www.semmelweis.hu/cemdc BASE MODULE 5

Module Leaders Regulatory affairs Prof. Jan Klimas, Comenius , , Pharmacovigilance Dr. Gábor Koncsik, Servier, Hungary

Place: Hotel Echo Presovská 39 82 108 Bratislava, Slovakia

Date: September 22-25, Thursday-Sunday, 2016

MODULE 5: REGULATORY AFFAIRS; DRUG SAFETY & PHARMACOVIGILANCE

LEARNING OUTCOMES

At the end of this Module the student should be able to demonstrate an understanding of:

1. General principles of regulation (both pre- and post-approval) at EU and global level.

2. Impact of medicines legislative requirements on regulatory activities within a pharmaceutical company.

3. Role of national agencies and international bodies in medicines regulation.

4. National provisions for of (1) off-label / unlicensed use of medicines (2) controlled drugs.

5. Place of International Conference on Harmonisation (ICH) in medicines regulation (including Common Technical Document [CTD]).

6. Regulatory processes in the EU / EEA areas.

7. Regulation and legal considerations of Product Information.

8. Principles and practical application of medical devices regulation.

9. Roles of the various stakeholders (including pharmaceutical and other healthcare professionals, investigators, regulatory authorities) in drug safety and pharmacovigilance.

10. Classification of adverse events / adverse drug reactions.

11. Safety reporting requirements (according to the type of adverse event / reaction) pre- and post- approval.

12. Ongoing management of drug safety issues pre- and post-approval (including Risk Management Plans [RMPs], Periodic Safety Update Reports [PSURs]); ongoing benefit / risk assessment throughout the life-cycle of a .

13. Role of pharmacoepidemiology in the life-cycle management of a medicine.

14. Factors influencing medication safety from the perspective of each stakeholder.

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Day 1 – September 22, 2016 - Thursday

Learning Time Name of Lecturers Syllabus outcomes Titles and topics of the lectures and cases reference reference Please list the topics to be covered by the lectures numbers number 9:00- Kerpel-Fronius, Sándor and Klimas, Jan 9:30 Welcome Introduction to Basic Module 5 9:30- Mazag, Jan and Klimas, Jan 10:50 General principles of medicines regulation; philosophy of 10.1, 10.2 1, 3, 6, regulatory oversight; input of international bodies and national agencies 10.3 Evolution of control mechanisms; general differences between agencies 10.4 International Conference on Harmonization (ICH) Regulatory Systems in Europe, US, Rest of the World 10.9 (ROW), and local special regulatory requirements Medicines regulation in EU in comparison with the USA, Japan and emerging markets 10.12 11:00- Klimasová, Jana 10.2 1, 3, 4 11:20 Overview of Regulatory Directives 10.6 11:30- Potúček, Peter 13:00 Regulatory Processes - Approval, Appeals and Referral 10.7 6 Procedures in Europe: Centralized procedure; Mutual Recognition Procedure, Decentralized procedure, national procedures); updating and maintaining Marketing Authorizations (variations regulation); aspects of confidentiality and transparency 10.23 Product withdrawal procedures CASE STUDY 13:00- Lunch 14:00 14:00- Petrovič, Matej 14:50 Good Practices (GMP, GLP, GCP), Inspections including 10.5 1 Pharmacopoeias 10.19 Product defects & recall 3 Parallel import 10.17 14:55- Klimasová, Jana 15:20 Common Technical Document (CTD & eCTD). Overviews 10.11 5 15:30- Slanar, Ondrej 17:00 Regulatory framework of clinical drug development. 10.10 2, 3, 4, Clinical trials regulation, guidance on clinical drug development, scientific advice, regulatory possibilities for 6, 9 early access to medicines. Divergent outcomes of registration procedures in different countries/regions. 17:15- Joint discussion by all participants 18:00 The EU regulatory concept

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Day 2 – September 23, 2016 - Friday

