Medical Biotechnology

Activity type

Attività formative affini o integrative

SSD

MED/46

Year

N/D

Semester

N/D

CFU

2

Hours distribution

16 classroom hours

Lecturers

LUCIA DI MARCOTULLIO

Activity type

Discipline medico-chirurgiche e riproduzione umana

SSD

BIO/14

Year

N/D

Semester

N/D

CFU

4

Hours distribution

32 classroom hours

Lecturers

DANIELA MELCHIORRI
DANIELA MAFTEI

To understand the principles of pharmacokinetics, their relevance in drug research and development, and importance in patient care.
To learn the main post-marketing drug monitoring activities.

At the end of the integrated course the student will:
1. know:
- the pathway that, starting from medical research, leads to the release of the marketing authorisation for a medicinal product.
- the type and structure of non-clinical and clinical studies requested during drug development
- the pathway that leads to the pre-clinical characterization of the drug safety profile
- the rational for the selection of primary and secondary endpoints of clinical studies
- the factors that drive and regulate the drug voyage in the human body, and their relevance in drug development.
- the role of pharmacokinetics in drug development
- the methods of research associated with the study of drug pharmacokinetics
- the tools made available by the legislation to foster the translation from basic science and research to medicinal products
- the tools available for the post-marketing safety monitoring of medicinal products
- the importance of a constant post-marketing safety monitoring of drugs
- the main signaling pathways involved in neoplastic and genetic diseases
- the main targeted therapies currently in use in Europe
- the different types of biological drugs and their molecular targets
- therapies based on the use of mono-clonal antibodies, small molecules and RNA drugs
- the principles of neuropharmacology and psychopharmacology
- the potential applications of biotechnological drugs for central nervous system disorders
- the experimental models used in the study of psychiatric disorders and their applications in behavioral pharmacology
2. be able to:
- plan drug development making use of all the tools provided by the European and Italian legislation to foster research and development
- make use of Good Laboratory Practise (GLP) guidelines to perform pre-clinical research according to the standards requested by the Regulatory Authorities
- understand and apply drug pharmacokinetic data to select drug posology and root of administration
- interpret drug preclinical and clinical data
- interact with the European and national pharmacovigilance system
- identify the most appropriate therapies and drugs for the treatment of neoplastic and genetic pathology
- understand the efficacy of a drug based on preclinical studies
- identify the most appropriate experimental models for the study of new pharmacological treatments in neuropsychiatric disorders
3. have acquired the ability to integrate the knowledge derived from attending the course to formulate judgements based on the available data. This will be accomplished by written quizzes and short reports on specific themes of the integrated course.
4. have acquired the ability to communicate their knowledge and conclusions to specialist and non-specialist audiences clearly and unambiguously. This will be accomplished through the public presentation and discussion of several scientific papers that will be made available as study material of the course.
5. have developed the learning skills that are necessary for them to continue to undertake further studies in the field of pharmacology and molecular therapies with an acceptable degree of autonomy. In particular, the student will be introduced to:
a. the consultation of the most relevant scientific websites where to find information on drug approval, pharmacovigilance issues, drug-drug interactions (i.e. The European medicines Agency, the AIFA and the Eudravigilance websites).
b. main tools to interpret the basic statistics used in clinical trials
c. main tools to interpret the results of pre-clinical and clinical studies
d. experimental models in neuropharmacology

Basic knowledge of cell biology (important) and pharmacodynamics (useful)
Basic concepts of molecular biology, inorganic and organic chemistry and immunology (important)

Module: Pharmacology
Molecular therapy: targeted therapies with small molecules, epigenetic drugs and nucleic acid based therapies (2 CFU)

1. Design and development of biologic drugs (2 hrs)
2. Molecular aspects of drug action (2 hrs)
3. Intracellular signaling pathways as target of innovative medicine (4 hrs)
4. Pharmacological regulation of cellular functions (2 hrs)
5. Nucleic acids as drug targets and as drugs (2 hrs).
6. Description of siRNA, microRNA, and nc-small RNAs as therapeutic agents (2 hrs).
7. Drug-delivery (2 hrs).


