EUROPEAN COMMISSION Brussels, 21.4.2016 SWD(2016) 129 final COMMISSION STAFF WORKING DOCUMENT on the application of Directive 2002/98/EC on setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components and amending Directive 2001/83/EC Accompanying the document Report from the Commission to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions on the implementation of directives 2002/98/EC, 2004/33/EC, 2005/61/EC and 2005/62EC setting standards of quality and safety for human blood and blood components {COM(2016) 224 final}

{SWD(2016) 130 final}



Table of contents 1. Introduction 2. Implementation of the EU blood legislation 2.1. General Provisions - Designation of competent authorities 2.1.1. Portfolio of competences of the national competent authorities 2.1.2. Responsibilities of national competent authorities 2.2. Obligations on Member State Authorities 2.2.1. Designation/authorisation/accreditation or licensing of blood establishments 2.2.2. Inspections and control measures 2.2.3. Inspections of blood establishments 2.2.4. Other inspections 2.3. Provisions for Blood Establishments 2.3.1. Responsible person 2.4. Quality management 2.4.1. Quality System for blood establishments 2.4.2. Record keeping 2.5. Haemovigilance

2.5.1. Traceability - Donor identification system 2.5.2. Notification of serious adverse events and reactions 2.5.3. Import/export 2.5.4. Shortages and surplus of blood and blood components 2.5.5. Cross-border movement of Donors 2.6. Quality and safety of blood and blood components 2.6.1. Provision of information to prospective donors 2.6.2. Information required from blood donors and examination of blood donors 2.6.3. Eligibility criteria for donors of whole blood and blood components 2.6.4. Testing of Donations 2.6.5. Storage, transport and distribution conditions 2.6.6. More stringent measures 2.7. Exchange of information, reports and penalties 2.7.1. Penalties 2.7.2. Difficulties in transposition or implementation Annex 1: Individual country responses to the survey on the implementation of the EU Blood and Blood Components Directives conducted in 2013 and based on 2012 information A.1.1. Survey response Austria A.1.2. Survey response Belgium A.1.3. Survey response Bulgaria A.1.4. Survey response Croatia

A.1.5. Survey response Cyprus A.1.6. Survey response Czech Republic A.1.7. Survey response Denmark A.1.8. Survey response Estonia A.1.9. Survey response Finland A.1.10. Survey response France A.1.11. Survey response Germany A.1.12. Survey response Greece A.1.13. Survey response Hungary A.1.14. Survey response Ireland A.1.15. Survey response Italy A.1.16. Survey response Latvia A.1.17. Survey response Liechtenstein A.1.18. Survey response Lithuania A.1.19. Survey response Luxembourg A.1.20. Survey response Malta A.1.21. Survey response Netherlands A.1.22. Survey response Norway A.1.23. Survey response Poland A.1.24. Survey response Portugal

A.1.25. Survey response Romania A.1.26. Survey response Slovakia A.1.27. Survey response Slovenia A.1.28. Survey response Spain A.1.29. Survey response Sweden A.1.30. Survey response United Kingdom Annex 2: Fractionation Facilities Annex 3: Number of positive test results in 2012 for HIV, hepatitis B and hepatitis C and the number of laboratories performing donor testing



ABBREVIATIONS EC = European Commission ECDC = European Centre for Disease Prevention and Control EEA = European Economic Area EU = European Union GMP = good manufacturing practices HBV = hepatitis B virus HCV = hepatitis C virus HIV = human immunodeficiency virus HLA = human leukocyte antigen HTLV = human T-cell lymphotropic virus

ISO = International Standards Organisation NAT = nucleic acid amplification test NCA = national competent authority RAB = Rapid Alerts for Blood SAE = serious adverse event SAR = serious adverse reaction SARE = serious adverse reactions and events SOP = standard operating procedures Member State and country codes: http://publications.europa.eu/code/en/en-370100.htm



1.Introduction This Staff Working Document summarises the results of a questionnaire survey of Member States on the implementation of the EU blood legislation. The survey was conducted in 2013 and the data reported was from 2012. Replies were sent to the Commission by the 28 Member States, Liechtenstein and Norway (Annex 1). The quality of reporting and information provided by Member States was satisfactory overall, but some answers called for additional clarifications and verifications, which are reflected in this document. Information on the application of the principle of “voluntary and unpaid donation” is summarised in a separate Staff Working Document. These two documents accompany the Report from the Commission to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions on the implementation of Directives 2002/98/EC, 2004/33/EC, 2004/33/EC, 2005/61/EC and 2005/62/EC setting standards of quality and safety for human blood and blood components. 2.Implementation of the EU blood legislation Overall, the implementation of the EU blood legislation by Member States is considered adequate. However, many Member States' experts reported difficulties in the interpretation of its scope. In particular, the inclusion of the donation, procurement and testing of blood and blood components 'whatever their intended use' in Article 2 on the scope of Directive 2002/98/EC has raised some questions for blood competent authorities, because it potentially extends the scope beyond transfusion. While it is clear that if the blood or blood components are for the purposes of transfusion, then the processing, storage and distribution are within the scope of the legislation, a number of questions for clarification have been raised at the competent authority meetings on scope issues. As the legislation in question does not provide a basis for full harmonisation, there are many differences between Member States in the approaches they have taken to implementation. These differences facilitate successful integration of the requirements into national legislation but in some cases they may limit the possibilities for sharing of resources, including blood and blood components themselves. 2.1.General Provisions - Designation of competent authorities Under Article 4(1) of Directive 2002/98/EC, Member States must designate the competent authority or authorities responsible for implementing the requirements of the Directive. All 28 Member States plus Norway and Liechtenstein have designated a competent authority in accordance with this provision.

