Regulatory aspects in toxicology
A.A. 2023/2024
Obiettivi formativi
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.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.
Risultati apprendimento attesi
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.
· 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.
Periodo: Secondo semestre
Modalità di valutazione: Esame
Giudizio di valutazione: voto verbalizzato in trentesimi
Corso singolo
Questo insegnamento può essere seguito come corso singolo.
Programma e organizzazione didattica
Edizione unica
Responsabile
Programma
· EU Pharmaceutical Law: aims and scope of Directive 2001/83/CE and Regulation (EU) No. 726/2004; EU law-making bodies and the European Medicines Agency (EMA).
· Definition of medicinal product: it's rationale and how it is meant to protect citizens' health (ref. Directive 2001/83/CE).
· 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 Manufacturing Authorisation of medicinal products: when it is necessary, how it is obtained (ref. Directive 2001/83/CE). Good Manufacturing Practice (GMP).
· 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); variations to the terms of the Marketing Authorisation.
· Conditional MA and Authorisation in exceptional circumstances.
· Orphan medicinal products.
· The Paediatric Investigation Plan (PIP).
· Summary of Product's Characteristics, Labelling and Package Leaflet of medicinal products.
· Pharmacovigilance.
· Introduction to nanotechnology. Definition of nanomaterials; main features of nanomaterials and biodistribution. Main classes of nanosystems, with particular focus on those available on the market. Characterization methods. Quality, safety and efficacy data for the approval of nanomedicine products.
· Skin permeability. The structure of the Stratum Corneum. Permeability coefficient, partition coefficient. Skin permeation studies.
· Cosmetic Products. Regulation (EC) No. 1223/2009 on cosmetic products. Definition of cosmetic product; the responsible person; product information file (PIF), the cosmetic product safety report (CPSR)
· Leachables and Extractables. EU regulations on chemicals and labelling and classification of substances: REACH, CLP, SDS
· Medical Devices: definition, classification, placing on the market.
· European Regulation on Medical Device, Classification of medical devices with focus on safety requirements; how to build up the technical documentation of a medical device;
· principles of ISO 10993-1 for the evaluation of the biocompatibility of medical devices key-points of the new regulation for medical devices;
· ISO 10993 in the evaluation of acute biological enpoints, testings and sample preparation;
· ISO 10993 in the evaluation of long term endpoints and testing;
· ISO 10993 in chemical characterization and alternative methods to in vivo.
· Toxicological risk assessment of medical device extracts.
· Biocidal products
· Definition of medicinal product: it's rationale and how it is meant to protect citizens' health (ref. Directive 2001/83/CE).
· 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 Manufacturing Authorisation of medicinal products: when it is necessary, how it is obtained (ref. Directive 2001/83/CE). Good Manufacturing Practice (GMP).
· 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); variations to the terms of the Marketing Authorisation.
· Conditional MA and Authorisation in exceptional circumstances.
· Orphan medicinal products.
· The Paediatric Investigation Plan (PIP).
· Summary of Product's Characteristics, Labelling and Package Leaflet of medicinal products.
· Pharmacovigilance.
· Introduction to nanotechnology. Definition of nanomaterials; main features of nanomaterials and biodistribution. Main classes of nanosystems, with particular focus on those available on the market. Characterization methods. Quality, safety and efficacy data for the approval of nanomedicine products.
· Skin permeability. The structure of the Stratum Corneum. Permeability coefficient, partition coefficient. Skin permeation studies.
· Cosmetic Products. Regulation (EC) No. 1223/2009 on cosmetic products. Definition of cosmetic product; the responsible person; product information file (PIF), the cosmetic product safety report (CPSR)
· Leachables and Extractables. EU regulations on chemicals and labelling and classification of substances: REACH, CLP, SDS
· Medical Devices: definition, classification, placing on the market.
· European Regulation on Medical Device, Classification of medical devices with focus on safety requirements; how to build up the technical documentation of a medical device;
· principles of ISO 10993-1 for the evaluation of the biocompatibility of medical devices key-points of the new regulation for medical devices;
· ISO 10993 in the evaluation of acute biological enpoints, testings and sample preparation;
· ISO 10993 in the evaluation of long term endpoints and testing;
· ISO 10993 in chemical characterization and alternative methods to in vivo.
