Significant progress has been made in recent months on the so-called Pharma package, launched by the European Commission at the end of 2008, with new legislation being published for the first two of the three proposals that were tabled together in the field of pharmaceuticals:

• Improving patient protection by strengthening the EU system for the safety monitoring of medicines (pharmacovigilance)
• Tackling the growing issues of counterfeiting and illegal distribution of medicines (falsification)
• Enabling citizens to have access to high-quality information on prescription-only medicines (information to patients).

Pharmacovigilance
Legislation published, implementation ongoing

In addition to a number of recent drug scandals, there were good reasons for the decision makers to speed up the work on this item. The Commission includes the following figures in its summary of the impact assessment:

• 5% of all hospital admissions are for Adverse Drug Reactions (ADRs)
• 197,000 deaths per year in the EU are caused by ADRs
• the total societal cost of ADRs in the EU is €79 billion per year.

The same summary suggests rather limited savings to EU society: between €237 million and €2.4 billion per year once the measures are fully operational with anything between 591 and 5,910 lives saved across the EU each year.

All the stakeholders will be involved to make the system workable and efficient: the patients, the healthcare professionals working with medicinal products, the regulatory authorities at European level (European Medicines Agency), the national medicinal products agencies in the EU and EEA countries, the pharmaceutical companies and the import and distribution companies.

ECHAMP E-news of March 2011 reported on the community legislative process on pharmacovigilance up to the publication on 31 December 2010 of Regulation N° 1235/2010 and Directive 2010/84/EU  in the Official Journal of the European Union.
The Member States now have until July 2012 to implement the new Directive, from which date onwards the Regulation will also fully apply.

Member States will adopt a series of implementation measures so as to harmonise the performance of the new pharmacovigilance activities introduced by the legislation. These measures supplement the essential details of the new pharmacovigilance system with the more technical details to be observed by marketing authorisation holders, national competent authorities and the European Medicines Agency in the daily practice of applying the new provisions.

In a consultation exercise that ended on 7 November 2011, the European Commission sought the views and feedback of stakeholders on the scope and content of the implementation measures under consideration and their contributions have been published on the Commission website. It also published a call for members of the new Pharmacovigilance Risk Assessment Committee (PRAC), which is planned to be operational from July 2012. A further stakeholder consultation took place on 22 November 2011. The Commission is now proceeding with the finalisation of the guidance after consulting the Member States through the advisory Pharmaceutical Committee.  

The Commission is envisaging a further tightening of the legislation on pharmacovigilance through the recently released amended proposals on information to patients (see below). These foresee in particular an automatic referral at European level of specific serious safety issues with nationally authorised products, so that they can be assessed and addressed in all the Member States where the medicinal product is authorised; and to avoid the case whereby a voluntary withdrawal of a marketing authorisation or product by the holder might lead to safety issues not being addressed in the EU.

The European Medicines Agency is playing an important role in the preparation of the guidance environment for the new pharmacovigilance legislation and has already published first extensive strategy and policy documents.  It will also play a major role in the management of data and information, and its ‘Pharmacovigilance and Risk Management’ unit is very active. It is obvious that much resource will be needed by the agency to organise these pharmacovigilance provisions, possibly one of the biggest changes in the legal framework for human medicinal products of the last twenty years.

Nevertheless, the legislation does not really bring any added value for homeopathic and anthroposophic medicinal products since existing pharmacovigilance data for these products show very limited adverse drug reactions, most of them very temporary and not serious, emphasising again the highly positive safety profile of these products. 

Falsification
Legislation published, implementation ongoing

Falsified medicines are fake medicines that pass themselves off as real, authorised medicines. They might contain ingredients, including active ingredients, which are of bad quality or in the wrong dose – either too high or too low. As they have not been properly evaluated to check their quality, safety and efficacy - as required by strict EU authorisation procedures - this could be detrimental to the health of citizens. Moreover, as falsifications become more sophisticated, there is an increasing risk each year that falsified medicines reach patients in the EU. They represent a serious threat to global health in general, thus requiring a comprehensive strategy both at European and pan-european level.

The major threat for public health is considered by the Commission as a serious and emerging problem, which urgently needs to be tackled with a rigid legal framework. On 1 July 2011, the legislative initiative started under the Pharma package was finalised with the publication of the new legislation on falsified medicines  in the Official Journal of the European Union. The new legislation will be fully applicable as of 2 January 2013.

Because of the technical complexity and the need for a rigid legal and regulatory environment, the European Commission is currently developing, via the so-called delegated acts, guidance for Good Manufacturing Practice (GMP) and Good Distribution Practice (GDP) for pharmaceutical ingredients as well as guidance for the risk assessment and appropriate GMP for excipients (to be published for public consultation the first half of 2012). The technical specifications of the safety features will be decided by means of delegated acts, as will the ‘white’ list of prescription medicines exempt from the obligation to carry a safety feature and the ‘black’ list of non-prescription medicines, for which a safety feature is mandatory. Criteria for this categorisation are listed in the Directive: price and sales volumes, number or frequency of past incidences of falsification, the characteristics of the medicinal product, the severity of the conditions to be treated and in general other elements contributing to a potential risk for public health. The final Directive also contains measures to regulate internet sales with the obligation to register that activity, in order to organise the control at EU and at national level.

While this new system is being put in place, the Member States will have an important role with respect to the European Commission to provide information and warning on products at risk of falsification. Together they will set up information campaigns and websites and organise and execute inspections at the premises of manufacturers and distributors of active pharmaceutical ingredients and excipients inside and outside the Community. Finally the Member States have to set up recall systems for potentially falsified measures.

Because of the differentiated approach that will become visible in the delegated acts, it is likely that homeopathic and anthroposophic medicinal products will fall outside the scope of the safety feature obligation. ECHAMP provided arguments for this to the European Commission some months ago, together with a list of the very small number of homeopathic and anthroposophic medicinal products which are prescription-only products in at least one Member State. As soon as the delegated acts consultation starts, ECHAMP will contact the European Commission in order to explain its position.

Information to patients
Still under discussion

The legislative process has been slower as regards this third part of the Pharma package. While the European Parliament was in agreement with the European Commission’s proposals as regards the major topics, the Council’s opinion was rather different, so no agreement has been reached on the Commission proposal.

The Commission has now finalised a revised proposal setting out clearer rules on information on prescription-only medicines and presenting a clear framework whereby companies with a marketing authorisation for a product may – and to some extent must – provide good quality and objective information on their prescription-only medicines to the general public. As a result, the proposals should lead to better empowered patients, more rational use of medicines, whilst, at the same time, maintaining the ban on advertising prescription-only medicines. As mentioned above, it also seeks to further strengthen the current system for monitoring the safety of medicines (pharmacovigilance).

The revised proposals will now go into a second reading by both the European Parliament and the Council of Ministers in line with the ‘Ordinary Legislative Procedure’ of the new Treaty of the European Union. 

Comprehensive information on the revised proposal can be found in the press release published by the European Commission on 11 October, on which day it also published the amended proposals of the Directive and the Regulation and an interesting Question & Answer document.

Since the legislative initiative will only cover information to patients on prescription-only medicines, it will only apply to very few homeopathic or anthroposophic medicinal products.  And were it to apply to any of the homeopathic or anthroposophic prescription-only products, it would be difficult to make the rules consistent with the existing restrictions on homeopathic medicinal products as regards communication to patients. ECHAMP will follow the legislative process in the coming months and if needed ask for amendments in the second reading in the European Parliament.

Nand De Herdt
President of ECHAMP