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REVIEW ARTICLE
Importance of Pharmacovigilance in Indian Pharmaceutical Industry
S. S. Shuka1*, Bina Gidwani1, R. Pandey1, S. P. Rao1, V. Singh1, Amber Vyas2
1
Columbia Institute of Pharmacy, Raipur (C.G.)
University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur (C.G.)
*Corresponding Author E-mail: [email protected]
2
ABSTRACT:
Pharmacovigilance is the pharmacological science relating to the detection, assessment, understanding and prevention
of adverse effects, particularly long term and short term side effects of medicines.
It is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers
and patients on the adverse effects of medications, biological products, herbalism and traditional medicines with a
view to:
Identifying new information about hazards associated with medicines
Preventing harm to patients.
Phase IV of the evaluation of a drug starts when the marketing license is granted and extends over many years. It
consists of pharmacoepidemiological studies to evaluate the effectiveness, safety, and utilization of the drug in large
populations, under real-life conditions. The results confirm or disprove the effectiveness of the drug in clinical practice
(confirmation of the therapeutic effect), determine whether approved uses should be expanded or restricted, any
untoward interactions (pharmacovigilance) and pharmacoeconomics of the drugs.
INTRODUCTION:
Generally, pharmacovigilance is the science of collecting,
monitoring, researching, assessing and evaluating
information from healthcare providers and patients on the
adverse effects of medications, biological products,
herbalism and traditional medicines with a view to:
• Identifying new information about hazards associated
with medicines
• Preventing harm to patients.
The etymological roots are: pharmakon (Greek), “drug;”
and vigilare (Latin), “to keep awake or alert, to keep
watch.”
The challenge of maximizing drug safety and maintaining
public confidence has become increasingly complex.
Pharmaceutical and biotechnology companies must not only
monitor, but also proactively assess and manage drug risk
throughout a product’s lifecycle, from development to postmarket.1
The word Vigilance simply means ‘to watch’ and it
basically refers to:
• Alert watchfulness
• Forbearance of sleep; wakefulness
• watchfulness in respect of danger; care, caution,
circumspection
• The process of paying close and continuous attention.
Pharmacovigilance is particularly concerned with adverse
drug reactions, or ADRs, which are officially described as:
"A response to a drug which is noxious and unintended, and
which occurs at doses normally used for the prophylaxis,
diagnosis or therapy of disease, or for the modification of
physiological function."3
Pharmacovigilance (abbreviated PV or PhV) is the
pharmacological science relating to the detection,
assessment, understanding and prevention of adverse
effects, particularly long term and short term side effects of
medicines.2
Recently, its concerns have been widened to include:
• Herbals
• Traditional and complementary medicines
• Blood products
• Biologicals
• Medical devices
• Vaccines.
Received on 25.10.2011
Accepted on 12.12.2011
© Asian Pharma Press All Right Reserved
Asian J. Res. Pharm. Sci. 2(1): Jan.-Mar. 2012; Page 04-08
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Asian J. Res. Pharm. Sci. 2012; Vol. 2: Issue 1, Pg 04-08
Continuous monitoring of their effects, side effects,
contraindications and outright harmful effects which can
result in a high degree of morbidity and in some cases, even
mortality, is essential to maximize benefits and minimize
risks. No degree of care and caution at the pre-clinical and
clinical testing stages can guarantee absolute safety, when a
drug is marketed and prescribed to large populations across
the Country and outside. Because clinical trials involve
several thousand patients at most; less common side effects
and adverse drug reactions are often unknown at the time a
drug enters the market. Even very severe adverse drug
reactions, such as liver damage, are often undetected
because study populations are small. Post marketing
pharmacovigilance uses tools such as data mining and
investigation of case reports to identify the relationships
between drugs and adverse drug reactions. The drug
regulatory agencies have the responsibility of having a
well-established pharmacovigilance system to monitor
adverse reactions of drugs. During the drug development
phase and later during the life time of a marketed drug.3
medicine might differ in the manner of their production and
ingredients. Additionally, adverse drug reactions might also
occur when drugs are taken along with traditional and
herbal medicines that have also to be monitored through
pharmacovigilance. In some cases, adverse drug reaction of
certain medicines might occur only in one country's or
region's citizens. To prevent all undue physical, mental and
financial suffering by patients, pharmacovigilance proves to
be an important monitoring system for the safety of
medicines in a country with the support of doctors,
pharmacists, nurses and other health professionals of the
country.
