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Article

Ensuring Patient Safety - Launching the New


Pharmacovigilance Programme of India
Dr. Y. K. Gupta*, Professor, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi
Co-ordinator, Pharmacovigilance Programme of India

Pharmacovigilance is defined by the World Health Organization (WHO) as "the science and activities relating to the detection,
assessment, understanding and prevention of adverse effects or any other drug related problem". An adverse drug reaction (ADR)
has been defined as any noxious, unintended and undesired effect of a drug which occurs at a dose used in humans for prophylaxis,
diagnosis, therapy or modification of physiological functions (WHO).

Adverse drug events lead to significant mortality and morbidity world over. In developing countries, comprehensive information on
the safety of drugs used in the patient population is meagre and very few studies have been carried out to detect the incidence of
ADRs in the young and the elderly population.

Although, the thalidomide tragedy stressed the need for an effective pharmacovigilance system, it was the withdrawal of rofecoxib
that renewed interest in drug safety mechanisms. Safety issues with other drugs like erythropoetin, rosiglitazone, rimonabant have
also highlighted the need for an effective and comprehensive pharmacovigilance system.

Brief history of The National Pharmacovigilance programme now rechristened as the


Program (NPVP) was overseen by the Pharmacovigilance programme for India
Pharmacovigilance in India National Pharmacovigilance Advisory (PvPI) is operational from mid July 2010.
Even though pharmacovigilance is still Committee based in the Central Drugs
in its infancy, the concept is not new to India. Standard Control Organization (CDSCO), Role of Pharmacovigilance
It was not until 1986 that a formal adverse New Delhi. Two zonal centers-the South- programme in drug safety
drug reaction (ADR) monitoring system West zonal centre (located in the
Department of Clinical Pharmacology, Seth
monitoring
consisting of 12 regional centers, each
covering a population of 50 million, was GS Medical College and KEM Hospital, Safety problems with pharmaceutical
proposed for India. In 1989, under the aegis Mumbai) and the North-East zonal centre products can be identified in Phase I, Phase
of the Drug Controller of India, six regional (located in the Department of Pharmacology, II, and Phase III clinical studies conducted
centres were set up in Mumbai, New Delhi, AIIMS, New Delhi), collated information from prior to regulatory approval of the drug.
Calcutta, Lucknow, Pondicherry and all over the country and sent it to the However, the numbers of patients enrolled
Chandigarh. In 1997, India joined the WHO Committee as well as to the Uppsala in these studies are usually inadequate to
Programme for International Drug Monitoring Monitoring centre in Sweden. Three regional allow for reliable detection of less frequent
managed by the Uppsala Monitoring Centre, centers reported to the Mumbai center and adverse events. The routine three phase
Sweden. The centre in New Delhi (at two to the New Delhi. Each regional center clinical trials do not always guarantee safety
Department of Pharmacology, AIIMS) was in turn would have several peripheral centers of a new drug as the human trials usually
identified as the national centre, while the reporting to it. The program had three broad cover only a few thousands of volunteers, but
centre in Mumbai (at KEM Hospital) was objectives: the short-term objective was to several lakhs of people take the drug after it
identified as the WHO special centre. Of the foster a reporting culture, the intermediate is allowed to be marketed. It is essential to
six centres, only the centres in Mumbai and objective was to involve a large number of
follow a drug from pre-marketing clinical
New Delhi were active, yet spontaneous healthcare professionals in the systems in
studies into the real life conditions. As a new
information dissemination and the long-term
reporting of ADRs was poor. The monitoring drug is released, safety issues can arise due
objective was for the program to be a
centres were considered ad hoc and to several reasons like trial participants not
benchmark for global drug monitoring.
appropriate levels of funding were not made being a true representative of end users,
However, the World Bank funding for the
available, which put severe constraints on genetic variations in the patient population,
national programme ended in mid 2009 and
them. Recognising the need for improved co-morbidities and concomitant medications
the programme was temporarily suspended.
ADR monitoring in India, the Government and little prior information on the use of drug
of India sent a proposal to the World Bank Recognizing the need to restart the in special populations like elderly, children
for funding. The World Bank approved the national pharmacovigilance programme, in and pregnant women. One option for
proposal with an annual grant of $US 0.1 a brainstorming workshop jointly organized improving the government's ability to detect
million for 5 years and the National by Department of Pharmacology, AIIMS and adverse events before a regulatory approval
Pharmacovigilance programme was CDSCO in late 2009, the framework of the is to increase the numbers of patients
launched in November 2004. new programme was formulated. The enrolled in pre-registration clinical trials,

