Drug Development Process| Overview of Preclinical & clinical phases

The drug development process is a continuous process stimulated by the emergence of new diseases and the requirement of new drugs for existing ones.

The process involves a sequence of steps like

  • Drug design (By Synthesis or Isolation)
  • Preclinical trials.
  • Scrutiny and grant of permission for clinical trials
  • The pharmaceutical formulation of the drug.
  • Clinical trials phase I, II, III.
  • Review and grant permission for marketing.
  • Post-marketing surveillance.

New drugs are developed systematically by using methods like

  1. Rational drug design
  2. Lead-based and
  3. Non-lead based drug design.

Drug design by Synthesis or Isolation

For synthetic drugs, methods like combinatorial chemistry are employed to develop a large number of libraries of drug molecules.

Even a scientific and definite protocol is needed to apply for patent rights on the new drug molecule by the investigator.

New drug molecules have to be discovered from natural sources or chemical synthesis.

Plant sources

Many drugs are found in plants ex: the digitalis plant yields digoxin, which is used for heart failure.

Vinca roseus plant yields vincristine, which can kill cancer cells. Similarly, the opium plant yields codeine, which is used in cough syrup to restrict cough.

Animals source

Few medicines are also obtained from animals. For example, Shark liver oil is used for Vitamin-A deficiency.

Mineral sources

Iron and calcium are examples of mineral drugs used for anemia and weak bones, respectively.

Chemical synthesis

Drug Development Process

It is one of the widely used approaches for the search for new drugs.

But doing it based on some lead molecule from natural products or already available drugs is easier.

This method employs techniques like molecular modeling and combinatorial chemistry.

Rational Drug Discovery

Here, a drug is discovered based on a pathological target or abnormality.

This needs knowledge of human anatomy, pathophysiology, etc. L-dopa in parkinsonism and insulin in diabetes are examples of this discovery.


Biotechnology is another method by which many vaccines, anti-sera, and hormones like insulin are synthesized.

So this is also a method for new drug discovery.

Preclinical trials. 

The newly discovered molecule is tested for its toxicity and efficacy in smaller animals like rodents, guinea pigs, etc.

The idea is to get the basic details of drugs in terms of activity, toxicity, dose, excretion, etc.

It is done to evaluate the following.

  1. Toxicity
  2. Pharmacokinetics (absorption, distribution, metabolism and excretion)
  3. Pharmacological activity.
  4. Specific activity on organs
  5. Test on human diseases induced in animals.
  6. Confirmation of activity
  7. Mechanism of action.
  8. Drug quantification.

Toxicity testing

This is the test done on animals to see if the molecule has any toxicity.

Lethal Dose 50 (LD50) is determined where the dose of a drug is required to produce death in 50% of the animals chosen for study.

This way, the concentration of drug that can lead to toxicity is determined.

This is done to study the toxicity of the drug. This is done under the following stages.

  • Acute toxicity.
  • Sub-acute toxicity.
  • Chronic toxicity.
  • Teratogenicity.
  • Mutagenicity.
  • Carcinogenicity.

Acute toxicity

This test is done for 1 to 3 days by giving increasing doses of the drug to a small group of animals.

The intention is to study LD50, which means a minimum lethal dose that kills at least 50% of animals in the group. 

Sub-acute toxicity

This test is done on animals for 2 weeks to 12 weeks. The drug is given to a group of animals to define ED50%. This is the effective dose that can cure 50% of animals. Besides, the effect on feeding, growth, body weight, and other parameters are noted.

Chronic toxicity

This is done for 6 months to 12 months. The drug is studied for any long-term toxic effects.


This test is done to see the toxic effects of drugs on reproduction, fertility and the effect on the growing fetus. 


This is the toxic study done to see if there is any genetic damage due to the drug.


This is done by the administration of the drug for the whole life of the animals.

The intent is to see if the drugs have any carcinogenic (cancer) producing potential.

Testing on organs

This test is done by giving the substance to isolated organs to see for a specific activity like vasodilation, uterine contraction, etc.

Tests on human diseases

Here the drug is tested to see if it can cure human disease.

For this, animals are induced with the said disease for which the drug is intended, and the efficacy is determined.

Confirmation of activity

This test involves confirmation of the activity and any analogous activity.

Like a drug, being sedative can also be anxiolytic.

Mechanism of action

Once the efficacy is confirmed, its mechanism of action is tested.

This gives an idea of how safe the drug is over a prolonged period of administration and how the dose and its adverse effects, if any, can be managed.

Test on body systems

This test is done to see if the drugs have any harmful effects on body systems like respiratory, circulatory, excretory and other systems in the body.


This test is key as it gives an idea of the drug’s absorption, distribution, metabolism, and excretion.

Drug quantification

This is a test to see the drug dose-response relationship, bio-availability, half-life, etc.

Drug dose relationship indicates how a drug effect is modified with different dose levels.

Bioavailability indicates the amount of drug that reaches the target site from the actual dose administered to the patient.

Half-life (t1/2) indicates the time duration required to reduce the drug to its initial concentration in the blood. This way, it helps us understand how long the drug acts and how frequently the drug has to be given.

This will help to fix the dose and time intervals for drug administration.

The pharmaceutical formulation of the drug.

Once the drug passes preclinical studies, it can be tested on humans. For this, the drug is formulated into a suitable dosage form for easy administration in humans.

Clinical studies

Testing is taken up over humans once the animal’s studies are complete with safety and efficacy data. This is done in 4 phases as

  1. Trial-I
  2. Trial-II
  3. Trial-III
  4. Trial-IV

The drug is released into the market after trial III, and it is monitored for any side effects and issues as a part of trial IV.


Here the drug is administered to healthy individuals.

It is conducted on a few people, like 10 to 30.

This study helps to determine the toxicity, side effects, and tolerance levels by using the new drug at sub-toxic concentrations.


Here the drug is tested on the patient with the actual disease for which the drug is intended.

It is conducted in a few hundred of patients to record the safety, efficacy, doses, and side effects.

This study helps determine if the drug is efficient in the treatment of the specific disease.


After trial II, the drug is then taken up for large-scale studies at multiple centers in diseased individuals.

This is mainly intended to ascertain further the efficacy of the new drug as well as record any variation in effects among ethnic groups.

Once the results are satisfactory, the drug is released into the market.


This is done after the drug is released into the market, and it is an ongoing process throughout the life of the drug in the market.

Any side effects recorded from the market usage are noted and sent to WHO.

One can study in detail the process as a part of a pharmacology course in medicine and pharmacy.

Review and grant permission for marketing.

Once Trial-III studies are completed, the new drug molecule is eligible for release into the market.

For this, the NDA application is made for FDA or respective drug control authority to review the data and approval for release of new drugs into the market.

Post-marketing surveillance

Once the drug is released into the market, it is monitored for its safety and other wide variety of effects and adverse reactions.


  1. What is Combinatorial Chemistry
  2. What does LD50 mean
  3. New Drug Application (NDA)

Leave a Comment