Introduction
Pre-clinical evaluations are the studies carried out on a new drug before it is tested on humans. These studies help determine whether the drug is safe, effective and suitable for clinical trials. They include laboratory experiments, animal studies and detailed safety assessments. Only a small number of molecules discovered in research reach the clinical trial stage, and even fewer become approved medicines.
Goals of Pre-Clinical Studies
- To identify a safe dose for the first human trial.
- To collect information on the drug’s safety profile.
- To study basic pharmacology — including pharmacodynamics and pharmacokinetics.
- To detect possible toxic effects and target organs affected by the drug.
Both in-vitro (test-tube or cell-based) and in-vivo (animal-based) studies are performed. All pre-clinical work is conducted under strict Good Laboratory Practices (GLP) to ensure accuracy and safety.
Types of Pre-Clinical Studies
1. Pharmacodynamic (PD) Studies
These studies explain how the drug acts on the body. They identify the drug’s mechanism of action and therapeutic effects.
2. Pharmacokinetic (PK) Studies
PK studies describe what the body does to the drug. This includes:
- Absorption
- Distribution
- Metabolism
- Excretion
These studies help determine whether the drug reaches the target organ in sufficient concentration.
3. Toxicological Testing
Toxicology studies identify harmful or unwanted effects of the drug. They also help in estimating a safe starting dose for humans.
Special Toxicity Studies
Some drugs require additional long-term or specialised toxicity testing:
a) Carcinogenicity
Tests whether the drug can cause or promote cancer after long-term use.
b) Mutagenicity
Checks whether the drug can cause genetic mutations or damage DNA.
c) Teratogenicity
Assesses whether the drug can harm the developing fetus when taken during pregnancy.
Animal Testing in Pre-Clinical Evaluation
Animal studies are essential for understanding the safety of new drugs before human trials. Pre-clinical toxicity studies usually involve at least two animal species:
- One rodent species (e.g., mouse, rat)
- One non-rodent species (e.g., dog, rabbit, monkey)
Selection of Animal Species
The choice of animal depends on how closely its physiology matches humans for that drug. For example:
- Dogs are commonly used for oral dosage forms.
- Primates or pigs may be used for drugs requiring similarities to human metabolism.
The digestive system, enzyme activity, and circulatory features are considered when selecting the appropriate species.
Regulatory Requirements
Guidelines from global authorities like USFDA and EMA require toxicity testing in at least two mammalian species before approving human trials. One must be a non-rodent species.
Importance of Animal Ethics
Ethical treatment of animals is mandatory. Studies must be approved by:
- An Institutional Animal Ethics Committee (IAEC)
- Regulatory bodies such as CPCSEA in India
Animal Welfare Requirements
Guidelines ensure humane care of animals regarding:
- Housing conditions
- Cleanliness and sanitation
- Food and water supply
- Safe handling and disposal of waste
Standard Operating Procedures (SOPs) must be maintained for:
- Animal husbandry
- Breeding programs
- Microbial monitoring
- Record keeping
Outcome of Pre-Clinical Studies
After completing pre-clinical evaluations, researchers can determine:
- The safe starting dose for human trials
- The potential risks and toxic effects
- Target organs that may be affected
- Whether the drug is suitable for further development
If the drug shows unacceptable toxicity or poor pharmacokinetics, it is usually rejected before clinical trials.
Detailed Notes:
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