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    ANNUAL REPORT 2017 European Directorate for the Quality of Medicines & HealthCare (EDQM) European Directorate Direction européenne for the Quality de la qualité of Medicines du médicament & HealthCare & soins de santé

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    ANNUAL REPORT 2017 European Directorate for the Quality of Medicines & HealthCare (EDQM) Council of Europe, EDQM

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    European Directorate for the Quality of Medicines & HealthCare (EDQM) 7, allée Kastner CS 30026 F-67081 Strasbourg - France French edition Tel.: +33 (0)3 88 41 30 30 Rapport annuel 2017 Fax: +33 (0)3 88 41 27 71 https://go.edqm.eu/HDpubs Translation of this publication Photos© Council of Europe, may be carried out by external Shutterstock, Fotolia parties. However, it must Layout and cover design: be authorised by the EDQM, Documents and publications Council of Europe before being production Department (SPDP), reproduced or published Council of Europe in any form or by any means, electronic (CD-Rom, Internet, This publication has not been etc.) or mechanical, including copy-edited by the SPDP Editorial photocopying, recording Unit to correct typographical and or any information storage grammatical errors. or retrieval system. Published by the Council of Europe All other correspondence F-67075 Strasbourg Cedex concerning this document www.coe.int should be addressed to the © Council of Europe, May 2018 EDQM (www.edqm.eu). Printed at the Council of Europe

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    Foreword by Susanne Keitel, Director ■ International cooperation and promoting science-based quality standards at global level also saw major achievements, with the EDQM signing two Memorandums of Understanding on co-operation in the field of medicines’ quality and on pharmacopoeial standards with ANVISA, the Health Surveillance Agency of Brazil. A Memorandum of Understanding was also signed with the Chinese Pharmacopoeia Commission to promote co-operation on the safety and quality of medicines in both Europe and China. ■ Throughout 2017, the EDQM’s cooperation with the European Union and its European Medicines 2 017 was another remarkable year for the EDQM Agency (EMA) continued to be strengthened for with various milestones reached on a number the benefit of European citizens and patients. The of our activities. Starting with the European Official Medicines Control Laboratories (OMCLs) Pharmacopoeia (Ph. Eur.), we are most pleased with carried on with their joint work programmes under the progress achieved in the fields of biotherapeutic the GEON Network coordinated by the EDQM: mutual products and animal protection, in addition to the recognition of test results, harmonisation of working 35 new and more than 220 revised texts adopted to methods, sharing of expertise, laboratory resources incorporate scientific and technological progress and and analytical data all featured high on the GEON regulatory changes. agenda in 2017. ■ In particular, in 2017 the European Pharmacopoeia ■ The work carried out by the EDQM on the Commission adopted the first monograph on a healthcare side led to some important achievements monoclonal antibody (mAb): Infliximab concentrated too. In the area of blood transfusion, the EDQM kept solution (2928), an important milestone in relation supporting European Blood Establishments (BEs) in to biotherapeutic products. The adoption of this implementing Quality Management (QM) elements monograph not only showed that setting public and addressing risk management, change control standards for a complex biological molecule is feasible, and validation/qualification, which are key aspects it also paved the way for the Ph. Eur. Commission’s for ensuring the optimal use of blood, as well as the horizontal approach for therapeutic mAbs: looking sound protection of both blood donors and recipients. into general requirements and methodologies In 2017, the EDQM also published the 3rd Edition of its applicable to this class of products. guidelines to ensure the quality and safety of tissues ■ Once more last year, much was achieved by the and cells for human application. This guidance aims Ph. Eur. Commission in terms of implementing and at helping healthcare and transplant professionals promoting animal welfare in pharmacopoeial testing on a practical level and supporting successful and in Europe. In line with the European Convention for the safe clinical use of tissues and cells. In the field of Protection of Vertebrate Animals used for Experimental cosmetics, a new guide on safer tattooing provided and other Scientific Purposes, the Ph. Eur. Commission an overview of current knowledge and challenges in decided to completely remove the test for abnormal the toxicological assessment of inks for tattoos and toxicity from the European Pharmacopoeia. permanent make-up. ► Page 5

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    ■ The support offered to the EDQM by Member ■ And of course – as always – I have to acknowledge States and their national competent authorities the fact that the EDQM’s achievements in 2017 would throughout the year has been of particular importance. not have been possible without the remarkable efforts I wish to express my gratitude to all; in particular, to the of our experts: joining us from national, European Hungarian authorities for their support in organising and international authorities, universities, scientific with us the annual meeting of the General European institutes and industry from across the world, they OMCL Network in Budapest; to the Cypriot authorities have made an invaluable contribution to our work for hosting the Network of Official Cosmetics Control with their excellent scientific competence. To all of Laboratories in Nicosia to discuss analytical challenges them, as well as to the dedicated staff at the EDQM, related to cosmetics control, during the Cyprus I offer my heartfelt thanks. Chairmanship of the Committee of Ministers of the Council of Europe; and to the Czech authorities for their support in hosting the International conference on the Certification Procedure in the global regulatory environment, which took place under the Czech Republic Chairmanship of the Committee of Ministers. Page 6 ► Annual report

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    Quality and use of medicines ■ To reflect this global status of the Ph. Eur. and keep THE EUROPEAN PHARMACOPOEIA pace with the far-reaching changes the pharmaceutical world has undergone over the past 50 years which What it is and how it works have created a globalised operating environment for medicinal products and their components, in 2015 the ■ The European Pharmacopoeia (Ph. Eur.) lays down Ph. Eur. Commission reviewed its working procedures quality standards for the manufacture and control to allow for the nomination of experts from non-Ph. of medicines in Europe and beyond. The texts of Eur. member states. This decision was part of a specific the Ph. Eur. are elaborated and revised by a panel policy to further involve observer states, as well as of 61 groups of experts and working parties which manufacturers from outside Europe, in the work of the may be convened or disbanded by the European Ph. Eur. This new policy is applied for the nomination Pharmacopoeia Commission, the decision-making of Ph. Eur. experts since November 2016. The wide body of the Ph. Eur., depending on current regulatory, variety of scientific and cultural backgrounds of these industrial and technical needs. Since the participation experts, all volunteers, testifies to the international of external stakeholders and users in the Ph. Eur.’s public scope and reach of the Ph. Eur. standards-setting process is vital for the development of authoritative and relevant monographs, these Key facts and figures groups comprise representatives of national competent authorities, academia and industry. Wide participation The importance of the Ph. Eur. in Europe ■ 38 Member States and the EU are signatories and beyond of the Convention on the Elaboration of a European Pharmacopoeia (the Republic of Moldova being the ■ The Ph. Eur., Europe’s legal and scientific latest Member State having accessed the Convention). benchmark for pharmacopoeial standards, is legally In addition, by the end of 2017, there were 29 observers binding in 38 European countries and used in over to the Ph. Eur. Commission: 27 countries from all over 100 countries worldwide. It delivers crucial information the world, the Taiwan Food and Drug Administration earlier than any other pharmacopoeia in Europe. and the World Health Organization. ► Page 7

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    The Work Programme 2017 product monographs help Official Medicines Control Laboratories (OMCLs) in their market surveillance tasks and can support the development of generic drugs, an essential point for the sustainability of healthcare systems. Finished product monographs also facilitate the assessment of marketing authorisation applications by regulatory authorities. ■ The European Pharmacopoeia works to provide its end-users with the most up-to-date and relevant information possible, elaborating new texts for products of high market relevance. The Ph. Eur. Commission adopted five new monographs on active substances elaborated under the P4 procedure. Pharmacotherapeutic group Active substances (source: EMA website) Raltegravir Antivirals for treatment of HIV ■ Year-on-year, the Ph. Eur. Commission works potassium (2887) infections, combinations to provide the users of the Ph. Eur. with the most Tigecycline (2825) Antibacterials for systemic use up-to-date and relevant information possible, revising Lacosamide (2292) Anti-epileptics existing monographs to incorporate newly developed All other therapeutic products methods and techniques, and approving new texts Deferiprone (2236) (iron chelator) for products of high market relevance. The work Rotigotine (3014) Anti-Parkinson drugs programme for 2017 continued to reflect these efforts: 35 new monographs were adopted and 222 texts ■ The Ph. Eur. Commission achieved an important were revised to incorporate regulatory changes and milestone in the field of biotherapeutic products scientific progress. with the adoption of the monograph for Infliximab concentrated solution (2928) in November 2017. This Scope of the 35 newly adopted Ph. Eur. Infliximab monograph is the outcome of a collaborative monographs (2017) effort by Ph. Eur. experts, and a successful example of the close cooperation between the Ph. Eur. and its key Scope Newly adopted Ph. Eur. Number of monographs monographs partners. The elaboration of the monograph included extensive and rigorous analytical testing by Ph. Eur. Single source products still under 7 experts from Official Medicines Control Laboratories patent amongst them: (OMCLs). This, together with the feedback received 2 – Finished products from stakeholders during the Pharmeuropa public – Active substances 5 consultation, demonstrated that it is feasible to set Multisource Monoclonal Antibody 1 meaningful quality requirements for a complex mAb (mAb) (150 kDa). The approach used to set the monograph Traditional Chinese Medicines (TCM) 7 specifications is oriented towards promoting flexibility, notably in addressing process-dependent product Herbal drugs and herbal drugs 3 preparations heterogeneity (e.g. glycosylation and charge profile). Significantly, criteria for verifying the performance of Concentrated solutions 1 analytical methods are included as a way of supporting for haemofiltration and haemodiafiltration robust methodologies, while the provision of examples of suitable procedures for complex assays enables the Radiopharmaceutical preparation 1 use of alternative methods. Other monographs 10 ■ Going forward, the Ph. Eur. Commission will carry ■ The Ph. Eur. Commission adopted two on setting public standards for therapeutic mAbs monographs on finished products, Raltegravir through the development of horizontal approaches: tablets (2938) and Raltegravir chewable tablets (2939), these aim to establish a suitable set of general elaborated under the P4 procedure (single-source requirements and methodologies applicable to various products still under patent). These two monographs quality attributes common to (classes/sub-classes of) follow on from the decision of the Ph. Eur. Commission mAbs (e.g. TNF-alpha product-based standards). in 2014, after the positive results of a pilot phase, ■ In 2017, the Ph. Eur. Commission also continued to make finished product monographs part of its its efforts in replacing animal testing whenever regular work programme. The decision was based on possible and endorsed the complete suppression various considerations including the fact that finished of the test for abnormal toxicity from the Ph. Eur. As Page 8 ► Annual report

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    part of this exercise, the Commission adopted 49 for testing Pyrrolizidine Alkaloids (2.8.26). This decision monographs revised to remove the test for abnormal was taken upon demand by European regulators and toxicity; of these, 36 monographs were on vaccines for following reports in some Ph. Eur. Member States that human use. In addition, the general chapter Abnormal herbal medicinal products, as well as food, were found Toxicity (2.6.9), which will no longer be referenced in to be contaminated with traces of plants containing any monograph, is likely to become obsolete and pyrrolizidine alkaloids. deleted completely from the Ph. Eur. In line with the Council of Europe Convention for the Protection of General matters and policies Vertebrate Animals used for Experimental and other Scientific Purposes1, the decision to suppress the test for abnormal toxicity demonstrates the Ph. Eur. Biological Standardisation Programme Commission’s commitment to reducing animal use wherever possible in pharmacopoeial testing. ■ The Ph. Eur. Commission also adopted a revised version of the general monograph on Vaccines for human use (0153) and the one on Vaccines for veterinary ■ The Biological Standardisation Programme (BSP) is use (0062), this followed on from the new general a joint European Union (EU)/Council of Europe initiative, chapter 5.2.14 on Substitution of in vivo method(s) partly funded by the EU. Its mission is to establish by in vitro methods for the quality control of vaccines, reference materials for biologicals and to develop and which was originally adopted in 2016. This chapter is validate new analytical methods for the quality control a guidance document (non-mandatory text) intended of biologicals, including alternative methods for the to facilitate the transition from in vivo to in vitro replacement of animals in laboratory experiments methods; it is an addition made available by the Ph. Eur. based on the 3Rs principle (Refine, Reduce, Replace). Commission to reduce animal testing and encourage ■ In 2017, the programme ran 29 projects the use of alternatives. Both general monographs in different fields, from vaccines for human and 0153 and 0062 contain a section titled “Animal tests” veterinary use to plasma-derived and biotechnology providing recommendations on how to meet the products. Six were concluded in the year, leading to the animal welfare requirements of the Convention for the establishment of 3 new and 5 replacement reference Protection of Vertebrate Animals Used for Experimental standards (see chapter on “Pharmaceutical Reference and Other Scientific Purposes, in the context of vaccine Standards”, page 12). control. The sentence, “Guidance on how to substitute in vivo methods by in vitro methods where a direct ■ The EDQM carried forward another 14 projects head-to-head comparison is not possible may be found aimed at establishing replacement batches for existing in general chapter 5.2.14” was added in the section reference standards for biologicals. Three projects “Animal tests” of these two general monographs: it for the elaboration of these reference standards removes any ambiguity as regards the non-mandatory for new monographs, or new requirements in character of the chapter, but still directs the user to existing monographs, were also pursued. Important the new chapter 5.2.14. achievements in this context were the establishment of assay standards, Biological Reference Preparations ■ The Ph. Eur. Commission also continued its (BRPs), for monographs on biotherapeutics, such as efforts in replacing the use of hazardous chemicals Etanercept and Infliximab. whenever possible. For example 4 monographs on sutures for human or veterinary use (Sutures, sterile ■ Nine projects focused on the development non-absorbable (0324), Polyamide 6/6 suture, sterile, of new compendial methods, and 6 of these were in distributor for veterinary use (0610), Polyamide 6 dedicated to applying the 3Rs principle to the field suture, sterile, in distributor for veterinary use (0609), of quality control of biologicals. The continued efforts Poly(ethylene terephthalate) suture, sterile, in distributor of the BSP to elaborate, validate and implement for veterinary use (0607)) have been revised in order analytical methods in line with the 3Rs principle were to replace the use of hazardous chemicals by infrared widely acknowledged in 2017. spectroscopy using attenuated total reflection for their identification and to include sutures composed Standard Terms database of blends of materials cited in the monographs. ■ In 2017, the Ph. Eur. Commission decided to cre- ate a new Working Party on Pyrrolizidine Alkaloids (PA WP), tasked with the definition of a general method ■ Initially drawn up at the request of the Commission 1. More information on the European Convention for the of the European Union for use in marketing Protection of Vertebrate Animals can be found here: authorisation applications, the lists of the “Standard https://go.edqm.eu/convprotectionanimals Quality and use of medicines ► Page 9