AIMS OF PHARMACOVIGILANCE
The aims of pharmacovigilance are 4
1. The identification and quantification of previously
unrecognized adverse drug reactions (ADR).
2. The identification of sub-groups of patients at
particular risk of ADRs (the risk relating to dose, age,
gender and underlying disease).
3. The continued monitoring of the safety of a product,
throughout the duration of its use, to ensure that its
risks and benefits remain acceptable. This includes
safety monitoring following significant newly
approved indications.
4. The comparative adverse drug reaction profile of
products within the same therapeutic class.
5. The detection of inappropriate prescription and
administration.
6. The
further
elucidation
of
a
product’s
pharmacological/toxicological properties and the
mechanism by which it produces adverse drug
reactions.
7. The detection of significant drug–drug interactions
between new products and co therapy with agents
already established on the market, which may only be
detected during widespread use.
STEPS IN PHARMACOVIGILANCE PROGRAMME
1. Finding the risk of drug
2. Clinical trials
3. Pharmaco epidemiological study
4. Case report
5. Developing case series
6. Analysis of case series
7. Use of data mining to identify product – event
combination
8. Spontaneous reporting
The Importance of Pharmacovigilance are as follows:5
1. Safety monitoring of medicinal products
2. Drug monitoring
3. Pharmaceutical preparations - adverse effects
4. Adverse drug reaction reporting
5. Product surveillance, Post marketing
6. Legislation
In Short, pharmacovigilance aims to improve patient care
and safety, public health, assessment of benefit, harm,
effectiveness and risk of medicines, promotes
understanding, education and clinical training
IMPORTANCE OF PHARMACOVIGILANCE:
When a pharmaceutical drug is introduced in the market
there are still a lot of things that are unknown about the
safety of the new drugs. These medicines are used by
various patients for different diseases. These people might
be using several other drugs and must be following different
traditions and diets which may adversely affect the impact
of medicine in them. Also the different brands of same
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Asian J. Res. Pharm. Sci. 2012; Vol. 2: Issue 1, Pg 04-08
PARTNERS IN PHARMACOVIGILANCE
A complex and vital relationship exists between wide
ranges of partners in the practice of drug safety monitoring.
Sustained collaboration and commitment are vital if future
challenges in pharmacovigilance are to be met in order to
develop and flourish.
•
Government
•
Industry
•
Hospitals and academia6
•
Medical and pharmaceutical associations
•
Poisons information centres
•
Health professionals7,8
•
Patients12,13
•
Consumers
•
Media
•
WHO
drug is marketed and prescribed to large populations across
the Country and outside. Because clinical trials involve
several thousand patients at most; less common side effects
and adverse drug reactions are often unknown at the time a
drug enters the market. Even very severe adverse drug
reactions, such as liver damage, are often undetected
because study populations are small. Post marketing
pharmacovigilance uses tools such as data mining and
investigation of case reports to identify the relationships
between drugs and adverse drug reactions. The drug
regulatory agencies have the responsibility of having a
well-established pharmacovigilance system to monitor
adverse reactions of drugs. During the drug development
phase and later during the life time of a marketed drug.7
Pharmacovigilance is fastest emerging as an important
approach for the early detection of unwanted effects of the
drugs and to take appropriate regulatory actions if
necessary. This may ensure the safer use of drugs.8
Historically, Indian market has always, except in very few
cases, seen the launch of only products, which have been
earlier approved and marketed in U.S.A., Western Europe
or Japan. Until now, the time lag between the first
marketing of a new drug in a foreign country and India has
been on an average around 4 years, and hardly any new
drug was introduced for the first time in India. In that kind
of scenario, it was not too critical that there was in place a
system of pharmacovigilance in India, since reports of sideeffects from outside India would have helped our regulatory
agencies to assess the rationale of continuing the drug in the
Indian market. Thus in the past, action on marketed drugs
has been triggered on the basis of reports on the harmful
effects of drugs marketed abroad. In a few cases, drugs,
which have been banned or withdrawn in foreign markets,
were allowed to be kept in the market in India. For
example, Chloramphenicol, Phenyl Butazone, Clioquinol,
Phenformin, Cisapride, all continue to be prescribed in
India on the basis of a conscious decision by the Regulatory
Agency that the benefit to risk ratio is in favour of the
former.8
PHARMACOVIGILANCE IN INDIA
It is related to the surveillance of drugs once they are
released for use in the community (post marketing
surveillance) and relies on voluntary reporting, prescription
monitoring, medical records and statistical studies in the
population.
