An update on the Pharmacovigilance Programme of India

Abstract

Pharmacovigilance is a pharmacological science related to the detection, assessment, understanding and prevention of adverse effects, particularly long-term and short-term adverse effects of medicines (WHO-Essential Medicines and Health Products, 2002). It has been observed that a medication that is proven efficacious in large patient population often fails to work in some other patients of different ancestry. Ancestral background of the patients are controlled by genetic factors that influence drug response-drug targets, drug-metabolizing enzymes, drug transporters, and genes indirectly affecting drug action can modulate drug toxicity and contribute to its individual variability (Ma and Lu, 2011). Thus, adverse drug reactions are highly variable in individuals and are major limiting factor in drug therapy and development. For example people with Asian ancestry are at greater risk for serious cutaneous reactions when starting treatment with carbamazepine. Therefore, even though the drug had already been approved in some other country, clinical trial with robust pharmacovigilance monitoring is needed in the population of different race & ethnicity.

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published: 22 September 2015
doi: 10.3389/fphar.2015.00194
Frontiers in Pharmacology | www.frontiersin.org 1September 2015 | Volume 6 | Article 194
Edited by:
Jean-Paul Deslypere,
Proclin Therapeutic Research Pte
Ltd., Singapore
Reviewed by:
Colin Ross,
University of British Columbia, Canada
Lisa Chan,
Besins Healthcare, UK
*Correspondence:
Ratan J. Lihite,
r.lihite@yahoo.com
Specialty section:
This article was submitted to
Pharmaceutical Medicine and
Outcomes Research,
a section of the journal
Frontiers in Pharmacology
Received: 21 May 2015
Accepted: 27 August 2015
Published: 22 September 2015
Citation:
Lihite RJ and Lahkar M (2015) An
update on the Pharmacovigilance
Programme of India.
Front. Pharmacol. 6:194.
doi: 10.3389/fphar.2015.00194
An update on the Pharmacovigilance
Programme of India
Ratan J. Lihite *and Mangala Lahkar
Department of Pharmacology, ADR Monitoring Centre (Pharmacovigilance Programme of India), Gauhati Medical College
and Hospital, Guwahati, India
Keywords: ADR, Pharmacovigilance, PvPI, AMC
Pharmacovigilance is a pharmacological science related to the detection, assessment, understanding
and prevention of adverse effects, particularly long-term and short-term adverse effects of
medicines (WHO-Essential Medicines and Health Products, 2002). It has been observed that a
medication that is proven efficacious in large patient population often fails to work in some other
patients of different ancestry. Ancestral background of the patients are controlled by genetic factors
that influence drug response-drug targets, drug-metabolizing enzymes, drug transporters, and
genes indirectly affecting drug action can modulate drug toxicity and contribute to its individual
variability (Ma and Lu, 2011). Thus, adverse drug reactions are highly variable in individuals and
are major limiting factor in drug therapy and development. For example people with Asian ancestry
are at greater risk for serious cutaneous reactions when starting treatment with carbamazepine.
Therefore, even though the drug had already been approved in some other country, clinical trial
with robust pharmacovigilance monitoring is needed in the population of different race & ethnicity.
In India, a formal ADR monitoring system was started in 1986 with 12 regional centers. In 1997,
India became the member of WHO Programme for International Drug Monitoring managed by
the Uppsala Monitoring Centre (UMC), Sweden. At inception, 6 regional centers were set up in
Mumbai, New Delhi, Kolkata, Lucknow, Pondicherry, and Chandigarh for ADR monitoring in the
country (Gupta, 2010). Of these 6 centers, only the centers in Mumbai and New Delhi were active
and thus spontaneous reporting of ADRs were poor. Therefore, in November 2004, Govt. of India
has launched National Pharmacovigilance Programme (NPvP) with an annual grant of US$0.1
million approved for 5 years from World Bank (Gupta, 2010). However, the World Bank funding
for this programme was ended in mid-2009 and this programme was temporarily suspended.
Recognizing the need for improved ADR monitoring in the country, in July, 2010, under the
aegis of Health Ministry, a nation-wide revised ADR monitoring programme was launched and
named as Pharmacovigilance Programme of India (PvPI) (Kalaiselvan et al., 2014a). Initially,
under this National programme, All India Institute of Medical Sciences, New Delhi was the
National Coordination Centre (NCC) and in April, 2011, it was shifted to Indian Pharmacopoeia
Commission (IPC), Ghaziabad. Dr. G. N. Singh, Scientific Director of IPC was designated as
a National Coordinator of PvPI for ADR monitoring in the country (Rehan, 2013). Under
PvPI, ADRs are being identified and spontaneously reported by the healthcare professional of
Adverse Drug Reaction Monitoring Centres (AMC). These AMCs are set up across the country
in medical colleges approved by Medical Council of India (MCI) (Rehan, 2013). These AMCs are
responsible for collecting adverse event as per Standard Operating Procedure (SOP), performing
follow up if require for the completeness of ADR reports and uploading these reports in net-
based software used for ADR reporting called as Vigiflow (Kalaiselvan et al., 2014b). These
drug safety information/Individual Case Safety Reports (ICSRs) are collected in predesigned
suspected ADR reporting form, broadly consist of 4 sections i.e., patient’s information, suspected
adverse reaction, suspected medication(s), and reporter’s information. These ICSRs are then
reported to NCC for Quality & Signal Review via Vigiflow after causality assessments of ADRs
performed using the WHO-UMC causality assessment system (Figure 1). The purpose of this

