(2002; 166 pages)
European contribution to a global approach to regulation
Dr Ramón Palop, Spain
The ICH requirements on registration of pharmaceutical products represent important initiatives that can lead to a reduction in costs. However, ICH has made it more difficult for countries that do not participate in the Conference to make decisions that are substantially different from those adopted by the ICH.
There are many European directives on the regulation of medicines, the most significant being Directive 93/39, which ensures mutual recognition of medication, and Regulation 2309 of the Council of Europe, which led to the establishment of the European Agency for Evaluation of Medicines.
There have been a number of major efforts to harmonize pharmacovigilance activities. Pharmacovigilance can be divided into risk analysis and risk management. Risk analysis includes identification of risk, quantification, and evaluation of social impact. To date, the focus of harmonization has been on the first stage of risk analysis, i.e. identification of risk. Risk identification seeks to generate a number of signals as soon as possible, by various means, e.g. through pharmaceutical laboratories, regional or national centres for monitoring of adverse drug reactions, and scientific publications. All this information is collected in national, international and regional databases, to allow generation and exchange of information among participating agencies. Once the data have been analysed, a number of actions could be taken to manage the risk, e.g. by adopting appropriate administrative measures, communicating information about the risk to health care providers and patients, and establishing specific prevention strategies.
In 1995, Europe established a system for exchange of information on suspected adverse drug reactions within 15 days. However, it was soon recognized that speedier exchange was needed; the Euroscape methodology was therefore introduced aimed at standardizing the electronic exchange of information on suspected adverse drug reactions, regardless of origin, destination, or drug approval period. Messages can be sent from and to drug regulatory agencies, industry and WHO.
For efficient electronic transmission, data and terminology need to be standardized. This led to the development of MedDRA, a unique terminology which industry and the regulatory authorities can use for entry, retrieval and evaluation of data. A pilot project is currently under way, aiming to incorporate MedDRA into electronic submission of data, in order to decrease administration in the different agencies responsible for pharmacovigilance within the European Union.
Regulatory agencies should promote the development and maintenance of other sources of information, such as drug-related registries of disease and follow-up of specific drug-exposed populations. These should help in risk identification.
The aim of risk quantification is to confirm or refute the causal relationship. It also indicates the strength of the association between the drug and the adverse reaction, thus allowing an estimation of the public health impact. Often epidemiological studies cannot be done because of lack of time, resources or sources of information. It is therefore important to carry out monitoring in the early postmarketing phase when exposure is still low. To quantify risk, it is also necessary to keep permanent disease registries, follow up exposed populations and keep automated databases.
Much work on evaluation and risk management is still to be done. The development of measures for prevention of risk and analysis of impact of action requires greater cooperation among agencies. It is incumbent on us to implement good management practices that will allow national agencies, WHO and the pharmaceutical industry to have access to all the information necessary to protect human health with greater transparency.