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    Terms” database provide users and prescribers with Pharmacopoeial Practices (GPhP). The Ph. Eur., JP, and harmonised vocabularies to describe dosage forms, USP will continue to share information and progress routes of administration, units of presentation, on these topics, which will however not be part of containers closures and delivery devices of medicinal the trilateral work programme until further notice. products. It also includes a mapped terms function, ■ Approvals at the 2017 PDG meeting included which allows external databases across the world to a new General Chapter on “Conductivity” and the introduce and map their own terms against Standard revision of 4 monographs, including Microcrystalline Terms, and web services (also known as application Cellulose, Hypromellose, Methylcellulose and Calcium programming interfaces), which allow registered users Phosphate Dibasic Anhydrous. In-depth discussions on to extract data directly from the database. By the end a number of additional items on the work programme of 2017, the free, online Standard Terms database had also took place with a view to resolving outstanding almost 20 000 registered users and held 977 individual issues and advancing items towards sign-off. Standard Terms concepts translated into 34 languages, for a total of more than 27 000 entries. ■ As a result, 28 of the 31 General Chapters and 45 of the 62 excipient monographs on the work ■ In 2017, a new tagging function was also programme were now harmonised between the PDG developed to allow the introduction of “non- Pharmacopoeias in 2017. traditional” Standard Terms intended for purposes other than marketing authorisation applications and Further harmonisation initiatives labelling. In particular, this meant that certain terms necessary for pharmacovigilance could be introduced ■ The Ph. Eur. is actively involved in a number and led to the International Council for Harmonisation of other harmonisation initiatives at international of Technical Requirements for Pharmaceuticals for level. It takes part in the International Meeting of Human Use (ICH) voting to use Standard Terms lists World Pharmacopoeias, which is organised under the for adverse event reports, hence further broadening auspices of WHO and brings together pharmacopoeias the global use of the database. from around the world to discuss possible ways of strengthening harmonisation and convergence. Amid The Pharmacopoeial Discussion Group the various projects carried out, the WHO initiative to and other international harmonisation draft Good Pharmacopoeial Practices (GPhP) stands initiatives out as a basis for improving cooperation and work- sharing among the pharmacopoeias of the world. ■ Through its active participation in the work of the Pharmacopoeial Discussion Group (PDG), the Ph. Eur. ■ The 8th International Meeting of World continued its efforts to reduce unnecessary duplication Pharmacopoeias took place in August 2017 in Brasilia of testing and reporting during drug development and (Brazil) and was hosted by ANVISA, the Brazilian routine manufacturing testing. The Group, which national health agency. This was an occasion for the comprises the Ph. Eur., the Japanese Pharmacopoeia pharmacopoeias to discuss and finalise the outstanding (JP) and the United States Pharmacopeia (USP) as annexes of the GPhP core document (glossary and members, as well as the World Health Organization future chapters on compounding and on monographs (WHO) as an observer, was set up in 1989 to harmonise on herbal medicines) and to discuss possible next pharmacopoeial standards across the world. One face- steps. In the context of this meeting, the EDQM and to-face meeting was held in 2017, hosted by the USP ANVISA signed a Memorandum of Understanding on in Rockville (USA, Maryland). strengthening co-operation in the field of medicines’ quality and pharmacopoeial standards. ■ In 2017, the PDG agreed to the implementation of significant changes to the work structure, including: Cooperation with national and f eliminating two stages of PDG harmonisation European regulatory authorities process to streamline and reduce the level of complexity; ■ Throughout 2017, the Ph. Eur. Commission continued to work closely with national competent f restructuring meeting format to engage more authorities and the European Medicines Agency effectively at the technical level with regards to (EMA). This on-going cooperation is crucial to ensuring resolving issues on specific topics; continued consistency between the approaches of f and maintaining a twice-yearly meeting licensing authorities and the Ph. Eur.; the EMA scientific frequency with a focus on strategic direction guidelines and the Ph. Eur. monographs and chapters setting. are complementary instruments for ensuring the ■ Under the new structure, the harmonisation of quality of medicinal products. More specifically, other several PDG topics will be carried out in other f the Ph. Eur. sets legally binding harmonised collaborative venues, such as bilateral discussions or specifications for pharmaceutical preparations, the adopt/adapt mechanisms mentioned in the Good their constituents and containers; and Page 10 ► Annual report

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    f the EMA guidelines provide advice on the best or Publications, databases and website most appropriate way to fulfil legal obligations. ■ The 9th Edition of the European Pharmacopoeia ■ Representatives of national authorities are (with its latest Supplement 9.5) contains 2 376 members of the Ph. Eur. Commission and its groups monographs (including dosage forms), 361 general of experts and working parties. National authorities texts (including general monographs and methods and the EMA also take part in the work of the Ph. Eur. by of analysis) and around 2 676 descriptions of reagents. submitting requests for revisions and reviewing draft texts issued for public consultation in Pharmeuropa online. Members of EMA working groups (i.e. for which Scope of monographs Ph. Eur. Edition 9.5 the EMA provides the Secretariat) or members of the EMA Secretariat itself are observers to some of the 1% 2% 1% Biologicals 0% 1% 4% Chemicals Ph. Eur. Commission’s groups of experts and working 3% 4% 6% Dosage forms parties. 3% Herbals 6% Fats ■ Likewise, the EDQM has observer status in a Radiopharmaceuticals number of EMA bodies, such as the Committee for 13% 55% Vaccines Human use Vaccines Vet use Advanced Therapies (CAT), the Herbal Medicinal Plastics Products Committee (HMPC), the joint CHMP/CVMP Blood deriv. Antibiotics Quality Working Party (QWP), the Biologics Working 1% Gases Party (BWP), the Immunologicals Working Party (IWP) Homeopathy and the GMP/GDP Inspectors Working Group. Med. Devices Cooperation with National Pharmacopoeia Authorities ■ Pharmeuropa online is the free online publication, ■ The EDQM organises an annual meeting of in which draft Ph. Eur. texts are launched for National Pharmacopoeia Authorities (NPAs) of Ph. Eur. public consultation. Easily and widely accessible, Member States to facilitate and coordinate activities Pharmeuropa online aims to optimise interactions of common interest, and to provide an informal forum between the Ph. Eur. Commission and its stakeholders: for exchanging information. The 2017 meeting was it provides interested parties with enough time to hosted by the EDQM in Strasbourg in June. Among comment on draft texts and ensures access to all other topics, discussions focused on the Ph. Eur. work stakeholders across the globe. Texts are published on programme and on process improvements. an on-going basis and comments can be submitted on the basis of 4 deadlines per year. In 2017, 157 draft Cooperation with other stakeholders texts were published on Pharmeuropa online, which was accessed from 155 countries worldwide in the ■ Stakeholders’ involvement in the elaboration and course of the year. revision of Ph. Eur. texts is of crucial importance, and the EDQM strives to ensure regular exchanges with all those concerned by its work. In 2017, various bilateral REFERENCE STANDARDS meetings were held with a variety of stakeholders to promote exchanges on all aspects related to the work What are reference standards and why of the EDQM, and also to ensure that the feedback are they needed? from users could be taken into account. Ph. Eur. reference standards ■ Official reference standards (RSs) are an essential part of the quality standards of the Ph. Eur.: they are used in conjunction with the documentary texts and are produced specifically for the intended use described. Reference standards include Chemical Reference Substances (CRSs), Herbal Reference Standards (HRSs), Biological Reference Preparations (BRPs), Biological Reference Reagents (BRRs) and reference spectra. The official Ph. Eur. reference standards are established and distributed by the EDQM and officially adopted by the Ph. Eur. Commission; only the official Ph. Eur. reference standards are authoritative in case of arbitration. Quality and use of medicines ► Page 11

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    Key facts and figures Distribution of RS across the world in 2017 Europe 1% 1% Asia 2% 2% 5% North America Africa 27% Near/Middle East South America Oceania 61% ■ The EDQM’s RSs portfolio constantly evolves, as new standards are introduced to complement new or revised Ph. Eur. texts, or to replace existing RS when ■ At the end of 2017, there were 2 838 reference corresponding stocks run out. The overall lifecycle standards available in the Ph. Eur. catalogue. management of the RS portfolio covers a wide range ■ Globalisation of the pharmaceutical industry of tasks: from the procurement, characterisation, means that Ph. Eur. RSs are widely used around the storage, establishment distribution, labelling and world: in 2017, the EDQM distributed its Ph. Eur. RSs packing of candidate materials, to quality control, directly to 115 countries. quality assurance, release and monitoring. Growth of the RS portfolio EDQM activities for WHO on Reference Standards 2900 ■ The EDQM is an observer to the World 2800 Health Organization (WHO) Expert Committee on 2700 Specifications for Pharmaceutical Preparations and Number of Reference 2600 the Expert Committee on Biological Standardisation. Standards The tasks entrusted to these Committees include 2500 the development of standards and guidelines to 2400 promote the quality assurance and quality control 2013 2014 2015 2016 of medicinal products around the world. In 2017, the 2017 EDQM Laboratory participated in two collaborative studies organised by the WHO for the establishment Ph. Eur. RSs adopted in 2017 of two International Standards: Activated Factor IX ■ In 2017, the Ph. Eur. Commission adopted 70 and anti-D Immunoglobulin. new and 247 replacement RSs. ■ The EDQM is responsible for the establishment, ■ The RSs used for assays must be thoroughly storage and distribution of WHO International characterised before they can be assigned a quantitative Standards for Antibiotics (ISAs), which are essential content value. In 2017, the EDQM Laboratory established for the standardisation and quality control of antibiotic 95 assay RSs, 46 of which required inter-laboratory drug substances and medicinal products. These studies involving official national control laboratories standards are supplied across the entire world for and other centres of excellence. microbiological assays performed in the context of the quality control of antibiotics. ■ The international collaborative studies performed by the Biological Standardisation Programme (BSP) ■ The establishment, monitoring and distribution in 2017 led to the conclusion of 6 projects and to the of WHO International Chemical Reference Substances adoption of 3 new reference standards by the Ph. Eur. (ICRSs) are also under the responsibility of the EDQM. Commission: Erythropoietin for SEC system suitability These reference substances are used in conjunction CRS, Etanercept BRP and Equine Influenza Subtype 2 with the monographs and texts of the International American-Like Strain A/eq/Richmond/1/2007 Horse Pharmacopoeia, which is published and maintained Antiserum BRP. Furthermore, 5 replacement standards by the WHO and used worldwide. were established: Hepatitis A vaccine ELISA detection Page 12 ► Annual report