· Toxicological risk assessment of medical device extracts.
· Biocidal products
Prerequisiti
No prerequisites apart from the general prerequisites of the Master Program.
Metodi didattici
Lectures and field trips.
Materiale di riferimento
· Lecture slides.
· Shorthose S (Ed.). Guide to EU pharmaceutical regulatory law, seventh edition (2017). Kluwer Law International. Available for free on UNIMI's digital Library, direct link: https://unimi.primo.exlibrisgroup.com/discovery/fulldisplay?docid=alma991017345717906031&c ontext=L&vid=39UMI_INST:VU1&lang=it&search_scope=MyInst_and_CI&adaptor=Local%20Searc h%20Engine&tab=Everything&query=any,contains,pharmaceutical%20law
· Official website of the European Medicines Agency (EMA). https://ema.europa.eu.
· 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. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:02004R0726-20190330&rid=1
· 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. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:02001L0083-20121116&rid=1
· Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:02009R1223-20180801&rid=1
· ISO10993 series, Biological evaluation of medical devices www.iso.org
· ISO14971:2007, Medical devices — Application of risk management to medical devices.
· 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 - https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm
· 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
· ICH HARMONISED GUIDELINE ASSESSMENT AND CONTROL OF DNA REACTIVE (MUTAGENIC) IMPURITIES IN PHARMACEUTICALS TO LIMIT POTENTIAL CARCINOGENIC RISK - M7(R1) - Current Step 4 version dated 31 March 2017
· 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
· 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 https://www.oecd-ilibrary.org/environment/oecd-guidelines-for-the-testing-of-chemicals-section-4-health-effects_20745788
· ECHA website http://echa.europa.eu
· ICH Safety Guidelines http://www.ich.org/products/guidelines/safety/article/safety-guidelines.html
· Shorthose S (Ed.). Guide to EU pharmaceutical regulatory law, seventh edition (2017). Kluwer Law International. Available for free on UNIMI's digital Library, direct link: https://unimi.primo.exlibrisgroup.com/discovery/fulldisplay?docid=alma991017345717906031&c ontext=L&vid=39UMI_INST:VU1&lang=it&search_scope=MyInst_and_CI&adaptor=Local%20Searc h%20Engine&tab=Everything&query=any,contains,pharmaceutical%20law
· Official website of the European Medicines Agency (EMA). https://ema.europa.eu.
· 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. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:02004R0726-20190330&rid=1
· 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. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:02001L0083-20121116&rid=1
· Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:02009R1223-20180801&rid=1
· ISO10993 series, Biological evaluation of medical devices www.iso.org
· ISO14971:2007, Medical devices — Application of risk management to medical devices.
· 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 - https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm
· 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
· ICH HARMONISED GUIDELINE ASSESSMENT AND CONTROL OF DNA REACTIVE (MUTAGENIC) IMPURITIES IN PHARMACEUTICALS TO LIMIT POTENTIAL CARCINOGENIC RISK - M7(R1) - Current Step 4 version dated 31 March 2017
· 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
· 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 https://www.oecd-ilibrary.org/environment/oecd-guidelines-for-the-testing-of-chemicals-section-4-health-effects_20745788
· ECHA website http://echa.europa.eu
· ICH Safety Guidelines http://www.ich.org/products/guidelines/safety/article/safety-guidelines.html
Modalità di verifica dell’apprendimento e criteri di valutazione
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.
Moduli o unità didattiche
Legislation in European Union
CHIM/09 - FARMACEUTICO TECNOLOGICO APPLICATIVO
IUS/14 - DIRITTO DELL'UNIONE EUROPEA
IUS/14 - DIRITTO DELL'UNIONE EUROPEA
Lectures: 24 ore
Docenti:
Franze' Silvia, Lioi Daniele
Regulatory Aspects of Medicaments, Medical Devices and Health products
CHIM/09 - FARMACEUTICO TECNOLOGICO APPLICATIVO
IUS/14 - DIRITTO DELL'UNIONE EUROPEA
IUS/14 - DIRITTO DELL'UNIONE EUROPEA
Lectures: 24 ore
Docente:
Rocco Paolo
Siti didattici
Docente/i
Ricevimento:
previo appuntamento via mail
Via G. Colombo 71, edificio 1, piano rialzato