Lihite and Lahkar An update on the Pharmacovigilance Programme of India
programme is to collect, collate and analyze this reported data
to arrive at an inference to recommend regulatory interventions
for safeguarding the health of Indian population by ensuring that
benefit outweighs the risks associated with the use of medicines.
Under PvPI, AMC plays a vital role in collection and follow-up of
ADR reports from healthcare professionals. Initially there were
22 AMCs in the country. At present there are 150 AMCs under
this programme and categorized into four zones i.e., North,
South, East and West (Pharmacovigilance Programme of India
(PvPI) newsletter, 2013)1. In coming year, there will be 350 AMCs
across the country to make this programme one of the largest
Pharmacovigilance Programme in the world.
Under previous National Pharmacovigilance Programme,
11633 ICSRs were reported from January 2006 to December
2008 whereas under PvPI, till June 2014, 78672 ICSRs are
reported (Kalaiselvan et al., 2014b). Thus, it can be observed
that the rate of reporting has been increased under PvPI.
The safety database of PvPI is growing with the increase in
number of AMCs in each year. This database allows healthcare
providers and consumers to browse and view data on suspected
adverse drug reactions of various medicinal products. All data
contained herein is sourced from VigiBase R
, the WHO global
database for ADRs, maintained by the UMC available at http://
www.vigiaccess.org. PvPI has generated helpline facility (Tel.
No. 18001803024) to make drug safety information available
1http://www.ipc.gov.in/PvPI/pv_about.html.
FIGURE 1 | Programme Communication & flow of ADR reports.
for Indian population. Beside suspected ADR reporting form,
PvPI have developed medicine side effect reporting form for
consumers/patients in their regional language. PvPI have also
extended its reach to other National Health Programmes within
country. National coordinating center has collaborated with
Revised National Tuberculosis Control Programme and National
Aids Control Organization to monitor the safety of drugs use in
their programme.
Under PvPI, several drugs are under scanner and quarterly
drug safety alerts on suspected unexpected serious adverse
reactions (SUSARs) are issued to healthcare professionals via
newsletters (Table 1). Based upon PvPI database, this year Drugs
Controller of India has instructed manufacturers to include
Steven Johnson Syndrome (SJS) in package insert of product
containing carbamazepine and advised to the physicians to
screen the patients for HLA-B*1502 allele before initiating
treatment with carbamazepine. However, India doesn’t have a
strong database on ADRs and has to depend on data from
Western countries to take decisions relating to banning and
suspension of drugs. The present database of PvPI available
on ADRs is not sufficient to represent the population which
consumes the drug or to which the drug has been prescribed
for. Epidemiological data on drug utility and outcomes of
treatments is inadequate. Therefore, for sufficient database on
ADRs, awareness among the healthcare providers of government
and corporate hospitals including rural areas are needed to be
created. The other healthcare institutes like dental, pharmacy,
Frontiers in Pharmacology | www.frontiersin.org 2September 2015 | Volume 6 | Article 194