Learning Name of Lecturers Syllabus Time outcomes Titles and topics of the lectures and cases reference reference Please list the topics to be covered by the numbers number lectures 9:00- Klimasová, Jana 9:50 Prescription-only versus over-the-counter medicines 10.8 6 10:00- Orphan drugs, paediatric data, advanced therapies, 10.15 10:50 biosimilars, generics, controlled drugs regulation CASE STUDY Baťová, Zuzana Regulation of Product Information: Summary of 10.13 1, 2, 7 11:00: Product Characteristics (SmPC), labelling, 11:50 Prescribing Information, Patient Leaflet; readability testing CASE STUDY Baťová, Zuzana 12:00- Provisions for and use of unlicensed medicines 10.16 4 13:00 Off-label use and misuse, drug abuse and 10.24, dependence 10.25 13:00- Lunch 14:00 Manduchová, Silvia 14:00: Medical device regulation 10.18 8 14:50 CASE STUDY Palágyi, Michaela 15:00- Integration of regulatory affairs in pre- and post- 10.6 2 15:50 marketing company activities; planning and reviewing product strategy, OTC switching strategies CASE STUDY Palágyi, Michaela 16:00- 10.12 1, 2, 3 The preparation and submissions of marketing 16:50 authorization applications Palágyi, Michaela 17:00- Advertising and promotion regulation: promotional 10.14 2, 3, 4 17:50 material, OTC switching strategies Direct health care professional communication 10.22 CASE STUDY

www.semmelweis.hu/cemdc Day 3 – September 24, 2016 - Saturday

Learning Time Name of Lecturers Syllabus outcomes Titles and topics of the lectures and cases reference reference Please list the topics to be covered by the numbers number lectures Koncsik, Gabor 10.21, 11.1, 9, 10, 11, 9:00- International and national organization and 11.2, 11.3, 9:50 tasks of the Pharmacovigilance and Risk 12, 14 Management Systems. 11.5, 11.7 Pharmacovigilance Risk Assessment 11.9, , 11.12, Committee (PRAC), PASS &PAES trials 11.13 Risk management plans (RMPs), in the EU; Risk evaluation and mitigation strategies (REMS) in the USA Koncsik, Gabor 10.21, 11.1, 9, 10, 11, 10:00- The organization and tasks of the 11.2, 11.3, 10:50 pharmacovigilance and risk management 12, 14 systems in the pharmaceutical industry 11.5, 11.7 Serious adverse events (SAEs) and 11.9, , 11.12, suspected unexpected serious adverse 11.13 reactions (SUSARs) The concept of benefit / risk assessment, Kerpel-Fronius, Sándor 10.25, 11.1, 9, 10, 11, Clinical pharmacologic evaluation of adverse 11.3, 11.4, 11:00- events. Evidence for association and 12, 14 12:30 causality. AE and ADR. Serious Adverse 11.5, 11.6, Events The organization and tasks of the 11,7, 11.8, pharmacovigilance and risk management 11.15 systems in the health care system. Safety issues related to clinical investigation of medicines, the special role of the clinical investigators Stanulovic, Vid 12:45 10.25, 11.6, 9, 10, 11, AEs of biological medicinal products 13:30 Differences and similarities of AE 11.8, 11.13, 12, 14 characteristics of small chemical and 11.14, 11.15 biological macromolecular drugs. Immunogenicity of biological drugs 13:30- Lunch 14:30 14:30: Stanulovic, Vid 11.10, 11.11, 13 15:15 Pharmacoepidemiology 11.12 Mazag, Ján 10.1 1 15:30- Medicines regulation from the perspective of 16:30 the Head of Medicines Agency All lecturers 11.3 9, 10, 16:30- Case presentations and discussion of AE 18:00 reporting. 11, 14 The students should evaluate and present AEs on CIOMS forms

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Day 4 – September 25, 2016 - Sunday

Time Name of Lecturers Syllabus Learning outcomes Titles and topics of the lectures and reference reference cases numbers number Please list the topics to be covered by the lectures 9:00- MCQ examination 10:45 Stara, Dagmar 11:00- 10.9 1, 6 The process of the marketing authorization, 12:00 the roles of the EMA and the EU 10.10 Commission. The organization of the EMA. Cooperation among the EU institutions in issues related to drug policy. Collaboration with the EU Member States. Emerging new concepts, guidelines and regulations. Kyselovic, Jan 12:00- 10.8 5, 6 Presence and future of advanced therapies 13:00 and their regulation in Europe 13:00- Lunch 14:00 Drs. Klimas, Jan and Kerpel-Fronius, S 14:00: Concluding evaluation and discussion of 16:00 Module 5

Enclosing joint discussion by all particpants