PHARMACOVIGILANCE

FROM:-
DEEPTI KUMARI
HIMANI ARORA
GEETA BHATT
HIMANI BORA
PALLAVI SHRIVASTAVA
TRIPTI KAUSHIK
EKTA JAIN

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CONTENTS
Introduction
The scope of pharmacovigilance
Need for pharmacovigilance
WHO Programme for International Drug Monitoring
Pharmacovigilance in India
Conclusion
References

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 INTRODUCTION
WHO definition:

The science and activities relating to the

detection, assessment, understanding and
prevention of adverse effects or any other drug-
related problem.
• Recently, its concerns have been widened to include herbals,
traditional and complementary medicines, blood products,
biologicals, medical devices and vaccines" (WHO, 2002).
 This applies throughout the life cycle of a medicine equally to the
pre-approval stage as to the post-approval.

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Pharmaco - Vigilance
Pharmaco = medicine
Vigilare = to watch
alert watchfulness
forbearance of sleep; wakefulness
watchfulness in respect of danger; care; caution;
circumspection
the process of paying close and continuous attention

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WHAT IS PHARMACOVIGILANCE
(PV)?
The science and activities relating to the detection,
assessment, understanding and prevention of
adverse effects or any other medicine-related problem -
WHO
HISTORY…..
Registration of New Chemical Entities was very much
dependant on the status of products in the reference countries
Changes to product information was mainly industry driven
Few pre-clinical studies conducted in the region and hardly any
Phase IV studies
Adverse drug reaction reporting was very minimal and mainly
involved reports submitted by health care professionals
CONT…….
Most reports were for known reactions involving older drugs
which were used in government-run hospitals
Signal detection not possible as there were too few reports
Only able to detect some quality defects of generics which
manifested as ADRs
Pharmacovigilance was mainly about getting ADR reports and
submitting them to WHO
No significant regulatory changes made based on these reports
CURRENT SCENARIO
Increased awareness and interest amongst doctors and
pharmacists to report ADRS as they have seen some benefit in
reporting
Increasing number of clinical trials being conducted especially
in Singapore, Thailand and Malaysia
GCP training for investigators served to increase awareness of
SAE and ADR reporting amongst health care professionals and
the industry
CONT…..
More hospitals and companies using on-line reporting system –
less hassle than submitting hard copy reports
Increasing involvement by hospital pharmacists in
pharmacovigilance – during clinical ward rounds and when
counseling patients
The Aims of Pharmacovigilance
To improve patient care and safety
To improve public health and safety
To contribute to the assessment of benefit, harm,
effectiveness and risk of medicines
To promote understanding, education and clinical
training
Who are the partners?
Government
Industry
Hospitals and academia
Medical and pharmaceutical associations
Poisons information centres
Health professionals
Patients
Consumers
Media
WHO
The scope of pharmacovigilance
Improve patient care and safety in relation to the use of
medicines, and all medical and paramedical interventions,
Improve public health and safety in relation to the use of
medicines,
Contribute to the assessment of benefit, harm,effectiveness
and risk of medicines, encouraging their safe, rational and
more effective (including cost-effective) use, and
Promote understanding, education and clinical training in
pharmacovigilance and its effective communication to the
public.

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Adverse Drug Reaction
 "A response to a drug which is noxious and unintended, and which
occurs at doses normally used in man for the prophylaxis,
diagnosis, or therapy of disease, or for the modification of
physiological function."
Adverse Event
 Any untoward medical occurrence that may present during
treatment with a pharmaceutical product but which does not
necessarily have a causal relationship with this treatment.
Side Effect
 Any unintended effect of a pharmaceutical product occurring at
doses normally used in man which is related to the
pharmacological properties of the drug.

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SERIOUS ADRS
 A serious adverse event (experience) or reaction is any untoward
medical occurrence that at any dose:
 results in death,
 is life-threatening,
 requires inpatient hospitalization of prolongation of existing
hospitalization,
 is a congenital anomaly/birth defect.