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    antibodies set BRR, Heparin low-molecular-mass for Sheets and Safety Data Statements, as well as leaflets calibration CRS, Human immunoglobulin for Fc function are also available in the EDQM’s Online Database2. BRP, Human immunoglobulin for anticomplementary ■ In 2017, the EDQM issued 352 leaflets giving RS activity BRP and Human immunoglobulin (molecular users additional information such as a chromatogram, size) BRP. (See chapter “The European Pharmacopoeia”, assigned value, etc. for a given substance. page 7). Celecoxib ■ The WHO ICRS board adopted 5 establishment Safety Data Sheet Safety Data Sheet in accordance with regulation (EC) No 1907/2006, as amended. reports submitted by the EDQM Laboratory: Artesunate Date of issue: 31/05/2017 Version: 1.0 SECTION 1: Identification of the substance/mixture and of the company/undertaking ICRS2, Lumefantrine ICRS2, Atazanavir sulfate ICRS1, 1.1. Product form Product identifier : Substance Lopinavir ICRS1, Trimethoprim ICRS2, whereas no Substance name Product code : Celecoxib : 201600175 Synonyms : Celecoxib, salts, hydrates, isomers and impurities where applicable further needs to establish replacement batches for Other means of identification : Ph.Eur. 2591 any of the existing ISA emerged in the course of 2017. 1.2. 1.2.1. Relevant identified uses of the substance or mixture and uses advised against Relevant identified uses Main use category : The product is intended for research, analysis and scientific education. Use of the substance/mixture : For professional use only Function or use category : Laboratory chemicals 1.2.2. Uses advised against General matters and policies Restrictions on use 1.3. Details of the supplier of the safety data sheet : Do not use : Ingestion, Inhalation, Dermal European Directorate for the Quality of Medicines & Healthcare EDQM, Council of Europe 67081 Strasbourg - France T +33(0)388412035 - F +33(0)388412771 Extended competence in RS sds@edqm.eu - www.edqm.eu 1.4. Emergency telephone number establishment Emergency number : +33(0)390215608 SECTION 2: Hazards identification 2.1. Classification of the substance or mixture ■ In line with its continuous effort to improve Classification according to Regulation (EC) No. 1272/2008 [CLP] Acute toxicity (oral), Category 4 H302 Full text of H statements : see section 16 characterisation and establishment of reference Adverse physicochemical, human health and environmental effects standards and remain abreast of rapidly evolving Expert judgement and weight of evidence determination. 2.2. Label elements technologies, the EDQM Laboratory has participated Labelling according to Regulation (EC) No. 1272/2008 [CLP] Extra labelling to displayExtra classification(s) to display Hazard pictograms (CLP) : in a pilot study on quantitative NMR in 2017 which was organised by the Bureau International des Poids Signal word (CLP) : Warning GHS07 Hazard statements (CLP) : H302 - Harmful if swallowed et des Mesures (BIPM), the international organisation Precautionary statements (CLP) : P301+P312 - IF SWALLOWED: Call a doctor if you feel unwell Labelling according to: exemption for inner packaging where the contents do not exceed 10ml dealing with matters related to measurement science No labelling required and measurement standards. 2.3. Other hazards No additional information available SECTION 3: Composition/information on ingredients 3.1. Substances Collaboration with the ISO ■ The EDQM also continued its participation as an observer in the activities of the International ■ In addition, Safety Data Sheets and outer labels Organization for Standardization (ISO) Committee have been either created or updated for hazardous on Reference Materials (REMCO). chemicals in accordance with EU regulations on the Registration, Evaluation, Authorisation and Restriction Collaboration with national laboratories of Chemicals (REACH) and on Classification, Labelling and Packaging (CLP). Safety Data Statements have ■ Some RSs, usually those for assay/potency tests, been either created or updated for biohazardous are established through collaborative studies involving materials within the scope of Directive 2000/54/EC. several laboratories. Continuous collaboration with This brings to a total of 788 Safety Data Sheets and 11 national laboratories and centres of excellence is Safety Data Statements directly downloadable from fundamental for these studies. In 2017, the establishment the EDQM website. Safety Data Sheets and labels are of RSs also benefited from contributions from a panel provided in 27 languages. of 38 Official Medicines Control Laboratories from 27 different countries contributed. Publications, databases and website ■ Throughout 2017, the EDQM continued to run and maintain its “Reference Standards Online Database” providing access to all standards officially valid for the uses prescribed in the European Pharmacopoeia monographs. The database has been further fine- tuned to help users find the standards as rapidly as possible: RSs can be searched by code, name, monograph number or CAS number; also, RS Batch Validity Statements (BVSs) are available to users for documenting the validity of the particular RS batch 2. The EDQM Online database can be accessed here: supplied at the time of use. Downloadable Safety Data https://crs.edqm.eu/ Quality and use of medicines ► Page 13

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    CERTIFICATION OF SUITABILITY ■ In the course of 2017, a total of 306 new TO THE PH. EUR. MONOGRAPHS certificates and 1505 revised certificates were issued. Overall, about 90% of applications, including new The Certification procedure is becoming applications and requests for revision, were dealt with increasingly recognised worldwide within official timelines. ■ In order to assess the applications, the EDQM’s ■ The Certificate of Suitability (CEP) procedure has Certification Department relied on a Network of been set up to evaluate and validate the capacity of about 100 assessors from competent authorities of Ph. Eur. standards to control the quality of substances 25 different countries. used in the manufacture of medicinal products. As the world’s economy continues to evolve, extra-European ■ In December 2017, there were more than 4800 production of pharmaceutical ingredients has become valid CEPs covering chemical purity, TSE and herbal increasingly common, creating challenges as regards drug preparations. the monitoring and quality control of substances used ■ As part of the EDQM inspection programme, 44 in the manufacture of medicines. manufacturing sites from all continents were inspected ■ To apply for a Certificate, manufacturers submit a in 2017 (including 25 inspections in India and 16 in dossier describing how their product is manufactured China). These inspections were conducted by the and how its quality is controlled, and demonstrating EDQM jointly with inspectors from national supervisory that Ph. Eur. monographs are suitable for its quality authorities. In addition, by exchanging data with control. The EDQM evaluates the data in this dossier inspectorates from Member States and international and may then grant a CEP. The procedure centralises partners, the EDQM obtained information on GMP the evaluation of data for the benefit of regulatory compliance for 37 other sites. In total 81 manufacturing authorities and industry alike, and contributes to sites were assessed for GMP compliance. keeping the relevant Ph. Eur. monographs up to date. ■ As part of its collaboration with international ■ The EDQM also carries out inspections of partners worldwide, the EDQM also performed manufacturing and/or distribution sites of drug 1 joint inspection with the Pharmaceuticals and substances covered by CEPs. Inspections ensure Medical Devices Agency (PMDA) of Japan in 2017, that Good Manufacturing Practices (GMPs) are and contributed to inspections coordinated by the enforced and that the information supplied under European Medicines Agency (EMA). the Certification Procedure is accurate. ■ An increasing number of licensing authorities Location of EDQM inspections in 2017 worldwide accept CEPs to support (fully or partially) the quality section of the registration file submitted India China for substances used in medicinal products. Other Asian countries 3% 2% EEA Key facts and figures ■ The EDQM received 291 new applications 37% in 2017, including 19 for the risk of transmissible spongiform encephalopathy (TSE) and 9 for herbal 58% preparations; these figures are stable compared to 2016. Additionally, an increasing number of requests for revision of CEPs were received: 1868 (10% more compared to the previous year). ■ Following non-compliance cases within concerned companies, the EDQM has suspended New certificates granted per year 20 CEPs and withdrawn 5 CEPs in 2017. In two cases in 2017, actions were taken on CEPs after EU/EEA Chemical TSE&double Herbals Total supervisory authorities issued statements of non- compliance for sites involved in CEP applications. 355 334 Certificates granted 307 299 314 299 306 287 291 271 General matters and policies ■ In 2017, the Certification Department also 14 6 14 7 13 7 11 4 4 3 published a number of guidelines and policies3 to 2013 2014 2015 2016 2017 3. Available on the EDQM website https://go.edqm.eu/CEPgl Page 14 ► Annual report

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    support applicants in their communication with the (OMCL), the GEON, which supports national authorities EDQM and in the preparation of their CEP dossiers. responsible for controlling the quality of medicinal This includes in particular the revised guideline products for human and veterinary use marketed “Management of applications for new CEPs and in Europe. The coordination of the OMCL Network is applications for revision /renewal of CEPs” (which partly funded by the EU Commission. describes the way CEP applications are treated), and ■ Created to prevent substandard medicinal the document “Top 10 deficiencies in CEP applications”. products from reaching patients and compromising ■ The EDQM continued to implement its roadmap the efficacy of their treatment and potentially their for the submission of CEP applications in electronic health, the OMCL Network brings together official format. The EDQM expects to move towards the laboratories based in more than 40 European member exclusive use of the Electronic Common Technical states. Operating independently of manufacturers and Document (eCTD) format by 2020 (with the exception of thus without any conflicts of interest, this Network TSE dossiers and of substances for veterinary use only). allows pooling resources and latest technologies with a view to saving public money and sharing expertise and best practices across Europe. Communication with partners and stakeholders ■ The Network operates on the basis of common standards, procedures and guidelines, as well as on ■ In 2017, the Certification Department took the basis of mutual recognition of test results. Its part in a number of international platforms for work gives Member States the support they need to collaboration, such as the International Generic Drugs monitor the quality of medicines. Regulatory Programme (IGDRP), the international Active Pharmaceutical Ingredients (API) inspection Quality Management programme programme, and the Pharmaceutical Inspection Co-operation Scheme (PIC/S). ■ In 2017, the Network continued to implement, maintain, assess and improve the Quality Management ■ In the context of the Certification procedure a (QM) programme for its members. The main goals are: Memorandum of Understanding was signed with f to ensure harmonisation of quality management ANVISA of Brazil in order to strengthen co-operation systems (QMS) among OMCLs, and and exchange of information on the quality of pharmaceutical substances and ANVISA will consider f to achieve appropriate quality levels for the use of CEPs as support documentation for the exchanging results among members (e.g. batch quality evaluation of substances. release of biologicals, market surveillance of CAPs). ■ Finally, a 2-day conference on the Certification Mutual Joint Audits/Visits and Training procedure took place in Prague in September 2017. Visits The event was aimed at exchanging information on recent developments and on the future of the ■ Mutual Joint Audits/Visits (MJAs/MJVs) are procedure with the pharmaceutical sector worldwide, designed to assess the compliance of OMCL QMS with authorities and manufacturers alike. The event was the requirements laid down in ISO/IEC 17025, the attended by 175 participants from all continents. Network QM guidelines and the European Feedback received during the conference shows that Pharmacopoeia. In 2017, 14 MJAs and 2 Training the EDQM’s CEP procedure is becoming increasingly Visits (TVs) were carried out, bringing the total number recognised and used beyond Europe. to 169 MJAs, 51 MJVs and 24 TVs/Tutorials since the programme was launched in 1997. THE EUROPEAN NETWORK OF OFFICIAL MEDICINES No. of Mutual Joint (MV) Audits Visits and Training (2013-2017) CONTROL LABORATORIES 16 14 12 10 MJVisit 8 MJAudit The importance of a network for 6 Training Visit pan-European cooperation 4 2 ■ Throughout 2017, the EDQM continued to 0 coordinate activities and programmes of its General 2013 2014 2015 2016 2017 Network of Official Medicines Control Laboratories Quality and use of medicines ► Page 15

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    Participants in the 22nd Annual Meeting of GEON in Budapest (Hungary) OMCL Network Quality Management Proficiency Testing Scheme studies Guidelines ■ The EDQM Proficiency Testing Scheme (PTS) ■ Quality Management Guidelines (QM) are provides laboratories with an objective means to elaborated by experts of the Network and updated assess and demonstrate the reliability of their data. on a regular basis, under the coordination of the In 2017, five studies were organised in the physico- EDQM Secretariat. They were established to support chemical field: “PTS176 Osmolality”, “PTS177 Liquid laboratories in the implementation of the ISO/IEC Chromatography”, “PTS178 Dissolution”, “PTS179 17025 requirements. The following table lists the Thin Layer Chromatography” and “PTS175 Gas QM Guidelines and Recommendation documents Chromatography”. On average 98 laboratories (OMCLs discussed in 2017.4 and other pharmaceutical control laboratories from industry, hospital pharmacies, universities and Status Guideline/Recommendation documents pharmacy associations) took part in each study. Adopted1 Change control ■ Five biological studies were organised in 2017, Qualification of Equipment – Core with on average 18 participating laboratories for each document study. They covered “PTS180 Hepatitis E virus detection Under Qualification of Mass Spectrometers by Nucleic-acid Amplification Techniques (NAT)”, adoption Qualification of Liquid “PTS181 Hepatitis A virus NAT”, “PTS185 Hepatitis C Chromatography Equipment virus NAT” and “PTS182 Human coagulation factor VIII potency assay”. Qualification of Piston Pipettes Validation of Computerised System Collaboration with the European Under revision Qualification of balances Co-operation for Accreditation (EA) Uncertainty of Measurements ■ The EDQM reached out to the European Training Courses/Workshops Co-operation for Accreditation (EA), with the aim of evaluating the cooperation opportunities between the ■ In order to share experiences among OMCLs and two institutions, focusing on exchanges of know-how, harmonise best practices, in 2017 EDQM organised a participation in mutual meetings as observers and training session on the revised Guideline on “Use and running joint audits with National Accreditation Bodies handling of non-compendial reference standards” (NAB) and EDQM/MJA auditors. For this purpose a and a workshop on “Uncertainty of Measurements”. joint EA-EDQM communication document has been elaborated and adopted in 2017. Two joint audits 4. Available on the EDQM website https://go.edqm.eu/QAQMgl were also carried out in 2017. Page 16 ► Annual report

