Biotechnology and Pharmacotoxicology

A.Y. 2021/2022
10
Max ECTS
88
Overall hours
SSD
BIO/14
Language
English
Learning objectives
The main objectives are:
1. to compare the characteristics of small molecule drugs, biotechnological agents, biosimilars and bioequivalent drugs
2. to characterize their molecular mechanisms of action, and to identify the mechanisms at the basis of the toxicity of small molecule drugs and biotechnological agents
3. to gain knowledge on the processes leading to the development and manufacturing of recombinant proteins for therapeutic use and on the possible related quality and safety issues
4. to learn about cell and gene therapy and their possible applications 5. to provide notions for a correct characterization and interpretation of genotoxic, cancerogenic, immunotoxic and reproductive adverse effects of xenobiotics.
6. to provide notions on preclinical toxicology for product development and the EU legislations concerning the following endpoints: genotoxicity, cancerogenicity, immunotoxicity, reproductive and developmental toxicity.
7. to compare the characteristics of small molecule drugs, biotechnological agents, biosimilars and bioequivalent drugs to identify the possible mechanisms at the basis of the toxicity of small molecule drugs and biotechnological agents 3. to gain knowledge on the processes leading to the development and manufacturing of recombinant proteins for therapeutic use and on the possible related quality and safety issues
Lectures will be dedicated to the introduction of the different topics and their toxicological evaluation, while the tutorials will be dedicated to the discussion of current OECD guidelines and case studies with a direct involvement of students.
Expected learning outcomes
Students will be able to identify the possible critical steps which could pose safety issues during the whole life of a pharmacologically active entity, from its synthesis and development up to its distribution and therapeutic use. They will also gain basic knowledge on the consequences of drug-drug interactions in multidrug therapy and on the critical issues about gene and cell therapy. Students will learn the basic principles of genotoxicity, cancerogenicity, reproductive toxicity and immunotoxicity and their assessment.
The tutorials aim to stimulate the student toward critical thinking and problem solving, promoting his/her attitude to growth and constant improvement (lifelong learning). At the end, to assess the actual learning of the student, an oral examination of approximately 30 minutes on the topics and issues related to the evaluation of these critical toxicity endpoints as discussed during lectures will be done. In addition, students will perform a literature search on a topic of their interest and will discuss it in light of subjects presented during lectures. This will promote their critical thinking and will set the bases for their future ability to successfully face different problems and to identify unforeseen critical safety issues in the field of pharmacology and biotechnology.
Course syllabus and organization

Single session

Responsible
Lesson period
Second semester
During the emergency teaching phase, the course program and the reference material will not change.
If classroom lessons will not be allowed, lessons will be implemented on line by synchronous lesson through the Microsoft Teams platform. The schedule and criteria for attending face-to-face lessons will be published in due time on the Ariel website along with any updates related to the Covid-19 emergency.
Course syllabus
Professor Corsini module
Modern toxicology involves the study of structure and mechanism related to the toxic effects of chemical agents, and encompasses technology advances in research related to chemical aspects of toxicology. Toxicology is strongly multidisciplinary, spanning computational chemistry and synthetic chemistry, proteomics and metabolomics, drug discovery, drug metabolism and mechanisms of action, bioinformatics, bioanalytical chemistry, chemical biology, and molecular epidemiology. Integration of all this information is central to hazard identification and proper risk assessment. Among possible adverse effects, those affecting the immune and the reproductive system together with genotoxic effects and the development of cancer, are the ones that should arouse the greatest concern.
The main purposes of this module are:
1. to provide notions for a correct characterization and interpretation of genotoxic, cancerogenic, immunotoxic and reproductive adverse effects of xenobiotics.
2. to characterize their molecular mechanisms of action.
3. to provide notions on preclinical toxicology for product development and the EU legislations concerning the following endpoints: genotoxicity, cancerogenicity, immunotoxicity, reproductive and developmental toxicity.
Lectures will be dedicated to the introduction of the different topics and their toxicological evaluation, while the tutorials will be dedicated to the discussion of current OECD guidelines with a direct involvement of students.

Professor Ceruti Module
Biotechnology and Pharmacology
Objectives:
The main objectives of the Biotechnology and Pharmacology module are:
1. to compare the characteristics of small molecule drugs, biotechnological agents, biosimilars and bioequivalent drugs
2. to identify the possible mechanisms at the basis of the toxicity of small molecule drugs and biotechnological agents
3. to gain knowledge on the processes leading to the development and manufacturing of recombinant proteins for therapeutic use and on the possible related quality and safety issues
4. to learn about cell and gene therapy and their possible applications

Program
- Introduction:
a. the drug discovery process with an historical perspective
b. prediction of adverse reactions and the evolution of clinical trials
- Biologics/Biosimilars, drugs/generics: characteristics and safety issues
- Therapeutic proteins: from synthesis to production and related safety issues
- Mechanisms of toxicity of small molecule drugs and of biotechnological agents
- Drug-drug and drug-natural compounds interactions
- Monoclonal antibodies: synthesis, characteristics and how their development affected regulatory agencies on clinical trials
- Cell and gene therapy: achievements, pitfalls and future perspectives
Prerequisites for admission
The student must have basic knowledge of anatomy, biology, physiology, pathology, and pharmacology.
Teaching methods
Frontal lessons and tutorials. To facilitate the acquisition of the necessary skills and abilities to work effectively in teams and to achieve objectives (i.e. autonomy, ability to plan and organize and manage information) working groups will be organized.

For the module Biotechnology and Pharmacology: this module will consist of seminars (40 hours).
Teaching Resources
Suggested study materials for Prof Corsini module:
- Casarett and Doull's Toxicology: The Basic Science of Poisons 8th Edition (Curtis D. Klaassen, Ed). Mc Graw Hill Education.
· Slides provided by the teacher through the ARIEL website (and the Teams app if online teaching will be utilized)
- Recent reviews and OECD guidelines on the subjects will be made available during class

Suggested study materials for Prof Cerruti module:
· Slides provided by the teacher through the ARIEL website (and the Teams app if online teaching will be utilized)
· Scientific articles provided by the teacher through the ARIEL website (and the Teams app if online teaching will be utilized)
· Textbook: Biotechnology and Biopharmaceuticals. Ho RJY, Gibaldi M - Wiley-Blackwell
· Textbook: Proteins. Biochemistry and Biotechnology. Walsh G - Wiley-Blackwell
· Textbook: Mechanistic Toxicology. Boelsterli UA - Taylor and Francis
Assessment methods and Criteria
Learning will be assessed by an oral examination of approximately 30 minutes on the topics and issues related to the evaluation of these critical toxicity endpoints as discussed during lectures.
Two separate examinations will be organized for the two modules. The final mark will be the average of the two marks.
Biotechnology and Pharmacology
BIO/14 - PHARMACOLOGY - University credits: 5
Lectures: 40 hours
Genotoxicology, Cancerogenicity, Immunotoxicology, Reproductive and Developmental Toxicity
BIO/14 - PHARMACOLOGY - University credits: 5
Tutorials: 16 hours
Lectures: 32 hours
Professor: Corsini Emanuela
Professor(s)
Reception:
By telephone or e-mail appointment
Dip. di Scienze Farmacologiche, Via Balzaretti 9, Milano