Q.

1 ANSWER THE FOLLOWING QUESTIONS (2 marks)

UNIT I

1. DEFINE PHARMACOVILANCE.
According to WHO it can be defined as the science and activities relating to the
detection, accessment, understanding and prevention of adverse effect or any possible
drug related problem.

2. DEFINE ADVERSE DRUG REACTION.

Any response to drug which is not yet and uninitiated and which occurs at the normal
used in the man for prophylaxis, diagnosis and therapy of disease or for the modification
of physiological function.

3. DEFINE ADVERSE EVENT

Any unwanted medical occurrence that may present during the treatment with a
pharmaceutical product but which does not necessarily have casual relationship with this
treatment.

4. DEFINE
A. Risk: - the probability of harm being caused: the probability (chances) of an
occurrence.

B. Absolute risk: - risk in population of the exposure person in the probability of an

event affecting members of the particular population.
Absolute risk can be measured overtime (incidence) or in the given time
(prevalence).

C. Suspected ADR: - the term suspected ADR means while a casual relationship in
individual case has not been proven, relationship is initially as used to exist
between the medicine taken and symptoms or diagnosis.

D. Casualty assessment: - the evaluation by a medicinal professional concerning

that the medicine or therapy has caused or contributed to the adverse event.

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 E. CDSCO :- (Central drugs standard control organization)
It is a central truck authority for discharging functions assigned to the central
government under the drug and cosmetic act.

F. PVPI :- (the pharmacovigilance program in India)

It is an Indian government organization which identifies and responses to the drug
safety.

G. Predictability: - it is a degree to which correct prediction or forecast of the

systemic state can be made either qualitatively or quantitatively.

H. Preventability: - knowledge about the drug and its potential reaction is required
for the prevent ADR to check for potential drug interaction computer based
analysis should be used.

5. WHAT IS SAFETY DATA ANALYSIS?

It is the use of advance analytical technique with the purpose of examining the large and
very data set containing safety information to uncover hidden pattern, unknown
correlation, trends, patient preference and other useful information that can help
organization make more informed.

6. INCREASE THE TYPE OF ADVERSE DRUG REACTION (ADR)

 TYPE A  Augmented
 TYPE B  Bizarre
 TYPE C  Chronic
 TYPE D  Delayed
 TYPE E  End of therapy
 TYPE F  Failure of Therapy

7. ENLIST ANY 4 ACCESSMENT CRITERIA.

 method in casualty assessment criteria
 severity accessment criteria
 seriousness accessment criteria
 predictability Accessment criteria
 preventability accessment criteria

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8. ENGLISH METHOD OF REPORTING IN THE PHARMACOVIGILANCE
 passive surveillance
 active survivelens
 stimulated reporting
 targeted clinical investigation

9. WHAT IS UMC?
(Uppsala monitoring center – Sweden) it is an independent setup for drug safety and
scientific research working for the word where the safe and effective use of medicine is
common place.

UNIT II
1. WHAT IS ATC
Anatomical, therapeutic, Chemical classification system the active chemical
substances are divided into different group according to the organ and system on which
they act and their therapeutic pharmacological and their chemical properties.

2. WHAT IS WHO-FIC
World health organization family of international classification is comprise of the
classification to describe various aspects of a health and health system in the consistent
manner.

3. ENLIST TYPE OF THE RELATED CLASSIFICATION.

 International classification of primary care
 International classification of external causes of injury
 ATC classification
 An ISO-9999 for technical aid for person with disability.

4. ENGLISH TYPE OF REFERENCE CLASSIFICATION

 International classification of functioning and disability of health.
 International classification of health internationalis

5. WHAI IS INN?
The international non proprietor name is an appreciation Eric and non proprietor name
given to the Pharmaceutical drug or an active ingredient which has been coordinated by
WHO.

6. DEFINE

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 A. MEdDRA: - it is and clinically validated international medical terminology used
by the regulatory authorities and regulated by pharmaceutical industries.

B. Eudravigilance: - European Union drug regulatory authorities’

pharmacovigilance is the European data processing network and management
system for reporting and evaluation of suspected ADR to medicine.

C. Vigiflow: - it is a management system for the recording and processing and

sharing report of address effect. it's a food domestic collection and processing of
individual case safety report data

D. Vigibase: - it is the unique collection of the international drug safety data, it is a

name of WHO-ICRS database.

E. Vigicare: - providing Pharmacovigilance service and expected to meet the

complex regulatory requirement in the pharmacovigilance.

7. ENGLISH FOUR SOFTWARE USED IN THE PHARMACOVIGILANCE

 Oracle orgus safety
 Aris-G
 Clin trance
 Oracle adverse event reporting system
 PVNET

8. ENLIST ANY FOUR INFORMATION SOURCES.

 Primary sources
 Secondary sources
 Treachery sources
 Internet sources

9. WHAT IS CRO ? ENLIST FOUR CRO.

Contract research organization is a service research organization which provides
support to the pharmaceutical industries.
It offers various pharmaceutical research that is essential for the conducting clinical trial
in present boom when various complications are involved in drug discovery process
 IQVIA

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  PAREXEL
 PRA-HEALTH SCIENCE
 ICON

10. DEFINE DDD.

Defined daily dose is the dose to is assumed average maintenance those per day for a
drug used for its main indication in adult.
It is unit of measurement of those not necessarily reflect recommended or prescribed
daily dose

UNIT III

1. DEFINE VACCINE SAFETY SURVIVALS.

The science and activity related to the detection, assessment, understanding and
prevention of the ADR following immunization and other vaccine and immunization
related issue and to the prevention of the unwanted effect on the vaccine or
immunization.

2. DIFFERENTIATE BETWEEN DRUG AND VACCINE

VACCINE Drug

Public campaigns common public campaigns rare

Mainly in field offices and clinic Mainly in clinic hospital and pharmacies

Gold chain of an critical biological product, Most a room temperature chemical product
lot rarization, stability

healthy prevention of the disease large It treat disease a small population mostly in
population mostly used in infants and adult adult
children

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3. CLASSIFY ADVERSE EVENT FOLLOWING IMMUNIZATION (AEFI)
 vaccine reaction
 program error
 coincidental reaction
 injection reaction
 unknown

4. WHAT IS PASSIVE AND ACTIVE SURVIVELENCE

Passive surveillance: - refers to collect the pharmacovigilance data from conventional
procedure of treatment.

Active pharmacovigilance: - it is a certain completely a number of the adverse event

why a continuous pre organised process.

5. WHAT IS STIMULATED REPORTING

A method used to encourage and facility by health professionals for new product or for
limited time period

6. DEFINE
Case control study: - it is the observation study in which subject are sample based upon
presents or absence of a disease and then their prior exposes status is determined.

Cross sectional study: - research study that involve multiple observation which may be
useful to determine how variable effects each other at the same time and period

Cohort study: - it is the study which is Undertaker to obtain additional evidence to

reflect or support existence of the association between suspected case and disease

7. WHAT IS TARGETED CLINICAL INVESTIGATION?

When significant risk are identified from pre-approved clinical trial further clinical
studies might because for the evaluate the mechanism of action of the adverse drug
reaction.

