Description of Individual Course Units
Course Unit CodeCourse Unit TitleType of Course UnitYear of StudySemesterNumber of ECTS Credits
300005452015TOXICOLOGY IN DRUG DEVELOPMENTElective593
Level of Course Unit
First Cycle and Second Cycle
Language of Instruction
Turkish
Objectives of the Course
The aims of this elective course are evaluating the drug development process such as testing the toxicity potential of drug candidates in preclinical and clinical phases, as well as post-approval monitoring (pharmacovigilance) and methods of determination the safe and toxic doses, and assessment and interpretation of test results in an interactive manner with the students.
Name of Lecturer(s)
Learning Outcomes
1To comprehend drug discovery and development as a whole process
2To understand the strategy of preclinical studies
3To have basic knowledge on both successful and unsuccessful examples of drug discovery and development studies
4To comprehend design techniques and outcomes interpretatiton of general and special toxicity tests applied to drug candidates
Mode of Delivery
Face to Face
Prerequisites and co-requisities
-
Recommended Optional Programme Components
Course Contents
Novel approaches in order to identify and diminish potential toxicity of candidates in drug discovery and development process and applied strategies and tests that used as tools in the process will be transferred to the students. Next to the global regulations, contemporary strategies of pharmaceutical industry will also be investigated. In addition to classical small molecules in the course content, biotechnological drugs that comprise a significant part of the agenda for the last 15 years together with successful and unsuccessful examples (investigational novel drugs (IND) that caused deaths in volunteers/patients in clinical phases or post-approval retracted drugs) are also discussed.
Weekly Detailed Course Contents
WeekTheoreticalPracticeLaboratory
1Introduction to drug discovery and development studies History / Preclinical - clinical phases and postapproval toxicology; pharmacovigilance--
2Biotransformation and testing the potential of reactive metabolite formation.
3Animal models in carcinogenic potential
4Small and large molecules (monoclonal antibodies, fusion proteins, antibody-drug conjugates): comparison of their toxicology New Chemical Entities (NCEs), New Biological Entities (NBEs)
5Cell culture and in vitro models in drug secreening and toxicity studies
6Early phase in vivo toxicity tests
7Identifying of administration route of tolerable and above doses MTD, MFD, 50-fold margin dose, limit dose, saturation of exposure, STD, FIH
8Unsuccessful examples of drug development due to toxicity - black box and retraction process
9Regulation – FDA / EMEA / PMDA International Conference for Harmonization (ICH) guidance compendium
10Toxicokinetics studeis of drug candidates under GLP conditions
11Protein-binding and drug-drug interaction tests at CYPs level
12Predictive safety assessment of drug candidates: In silico, hERG, phospholipidosis, toxicology species target expression profiling & tissue cross reactivity studies, predictive hepatotoxicity, predictive cardiovascular & ion channels toxicity, predictive teratogenicity
Recommended or Required Reading
Han C, Davis CB, Wang B. Evaluation of drug candidates for preclinical development: pharmacokinetics, metabolism, pharmaceutics and toxicology. John Wiley&Sons, New Jersey, 2010. ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals. EMA/CPMP/ICH/286/1995, December 2009. ICH guideline S6 (R1) – preclinical safety evaluation of biotechnology-derived pharmaceuticals. EMA/CHMP/ICH/731268/1998, Committee for medicinal products for human use (CHMP) June 2011. Alexander JC, Salazar DE. Modern drug discovery and development. In: Robertson D, editor. Clinical and Translational Science: Principles of Human Research. Academic Press; London: 2009. pp. 361–380. Denny KH, Stewart CW. Acute, subacute, subchronic, and chronic general toxicity testing for preclinical drug development. In: A comprehensive guide to toxicology in nonclinical drug development Faqi AS (ed.) , Second Edition, Academic Press, 2017.
Planned Learning Activities and Teaching Methods
Assessment Methods and Criteria
Term (or Year) Learning ActivitiesQuantityWeight
Midterm Examination1100
SUM100
End Of Term (or Year) Learning ActivitiesQuantityWeight
Final Sınavı1100
SUM100
Term (or Year) Learning Activities40
End Of Term (or Year) Learning Activities60
SUM100
Work Placement(s)
-
Workload Calculation
ActivitiesNumberTime (hours)Total Work Load (hours)
Midterm Examination122
Final Examination122
Attending Lectures14228
Individual Study for Mid term Examination5420
Individual Study for Final Examination8432
TOTAL WORKLOAD (hours)84
Contribution of Learning Outcomes to Programme Outcomes
PO
1
PO
2
PO
3
PO
4
PO
5
PO
6
PO
7
PO
8
PO
9
PO
10
PO
11
PO
12
PO
13
PO
14
PO
15
PO
16
PO
17
PO
18
PO
19
PO
20
PO
21
LO1344435555 52422333545
LO2344535555552422333545
LO3354535555552422333545
LO4344535555552422333545
* Contribution Level : 1 Very low 2 Low 3 Medium 4 High 5 Very High
 
Ege University, Bornova - İzmir / TURKEY • Phone: +90 232 311 10 10 • e-mail: intrec@mail.ege.edu.tr