Module: Molecular therapies
The integrated course will provide basic knowledge in the field of research and drug development. The course is articulated in 3 strictly connected modules. Module 1 will provide the knowledge and tools to act in the research and drug development field. Module 2 and 3 will provide examples of research and development of drugs for advanced therapies (module 2) and central nervous system diseases (module 3)
Module 1 will be developed through 3 teaching units:
Unit 1 (6h) will focus on research, drug development and post-marketing monitoring. The main part of the teaching will focus on the pre-clinic and clinic phases in drug development with particular reference to the type and design of non-clinical and clinical studies requested for drug development, the tools to interpret study results, and European guidelines for the redaction of the marketing authorisation dossier. Differences in the development of chemical drugs and biotechnological drugs will be described, with a dedicated focus on advanced therapy medicinal products (ATMPs). The legislation on innovative drugs will be discussed, together with the available tools aiming at facilitating development and authorisation of innovative drugs.
The Unit will also focus on the Competent Authorities for the release of the marketing authorisation (MA) of medicinal products in Europe, US and Japan. There are two ways to obtain a MA: via the Centralised Procedure or via a non-centralised procedure. The latter includes the Decentralised Procedure, the Mutual Recognition Procedure, and the National Procedure. The Unit will deal with the legal provisions and responsibilities for the competent authority and MA holders in both systems.
Post-marketing activities and safety monitoring of authorised medicinal products in Europe will represent the object of the last section of this Unit, that will deal with the responsibilities of the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency, the Eudravigilance system for reporting of adverse reactions to medicinal products, and the redaction and use of the Periodic Safety Update Report (PSUR).
Unit 2 (8h) will deal with Pharmacokinetics and focus on absorption, distribution, metabolism and excretion of drugs.
The Unit will address the role and importance of pharmacokinetic studies in drug development and in particular for the selection of the correct posology and the identification of drug-drug interactions. Several examples will be given of how the pharmacokinetics knowledge is reflected in the relevant sections of the Summary of Product Characteristics (SmPC).
The Unit will focus on bioequivalence studies and their role in the clinical development of drugs. Differences between generics and biosimilar drugs will also be addressed.
Unit 3 (2 ore) will consist of a discussion meeting with students on the subjects of the previous two units in order to foster learning and comprehension of the core elements of the course
Modulo 2 Molecular Therapies
Module 2 will be developed through 7 teaching units:
1. Design and development of biologic drugs (2 hrs)
2. Molecular aspects of drug action (2 hrs)
3. Intracellular signaling pathways as target of innovative medicine (4 hrs)
4. Pharmacological regulation of cellular functions (2 hrs)
5. Nucleic acids as drug targets and as drugs (2 hrs).
6. Description of siRNA, microRNA, and nc-small RNAs as therapeutic agents (2 hrs).
7. Drug-delivery (2 hrs).
Modulo 3 Drugs of the Central Nervous System
Module 3 will be developed through 6 teaching units:
1. Introduction to pharmacogenomics (2 hours).
2. Gender medicine and principles of developmental toxicology (2 hours).
3. Pharmacology of the Autonomic Nervous System (3 hours).
4. Principles of neuropharmacology and experimental animal models in behavioral pharmacology (5 hours).
5. Biotechnological drugs for the treatment of central nervous system disorders (2 hours).
6. Pharmacological treatment of schizophrenia (2 hours).

Module: Pharmacology
N/D
Module: Molecular therapies
Powerpoint presentations of the course and scientific articles on topics of the lessons will be provided

Module: Pharmacology
N/D
Module: Molecular therapies

Scientific articles on topics of the lessons will be provided

Up-front teaching followed, in the final phase, by discussion of scientific paper articles addressing the issues of the lessons. This type of self-directed and mindfulness-oriented learning will develop student’s critical approach to scientific issues and provide tools for constant knowledge upgrading during professional life.

Class attendance is mandatory.

Final examination will take into account:
i. active participation during lessons (25%)
ii. results from written examination (50%). Multiple choice-quizzes will be the standard test for module 1 and 3. Duration of the written examination will be 10 minutes for each module. At least 4 correct answers are needed to pass the test. In case the student will fail the written exam, he will be offered oral examination.
iii. oral examination (25%). This will be the standard procedure for module 2, aimed at assessing the student's communication skills of scientific themes. During the oral exam, the student will be asked to discuss a number of scientific papers provided during module 2.
For the oral examination, some of the elements that will be taken into consideration are: the logic applied to the resolution of the question; the adequacy of the response in relation to the knowledge the student should have acquired at the end of the course; the use of appropriate scientific language. Svolgimento della didattica

- How does originator and equivalent drug development differ?
-which are the scientific-regulatory supports for drug development offered to University spin-off and start-up?
- What are the consequences of prenatal exposure to antiepileptic drugs on the developing fetus?
Students will be asked to orally discuss selected scientific papers

Module: Pharmacology

• Design and development of
  biologic drugs 
  • Books: teaching
    
    materials provided by the instructor 


• Molecular aspects of drug
  action (2 lessons)
  • Books: teaching
    
    materials provided by the instructor 


• Intracellular signaling
  pathways as target of innovative medicine 
  • Books: teaching
    
    materials provided by the instructor 


• Pharmacological regulation
  of cellular functions 
  • Books: teaching
    
    materials provided by the instructor 


• Nucleic acids as drug
  targets and as drugs 
  • Books: teaching
    
    materials provided by the instructor 


• Description of siRNA,
  microRNA, and nc-small RNAs as therapeutic agents 
  • Books: teaching
    
    materials provided by the instructor 


• Drug-delivery systems
  • Books: teaching
    
    materials provided by the instructor 

• ·       Phases
  of non-clinical and clinical drug development; types and design of studies
  required for drug registration; European guidelines for the composition of the
  registration dossier.
  
  ·       
  The
  regulatory authorities responsible for drug authorisation in Europe, the United
  States, and Japan, and the various procedures for obtaining marketing
  authorisation in Europe.
  
  ·       
  Differences
  in the development of synthetic drugs and biotechnological drugs, particularly
  those for advanced therapies.
  
  ·       
  Innovative
  drugs: definition of an innovative drug; regulations aimed at facilitating the
  development and marketing of regulatory drugs.
  
  ·       
  Interpretation
  of the results of non-clinical and clinical studies: general principles.
  
  ·       
  Post-marketing
  surveillance activities for drugs in Europe; the PRAC committee for
  pharmacovigilance; the European Eudravigilance system for reporting and
  analysing adverse drug reactions, and the purpose of the Pharmacovigilance
  Safety Update Report (PSUR).
  • Books: The topics
    
    covered in the lessons will be presented through PowerPoint presentations,
    
    which will serve as the study material.