Saturday, August 29, 2009

Drug Development: Non-Clinical Toxicity Study

Majority of allopathic drugs are developed from the organic or inorganic chemicals. The most important part of the process of drug development is the decision to take a new chemical entity (NCE) from a non-clinical to clinical phase. A lot of data needs to be generated through non-clinical safety study to evaluate the toxicity level of the NCE before it could be passed on for clinical phase of testing. The fundamental aim of non-clinical or pre-clinical studies is to generate biological, pharmaceutical and toxicological data to ascertain that NCE would not cause any serious harm to the humans. The limits of toxicological study of a NCE are decided with reference to the mode and duration of its use as a drug. Guidelines for such studies can be obtained from the regulatory agencies like FDA (USA), DCGI (India) and EMEA (Europe).

Why toxicity studies are necessary?

All chemical substances are poisons. Even the large doses of common salt (Sodium chloride) are poisonous and may affect our kidneys, heart and liver. Only a right dose differentiates a poison from a remedy. So, it is mandatory to conduct non-clinical or pre-clinical toxicity study for a NCE to generate pharmacological, toxicological and physicochemical data. There may be a dose which is safe and effective for humans otherwise a low dose would not generate any ill effect and a higher dose may produce deleterious effects. Non-clinical or pre-clinical toxicity studies of a NCE are performed in animals before it is declared as a drug and given to humans. Animal species usually used are mice, rats, guinea pigs, dogs and rabbits as lot of background knowledge about biological and physiological parameters of these animals is available.

Major goals of non-clinical toxicity studies:

  1. Generation of data regarding dose response and physiological and biological toxic effects.
  2. Identification of toxicities with respect to target organs if any.
  3. Evaluation of time-dependence of effects or reversibility of toxic effects
    after discontinuation of NCE under study.
  4. Identification of parameters required to be monitored effectively in human beings. Like liver function, renal function or thyroid function studies.
  5. Evaluation of safe starting dose for the first-in human trial, and
  6. Detection, identification and management of consequences of overdoses.