Drug Development Process| Overview of Preclinical & clinical phases

The drug development process is a never-ending process as there is the emergence of new diseases and disorders. It is studied as a part of a pharmacology course in medicine and pharmacy.

Also, due to side effects and lack of response for established drugs, it is a requirement by health care for the development of new drugs.

New drugs are developed by a systematic process called the drug development process.

It is systematically controlled to ensure the authenticity and also the safety of humans and animals.

Also, carrying out scientific protocols helps one understand the mechanisms and other aspects of the drug, which will lead to the widespread use of the drug.

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

The drug development process is carried under the following steps.

  1. Isolation, synthesis.
  2. Preclinical trials.
  3. Scrutiny and grant of permission for clinical trials
  4. The pharmaceutical formulation of the drug.
  5. Clinical trials phase I, II, III.
  6. Review and grant of permission for marketing.
  7. Post marketing surveillance.

Isolation /synthesis:

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

Plant sources: Many drugs are found in plants ex: 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: 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, combinatorial chemistry.

Rational approach: Here, a drug is discovered based on pathological deficiency or abnormality. This needs the knowledge of human anatomy, pathophysiology, etc. L-dopa in parkinsonim, insulin is diabetes are the examples of this discovery.

Biotechnology: Biotechnology is another method by which many vaccines, anti-sera, 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 activity 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 as per the following.

  1. Testing of activity.
  2. Tests for specific activity on organs
  3. Test on human diseases induced in animals.
  4. Confirmation of activity
  5. Mechanism of action.
  6. Test on body systems.
  7. Pharmacokinetics
  8. Drug quantification.
  9. Toxicity studies.

Testing of activity: This is the test done on animals to see if the molecule has any activity.

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

Tests on human diseases: Here drug is tested to see if it can cure human disease.

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 activity is confirmed, its mechanism of action is tested. This gives an idea of how safe the drug is and how effective it can be in a patient.

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.

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

Drug quantification: This is a test to see the drug dose-response relationship, bio-availability, half-life, etc. This will help to fix the dose and time intervals for drug administration.

Toxicity studies: 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 is the test 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 minimum lethal dose that kills at-least 50% of animals in the group. 

Sub-acute toxicity: This test is done in 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.

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

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

Carcinogenicity: 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.

Clincial studies

Once the animals studies are complete with safety and efficacy data, testing is taken up over humans. This done in 4 phases as

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

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

Trial-I

Here the drug is administered to healthy individuals to determine the dose, side-effects and tolerance levels. It is conduced in few hundreds of people.

Trial-II

Here the drug is tested on diseases individuals for whom the drug is intended to treat. It is conduced on few hundred to thousand people to record the efficacy, dose, side-effects.

Trial-III

After trial-II, the drug is then taken up for large scale studies at multiple centers in diseased individuals. Once, the results are satisfcatory, the drug is released into market.

Trial-IV

This is done after drug is released into market and it is an ongoing process through out the life of drug in the market. Any side effects recorded from the market usage are noted and sent to WHO.

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