SAFETY DATA GENRATION

SUPERVISED BY : PROF. ABHINAV BHATEJ

DEPARTMENT:P(PHARMACOVIGILANCE)
SUBMITTED BY:NAVJOT
B.PHARMACY 8TH SEMESTER
ROLL NO.:789568
SETH G.L BIHANI S.D. COLLEGE OF TECHNICAL EDUCATION
GANGAPATH,SRIGANGANGAR (RAJ.)335001,INDIA
 CONTENT:
1. Introduction
2. Drug development pipeline
3. Drug discovery cycle
◦ Preclinical trials
◦ Clinical trials
◦ Post marketing
 INTRODUCTION
1. Modern drug safety and pharmacovigilance began in the early 1960s following the
thalidomide disaster
2. Thalidomide a drug design to prevent morning sickness,with released in 1959 and
resulted is over 10,000 children in 46 countries being born with birth defects in the
wake thalidomide.
3. The WHO(world health organization) set up the programme for international drug
monitoring(PIDM).
4. Today PIDM has more than 150 participating countries with over 16 million adverse
events reports.(ADRs) collected.
5. In parallel, the United states Congress passed the kefauver-Harris drug amendments
(1962),for the first time these laws required drug maker to prove their drugs worked
safely before the food and drug administration (FDA) would approve them for sale.
 Drug development pipeline

The diagrams below show the timing of the main safety assessment studies conducted
during the drug development process.
Preclinical trials
1. This phase generally deals with elucidating the mode of action the molecules and
getting an idea about the pharmacokinetic and pharmacodynamic of
pharmacodynamic molecules.
2. The most important is the toxicological data obtained from the animal study.
3. Which give the rough estimate about the possible adverse reactions that may be
likely to be seen during the course of the therapy.
4. These are carried out in two stages
◦ 1. In vitro studies
◦ 2. In vivo studies
1. In vitro studies:
The in vitro studies make use of different cell-liness and tissue preparations
2. In vivo studies:
the in vivo studies are performed on live animals and are observed the
changes in the animals behavior.
◦ These regulation set the minimum basic requirements for:
1. Study conduct
2. Personal
3. Facilities
4. Equipment
5. Written protocols
6. Operating procedures
◦ Preclinical studies are not very large.
◦ These study most provided detailed information on dosing and toxicity levels.
◦ After preclical testing,researchers review their findings and decide whether the
drug should be tested in people.
◦ This includes in vitro and in silico testing of the compounds to identify the best
members of a series a taken in to clinical trials.
◦ This is also where the first stages of safety assessment are undertaken via
toxicity testing in animals
Clinical trials
1. The next stage after preclinical studies is the clinical studies actual testing of the
molecules in human volunteers.
2. This phase allows to assess the safety and efficacy of the new molecule.
3. This phase also allow together information about the toncology effects in human
body.
4. The FDA approved based on the preclinical data, the innovator can proceed for
priclinical studies.
5. This stage consist of three phages:
◦ phase 1
◦ Phase 2
◦ phase 3
◦ Phase 4
Phase1Clinical trials
◦ Phase 1st clinical trials are concerned primarily with establishing how a drug is
absorbed,distributed, metabolized and excreted by the human body-a study
known as pharmacokinetics (PK).
◦ The dosage range of a new drug is determined by administering increasingly
large doses too more groups of subjects.

Phase 2 clinical trials

◦ Phase 2 clinical studies are randomized, with subjects assigned randomly to
receive the experimental drug,a standard treatment and
placebo(harmless,inactive substance).
◦ Large number of patients receive a treatment in phase 2 clinical trials
◦ There a greater chance to observe and compile information on potential side
effects

Phase 3 clinical trials:

◦ Phase 3 clinical trials are conducted at multiple centers with hundreds or
thousands of patients for whom the drug is intended.
◦ Testing on larger population allows continuous genration of data on a drug
safety and efficacy
◦ As in phase 2,most phase 3 clinical trials are randomized and blinded.
NDA(New drg application)

◦ The phase 3 clinical trials are complete a pharmaceutical company can

request FDA approval to market the drug with in the USA.
◦ This is called a new drug application.

Regulatory (GLP) toxicology:

◦ These studies are performed to good laboratory practice (GLP)standards and
compromise those required by local regulatory authorities or ethics
committees before a drug can be given to a human subjects for the first time.
◦ Regulatory toxicology also covers the studies required to support a new drug
applications(NDA)
Post market survellance
ost marketing surveillance is design to ensure the safety of a drug once it releases on to the market.

Shortcomings of the drug development process:

There are number of problems associated with the drug development
process as it stands, but they can be distilled in three factor-

1. Cost
2. Time
3. Effectiveness
◦Time to market:
on average l,it takes 12 year to bring a new
drug to market.
1. This is one reason why the process is so expensive.

◦Effectiveness:
almost 90%of drug that start testing in patients
don’t reach the market because they are unsafe and ineffective.