Since very few new drugs were discovered in India and
hardly any new drug was launched for the first time in India
in the past, there was no major compulsion to have a strong
Pharmacovigilance system to detect adverse reactions of
marketed drugs. The experience from the markets where the
drug was in use for several years before introduction in
India, was used by the Companies and the Regulatory
Agencies to assess the safety parameters and take corrective
actions , such as the withdrawal or banning of the drug in
question. With the Indian Companies'' capacity to develop
and market new drugs out of their own research efforts, it is
important that adequate Pharmacovigilance standards are
introduced to monitor adverse reactions of products, first
launched in India.
The evolution of a new Patent regime in the Indian
Pharmaceutical Industry (the Post-2005 scenario) as a
consequence of India being a founder member of WTO, and
her obligations under Trade Related Intellectual Property
Rights and Services (TRIPS), makes it incumbent that India
can no longer copy patented products and market them
without license from the innovator company. The leading
Indian companies realizing the compulsions of the new
regime have already initiated investments of substantial
resources for the discovery and development of new drugs
needed for both Indian and International markets. This in
turn means that during the coming years Research and
Development by the Indian Pharmaceutical companies will
hopefully lead to new drugs based on pre-clinical and
clinical data generated mostly in India. In such cases, the
Indian regulatory agencies cannot count on the experience
of other markets to assess the incidence and prevalence of
Continuous monitoring of their effects, side effects,
contraindications and outright harmful effects which can
result in a high degree of morbidity and in some cases, even
mortality, is essential to maximize benefits and minimize
risks. No degree of care and caution at the pre-clinical and
clinical testing stages can guarantee absolute safety, when a
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Peripheral Pharmacovigilance Centres
Primary pharmacovigilance centers. Relatively smaller
medical institutions including individual medical
practitioners’ clinics, private hospitals, nursing homes,
pharmacies etc. First contact Adverse drug reaction data
collection unit at a health care facility. They would be
identified and coordinated by Regional pharmacovigilance
NATIONAL PHARMACOVIGILANCE CENTRE
centre or Zonal pharmacovigilance centre in consultation
At present, post – marketing survillence of medicines is with Central Drugs Standard Control Organization
mainly coordinated by National Pharmacovigilance (CDSCO) .10
Centres. The Central Drugs Standard Control Organization
(CDSCO) has initiated a country-wide Pharmacovigilance Regional Pharmacovigilance Centers (RPCs)
programme under the aegis of DGHS, Ministry of Health
Secondary pharmacovigilance centers. Relatively larger
and Family Welfare Government of India.
healthcare facilities attached with medical colleges. They
would act as second level centers in the administrative
The programme is coordinated by the National
structure of the NPPI. They will function as first contact
Pharmacovigilance Centre at the Central Drugs Standard
Adverse Drug Reactions data collection units also. They
Control Organization (CDSCO). The National Centre is
would be identified and coordinated by Zonal
operating under the supervision of the National
Pharmacovigilance Centers in consultation with the Central
Pharmacovigilance Advisory Committee to recommend
Drugs Standard Control Organization (CDSCO). 10
9
procedures and guidelines for regulatory interventions.