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 UNIT IV

1. ENLIST ICH GUIDELINE.

 Quality guideline
 Safety guideline
 efficacy guideline
 Multi disciplinary guideline

2. ENLIST EFFICIENCY GUIDELINE

 E1 :- clinical safety for drug used in the long term treatment
 E2 A- E2 F :- pharmacovigilance
 E3 :- clinical study report
 E4 :- dose response studies
 E5 :- ethnic factor
 E6 :- good clinical practice
 E7 :- clinical trial in geriatric population
 E8:- general consideration for clinical trials.

3. WRITE SHORT NOTE ON PHARMACOKINETIC AND TOXICOKINETIC

PHARMACOKINETIC:-
 It is the branch of pharmacology which deals with the study of what does the
body does to drug.
 It studies the absorption, distribution, metabolism and excretion of the drug
 The therapeutic effect of the drug can be calculated by the amount of the act of
pharmaceutical ingredient present inside the body mainly at the site of the target.
 this consequently depend upon the ADHE of the drug which however help to
determine the change in the plasma concentration of the drug in the body
 ADHE profiling is critical for the establishing dose range and is a kid determinant
in the selection of viable candidate.
 It also facility in the determining the administration scheduled for the subsequent
clinical trial phase.

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 TOXICOKINETICS:-
 It Toxic kinetics in points are similar to the pharmacokinetic expect that the
sample are collected from animal during the toxicology and side effect studies.
 The studies helps the investigator in understanding the behavior of the drug at the
maximum dose level used in the toxicology studies along with steady state
accumulation after repeated administration
 The same bio analytics method as developed for in Vivo pharmacokinetic
evaluation are suitable for usually measuring the concentration of the drug in the
relevant biological Matrix ex- plasma.

4. WHAT IS GENOTOXICITY?
o Essay for the Jain mutation is generally considered sufficient to support all single
doors clinical development trial.
o it's support to multiple doors clinical development trial two type of test are
suggested
o Second type of taste if selected should be complete prior to first human use in
multiple dose studies.
o The in vitro component of the first type if selected should be first prior to multiple
do human study.
o The IN vivo component of the type one should be completed prior to phase II

5. WHAT IS IMMUNOTOXICITY?
o all new human pharmaceutical should be evaluated for the potential to produce
immunotoxicity using standard toxicity protocol study
o Additional immune toxic studies be conducted as an appropriate based on the
weight of the evidence review including immune related signals from the standard
of the standard toxicity studies.
o If there is an indication for the additional immune to the city studies their should
be complete during the phase 3 before exposure to the large population of the
patient.

6. WHAT IS UNEXPECTED ADR?

 An ADR whose nature, specificity, severity or outcome is not consistent with
term description used in the local or regional product labeling is considered as an
expected.
 When a marketing authorization holders is ascertain weather and ADR is
expected or unexpected the area should be treated as unexpected.

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  And expected dear with the fetal outcome should be considered unexpected unless
the labelling specification stated that the area might bi associated with the fatal
outcome.
 class ADR should not be automatically considered to be expected for the
subjected drug
 They should be considered expected only if described in the product labeling.

UNIT V

1. DEFINE
Pharmacogenetics: - it is the study of the house genetic variation affects the deposition
of the drug including their metabolism, transport, there safety and efficacy
.
Pharmacogenomics’: - the study of the genetic variation to result in variable drug
responses and including the shape of the genetic polymorphism of the drug metabolism
enzyme drug transporters and drug receptor.

Single polymorphism: - genetic variation that are common (occurring in at least in 1%

of the population) are known as polymorphism and mutation of the single nucleotide are
known as the single nucleotide polymorphism.

2. WRITE SHORT NOTE AND THE AGE CLASSIFICATION OF PAEDIATRIC

PATIENT AND PAEDIATRIC FORMULATION.

Age classification of the pediatric patient

 Preterm Neonatal :- the period when a newborn is born before full gastrointestinal
period
 Nonet :- birth to 1 month
 Infant :- 1 year
 Toddler :- 2 year
 Early childhood :- 2 year to 5 year
 Middle childhood :- 6 year
 Early adolescent :- 12 year to 18 years
 late adolescent :- 18 year to 21 years
Pediatric formulation need to be appropriate for the child in the term of the doors conveying
and acceptability to ensure complaints with the medication

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 There are difference in the pediatric anatomy and physiology that can impact upon the
performance of the drug that is different from that observed in adult.

3. CLASSIFICATION OF DRUG IN PREGNANCY AND LACTATION

Classification of drug in pregnancy.

The FDA established 5 letter risk category

A) Controlled study in human show no risk to the fetus

B) no control studies have been conducted in human, animal studies show no risk to
the fetus
C) not controlled study in animal or human
D) evidence of risk to human fetus
X) Contraindicated in pregnancy

Classification of drug in lactation

L1 (SAFEST):- medication that has taken by a large number of the breast feeding mothers
without any observed increase in the adverse effect in the infant

L2 (SAFER):- studied in limited number of the breastfeeding women without increase in the
adverse effect in their infant

L3 (MODERATORY SAFE):- no control studies in the breast feeding women

L4 (POSSIBALY HAZZARD ) :- there is evidence of the risk to the breastfeed in infant or to
breast milk production but the benefit from use in breastfeeding mother may be acceptable
despite the risk to the
Infant.

L5 (CONTRAINDICATED):- studies in the breastfeeding mother have demonstrated

significant and documented risk to their infant based on the human experiment.

4. ENLIST THE CIOMS FORM

 CIOMS I  reporting of ADR
 CIOMS II  reporting of pediatric drug safety update summarized

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  CIOMS III  guideline for preparing care clinical safety information on drug
 CIOMS IV  benefit risk balance for marketed drug
 CIOMS V  current challenges in Pharmacovigilance
 CIOMS VI  management of safety information from clinical trial
 CIOMS VIII  development of safety update report
 CIOMS VIII  practical aspect of signal detection in Pharmacovigilance
 CIOMS IX  practical approach for risk minimization for medical product
 CIOMS X  evidence synthesis and Meta-analysis of drug safety.

5. WHAT IS SCHEDULE Y?
 Requirement and guideline for permission to import and manufacture of a new
drug for sale or to undertake in clinical trial.
 to frame guideline for conduct of the clinical research control and regulation for
new drug
 CDSCO and DTAB formulated GVP under schedule Y In 2005

6. WHAT IS PHARMACOVIGILANCE STUDY IN GERIATRIC PATIENT?

 Main goal of pharmacovigilance in geriatric patient is to improve the safe and
rational use of the medicine and their by improving the patient care health and
safety
 pharmacovigilance is party particularly concern with ADR
 It focus on elderly individuals with complex problem emphasizes functional status
and quality of life.

