by an independent system of review.
information between national pharmacovigilance centers, This would consider contentious and important drug
the coordination of such exchange, and the linking of safety issues that have the potential to affect public
clinical experience of medicine safety with research and health adversely beyond national boundaries. The Erice
health policy, all serve to enhance effective patient care. Declaration provides a framework of values and practice
A regular flow and exchange of information in this way for collection, analysis and subsequent communication of
means that national pharmacovigilance programmes are drug safety issues. Today, the burden of ADRs on public
ideally placed to identify gaps in our understanding of health despite the progress in pharmacovigilance that
medicine-induced diseases.[1] has been made, the burden on public health of ADRs
remains significant.[17] Pharmacoeconomic studies on
Post marketing safety drug monitoring: These includes detection the costs of adverse reactions suggest that governments
of drug interactions, measuring the environmental burden pay considerable amounts from health budgets towards
of medicines used in large populations, assessing the covering costs associated with them. [18] However, it
contribution of ‘inactive’ ingredients to the safety profile, has become increasingly clear that the safety profile of
systems for comparing safety profiles of similar medicines, medicines is directly linked with socio-political, economic
surveillance of the adverse effects on human health of and cultural factors that in turn affect access to medicines,
drug residues in animals, e.g. antibiotics and hormones. their utilization patterns and public perceptions of
The Council for International Organizations of Medical them. [19,20]
Sciences (CIOMS) report on benefit-risk assessment of
medicines after marketing has contributed to a more Drug utilization: Drug utilization patterns are a major
systematic approach to determining the merit of available determinant in drug safety. For instance, the use of
medicines.[16] injectable medicines is more common in developing
countries. [21] Direct advertizing to the consumer of
Pharmacovigilance in national drug Policy: The provision prescription medicines has become commonplace in many
of good quality, safe and effective medicines and countries. With this information patients feel more able to
their appropriate use is the responsibility of national make their own therapeutic decisions, without assistance
governments. Multidisciplinary collaboration is of great from doctor or pharmacist. The result has been increasing
importance in particular, links need to be forged between self medication, licit and illicit sale of medicines over the
various departments of the ministry of health and also Internet, and over-prescribing by doctors on patients’
with other stakeholders, such as the pharmaceutical demand. This has had considerable effect on increased
industry, universities, nongovernmental organizations prescribing.[22,23] Such public health programmes, however,
(NGOs) and those professional associations having need not focus only on patients but could be used for
responsibility for education on rational use of medicines the benefit of the general public as well. Such awareness-
and pharmacotherapy monitoring. building and educational initiatives should also include
children and elderly populations and could be greatly
Pharmacovigilance in Disease Control Public Health Programmes: facilitated through partnerships with the media, educational
The monitoring of medicine safety in countries where institutions, governmental and non-governmental
there is no regulatory or safety monitoring system in organizations. The success of WHO International Drug
place, or in remote areas with little or no health care Monitoring Programmes is entirely dependent on the
surveillance or infrastructure, has been identified as a contributions of national pharmacovigilance centers.
matter for concern. The problems are especially apparent Ideally every country should have a pharmacovigilance
in situations that involve the use of medicines in specific centre.[1]
communities, for example, for the treatment of tropical
diseases such as malaria, leishmaniasis and schistosomiasis, THE ERICE DECLARATION
and for the treatment of HIV/AIDS and tuberculosis.
Pharmacovigilance should be a priority for every country The Erice Declaration represented significant progress
with a public health disease control programs.[1] in the light of these changes for pharmacovigilance The
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Declaration challenges all the players like public health continues to be positive. To date, no unexpected serious
administration, health professionals, the pharmaceutical safety issues have been identified. The most frequent
industry, government, drug regulators, the media, consumers adverse reactions that have been reported are non-serious
to strive towards the highest ethical, professional and and as expected. The EMEA issued a press release on
scientific standards in protecting and promoting safe use of November 2009 reaffirming the efficacy and safety of the
medicines. The Declaration urges governments and others centrally authorized vaccines. With vaccination campaigns
involved in determining policies relating to the benefit, harm, ongoing in the European Union, it is estimated that about
effectiveness and risk of medicines to account for what they 10 million people have been vaccinated so far. The vaccine
communicate to the public and patients. adverse effects reported so far have mainly been symptoms
such as fever, nausea, headache, allergic reactions and
Challenges for the Erice Declaration: There are several challenges injection site reactions, confirming the expected safety
facing pharmacovigilance programmes in achieving the profile of the three vaccines. New clinical trial data showed
aspirations of the Erice Declaration. Like The difficulties greater incidence of fever following the second dose of
and risks in communicating conflicting or contentious Pandemrix in infants from 6 months to 35 months. An
messages to the public. For instance, during the course assessment of these data is ongoing.[26]
of immunization programmes, communication of new
safety concerns associated with the vaccine(s) or with
CONSIDERATIONS FOR THE FUTURE AND ITS
programmatic errors may result in a dramatic fall in
CHALLENGES
coverage. Nonetheless, an approach of secrecy in such
circumstances is likely to erode public trust and confidence, Some of the serious challenges facing pharmacovigilance
and it fails to respect the rights of the public to participate programmes in the next ten years, describing in brief the
in decision-making. Not only do facts and figures need to potential implications of such trends on the evolution of
be shared with the public, but also the process by which the science.
the data is assessed and how decisions are made should
be shared openly. Another challenge is Communication Some key points for future consideration which may be
between national drug regulatory authorities and national improved to make better pharmacovigilance practice:
pharmacovigilance centers needs to be improved so 1. Pharmacovigilance should be less focused on finding
that regulatory decisions with possible international harm and more on extending knowledge of safety.
implications are rapidly communicated to regulators, to 2. Complex risk-benefit decisions are amenable to, and
avoid widespread public concern or panic.[24] likely to be improved by, the use of formal decision
analysis.