*E-mail : yk.ykgupta@gmail.com

Pharma Times - Vol 42 - No. 08 - August 2010 21


particularly in the larger Phase III trials. After is also emerging rapidly as a hub of Global of drugs there is a huge mine of data that
new drug products have received approval Clinical trials & a destination for Drug can be explored to learn more about the
for marketing, the Drug regulatory authorities Discovery & Development. safety profile of our drugs.
rely largely on a voluntary spontaneous
Further, more & more new drugs are (b) Weaknesses
reporting system to generate signals of a
safety problem. being introduced into the country which As per the estimates during 2009-10,
include New Chemical Entities (NCE), high the allocation of budget for health by the
The need for pharmacovigilance is well tech pharma products, vaccines as well as Centre stood at Rs 21680 crore, which
understood by the government and the new dosage forms, new routes of drug accounted for 2.1 per cent of the total
scientific community in the country, in the administrations and new therapeutic claims expenditure and 0.35 per cent of the GDP
context of increasing number of recalls of of existing drugs. of India. The overall spend for the vital
drugs worldwide from the market due to their healthcare sector always remained far less
serious side effects. Recent withdrawal of Such rapid induction of NCEs and High
than half a percent of the India's GDP
certain blockbuster drugs in the US and tech Pharma products in the market throw
hovering around a maximum of 2% of the
Europe is a testimony to the successful up the challenges of monitoring Adverse
total budget.
functioning of ADR reporting system in Drug Reactions (ADRs) over large
developed countries. population base. In comparison The United States spent
16% of its national income (GDP) on health
All medicines (pharmaceuticals and (a) Strengths
in 2007. France, Switzerland and Germany,
vaccines) have side effects. Some of these The biggest strength of India is its large the countries which, apart from the United
side effects are known, while many are still population and a large pharmaceutical and States, spend the greatest proportion of
unknown even though that medicine has biotech industry base. According to the national income on health, spent over 5
been in clinical use for several years. It is report of the National Commission on percentage points of GDP less: respectively
important to monitor both the known and population in the year 2000, India was 11.0%, 10.8% and 10.4% of their GDP.
hitherto unknown side effects of medicines projected to have 1 billion people, i.e. 16
in order to determine any new information Thus low availability of spend on health
percent of the world's population
available in relation to their safety profile. In has an impact on the manpower and
a vast country like India, with a population of If current trends continue, India may resources that are available for
over 1.2 billion which has vast ethnic overtake China in 2045, to become the most implementing programs and issues of
variability, different disease prevalence populous country in the world. While global national importance such as
patterns, practice of different systems of population has increased threefold during pharmacovigilance. A case in point is the
medicines, different socioeconomic status this century, from 2 billion to 6 billion, the erstwhile National Pharmacovigilance
it is important to have a standardized and population of India has increased nearly five program launched in 2004. One of the
robust Pharmacovigilance and drug safety times from 238 million (23 crores) to 1 billion reasons for the failure of the program was
monitoring programme for the nation. in the same period. the continuous availability of funds to sustain
Collecting this information in a systematic the program.
manner and analyzing the data to reach a According to the OPPI and Ernst and
Young report published in 2009, It has (c) Opportunities
meaningful conclusion on the continued use
of these medicines is the rationale to institute manufacturing prowess in both APIs, India The opportunities are immense. India
this program for India. is the 3rd largest player in the world with constitutes 16% of the world's population
500 different APIs and in formulations where and is one of the largest source of human
Since, there are considerable social it manufactures 60,000 packs across 60 biodiversity, consisting of 4635 culturally and
and economic consequences of ADRs therapy areas. India currently accounts for anthropologically well-defined populations
there is a need to engage health-care 8% of the global pharmaceutical production with little or no gene flow between them.
professionals, in a well structured making it the world's 4th largest
programme to build synergies for pharmaceutical producer. Hence, study on Indian populations,
monitoring ADRs. The purpose of the who are known for their cultural and genetic
Pharma-covigilance Program of India is to Also, the focus is on to further enhance diversity, not only provides insight into their
collect, collate and analyze data to arrive India's capability to contribute more complex origin, history and relatedness, but
at an inference to recommend regulatory medicines to the world by increasing the also helps in understanding molecular
interventions, besides communicating focus on research and development. The pathology of genetic diseases. As each
risks to healthcare professionals and the Indian government has recognized the need Indian population is unique in their genetic
public. to build an environment conducive for composition, etiologies of genetic diseases
research and innovation and has planned/ are often different from other global
SWOT analysis of implemented a number of initiatives to populations. Indian populations are unique
provide the much needed impetus to in their genetic origin as well as in the
Pharmacovigilance in India research and innovation in pharma & biotech. mutations underlying in the susceptibility to
The Pharmaceutical industry in India is The Government of India is embarking on a disease. Therefore, what is true for other
valued at Rs. 90,000 Crore and is growing major multi-billion dollar initiative with 50% global populations, in terms of their genetic
at the rate of 12 - 14 % per annum. Exports public funding through a public private basis for disease susceptibility, may not be
are growing at 25 % Compound Annual partnership model to harness India's true for Indian populations.
Growth Rate (CAGR) every year. The total innovation capability. The vision is to catapult
exports of Pharma products are to the extent India into one of the top five pharma Collection of vital data on the behavior
of Rs. 40,000 Crore. India is now being Innovation hubs by 2020 with one out of of drugs in the Indian population will reveal
recognized as the 'Global pharmacy of every five to ten drugs discovered worldwide additional information on the safety profile
Generic Drugs' & has distinction of providing by 2020 coming from India. With a large of these drugs. Once the ADR data is
generic quality drugs at affordable cost. India population being exposed to a large portfolio collected, signaling can help determine if a