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    General OMCL Network (GEON) activities it covers “medicines in disguise” that contain non- declared active pharmaceutical ingredients in GEON Annual General Meeting quantities similar to authorised medicines. ■ The 22nd GEON Annual Meeting was held in ■ The Group also discussed the outcome of the 3rd Budapest (Hungary) from 15 to 19 May 2017 and was Counterfeit Symposium for OMCLs (Nicosia, Cyprus, organised with the support of the Hungarian National 28-29 March 2017) which brought together more than Institute of Pharmacy and Nutrition (NIP). More than 90 experts. Closer collaboration with stakeholders is 230 experts from 61 OMCLs and national medicine one of the top priorities of the Working Group and for agencies from 38 countries, including non-European the two group meetings in 2017, police and customs countries, such as Canada, Israel, Kazakhstan and experts were invited to exchange their expertise in Singapore, attended the meeting, which was divided the field of falsified medicines with the OMCLs. into 9 individual sessions. ■ Three technical training sessions for OMCL members were organised by the EDQM jointly with General market surveillance studies the Swedish and Belgian OMCLs. They covered NMR, ■ Market Surveillance Studies (MSSs) provide an LC-MS and chemometric methods applied for the overview of the quality of medicinal products available analysis of falsified medicines. on the European market in a given therapeutic class. ■ The EDQM’s Know-X database is secure and ■ In 2017, 3 MSSs, 1 MSS on Subdivision of Tablets restricted and stores comprehensive information on (MSS048), 1 MSS on Repaglinide Tablets (MSS052) individual cases of falsified medical products. The and 1 MSS on Leflunomide Tablets (MSS053), were Know-X database, which was launched in March 2014, carried out. underwent a major re-structuring in 2017 to make it more user-friendly and attractive in particular for ■ The testing phases of two MSSs launched in specific user groups, such as police, customs and 2016 on Foreign Matter in Herbal Drugs (MSS051) health authorities, but also to introduce new features. and Hyaluronic acid-based Dermal Fillers (MSS050) By the end of 2017 more than 3 600 individual cases were also completed. had been uploaded by OMCLs on the Know-X database ■ Two new MSSs on Zoledronic Acid Preparations (see “Know-X database”, page 20). for Parenteral Application (MSS055) and on Meloxicam APIs and Solutions for Injection (MSS056) were initiated. Gene Therapy Products Working Group ■ The OMCL Working Group for Gene Therapy ■ On average 12 OMCLs from the General European Products (GTP) was created in 2008 to foster OMCL Network participated in each of these studies. collaboration between OMCLs working in the GTP field, and to save time and resources through sharing Active Pharmaceutical Ingredients (API) of knowledge and latest technological advancements. Working Group Currently, 11 OMCLs are active members of this ■ The 10th meeting of the API Working Group Working Group. took place in October 2017. Discussions focused on ■ The validation of standard methods for the Fingerprint MSSs, on omeprazole and morphine and determination of viral and infectious genomes in on other classical API MSSs. Other core topics were Adeno-Associated Virus (AAV) vector products was also addressed, such as the API testing database – a pursued throughout 2017. Furthermore, preliminary common working tool for OMCLs, the application of work for the validation of the ELISA method for chemometric analysis for OMCLs and ways of improving AAV8 Physical Particles Titre (PPT) was satisfactorily the collaboration with Good Manufacturing Practices completed in 2017, while the collaborative study for its (GMP) inspectors for the collection of API samples. full validation will be organised in the course of 2018. ■ Lessons learned from the first fingerprint MSSs The validation of the AAV2 PPT ELISA is also expected were discussed to further improve the testing scheme to be completed in early 2018. The preliminary work in preparation for future studies. In order to facilitate on the standard method for determination of residual the access to API samples, the group reconsidered the mammalian host cell DNA in GTPs was initiated in 2017 possibility of combining classical API MSSs with the with 3 OMCLs. Various methods are being investigated, fingerprint programme. with the aim of identifying a method which would be applicable also to different types of products, such as Counterfeit/Illegal Medicines Working vaccines or recombinant DNA technology products. Group ■ A manuscript on the validation of UV- ■ The Counterfeit/Illegal Medicines Working spectrophotometry methods for the determination of Group met twice in the course of 2017. A new MSS plasmid DNA concentration and purity was published on Suspected Illegal Products (MSSIPs) was initiated; in Pharmeuropa Bio and Scientific Notes. Quality and use of medicines ► Page 17

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    CombiStats™ 1 case. In addition to the regular CAP programme, 2 generics programmes were run in 2017, during which ■ CombiStatsTM is a computer software, developed 7 branded Zoledronic acid products and 12 branded by the EDQM, for the statistical evaluation of biological Meloxicam products (generic medicinal products dilution assays in accordance with Chapter 5.3 of the and their respective reference medicinal products) Ph. Eur. Initially designed for OMCLs, CombiStatsTM were tested. In addition, 10 samples of meloxicam is now available also to other laboratories. The API were also tested. current version 5.0 introduced new features such as equivalence testing, robust regression, 5-parameter ■ As part of the 2017 CAP Programme, 152 sampling asymmetric sigmoid curves and password protection operations were performed from 28 countries, and of datasheets. The on-line manual, a tutorial and other 33 OMCLs were involved in the testing operations. The background information for CombiStats are available results showed that the vast majority of the products on the EDQM website5, while training courses for users tested were of the expected quality and complied are organised at the EDQM once a year. with authorised specifications. Two “confirmed out- of-specification” results and several regulatory or ■ In 2017, a total of 615 licences were issued, and technical findings were reported and followed up CombiStatsTM was used in 31 countries in Europe and by the EMA. 26 countries in the rest of the world. CombiStatsTM has thus evolved into a common internationally agreed reference in its domain and contributes to the mutual Mutual Recognition Procedure (MRP)/ recognition of data and results by all interested parties. Decentralised Procedure (DCP) post- marketing surveillance scheme ■ The OMCLs involved in the programme met CombiStats™ licences per region twice in 2017 (29th and 30th meeting) to evaluate the programme and discuss ways of optimising collaboration. Progress was made with discussions 3% 1% 8% 18% OMCL & Autorités on common risk-assessment procedures. In the future 17% programmes, the strong points of the CAP generics Europe and MRP/DCP testing schemes will be combined in order to further optimise the testing coverage of Asie, Océanie generics available on the European market. Amérique (Nord & Sud) ■ The 13th regular programme for the market Moyen-Orient surveillance of medicinal products authorised in the EU/EEA via the MRP or DCP was carried out in 2017. 53% Afrique About 1 400 product testing records were added to the 2017 programme, representing an increase of more than 20% compared to 2016. The testing reports for EU/EEA-specific activities 2017 were submitted by 28 different OMCLs and 9% of the tested products were for veterinary use. The Market Surveillance for Products with a generic products tested included most frequently Centralised Marketing Authorisation the APIs hydrochlorothiazide, amlodipine, valsartan, telmisartan and perindopril (treatment of high blood ■ Every year since 1999, the EMA and the EDQM have pressure), quetiapine and aripiprazole (antipsychotic), joined forces on an annual programme for Centrally pregabalin (antiepileptic), pantoprazole (gastric acid Authorised Products (CAPs) Sampling & Testing. blocker) and voriconazole (antifungal). The EMA sponsors the programme and has overall responsibility for it, while the EDQM coordinates the ■ Regulatory issues were identified in around 3% sampling and testing operations. The list of products to of the materials tested. These mostly consisted of be included in the annual programme is prepared by insufficient details on testing methods and labelling the EMA Secretariat together with the EMA Scientific issues; in addition, one or more out-of-specification Committees on a risk-based approach. In 2017, the results were reported in a further 2% of the cases. work programme featured 33 products for human use (12 biologicals and 21 chemical products, including ■ As of January 2018, the MRP/DCP Product 1 radiopharmaceutical product) and 6 products for Testing Database, set-up in 2007 for planning, veterinary use (3 immunobiological products and sampling and reporting activities carried out within 3 chemical products). API testing was performed in the Post Marketing Surveillance Scheme for Mutual Recognition Procedure (MRP)/Decentralised Procedure 5. These publications are available on the EDQM website (DCP), held some 9900 MRP- and DCP-product testing https://go.edqm.eu/combistats records, with contributions from 34 different OMCLs. Page 18 ► Annual report

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    Official Control Authority Batch Release competencies and readiness to intervene with test- of Biologicals for Human Use ing as needed. The VBRN’s testing priorities were re-evaluated using a risk based approach and it was ■ The harmonised application of Article 114 of agreed to remove erysipelas vaccine (inactivated) from EU Directive 2001/83/EC across Europe is carried the list of products eligible for OCABR. At the same out through the activities of the Network for Official time, the VBRN put in place a pilot phase to better Control Authority Batch Release (OCABR) of Biologicals coordinate activities for post-marketing surveillance for Human Use. This Network fosters the mandatory of this and other products. The VBRN Advisory group mutual recognition of batch release for human vac- met twice during the year to advance important issues cines and medicinal products derived from human and met on 1 occasion with representatives from the blood and plasma, which involves a quality review manufacturers’ association to foster exchange on through testing and protocol review. OMCLs remained issues of common concern. vigilant and over the course of the year evaluated tens of thousands of final lots and plasma pools, so that products’ quality could be independently confirmed ANTI-COUNTERFEITING ACTIVITIES before they reach patients. ■ The OCABR sessions of the Annual Meeting in Combating crime to protect public health Budapest were attended by more than 70 participants, ■ The EDQM continued to promote cooperation who used this opportunity to exchange expertise among authorities at national and international level in with the goal of optimising resources for solving the fight against falsified/counterfeit medical products common problems. The OMCLs discussed technical (medicinal products and medical devices). One of the issues and strategies that would lead to better and most powerful tools at its disposal is the Council of more efficient control of products such as vaccines Europe’s MEDICRIME Convention, the first and only for children and combination vaccines containing binding international instrument in the field of crimi- Diphtheria, Tetanus and acellular Pertussis. To further nal law that addresses the falsification/counterfeiting extend co-operation on a global level, the OCABR of medical products. The experts in the European Network, jointly with the OMCL from Israel, signed Committee on Pharmaceuticals and Pharmaceutical a Memorandum of Understanding to exchange data Care (CD-P-PH), the steering body, together with its and expertise in the field of human blood derived subordinate Committee of Experts on Minimising the medicinal products. The Network also looked closely at the potential impact of Brexit in order to put in Public Health Risks Posed by Falsification of Medical place strategies for handling any necessary changes. Products and Similar Crimes (CD-P-PH/CMED) con- tinued to develop and promote programmes and ■ In the course of 2017, 3 revised guidelines for projects aimed at disseminating best practices in the vaccines came into force, as did 2 revisions of the EU fight against falsified/counterfeit medical products. Administrative Procedure for OCABR and a number of internal Network Guidelines. The OCABR Advisory Group and drafting group for vaccines each met twice Key facts during the year to further the work of the OCABR ■ Efforts focused on encouraging authorities Network in between annual meetings. A workshop and governments to sign and ratify the Convention. to foster harmonised testing in the safety of oral Together with the Council of Europe’s Criminal Law polio bulks was also held for OMCLs and involved Division of the Directorate General Human Rights manufacturers. and Rule of Law, the EDQM contributed to various regional conferences and workshops promoting the Official Control Authority Batch Release MEDICRIME Convention, which entered into force of Immunological Veterinary Medicinal on 1 January 2016, following its 5th ratification, by Products Guinea. As of the end of 2017, the Convention had ■ Together with competent authorities at national been ratified in total by 11 countries. The 10th ratifi- level, this subset of specialised OMCLs is responsible for cation, by Burkina Faso, will trigger the set-up of the the independent control of immunological veterinary convention’s monitoring body – the Committee of the medicinal products (IVMPs) according to Articles 81 Parties, expected to take place in the course of 2018. and 82 of EU Directive 2001/82/EC as amended. The future MEDICRIME Committee of the Parties will play an active role in supervising implementation of ■ Twenty-four participants from 17 Member States the Convention by the signatory states. took part in the Veterinary Batch Release Network (VBRN) session of the OMCL annual meeting. The focus ■ The promotion of the MEDICRIME Convention was on communication and cooperation. Network goes hand-in-hand with the actions taken by the members reacted to the Lumpy Skin Disease crisis EDQM and its experts to implement the Convention and have signalled to competent authorities their and its tools. One example is the creation of a Network Quality and use of medicines ► Page 19