7. WHAT IS PHARMACOVIGILANCE STUDY IN PEDIATRIC PATIENT?

 Intensive pharmacovigilance is needed in pediatric population due to increase the
suspect ability to ADR and predisposing factor.
 Intensive pharmacovigilance is the systemic monitoring as the occurs of the
adverse event resulting from drug used during the entire length of the
prescription.

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 
Q. 2 ANSWER TO THE FOLLOWING QUESTIONS (5 MARKS)

UNIT I

1. IMPORTANCE OF DRUG SAFETY MONITORING.

An adverse drug reaction could be any unintended reaction in patient body which occurs
as a result of administration of the drug.
Drug safety monitoring is a risk mitigation exercise in which the ADRs caused by the
therapeutic drug, biological or medical devices can explode, prevented or minimized.
Drug safety is an essential element for the effective use of medicine and for High quality
medical care.
It has a potential to inspire confidence and trust among people and health professionals in
medicine and contribute to raising standard of the medical practice.
ADR can significantly diminish the quality of the life.
Increase the rate and duration of the hospitalization can increase the mortality and
morbidity.
Financial burden on healthcare authorities increase in enormously.
As the newer discoveries are becoming available to the needy population at the faster
rate, drug related adverse reaction are also becoming more common, sever and more
complex.
Pharmacovigilance is the process of identifying of expected and unexpected adverse
reaction resulting from the use of medicine in the post marketing phase.
Pharmacovigilance benefit everyone and patient care protected from unsafe drug.
Drug regulator review patient data that help them to take regulatory decision.
Analysis of ADR data help to make regulatory decision.

2. WHO INTERNATIONAL DRUG MONITORING PROGRAM.

Whose program for international drug monitoring begin in 1968 with Uppsala monitoring
center in Sweden begin the collaborating center for this global initiative.
The main function of the coordinating center is communication of safety signals
recognized through analysis of the global data.
WHO Promote pharmacovigilance at the country level, at the end of 2010- 127 countries
where part of the WHO PHARMACOVIGILANCE PROGRAM?
India became the member of WPIDM in 1998.

Functions:-
 Identification and analysis of new adverse reaction signal from the case report
information submitted to National center and from them to the database.

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  Information exchange between World health organization and national center
mainly through VIGIMADE an email information exchange system.
 Publication of the periodical new letters, guideline and books in
Pharmacovigilance and risk management area.
 Provision of training and consultancy support to National center and countries
establishing Pharmacovigilance system.
 Methodological research for development of the pharmacovigilance as a science

3. PHARMACOVIGILANCE PROGRAM IN INDIA

Launched with broad objective to safe guard the health of the people of India.
The Central drug standard control organization (CDSCO) initiated a national wide
pharmacovigilance program under the ministry of health and family welfare in 2010 with
AIIMS as national coordinating center for monitoring adverse drug reaction.
Adverse drug reaction are reported from all over country to NCC-PvPI
it work in collaboration with the global ADR monitoring center (WHO-UMC) Sweden
two contribute in the global ADR database.
NCC-PvPI monitor and the adverse D reaction among Indian population and help the
regulatory authority of India (CDSCO) in taking decision for safe use of medicine.

Mission: - safeguard with the health of Indian population by insuring that the benefit of
use of medicine outweigh with the risk associated with it is.

Vision: - to improve patient safety and welfare in Indian population by monitoring the
drug safety and their by releasing the risk associate with the use of medicine.

Functions of Pharmacovigilance system:-

 To promote rational use of medicine is one of the objective of the program.
 To create the national wide system for patient safety reporting.
 To identify and analyse the new signals from the reported cases.
 To analyse the benefit risk ratio of marketed medication.
 To support regulatory agencies in the decision making process on use of
medication.
 To emerge as a national center of excellence for pharmacovigilance activities.

4. INTRODUCTION TO ADVERSE DRUG REACTION.

DEFINITIONS
Adverse event: - it is define as any medical occurrence temporally associated with the
use of medicinal product but not necessarily casually related.
Adverse drug reaction: - according to WHO it is defined as a response to a drug which
is noxious unintended which occurs for those normally used in human being for

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 prophylaxis, diagnosis or therapy of a disease or for the modification of the physiological
function.

CLASSIFICATION OF ADR:-
The adverse drug reaction can be classified on the basis of effect

Type An effect:-
 Augmented pharmacological effect
 adverse event that are known to occur from the pharmacology of the drug and
orders repeated they are seidomfetal and relatively common.
 Ex:- hypoglycemia due to insulin injection
 Ex: - hemorrhage due to anticoagulant.

Type B effect:-
 Bizarre effect
 Adverse effect that occur unpredictably and open have the high rate of morbidity
and mortality.
 They are uncommon
 Ex:- anaphylaxis due to penicillin
 Ex: - bone marrow suppression by chloramphenicol.
Type C effect
 Chronic effect
 Adverse effect that only occur during the prolong the treatment and not with
single doses.
 Ex: - chronic dysfunction due to laxatives.
 Ex :- erotogenic causing syndrome with prednisolone

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Q.3 ANSWER TO THE FOLLOWING QUESTIONS (10 MARKS)

UNIT I

1. METHOD OF CASUALTY ASSESSMENT.

With few exception case report describe suspected adverse drug reaction.
Various approaches have been developed for the structural determination of the life
would of the casual relationship between drug exposure and adverse event.
Ex: - by the WHO drug monitoring program the European commission and the French
National pharmacovigilance program

CASUALTY CATEGORIES
The casualty categories describe by the Uppsala monitoring center are as follow.

A. Certain :-
 A clinical event, including laboratory test abnormality occurring in the
plausible time relationship to drug administration and which cannot be
explained by the concurrent disease or other drug or chemical.
 The response to the withdrawal of drugs should be clinically plausible.

B. Probable/ likely :-
 Event or laboratory test abnormality with responsible time relationship to drug
intake.
 Response to withdrawal clinically responsible
 re challenge not required

C. possible :-
 Event or laboratory test abnormality with reasonable time relationship to the
drug intake.
 Could also be explain by disease or other drug
 Information on drug withdrawal maybe lacking or unclear

D. Unlikely :-
 Event or laboratory test abnormality with a time to drug intake that make a
relationship improbable.

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  Disease and other drug provide plausible explanation.

E. Conditional :-
 Event or laboratory test abnormality
 More data for proper assessment needed
 additional data under examination

NARANJO SCALE METHOD:-

 widely accepted method
 Method used to determine the like food of the weather the ADR is actually due to the
drug rather than the result of other factor.
 It consists of 10 question that are answered yes, no or unknown
 these answer are designed a score term definite, probable, possible or doubtful
Definite – when total score is > 9
Probable – when total score is > 5-8
Possible – when total score is > 1-4
Doubtful – when total score is <0

Limitations:-
Method only explain the casualty of one individual drug not explain the casualty occur due to
drug interaction.
The Naranjo scale advanced drug reaction probability skills to access the adverse drug reaction
please answer the following questions and give patient score.
 Are there previous conclusion report on this reaction?
 Did the adverse event occur after the suspected drug was administered?
 Did the adverse reaction improve when drug was discontinued or specific antagonist was
administered?
 Did the adverse reaction reappeared when the drug was administered?
 Are there alternative causes that could have on their own cause the reaction?
 Did the reaction reappear when placebo was given?
 Was the blood detector in blood concentration known to be toxic?
 Was the reaction more saver when dose was increased or less sever when the dose was
decreases?
 Did the patient have a similar reaction to the same or similar drug in any previous
exposure?