22 Pharma Times - Vol 42 - No. 08 - August 2010


particular ADR was caused by a particular Coordinating Centre and give feedback of the reporting rates, only few, such as
drug and if it had any correlation with the the programme progress to the Health Care awareness and training programmes,
genetic diversity of the Indian population. Professionals. provision of feedback to reporters, involving
nurses and giving small economic incentives
Moreover, with more 300 medical Attitude towards ADR for reporting have actually been tested and
colleges, 230 dental colleges, 830 pharmacy
reporting and practices of proven to increase the reporting rates.
colleges and 657 recognized nursing
colleges, there is a great opportunity for India health care professionals Stakeholders in
to tap the potential human resources towards ADR reporting Pharmacovigilance
required for an effective pharmacovigilance
system. Adverse events are preventable if the Patients
clinician maintains a high degree of
(d) Threats The patients are the most important
suspicion and pays close attention to details
Ensure availability of and management of stakeholders in drug safety monitoring
regarding adverse events following drug
funds: system as they are the ones who experience
administration. Another way of prevention is
the adverse drug reactions. Prompt
Advance contingency fund and salary by efficient reporting and monitoring of ADRs
identification and feedback to the prescribing
of the technical associates appointed at the which can help in generation of safety
physician regarding ADR following usage of
ADR monitoring centre should reach to the signals. However, under-reporting of ADRs
a drug is imperative to capture the harmful
centre coordinator a month in advance i.e. by health care physicians is a major
effects of the drug early in the product cycle.
in the month of December for first half and problem, even in countries like, UK, US and
Moreover, it is also important for patients to
May for second half of the year. Centre Japan, where pharmacovigilance systems
coordinator should send the utilization maintain a high index of suspicion for
have been well established.
certificate along with original bills duly counterfeit drugs especially when a drug that
verified to the CDSCO zonal office within 15 Numerous studies have attempted to is usually effective fails to provide the same
days of the following month. understand the attitude of physicians level of effectiveness. Generally, in the more
towards reporting ADRs. European studies developed countries, patients can directly
Conduct frequent training and awareness of have revealed that physicians inclined to report ADRs to the pharmacovigilance
Pharmacovigilance: report only adverse reactions that are centres. However, in India due low literacy
AMC coordinator must organize at least serious, unusual or rare and are do not report and lack of understanding of medical signs
two meetings with HCP in their areas. non-serious or common adverse reactions. and systems, patients notifiy the physician
Expenses should be met from the Unlike that in the west, few such studies who after proper history taking report the
contingency fund. Coordinator should be the have been carried out in India. Surprisingly, ADR to the pharmacovigilance centres.
resource person for such meetings. these studies have revealed that many
Pharmaceutical Industry
Detect and respond to under reporting of physicians are unaware of the pharma-
covigilance programme and the ADR The amended schedule Y (2005) of the
ADRs:
reporting systems existing in the country. Drugs and Cosmetics Act mandated the
Periodic sensitization of HCP through submission of periodic safety update reports
Other reasons for low ADR reporting rates
various modes viz poster, pamphlets, SMS, (PSURs) for a period of four years
are lack of feedback regarding the reports
etc. by the center coordinator will improve
and lack of time due to high clinical load. postmarketing. Moreover, it was recognized
AE reporting. The technical associate
Nevertheless, many of these factors are that there was a need to carry out safety
appointed at the centre should visit daily to
potentially modifiable. surveillance studies to answer specific drug
wards, OPDs and private clinics etc.
related issues. In addition, as many drugs
Undertake appropriate measures to create The studies have also attempted to are also licensed in other countries, safety
awareness among the public through mass identify, possible measures that may
media to increase the reporting. data from those regions was required to be
enhance involvement of physicians in the collected, analyzed and reported in PSURs.
Ensure quality of filled ADR forms: ADR reporting system. These measures
This change has led to massive expansion
include, creating awareness about
Quality Review Panel (QRP) will ensure of pharmacovigilance activities in the
pharmacovigilance, implementing ADR
quality of reports during their visit to the AMC industry. However, the nature of such
reporting as integral part of UG, internship
and also at the PvPI National Coordinating activities remains focused to only those
Centre (NCC). and PG training, providing active manpower
drugs manufactured by it. Unfortunately,
to collect ADR reports from busy clinicians,
even after amendments in the regulations,
Proper supervision of functioning of the provision of feedback to reporting health care
the quantity and quality of ADR data provided
centers: professionals, automatic membership to
by the industry is often below specified
A Quality Review Panel (QRP) shall "ADR reporters club", provision of
standards. Further, as industry driven
visit a sample set of AMCs at least once a information about drug safety and
pharmacovigilance is mandated only for new
year to monitor functioning of these centres. medication errors, involvement of nurses
drugs, ADRs related to generics may be
If functioning of the Centre is found and paramedical staff in reporting ADRs and
missed. This may be due to lack of staff
unsatisfactory or not working as per SOPs, giving small economic incentives to regular
experienced in pharmacovigilance.
an appropriate warning shall be issued. The reporters. In addition, impressing upon the
report should decide the status of the centre. Nevertheless, as awareness about drug
clinicians the importance of reporting
If performing well, the AMC shall be given safety monitoring is increasing, the industry
relatively common ADRs, in order to identify
due recognition for its achievements. has the responsibility of training its
drug epidemics, may also help in increasing
professional sales representatives and
Feed back to the Health Care Professionals the volume of ADR reports.
pharmacovigilance executives to interact
AMC coordinator will circulate the However, although many of these with treating physicians and collect ADR
reports generated by the PvPI National measures have been suggested to increase reports.

