Drug discovery process: Principles techniques and statergies used in
new drug discovery. High throughout
screening. Human genomies robotics and economics of drug discovery,
Regulations, for laboratory animal care and ethical requirements.
Bioassays : Basic principles of bioassays official bioassays, experimental models and
statistical designs employed in biological standardization. Biological standardization of vaccines and sera with
certain examples with reference to IP. Development of new bio assay methods.
Preclinical
models employed in the screening of new drugs belonging to following
categories.
Antifertility agents, sympathomimetics,
parasympathomimetics, muscle relaxants (both central and peripheral).
Sedatives, hypnotics, antiarrhythmic agents, cardiac stimulants, cardiotonic
agents bronohodilators, antihistaminics, eicosanoids.
Antipsychotic agents, antianxiety agents
nootropic drugs antidepressant drugs; antiparkinsonism agents, anticpileptics;
analgesics and anti-inflammatory agents; antiulcer agents; infarction;
antiatherosclerotic drugs; antidiabetics; models for status epilepticus drugs.
cerebroventricular and other newer techniques of drug administration and
development; transgenic animals and other genetically prone animal models.
Alternatives to animal screening procedures,
cell-line handling and maintenance and propagation of cell lines, patch-clamp
technique, in-vitro cell line based assays diabetics and arthraitis models,
molecular biology techniques.
Principles of toxicity evaluations, ED50, LD50
and TD values, International guidelines (ICH Ethics and animal experimentation
recommendations).Guidelines and regulatory agencies – CPCSEA,OECD,FDA,
FHSA,EPA,EEC,WHO etc,
Introduction to biostatistics, parametric and
non-parametric tests. Regression and
correlation: Linear regressions, Method of least squares; correlation
coefficients, rank correlation, multiple regression Tests of significance:
testing hypotheses, tests of significance based on normal distribution. t-test;
significance of correlation coefficient. F-test and Analysis of Variance:
1-Way, 2-Way and 3-way classification, Chi-square test of (i) Variance of a
normal population (ii) Goodness of fit, (iii) Independence in contingency
tables. Non parametric tests, order statistics, sign test, run test, Median
test.
BASIC PRINCIPLES OF TOXICOLOGY
General principal of regulatory toxicology. Use of
animals in preclinical toxicology studies, role of preclinical toxicology in
drug discovery and development process. Experimental considerations for
assessing possible human risk. Flow chart for development of preclinical
testing. Dose conversion factors, clinical signs toxicity.
Single dose and repeat dose toxicity studies; Factors
influencing such studies such as species, sex, size, route ,dose level; Data
evaluation and regulatory requirements. Determination of Maximum Tolerated Dose
(MTD) and LD 50 as per revised OECD guidelines. Allergenicity testing, dermal
toxicity, immunotoxicology and in vitro methods of toxicology.
Reproductive toxicology assessment of
male reproductive toxicity, spermatogenesis; Risk assessment in male
reproductive toxicity; Female reproductive toxicology; Oocyte toxicity;
alterations in reproductive endocrinology; Relationship between maternal and
developmental toxicity.
Mutagenicity; Mechanisms of mutagenesis, point
mutations,; Individual chromosomes and complete genome mutations, germ cell
mutations, somatic cell mutation; Tests systems in vitro, chromosome damage and
chromosomal aberration test, gene mutation, in vivo micronucleus tests in
rodents, metaphase analysis.
Preclinical toxicological requirements for biologicals
and biotechnological products; safety analysis; problems specific to
recombinant products, toxicokinetics, principles of GLP as per OECD guidelines
for conducting preclinical toxicity studies