Learning outcomes of the course unit
At the end of the course the student has become familiar with basic notions on the production of biotech proteins and on their therapeutic and diagnostic application. The examples of biotech proteins treated during the course will provide an overview of the variety of products, production, purification and characterization techniques, as well as of application of biotech products currently available. In particular, at the end of the course, the student is expected to:
1. Understand the processes, techniques and issues related to the production, characterization and application of biotech drugs. Know in detail the structural properties, function, production techniques and application of the biotech drugs treated during the course. Know the meaning and examples of biosimilar and biobetter drugs. (Knowledge and understanding).
2. Interpret and critically comment information on biotech drugs in the wider context of production and application of biotech pharmaceuticals (Applying knowledge and understanding).
3. Identify relevant properties of specific biotech drugs and draw conclusions on their production, potential for structural modification and application. Analyze pros and cons of techniques for the production of biotech drugs (Making judgements).
4. Report with proper language, to specialists and non-specialists, knowledge and concepts related to biopharmaceuticals, concerning general aspects related to the production of biotech drugs as well as more detailed information about the properties of the specific drugs treated during the course (Communication skills).
5. Autonomously deepen his/her knowledge and expertise in the development, application and therapeutic application of biotech drugs, using proper bibliographic resources, with integration of information from other disciplines (Learning skills).
Basic concepts of medicinal chemistry, biochemistry, organic chemistry, immunology and pharmacology are needed to understand the structure, action, application and critical issues of recombinant therapeutic proteins. In particular, the student should be familiar with structure and function of amino acids and proteins, of nucleotides, DNA and RNA and he/she should know the processes of DNA replication and transcription and of protein synthesis. Basic principles of immunology, structure and function of antibodies. Knowledge of functional groups of organic chemistry and of the main metabolic transformation of drugs is another prerequisite of the course.
Course contents summary
The first part of the course provides basic knowledge about biotech methodologies and biotechnology-related techniques and their application to the design, production, downstream processing and characterization of biopharmaceuticals. The second part of the course will cover the most important biotech drugs used in different therapeutic areas, such as hormones, enzymes, cytokines, vaccines and monoclonal antibodies. For each drug, relevant aspects related to production, mechanism of action, therapeutic application, as well as pharmacokinetic properties and toxicity will be treated. For biotech drugs different from physiological proteins, structure-activity and structure-property relationships will be discussed, relevant to their modified/improved pharmacodynamic and pharmacokinetic properties. Examples of biosimilars and biobetter drugs will be presented and discussed. Basic notions related to diagnostic and analytical application of protein biologics will also be provided.
Introduction to biotechnology. Basic concepts of molecular biotechnology. Production of biotech products: cultivation and downstream processing. Biophysical and biochemical analyses of recombinant proteins. Chemical and physicochemical properties and reactivity of recombinant proteins; stability of proteins and mechanisms of degradation. Immunogenicity of biopharmaceuticals. Pegylation of therapeutic proteins. Fusion proteins and soluble receptors. Biosimilars and biobetters.
Hormones: insulin, growth hormone, follicle-stimulating hormone, luteinizing hormone.
Cytokines: interleukins (IL-1, IL-2); interferons; hematopoietic growth factors (G-SCF, erythropoietin).
Blood proteins: tissue-type plasminogen activator, clotting factors (VII, VIII, IX).
Enzymes: human deoxyribonuclease, beta-glucocerebrosidase, alpha-galactosidase. R
ecombinant vaccines: genetically improved live vaccines, live vectors, genetically improved subunit vaccines.
Monoclonal antibodies, immunoconjugates and radioimmunoconjugates: rituximab, ofatumumab, ibritumomab tiuxetan, brentuximab vedotin, muromonab, catumaxomab, daclizumab, basiliximab, infliximab, adalimumab, certolizumab pegol.
Soluble receptors: etanercept.
Maria Luisa Calabrò, Compendio di Biotecnologie Farmaceutiche, EdiSES, Napoli, 2008.
Daan J.A. Crommelin, Robert D. Sindelar, Biotecnologie Farmaceutiche, Zanichelli, Bologna.
Thomas L. Lemke, David A. Williams, Victoria F. Roche, S. William Zito, Foye’s Principi di Chimica Farmaceutica, sesta edizione italiana, Piccin, Padova, 2013. (for the specific chapter related to pharmaceutical biotechnology. An English version of this book is available)
Daan J.A. Crommelin, Robert D. Sindelar, Bernd Meibohm, Pharmaceutical Biotechnology, Fourth Edition, Springer, 2013.
Pdf files of the slides commented during the lessons will be available for students before the beginning of the course at the Elly web site (http://elly.farmacia.unipr.it/2018/).
Teacher-led lessons (40 hours corresponding to 5 CFU)with slides used to describe and discuss the topics of each lesson. The student is expected to study and understand the content of the lessons using the textbook and the material provided through the ELLY platform (slides and supplementary material). The teacher is available for explanation and discussion of the course contents at the end of the lesson, during lesson breaks or by appointment (e-mail request).
Assessment methods and criteria
An oral examination, with questions related to all the topics treated during the course, will be used to assess the knowledge and comprehension of the contents of the course achieved by the student. The ability of the student to apply the acquired knowledge will be also evaluated through connections among topics. Preparation is considered sufficient if the student proves knowledge and understanding of the basic aspects of each topic and is able to apply this knowledge to the discussion. During the examination use of a proper terminology will also be assessed. The grade for the course of Biotechnological Drugs/ Supplement to Pharmaceutical Chemistry will be the average grade obtained for the two modules.