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    of Single Points of Contact (SPOCs) involving health Verification Organisation (EMVO), which is comprised authorities, customs and law enforcement agencies of various European supply-chain operators, the and other competent authorities at local, national EDQM performed two conformity assessments of and international level, through which information the EMVO’s traceability system. In 2017, the EDQM and data on counterfeit products is collected and started verifying that the system is designed, managed shared. In 2017, the EDQM organised an event with and operated in accordance with the standards in the Belgian Health Authority (FAMHP) for the SPOC the delegated regulation on the Unique Identifier Network with the aim of establishing best practices, (EU) 2016/161 which implements the EU Falsified improving cooperation within and between countries, Medicine Directive (Directive 2011/62/EU). This optimising data sharing and enhancing cooperation initiative will help establish Member States in their with other international organisations. SPOC contacts role as supervisors of traceability systems. from 22 countries participated in this event, together with representatives from WHO, the International Criminal Police Organization (Interpol) and the World Publications, databases and website Customs Organization (WCO). ■ The EDQM’s Know-X database is secure and ■ In October 2017, the second MEDICRIME restricted and stores comprehensive information workshop for Good Distribution Practices (GDP), on individual cases of falsified medical products. Good Manufacturing Practices (GMP) and Pharmacy The database is a tool for sharing information and Inspectors took place in Warsaw (Poland). Jointly enables health and law enforcement authorities organised with the Chief Pharmaceutical Inspectorate, across Europe to act more rapidly on cases of suspect this technical workshop was attended by 23 inspectors, medical products. The information provided in the plus two participants with legal background, coming Know-X database covers the analytical identification of from Poland, the Czech Republic, the Slovak Republic, medicinal products and the related follow-up actions Hungary and Ukraine. undertaken by the competent health or enforcement authorities. The CD-P-PH/CMED assists the OMCL Mass serialisation systems for medicines Counterfeit/Illegal Medicines Working Group with the ■ The EDQM continued to support the development of mass serialisation systems as tools to prevent the contamination of the legal supply chain with counterfeit, falsified medicines. To this end, the EDQM strived to promote a harmonised approach in the management of mass serialisation systems in Europe by working closely with supervisory authorities and supply chain operators in charge of developing and managing systems for secure data handling. ■ As a result of the agreement signed in 2015 between the EDQM and the European Medicines Page 20 ► Annual report

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    maintenance of the database and is also involved in of Medical Products and Similar Crimes (CD-P-PH/ promoting it and training users. The database has gone CMED) (see also the “List of Committees coordinated through a major update in the course of 2017. This was by the EDQM”, page 35). done in cooperation with the OMCL Network and with the involvement of experts coming from the OMCLs Key Facts and the CMED committee. The new database will be launched in early 2018 (see also the chapter “The Official ■ The final report of the EDQM Pharmaceutical Care Medicines Control Laboratories Network”, page 17). Indicators Project was published in 2017; it presents ■ Between 2007 and 2017, the EDQM has organised the results of the multinational validation study aimed or contributed to 18 trainings and 6 conferences. A at validating 4 basic sets of indicators to assess the quality of pharmaceutical care in Europe. It also total of 423 participants from 58 countries mostly in contains the data collection forms developed for and Europe, but also in other parts of the world6, have used in the validation study. The Pharmaceutical Care participated in training sessions related to counterfeit Indicators Project is aimed at supporting stakeholders and falsified medical products. involved in the medication process and competent authorities alike, in their tasks of assessing the impact Communication with partners and of pharmaceutical care and promoting the efficient stakeholders and safe use of medicines7. ■ Throughout 2017, representatives of the EDQM ■ In the course of 2017, significant progress was have participated regularly in the meetings of the also made on the drafting of a Council of Europe EU Heads of Medicines Agencies’ Working Group of resolution for the promotion and implementation Enforcement Officers (HMA-WGEO), and have attended of pharmaceutical care in Europe. The resolution a number of conferences in Europe and Africa with will promote patient-centred care and advance the purpose of raising awareness for the MEDICRIME appropriate and safe use of medications through the Convention. implementation of the pharmaceutical care philosophy and its working methods in daily practices. The resolution will also encourage the evaluation of the quality of pharmaceutical care practices, as a way of monitoring, assessing and improving the medication use process and quality of care between member states. ■ Following a public consultation among a wide range of concerned parties, the draft guidelines on best practices for Automated Dose Dispensing (ADD) were adopted in 2017. These guidelines recommend standards and approaches for regulating and providing ADD services across Europe; in particular, they will assist ADD providers and national authorities in ensuring that ADD services are provided at a consistently high standard that can maintain the safe supply of medicines to patients. The guidelines are expected to be made available to the public in 2018. PHARMACEUTICALS AND PHARMACEUTICAL CARE ■ The CD-P-PH/PHO issued its annual recommendations on the classification of medicines Optimal use of medicines for improving and their supply conditions (prescription and non- patients’ quality of life prescription). This work is of relevance to health authorities and all stakeholders across the medication ■ Activities in this area are led by the European supply chain, it helps ensure patient safety and Committee on Pharmaceuticals and Pharmaceutical accessibility of medicines in Europe. The annual Care (CD-P-PH) and its subordinate bodies, the recommendations of the CD-P-PC/PHO are included in Committee of Experts on Quality and Safety Standards the Melclass database8, which provides information on in Pharmaceutical Practices and Pharmaceutical the classification and conditions for supply of medicines. Care (CD-P-PH/PC), the Committee of Experts on the ■ With a view to avoiding duplication of work Classification of Medicines as Regards their Supply and promoting synergies in the area of classification (CD-P-PH/PHO) and the Committee of Experts on Minimising Public Health Risks Posed by Falsification 7. The EDQM publications are accessible here: https://register.edqm.eu/freepub 6. Overview of activities related to MEDICRIME: 8. The Melclass database is accessible here: https://go.edqm.eu/MDCRacts16 https://melclass.edqm.eu/ Quality and use of medicines ► Page 21

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    of medicines, cooperation was established between EUROPEAN PAEDIATRIC FORMULARY the CD-P-PH/PHO and the Co-ordination Group for Mutual Recognition and Decentralised procedures – A future pan-European free online Human (CMDh) Non-prescription Medicinal Products platform to improve the health of Task Force. children patients ■ The European Committee on Pharmaceuticals Publications, databases and website and Pharmaceutical Care (CD-P-PH) and the Ph. ■ The review of the classification of medicines Eur. Commission carried on their programme for containing anti-inflammatory and anti-rheumatic developing a European paediatric formulary. With active substances was completed and will be available authorised medicines not always suitable for the on the EDQM website in the course of 2018. treatment of children, national or regional formularies on pharmacy preparations still play an important role in this field and the European paediatric formulary project aims at improving the availability of extemporaneous formulations of quality paediatric medicines across Europe. ■ The European Paediatric Formulary is a collection of formulations currently in national formularies or in general well-established in European countries, which aims at supporting clinicians and pharmacists in accessing appropriate formulations and delivering preparations when no licensed products are available. Most importantly, the European Paediatric Formulary also aims to address requirements in EU and international legislation to increase the number of ■ The Melclass database was continually updated authorised paediatric medicines. throughout 2017 with relevant recommendations from ■ Following the definition of criteria for inclusion the Committee of Experts CD-P-PH/PHO to national and evaluation of formulations in 2015, a dedicated health authorities on the classification of medicines working party - composed of experts from hospital and their supply conditions. The Melclass database also pharmacies, academia and national authorities contains national information about the classification from 14 countries - was set-up under the auspices status and supply conditions of medicines across of the European Pharmacopoeia Commission to signatory Member States to the Convention on the prepare the content of the formulary. The first phase Elaboration of a European Pharmacopoeia. of the work was partially completed in 2017 and was based on the recommendations on paediatric Communication with partners and needs by the European Medicines Agency’s (EMA) stakeholders Paediatric Committee and on other sets of criteria, such as recently filed Paediatric Investigation Plans. ■ Various interactions took place in 2017 with For the next phase, some selected high priority international organisations and professional bodies formulations are being prepared to be launched for active in the field of public health and pharmacy public consultation, so as to obtain feedback from all practice, such as the South-Eastern Europe Health concerned parties before finalisation. Network (SEEHN), the European Association of Hospital ■ At the end of 2017, 8 monographs were on the Pharmacists (EAHP) and the European Federation of work programme, of which two pilot monographs Nurses Associations (EFN), in order to align efforts – Hydrochlorothiazide 0.5 mg/mL oral solution and aimed at ensuring safe and appropriate use of Sotalol 20 mg/mL oral solution – were already in the medicines in Europe. drafting phase and will be published soon for public ■ Resolution CM/Res(2016)2 on “Good enquiry. Reconstitution Practices in Health Care Establishments for Medicinal Products for Parenteral Use” was presented at the 22nd Congress of the EAHP in Cannes (France) in March and at the 20th European Conference of the professional international association Group of Evaluation and Research for Protection in Areas under Control (GERPAC) in Hyères (France) in October to promote its use. Page 22 ► Annual report

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    HealthCare T hroughout 2017, the EDQM has continued to work diligently to protect public health in Europe by proposing trusted and ethical safety Key facts and figures and quality standards for the collection, preparation, storage, distribution and appropriate use of blood components for blood transfusions, as well as for the transplantation of organs, tissues and cells. The work related to enhancing and developing standards in the field of food contact materials was also continued, along with the coordination of market studies and ■ The EDQM continued to run the Blood Proficiency proficiency schemes in the area of quality control Testing Scheme (B-PTS) and the Blood Quality for cosmetics. Management (B-QM) Programme. Both support BEs in the implementation of current EU blood legislation, the Blood Guide and the GPGs. Both programmes BLOOD TRANSFUSION benefit from financial support by the EU Commission. Promoting blood safety and quality in Europe and beyond ■ The EDQM is responsible for the Council of Nucleic Amplification Europe’s activities in the area of blood transfusion. Techniques (NAT) These are built around three major principles: promoting voluntary and non-remunerated donation, optimal use of blood and protecting both donors and B-PTS030 HBV, HCV, recipients of labile blood components. The EDQM HIV NAT addresses ethical, legal and organisational aspects B-PTS031 HEV NAT of blood transfusion to ensure the safety, quality and optimal use of blood supplies, increasing their availability and avoiding wastage. Serology ■ The European Committee on Blood Transfusion (CD-P-TS) is the Steering Committee for blood transfusion activities at the EDQM; it elaborates B-PTS032 Anti-HCV guidelines and recommendations and oversees B-PTS033 Anti-HIV/p24 the tasks of its subordinate working groups. It is composed of internationally recognised experts from B-PTS034 Anti-Treponema Council of Europe member states, observer countries, the EU Commission, WHO, the US Food and Drug B-PTS035 HBsAg/Anti-HBc Administration (US FDA) and the Council of Europe’s Committee on Bioethics (DH-BIO). Immuno-Haematology B-PTS036 ABO, Rhesus, Kell, extended phenotyping and Irregular antibodies B-PTS studies conducted in 2017 ► Page 23

