Drug Discovery & Development

Kaweesa Simon Peter

Pharmacology Department, College of Health
Kampala international University
Drug Discovery & Development
During last 50 years, hundreds of new drugs have
been introduced, & many older drugs have been
(withdrawn).

And only less than 1% of compounds that were

tested have eventually become licensed
medicines.
The process of drug discovery is very interesting
and exciting but I would like to say to you that it is
 Very painful
 Time consuming and very expensive to undertake.
 Requires enough resources
 Requires well maintained facilities
 Requires given expertise
 And also Requires hard work & patience
•
Drug Discovery & Development

What exactly happens during drug

Discovery and Development?

There are nine steps that we need to

clearly understand or undertake in
order for us to understand drug
discovery and development process
And for this case, I intend to discuss
them step by step.
Step 1: Drug discovery

• The first footstep in the drug development process is finding a

promising molecule (a “lead compound”) that could become a
drug. After finding a drug compound,

• Here biologists and chemists work together closely: The biologists

initially test the effects of analogues on biological systems.
chemists take this information to make additional alterations that
are then retested by the biologists. The resulting compound is
then initially taken as a candidate drug or lead compound.
Step 1: Drug discovery & Preliminary Validation
• Lead compound : – Lead compound or substance is one that is believed to
have potential to treat disease. Laboratory scientists compare known
substances with the lead compounds to determine their likelihood of
success

• Testing is then done in many ways to confirm its effect on drug target.

• The goal of this stage is to initially confirm if the drug is indeed

involved with the disease in question.
Step 2: Preclinical testing
• Preclinical trials are testing studies of the promising drug a way
from humans or studies done in the laboratory or in experimental
animals

• The goal of pharmacological studies is to identify if the promising

drug is effective and also to determine whether the
pharmacological information is good enough to proceed for clinical
trials
• Such preclinical studies can take up to 3 years to complete
• Preclinical studies involve both pharmacological and toxicological
studies
Step 2: Preclinical testing
Preclinical Pharmacologic studies : –During Preclinical trials
pharmacological screening of candidate molecules investigation are done
on either isolated organ system (Invitro)or in whole animal experiment (in
vivo)
Examples of Invitro pharmacological studies
The purpose of this is find out the effects of potential drug candidate
on different systems (CVS, CNS, RS etc.)
Pharmacological testing also bring out the effects of drugs on
specific biological activities,
• Their mechanism of action,
• Their pharmaco kinetics
• And the effective dose range of the test compounds
Step 2: Preclinical testing

Preclinical Toxicity studies : – Are carried out in vivo or in vitro to evaluate the toxicity potential
risk of the promising drug. Detailed toxicity studies are conducted on compounds to determine
the safety of the promising drug; there are two forms of toxicity studies and these are;
In vitro toxicity studies; Involve use of isolated cell line for example cytotoxicity studies
In vivo toxicity studies; Involve use of experimental animals such as mice, rats, guinea pigs.
Examples of toxicity studies
1) Acute toxicity
2) Sub chronic toxicity
3) Chronic toxicity

• The goal of safety or toxicity studies is to identify if the promising drug is safe but also to
determine the relevant toxicities to be monitored in clinical trials
Step 2: Preclinical testing

• During pre-clinical trials, Although efficacy of the test drug is done, safety is
paramount as the regulatory agency FDA never let preclinical studies move into
human trials without extensive data on safety.

• This is the stage where researchers will whittle thousands of drug molecule
candidates down to between one and five. By the time preclinical testing has
concluded, about three years may have gone.
Patenting of the promising Drug

• A patent is a monopoly granted by a government to an inventor,

such that only the inventor may exploit the invention/innovation for
a fixed period of time (up to 20 years).
Step 3; Patenting of the promising Drug

• After preclinical trials or after the discovery any lead compound or

after optimization of any substance of potential pharmaceutical
application, patenting is done.

• Patenting may never take place until preclinical trials and phase I
clinical trials are completed.

• This is because a drug must be proven safe and effective before

subsequent clinical trials.
Step 4; Applications and Safety File (IND) to FDA

Before testing the drug in humans begins or what we know as clinical trials

• The researchers must file an Investigational New Drug (IND) application with
the FDA.

The application includes :

• The results of preclinical work,

• Candidate drug’s chemical structure

• How it is thought to work in the body,

• A listing of any side effects ,

• Method of product manufacture

• And proposed protocol for initial clinical trials

Step 4; Applications and Safety File (IND) to FDA
The IND also provides a detailed clinical trial plan that outlines how, where and by
whom the studies will be performed.

• The FDA reviews the application to make sure people participating in the clinical
trials will not be exposed to unreasonable risks.

