1. I&EHL: EU Pharmaceutical Law André den Exter Andre.denExter@ua.ac.be

2. 1 Outline History Legal framework: Pharmaceutical chain Latest developments

3. 2 History -Thalidomide drama -Pharmaceutical strategy (Directive 65/65/EEC) -Divergence in interests between different stakeholders

4. 3 EU Pharmaceutical Policy: Regulating the pharmaceutical chain -From R&D towards using medicines: R&D, clinical trials, patents, registration, distribution, wholesale, packaging and labelling, pricing, retail, advertising, and privacy)

5. 4 Legal Framework Public Health, Art 168 TFEU (4): (c) measures setting high standards of quality and safety for medicinal products and devices for medical use. Pharmaceutical law (pharma chain) Internal market and competition rules

6. 5 What’s a medicine?

7. 6 What is a medical product? Directive 2001/83/EC Art. 1: presentation or function CJEU case law: case-by-case approach - Borderline products - Differences in classification Relevance

8. 7 Research & Development: Clinical Trials CTDirective 2001/20/EC Protection of clinical trial subjects Ethics Committee: pre-trial approval Notification adverse effects Good clinical practices

9. 8 Manufacturing: Directive 2001/83/EC Basic requirements manufacturing: -Manufacturing authorization MS -Labelling and package leaflet -Classification -Advertising and information -Pharmacovigilance

10. 9 Marketing Authorization Directive 2001/83/EC Regulation 726/2004/EC -Art. 6: MA required to place a medicinal product on the market, UNLESS… Compassianate use supply Pharmacy exemption (“Magistral formula”) Renewal of MA (art 24) Refusal of MA (art 26)

11. 10 MA procedures National Procedure: -Application to national competent authority -Procedures governed by national law -Transparency -First step towards MR procedure Mutual Recognition/Decentralised Procedure -Application to reference member state (RMS) -Grounds for refusing to recognise RMS approval -EMA Commission referral for arbitration Centralised Procedure -Scope: high-technology medicinal products -Application to EMA: Eur. Cie.

12. 11 Specific procedures Orphan Drug Products (Reg. No 141/2000 (ODR) -Purpose -Community marketing authorisation -Market exclusivity (art 8) -‘breaking’ market exclusivity -Criticism ODR Medicinal products for paediatric use( Reg.1901/2006) -Purpose -Paediatric population -Paediatric Committee -Marketing Authorization requirements

13. 12 Information and Advertising (ART. 86-100) Complete harmonization Classification of products General/specific conditions advertising Latest regulatory proposal: information to patients

14. 13 Inducement: GSK vioxx training course at Arabella Golf Resort Mallorca

15. 14 Retail sale: Pharmacies -No harmonized rules (except for labelling/ leaflets and advertising) -Only rules on classification -Ownership, free movement, and public health exception -Infringement proceedings

16. 15 Pricing Directive (89/105/EEC) -Transparency pricing measures: Directly controlled price Use of international price comparisons: maximum price Profit controls Not harmonised: Reimbursement -Assessment of therapeutic benefits/clinical relevance, cost-effectiveness and outcomes -Positive and negative lists -Reference price systems -Co-payments, substitution and bonus system

17. 16 Pharmacovigilance What is pharmacovigilance? Legal requirements pre- and post authorization phases: -2001/83/EC and 726/2004/EU: Establishing pharmacovig. system MS (art 102) Qualified person and systems (art. 103) Reporting of Adverse reactions -Spontaneous reporting -Periodical reports all adverse reactions 104(6) -Eudravigilance system Pharmacovig. inspections (art. 111) EMA’s role in pharmacovigilance Supervision and sanctions (art 116 )

18. 17 Latest developments Legislative proposals: -Tackle counterfeit medicines (Dir 2011/64/EU) -Information prescription-only medicines -Pharmacovigilance 2012 amendments Outsourcing/offshoring CTs in developing countries Seizures of In-Transit Medicines