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    Blood Proficiency Testing Scheme (B-PTS) ■ The external assessment of the testing capability of European BEs continued in 2017 through PTS studies9. A total of 7 studies were organised and an average of 72 laboratories participated in each study. Blood Quality Management (B-QM) Programme ■ This programme10 provides tools enabling European BEs to develop, implement and improve Participants in the Conference Sharing Best Practices: their Quality Management Systems (QMS). The Quality Risk Management, Change Control, Validation programme offers 3 types of schemes which are all and Qualification, Strasbourg (France) run by experts from European BEs: Risk behaviours with an impact f Blood Training Visit (B-TV): on-site visit and tailor- on blood donor management and made training on technical and QMS topics; transfusion safety f Blood Mutual Joint Visit (B-MJV): audit to as- sess the QMS against minimum European stan- ■ As required by Resolution CM/Res(2013)312, dards11, report on it and issue recommendations; a dedicated Working Group is responsible for the continuous collection of data on the incidence f Blood Mutual Joint Audit (B-MJA): audit to and prevalence of sexually transmitted infections check compliance of the QMS against minimum jeopardising the safety of transfusions. Member States European standards11 report on it and follow-up took different decisions on the deferral policies for of corrective and preventative actions. men having sex with men: the Working Group will map f In 2017 3 B-MJVs were carried out. these policies to illustrate the lack of harmonisation ■ The conference “Sharing Best practices: Quality and will also provide advice on the need for future Risk Management, Change Control, Validation and revisions of the Resolution. Qualification”, which was organised in October in Strasbourg and attended by 134 participants Optimal use of clotting factors including BEs, national authorities and suppliers from ■ Resolution CM/Res(2017)4312 on principles 33 countries, was not only an opportunity for concerning haemophilia therapies (replacing CM/ exchanging on these topics and on their practical Res (2015)3) was adopted by the Committee of implementation, but also a way of supporting BEs in Ministers in December 2017, a major outcome of the implementing the Good Practice Guidelines (GPG). recommendations made at the European Symposium: The proceedings, including recommendations and “Wildbad Kreuth Initiative - Optimal use of clotting conclusions, will be issued in 2018. factors and platelets” which took place in Freising, Germany in May 2016, organised by the EDQM, the General matters and policies Paul Ehrlich Institut (PEI) and the University of Munich. Good Practice Guidelines (GPGs) Publications, databases and website ■ The EU Commission included in its Directive ■ The 19th edition of the “Guide for the Preparation, 2016/1214 published in July 2016, the Good Practice Use and Quality Assurance of Blood Components” Guidelines issued in the 19th edition of the Blood Guide. (commonly referred to as the “Blood Guide”)13 was As a result, the EDQM’s Good Practice Guidelines published in March 2017, elaborated by the dedicated will function as a new legal instrument; EU and EEA Working Group entrusted with updating the Blood Member States will have to bring it into force by 15 Guide and keeping it abreast of the scientific February 2018. developments and regulatory changes that have occurred in the two-year period between editions of the guide. ■ The first edition of Guidance on Root Cause Analysis of non–satisfactory external quality assess- 9. https://go.edqm.eu/BPTS ment results13 was issued in June 2017. 10. https://go.edqm.eu/BQM 11. Minimum Standards: the EU blood legislation, the GPG and 12. Available on the EDQM website https://go.edqm.eu/BTrec the Blood Guide. Other standards followed by visited BEs (e.g. 13. The EDQM publications are available here: ISO Standards, GMP) may also be used. https://register.edqm.eu/freepub Page 24 ► Annual report

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    Guide to the GUIDANCE FOR preparation, use and ROOT-CAUSE ANALYSIS quality assurance of OF NON-SATISFACTORY BLOOD EXTERNAL QUALITY ASSESSMENT RESULTS COMPONENTS ORGAN TRANSPLANTATION AND TISSUES AND CELLS FOR HUMAN APPLICATION Promoting strict quality and safety European Committee (Partial Agreement) on Blood Transfusion (CD-P-TS ) EDQM 19th Edition 2017 1st Edition 2017 standards B-PTS Programme European Directorate Direction européenne for the Quality de la qualité of Medicines du médicament & HealthCare & soins de santé ■ The European Committee on Organ Transplantation (CD-P-TO) is the Steering Committee in charge of transplantation activities at the EDQM. ■ The European database of Frozen Blood Units Its mandate includes elaborating guidelines and of Rare Blood Groups, the tool that supports blood recommendations aimed at improving access to establishments in their searches for frozen blood units transplantation and strict safety, quality and ethical of rare blood groups, has been fully operational since standards. The CD-P-TO is composed of internationally January 2016. Six Blood Establishments (BEs) have recognised experts from Council of Europe member already provided on a voluntary basis their lists of frozen states, observer countries, the EU Commission, WHO, units of rare blood groups available to patients in need. relevant professional associations and the Council of Europe Committee on Bioethics (DH-BIO). Communication with partners and stakeholders General Matters and Policies ■ Transplantation is now a well-established, life- Cooperation with the European saving therapy; however, the supply is unable to keep Commission pace with the demand for organs. ■ 2017 was a year of intense and fruitful ■ Many countries are developing and optimising collaboration with the EU Commission. In particular, living donor programmes either to complement the this included the analysis of the EU Serious Adverse limited availability of organs from deceased donors Reactions and Events (SARE) related to blood or as the only source of organs, while they develop components and the contribution of the EDQM to the deceased donor programmes. public consultation on the evaluation of the EU blood legislation. This collaboration is expected to continue ■ While in present globalised times, many countries steadily for the near future, as the EDQM pursues its are accepting non-resident living donors, relevant goal of supporting the implementation of the EU blood differences remain in how countries accept these legislation and maintaining an ongoing dialogue with donors, such as in the screening and consent process, the EU Commission in relation to regulatory changes the reimbursement of justifiable expenses and the and new scientific advancements in the field. access to post-operative and follow-up care. In view of this situation, the Committee of Ministers of the ■ The EDQM will continue to participate as an Council of Europe has adopted Resolution CM/ observer in the meetings of the EU competent Res(2017)114 on principles for the selection, evaluation, authorities for blood, which are organised by the EU donation and follow-up of the non-resident living Commission. organ donors. Pharmaceutical Inspection Co-operation ■ This new resolution is aimed at protecting non- Scheme (PIC/S) resident living donors who, for a number of reasons – economic, emotional, cultural or physical – may be ■ In the context of the revision of the PIC/S GMP particularly vulnerable, and whose post-donation care Guide for Blood Establishments, the EDQM was invited and follow-up may be difficult to guarantee. to join the drafting group in charge of revising the text. Its participation aims at harmonising the PIC/S ■ There are exceptional circumstances in which document with the GPG in the Blood Guide. some of the patients may be properly referred for transplantation abroad by their treating physicians. International Society of Blood In addition, organ shortages, or lack of access to Transfusion (ISBT) a deceased-donor programme, may lead patients awaiting an organ to seek their transplant through ■ The EDQM has observer status on the ISBT Board illegal and dangerous practices, such as organ of Directors and is a member of various dedicated ISBT trafficking or human trafficking for the purpose working groups: the Standing Committee of Ethics and of organ removal. Patients who have received an the Quality Management Working Party. The EDQM also participated in the annual ISBT congress held in Copenhagen (Denmark) in June 2017. 14. Available on the EDQM website https://go.edqm.eu/OTrec HealthCare ► Page 25

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    organ transplant abroad, either upon referral of their treating physician or illicitly, typically return to their country of origin shortly after the transplantation procedure to receive post-transplantation care. The new Resolution CM/Res(2017)2 establishes procedures for the management of patients having received an organ transplant abroad upon return to their home country to receive follow-up care, regardless of the circumstances in which the transplant was obtained. The proposed measures protect patients, reinforce transparency of practices and facilitate traceability. ■ In the context of Resolution CM/Res(2013)55 and Resolution CM/Res(2017)2, Member States designated National Focal Points (NFP) on transplant related- crimes, based at national transplantation bodies or Ministries of Health. ■ In June 2017 the “International database on Travel for Transplantation” was launched. Through this data collection exercise, NFPs were requested to provide information about all patients who received a kidney transplant abroad in 2015. The exchange of information on these patients at international level will help better understand and analyse the phenomenon of “transplant tourism”, appreciate the long-term outcomes and potentials risks to both individuals and public health and identify hotspots of transplant tourism. process, thus ensuring that the standards set out under ■ During the “2nd Workshop for NFP on Transplant EU Directives are compatible with and complemented Related Crimes” (Strasbourg, November 2017), NFP by the Council of Europe’s guidance. Several professional jointly examined the data collection exercise, shared associations actively participated in the elaboration of the lessons learned after their first year in their role this Guide, in particular, the American Association of as NFPs and participated in breakout sessions where case studies were analysed in order to develop tools Tissue Banks (AATB), the European Eye Bank Association and reach conclusions on the best practices to prevent (EEBA), the European Society for Human Reproduction and address illicit transplantation practices. and Embryology (ESHRE), the European Society for Blood and Marrow Transplantation (EBMT), the Joint Publications and website Accreditation Committee-ISCT & EBMT (JACIE) and the International Council for Commonality in Blood ■ The “Guide to the Quality and Safety of Organs Banking Automation (ICCBBA). for Transplantation” (usually referred to as the “Organ Guide”) and the “Guide to the Quality and Safety of ■ A compilation of Council of Europe resolutions, Tissues and Cells for Human Application” (referred to recommendations and reports – 3rd Edition (2017) as the “Tissues and Cells Guide”) have become gold was also published. standard references in Europe and beyond. In order to ensure maximum dissemination, the electronic ■ The EDQM/Council of Europe publishes versions of both Guides are available free of charge15. “Newsletter Transplant”, the only official source of international figures on organ, tissue and haematopoietic stem cell donation and transplantation in Europe. The information provided in it allows analysing trends and amending policies accordingly. This work is coordinated by the Spanish National ■ In 2017, the 3rd edition of the Tissues and Cells Transplant Organisation (ONT) which, every year, Guide was published. The EU Commission has partially analyses international figures collected through a funded its elaboration and was involved in the drafting Network of health authorities and officially designated 15. The EDQM publications are available here: focal points worldwide. The latest issue provides https://register.edqm.eu/freepub figures from 67 countries for the year 2016. Page 26 ► Annual report

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    Communication with partners and is facilitated by the European Network of Official stakeholders Cosmetics Control Laboratories (OCCLs). Cooperation with the European Key facts Commission ■ Under the framework of its standing cooperation OCCL Network with the European Commission, the EDQM took over ■ The European OCCL Network was set up in 2010; the international annual vigilance exercise on Serious to date, more than 40 OCCLs participate regularly in Adverse Reactions and Events (SARE) in the EU in the the Network activities, among these are laboratories fields of blood and tissues and cells (see also the “Blood from 19 Member States of the European Union. transfusion” chapter, page 23). The main task of an OCCL is to check the quality of products on the market. Under the aegis of the Cooperation with professional EDQM, testing competences are made accessible to associations all network members, hence bringing considerable ■ Key professional associations in the field of organ, added value in terms of better use of resources and tissues and cells transplantation are participating in enhanced management of quality in accordance with the work of the EDQM. international standards. ■ When Cyprus chaired the Committee of Ministers COSMETICS AND FOOD of the Council of Europe from November 2016 to CONTACT MATERIALS May 2017, health authorities were invited to Nicosia in order to discuss analytical challenges related to Protecting consumer health cosmetics control. This event organised in March 2017 was attended by 30 experts from 15 countries and the ■ The Consumer Health Protection Committee programme also covered national perspectives on (CD-P-SC, Steering Committee), composed of how to step up cooperation in the field of cosmetics. representatives from national ministries with ■ Most sunscreens on the market indicate the public health responsibilities, establishes the work level of protection against harmful effects of UV programme for cosmetics and for materials that come radiation. The so-called Sun Protection Factor (SPF) into contact with food. In 2017, approximately 280 is typically set based on data from human studies. In experts in 34 Member States and 3 observers to the 2017, collaborative trials were initiated to develop Ph. Eur. Convention contributed actively to the work an in vitro test protocol that could be used instead of this Committee. of protocols involving humans. ■ The work programme in the field of food contact materials aims at harmonising quality and safety Quality check for cosmetics: Market requirements across Europe, together with efforts Surveillance Studies in the development and update of testing methods. ■ Following some alarming findings in cosmetic ■ In the field of cosmetics, the work of the EDQM products, the EDQM has been collecting national data focuses on product safety and surveillance; the on the quality of shampoos for children, creams and cooperation among Member States on this topic make-up, lotions and several other types of products for the past years. Initial findings confirmed the earlier observation that most of the cosmetic products for skin care comply with the regulations. However, decorative cosmetics (face-paint for children, shower gels with cartoon characters and other “children cosmetics”) continue to raise concerns. In conclusion, national authorities will need to intensify their controls of certain product categories. ■ National data were also collected on tooth whitening products and a report on their compliance with EU Regulation No 1223/2009 can be expected in early 2018. Proficiency Testing Scheme (PTS) studies ■ Proficiency testing is an essential part of quality control management in testing laboratories. HealthCare ► Page 27