Pharma Times - Vol 42 - No. 08 - August 2010 23


Regulators Role of other partners After submission of PSURs were made
The drug regulator is one of the most Role of other stakeholders like media mandatory in India as per the amended
important stakeholders in the Pharma- representatives, lawyers, health insurance schedule Y of the Drugs and Cosmetics Act,
covigilance system. The onus of constantly providers and non-governmental pharmacovigilance as a core activity within
reviewing updated drug safety information organizations in development of robust the pharmaceutical industry increased
and ensuring that public at large is protected pharmacovigilance system and sound drug tremendously. However, within a company,
from the possible adverse effects of drugs policies cannot be undermined. Media by the nature of such activities remains focused
constantly lies with the drug licensing promoting good ADR reporting practices and to only those drugs manufactured by it.
authority. Moreover, regulators are often their relevance to the patients and consumer Therefore to broaden the scope of drug
faced with the prospect of either banning, groups can play an important role in safety monitoring, it is proposed that industry
suspending the marketing, or changing the encouraging them to report the adverse synergizes and supports the initiative of
safety specifications in the label of drugs with events to their clinicians. These groups by academia in undertaking pharmacovigilance
potential safety issues reported from other voicing public opinion and expectations can projects, especially cohort event monitoring,
regions of the world. Therefore facilitate the evolution of a pharma- safety trials and other pharma-
pharmacovigilance data becomes a major covigilance programme that enjoys favorable coepidemiological studies. Further, industry
decision making tool in the hands of the public opinion and trust. Co-operation and inputs and support for organizing training
regulator. In addition, constant generation communication with these partners needs workshops, symposia etc, in collaboration
and review of safety data of drugs also to be as clear and open as possible. with the academia and regulators will also
bolsters public confidence in the licensing Misrepresentation of facts in the form of help in increasing the awareness and
authority. 'attention grabbing' drug safety concerns can outreach of the programme amongst the
wreak havoc on the public confidence in the prescribers and will make it more effective.
Academicians - Post graduate and
existing drug safety policies as well as the Data generated from the collected ADR
undergraduate training and curriculum
pharmaceutical industry. reports enable the regulators to make
One of the key skills that undergraduate
Synergy between academia, regulator important regulatory decisions such as
medical students should develop during their
and industry for effective banning, restricting the use or making
undergraduate training is to be prepared for
pharmacovigilance changes in the label of a drug. However, in
safe medical practice. This concept is
India due to the absence of any substantial
usually diluted or ignored in most medical Pharmacovigilance cannot be an
ADR data, regulators are often forced to rely
curricula and course designers usually focus exercise in isolation. In order to be
on western ADR data to make such
on content such as causes of diseases, meaningful, it has to involve all the major
decisions. Under the new pharmacovigilance
pathogenesis, clinical picture, investigations, stakeholders. A collaborative model involving
programme, a proactive role for regulators
differential diagnosis and case management. the three major stakeholders; the academia,
has been envisaged, wherein they do not
