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Drug Discovery & DevelopmentDr Sameh AM AbdelghanyMansoura
Faculty of medicineClinical Pharmacology Department
#of 33IntroductionThe discovery and development of new medicines
is a long process. For every 5,000- 10,000 compounds, only one of
them finally receives approval.The average cost to develop a
successful drug is estimated to be $1-2 billion. The whole process
takes an average of 10-15 years.
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#of 33A- THE DISCOVERY PROCESS Step 1: Understanding the disease
(Pathogenesis)how genes are altered?how specific proteins interact
with each other to affect the cellular functions?why something went
wrong?It may take many years of work to turn this basic knowledge
into a new treatment.
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#of 33Step 2: Find a Target: A target is any single molecule,
such as a gene, enzyme, receptor, or protein, which has a major
role in the pathogenesis of the disease.
#of 33Step 3: Find a promising molecule (lead compound):
search for a lead compound, that may act on the target to alter
the disease course.
#of 33How to find a lead compound ?
Nature: Microorganism: many useful antibiotics are derived from
bacteria (e.g. penicillin and aminoglycosides).Plants: many plants
give active ingredients such as atropine and morphine.Minerals and
elements: e.g. calcium.
#of 33High-throughput screening: is the most common. Researchers
can test thousands of compounds against the target by the aid of
advanced computer software. The software has a library containing
thousands of compounds that can be tested one by one against the
target and detects which one can interact with the target.
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#of 33Biotechnology: Scientists can genetically engineer living
systems to produce biological molecules e.g. insulin from
genetically modified yeasts.
#of 33Step 4: Preclinical Testingresearchers turn their
attention to test drugs extensively in animals before testing them
in humans.Drugs also undergo tests (in more than one animal
species) to determine the possible effects on a fetus. These
experiments are conducted under controlled conditions in relation
to animal ethics.
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#of 33At the end of several years of intensive work, and after
starting with ~ 5,000 to 10,000 compounds, scientists now have
between 1-5 candidate drugs, which will be studied in human through
clinical trials.
#of 33B- THE DEVELOPMENT PROCESSInvestigational New Drug (IND)
Application and SafetyBefore any clinical trial can begin, the
researchers must file an Investigational New Drug (IND) application
with the U.S. Food and Drug Administration (FDA)The FDA reviews the
application to make sure people participating in the clinical
trials will not be exposed to dangerous risks. It also can stop the
trial at any time.
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Phase 1 Clinical TrialThe candidate drug is tested in about 20 -
100 healthy volunteers for the first time. The main goal of Phase 1
trial is to discover if the drug is safe in humans.Researchers
examine the pharmacokinetics, pharmacodynamics, and side effects of
the new drug. They also determine the safe dosing range.
#of 33Phase 2 Clinical Trial
The candidate drug is tested in about 100 - 500 patients with
the disease under study. The main goal of Phase 2 trial is to
evaluate the effectiveness of the new drug and examine the possible
short-term side effects. In the design of this trial, some patients
receive the drug, and the other part receive placebo (= false
drug).
#of 33Cont.
Both the researcher team and patients do not know which group is
taking the drug or the placebo (i.e. double blind trial). This is
done to eliminate any psychological factors or bias regarding the
effect of the drug.If the drug continues to show promise, they
prepare for the Phase 3 trials.
#of 33Phase 3 Clinical Trial
In Phase 3 trials researchers study the drug candidate in a
larger number (about 1,000-5,000) of patients to generate
statistically significant data about safety, efficacy and the
overall benefit-risk relationship. Phase 3 trials are both the
costliest and longest phase. Hundreds of sites around the world
participate in the study to get a large and diverse group of
patients.
#of 33Drug ApprovalOnce all three phases of the clinical trials
are complete, the sponsoring company requests FDA approval to
market the drug. FDA experts review the application and can either:
1) approve the drug 2) requesting more information or studies 3)
reject approval.For most drugs, the developing company has the
exclusive rights to manufacture and sell the drug for 20 years
(intellectual property rights).
#of 33Post-marketing surveillance (Phase 4):
Research on a new medicine continues even after marketing.
Scientists must continue to monitor it carefully and submit
periodic reports, including cases of rare adverse events, to the
FDA. In addition, the FDA sometimes requires a company to conduct
additional studies on an approved drug to evaluate long-term safety
or possible risk in a specific subgroup of patients.
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#of 33DRUG NOMENCLATURE Chemical name: is the name given
according to chemical structure of the drug. It is usually complex
and difficult to be used in prescription.Generic name: it is the
name listed in the national formulary and used in textbooks.Brand
name: it is the name owned by the pharmaceutical company that
manufactures the drug.
#of 33CATEGORIES OF DRUGSOver-The-Counter drugs (OTC)drugs that
are considered relatively safe and can be sold without physician's
prescription e.g. vitamins, antacids, paracetamol, etc.
#of 33Prescription-only drugs drugs that are used under medical
supervision because they are considered to be unsafe. So they are
dispensed only by registered physician e.g. antibiotics,
antidiabetics, antidepressant, etc.
#of 33Controlled substancesdrugs that are prescribed only by
specialized physicians and must include their registration number
on all prescriptions forms. Nurses are responsible for storing
controlled substances in locked containers.
#of 33Categories of controlled substances
Schedule I:Drugs that are not approved for medical use and have
high abuse potentials e.g. flunitrazepam (Rohypnol),
heroin.Schedule II :Drugs that are used medically and have high
abuse potentials: opioid analgesics (e.g., codeine,morphine), CNS
stimulants (e.g., cocaine).
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Schedule III:Drugs with less potential for abuse than those in
Schedules I and II, but abuse may lead to psychological or physical
dependence e.g. benzodiazepines.Schedule IV :Drugs with some
potential for abuse e.g. some appetite suppressants (e.g.,
mazindol, phentermine).
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Schedule V:Products containing moderate amounts of controlled
substances e.g. antidiarrheal drugs, such as diphenoxylate and
atropine (Lomotil).
#of 33EXAMPLE OF DRUG LABELING INFORMATION
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Thanks For Listening
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