The document discusses pre-clinical trials, which are essential studies conducted on animals to test the safety and efficacy of new drugs before human trials. It explains different types of pre-clinical trials, including in vitro and in vivo methods, and outlines the stages, goals, and considerations involved in these studies. The ultimate aim is to ensure that promising treatments are safe for human testing by collecting vital safety data and identifying initial effective dosages.

1. PRE-CLINICAL TRIALS
SUBMITTED BY
R. Anbarasan
2nd M.Sc Biotechnology
ANNAMALAI UNIVERSITY

2. CONTENT
 Introduction
 History
 Pre-clinical trial
 Types
 Invitro preclinical trial
 Invivo preclinical trial
 Stages
 Consideration for trials
 Steps

3. INTRODUCTION
 Pre-clinical trials is a study to test a drug, a procedure or another
medical treatment in animals
 In drug development, pre-clinical development, also named pre-
clinical studies and non-clinical studies, is a stage of research that
begins before clinical trials (testing in humans) can begin, and
during which important feasibility, iterative testing and drug safety
data is collected
 It also means invivo or invitro experiments in which test articles are
studied prospectively in test systems under laboratory conditions to
determine their safety

4. HISTORY
 The first ever clinical trial was demonstrated by James Lind’s in
1753 that citrus fruits cured scurvy
 He compared the effects of various different acidic substances
ranging from vinegar to cider, on groups of sailors, and found that
the group who were given oranges and lemons had largely recovered
from scurvy after 6 days

5. PRE-CLINICAL TRIALS
 Definition- a laboratory test of a new drug or a new medical
device, usually done on animal subjects, to see if they hoped for
treatment really works and if it is safe to test on humans
 GOALS of this is to;
 identify initial safe dose and dose escalation schemes in humans
Identify target organs for toxicity
Study of such toxicity whether reversible
Identify safety parameter for clinical monitoring

7. TYPES
 TYPES OF CLINICAL TRIALS:
1. Invitro pre-clinical trials
1. Pharmacodynamics
2. pharmacokinetics
2. Invivo pre-clinical trials
• Screening
• Isolated organ
• Bacterial culture
• Animal models
• General observation
• Confirmatory
• Mechanism of action
• Systemic pharmacology
• Quantitative tests
• Toxicity tests

8. INVITRO PRE-CLINICAL TRIALS
PHARMACODYNAMICS STUDIES:
 Needed for better characterisation by providing evidence for the
desired biological effect of a drug
 Providing insight into potential toxicities to establish a human
starting dose
PHARMACOKINETIC STUDY:
 The ADME, volume of distribution and half-life of drug are
quantified

9. INVIVO PRE-CLINICAL TRIALS
 SCREENING - simple and rapidly performed tests to indicate
presence or absence of a particular activity
 ISOLATED ORGAN – study of activity on isolated organ.
Eg: Antipyretics
 BACTERIAL CULTURES – study of any activity using bacterial
cultures. Eg: Antibiotics
 ANIMAL MODELS – animal models used. Eg: genetically
hypersensitive rats, experimental tuberculosis in mouse
 GENERAL OBSERVATIONS – drug is injected in tripling doses
to small groups of mice which are observed for overt (hidden)
effects. Preliminary cluses are drawn from the profile of effect
observed

10.  MECHANISM OFACTION – attempts are made to find out the
mechanism of action. Eg: whether an anti-hypertensive is an β
blocker/ α blocker
 SYSTEMIC PHARMACOLOGY – irrespective of the primary
action of the drug, its effect on major organ systems such as
nervous, cardio-vascular, respiratory, renal are worked out
 QUANTITATIVE TESTS – the dose-response relationship,
maximal effects and comparative efficacy with existing drug is
carried out
 CONFIRMATORY TEST – compounds found active are taken up
for detailed study by more elaborate (complex) tests which confirm
and characterize the activity

11. STAGES
 Lead selection (like structural characterization, impurity identification,
solubility assessment, prototype formulation, stability testing) and
optimisation (like screening efficacy, early ADME, early toxicology)
 Drug candidate confirmation (data from lead selection and optimisation)
 Preliminary chemistry, manufacture, control
 Invivo models
 ADME profiling
 Preliminary toxicology
 Preclinical drug characteristics (data from previous stage)
 Detailed preclinical CMC
 Comprehensive ADME
 Toxicology package

12. CONSIDERATION FOR TRIALS
 Selection of relevant animal species
 Age
 Physiological state
 Manner of delivery
 Stability of test material

13. STEPS
Get idea for drug
Develop a bioassay
Screen chemical compounds in assay
Establish effective and toxic amounts
File for approval (leads to clinical trials)

14. THANK YOU