UNEXPECTED ADVERSE REACTION:

 An adverse reaction, the nature, severity or outcome of which is
not consistent with the summary of product characteristics.

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Adverse Reactions:Possible Causes
Intrinsic factors of the drug
 Pharmacological
 Idiosyncratic
 Carcinogenicity, Mutagenicity
 Teratogenicity
Extrinsic factors
 Adulterants
 Contamination
Underlying medical conditions
Interactions
Wrong usage
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Congenital limb defects due to the use of Thalidomide

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Need for pharmacovigilance

Reason 1:
 Humanitarian concern –
 Insufficient evidence of safety from clinical trials
 Animal experiments
 Phase 1 – 3 studies prior to marketing authorization

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Registration Criteria
Efficacy
 Evaluated from data obtained from clinical trials
Quality
 Compliance to established standards, manufacture by GMP
licensed premise
Safety **
 Toxicology, clinical trials

** (Very limited information)

(Further established through post registration studies)
(Discovering new dangers of drugs after marketing is common)

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Drug Development
Clinical development of medicines

Phase I Phase III

20 – 50 healthy volunteers 250 – 4000 more varied
to gather preliminary data patient groups – to
determine short-term safety
and efficacy
Animal experiments for
acute toxicity, organ
damage, dose dependence, Phase II
metabolism, kinetics, Phase IV
carcinogenicity, 150 – 350 subjects with
mutagenicity/teratogenicity Post-approval studies to
disease - to determine
determine specific safety issues
safety and dosage
recommendations

Preclinical
Phase IV Spontaneous
Animal Phase I Phase II Phase III
Experiments Post-approval Reporting

Development Post Registration

Naresh.K, M.Pharm, 1st sem(IP), SPIPS, HNK 19

Limitations of phase 1 -3 clinical trials
limited size: no more than 5000 and often as little
as 500 volunteers
narrow population: age and sex specific
narrow indications: only the specific disease
studied
short duration: often no longer than a few weeks

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ACTIVE INGREDIENTS WITHDRAWN
 THALIDOMIDE (1961) Congenital limb defects
 BENOXAPROFEN (1982) Hepatotoxicity
 PHENFORMIN (1982) Lactic acidosis
 FENFLURAMINE (1997) Heart-valve abnormalities
 ASTEMIZOLE Many drug interactions
 PHENYLPROPANOLAMINE(2000) Haemorragic stroke
 KAVA KAVA Liver abnormalities
 CERIVASTATIN Rhabdomyolysis
 CISAPRIDE Cardiac arrythmias
 ROFECOXIB (2004) Cardiovascular events
 VALDECOXIB (2005) Cardiovascular events,
serious skin reactions
 COMFREY, SENECIO Nephrotoxicity
 TEGASEROD (2007) Cardiovascular events
 CLOBUTINOL (2007) Cardiac arrhythmia

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Reason 2:

• Medicines are supposed to save lives

Dying from a disease is sometimes unavoidable; dying
from a medicine is unacceptable. Lepakhin V. Geneva
2005

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UK:

It has been suggested that ADRs may cause 5700 deaths per
year in UK.
Pirmohamed et al, 2004
US:

ADRs were 4th-6th commonest cause of death in the US in 1994

Lazarou et al, 1998

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Reason 3: ADRs are expensive !!

Cost of drug related morbidity and mortality

exceeded $177.4 billion in 2000 (Ernst FR &
Grizzle AJ, 2001: J American Pharm. Assoc).
ADR related cost to the country exceeds the
cost of the medications themselves.

