The Interplay of Global Standards and EU Pharmaceutical Regulation

The International Council for Harmonisation

Sabrina Röttger-Wirtz

• Éditeur: Hart Publishing
• Année: 2021
• ISBN:
  9781509943005
• Édition: 1
• Sujet: Law
• Sous-sujet: Medical Law

This book analyses the implementation of global pharmaceutical impact standards in the European risk regulation framework for pharmaceuticals and questions its legitimacy. Global standards increasingly shape the risk regulation law and policy in the European Union and the area of pharmaceuticals is no exception to this tendency. As this book shows, global pharmaceutical standards set by the International Council for Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH), after they are adopted through the European Medicines Agency (EMA), are an important feature of the regulatory framework for pharmaceuticals in the EU. In addition to analysing the influence of these global standards in the EU legal and policy framework, the book questions the legitimacy of the Union's reliance on global standards in terms of core administrative law principles of participation, transparency and independence of expertise. It also critically examines the accountability of the European Commission and the European Medicines Agency as participants in the global standard-setting and main implementation gateway of the global pharmaceutical standards into the European Union.

Part I

1

Regulating Pharmaceuticals in the European Union: Law and Administrative Rule-Making

The European Union can look back on over 50 years of pharmaceutical regulation, and today it is an important part of the ‘patchwork’¹ of different policy domains that constitute EU health law,² constituting a central part of the Union’s commitment to a ‘high level of human health protection’.³

Pharmaceuticals, or ‘medicinal products’ as they are called in the EU legislation,⁴ are defined with regard to their function and presentation,⁵ as:

(a)Any substance or combination of substances presented as having properties for treating or preventing disease in human beings; or

(b)Any substance or combination of substances which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis.⁶

This chapter will introduce and analyse the regulatory framework, to provide the background for the following discussion of the impact of global standards on EU pharmaceutical regulation.

It will first examine the increasing regulatory harmonisation and subsequently discuss the status quo. In this chapter special attention is devoted to the analysis of the marketing authorisation requirement.⁷ Moreover, the chapter will highlight the role of non-binding administrative guidelines as forming an important cornerstone of pharmaceutical regulation.

I.EU PHARMACEUTICAL REGULATION: PAST AND PRESENT

Modern pharmaceutical regulation – placing an emphasis not only on the quality of the medicinal product, but also on safety and efficacy – is a relatively young phenomenon, as pharmaceuticals were not subject to governmental control until the 1960s in most countries.⁸ This changed with the 1961 Thalidomide tragedy,⁹ in response to which many European countries established regulatory bodies as well as systems of pre-marketing approval for medicines.¹⁰ Also, the EU actively aimed for the regulation of pharmaceuticals and their related risks, in order to establish an internal market for medicinal products.

As in many areas of EU health law, the establishment and functioning of the internal market has been the key driving force in the development of EU pharmaceutical law.¹¹ As the free movement of goods on the internal market leads to deregulation by removing national legislation as obstacles to trade, harmonised regulatory measures are put in place to maintain safeguards for the protection of human health.¹² Thus, the core of EU pharmaceutical law – the marketing authorisation procedure with pharmaceutical standards governing the quality, safety and efficacy of medicinal products – is a form of risk regulation. Risk regulation aims to identify and prevent harm to human or animal health and the environment.¹³ In the case of pharmaceuticals a large part of the regulation is aimed at making sure that medicinal products are safe to use for patients, while the harmonisation of those rules aims to facilitate the functioning of the internal market. As a result, pharmaceuticals are one of the most vigilantly regulated categories of goods in the EU.¹⁴

Nowadays, the EU’s competence for regulatory actions in this area of pharmaceuticals is based on the shared competences of regulating the internal market (Article 4(2)(a) TFEU) and Article 4(2)(k) TFEU, covering ‘common safety concerns in public health matters, for the aspects defined in this Treaty’. It should be noted that the protection and improvement of human health in general only provides the EU with a supportive competence according to Article 6(a) TFEU. In this regard, the public health mandate of the EU adopted in the Treaty of Maastricht, and currently enshrined in Article 168 TFEU, formalised the EU’s growing health policies and at the same time delimited them.¹⁵ Therefore, in field of pharmaceuticals the legal basis for EU measures is to be found in the provision on approximation of laws (Article 114 TFEU) in conjunction with Article 168(4) TFEU, which allows for EU legislative action in order to contribute to the achievement of public health objectives through ‘(m)easures setting high standards of quality and safety for medicinal products and devices for medical use’.

