Animal & Veterinary
The Role of the European Medicines Agency in the Authorisation of Veterinary Medicines in the European Union
FDA Veterinarian is excited to have Rex Horgan from the European Medicines Agency as Special Guest Writer
Development and Evaluation of Veterinary Medicines
European Medicines Agency
7 Westferry Circus, Canary Wharf
London E14 4HB - United Kingdom
The European Medicines Agency (‘the Agency’) is a decentralised body of the European Union (EU) with the primary responsibility to protect and promote public and animal health, through the evaluation and supervision of medicines for human and veterinary use. The Agency is responsible for coordinating the scientific evaluation of applications for European marketing authorisations for both human and veterinary medicines (under the so-called ‘centralised procedure’). This article provides an overview of the activities carried out by the Agency and how it interacts with the other participants in the European Regulatory Network to deliver its mission of regulating medicines in the EU.
Committee for Medicinal Products for Veterinary Use
In the case of veterinary medicines, the Agency has established a specific scientific committee to perform these evaluations named the Committee for Medicinal Products for Veterinary Use (CVMP). The CVMP considers applications submitted by companies for the marketing authorisation of individual veterinary medicines and evaluates whether or not the medicines meet the necessary quality, safety and efficacy requirements. Assessments conducted by the CVMP are based on purely scientific criteria and ensure that veterinary medicines reaching the marketplace have a positive benefit-risk balance in favour of the animal population they are intended for. Based on the Committee’s recommendation, a centralised (or ‘Community’) marketing authorisation is granted by the European Commission which allows the product to be marketed in any of the EU (27 Member States) and EEA-EFTA1 States (Iceland, Liechtenstein and Norway). The CVMP is also responsible for various post-authorisation and maintenance activities, including the assessment of modifications or extensions (‘variations’) to an existing marketing authorisation. Another core activity of the CVMP is the establishment of MRLs: the ‘maximum residue limits’ of veterinary medicines permissible in food produced by or from animals for human consumption, including dairy products, meat, honey, etc. These limits must be established for all pharmacologically active substances contained in a medicine before it can be granted a marketing authorisation.
While the Agency is involved in the scientific evaluation of all medicines that fall within the scope of the centralised procedure, many other medicines do not fall within this scope and are still marketed in the EU, either in individual Member States in accordance with their national authorisation procedures, or in multiple Member States through the ‘decentralised’ or ‘mutual-recognition’ procedures. Nevertheless, the CVMP can also be involved in examining such products, arbitrating in decentralised or mutual-recognition procedures where there is a disagreement between Member States concerning the marketing authorisation of a particular veterinary medicine, or in referral cases initiated where there are concerns relating to the protection of public health or where other Community interests are at stake. Such cases are referred to the Agency due to a disagreement between two or more Member States about the authorisation or use of the medicine, or due to some other issue that requires resolution in the interest of protecting public health.
While the monitoring of the safety of authorised medicines is conducted through the EU’s network of national veterinary medicines agencies, in close cooperation with veterinary professionals and the pharmaceutical companies themselves, the CVMP also plays an important role in this EU-wide ‘pharmacovigilance’ activity by closely monitoring potential safety concerns and, when necessary, making recommendations to the European Commission regarding changes to a medicine’s marketing authorisation, or recommending its suspension/withdrawal from the market. The CVMP is further supported by the work of the Agency’s Compliance and Inspection Sector which is responsible both for coordinating inspections for compliance with Good Manufacturing Practice (GMP) and for overseeing the Sampling and Testing Programme. This is a scheme operated together with the European Directorate for the Quality of Medicines and Healthcare (EDQM) to monitor the quality of centrally authorised medicines available on the European market.
Working Parties and Scientific Advisory Groups
The CVMP has established a number of working parties with expertise in a particular scientific field which it consults on scientific issues relating to their particular field of expertise, and to which it delegates certain tasks associated with the scientific evaluation of marketing authorisation applications and the drafting and revision of scientific guidance documents. Such activities of the CVMP and its working parties include the provision of assistance to companies researching and developing new veterinary medicines, the preparation of scientific and regulatory guidelines for the veterinary pharmaceuticals industry and cooperation with international partners on the harmonisation of regulatory requirements for veterinary medicines.
Current CVMP working parties include the Efficacy Working Party, Immunologicals Working Party, Joint CHMP2/CVMP Quality Working Party, Pharmacovigilance Working Party, Safety Working Party, Scientific Advice Working Party and Environmental Risk Assessment Working Party.
Scientific Advisory Groups (SAGs) are also established by the CVMP to provide advice related to the evaluation of specific types of medicinal products or treatments. For example, the Scientific Advisory Group on Antimicrobials (SAGAM) provides advice to the Committee on all issues relating to antimicrobials, in particular on how to minimise the risk of the development of resistance arising from the use of antimicrobials in veterinary medicine.
