Pre Clinical Trials - Introduction

This powerpoint presentation will help to know the introduction of Pre Clinical Trials.Hope you understand well.If you need more notes refer some pharma and Biotechnology books.

1. PRE-CLINICAL TRIALS SUBMITTED BY R. Anbarasan 2 nd 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

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

7. 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

8. 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

9. MECHANISM OF ACTION – 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

10. 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

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

12. 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)

13. THANK YOU