However, the extensive regulatory framework for medicinal products currently in place is the result of a history of European integration of pharmaceutical regulation that can be described as a rocky road of continuous reformation and step-by-step centralisation of decision-making power. The regulation of pharmaceuticals is politically sensitive and an important trait of national sovereignty, having an impact on health as well as industrial policies. Medicinal products proved to be a difficult case for the establishment of the internal market: the free movement of goods was not easily introduced for a product so thoroughly regulated on the national level, with nationally divergent policy approaches and interests.¹⁶

A.The Rocky Road to Harmonisation: The History of EU Pharmaceutical Regulation

The first pharmaceutical legislation adopted in the EU, Council Directive 65/65,¹⁷ was adopted quite early in the history of EU law, predating any formal legal basis for EU health law.¹⁸ The Treaty of Rome of 1957 only mentioned health as a potential restriction for free movement of goods and did not include a legal basis for health policy as such.¹⁹ The Directive, in response to the Thalidomide tragedy, introduced a pre-marketing authorisation requirement based on the assessment of the criteria of quality, safety and efficacy for pharmaceuticals by national competent authorities.²⁰ This mandatory marketing authorisation requirement is still the ‘fundamental principle’²¹ of EU pharmaceutical regulation. At the time, the Council Directive provided a list of documentation including preclinical and clinical studies required for an application.²² Although this was meant to pave the way for future mutual recognition of marketing authorisations, the implementation of these general requirements left considerable discretion to the Member States.²³

Further harmonisation only took place 10 years later with the adoption of Council Directive 75/318/EEC, which provided more detail on the documentation required for applications to national authorities under Directive 65/65/EEC.²⁴ Its Annex contained detailed information on the trials required to prove the safety as well as efficacy of a medicine, and the data that needs to be provided by the applicant in a marketing authorisation procedure. This contributed to further harmonisation of the quality, safety and efficacy assessment, forming an important step towards the approximation of the regulatory systems of the Member States.²⁵

Additionally, the complementary Council Directive 75/319/EEC introduced the Community Procedure,²⁶ providing the opportunity for a company that had obtained marketing authorisation in one Member State, to apply for approval in at least five other Member States, which would take into account the evaluation of the first state.²⁷ This was a first step towards the proceduralisation of mutual recognition. The Directive established the Committee for Proprietary Medicinal Products (CPMP), composed of national representatives, set up in order to advise national authorities on the authorisation of medicinal products.²⁸ In case of an objection by a Member State to the authorisation of a product under the Community Procedure, the CPMP could pass an advisory opinion on the issue.²⁹ However, the procedure was not favoured by industry nor by the national authorities. In the eight years it operated, only 41 applications were filed.³⁰ Council Directive 83/570/EEC transformed it into the so-called Multi-state Procedure with the number of receiving states required reduced to two.³¹ However, also this change did not lead to greater success in terms of Member States accepting each other’s assessments, and no procedure took place without an objection from the receiving states and discussion in the CPMP.³²

The harmonisation of pharmaceuticals regulation gained new impetus due to the Single European Act and the envisaged goal of a Single Market by 1992.³³ As the harmonisation process was still severely hampered by persisting differences in the evaluation of the marketing authorisation applications and delay in the national procedures,³⁴ the introduction of the Concentration Procedure aimed to facilitate discussion of divergent views in the Member States.³⁵ An application had to be filed with a national authority as well as with the CPMP where the evaluation was subsequently discussed. Yet the procedure left the final decision on authorisation to the Member States individually,³⁶ and the CPMP opinion was not binding upon the Member States.^37...