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    Analytical studies are carried out on identical samples on the safety of tattoos and permanent make-up in different laboratories to verify each laboratory’s provided input for the preparation of related restriction ability to quantify, for example, the amount of proposals by the Chemicals Agency of the European prohibited substance, and to ensure that test Union (ECHA). results are comparable across Europe. The EDQM PTS programme is designed as a benchmarking tool Communication with partners and for study participants, it allows them to share their stakeholders expertise and improve their technical skills in the field of analytics. ■ Representatives of the EU Commission, its Joint Research Centre (JRC) and EFSA attend the ■ The amounts of parabens found in lipsticks were meetings of Steering Committees and subordinate the focus of this activity in 2017. Testing lipsticks Working Groups. The EDQM exchanges views on can be challenging since colourants, waxes, oils and market surveillance with the Working Groups of the other ingredients can interfere with the quantification EU PEMSAC (Platform of European Market Surveillance of parabens when using High Performance Liquid Authorities for Cosmetics of the European Union) and Chromatography (HPLC). notably, in response to a great number of products that do not comply with the European regulations Food contact materials and articles on cosmetics. The long-standing experience with the ■ Throughout 2017, the Committee of Experts OMCL Network is an asset for the coordination of the on Food Contact Materials (P-SC-EMB) continued OCCL Network. to review resolutions and technical documents elaborated in the past; the Federal Institute for Risk Publications and website Assessment (BfR) of Germany and the Agency for Health and Food Safety (AGES) of Austria both hosted ■ To facilitate the work of control laboratories, expert meetings aimed at updating the provisions reliable and reproducible analytical procedures for for materials such as printed paper and paperboard. cosmetics can be downloaded free of charge from the EDQM website (e.g. method for the determination ■ Food contact materials made from metals and of free formaldehyde and of hydrogen peroxide in alloys have been addressed in a practical guide cosmetics16). for manufacturers and regulators, which was first published in 2013. Amendments have been foreseen ■ The guide “Safer tattooing” provides an overview on the work programme in 2017 and will be included of current knowledge and challenges of toxicological in the second edition of assessment16. A dedicated webpage on this topic can Metals and alloys the guide. To this end, an be found on the EDQM website17. used in food contact materials and articles ad-hoc working group, composed of experts from A practical guide for manufacturers and regulators SAFER TATTOOING competent authorities, Overview of current knowledge and challenges official and private control of toxicological assessment laboratories and industry, held two meetings in 2017; European Committee of 2013 1st Edition Directorate for the Quality of Medicines & HealthCare both were hosted by the Experts on Packaging Materials for Food and Pharmaceutical Products  P-SC-EMB Scientific Institute of Public Health (known as WIV-ISP) Consumer Health Protection Committee (CD-P-SC) EDQM 1st Edition 2017 of Belgium. ■ The EDQM, national authorities and the Food Ingredients and Packaging (FIP) Network coordinated by the Food Safety Authority of the European Union (EFSA) joined forces and defined a work programme to ensure the safety of coatings that are used in food packaging such as beverage cans. This work is expected to be finalised in 2019. Tattoos and permanent make-up ■ In order to implement the recommendations of Council of Europe Resolution ResAP(2008)1, the EDQM compiled safety and documentation requirements for 16. The EDQM publications are available here: tattoos and permanent make-up in a report which https://register.edqm.eu/freepub was finalised and published in 2017. The EDQM work 17. https://go.edqm.eu/tattoospmu Page 28 ► Annual report

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    Quality management system I nvestment in EDQM’s quality management system continued to be a priority in 2017, with the ISO 9001 first surveillance audit according to the 2015 version of the standard, and the surveillance audit of the laboratory ISO 17025:2005 accreditation. The ISO 17025 technical scope has been extended with eight “limit tests” such as acid value (Ph. Eur. 2.5.1.) and iodine value (Ph. Eur. 2.5.4.), in addition to analytical 493-TEST techniques already covered. The EDQM is committed not only to maintaining, but also to continuously improving its standards for quality throughout all its activities; its customers and stakeholders can rest assured that the goods and services provided are of consistent quality. ► Page 29

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    2017: A year rich in events and meetings ■ The conference was held under the Czech Republic’s Chairmanship of the Committee of Ministers SYMPOSIA AND WORKSHOPS - of the Council of Europe. The EDQM is grateful to the FOCUSED TOPIC MEETINGS Czech authorities, in particular the Ministry of Health and the State Institute for Drug Control (SUKL), for their support and assistance in preparing this event. International conference on the place of the Certification Procedure in the global regulatory environment International Microbiology Symposium (19-20 September, Prague) (10-11 October, Strasbourg) ■ With the EDQM’s Certification Procedure ■ In October, the EDQM organised a symposium becoming increasingly used worldwide, this two- on microbiology in the pharmaceutical sector. The day conference was aimed at keeping authorities and aim of this event was to gather feedback from users manufacturers alike informed of recent developments of the Ph. Eur. on alternative testing methods for and of its future in the global regulatory environment. microbiological control and sterilisation processes. The conference was attended by 175 participants ■ Among topics covered was the use of modern from all continents. methods for microbiological control, with specific ■ The programme covered the experience of sessions focusing on sterilisation and biological European regulators and trade associations from indicators, rapid microbiological methods and control Europe, China and India, as well as international methods for cell therapy products and pharmaceutical initiatives and the use of CEPs by authorities beyond water. Reports on successful new methods gave an Europe. The conference also included dedicated overview of the potential benefits in terms of costs workshops that focused on specific aspects of the and time efficiency and, most importantly, in terms Certification procedure, such as the content of a CEP of quality. Authorities, manufacturers and suppliers application, the change to electronic submissions, and of new technologies also discussed the current information on GMP (Good Manufacturing Practices) acceptance of these new methods at regulatory level inspections. across the world. Participants in the international conference on the certification procedure, Prague (Czech Republic) ► Page 31

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    TRAINING SESSIONS ■ The EDQM organised two European Pharmacopoeia specific training sessions last year. The first focused on biologicals and enabled participants to expand their knowledge on the work and procedures of the Ph. Eur. on the topic. Specific workshops were organised in the programme on various classes of biologicals (e.g. biotherapeutic products including monoclonal antibodies, vaccines for human use, plasma-derived products and synthetic peptides) Participants in the International Symposium on based on real case studies. Microbiological control, Strasbourg (France) ■ In addition participants were given the ■ During the symposium, a consensus emerged opportunity to attend a Joint EDQM/EMA Satellite among participants that alternative methods for Meeting on Biosimilars. The Ph. Eur. has driven the detection, enumeration and identification the setting of quality standards for biotherapeutic of microorganisms are at present sufficiently well products in Europe for more than two decades. The covered in Pharmacopoeias world-wide. General aim of this meeting was to clarify the role that the agreement was also reached that developments Ph. Eur. monographs play in the assessment and in Pharmacopoeias now allow manufacturers of marketing authorisation of a biosimilar medicine at medicines to start using modern technologies for European Union level. The event and the Q&A session effective microbiological control. that followed were broadcast live on the internet, thus allowing greater visibility, reach and engagement with ■ The symposium was attended by a wide range concerned stakeholders. of experts in the pharmaceutical and microbiological fields who reviewed the latest trends and innovations in ■ The second training focused on European the field of microbiology, in addition to pharmacopoeial regulations for medicines, references standards approaches and related regulatory requirements. and the certification procedure and its inspection programme. Participants had the opportunity to ask Workshop for National Focal Points questions directly to EDQM experts. on Transplant Related Crimes (9-10 ■ The sessions were recorded and the videos made November, Strasbourg) available on the EDQM website18. ■ The EDQM organised the 2nd workshop for National Focal Points (NFP) on transplant related WEBINARS crimes. The aim was to examine the data collected ■ Webinars are an important tool for reaching out through the ”International Travel for Transplantation” to the EDQM’s stakeholders who benefit from detailed database on patients who received organ transplants information on the EDQM’s expertise and activities, abroad and later returned to their country of origin while being able to express their needs and challenges to receive follow-up care. The initiative is essential directly to the EDQM and without having to travel. to cast a light on the phenomenon of travel for transplantation and will allow looking into ensuring ■ Two webinars were organised on “Elemental comprehensive support against transplant-related Impurities: Implementation of ICH Q3D”, in January crimes and to victims and patients. (See the “Organ and May. The ICH Q3D guideline, which establishes transplantation and tissues and cells for human acceptable safety limits for elemental impurities and application” chapter, page 25). applies to new finished medicines, as well as new medicines containing existing active substances, has been applicable since June 2016. The webinars Conference “Sharing Best practices: illustrated the impact of the guideline on the texts of Quality Risk Management, Change the Ph. Eur. and on the assessment of CEP applications Control, Validation and Qualification” and introduced a number of practical case studies (17-19 October, Strasbourg) providing users with greater understanding of ■ The conference was an opportunity for the requirements in the guideline. A total of 1 700 exchanging on these topics and on their practical participants connected to these webinars. implementation, and also a way of supporting BEs ■ A webinar was also organised on raw materials in implementing the Good Practice Guidelines for cell-based and gene therapy products; it provided (GPG). Proceedings, including recommendations and conclusions, will be issued in 2018. (See the “Blood 18. Training resources available here: Transfusion” chapter, page 23). www.go.edqm.eu/pheurtraining Page 32 ► Annual report

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    participants with an insight into the context of the f AESGP Meeting (AEGSP Association of the elaboration of the new Ph. Eur. general chapter on European Self-Medication Industry), (Belgium), “Raw materials of biological origin for the production f 20th Annual Meeting of the Israel Analytical of cell-based and gene therapy medicinal products” Society, (Israel), and its scope. Topics covered included an introduction f 9th European Paediatric Formulation Initiative to the general Ph. Eur. chapter 5.2.12 and its place Conference, (Poland), within the EU regulatory Network, the context of its elaboration, and an overview of the raw materials of f 9th NIFDC National Drug Reference Standards biological origin covered by the chapter. Committee (China), f 6th International Conference on Reference ■ Another webinar focused on the Certification Materials (China), Procedure and more specifically on “How to get acceptance of CEP revisions quickly”. The way to use f 8th International Meeting of World the “Guideline on requirements for revisions and Pharmacopoeias in Brasilia (Brazil), hosted by renewals” was explained, the different categories of the Brazilian national health agency ANVISA, changes and the supporting documentation required, f 19th Annual Conference PharmMed Obrashenie best practices and the do’s and don’ts when preparing (Russian Federation). a revision application. This webinar attracted a lot of interest with over 750 participants joining in. ■ The EDQM and EMA organised a joint webinar on “Water for Injections (WFI)”, focusing on the recently updated Ph. Eur. monograph for WFI and progress made towards the elaboration of additional guidance on GMP requirements for WFI production by non- distillation methods and biofilm control strategies. This webinar was specifically targeted towards regulators from all EEA National Competent Authorities (NCAs) and to Pharmaceutical Inspection Co-operation Scheme (PIC/S) participating authorities. ■ Live Q&A sessions followed each of the webinars, allowing delegates to raise specific issues covered in the presentations. All webinar recordings were posted on the EDQM website and made available INTERNATIONAL FAIRS & CONGRESS for later access.19 – EXPANDING GLOBAL PRESENCE ■ The EDQM participated in three pharmaceutical PARTICIPATION IN KEY fairs in 2017, namely CPhI China (Shanghai), CPhI INTERNATIONAL MEETINGS Worldwide (Frankfurt) and CPhI India (Mumbai). These specialised tradeshows bring together a ■ In 2017, the EDQM took part in several major whole spectrum of chemical and pharmaceutical international meetings and events worldwide, industries - every sector of the pharmaceutical market including: is represented under one roof. Hence they provided f Indian Pharmaceutical Association (IPA) the EDQM with a one-stop-shop for engaging with Conference: “Towards excellence in Quality”, existing clients and partners, along with meeting and (India), growing a new audience. f Annual Conference of International ■ In addition, the EDQM participated in the 27th Pharmaceutical Excipients Council (IPEC), Regional Congress of the International Society of Blood (Monaco), Transfusion (ISBT) which was held in Copenhagen f 22nd Congress of the European Association of (Denmark). The Congress was organised in conjunction Hospital Pharmacies (EAHP), (France), with the 35th Annual Conference of the British Blood f Meetings of the ICH Assembly and Expert Transfusion Society. The event attracted healthcare Working Groups, (Canada and Switzerland), professionals involved in blood transfusion and transfusion medicine to discuss state of the art topics f China Chamber of Commerce for Import and in the field of transfusion medicine. The latest edition Export of Medicines and Health Products of the Blood Guide was presented at the fair and (CCCPMHPIE) symposium, (China), visitors were able to collect information on the EDQM’s 19. Training resources available here: activities in this area and learn more on the EDQM’s www.go.edqm.eu/pheurtraining Blood-PTS Scheme and Blood Quality Management and here: www.go.edqm.eu/CEPtraining Programme (B-QM). 2017: A year rich in events and meetings ► Page 33