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 Was the adverse event confirm by any objective evidence?

2. HISTORY AND DEVELOPMENT OF PHARMACOVIGILANCE

The historical phase help us to understand why pharmacovigilance help us to achieve
such important result for means health and for pharmacology itself, and to identify the
challenges that await pharmacovigilance in future year.

 1948 :- 15 year old patient died in course of the routine anesthesia with
chloroform the patient had problem of ingrow nail of the toe, and was given
chloroform to remove it and it cause the fibrillation of ventricle which result in
the patient death. (Hannah Grenor)

 1893:- Lancer initiated foundation of the commission and starting collection of

the notification about side effect.

 1836 :- USA leather cases after sulfanilamide elixir containing die ethyl glycol
as a solvent caused death of 107 persons

 1938 :- US federal food and drug act (US-FDA) required that the pharmaceutical
should be pure and free of any contamination

 The thalidomide tragedy (1957-1961) :-

Thalidomide first enter the German market in 1957 as an over the counter remedy
best run the maker safety claim.
He started (Australian obstruction (Dr William matrixide) recommending this of
level use of the drug to his pregnant patient setting worldwide Trend.
Many children in 1960 like a kindergartener were born with the phecomelia as a
side effect of drug thalidomide resulting in the shortening observance of limb.

 1961 :- Dr McBride reported 20% increase in the fetal abnormalities and

phocomelia in relation with thaledomide use letter the numerous report from other
countries

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 1962 :- USA KEFAUVER HARRIES amendment to law ( requirement to prove
safety and efficacy before issuing MA)

 1963 :- resolution WHA 16.36 reformed the need for early action in regard to
adverse the reaction

 1964 :- UK started yellow card system

 1965 :- European union issued EC directed 65/65 – first European pharmaceutical

directive

 1968:- WHO pilot project started to pull adverse drug reaction from multiple
countries.

 1997 :- ICH E2B adopted electronic reporting standard agreed worldwide

 1999:- institute of medicine report on error and risk issued introduction of risk
management concept.

 2001:- post marketing safety reporting guideline FDA guidance on how to report
adverse event in post marketing phase.

 2002 :- PDUFA iii prescription drug user fees act allowed FDA to charge piece

 2003 :- the Tome-94 pages of proposal rule on adverse event reporting

premarketing action finalized in 2010

 2004 :- profit risk management guideline

 2005 :- final risk management guideline specific how to perform signal detection,
risk assessment and risk mitigation

 2007 :- FDA amendment act

 2008 :- volume 9A in pharmacovigilance

 2010:- new IND reporting value and European pharmacovigilance legislation

process.

 2011 :- volume to detail guideline on the correction, verification and presentation

of the address event or reaction report arising from clinical trial on medical report
for human use

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  2012 :- European pharmacovigilance legislation effective

 2014:- MHRA good pharmacovigilance practice for medicine.

UNIT II
1. WHAT IS ATC? CLASSIFIED ATC IN DETAIL.
ATC: - the anatomical therapeutic chemical system the active substances are
divided into different group according to the organ of system on which they
act and their therapeutic pharmacological and chemical properties.

Classification of ATC.
Drug are classified in group of five different level
A. ATC first level :- the system have 14 men anatomical main group
B. ATC second level :- therapeutic sub group
C. ATC third level :- pharmacological sub group
D. ATC fourth group :-: chemical sub group
E. ATC fifth level :- chemical substances

ATC system is able to classify the active ingredient of a drug under the strict
hierarchy so that is appropriate used and not mistaken for another drug
It control by the WHO coordinating center for drug statistic methodology
The drug are delivering to 14 main group in first level
Second third fourth layer are often used to identify pharmacological subgroup and
that is considered more appropriate than therapeutic or chemical subgroup

ATC main group

 A  eliminatory track and metabolism
 B  blood and blood forming organs
 C  cardiovascular system
 D  dermatological
 G  genitor urinary system and sex hormone
 H  systemic hormonal properties except sex hormone and insulin

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  J  anti-infective for systemic use
 L  antineoplastic and immune modulating agent
 M  muscular skeletal system
 N  nervous system
 P  anti parasitic product insecticide and repellent
 R  respiratory system
 S  sensory organ
 V  various

Anatomical classification is based on the different system of human body

 Drug acting on nervous system
 Cardiovascular system
 Respiratory system
 Skeletal system
 Reproductive system
 gastrointestinal system
 excretory system
 endocrine systems

Therapeutic classification of drug is based on the clinical use of the drug

 drug acting on depression
 schizophrenia
 anxiety
 ulcer
 asthma
 congestive cardiac failure
 hypertension
 diabetes
Chemical classification of drug is based on the basic chemical class to which drug belongs
 purines
 pyramids
 sulphonylureas
 pyrazolones
 thiazides - steroid

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2. WHAT IS WHO-FIC? GIVE THE CLASSIFICATION

WHO – FIC, WHO family of international classification in comprise of the classification

to describe various aspect of the health and health system in the consistent manner.

CLASSIFICATION
The purpose of FIC is to development of the reliable statistical system at local National
and international level with the aim of improving his status and healthcare

RELATED REFERENCE DERIVED

CLASSIFICATION CLASSIFICATION CLASSIFICATION

International classification of International classification of International classification of

primary case disease disease for oncology 3rd
edition
International classification of International classification of the ICD 10 classification of
external cause of injury functioning disability and mental and behavior disorder
health
The anatomical therapeutic International classification of Application of ICD to
chemical classification health intervention dentistry and stomatology 3rd
system with defined daily edition
dose
ISO 9999 technical ads for Application of the ICD to
people with disability neurology

3. DISCUSS THE HISTORICAL DEVELOPMENT OF MEdDRA

Pre MEdDRA ERA:-
the essentially and importance for an essentially accepted medical terminology classification
system was recognized at the first international statistic conference in Brussels in 1953 to
evaluate medical data statistically to optimize and regular public health issue globally
The standardization effect before fruit in 1969 with the everyday use of the COSTART (coding
symbol for the service of adverse drug reaction term) dictionary
For the next quarter century address event coding was dominated by WHOART (World health
organization adverse reaction terminology) required by EU and COSTART (required by FDA)

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Post- MEdDRA Era:-
 1989 :- United State Medical control agency 25 need for single medical terminology to
support new computer database

 1991 :- ADROTI ( advanced drug reaction online information tracking ) medical

terminology created by MCA

 January 1993:- identification of need for medical terminology to support European

community drug regulatory system.