INTERNATIONAL RESPONSE TO DRUG SAFETY 3. Pharmacovigilance should operate in a culture of
ISSUES scientific development. This requires the right balance
of inputs from various disciplines, a stronger academic
Certain safety issues are likely to have a global impact base, and greater availability of basic training, and
with possibly serious consequences for public health. resource which is dedicated to scientific strategy.
When this happens, a cohesive international assessment 4. Systematic audit of pharmacovigilance processes and
and response is needed. The WHO has supported the outcomes should be developed and implemented based
creation of an independent advisory panel composed on agreed standards (‘good pharmacovigilance practice’).
of a broad spectrum of medical disciplines including
clinical pharmacologists, regulators, academics and Some Major challenges face pharmacovigilance are as
epidemiologists. The functions of this panel will be follows:
to provide advice to WHO on safety issues relating to
medicinal products, including its Collaborating Centre Globalization: The globalization of drug distribution and the
for International Drug Monitoring and through it to the increased exposure of massive populations to large volumes
Member States of WHO.[25] of medicines. These include novel chemical entities used
for symptomatic relief and lifestyle modification as well
NEWS BROADCAST RELATED TO PANDEMIC as medicines used in developing countries to curb the
PHARMACOVIGILANCE UPDATE prevalence of pandemic diseases such as HIV/AIDS,
malaria and tuberculosis.
The benefit and risk balance of the pandemic vaccines and
antiviral used for the current H1N1 influenza pandemic Web-based sales and information: The Internet, in addition to

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 Pharmacovigilance: A worldwide master key for drug safety monitoring

its many benefits, has also facilitated the uncontrolled sale Outcomes and Impact: Along with increased public awareness
of medicines across national borders. Drug information in over safety of medicines, there is an increasing public stare
all forms and with varying levels of accuracy is distributed on the performance of the health professions, industry
internationally through this medium. Such information and regulators. Increased accountability must lead to more
covers prescription drugs, unregistered medicines, highly research into the effectiveness of pharmacovigilance and its
controlled substances and traditional and herbal medicines place in improving public perception. A major focus must
with questionable safety, efficacy and quality. be to empower health practitioners and patients themselves
with useful information that improves individual therapy,
Broader safety concerns: The scope of pharmacovigilance aids the diagnosis and management of medicine-induced
continues to broaden as the array of medicinal products disease, and generally leads to a reduction of iatrogenic
grows. There is a realization that drug safety is more than the diseases.[27-29]
monitoring, detection and assessment of ADRs occurring
under clearly defined conditions and within a specific dose CONCLUSION
range. Rather, it is closely linked to the patterns of drug use
within society. Problems resulting from irrational drug use, Pharmacovigilance continues to play a crucial role in
overdoses, polypharmacy and interactions, increasing use meeting the challenges posed by the ever increasing range
of traditional and herbal medicines with other medicines, and potency of medicines, all of which carry an inevitable
illegal sale of medicines and drugs of abuse over the and some- times unpredictable potential for harm.
Internet increasing self medication practices substandard When adverse effects and toxicity do appear, especially
medicines, medication errors, lack of efficacy are all within when previously unknown, it is essential that these are
the domain of pharmacovigilance. Current systems need reported, analyzed and their significance is communicated
to evolve in order to address this broad scope adequately. effectively to the audience having knowledge to interpret
the information. For all medicines, there is a trade-off
Public health versus pharmaceutical industry economic growth: There between the benefits and the potential for harm. The harm
may be shortcomings and at times conflicting interests can be minimized by ensuring that medicines of good
within the pharmaceutical industry when dealing with quality, safety and efficacy are used rationally, and that the
public health concerns arising from drug safety issues. expectations and concerns of the patient are taken into
The industry needs to overcome weaknesses in safety account when therapeutic decisions are made. To achieve
monitoring during clinical trials and post-marketing this is to serve public health, and to foster a sense of trust
surveillance. among patients in the medicines they use that would extend
the confidence in the health service in general, ensure that
Monitoring of established products: The generic sector of the risks in drug use are anticipated and managed, provide
pharmaceutical industry has not fully recognized and its regulators with the necessary information to amend the
responsibility to continuously monitor the safety of its recommendations on the use of the medicines, improve
products throughout the world. There is the erroneous communication between the health professionals and the
public and educate health professionals to understand the
belief that generic drugs are inherently safe even when
effectiveness or risk of medicines that they prescribe.
they interact with other medicines. The generic sector is
the largest supplier of essential drugs.
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