In 16 Member States (AT, BE, BG, CY, DK, EE, ES, HR, HU, IE, LU, LV, MT, RO, SI and UK) plus Liechtenstein, there is one designated national competent authority. In nine Member States (CZ, DE, FI, FR, IT, LT, NL, PT and SK), there are two competent authorities at national level. In three Member States (Greece, Sweden, Poland) plus Norway, there are three. More than one competent authority exists in particular where oversight is divided between various activities or types of substances. 2.1.1.Portfolio of competences of the national competent authorities Four Member States (EL, ES, LT and LU) reported that their competent authorities were empowered solely for blood and blood components. Figure 1 shows the additional areas of competences of the competent authorities responsible for blood and blood components. Some Member States reported that their competent authorities have further specific competences, e.g. for: cosmetic products, veterinary products (France, Ireland); tattoo inks, biocides, ancillary products, human breast milk (France); clinical trials approval, protection of animals (Ireland). Comments All Member States have appointed competent authorities for blood, which can be considered satisfactory. It is for the Member States to decide on the organisational set-up of their authorities and the designation of different oversight responsibilities. In most countries, national competent authorities for blood and blood components are also competent for other sectors (primarily tissues & cells, organs, pharmaceuticals and medical devices). 2.1.2.Responsibilities of national competent authorities There is diversity in the responsibilities assigned to (each of) the designated competent authority(ies) as represented in Table 1. Role/ tasks of national competent authorities* NCA1, NCA2, NCA3 Authorisation/ Designation/ Accreditation/Licensing Inspection Haemovigilance Others AT NCA1 NCA1 NCA1 BE NCA1 NCA1 NCA1 BG NCA1 NCA1 NCA1 CY NCA1 NCA1 NCA1 NCA1 CZ NCA2, NCA2 NCA2 NCA1; NCA2 DE NCA2 NCA1;NCA2 NCA1; NCA2 NCA1 DK NCA1 NCA1 NCA1 NCA1 EE NCA1 NCA1 NCA1 EL NCA1 NCA2 NCA1; NCA2; NCA3 ES NCA1 NCA1 FI NCA1 NCA1 NCA1 FR NCA1 NCA1 NCA1 NCA1; NCA2; HR NCA1 NCA1 NCA1 HU NCA1 NCA1 IE NCA1 NCA1 NCA1 NCA1 IT NCA2 NCA1; NCA2 LI NCA1 NCA1 NCA1 LT NCA2 NCA1, NCA2 NCA1 NCA1 LU NCA1 NCA1 NCA1 LV NCA1 NCA1 NCA1 MT NCA1 NCA1 NCA1 NL NCA1 NCA2 NO NCA1 NCA2; NCA3 NCA1 NCA1 PL NCA1 NCA2 NCA2 NCA2; NCA3 PT NCA1 NCA1 NCA2 RO NCA1 NCA1 NCA1 NCA1 SE NCA1; NCA2 NCA1; NCA2 NCA1 NCA2; NCA3 SI NCA1 NCA1 NCA1 SK NCA1 NCA2 NCA2 UK NCA1 NCA1 NCA1

*NCA1 – National Competent Authority 1 *NCA2 – National Competent Authority 2 *NCA3 – National Competent Authority 3 National competent authority 1 (NCA 1) In 22 Member States plus Norway, the NCA1s are responsible for designation, authorisation, accreditation and/or licensing of blood establishments, for inspection in 22 Member States plus Liechtenstein and for haemovigilance in 20 Member States plus Norway and Liechtenstein. Many Member States and Norway mentioned that NCA1 has additional functions and responsibilities: Coordination of blood services/donation/transfusion (EL, IT, LT, RO, SK); National guidelines, implementation of national legislation, policies, legal matters (BG, CZ, DK, EL, IE, ES, IT, RO); Import and export of blood components (ES, IT, RO, SK, CZ); Personal data protection (EL, SK); Recalls of blood components (EL, IE). National competent authority 2 (NCA2) The second competent authorities (NCA2) have one or more responsibilities that differ among countries. In seven Member States, the NCA2 is also responsible for haemovigilance. Six Member States plus Norway mentioned inspection as a main task of NCA2. Four Member States reported designation, authorisation, accreditation and licensing of blood establishments as a main task of NCA2s. Some Member States reported NCA2s being responsible for other tasks such as: Epidemiological surveillance of transfusion transmitted infections (EL); Coordination and control of national and European provisions, monitoring actions, production of guidelines for quality, safety and appropriate use of blood resources, education and qualification of blood inspectors (IT, SK); Pharmaceuticals and medical devices (SE, SK); Quality of practices and ethics, health policy, elaboration of legislation proposals, supervision of health agencies (FR); Supervision of hospital blood banks (FI, SK, CZ). National competent authority 3 (NCA3)