 1993 :- working party setup of European regulator and pharmaceutical industry

represented to evaluate water applicability of MCA terminology

 November 1993 – to October 1994 :- working party review amended MCA terminology
now called MedDRA

 December 1993:- European committee for proprietary medicinal product approved

MEdDRA project.

 OCTOBER 1994:- ICH steering committee released a draft version 1.1 of terminology
for review and evaluation.

 March 1995:- ICS working group evaluated the Alpha test result and evaluated
suggested changes.

 February 1996:- MEdDRA version 1.1 release for the view in US and Japan.

 July1997 :- ICH approval of international terminology

 November 1998 :- IFD MA ( trustee of ICH during committee holder of intellectual

property ) selected BDM international Inc. ( subsidiary of IRW INC. ) as the maintenance
and support service organization

 March 1999:-Med DRA version 2.1 released.

22
4. DESCRIBE ICD ( INTERNATIONAL CLASSIFICATION OF DISEASE )
International statistical classification of disease and related help problem in short ICD is the
international standard diagnostic tool for the epidemiology health management and clinical
purpose
ICD is designed as a health care classification system which provide the diagnostic code for the
classifying disease including classification of the wide variety of science symptoms abnormal
finding complaint social circumstance and external cause of injury or disease
This include the analysis of the general growth situation of population group
It is used to monitor the evidence and prevalence of disease and other health program
It is used for the reimbursement and resource association decision making by countries.

HISTORICAL SYNOPSIS
 In 1860 :- florescene nighitingle made first model of systemic collection of hospital data

 In 1893 :- French physician Jacques Bertillon introduce Bertillon classification of cause

of death

 In 1898 :- American public health association recommended division of ICD system

every 10 year

The revision followed minor changes until 6th version of ICD morbidity and motility
condition and section on mental disorder

WHO responsibility for preparing and publishing the ICD version every 10 year
ICD 10 was formed in 1893 as a Bertillon classification of international list of cause of
death

The work on ICD 10 started in 1983 approved in 1990 at 43rd world is assembly.

CLASSIFICATION
SCIENTIFIC APPROACH WAS ADOPTED IN CLASSIFYING DISEASE
According to certain characteristics of disease or injuries such as
 The part of the body affected

23
  The etiological agent
 The kind of morbid change produced by the disease

5. WHAT IS CRO? ROLE OF CRO

CRO is a service organization which provides support to the pharmaceutical industry
It offer various pharmaceutical research that is essential for conducting clinical trial in the
present boom when various complication are involved in the drug discovery process.
Various complications are involved in his type of development main example are like Lupine,
1uintiil, Cipla, Zydus, Cadeila
Rules of CRO in well-established for clinical trial
 CRO makeover as a helping hand in bio pharmaceutical development clinical trial
conduct and Pharmacovigilance
 also said there service to government institute, foundation tradition University
 main provide support to clinical study conduct for drug and medical device companies
 focus on clinical trial in which customer can expert is of a new treatment regimen or
health care device
 truly train in conducting complex drug development program

6. EXPLAIN DRUG INFORMATION RESOURCES

Drug information is current critically examine reveal and data about drug and use in a given
patient or situation
A. Current information use the most recent up to date source possible
B. critical examined information should meet following criteria
 more than one so should be used when appropriate
 the extent of agreement of source should be determined
 the plausibility of information based on clinical circumstance

C. Relevant information must be presented in the manner that applies directly to

circumstance under consideration.

TYPE OF INFORMATION RESOURCES

PRIMARY RESOURCES:-

24
  Researchers and manufacturers information patient containing original information
regarding the discovery of data.
 report contains specific data before product can be sold applied or represented
 scientific journals
 provide original study or report example clinical trial
 scope is narrow
 good went topic is new

SECONDARY SOURCES
 extract or index which summaries the information arising in primary source
 indexing and abstracting service are valuable tools per quick and selective screening of
primary literature for specific information data article
 three types of abstract
Telegraphic express (only string of words)
Indicative extract (structured in sentence)
Informative extract

TERTIARY RESOURCE:-
 complication of knowledge in field
 provide compressive information
 information replied views of multiple expert in field

INTERNET RESOURCES
 search for recently published our discussed in the media
 company specific information
 issues ( currently in the news,)
 government agencies news

7. EXPLAIN WHO-ART (ADVANCED REACTION TERMINOLOGY)

The world health organization adverse reaction terminology is the dictionary mean to serve as a
basic for rational coding of the adverse reaction terms
The system is maintain by the Uppsala monitoring center the world is organization collaborating
center for international drug monitoring

25
The system is no longer actively maintained
It is the four level hierarchial terminology which begin at the body system/ organ level class
10 classes consist of broad grouping term which consists of the most specific preferred term
World health organization also contain commonly used term called as an included term that act
as entry term for the preferred term...
FEATURES
 four level hierarchial structure
 open ended new term added as a necessary
 it is updated with the MEdDRA term appearing on who address reaction report
 used by drug regulatory agencies and pharmaceutical manufacturer and many countries

STRUCTURE
 32 – system organ classes / body organ classes
 180 – high level term for grouping prefer terms
 2000 – preferred term ( principal term for describing adverse reaction)
 3032 – inclided term synonyms to preferred term

8. WHAT IS MEdDRA AND STANDARDIZED MEdDRA QUARIRS

MEdDRA: - it is define as a clinically validity international medical terminology used by the
regulatory authority and regulator biopharmaceutical industry.
The terminology is used to the entire regulatory process from pre marketing to post marketing
and for data entry retrieval evaluation and presentation.

STANDARDIZED MEdDRA QUARIES:-

MEdDRA is mainly design for use in the registration documentation and safety monitoring of the
medical product through all pages of the development life cycle
The single stand terminology offers several clear advantages for regulator industry and others
skate holders

26
Remove of the need to convert data from one terminology to another preventing a loss or
distortion of data and allowing saving in the resources.
Improvement in the case quality and timelines of data available for the effective analysis
exchange and decision making.
Consistency of terminology throughout the difference pages of the development of a medical
product allowing effective cross reference and analysis of data
Solution of the electronic exchange of data relating to medical product

9. WHAT IS INN DESCRIBE IN BRIEF ( INTERNATIONAL NON PROPRIETORY

NAME )
Drug add generally marketed by their brand name though there is a legal requirement to mention
generic name in the label
A non proprietor name is also called as a generic name
Initiated in 1950 by a word assembly reservation
Being operating in 1953
Community list of INN now stand at some 7000 name designs is that time
130-150 New INN

AIMS OF INN
 To provide health professional with the unique and universal available design name to
identify each pharmaceutical substance
 For the clear identification safe prescription and dispensing of the medicine to patient
 For communication and exchange of the information among health professional and
scientist worldwide

TRADE NAME AND NON PROPRIETORY NAME

Most product available on the market are now days advertised promoted and identified by the
trade name.
In pharmaceutical field trade name are used in prescribing dispensing selling promoting or
buying a medicament.
Various trade name are for the various substances (Ex: - paracetamol)