The focus should also be on risk assessment the industry and the regulators has been
merely end-users of ADR data but also
of medications, evaluation of adverse envisaged to enhance the effectiveness of
facilitate and oversee academia-industry
effects, contraindications and drug the pharmacovigilance system in India.
collaborative pharmacovigilance projects.
interactions while designing the course for
Under the erstwhile pharmacovigilance The new programme also seeks to actively
pharmacology and medicine curricula. The
programme, drug safety monitoring activities involve the regulators in drug safety training
undergraduate students should especially be
was more or less restricted to a few centres programmes, providing operational support
taught about common medication errors that
and were carried out by highly motivated to the ADR monitoring centres, carrying out
occur with high risk drugs such as warfarin,
people (mostly pharmacologists) despite periodic quality assurance activities and
hypoglycaemic agents, opioids and
financial / resource constraints. Moreover, assuring continued funding for sustaining the
corticosteroids and measures to prevent
these activities were secondary to their programme.
them. The students can also play active role
primary job of teaching. Owing to manpower
in collecting ADR reports during their clinical
and resource constraints (lack of dedicated Pharmacovigilance
wards posting.
computers, access to literature sources, Programme for India (PvPI)
Interns and PG students can play a poor archiving facilities etc.) the quantity and
major role in interacting with patients and the quality of ADR data collected was The Central Drugs Standard Control
their peers in the clinical departments. Their insufficient to propel any real regulatory Organization (CDSCO) under the aegis of
training should be oriented towards, decision regarding drug safety. Further, as Ministry of Health & Family Welfare,
identifying ADRs, assessing their the onus was on "all drugs and all ADRs", Government of India in collaboration with
preventability and reporting them. Besides and there was a definite loss in focus. Department of Pharmacology, All India
they can, by interacting with their peers and However, the new pharmacovigilance Institute of Medical Sciences (AIIMS), New
other para medical staff, increase the programme envisages involving most of the Delhi has initiatited a nation-wide
awareness about pharmacovigilance approximately 300 registered medical pharmacovigilance programme for
systems and enhance ADR reporting rates. colleges across the country to ensure that protecting the health of the patients by
Moreover, interns and PG students are an meaningful and country specific data assuring drug safety which will include data
invaluable source for collecting, analyzing regarding ADRs can be collected from all for drugs, biologicals, vaccines, diagnostics
for causality and reporting ADRs and parts of the country. Not only spontaneous and medical devices from public and private
authoring case reports and case series and report collection, the new programme will sector. The comprehensive national
cohort event monitoring studies. However, also encourage and facilitate monitoring programme is coordinated by the
their training should be largely self directed centres to undertake and report
Department of Pharmacology at AIIMS as a
and dynamic, albeit with proper mentoring, postmarketing safety studies, drug use
National Coordinating Centre. The centre
thus enabling them to provide appropriate reviews and registry/database based studies
operates under the supervision of a Steering
and up-to-date feedback regarding ADRs independently or in collaboration with
Committee.
and other drug related problems to others. industry partners.

