The European Medicines Agency (EMA) issued an annual report to highlight the agency's progress in 2014 in advancing key initiatives and providing regulatory oversight of medicines in the European Union (EU). The overall goals of the agency were to strengthen its support of the work of the scientific committees, improve knowledge sharing with the European medicines regulatory network, and better meet the needs of its stakeholders.
On a product level, the EMA recommended 82 medicines for human use for marketing authorization in 2014, which included 41 recommendations for new active substances, which is on par with the 41 new molecular entities approved by the US Food and Drug Administration's Center for Drug Evaluation and Research. As in the US, the number of new drug approvals for orphan drugs reached a record level in 2014 with the EMA recommending 17 medicines for marketing authorization to treat rare diseases, the highest number of orphan designations granted in a year since the EU Orphan Regulation came into force in 2000. Twenty-nine percent of these opinions for orphan designation were for oncology products, the most represented therapeutic area The EMA also approved the first therapy based on stem cells in 2014.
The EMA also progressed initiatives relating to manufacturing and the supply chain. In 2014, the EMA continued to support member states and the European Commission in the implementation of the Falsified Medicines Directive (Directive 2011/62/EU). The directive introduces a new paradigm for global medicines regulation. It provides a clear basis and framework for strengthened international cooperation and dialogue on the supervision of active substances manufacturing, sharing of responsibilities with regulators outside the EU, and development of local supervision.The agency developed further guidance for good manufacturing practice (GMP) and good distribution practice (GDP) inspections and also supported the assessment of third countries for equivalent GMP requirements and supervision arrangements. By the end of 2014, four countries (Japan, Australia, Switzerland, and the US) were listed by the European Commission as equivalent. Those countries no longer have to issue written confirmation per manufacturing site and per active substance that the site in question complies with GMP requirements.
As in previous years, the number of inspections increased in 2014, mainly due to the increase of GMP inspections, linked to the growing number of centrally authorized products and the increasing number of manufacturing sites located outside the European Economic Area (EEA), which includes the 28 EU member states and three of the four member states of the European Free Trade Association, Iceland, Liechtenstein, and Norway.
There was also an increase in the number of pharmacovigilance inspections, mainly reflecting the evolving process of pharmacovigilance inspections as well as a number of cases where the EMA had requested additional inspections to investigate particular situations. In 2014, the EMA conducted 420 GMP inspections, up from 397 inspections in 2013, 368 inspections in 2012, and 375 inspections in 2011.
The EMA also forwarded three main initiatives on transparency in 2014: the adoption of the EMA policy on the publication of clinical data, the extension of the European database of suspected adverse drug reactions, and the publication of the agendas and minutes for the meetings of all scientific committees.
Under its first initiative, in 2014, EMA decided to publish the clinical reports that underpin the decision-making on medicines. The EMA Management Board’s adoption of the landmark policy on the publication of clinical data for medicinal products for human use on October 2, 2014 was seen as an advance in transparency and open access to published clinical trial data. Under the policy, the Agency proactively publishes the clinical reports submitted as part of marketing-authorization applications, regardless of whether an authorization is granted. The policy allows identified individuals to download, save, and print clinical data for academic and non-commercial research purposes.The policy came into force on January 1, 2015. Once a medicine has received a marketing authorization or when an application is withdrawn or a negative opinion issued, the EMA will publish the supporting clinical reports. For line extensions and additional indications of already approved medicines, the agency will give access to clinical reports for applications submitted as of July 1, 2015 after a decision has been taken.
In October 2014, EMA expanded the publication of data from the European database of suspected adverse drug reactions to nationally authorized medicines. This website was first launched in 2012 as part of the agency’s continuing efforts to ensure EU regulatory processes are transparent and open. Initially, this website provided public access to reports of suspected reactions to centrally authorized medicines. Due to the extension to nationally authorized medicines, European citizens can now obtain information on suspected adverse drug reactions of many more active substances contained in medicines
approved in the European Union (EU).
In its third initiative for transparency, the EMA now routinely publishes all agendas of its scientific committee meetings at the start of each meeting, and the minutes after their adoption, usually the following month. The minutes are a record of all of the topics discussed during the meetings of the committees.
In January 2014, the meeting minutes of the Committee for Medicinal Products for Human Use (CHMP), the Committee for Medicinal Products for Veterinary Use and the Committee for Advanced Therapies were published for the first time.
In 2014, the implementation of the pharmacovigilance legislation, the most substantial change in the agency’s legal framework since its establishment in 1995, remained a priority. The pharmacovigilance fee regulation was published in the Official Journal of the European Union on June 27, 2014 and
has applied to procedures starting from August 26, 2014 although annual fees to support information technology systems and literature monitoring activities will not be levied until 2015. The EU pharmacovigilance legislation has been operational since July 2012 and foresees various information systems to enhance pharmacovigilance, particularly to support the collection, management and analysis of data, information, and knowledge. The pharmacovigilance fee regulation now allows the EMA to collect fees from marketing authorization holders to finance these pharmacovigilance activities conducted at EU level for medicinal products for human use.
The EMA also launched a public consultation on its draft guide on the monitoring of medical literature for safety information and the entry of relevant information into the EudraVigilance database. Literature monitoring is a new responsibility for the EMA aimed at improving safety monitoring of medicines. It
will be provided as a service to industry who will no longer have to enter the literature cases into EudraVigilance. Literature monitoring will be outsourced by EMA to a service provider. A public procurement procedure to select a provider with the necessary experience and knowledge in this area
was launched in November 2014. A service provider is expected to be selected in 2015.
Also in 2014, working with representatives of European pharmaceutical-industry associations through the Joint Implementation Working Group (IWG), the agency published guidance and formats for a data-maintenance submission process to help marketing authorization holders to keep the information held on their medicines up-to-date. In July 2014, the EMA started the review of quality and integrity of medicinal product information and began to provide feedback to
marketing authorization holders by the end of the year.
Also of note, in 2014, the EMA’s Committee for Medicinal Products for Human Use (CHMP) received more requests for scientific support in the early stages of medicine development than previous years. Almost 70% of applicants received scientific advice during the development phase of their medicine, and this figure rises to 80% when it comes to innovative medicines. Seven positive opinions were granted after an accelerated assessment in 2014. This mechanism aims to speed up the assessment of medicines that are expected to be of major benefit for public health. EMA used the accelerated assessment tool for four new medicines for the treatment chronic hepatitis C virus (HCV) infection.