I&EHL: EU Pharmaceutical Law

André den ExterAndre.denExter@ua.ac.be

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Outline • History

• Legal framework: Pharmaceutical chain

• Latest developments

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History

- Thalidomide drama

- Pharmaceutical strategy (Directive 65/65/EEC)

- Divergence in interests between different stakeholders

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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)

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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

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What’s a medicine?

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What is a medical product?

Directive 2001/83/EC

Art. 1: presentation or functionCJEU case law: case-by-case approach

- Borderline products- Differences in classification

Relevance

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Research & Development: Clinical Trials

• CTDirective 2001/20/EC

• Protection of clinical trial subjects

• Ethics Committee: pre-trial approval

• Notification adverse effects

• Good clinical practices

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Manufacturing: Directive 2001/83/EC

Basic requirements manufacturing:

- Manufacturing authorization MS

- Labelling and package leaflet

- Classification

- Advertising and information

- Pharmacovigilance

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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)

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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.

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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

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Information and Advertising (ART. 86-100)

• Complete harmonization

• Classification of products

• General/specific conditions advertising

• Latest regulatory proposal: information to patients

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Inducement: GSK vioxx training course at Arabella Golf Resort

Mallorca

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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

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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

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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 )

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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