Course content

• Identification of target or drug leads associated with a particular disease by a number of different techniques including combinations of molecular modeling, combinatorial libraries and high-throughput screening (HTS);
• Conceptualizing the automation of the HTS process and the importance of bioinformatics and data processing in identification of lead compounds;
• Rational drug design, based on understanding the three-dimensional structures and physicochemical properties of drugs and receptors;
• Modelling drug/ receptor interactions with the emphasis on molecular mechanisms, molecular dynamics simulations and homology modelling; Conformational sampling, macromolecular folding, structural bioinformatics, receptor-based and ligand-based design and docking methods, in silico screening of libraries, semi-empirical and ab-initio methods, QSAR methods, molecular diversity, design of combinatorial libraries of drug-like molecules, macromolecular and chemical databases.
• Identification of relevant groups on a molecule that interact with a receptor and are responsible for biological activity; Understanding structure activity relationship; Structure modification to increase potency and therapeutic index; Concept of quantitative drug design using Quantitative structure–activity relationship models (QSAR models) based on the fact that the biological properties of a compound are a function of its physicochemical parameters such as solubility, lipophilicity, electronic effects, ionization, stereochemistry, etc.;
• Bioanalytical assay development in support of in vitro and in vivo studies (LC/MS/MS, GC/MS and ELISA).
• Principles of drug absorption, drug metabolism and distribution - intestinal absorption, metabolic stability, drug-drug interactions, plasma protein binding assays, metabolite profile studies,
• Principles of toxicology, Experimental design for preclinical and clinical PK/PD/TK studies, Selection of animal model; Regulatory guidelines for preclinical PK/ PD/TK studies; Scope of GLP, SOP for conduct of clinical & non clinical testing, control on animal house, report preparation and documentation Integration of non-clinical and preclinical data to aid design of clinical studies.
• Requirements of GMP implementation, Documentation of GMP practices, CoA,
• Regulatory certification of GMP, Quality control and Quality assurance, concept and philosophy of TQM, ICH and ISO 9000; ICH guidelines for Manufacturing,
• Understanding Impurity Qualification Data, Stability Studies. Objectives of Phase I, II, III and IV clinical studies, Clinical study design, enrollment, sites and documentation, Clinical safety studies: Adverse events and adverse drug reactions, Clinical PK, pharmacology, drug-drug interaction studies, Statistical analysis and documentation.
• Global Regulatory Affairs and different steps involved, Regulatory Objectives, Regulatory Agencies; FDA guidelines on IND and NDA submissions, Studies required for IND and NDA submissions for oncology, HIV, cardiovascular indications, On-label vs. off-label drug use GCP and Requirements of GCP Compliance, Ethical issues and Compliance to current ethical guidelines, Ethical Committees and their set up, Animal Ethical issues and compliance.

References

• Krogsgaard-Larsen et al. Textbook of Drug Design and Discovery. 4th Edition. CRC Press.
• Kuhse, H. (2010). Bioethics: Anthology. Malden, MA: Blackwell.
• Nally, J. D. (2006) GMP for Pharmaceuticals. 6th edition. CRC Press
• Brody, T. (2016) Clinical Trials: Study Design, Endpoints and Biomarkers, Drug Safety, and FDA and ICH Guidelines. Academic Press.