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Reason 4:
Promoting rational use of medicines and
adherence
Reason 5:
Ensuring public confidence

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Reason 6:
Ethics
To know of something that is harmful to
another person who does not know, and not
telling, is unethical

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Partners
Government
Industry
Hospitals and academia
Medical and pharmaceutical associations
Poisons information centres
Health professionals
Patients
Consumers
Media
WHO
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What should be reported
New drugs
Report all suspected reactions including minor ones
For established or well known drugs
 All serious, unexpected, unusual ADRs
Change in frequency of a given reaction
ADRs to generics not seen with innovator products
ADRs to traditional medicines

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All suspected drug-drug, drug-food, drug-food
supplement interactions
Statement highlighting marine source of supplements
such as glucosamine so that can be avoided by those
with allergy to sea food
ADRs associated with drug withdrawals
ADRs due to medication errors
eg vincristine given IT
ADRs due to lack of efficacy or suspected
pharmaceutical defects

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 Innovator products
 Limited information available at time when drug is first
marketed.

 Conduct intensive monitoring to identify new, unlabeled

adverse reactions, monitor for “rare” reactions.

 Provide updates to prescribers on new findings, labelling

changes, safety issues.

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 Generic products
 Monitor efficacy

 Monitor adverse effect profile to study differences in ADR

pattern with respect to innovator products

 Help in improving quality of generics used

 Whether the problem arose due to ADR or quality defects

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WHO Programme for International Drug
Monitoring

Started 1968
Located in Uppsala, Sweden
Collaborating centre for maintaining global ADR
database - Vigibase

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Roles of WHO Collaborating Centre
Identify early warning signals of serious adverse
reactions to medicines
Evaluate the hazard
Undertake research into the mechanisms of action to
aid the development of safer and more effective
medicines

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Pharmacovigilance in India
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 .
National Pharmacovigilance Centre
CDSCO has initiated a country-wide
Pharmacovigilance programme under the aegis of
DGHS, Ministry of Health & Family Welfare
Government of India.
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National Pharmacovigilance Programme
The Programme aims to foster the culture of ADR
notification in its first year of operation and
subsequently aims to generate broad based ADR data
on the Indian population.
Sponsored and coordinated by the country’s central
drug regulatory agency – (CDSCO)
 Peripheral Pharmacovigilance Centres
 Regional Pharmacovigilance Centers (RPCs)
 Zonal Pharmacovigilance Centre (ZPCs)

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SO….WHAT IS OUR ROLE?
SEND NOT ONLY
QUANTITY BUT….

QUALITY
REPORTS
HOW?
Monitor clinical status of patients
Identify the correct ADRs not side effects
Get more information
Investigate at hospital level
Help doctors to fill-up the forms
Keep patient’s record if more information needed

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 CONCLUSION
Pharmacovigilance looks at all available information to
assess the safety profile of a drug.
Pharmacovigilance should also take the benefit of the
drug in account.
Pharmacovigilance required for systematically
identifying and correlating drugs and side-effects and
taking corrective actions, especially for the product
launching first time in India.

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A wise man can see as much as he ought; not as much
as he can.

Michel de Montaigne (1533-92) french phelosopher

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Pharmacovigilance is Essential

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 REFERENCES
1. The need for Pharmacovigilance, WHO,technical brieflig seminar,
sept, 2008.
WHO Pharmacovigilance:ensuring the safe use of medicines. WHO
policy perspective on medicines.Geneva:WHO;2004
2. The Importance of Pharmacovigilance, World Health Organization
2002
3. World Health Organization Technical Report No, 498 (1972)
4.H.P.Rang,M.M.Dale,J.M.Ritter,P.K.Moore,“Pharmacology”,CURCHILL
LIVINGSTONE, 5th edition,5
5. National Pharmacovigilance Protocol, Ministry of Health and Family
Welfare, Govt. of India

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6. Ronald D. Mann Elizabeth B. Andrews
“Pharmacovigilance” WILEY, 3
7. www.pharmainfo.com
8. www.pharmabiz.com

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Naresh.K, M.Pharm, 1st sem(IP), SPIPS, HNK 46