Pharmaceutical Biotechnology

Biological medicines. Definition, pharmacological characteristics, examples, main therapeutic areas. Drug development. Experimental models. Assays for in vitro pharmacodynamic activity. Cellular, systemic, functional toxicity. Main mechanisms of cellular toxicity. Damage caused by the body's response. Inflammation and fibrosis. Co-exhibitions, interactions. Acute, chronic, delayed toxicity. Mechanisms of tolerance, rebound. Experimental toxicological studies. Duration of studies. Acute toxicity studies: purposes; lethality curves; acute exposure limits. Toxicity studies after repeated administration: doses, target organs, objectives. Safety pharmacology studies. Predictivity of animal studies. Doses used and extrapolation to humans. Limitations of toxicology studies for biological drugs, the relevant species. Chemical carcinogenesis. The multi-stage model of chemical carcinogenesis: initiation, promotion, progression. Definitions. IARC groups. Complete carcinogens, initiators, promoters, progression agents. Genotoxic and epigenetic carcinogens. Direct and indirect carcinogens. Epigenetic carcinogens: promoters, immunosuppressants. Animal carcinogenicity studies and interpretation problems. Genotoxicity studies; mutagenesis, clastogenesis tests, tests for other genetic damage, structure-activity relationship. Guidelines on genotoxicity studies for drugs. Use of drugs in pregnancy. Reproductive and developmental toxicology. Problems of identification and determination of 'safe' exposures. Critical periods of susceptibility: effects of exposure in the pre-implantation period, during organogenesis, and in the fetal period. Experimental studies. Information on the risk of using drugs in pregnancy. Medicines recognized as toxic for development. Regulatory classification of drugs based on developmental toxicity data. Pharmacokinetics. Aims of pharmacokinetic studies. Importance of drug metabolism for the elimination of activity; bioactivation. General mechanisms: passive diffusion, transporters; interactions at the level of transporters. Gastrointestinal absorption. Distribution. Routes of excretion. Kinetics of order I and order 0. Kinetic parameters and their uses. Pharmacokinetics of biological drugs (proteins). Routes of administration, mode of elimination. Formation of anti-drug antibodies and their clinical relevance. Biosimilar drugs. Synthetic drug metabolism. Purpose and effects on metabolism toxicity. Metabolism and pharmacological activity. General characteristics of biotransformation reactions. Multiple metabolic pathways. Variability of metabolizing enzymes. Genetic polymorphism of metabolizing enzymes. Interactions: enzyme induction and inhibition. Clinical trial. Phase 1, 2 and 3 studies. Aims of the studies. Endpoints used in clinical trials. The design of the studies; blinding, use of control groups, randomization. Regulatory aspects. The Summary of Product Characteristics. Pharmacovigilance and post-authorization studies. Aims of pharmacovigilance. Definitions of adverse drug reaction and adverse event. Severe reactions, unexpected reactions. Classification of adverse reactions by type. Characteristics of type A and B reactions. Immune-mediated hypersensitivity reactions. Idiosyncrasies. Pharmacovigilance: how to identify adverse reactions; criteria of imputability; spontaneous reports. The Risk Management Plan. Active pharmacovigilance: pharmacoepidemiology studies, PASS studies.

Essential prerequisites: knowledge of physiology, biochemistry, pharmacology.

Lecture slides

Attendance is not mandatory but strongly recommended

In the oral exam, the student is asked questions in order to assess the acquisition of the expected learning outcomes. The ability to make connections between the different aspects of the program will be assessed with particular attention. Students also have the opportunity to complete a part of the exam by carrying out a project (for example, the clinical development project of a new drug), to be agreed with the teacher. During the execution of the project, 3-5 meetings with the teacher are held, during which the progress of the project is critically discussed.

Biological Drug Products: Development and Strategies 1st Edition by Wei Wang (Editor), Manmohan Singh (Editor)

Frontal lessons