Learning outcomes of the course unit
At the end of the course the student will be familiar with basic notions on the production of biotech proteins and on their therapeutic and diagnostic application. The biotech drugs presented will provide not only specific information on these drugs, but also an overview on the variety of products, production, purification and characterization techniques and application of biotech products currently available. In particular, at the end of the course, the student is expected to:
1. Know and understand the processes, techniques and specific issues related to the production, characterization and use of biotech drugs. Know in detail the structure, properties, functions, production techniques and application of biotech drugs treated during the course. Know the definition and examples of biosimilar and biobetter drugs and understand the rationale for pegylation and hyper-glycosylation of drugs, production of fusion proteins and conjugation of small molecules with macromolecules (Knowledge and understanding).
2. Interpret and critically comment information on biotech drugs, also in the wider context of production and use of biotech pharmaceuticals. Apply acquired notions to the understanding of strategies of protein modification aimed at improving product properties (Applying knowledge and understanding).
3. Identify relevant properties of specific biotech drugs and make inference on their production, potential for structural modification and application. Analyze pros and cons of techniques for the production of biotech drugs. Properly answer to questions, suggestions and criticisms, and formulate opinions on the topics treated in the course (Making judgements).
4. Report with proper language, to specialists and non-specialists, knowledge and concepts related to biopharmaceuticals, concerning both general aspects on the production of biotech drugs and detailed information on the drugs treated during the course (Communication skills).
5. Autonomously deepen his/her knowledge and expertise in the development and therapeutic application of biotech drugs, using bibliographic resources, integrating information from other disciplines (Learning skills).
Basic concepts of organic and medicinal chemistry, biochemistry, pharmacology and immunology are needed to understand the structure, action, application and critical aspects of recombinant therapeutic proteins. In particular, the student should be familiar with structure and function of amino acids and proteins, nucleotides, DNA and RNA and he/she should know the processes of DNA replication and transcription and of protein synthesis. Basic principles of immunology, knowledge of structure and function of antibodies are also required. Knowledge of acid-base equilibria, redox reactions, functional groups of organic chemistry and of the main mechanisms of action of drugs is another prerequisite of the course.
Course contents summary
The first part of the course provides basic knowledge on biotech methodologies and biotechnology-related techniques, and on their application to the design, production, downstream processing and characterization of biopharmaceuticals. The process and aim of drug pegylation are described, with examples of pegylated drugs, together with other strategies to increase the half-life of biotech drugs. Examples of biosimilars and biobetter drugs are also presented and discussed, in comparison with generic drugs. Basic notions related to diagnostic and analytical application of protein biologics are also provided. The second part of the course covers the most important biotech drugs used in several therapeutic areas, including hormones, enzymes, cytokines, vaccines, monoclonal antibodies and immunoconjugates. For each drug, relevant aspects related to structural properties, production, mechanism of action, therapeutic application, as well as pharmacokinetics and toxicity are described. Immunoconjugates and radioimmunoconjugates are presented, with examples of drugs used in the clinics. Structure-activity and structure-property relationships will be discussed to rationalize the production of analogs of physiological proteins with modified or improved pharmacodynamic and/or pharmacokinetic properties.
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. Pharmacokinetics and metabolic processes. 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) and derivatives; interferons; hematopoietic growth factors (G-SCF, erythropoietin).
Blood proteins: tissue-type plasminogen activator, clotting factors (VIII, IX).
Enzymes: human deoxyribonuclease, beta-glucocerebrosidase, alpha-galactosidase.
Recombinant vaccines: genetically improved live vaccines against salmonella and cholera; vector vaccines for veterinary use against covid-19; genetically improved subunit vaccines against hepatitis B, papillomavirus, diphtheria and whooping cough; glycoconjugated vaccines against pneumococcus and meningococcus.
Monoclonal antibodies, immunoconjugates and radioimmunoconjugates; murine, chimeric, humanized, human, bispecific antibodies and antibody fragments; rituximab, ofatumumab, ibritumomab tiuxetan, brentuximab vedotin, muromonab, catumaxomab, basiliximab, infliximab, adalimumab, certolizumab pegol, abciximab, ibalizumab.
Soluble receptors: etanercept.
Fusion proteins: denileukin diftitox.
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.
Teacher-led lessons (40 hours corresponding to 5 ECTS) with slide projection. The student is expected to study using the textbook and the material provided on the ELLY platform (slides and supplementary material). Lessons will be in presence, in compliance with safety standards. In case the sanitary emergence will continue, lessons will be in mixed mode (presence + online) or completely online. The way in which lessons will be delivered will be publicized through the Pharmacy degree web site. The teacher is available for explanations and discussion of the course contents at the end of the lesson, 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 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 is also evaluated through connections among topics and personal comments/evaluations related to the content of the course. 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 a simple discussion. During the examination, use of a proper terminology and language will be also assessed. Examinations will be in presence; however, in case the sanitary emergency will continue, it will be possible to sustain online examinations though MS Teams software ((http://selma.unipr.it for user guide). Online exams will be structured in the same way as those in presence. The grade for the course of Biotechnological Drugs/Supplement to Pharmaceutical Chemistry will be the average grade obtained for the two modules.