27
Non properties name are intended to be used as a public property without restraint
Does names are usually designate by national or international nomenclature commission
Non property name are designation to identify the active pharmaceutical terms of substances
rather than the final product
The selection of a non proprietor name itself communicate to the medical and pharmaceutical
health professional to which the active drug substances the belong

SELECTION OF INN:-
The status of INN are selected by WHO on advice of expert from the WHO expert advisory
panel on international pharmacopoeia and pharmaceutical preparation.
The process of INN selection follow 3 main steps
 A request or application is made by a manufacturer or inventor
 After a review of the request a proposed INN is selected and published for the comment
 After a time period for objection has lapsed the name will obtain the status of
recommended INN and will be published as an if no objection has been raised.
change the name is available in the public domen if maybe used the 3D however it should not be
registered as a trademark since this world prevent it use by other party.
10. WHAT IS DDD (DEFINED DAILY DOSE )
The assumed average maintenance stores per day for a drug used for its main indication in adult
Define daily dose assigned for medicine given on ATC course
define daily dose are allocate to drug by a World health organization collaborating center in also
working in close association with the World health organization international working group on
drugs statistics methodology.
It is a unit of measurement of those not necessarily correspond to the recommended or prescribed
daily dose.
Therapeutic dose for individual patient and patient group will often differ from DDD as they will
be based on individual characteristics such as a weight age ethnic difference type and security of
disease and pharmacokinetic consideration.
Only one DDD are assign for ATC code and root of administration.
The DDD is sometime a door that is really or never prescribed the because it is an average of two
or more commonly used to doses
DDDs are not established for all medicines with an ATC code

28
 UNIT III
1. EXPLAIN THE METHOD OF COMMUNICATION IN
PHARMACOVIGILANCE
Communication through any of the following best practices and communication method should
be conducted through the FDA project manager topic the review division RPM rather than FDA
review team leader or senior management to ensure that the advice is appropriately velted and
documented

A. Meeting between FDA and sponsors

Sponsor can request meeting with FDA at any time during the development to visual
questions and issues.
These meetings may also help to minimize wastage expenditure of time and resources
and does help to Speed the truck development and evaluation process.
FDA guideline describe detail information about meeting request, packages,
scheduling, preparation, documentation, and timelines for FDA feedback

B. written correspondence from FDA :-

FDA project manager will use established later template to ensure consistency and
accuracy in regulatory communication.
Project manager should send a curtains the copy of return FDA corresponds to
sponsor when such communication are Times institute or communicate action.

C. Submission from sponsors

FDA regulation describe general principle of as well as content and format
requirement for INDS
Complete and will organized sponsor submission can increase the efficiency of FDA
review.

D. acknowledgement receipt of communication

29
 FDA project manager will send return acknowledgement of receipt of certain
submission that have review timelines.
Sponsor should acknowledge receipt of FDA information request and provide the
RPM with the estimated response time.

E. Email between FDA and sponsor

Sponsor should established secure email with FDA to allow for informal
communication that may include commercial confidential information
Use of secure email allot transparent and complete communication between FDA
and sponsor.

F. General telephone calls between FDA and sponsor

General or administrative question are suitable for informal telephone
communication between sponsor and FDA project

2. DESCRIBE IN DETAIL COMPARATIVE OBSERVATIONAL STUDIES

There are a number of observation study design that are useful in the validity signals from the
spontaneous report for case report.
Major type of these designs are
 Cross sectional study
 Case control study
 Cohort study

CROSS SECTIONAL STUDY:-

Data collected on a population of patient of a single point in time regardless of exposure or
disease status constitute cross sectional study.
10 type of studies are primarily used to gather data for survey or economical analysis.
Cross sectional study are best utilizer when exposure do not change over time
The major drawback of cross sectional studies is that the temporal relationship between exposure
and outcome cannot be directly addressed

CASE CONTROL STUDIES:-

In case control study case of diseases are identified
Control or patient without the disease or event of interest are then selected from the source
population that give raised to the cases.

30
Case control studies are particularly useful when the goal is to investigate whether there is
association between a drug and one specific rare adverse event. As well as to identify risk factors
for adverse event.
Risk factor can include conditions such as renal and hepatic dysfunction that might modified the
relationship between the drug exposure and adverse event.
Under specific condition a case control study can provide absolute incidence rate of the event.

COHORT STUDY:-
In a cohort study a population at risk for a disease is followed overtime for occurrence of disease.
Information on exposure status is known throughout the follow up period for each patient
Operation might be exposed to a drug at one time during follow up but none exposed at another
time point.
In many cohort studies involving drug exposure comparison cohort of the interest are selected on
the basis of drug used and followed overtime.
Cohort studies are useful when there is a need to know the incidence rate of adverse event in
addition to the relative risk of the adverse event
In addition cohort studies can be used to examine safety issue in special population through over
sampling of these patient or by stratifying the cohort if sufficient number of patient exist

3. DESCRIBE THE COMMUNICATION WITH REGULATORY AGENCIES,

BUSINESS PARTNERS, HEALTHCARE FACILITIES AND MEDIA.
PHARMACOVIGILANCE IN REGULATION OF MEDICINE
Robust regulatory arrangement provide the foundation for the national methods of medicine
safety and for public confidence in medicine.
To be effective the remit of drug regulatory authorities need to go further than the approval of
the new medicine to encompass the wider range of issue relating to the safety medicine namely
 clinical trial
 the safety of complementary and traditional medicine, vaccine and biological medicine
 the development of line of the communication between all the parties which have an
interest in medicine safety, insuring that they are able to function efficiently and ethically
particularly at time of the crisis

31
  In order to achieve their respective objectives pharmacovigilance program and drug
regulatory authority is must be mutually supporting.

PHARMACOVIGILANCE IN PRACTICE:-
cerivastatin was first approved as a liquid regulating agent in 1997
By 2000 total of 549 cases associated with the cerivastatin use had been reported to the who
collaborator center for international drug monitoring.

PHARMACOVIGILANCE IN CLINICAL PRACTICE:-

Safety monitoring of medicine in common use should be an integral part of the clinical practice
Education and training of health professionals in medicine safety exchange of information
between National pharmacovigilance center the coordination of such exchange and linking of
clinical experience of medicine safety with research and health policy all serve to enhance
effective patient care.

PV IN DISEASE CONTROL PUBLIC HEALTH PROGRAM:-

The pharmacovigilance should be a priority for every country with a public health disease
control program
the monitoring of a medicine safety in countries where there is no regulatory or safety
monitoring system in place or in remote areas with little or no health care survivals or
infrastructure has been identified as a matter for concern.
The problem are specially apparent is situation that involve the use of medicine in specific
communities

32
 UNIT IV
1. DESCRIBE COMPONENT OF PRE CLINICAL STUDIES FOR SAFETY
REPORTING.
The main goal of the freaky clinical studies are to determine the product ultimate safety profile.
Product main include new medical devices drugs gene therapy solution
The purpose of preclinical study is to develop the adequate data to decide that it is responsible
safe to proceed with human trial of the drug.

