Regulatory Aspects in toxicology

A.Y. 2020/2021
Overall hours
CHIM/09 IUS/14
Learning objectives
The course will focus on the regulatory and legislative aspects related to the manufacturing and marketing of health products. The course will provide students with a complete overview of the relevant guidelines and standardised methods to evaluate biocompatibility of medical devices and the toxicological assessment of chemical, biocidal and pharmaceutical products. It will also outline the steps required for the manufacturing and placing on the market of medicinal products (biotechnological products and radiopharmaceuticals in particular), cosmetic products and food supplements.
Expected learning outcomes
At the end of the course the student should
· understand the classification of health products;
· understand what defines biotechnological and advanced therapy medicinal products, medical devices and biocidal products and what are their specific requirements;
· be able to outline in broad terms the steps required to place a medicinal product on the market in the EU;
· understand the requirements of EU regulation for medical devices;
· understand the EU regulation for chemicals and biocidal products;
· be able to navigate OECD Guidelines for the Testing of Chemicals, in particular Section 4 "Health Effect";
· be able to retrieve and understand the relevant parts of EU legislative acts.
Course syllabus and organization

Single session

Lesson period
Second semester
Due to the covid-19 emergency, the following organization is planned:
1. online synchronous lessons are delivered on MS Teams;
2. lesson recordings will be available on MS Stream;
3. the exam consists in oral tests on MS Teams;
4. field trips are suspended.
Course syllabus
EU law-making bodies and the European Medicines Agency
Definition of medicinal product: it's rationale and how it is meant to protect citizens' health (ref. Directive 2001/83/CE).
The Manufacturing Authorisation of medicinal products: when it is necessary, how it is obtained (ref. Directive 2001/83/CE). Good Manufacturing Practice (GMP).
The Marketing Authorisation (MA) of medicinal products. The 4 procedures for applying for a MA (ref. Directive 2001/83/CE and Regulation CE no. 726/2004).
The dossier in a MA application and the Common Technical Document (CTD). Full, partial, simplified dossiers (ref. Directive 2001/83/CE). European Public Assessment Reports (EPARs).
Conditional MA and Authorisation in exceptional circumstances. Orphan medicinal products.
The stability of therapeutic proteins. Biotechnological medicinal products Regulation CE no. 726/2004. Biosimilars (ref. Directive 2001/83/CE).
Ionizing radiation. Rate of radioactive decay. Example of Radiopharmaceuticals. Regulation of Cosmetic products in the EU (Regulation CE no. 1223/2009). Definition of cosmetic product. Product information file (PIF). The cosmetic product safety report (CPSR). Safety assessor. Notification. Restrictions for certain substances. Outline of safety evaluation of cosmetic ingredients (ref. SCCS NoG).
Skin structure and permeability to chemicals. Semiempirical models for predicting skin permeability.
REACH regulation, key European regulation aimed to improve the protection of human health and the environment from the risk that can be posed by chemicals
CLP regulation for the classification, labelling and packaging of chemicals
BPR regulation concerning the placing on the market and use of biocidal products used to protect humans, animals, materials or articles against harmful organisms
European Directive on Medical Device with focus on essential requirements; basic principles of ISO 10993-1 for the evaluation of the biocompatibility of medical devices (pre-clinical tests on animals); key-points of the (not-yet officially released) new regulation for medical devices;
Permitted Daily Exposure (PDE) determination -EMA Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities (cleaning validation); Tolerable Exposure (TE) determination for the release of compounds from pharmaceutical packaging and medical devices
OECD Guideline: principles behind in vivo and in vitro testing
Prerequisites for admission
No prerequisite is needed.
Teaching methods
Classroom demonstrations
Vistits to external facilities (suspended due to Covid-19)
Teaching Resources
Official website of the European Union. EU institutions and bodies in brief. Available at:
Treaty on European Union.…
Treaty on the Functioning of the European Union.…
Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Union procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency.…
Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use.…
Consolidated text: Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products.…
Crommelin, Daan J. A., Sindelar, Robert D., Meibohm, Bernd (Eds.). Pharmaceutical Biotechnology: Fundamentals and Applications (Fifth edition). Springer, Cham, 2019. ISBN 978-3-030-00710-2 (eBook).
Guidance For Industry And FDA Staff - Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process".
ISO10993 series, Biological evaluation of medical devices
ISO14971:2007, Medical devices — Application of risk management to medical devices.
European Parliament And Council Of The European Union, REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC. 2017: Official Journal of the European Union.
US CFR-Code of Federal Regulations Title 21 - Chapter 1, subchapter A - Part 73 and 74.
FDA Recognized Consensus Standards -…
United States Pharmacopoeia: USP40-NF35 . The United States Pharmacopeial Convention.
Crump, K. (1984). A new method for determining allowable daily intakes. Fund. Appl. Toxicol. 4, pp. 854-871
A. Woolley "A guide to practical toxicology - 2 edition" Informa 2008
International Conference On Harmonization Of Technical Requirements For Registration Of Pharmaceuticals For Human Use Draft Consensus Guideline For Elemental Impurities Q3D - Current Step 4 version dated 16 December 2014
Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities - EMA/CHMP/ CVMP/ SWP/169430/2012 - 20/11/2014
Scientific Opinion on Exploring options for providing advice about possible human health risks based on the concept of Threshold of Toxicological Concern (TTC) EFSA Journal: 2012;10(7):2750 [103 pp.].
Munro IC, Ford RA, Kennepohl E and Sprenger JG, 1996. Correlation of a structural class with No-Observed-effects-Level: a proposal for establishing a threshold of concern. Food Chem. Toxicol. 34, 829-867
OECD guidance ENV/JM/MONO(2009)5 ("Guidance document for using the OECD (Q)SAR application toolbox to develop chemical categories according to the OECD guidance on grouping of chemicals")
Scientific Committee on Health and Environmental Risks SCHER - Scientific Committee on Consumer Products SCCP - Scientific Committee on Emerging and Newly Identified Health Risks SCENIHR "Risk assessment methodologies and approaches for genotoxic and carcinogenic substances" 2009
OECD Guidelines for the Testing of Chemicals, Section 4…
OECD eChemPortal
ECHA website
ICH Safety Guidelines…
Assessment methods and Criteria
The examination consists of an oral exam covering all topics discussed during the course, with the aim of assessing students' knowledge of theoretical concepts and their applications for regulatory purposes.
Legislation in European Union
IUS/14 - EUROPEAN UNION LAW - University credits: 0
Lectures: 24 hours
Professor: Pescio Paolo
Regulatory Aspects of Medicaments, Medical Devices and Health products
IUS/14 - EUROPEAN UNION LAW - University credits: 0
Lectures: 24 hours
Professor: Rocco Paolo
appointment only