Lihite and Lahkar An update on the Pharmacovigilance Programme of India
TABLE 1 | SUSARs reported during 2011–2013.
Sl. No. Drug name Reported ADR SUSARs in PvPI database Global drug safety database (Vigibase)
1 Sodium valproate Slurred speech 11 14
2 Streptokinase Hepatitis 4 18
3 Liraglutide Ischemic coronary artery disorder (Anginal pain) 2 45
4 Bupivacaine Confusional state 2 13
5 Omeprazole Hypokalemia 1 49
6 Furosemide Breathing abnormalities (Tachypnoea) 1 33
7 Nitrofurantion Lip oedema 1 9
8 Amphotericin-B Hypernatremia 1 6
9 Tramadol Renal & urinary tract neoplasm 1 5
10 Metronidazole Thrombophlebitis 1 2
11 Gentamicin Thrombophlebitis 1 1
nursing, paramedical etc. associated with patients care by
providing safe and effective medication should be encouraged
for ADR reporting. Beside these, pharmaceutical companies need
to be involved in PvPI for better pharmacovigilance system.
Furthermore, incorporating a chapter on pharmacovigilance in
education curriculum of medicine, pharmacy, nursing etc. could
generate the culture of ADR reporting among young scholars.
It was observed that the percentage of ADR reporting by
physicians was higher as compare to pharmacists and other
healthcare providers (Kalaiselvan et al., 2014a). In India, system
of distribution does not leave much scope for pharmacists,
nurses, and other healthcare providers to be a significant source
of ADR reporting. Even though nurses are in closer contact
with the patients for a longer duration, in the event of ADRs
observed by them, they have to inform to the treating physician.
Similarly, pharmacist’s can also promote the development,
maintenance, and ongoing evaluation of a programme to reduce
the risks of ADRs by detecting, reporting, and assessing any
suspected ADRs. Therefore, co-ordination among clinician,
pharmacist, and nurse appears vital in contributing each of their
respective expertise and experience to promote the rational use
of medicines. It was also observed that the lack of knowledge
of where, what and how ADRs should be reported is also
affects reporting. The reason for poor reporting may also include
financial incentives, ignorance (only serious ADRs are to be
reported), apprehension of reporting serious ADRs, and lack
of time or over load. Thus, healthcare professionals should be
under an obligation to report ADR if detected while clinical
practice. However, several steps are taken to tackle the problems
of under reporting by addressing various issues in various
forum and conferences, circulating questionnaire form, writing
to professional bodies, scientific journals, etc. In an effort
to extent awareness among healthcare providers, continues
medical education are being organized in various medical
colleges across the country. In addition, Technical Associates are
recruited at AMC to facilitate ADR reporting from healthcare
providers.
In year 2013, India’s contribution to WHO–UMC’s global
drug safety database (Vigibase) was 2%. India was 7th in
position among top 10 counties contributing to global drug
safety database. Among Asian countries, India is the only country
having more than 1 lakhs ICSRs in Vigibase. According to WHO-
UMC Documentation Grading-Completeness Score, the average
completeness score of India in 3rd quarter of 2014 was 0.94 out
of 1 [(WHO-Uppsala Monitoring Centre (UMC), 2014)]. Thus,
from this completeness score it can be predicted that AMCs of
PvPI are collecting all the necessary information required for
ADR reporting via Vigiflow.
In conclusion, awareness about the ADR reporting among the
healthcare providers can improve the rate of reporting across
the country. Moreover, by developing own national database and
sharing information with other regulatory agencies will provide
the much needed information from worldwide data to take the
correct decision on medicines and products.
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Conflict of Interest Statement: The authors declare that the research was
conducted in the absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
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