COMPONENT OF PRE CLINICAL STUDIES

SAFETY PHARMACOLOGY STUDIES
 ICH S7A-S7B guideline provide a definition Ranger principal and recommendation for
safety pharmacological studies.
 Guideline where developed to help protect clinical trial participant and patient receiving
marketed product from potential adverse effect of pharmaceuticals.
 Safety pharmacology is essential part of the drug development that came to identify and
predict adverse effect prior to clinical trial

TOXICOKINETICS AND PHARMACOKINETIC STUDIES

In vitro metabolic data for animal and human should be evaluated prior to initiating human
clinical trial
Further information on ADME in animal should be available prior to exposing large number of
human subject or treating for long duration

ACUTE TOXICITY STUDIES:-

Acute toxicity information is obtained from signal dose toxicity studies into mammalian spaces
using both the clinical and parenteral root of administration.
Such information can be obtained from approximate conducted escalation studies.

REPEATED DOSE TOXICITY STUDIES:-

ICH M3 guideline addresses the duration of repeated dose toxicology studies required to support
human administration.

33
Repeated toxicity studies is usually related to the duration therapeutic indication and scope of the
proposal clinical trial.

CASINOGENECITY:-
The studies are recommended for the clinical indication
This should be conducted for the marketing application
Only circumstance where there is a significant cause for concern for carcinogenic risk should the
study result this submitted to support clinical trial.

2. DESCRIBE CLINICAL SAFETY DATA MANAGEMENT

Clinical data management is critical phase in the clinical research which lead to generation of
high quality reliable and statistically sound data from clinical trial.
Clinical data management as your collection integration and availability of data at appropriate
quality and cost
Clinical data management encompasses the entry verification validation and quality control of
data gather during the conduct of clinical trial.
The key member in world in data management are
 clinical data manager
 database administrator
 database programmer
 clinical data coordinator
 clinical data associate
OBJECTIVE
 The integrity and quality of data being transferred from trial subject to the database
system.
 That collected data is completed and accurate so that result are correct.
 The trial database is complete and correct and true representation of what took place in
trial
 That trial database is significantly clean to support statistical analysis and its subsequent
presentation and interpretation.
The ultimate goal of the control safety data management used to assure that data support
conclusion drawn from the research.

34
Achieving this goal protect public health and confidence in marketed therapeutics.
The clinical trial data gathered at the investigator site in the CRF are stored in the control data
monitoring system and this system employee various means to verify the data to reduce
possibility of error due to human entry.

3. DESCRIBE PSUR ( PERIODIC SAFETY UPDATE REPORT)

It is the pharmacovigilance document required to providing and update of the safety profile of
the medical drug occurring across the word to the regulatory authorities at same specific time
point after their approval for the marketing.
These are the pharmacovigilance document intended to provide evaluation of the risk benefit
balance of a medical product at define time point after its authorization
The main object of this is reporting in East to present a critical and compressive analysis of the
risk benefit ratio of the therapeutic product.
The source of efficacy effectiveness and safety information that can be used in PSUR of
preparation include following example.
 Clinical and non clinical studies data
 Spontaneous report
 data from product uses and drug utilization information
 Observation of studies including registers.
 scientific literature

The most important aggregate report all around the World is PSUR it is submitted to truck
regulatory agencies in Europe, US and Japan as well as other countries across the world
In 2012 the PSUR was updated and now in many countries it is referred to as the periodic
beneficial evaluation report which focus on the benefit is profile of the drug

4. DESCRIBE THE EXPENDATED REPORTING

Expenditure reporting include sports serious and unexpected adverse reaction
This applied to report from any type of the clinical epidemiological investigation from the
independence of the purpose

35
This type of reporting you also applied to case not reported directly to the manufacturer of
sponsor
The sources of report should always be specific that weather it is an investigational report
spontaneous report or any other report
Data information obtained by the manufacturer on any sponsor on serious or unexpected report
from any source should be submitted on an unexpected basis to suitable regulatory authority if it
matches the minimum criteria for expenditure reporting.
Report of any serious unexpected area that are not fatal must be submitted to the FDA within 15
days’ time frame from time the pharmaceutical companies receive notification on day '0’ offer
it meet the minimum criteria for explodecated reporting.
In case any reporting in clinical trial such type of case are known as the suspected unexpected
serious adverse reaction. (SUSAR)
if it involve and fatal event or unexpected ADR then the time frame required for submitting the
report becomes 7 days clock followed by as complete a report as possible within 8 additional
calendar days

5. EXPLAIN IMPORTANCE OF CLINICAL PHASE SAFETY STUDY

clinical trial is a research study that test a new medical treatment are a new of using an
existing treatment to see if it will be a better way to prevent and screen for diagnose or treat
the disease.
Trial RC to be controlled if effect of the treatment is measured against a comparison
treatment administered over the same time period and under similar condition.
Clinical phase hold enormous potential for benefiting patient improving therapeutic regimen
and ensuring advancement in the medical practice that is evidence based
 to improve the quality of care
 patient participating in trial tens to receive better care
 to increase knowledge
 to provide evidence base patient care or prevention of disease
After conducting clinical trial it deals with
 drug input
 Pharmacogenetics
 pharmacokinetic
 pharmacodynamics
 actor affecting drug response

36
  toxicity and side effect

6. EXPLAIN IN DETAIL ABOUT ORGANISATION OF ICH

It is international conference on harmonization of technical requirement for the registration of
the pharmaceutical for human use.
The structure of the ICH consist of 4 main group
 ICH steering committee
 ICH coordinator
 ICH secretariat
 ICH working group

ICH STEERING COMMITTEE

This committee perform following functions
 determine the policies and producers for ICH
 select topic for harmonization
 monitor the progress of harmonization initiative

ICH COORDINATOR:-
 the coordinator are fundamental to the smooth running of the ICH and are nominated by
each of 6 parties of ICH
 coordinator act as a main contact point with the ICH secretariat
 the coordinators operate from IFPMA office located in Geneva Switzerland
 the ICH coordinator perform following responsibilities
Provide support to the ICH steering committee
Document the meeting of the steering committee
Promote coordination between working group
Provide information on the ICH guideline and ICH purchase
Provide administrative support for MEdDRA management board
Provide administrative support for global corporation group

37
ICH SECRETARIAT:-
Function of ICH secretariat include
 preparation for documentation of meeting of steering committee
 coordinate preparation for working group and discussion group meeting

OCH WORKING GROUP:-

Depending on type of harmonization activity required the steering committee will endorse
establishment of the one of the following working group especially
 expert working group
 implementation working group
 informal working group
 discussion group