Eligibility and Assessment of a Marketing Authorisation Application under the Centralised Procedure
All medicines derived from biotechnology and other high-tech processes must be approved via the centralised procedure, as well as veterinary medicines intended for use as performance enhancers used to promote the growth of treated animals or to increase yields from treated animals. For other medicines that do not fall under these categories, companies can submit an application for a centralised marketing authorisation provided that the medicine constitutes a significant therapeutic, scientific or technical innovation, or for which centralised assessment is in any other respect in the interest of animal health.
For any application, a Rapporteur and Co-Rapporteur are appointed from the CVMP members whose role is to lead the scientific evaluation and to prepare an assessment report. This report will be critiqued by the Co-Rapporteur and commented upon by other CVMP members before the Committee agrees on its final position on whether the benefit-risk balance for the product is considered favourable. The Agency’s internal secretariat coordinates and manages this assessment procedure.
The Rapporteurs can also utilise additional experts to assist in performing their assessment. The Agency works with a network of over 4,500 ‘European experts’ who serve as members of the Agency's scientific committees, working parties or scientific assessment teams. These experts are made available to the Agency by the national competent authorities of the EU and EEA-EFTA states. Members of the CVMP and their experts are not permitted to have any direct financial or other interests in the pharmaceutical industry which could affect their impartiality. To this end, the Agency has established a procedure and policy on the handling of potential conflicts of interest for Agency staff, scientific committee members and experts.
Normally, the final opinion of the CVMP is given within 210 days but this period can be shortened in exceptional cases, for example, if a product is of major interest from the point of view of animal health or therapeutic innovation (e.g., avian influenza, bluetongue).
Stimulating Innovation and Assistance to Companies
The Agency plays an important role in stimulating innovation and research in the pharmaceutical sector, including providing scientific advice and other assistance to companies for the development of new medicines and publishing guidelines on the requirements for authorisation in terms of quality, safety and efficacy. Often, scientific advice is requested during the initial development of the medicinal product, where guidance is needed on the selection of tests for product development and the design of clinical trials. Scientific advice may also be requested on the interpretation of a scientific aspect of an existing guideline. Over recent years, closer cooperation has been established with other regulatory authorities, such as the U.S. Food and Drug Administration (FDA), with a view to offering parallel scientific advice, thereby increasing the chance of companies being able to follow a single development pathway that will satisfy both regulators.
Incentives for Small- and Medium-sized Enterprises (SMEs)
A dedicated SME Office within the Agency provides special assistance to small- and medium-sized enterprises and aims to facilitate communication with SMEs through dedicated personnel to respond to practical or procedural enquiries, monitor applications, and organise workshops and training sessions for SMEs. Incentives offered to SMEs include: administrative and procedural assistance from the SME Office, fee reductions for scientific advice, inspections and the establishment of MRLs, fee exemptions for certain administrative services of the Agency, deferral of the fee payable for an application for marketing authorisation or related inspection, conditional fee exemption where scientific advice is followed and a marketing authorisation application is not successful and assistance with translations of the product information documents submitted in the application for a marketing authorisation.
Availability of Medicines for Minor Uses and Minor species (MUMS)
Recognising that the availability of safe and effective veterinary medicinal products will improve both animal welfare and public health, the Agency has recently developed a policy to stimulate the development of new veterinary medicines for minor species and for rare diseases in major species. Once a veterinary product has been classified as falling within the scope of this procedure, then assistance with scientific advice, developing or extrapolating MRLs, and/or compiling a dossier for a marketing authorisation may be provided. The assistance may be of a procedural or financial nature or both.
The Agency can be considered as the ‘hub’ of a European medicines network comprising over 40 national competent authorities in 30 EU and EEA-EFTA countries, the European Commission, the European Parliament and a number of other decentralised EU agencies. The Agency works closely with its European partners to build the best possible regulatory system for medicines for Europe and promote public and animal health. In view of the continuing globalisation of the pharmaceutical sector, the Agency also continues to work to forge close ties with partner organisations around the world, including the World Health Organisation (WHO), the World Organisation for Animal Health (OIE) and the regulatory authorities of non-European nations such as the United States. The Agency is continually involved in a wide range of cooperation activities with its international partners, designed to foster the timely exchange of regulatory and scientific expertise and the development of best practices in the regulatory field.
Stakeholders, including the pharmaceutical industry, veterinarians and the public are regularly invited to input their views on the Agency’s activities and future strategic vision, recently elaborated in ‘The European Medicines Agency Road Map to 2015: The Agency’s Contribution to Science, Medicines, Health.’ Building on the achievements to date, the focus of the new Road Map to 2015 is on continuous high-quality delivery of the Agency’s core business in an increasingly complex regulatory and scientific environment with three priority areas for future actions: addressing public health needs, facilitating access to medicines and optimising the safe use of medicines. Ongoing cooperation with international partners, such as the FDA, will be crucial in delivering on these ambitions.
1European Economic Area (EEA)-European Free Trade Association (EFTA)
2Committee for Medicinal Products for Human Use (CHMP)