24 Pharma Times - Vol 42 - No. 08 - August 2010


The Goal of the program is to ensure Phase Ib will include the rest of the 40 transmitted through vigiflow interface into the
that the benefits of medicine used outweigh centres by end of 2010. The centres for UMC ADR database where signal processing
the risks and thus safeguard the health of Phase Ia have been shortlisted based on can be carried out.
the Indian population. The objectives are: letter of intent received from interested
faculty, duly forwarded by the head of the Collaboration with World
z To monitor Adverse Drug Reactions
(ADRs) in Indian population institution. The AMCs will get operational and Health Organization and
logistic support from their respective zonal
z To create awareness amongst health the Uppsala Monitoring
CDSCO centres, situated at Ghaziabad,
care professionals about the
Kolkata, Mumbai and Chennai. The zonal Centre (UMC)/WHO
importance of ADR reporting in India
CDSCO centres will be under administrative
WHO and UMC work with and/or
z To monitor benefit-risk profile of control of the CDSCO headquarter at New provide technical support to more than 94
medicines Delhi. countries worldwide. The long term objective
z Communicate findings with all key of the PvPI is to establish a 'Centre of
The coordinating centre of
stakeholders Excellence' for Pharmacovigilance in India.
Pharmacovigilance Programme for India will
z Generate independent, evidence based be housed at Department of Pharmacology, To achieve this objective, the PvPI National
recommendations on the safety of All India Institute of Medical Sciences, New Coordinating Centre will collaborate with the
medicines WHO Collaborating Centre - Uppsala
Delhi and will provide technical support to
Monitoring Centre (UMC) based in Sweden.
z Support the CDSCO for formulating the CDSCO headquarter. All the centres
safety related regulatory decisions for under the programme will function in z Training of the staff at the PvPI national
medicines accordance with the protocol and SOPs coordinating centre at AIIMS, the ADR
developed by expert committees. Monitoring centres in medical colleges
z Create a national centre of excellence
across the country
at par with global drug safety monitoring
standards
Key features of this programme
1. There is an organized project
management approach to the
programme.
2. All the key stakeholders have been
involved in this namely (and not limited
to) Government, Academia, Health
Care professional bodies, Industry,
National Immunization programmes,
WHO-Uppsala monitoring centre, Fig. 1. Proposed growth phases of
Industry professional bodies, Medical Pharmacovigilance Programme for India
colleges, autonomous institutes,
corporate hospitals, CDSCO Zonal
centres. ADR data flow
z Usage of UMC's Vigiflow software (for
3. Data on Indian population will enable Adverse drug reaction reports will be medicines) and Paniflow (for vaccines)
informed decision making by the Indian collected at the ADR monitoring centres
regulatory authority by performing (AMCs). The pharmacovigilance staff at the z Access to Vigibase, which contains
signal detection once the data reaches AMCs will check for validity of the report and worldwide medicines safety data
a threshold size if possible conduct provisional causality z Access to early information about
assessment. The ADR forms will then be potential safety hazards of medicines
4. The CDSCO Zonal centres will provide
dispatched to the co-ordinating centre as per (worldwide data)
administrative oversight to the ADR
the SOPs. The AMC staff will also maintain
monitoring centres at the medical z Technical collaboration for Pharma-
a log of all the centre activities. Selected
colleges. AMCs will also carry out focused ADR covigilance Programme of India
5. Training and Quality assurance are key monitoring of drugs in the focused ADR z Technical collaboration for a regular
essential elements intertwined with monitoring watch list. The co-ordinating publication that will be issued by the
every aspect of the programme. centre will conduct causality assessment PvPI National Coordinating Centre for
and upload the reports into the national distribution to the ADR Monitoring
Framework of the new programme pharmacovigilance database. The co- centres and other health care
ordinating centre will prepare a consolidated professionals.
The programme is envisaged to be
report of ADRs collected at defined time
rolled out in three phases. Phase I would
intervals. All the ADRs from all other sources
include 40 adverse drug reaction monitoring (industry, Health care professionals, national Linking Pharmacovigilance
centres (AMC) and will be rolled out in 2010. immunization programmes etc.) will also be
The programme would be expanded in databased at the co-ordinating centre.
with Public Health
Phase II to include up to 140 MCI recognized Programmes
medical colleges by 2011. Phase III would The centre will also implement and
ultimately cover the healthcare system by integrate pharmacovigilance activities into Drug safety concerns one and all and
2013. Phase I will be further divided into public health programmes involving mass hence a robust pharmacovigilance system
phase Ia and Ib. Phase Ia will involve usage of drugs, such as for anti-malarial, is the clear need of the present and future
upgrading 10 centres in terms of anti-tubercular and anti-retroviral drugs. times. A good plan is half the job done.
infrastructure (computer and ancillaries). Lastly, the integrated ADR data will be However successful start is just the