In three Member States (Greece, Sweden, Poland) plus Norway, there are three NCAs: PL mentioned that NCA3 is responsible for legal issues, data collection, emergencies, budget and funding issues as well as contract management with different blood establishments; SE reported that NCA3 is responsible for legislative matters; In PL, the main task of NCA3 is organisation and financing; NO specified inspection as a main task of the NCA3. Member States with federal or decentralised systems In Member States with federal or decentralised systems (IT, DE, HU, ES), the regional competent authorities are responsible for designation, authorisation, accreditation, or licensing of blood establishments, inspection and haemovigilance. Germany explained that the regional competent authorities are entrusted with supervision and continuous monitoring of compliance with legal provisions. For these purposes, regional authorities grant authorisations of blood establishments and organise inspections. Finland reported that the national competent authority (Valvira) and the six regional state administrative agencies supervise hospital blood banks as a part of other healthcare service providers. Relations between National and Regional Competent Authorities Five Member States described existing relations between national and regional competent authorities (DE, FI, FR, ES and IT). Germany reported that the national competent authority, the Paul-Ehrlich-Institut (PEI) and the regional competent authorities of the Laender work together on some activities such as inspections, but have different competences. Regional competent authorities are responsible for activities related to Articles 5 and 8 of Directive 2002/98/EC: monitoring compliance with legal provisions and imposing penalties/sanctions. The national authority is responsible for the marketing authorisation of blood products and pharmacovigilance. The German Federal Government and PEI have different roles and responsibilities to the authorities in the regions (Laender). In Finland, the Finnish Medicines Agency (Fimea) has a centralised supervision of blood establishments, while the supervision of hospital blood banks by the National Supervisory Authority for Welfare and Health (Valvira) and the six regional state administrative agencies is decentralised. Supervision is based on agreed programmes as a part of other healthcare services, which provide guidance and manage related licensing activities. Valvira guides the six regional state administrative agencies and local authorities in the areas of health and social care, alcohol administration and environmental health. Spain is divided in 17 autonomous communities or regions. Each of these regions has a competent organisation for implementing health policies and for developing regulations at the community level. In Italy, regional competent authorities are by law entrusted with inspection-based authorisation and accreditation of blood establishments and blood collection units. Inspection programmes and teams are managed by the regional competent authorities, which must include at least one nationally qualified blood inspector. Authorisation and accreditation requirements are defined by national State-Region agreements in compliance with the EU Blood Directives and, where applicable, EU GMPs. The regional blood centres are entrusted, among others tasks, with regional self-sufficiency of blood, components and products, haemovigilance data collection and reporting to the National Blood Centre, regional coordination of blood establishments and blood collection units and interactions with plasma fractionation providers. Comments In half of the countries, all main oversight tasks (inspection, authorisation, vigilance) are handled by a single national competent authority. Where more than one competent authority is involved, and in particular where regional/local authorities perform some of these tasks, it is essential to ensure appropriate coordination and communication between all authorities concerned. To facilitate good regulatory communication between Member States, as well as to comply with the annual reporting requirements to the Commission, a well-informed national coordinating contact is essential, even where competent authority responsibilities are shared among multiple organisations or regions. Irrespective of the organisational set-up in each country, it is important that authorities have appropriate resources at their disposal in order to ensure their independence from industry, from the professional sector and from other influences. In this respect it could be problematic if an expert works for a national competent authority and – at the same time – for a blood establishment. Several countries suggested addressing this e.g., through regional collaborations between competent authorities of multiple countries. Some Member States called for a common reflection on the organisation of national competent authorities. Inadequate staffing, e.g. in the inspection department, can bring other, significant risks in terms of oversight. It is also important that staff are adequately trained, an issue that Member States and the Commission have addressed partially in the past and continue to address through ongoing joint actions. 2.2.Obligations on Member State Authorities 2.2.1.Designation/authorisation/accreditation or licensing of blood establishments

Under Article 5(1) of Directive 2002/98/EC, Member States must ensure that activities relating to the collection and testing of human blood and blood components, whatever the intended purpose, and to their preparation, storage and distribution when intended for transfusion, are undertaken only by blood establishments which have been designated, authorised, accredited or licensed by the competent authority for that purpose. Information provided by Member States Twenty-five Member States plus Norway and Liechtenstein reported that they have a system in place for accreditation/designation/authorisation/licensing of blood establishments and that the responsible NCAs are empowered to give accreditation, designation, authorisation or licences. In particular, Member States reported that blood establishments are provided with an: Authorisation (BG, BE, CZ, ES, DE, DK, FR, HR, IE, NO, SK, SI, UK); Accreditation (PL); Designation (CY, NL); Licence (EE, MT, FI, LT); Authorisation/accreditation (IT); Authorisation/designation (LV, RO); