European Directorate for the Quality of Medicines
The European Directorate for the Quality of Medicines & HealthCare is a Directorate of the Council of Europe that traces its origins and statutes to the Convention on the Elaboration of a European Pharmacopoeia. The signatories to the convention – 39 member states and the European Union as of October 2018 – are committed to achieving harmonisation of the quality standards for safe medicines throughout the European continent and beyond. The EDQM’s standards are published in the European Pharmacopoeia, which is recognised as a scientific benchmark worldwide and is legally binding in member states.
Today, direct reference is made in the EU’s pharmaceutical legislation to the European Pharmacopoeia and to other activities under the responsibility of the EDQM, demonstrating the strong collaboration between the European organisations in protecting public health.
The EDQM is also involved in a number of international platforms for collaboration and harmonisation, such as the Pharmacopoeial Discussion Group, the International Generic Drug Regulators Programme, the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme and the International API Inspection Programme.
In addition to the PDG, the EDQM is actively involved in a number of other international harmonisation initiatives, such as the World Health Organization initiative to draft “Good Pharmacopoeial Practices”, which may serve as a basis for future work-sharing and collaboration amongst pharmacopoeias worldwide. The EDQM also collaborates with WHO in a number of other ways; for example, the EDQM establishes, monitors and distributes WHO International Standards for Antibiotics and WHO International Chemical Reference Substances.
In this context, the EDQM plays an essential role in the complex regulatory framework for medicines in Europe. Its fundamental aim is to protect public health by enabling the development, supporting the implementation, and monitoring the application of quality standards for safe medicines and their safe use.
The EDQM’s mission
Within the Council of Europe, the EDQM’s mission is to contribute to the basic human right of access to good quality medicines and healthcare, and to promote and protect human and animal health by:- establishing and providing official standards which apply to the manufacture and quality control of medicines in all the signatory states of the Convention for the Elaboration of a European Pharmacopoeia and beyond;
- granting Certificates of suitability which verify the compliance of pharmaceutical substances with European Pharmacopoeia standards and carrying out inspections of manufacturers of these substances;
- co-ordinating a network of Official Medicines Control Laboratories to collaborate and share expertise between member states and optimise the use of available resources, with the aim of achieving effective public quality control of medicines in Europe and beyond;
- proposing ethical, safety and quality standards for blood transfusions and the transplantation of organs, tissues and cells;
- working with national, European and international organisations in efforts to combat counterfeiting/falsification of medical products and similar crimes;
- providing policies and model approaches for the safe use of medicines in Europe, including guidelines on pharmaceutical care; and
- establishing standards for cosmetics and food contact materials and co-ordinating the public control of cosmetics.
Activities related to the quality of medicines
The [European Pharmacopoeia]: Setting quality specifications and pharmaceutical reference standards
Published and regularly updated by the EDQM/Council of Europe in English and French, the two official languages of the Council of Europe, the European Pharmacopoeia is a single reference work for official European quality standards. It thus helps define the requirements for obtaining a marketing authorisation of a medicinal product in Europe, but its standards are recognised as a scientific benchmark worldwide in the field of quality control for human and veterinary medicines. The European Pharmacopoeia’s common, harmonised quality standards define strict specifications for medicines and substances used in their manufacture, which apply throughout the product’s entire life-cycle. When adopted, they are legally binding and become mandatory on the same date in the 39 Council of Europe member states that are signatory states to the European Pharmacopoeia Convention, applying to all medicines on their markets.The contents of the European Pharmacopoeia are elaborated and updated by the European Pharmacopoeia Commission, which is responsible for overseeing the practical work of 800 or so experts in every field of the pharmaceutical sciences – all volunteers – who participate in more than 70 Groups of Experts and Working Parties. The European Pharmacopoeia Commission decides on the work programme, appoints the experts, and adopts the monographs. It meets three times a year in Strasbourg and all technical decisions are taken by a unanimous vote. The EDQM of the Council of Europe provides the scientific secretariat and logistical support for the work of the European Pharmacopoeia Commission, and facilitates the activities of its Groups of Experts and Working Parties.
The texts of the European Pharmacopoeia cover all therapeutic areas and consist of:
- individual monographs describing legally binding quality standards for substances used in the manufacture of medicines or medicine ingredients ;
- individual monographs describing legally binding quality standards for finished products;
- general monographs describing legally binding quality standards for classes of substances or for the dosage forms that medicines can take ; and
- general methods of analysis of substances used in the manufacture of medicines, which are not legally binding and may also be used for substances and medicines not described in the European Pharmacopoeia. All analytical methods described in the monographs are experimentally verified. In addition, the EDQM is also responsible for establishing official reference standards, which are an essential component of most texts of the European Pharmacopoeia, and supplying these to users of the European Pharmacopoeia. Users include manufacturers located both in Europe and around the world, as well as national and European authorities involved in controlling the quality of medicines. The EDQM publishes a new edition of the European Pharmacopoeia every three years.
The Certification procedure: Evaluating quality in the manufacture of substances for pharmaceutical use and the related inspections programme
The Certification procedure is not compulsory – it is a service that is offered to manufacturers, who can use a Certificate of Suitability in an application for a new market authorisation or for a variation of an existing MAA. The Certification procedure centralises the evaluation of data for the benefit of regulatory authorities and industry alike, thus saving time and resources. For example, on average it takes three days for a regulatory authority to assess an Active Substance Master File, which is the document submitted by a manufacturer of a medicine as part of its application for MAA.
Also, the Certification procedure provides the European Pharmacopoeia Commission with current information on the quality of substances on the European market, thus helping to identify whether or not a revision of specific European Pharmacopoeia monographs is needed.
CEPs – which are referred to in EU pharmaceutical legislation – are recognised by the European Pharmacopoeia member states and by a number of other countries and regions, such as Australia, Canada, New Zealand, Saudi Arabia, Singapore, South Africa, Taiwan and Tunisia. An increasing number of licensing authorities worldwide accept CEPs to support the data related to the quality of APIs used in medicinal products.
In order for a specific manufacturer to be granted a CEP, the EDQM’s panel of assessors review a detailed dossier submitted by the manufacturer. This dossier describes the manufacturing process and the tests performed on the raw materials and on the substance produced, as well as the necessary in-process controls. The manufacturer must demonstrate that its product complies with the quality standards required by the European Pharmacopoeia and EU legislation and, in particular, that the monograph can be used to control impurities. The applicant must also agree to comply with the relevant Good Manufacturing Practice as defined in Part II of the EU GMP Guide, and to accept a site inspection at any time at the request of the EDQM.
The OMCL Network: quality control of medicines on the market
On 26 May 1994, in a new co-operative venture in the area of the quality control of medicines for human and veterinary use on the market, the European Commission and the Council of Europe decided to establish a European Network of Official Medicines Control Laboratories on a co-funded basis. The OMCL Network, which is open to member states and observers of the European Pharmacopoeia Convention, thus ensures that patients receive the same quality of pharmaceutical products throughout Europe.This international collaboration reduces public health expenses by sharing resources, and also influences future development through harmonised common standards. The sharing of workloads, resources and expertise among the OMCLs makes it possible to avoid duplication of work and gives them access to the latest technologies and selective methods of different types of analysis. The EDQM is responsible for co-ordinating the Network’s technical activities and ensuring the smooth running of its various joint programmes.
This network is made up of independent public laboratories that have been appointed by their respective national authority.
The network performs studies on medicinal products already on the market. The EDQM organises inter-laboratory testing activities for OMCLs to improve their laboratory performance and promotes common quality management systems in all OMCLs to enable their work-sharing and mutual recognition of test results.
The EDQM is also the technical secretariat for the Official Control Authority Batch Release procedures of the Network for certain products and in testing activities related to counterfeit medicines. The OCABR procedure guarantees that for the vast majority of, for example, vaccines used in the European Union, no batch of vaccine is released for marketing in member states without first undergoing an independent quality examination by a laboratory of the OMCL Network.
Pharmaceutical care and combating counterfeit medicines
Worldwide, it is estimated that half of all medicines are inappropriately prescribed, dispensed or sold, and that half of all patients fail to take their medicines properly. Errors relating to medication use, lack of documentation on how medicines are prescribed, used and dispensed, as well as insufficient communication have a considerable impact on national mortality rates and levels of ill-health. Therefore the safe and appropriate use of medicines, which depends on the right information being available to everyone that needs it, is as important as product quality.In order to face this challenge, the European Committee on Pharmaceuticals and Pharmaceutical Care, co-ordinated by the EDQM, oversees the work of experts in three main areas, which today also has to take into account constraints on public health budgets and social inequality in access to healthcare:
- The classification of medicines authorised in Europe into prescription and non-prescription medicines: Although individual countries are responsible for classifying medicines in this way, the EDQM’s committee of experts for this activity makes classification recommendations, which, due to the range of European Pharmacopoeia member states that participate in this activity, can include medicines that are not licensed for use in the EU. These recommendations are updated annually and published on the EDQM’s website. The EDQM also hosts the Melclass database, which presents the classification status of medicines in European Pharmacopoeia member states.
- Setting quality and safety standards in pharmaceutical practices and pharmaceutical care: Public authorities and the sectors of the pharmaceutical industry that focus on manufacturing and distribution devote a lot of their resources to the quality, safety and efficacy of medicines. However, the safe and appropriate use of medicines is just as important as product quality for ensuring that a patient obtains the best possible outcome from his/her medicine. The EDQM’s committee of experts for this activity develops scientific indicators for measuring the quality of pharmaceutical care in Europe. Pharmaceutical care is understood as a quality concept and working method for the responsible provision of medicine therapy for definite outcomes in the interest of patients’ quality of life. The indicators developed by the EDQM provide information that is of practical use on a day-to-day basis for policy-makers and professional associations, helping to make healthcare systems more responsible and cost-effective.
- Preventing and managing risks posed by counterfeit/falsified medicines: Counterfeit/falsified medicines pose a growing and real threat to public health in Europe. These medicines may contain low quality ingredients or the wrong doses, they may be deliberately mislabelled or have fake packaging or ingredients. To combat this problem, the Council of Europe established the MEDICRIME Convention. It is the first international treaty that criminalises the counterfeiting of medical products and similar crimes with a view to public health protection. The convention entered into force on 1 January 2016.
Activities related to patient and consumer protection
Blood Transfusion
The work of the EDQM in the area of blood transfusion is co-ordinated by the European Committee on Blood Transfusion. This committee consists of 65 representatives drawn from 35 Council of Europe member states and signatories of the European Pharmacopoeia Convention, as well as 10 observer states and other observers such as the EU Commission and WHO. These experts work together on the ethical, legal and organisational aspects of blood transfusion. The “Guide to the preparation, use and quality assurance of blood components” contains recommendations on blood collection, blood components, technical procedures, transfusion practices and quality systems for blood establishments.More specifically, through its regular work the Committee assists Council of Europe member states to improve their blood transfusion services, ensures the transfer of knowledge and expertise through training and networking, and monitors practices in Europe and assesses epidemiological risks, in particular those related to the emergence of new infectious agents transmissible by blood transfusion.
Organ, tissue and cell transplantation
The work of the Council of Europe in the area of organ, tissue and cell transplantation began in 1987. The guiding principles for the EDQM’s activities in this area are to guarantee human rights and dignity and to protect donors and recipients. This latter principle means improving and promoting strict standards for quality and safety in order to protect not only the donor and recipient, but also the graft itself, which is a rare and precious resource.The European Committee on Organ Transplantation is the steering committee in charge of transplantation activities. This committee consists of 91 experts representing 54 countries, plus the EU Commission and WHO. It actively promotes the non-commercialisation of donations, the fight against organ/tissue trafficking and the development of ethical, quality and safety standards in the field of organ, tissue and cell transplantation. An important part of their work is the elaboration of guides such as the “Guide to quality and safety of organs for transplantation” and the “Guide to the quality and safety of tissues and cells for human application”.
The EDQM organises a European Day for Organ Donation and Transplantation together with a different member state every year, to promote organ donation and transplantation in its member states.
Cosmetics and food contact materials
Since 1 January 2009, the EDQM has also been engaged in efforts to strengthen consumer health protection in Europe, with a focus on the safe use and quality of cosmetics and materials designed for packaging or other purposes involving contact with foodstuffs.The Consumer Health Protection Committee is in charge of managing the work programme. It has two groups of experts – the Committee of Experts on Cosmetic Products and the Committee of Experts on Food Contact Materials – that examine health-related matters and prepare reports and recommendations concerning regulatory approaches.
A network of Official Cosmetics Control Laboratories was established in 2010 to share the work linked to cosmetics surveillance by strengthening inter-laboratory collaboration and the sharing of resources among market surveillance authorities. Several control laboratories in Asia also take part in the work programme.
Network activities include market-surveillance studies, analytical development, proficiency testing scheme studies and the implementation of harmonised QM systems. Priority is given to testing products that may present a health risk for consumers, either linked to the presence of prohibited or restricted substances or to trace metals. In addition, the Network also publishes test methods after performing inter-laboratory trials to confirm that these methods are fit for purpose.