Pharma Times - Vol 42 - No. 08 - August 2010 25


beginning and it is important to stay focused. following drug administration. These metabolism and therapeutic targets, public
A continued interest of all the stake holders conditions are clinically significant and often private sector cooperation, funding of
in pharmacovigilance activities will linked to drug therapies, but they cannot be research, ensuring privacy and
determine the success of the programme. easily or solely attributed to a drug exposure. confidentiality of data to prevent
One of the many ways to ensure ongoing Pharmacogenetics can help identify stigmatization as well as educating the
interest in pharmacovigilance is to include it individuals who are susceptible to adverse medical and lay communities.
in the public health programme. This will drug reactions (ADRs) has the potential to
serve the dual purpose of continued interest reduce the personal and population costs of India's 2020 Vision for
in drug safety at the grass root level of health drug-related morbidity. Pharmacovigilance
care system as well as catering to the safety
The most common enzyme deficiency 1. Being the second most populous
issues important for public in general.
worldwide is glucose-6-phosphate country in the world, it should constitute
One such issue important for India is dehydrogenase (G6PD) deficiency, with the largest contributor to the adverse
the recent switch over to artemisinin many allelic variants. It is associated with event database as a result of a large
combination therapies for treatment of acute haemolysis on exposure to oxidising number of ADRs being reported to the
malaria in view of increasing chloroquine drugs such as primaquine, chlorproguanil- national drugs regulatory authority.
resistance. In this respect, the National dapsone, sulfonamides, and sulfones,
2. The actual number of ADRs should
Institute of Malaria Research, in nitrofurantoin, nalidixic acid, quinine,
actually show a declining trend as the
collaboration with the National Coordinating flutamide Phenotypic tests for G6PD
country should aim to achieve the real
Centre at Department of Pharmacology, deficiency are recommended before using
aim of pharmacovigilance i.e. to provide
AIIMS initiated a World Bank funded study drugs such as primaquine, but it is not known
safer medicines for the population of
for pharmacovigilance of anti-malarial how often this is carried out. Abacavir an HIV-
India. The aim therefore should be to
medicines. This is the first attempt to involve 1 reverse transcriptase inhibitor, causes a
collect data and learn from that data
pharmacovigilance in a public health hypersensitivity reaction (skin rash, fever,
so much that we are able to take a
programme in India. The study aims to gastrointestinal and respiratory effects) in
decision on continuing or discontinuing
assess the safety of artemisinin combination about 5% of patients and is associated with
the use of a drug based on its ongoing
therapies in real life settings in India. The an HLA allele, HLA-B*5701. Pre-prescription risk benefit assessment. The focus
ultimate goal is to influence the behavior of genotyping prevents abacavir hyper- should move from pharmacodiligence
the healthcare physicians in the remote sensitivity and is cost-effective. In Europe, to pharmacovigilance. The target
areas of the country with respect to adverse screening for HLA-B*5701 is now mandatory should be to prevent ADRs and the
event reporting. before prescribing abacavir. Similarly, severe associated loss of costs in managing
immune-mediated adverse effects including those ADRs.
Following successful implementation of
Stevens-Johnson syndrome and toxic