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    ■ A delegation from the Brazilian Pharmacopoeia interested in the working policies of the Ph. Eur. Commission visited the EDQM in Strasbourg to strengthen the collaboration between the two Pharmacopoeias. On the occasion, the Brazilian Pharmacopoeia representatives were given a tour of the EDQM’s laboratory facilities. ■ The Shandong Food and Drug Administration The Eurasian Economic Commission visit, Strasbourg and the China Institute of Veterinary Drug Control (IVDC) were at the EDQM to establish preliminary grounds for international exchanges and cooperation VISITS in the field of medicines quality. The visits were an The Eurasian Economic Commission visit, Strasbourg opportunity for the EDQM and the Chinese Authorities to become familiar with their respective missions. ■ A high-level delegation of the Eurasian Economic Commission (EEC), headed by the Minister for Technical Regulation of the EEC, Valery Nikolaevich Koreshkov, PUBLIC AWARENESS CAMPAIGNS visited the EDQM in November 2017. Discussions included the collaboration between the Eurasian Organ, Cells and Tissue Transplantation Economic Union Pharmacopoeia and the Ph. Eur. and ■ The 18th European Day for Organ Donation and other topics of common interest. Transplantation (EODD) took place on 9 September in ■ The EDQM Certification Department received Bern (Switzerland). The EDQM run a campaign in the the visit of officials from ANVISA (Brazil), and from the months leading up to the EODD; it was based on the Saudi Arabia Food & Drug Administration respectively, theme “Bring back hope to the thousands of patients in 2017. Visitors were given an overview of the on waiting lists in Europe!”. Activities included the assessment and inspection activities related to the production of posters, videos and infographics, as Certification (CEP) procedure; the visits were also an well as social media presence with a new Facebook opportunity to strengthen the collaboration between account showcasing the EDQM’s own activities, as well EDQM and these authorities. as those of national competent authorities, in the field of organ, cells and tissue donation and transplantation. ■ In April, the EDQM received a delegation from the Swiss competent authority Swissmedic interested Blood Transfusion in learning more about the EDQM and the general ■ On the occasion of World Haemophilia Day working policies of the Ph. Eur. Commission. 2017, the EDQM hosted an event, organised by the ■ The European Union Commissioner for Health European Haemophilia Consortium (EHC). The focus & Food Safety, Vytenis Andriukaitis, came for an was on an important set of new recommendations official visit to the EDQM on 13 June to participate in a directed at improving haemophilia care and treatment roundtable on the on-going cooperation in protecting throughout Europe. public health between the EDQM and the Commission ■ Two blood donor sessions were also organised of the European Union, a signatory party to the Ph. Eur. by the EDQM for Council of Europe staff and their Convention since 1994. Topics covered the role of the families, in order to raise awareness on blood donation OMCLs, blood transfusion and organ transplantation. among staff based in Strasbourg. The EU Health & Food Safety Commissioner Vytenis Andriukaitis visiting the EDQM Page 34 ► Annual report

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    List of committees coordinated by the EDQM THE EUROPEAN PHARMACOPOEIA COMMISSION ■ The Ph. Eur. Commission was set up in 1964 in accordance with the Convention on the Elaboration of a European Pharmacopoeia. The Commission has 39 members, all signatory parties to the Convention NETWORK OF OFFICIAL MEDICINES (38 Member States and the European Union). Also, CONTROL LABORATORIES 29 observers from all over the world confirm the ADVISORY GROUPS importance of the work of the Ph. Eur. Commission ■ The role of this Network is to ensure that the at international level. The Commission sets out the quality of medicines marketed in the Member States work programme and adopts the quality standards is consistent; this also happens through the mutual for medicines and their components to be applied recognition of results of the processes for the control in the territories of its member states. A total of 61 of medicines quality. Major decisions are taken expert groups and working parties established by the during the annual plenary meetings of the OMCL Commission carry out the Ph. Eur. work programme. Network. Advisory groups prepare and ensure the The texts are regularly revised in order to keep pace implementation of the annual work programme. There with the latest technical and scientific advances in are two levels of collaboration within the Network: the development, production and quality control of medicines. The Ph. Eur. is essential for the protection f general activities involving all of the Member of public health. It is intended for use by healthcare States of the Ph. Eur. Convention and the professionals working with medicines, and has observer states. These activities cover work become the gold standard reference in the sector. in the area of quality management systems (QMS), such as audits and proficiency testing studies, as well as market surveillance studies THE BIOLOGICAL STANDARDISATION and contribute towards combating counterfeit PROGRAMME (BSP) and illegal medicines. General activities are STEERING COMMITTEE prepared and followed by the General OMCL ■ The BSP focuses on the standardisation of Advisory Group; and, the methods and tools for the quality control of f activities restricted to the EU and the European biologicals by establishing reference standards and Economic Area (EEA), and concerning products validating new methods with particular focus on approved via the centralised procedure and the reducing, refining and replacing the use of animals mutual recognition or decentralised procedure (3Rs initiative). These activities are supervised by the (MRP/DCP) and the Official Control Authority BSP Steering Committee which is composed of the Batch Release (OCABR) system for biological chairs of Ph. Eur. Groups of Experts 6 (Biological and products (human and veterinary). The latter biotechnological substances), 6B (Human plasma and activity also involves Switzerland and Israel plasma products), 15 (Human vaccines and sera), 15V (for human vaccines only). For the CAP and (Veterinary vaccines and sera) as well as co-opted the OCABR activities, advisory groups ensure experts and delegates from the EU Commission, EMA, continuity of operations in the interval between BWP, IWP and WHO and the EDQM Director. the annual meetings of each specific network. ► Page 35

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    CERTIFICATION OF SUITABILITY EUROPEAN COMMITTEE ON TO PH. EUR. MONOGRAPHS PHARMACEUTICALS AND STEERING COMMITTEE PHARMACEUTICAL CARE ■ A Network of about 100 assessors and 30 national ■ This Steering Committee (CD-P-PH) is in charge of inspectors participates in the work required for the activities in the field of the classification of medicines evaluation of API quality dossiers and the inspection as regards their supply, pharmaceutical practices and of manufacturing sites. The activities associated with pharmaceutical care, and combatting falsified medical the procedure for certification of suitability to Ph. Eur. products and similar crimes. It is supported by its monographs are guided by a Steering Committee subordinate committees: the Committee of Experts and 3 Technical Advisory Boards (TAB). This Steering on the Classification of Medicines as Regards their Committee is composed of representatives of Supply (CD-P-PH/PHO); the Committee of Experts European licensing authorities and inspectorates. on Quality and Safety Standards for Pharmaceutical It takes decisions on general policy, examines and Practices and Pharmaceutical Care (CD-P-PH/PC); and comments on matters brought to its attention by the the Committee of Experts on Minimising Public Health Technical Advisory Boards, adopts guidelines and the Risks Posed by Falsification of Medical Products and inspection programme and co-ordinates questions Similar Crimes (CD-P-PH/CMED). amongst the represented parties. It is also responsible for appointing assessors, as well as the members of EUROPEAN COMMITTEE ON the Technical Advisory Boards and their Chairs. CONSUMER HEALTH PROTECTION ■ In 2017, the Steering Committee (CD-P-SC) was EUROPEAN COMMITTEE ON responsible for managing work programmes and BLOOD TRANSFUSION decision-making processes in the areas of cosmetics ■ This Steering Committee (CD-P-TS) addresses and food contact materials. The Committee examined ethical, legal and organisational issues related to health-related issues, evaluated their risks and blood transfusion, in order to ensure the safety and drafted reports and recommendations for regulatory quality of transfusions and the protection of donors approaches. Two sub-committees supported the work: and recipients, and to promote the optimal use of the Committee of Experts on Food Contact Materials blood and minimal wastage. It supervises the work of (P-SC-EMB) and the Committee of Experts on Cosmetic a number of individual projects and working groups, Products (P-SC-COS). At the end of term, the CD-P-SC e.g. the European database of Frozen Blood of Rare was dissolved and separate committees established Groups, Plasma Supply Management and the ad hoc for the two activity areas, based on the corresponding Working Group on the Guide to the Preparation, Use decision of the Committee of Ministers. The work and Quality Assurance of Blood Components. programme of the subordinate Committees of Experts will be pursued under the new structure. EUROPEAN COMMITTEE ON ■ In addition, the European Network of Official ORGAN TRANSPLANTATION Cosmetics Control Laboratories (OCCLs) contributes to consumer health protection and supports market ■ This Steering Committee (CD-P-TO) focuses on surveillance activities of the competent authorities. elaborating and promoting the principle of non- The Network was set up on a voluntary basis; more commercialisation of organ, tissue and cell donation, than 40 OCCLs participate in regular Network strengthening measures to avoid trafficking and activities, including laboratories in Member States elaborating high ethical, quality and safety standards of the European Union. Besides the EU, participation is in the field of transplantation. It supervises the open to other Council of Europe states having signed activities of a number of individual projects and the the Convention on the Elaboration of a European ad hoc Working Groups on the “Guide to the Quality Pharmacopoeia. and Safety of Organs for Transplantation” and the “Guide to the Quality and Safety of Tissues and Cells for Human Application”. Page 36 ► Annual report

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    Glossary 3Rs Refine, Reduce, Replace (animal testing) AAV Adeno-Associated Virus ANVISA Brazilian National Health Agency B-MJA Blood Mutual Joint Audit B-MJV Blood Mutual Joint Visit B-PTS Blood Proficiency Testing Scheme B-QM Blood Quality Management B-TV Blood Training Visits BE Blood Establishment BRP Biological Reference Preparation BRR Biological Reference Reagents BSP Biological Standardisation Programme BWP Biologics Working Party CAP Centrally Authorised Product CD-P-PH European Committee on Pharmaceuticals and Pharmaceutical Care Committee of Experts on Minimising the Public Health Risks Posed by CD-P-PH/CMED Falsification of Medical Products and Similar Crimes Committee of Experts on Quality and Safety Standards in Pharmaceutical CD-P-PH/PC Practices and Pharmaceutical Care Committee of Experts on the Classification of Medicines CD-P-PH/PHO as Regards their Supply CD-P-SC European Committee on Consumer Health Protection CD-P-TS European Committee on Blood Transfusion CD-P-TO European Committee on Organ Transplantation CEP Certificate of Suitability to the Monographs of the European Pharmacopoeia CHMP Committee for Medicinal Products for Human Use (EMA) CM Committee of Ministers CRS Chemical Reference Substance CVMP Committee for Medicinal Products for Veterinary Use (EMA) DCP Decentralised Procedure DH-BIO Council of Europe’s Committee on Bioethics EAHP European Association of Hospital Pharmacists EBMT European Society for Blood and Marrow Transplantation EDQM European Directorate for the Quality of Medicines & HealthCare EEA European Economic Area EFSA European Food Safety Authority ► Page 37

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    EMA European Medicines Agency EODD European Day for Organ Donation and Transplantation ESHRE European Society for Human Reproduction and Embryology EU European Union General European Network of Official Medicines Control Laboratories GEON (OMCLs) GMP Good Manufacturing Practice GPhP Good Pharmacopoeial Practices GTP Gene Therapy Products International Council for Harmonisation of Technical Requirements for ICH Pharmaceuticals for Human Use ICRS International Chemical Reference Substance ISA International Standard for Antibiotics ISBT International Society of Blood Transfusion International Organization for Standardization/International ISO/IEC Electrotechnical Commission IWP Immunologicals Working Party JP Japanese Pharmacopoeia MAA Marketing Authorisation Applications MAB Monoclonal Antibody MJA Mutual Joint Audit MJV Mutual Joint Visit MRP Mutual Recognition Procedure MSS Market Surveillance Studies NMR Nuclear Magnetic Resonance NPA National Pharmacopoeia Authorities OCABR Official Control Authority Batch Release OCCL Official Cosmetics Control Laboratory OMCL Official Medicines Control Laboratory P4 Procedure 4 P-SC-COS EDQM Committee of Experts on Cosmetic Products P-SC-EMB EDQM Committee of Experts on Food Contact Materials PDG Pharmacopoeial Discussion Group Ph. Eur. European Pharmacopoeia PIC/S Pharmaceutical Inspection Co-operation Scheme PTS Proficiency Testing Scheme Q3D Code for ICH Guideline on Elemental Impurities QM Quality Management QMS Quality Management System QWP Quality Working Party (EMA) REACH Regulation (EC) No 1907/2006 SPOC Single Point of Contact (MEDICRIME Convention) Page 38 ► Annual report

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    TAB Technical Advisory Boards TV Training Visits US FDA United States Food and Drug Administration USP United States Pharmacopeia VBRN Veterinary Batch Release Network WFI Water For Injections Working Group of Enforcement Officers of the Health and Medicines WGEO HMA Agencies of the European Union WHO World Health Organization Glossary ► Page 39

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    This publication presents the work carried out in 2017 by the European Directorate for the Quality of Medicines & HealthCare, Council of Europe, highlighting its particular achievements. PREMS 016618 – PRDD-18-01 ENG The Council of Europe is the continent’s leading human rights organisation. It comprises 47 member states, 28 of which are members of the European Union. All Council of Europe member states have signed up to the European Convention on Human Rights, a treaty designed to protect human rights, democracy and the rule of law. The European Court of Human Rights oversees the implementation of the Convention in the member states. European Directorate Direction européenne for the Quality de la qualité of Medicines du médicament & HealthCare & soins de santé

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