• FDA will use approvals from the Institutional Review Board (IRB) at the institutions
where the trials will take place. This process includes the development of
appropriate informed consent, which will be required of all clinical trial participants.

Before approval FDA is keen at the

• The informed consent, for the participants to be used in the clinical trial

• Statisticians and others researchers are constantly monitoring the data as it

becomes available
Step 5; Clinical Trials

Clinical trials are studies on the candidate drug that take place in humans
• The purpose of Clinical trials is to assess the safety and efficacy of any potential new
therapeutic
• Safety’ generally refers to a favourable risk : benefit ratio, i.e. the benefits should
outweigh any associated risk .

• efficacy’ the drug being able to give therapeutic effects in humansby a specific time-
frame .
• Clinical trials may be divided into three consecutive phases (phase 1,11, 111, 1V)

Phases of clinical trials are designed to establish

• the optimum pharmacological properties of the drug in humans,

• the toxicological properties of the drug in humans
• or the appropriate route of administration of the drug to humans
Step 5 ; Clinical Trials
Phase 1 Clinical Trial

Phase 1 testing is done in healthy human volunteers (20–80)

• The main goal of a Phase 1 trial is to discover if the drug is safe in

humans.

• More on to safety researchers are able to investigate the pharmacokinetics

of a drug
• How the candidate drug is absorbed?
• How it ismetabolized?
• How it is eliminated from the body?
• The drug’s pharmacodynamic is also investigated:
• And how the drug causes undesired effects?
Step 6; Clinical Trials
Phase 2 Clinical Trial

• In Phase 2 trials is an Efficacy and safety testing phase in small number

of patients (100–300)

• During phase 2, researchers evaluate the candidate drug’s effectiveness,

and examine the possible short-term side effects.

• They also strive to answer these questions: Is the drug working by the
expected mechanism?

• Does it improve the condition in question?

• Researchers use this phase to analyze optimal dose strength and

schedules for using the drug
Step 7; Clinical Trials
Phase 3 Clinical Trial

• Phase 3 clinical trial is a large-scale efficacy and safety testing in

substantial numbers of patients (1000–3000)

• This phase of research is key in determining whether the drug is safe and
effective in large number of patients.

• It also provides the basis for labelling instructions to help ensure proper
use of the drug (e.g., information on potential interactions with other
medicines).

• Phase 3 trials are both the costliest and longest trials. Hundreds of sites
around the world participate in the study to get a large and diverse group
of patients.
• The material used for preclinical and clinical trials should be produced
using information from this phase.
Step 7; Clinical Trials
Phase 3 clinical trials

A comprehensive phase III trial normally requires at least several hundred

patients.

• However sometimes smaller trial suffice in situations for example: the

where the target disease is very serious/fatal or where there are no
existing acceptable alternative treatments;

• In this case the target disease population may be small and the candidate
drug is clearly effective and exhibits little toxicity.
 Step 8; Clinical Trials
Ongoing Studies and Phase 4 Trials
• Research on a new medicine continues even after approval.
• As a much larger number of patients begin to use the drug, companies must
continue to monitor it carefully and submit periodic reports, including cases of
adverse events, to the FDA.
• In addition, the FDA sometimes requires a company to conduct additional studies
on an approved drug in “Phase 4” studies.
• These trials can be set up to evaluate long-term safety or how the new medicine
affects a specific subgroup of patients.
• Even following approval, safety remains the top priority of the on the side of FDA.
This stage is also is what we know as phase 4 or Post market stage.
• The drug is used during this stage but it is also being monitored. In case of any
undesired effects, the drug can be withdrawn from the market. Drugs such as
celecoxib's and others have faced this trend
Clinical Trials
Step 9; Systematic Review & Meta analysis
• Basically a systematic review is used during drug discovery &
development.

• It is used to describe trends in the research and it shows how

many studies have used which methods were used and where the
studies were carried out etc...

• Whereas a meta-analysis combines RESULTS from given studies

in a new statistical framework to test hypotheses.

• Both methods can be used together make the clinical trial

information more accepted and valid.
Conclusion

• From start to finish, the entire drug development process (steps 1 to step
8) usually takes about 10 to 15 years,

• Leaving drug developers with around a decade to do branding and

recover their money invested with profits.

• This gives the main reason why new drugs are initially quite expensive to
the patients.

• After the patent other companies can now take advantage to own
production and business of the drug.
Conclusion
• The discovery and development of new medicines is a long, expensive
and complicated process.

• Each success is built on many struggles and failures.

• Advances in understanding human biology and disease are opening up

exciting new possibilities for breakthrough medicines.

• At the same time, researchers face great challenges in understanding and

applying these advances to the treatment of disease.

• These possibilities will grow as our scientific knowledge expands and

becomes increasingly complex.