Drug Development Process| Overview of Preclinical & clinical phases

Drug development process is a never ending process as there is emergence of new diseases and disorders. It is studied as a part of 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 development of new drugs.

New drugs are developed by systematic process called as drug development process.

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

Also carrying out scientific protocols help one understand the mechanisms and other other aspects of drug which will can lead to wide spread 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 following steps.

  1. Isolation, synthesis.
  2. Preclinical trials.
  3. Scrutiny and grant of permission for clinical trials
  4. 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 opium plant yields codeine which is used in cough syrup to restrict cough.

Animals source: Few medicines are also obtained from animals. For examples 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 approach for search of new drugs. But doing it based on some lead molecule from natural products or already available drugs is easier. This method employ techniques like molecular modelling, combinatorial chemistry.

Rational approach: Here a drug is discovered based on the pathological deficiency or abnormality. This needs the knowledge of human anatomy, pathoohysiology 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 related.

Testing on organs: This test is done y giving the substance on to isolated organs to see for 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 the drug can be in patient.

Test on body systems: This test is done to see if the drugs has 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 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 following stages as

a. Acute toxicity.

b. Sub-acute toxicity.

c. Chronic toxicity.

d. Teratogenecity.

e. Mutagenicity.

 f. Carcinogenicity.

Acute toxicity: This is the test done for 1 to 3 days by give increasing doses of 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 in group of animals to define ED50%. This is the effective dose which can cure 50% of animals. Besides, the effect on feeding, growth, body weight and other parameters are noted.

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

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

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

Carcinogenecity: This is done by administration of drug for whole life of the animals. The intent is to see if the drugs have any carcinogenic (cancer) producing potential.

To be continued shortly…


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