adverse reactions from drug usage, and therein lies the
importance of a properly designed pharmacovigilance
system in India. For an effective Pharmacovigilance system
to be functional and efficient all the stakeholders need to be
alert and attentive throughout the lifetime of the drug in the
market.9
National Pharmacovigilance Programme
The National Pharmacovigilance Programme was officially
inaugurated by the Honorable Health Minister
Dr.Anbumani Ramadoss on 23 November, 2004 at New
Delhi. The National Pharmacovigilance Programme for
India, sponsored by the World Health Organization (WHO)
and funded by the World Bank, became fully operational in
January 2005.9
Zonal Pharmacovigilance Centre (ZPCs)
Tertiary pharmacovigilance centers. Large healthcare
facilities attached with medical colleges in metro cities
identified by the Central Drugs Standard Control
Organization (CDSCO) for the purpose. They would act as
third level centers in the administrative structure of the
NPPI. They will function as First contact Adverse drug
effect data collection units also.10
The Programme aims to foster the culture of adverse drug
reactions notification in its first year of operation and
subsequently aims to generate broad based Adverse drug
reactions data on the Indian population and share the
information with global health-care community through
WHO-UMC.
The National Pharmacovigilance Advisory Committee
(NPAC)
Oversee the performance of various Zonal, Regional and
Peripheral Pharmacovigilance centers as well as
recommend possible regulatory measures based on the data
received from various centers. It also oversees data
collection and assessment, interpretation of data as well as
publication of adverse drug reactions monitoring data. The
Committee also periodically evaluates their protocol
compliance levels to ensure that the data received is
homogenous and can be scientifically pooled for informed
regulatory decisions. Wherever necessary, National
Pharmacovigilance Advisory Committee also seeks the
opinion of experts in various specializations. 10 The specific
aims of the Pharmacovigilance Programme are to:
• Contribute to the regulatory assessment of benefit,
harm, effectiveness and risk of medicines, encouraging
their safe, rational and more effective (including cost
effective) use.
• Improve patient care and safety in relation to use of
medicines and all medical and paramedical
interventions.
• Improve public health and safety in relation to use of
medicines.
• Promote understanding, education and clinical training
in pharmacovigilance and its effective communication
to the public.
The nationwide programme, sponsored and coordinated by
the country’s central drug regulatory agency – Central
Drugs Standard Control Organization (CDSCO) – to
establish and manage a data base of Adverse Drug
Reactions (ADR) for making informed regulatory decisions
regarding marketing authorization of drugs in India for
ensuring safety of drugs.
Under the program 26 peripheral centers, 5 Regional
Centers and 2 Zonal Centers were established. The
Peripheral centers will record the Adverse Events (AE) and
send to the Regional Centers. They in turn collate and
scrutinize the data received from the Peripheral Centers and
submit to the Zonal Centers. The Zonal Centers will
analyze the data and submit consolidated information to the
National Pharmacovigilance Centre. The Zonal Centre will
also provide training, general support and coordinate the
functioning of the Regional Center.
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•
•
•
•
•
•
Monitoring medicines as used in everyday practice to 10. National Pharmacovigilance Protocol, Ministry of Health and
Family Welfare, Govt. of India.
identify previously
unrecognized adverse effects or changes in the patterns
of their adverse effects
Assessing the risks and benefits of medicines in order
to determine what action,
if any, is necessary to improve their safe use
Providing information to users to optimize safe and
effective use of medicines
Monitoring the impact of any action taken
CONCLUSION:
For all medicine there is a tradeoff between the benefits and
the potential for harm. To minimize the harm, it is
necessary that medicines of good quality, safety and
efficacy are used rationally.
Efficacy: evaluated from data obtained from clinical
trials
Quality: compliance to established standards,
manufacture by Good Manufacruring Practices
licensed premise
Safety : toxicology, clinical trials
In all, Pharmacovigilance will promote:
Systematic and rational use of medicines
Boost confidence for safety.
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