38
 UNIT V
1. DEFINE SCHEDULE Y AS PER DRUG AND COSMETIC ACT 1940
SCHEDULE Y
Requirement and guidelines for permission to import or manufacture of new drug for sale or to
undertake clinical trial.
APPLICATION FOR PERMISSION
Application for permission to import or manufacture new drug for sale or to undertake clinical
trial shall be made in form 44 accompanied with following data in accordance with the
appendices.
Chemical and pharmaceutical information as described in item 2 of appendix 1 animal
pharmacology data.
 Specific pharmacological action
 General pharmacological collection
 Pharmacokinetics data related to the absorption
 Distribution metabolism and excretion of test substances
 animal toxicology data
 human clinical pharmacology data
 regulatory studies in other country
 full prescribing information

CLINICAL TRIAL
 approval for clinical trial
 responsibilities of sponsor
 responsibilities of the investigator
 informed consent
 responsibilities of the ethics committee
 human pharmacology phase 1
 therapeutic exploratory trial phase 2
 therapeutic confirmatory trials phase 3
 post marketing trial phase 4

39
APPROVAL FOR CLINICAL TRIAL:-
Clinical trial on the new drug shall be initiated only after the permission has been granted by the
licensing authority under the root 21 B and the approval obtained from the respective ethics
committee
All tribe investigator fastest appropriate qualification training experience and shall have access to
search investigation and treatment facilities are as relevant to proposed trial protocol
RESPONSIBILITY OF SPONSOR
Sponsor is responsible for implementing and maintaining quality assurance system
Sponsor are required to submit the status report on clinical trial to the license in authority at the
prescribes periodicity

RESPONSIBILITY OF THE INVESTIGATOR

The investigator shall be responsible for the conduct of the trial according to the protocol and the
GCP guideline and also for the compliances.
The investigator should ensure that adequate medical care is provided to the participant for any
adverse event.

2. WHAT IS IMPORTANCE OF THE 0HARMACOGEBOMICS :-

The completion of the human genome project pharmacogenomics has been to user as a killed
with greatest clinical potential to improve patient care through implementation of the
personalized medicine.
The term personalized medicine and pharmacogenomics are often used together as both aims to
maximize therapeutic benefit and avoid adverse drug reactions.
There are many commonly prescribed truck that fill to wrote for some patient.
To improving patient care Pharmacogenomics is based personalized approach have the potential
to see money by improving cost effectiveness of healthcare delivery
Adverb drug reaction can measure cause of death and illness in the patient and important of drug
attrition in pharmaceutical industry both during drug development and after licensing.
this reaction are normally class discrerating reaction that are not related directly to drug
concentration but instead may be due to unusual patient phenotype.

40
Most serious advanced drug reaction clans classified as either type A which is those dependent
Type B where the reaction is not predictable from normal drug pharmacology and it’s generally
independent of the dose.
Based on this FDA has reliable over 100 approved drugs to including genetic information
A list of valid genomic biomarkers for clinical guidance can we found on the FDA website

3. DESCRIBE THE DRUG IN PREGNANCY AND LACTATION

Drug use during pregnancy and electrician required special consideration because both the
mother and child are affect.
Majority of drug attend concentration in close to dose of maternal plasma
Drug used in pregnancy classified as: - A, B, C, D, X

 A  control studies in human so no reached to fetus.

Eg. Vit- B, C, D, E

 B  no control studies have been in human animals that is show in risk to fetus
Eg: - metronidazole, paracetamol, penicillin, erythromycin.

 C  no control study conducted in animal and human

 D  evidence of risk to human fetus

 X  contraindicated in pregnancy
Ex: - Teratogenicity drug

DRUG TO BE USED IN DISEASE CONDITION IN PREGNANCY

 Nausea and vomiting :- Cyclizing, Meclizine
 Hypertension :- methyldopa
 Cough :- diphenhydramine, codeine
 Headache :- paracetamol, aspirin, codeine
 Constipation :- milk of magnesia
 TB :- isoniazid and ethambutol

41
DRUG DURING LACTATION
Breastfeeding mother should avoid taking drug if possible when drug therapy is necessary the
mother should avoid contraindicated drug and drug that suppresses lactation.
Drug pass into milk by passive diffusion of free and unionized form.
They are distributed within aqueous protein and liquid phase of milk
So drug which are highly lipid soluble with low protein binding and unionized at physiological
higher concentration in milk.

DURING LACTATION
 Anti-microbial :- penicillin
 Analgesic :- paracetamol , morphine
 Anti-hypertensive :- Beta blocker
 Anti tubercular :- Rifampin
 Anti malaria :- quinine
 Diuretics :- chlorothiazide

6. GIVE THE IMPORTANCE OF ADVERB DRUG REACTION IN GERIATRIC

POPULATION
In elderly patient the adverse the reaction occurs due to multiple comorbidities as due to
increasing is there will be a several incidence of one or more chronic condition.
Medication name play crucial role in geriatric healthcare as they trade chronic disease alleviate
improve quality of life.
Age related change in drug disposition and pharmacodynamics response have significant unicorn
implications.
Increase the use of a number of medication in elderly increases the risk of occurs of the medicine
related problem.
In spontaneous reporting studies there is a higher probability of lack of identification and under
reporting of adverse drug reaction due to various reported factors
Available advanced drug event are the series of consequences of inappropriate drug prescribing

42
Pharma marketing drug trial often exclude geriatric patient and approved dosage may not be
appropriate for older adult.
Conducted studies have relieved high prevalence of irritation use of drug among Indian elderly
person

7. GIVE THE IMPORTANCE OF ADVERSE THE REACTION IN PAEDIATRIC

POPULATION
Monitoring of the safety of drug used in the children is a supreme importance during the clinical
development of medicine only limited data on this aspect our generated through the clinical trial.
Use of medicine outside the describe the specification as mentioned in the license search as in
term of the indication formulation contraindication or age include off label off license use which
however become a major area of concern.
Therefore a guideline have been improvised to improve awareness of medicine safety issue
among everyone who has an interest in the safety of the medicine in children and to provide
guideline on the effect to system for monitoring medicines safety in the pediatric population

8. EXPLAIN ABOUT CIOMS WORKING GROUP

The council for international organisation of Medical science is an international non government
non profit organisation established jointly by WHO and UNESCO in 1949

In order to access and monitor adverse drug reaction and pharmacognitive following CIOMS
working group

CIOMS I (1990)  the group is for reporting adverse drug reaction

CIOMS II (1992)  the group is for reporting of periodic drug safety update summaries
CIOMS III (1999)  the group for indicating guideline for preparing core clinical safety
information on drug including new proposal for investigator brochure
CIOMS IV (1198)  the group for report benefit risk balance for marketed drug it mentioned
about evaluating safety signals
CIOMS V (2001)  it was form to consider current challenges in pharmacovigilance it
mentioned about programmatic approaches for challenge

43
CIOMS VI (2005)  the group was to consider issue related to the surveillance assessment and
reporting of the drug safety data from clinical trial
CIOMS VII (2006)  the working group considered the rational format and content of a
periodic development safety update report to inform drug regulatory authorities on safety of
medicine
CIOMS VIII (2006)  this working group deals with signal detection

44