pharmacovigilance in malaria, the next step 3. Each stakeholder to not only be
epidermal necrolysis has been reported with
should be involvement of other public health conscientious of their rights but also
carbamazepine. In Han Chinese patients this
programmes like HIV, Leprosy, Tuberculosis their responsibilities towards the
is associated with HLA-B*1502, and the drug
etc. Such efforts will help in making the patients and the society at large
is avoided in those with this phenotype. In a
pharmacovigilance programme a self- 4. The Program for Pharmacovigilance in
recent study, the investigators evaluated the
sustaining system if the logistics can be India should be viewed as a centre of
implications of single nucleotide
taken care of. It will also help in building excellence and the model pursued and
polymorphism of CYP2C9 and CYP2C19
patient trust in the healthcare system which demonstrated in the past 10 years
genes on phenytoin pharmacokinetics in
is the eventual expectation from the should become a role model for the rest
healthy South Indian voulnteers and
Pharmacovigilance programme in India. of the world to follow.
concluded that *2 - *3 alleles of CYP2C9
led to decreased hydroxylation of the drug,
Linking 5. India should aim to be self dependent
thereby increasing the risk of ADRs and have its own National Drug Safety
pharmacogenomics with database with electronic reporting
Although promising, the eventual
pharmacovigilance impact of pharmacogenomic profiling for
capabilities to all the other major Global
regulatory agencies
Many different types of drugs are identification of ADR susceptibility among
available to treat a wide variety of disorders. individuals would depend upon incidence of 6. Globally regulatory agencies in the
Why some patients respond to a particular drug related toxicity, prevalence of variant world should view India as the Global
drug and others do not respond, or why alleles, severity of consequences and also Pharmacy of the world and as a
the availability of rapid, reliable and cost resource of knowledge and a treasury
some patients tolerate a drug well and others
effective assays. Several researchers have of information related to the safety of
are intolerant of the same drug, are important
proposed the integration of genomic molecules.
clinical issues in medicine. Genetic
differences among patients may contribute information with the pharmacovigilance 7. Not only will the safety database cover
to differences in medication response, as databases, which can not only enhance pharmaceutical products, but also
well as the development of adverse effects. signal detection but also aid in determining biological, devices, vaccines and stem
'Pharmacogenomics' and 'pharma- whether genotyping should be performed cell therapies.
cogenetics' refer to the use of molecular prior to initiation of drug therapy. However,
genetic approaches to understand several key operational, regulatory, ethical Acknowledgements
differences in drug response and tolerability. and legal issues need to be addressed
before the potential role of pharma- l gratefully acknowledge the
Many types of putative ADRs are likely to be
cogenomics in ADR detection and contributions of Dr. Vivek Ahuja, Mr. Paul
complex and to have multifactorial etiologies.
prevention can be realized. These include Lalvani, Dr. Biswa Mohan Padhy, Dr. Pooja
Examples include the metabolic syndrome,
the complexity of database which integrates Gupta and Dr. Ashish Kakkar in preparation
tardive dyskinesia, suicidality, hepatic
information on drug transporters, of the article.
dysfunction and cardiac abnormalities

26 Pharma Times - Vol 42 - No. 08 - August 2010