Pre Clinical Study

Type of studies Observation Timing of study
Pharmacodynamic studies

Amount of drug required for optimal activity in animal model

To estimate how much drug would be required for human use

Herbal Drug Discovery
Pharmacokinetic studies

Pharmacokinetic data (adsorption, distribution, metabolism, excretion (ADME))

Important values of the concentration curves include as below:

i. Maximum plasma concentration of the drug (Cmax)

ii. Time taken to achieve Cmax (Tmax)

iii. T1/2: half-life of the drug or the time taken for the drug to be reduced to 50% of its starting concentration

iv. Area under the curve (AUC)

Prior to first administration in human (Preclinical testing)
Safety pharmacology To establish the No Adverse Effect Level (NOAEL) value. Effect on core system of the body: Central Nervous System, Respiratory System, Cardiovascular System.        

Prior to first administration in humans (Preclinical testing): Conducted on core system of the body

Any follow-up or supplemental studies identified as appropriate, based on a cause for concern

During Clinical Development: Additional studies may be warranted to clarify observed or suspected adverse effects in animals and humans

Before clinical trial and product registration: Supplemental studies (if warranted)

Toxicokinetic studies The study is conducted to quantify exposure of: plasma (serum or blood) concentrations, or the AUCs of parent compound and/or metabolite(s), or tissue concentrations, or the exposure and dose-dependence in humans at therapeutic dose levels (either expected or established), or species differences (either qualitative or quantitative)

Single-dose toxicity studies: Early phase of development

14 days duration or longer   Repeated-dose toxicity studies: Related to the duration, therapeutic indication and scope of propose clinical trial

Genotoxicity studies: In vitro (Preclinical testing) In vivo (During clinical trials)

Reproductive studies: Before phase III

Carcinogenicity studies: Case- by- case

General toxicity studies

These studies are conducted to obtain values as below: LD50: dose at which half of animals treated with a single dose of test compound die

NOAEL (no-observed adverse effect level): highest dose at which treatment related findings occur but that are not considered to be adverse

NOEL (no-observed effect level): highest dose at which no treatment related findings occur

MTD (maximum tolerated dose): highest dose tolerated by test animals

During Preclinical testing
Single-dose toxicity studies The study is conducted in two mammalian species using both clinical and parenteral route of administration, with the objective to determine the mode of death and a quantitative evaluation of the approximate lethal dose. Prior to first administration in humans (Preclinical testing)
Repeated-dose toxicity studies The study is conducted in two mammalian species (one non-rodent) to obtain toxicity profile: MTD NOAEL  

Prior to first administration in humans (2 Weeks)

During clinical development

Before phase II: 2W – 6M

Before phase III: 1M – chronic  

Genotoxicity studies Assessment of mutagenicity in a bacterial reverse gene mutation test. Evaluated in mammalian cells in vitro and/or in vivo Prior to first administration in humans (Genotoxicity in vitro)   During Clinical Development (Genotoxicity in vivo)
Carcinogenicity studies To identify a tumorigenic potential in animal

To assess the relevant risk in humans

Expected clinical use is continous for at least 6 months

For pharmaceuticals used frequently in an intermittent manner in the treatment of chronic or recurrent conditions

Reproduction toxicity studies

The data should be obtained are as below:

– Preliminary embryo- foetal study data:

  • Foetal survival
  • Body weight
  • External and visceral examination

– Fertility studies

– Precautions on prevention of pregnancy

– Pre-postnatal development study

Prior to phase III
Local tolerance studies

The data should be obtained are as below:

Clinical signs Macroscopic and microscopic examination of application site

According to site/s in clinical use
Immunotoxicity studies Case-by-case Case-by-case
Photosafety testing Case-by-case Case-by-case


  1. International Conference on Harmonisation (ICH) Tripartite Guideline. Preclinical Safety Evaluation of Biotechnology – Derived Pharmaceuticals S6 (R1). 12 June 2011.
in this scope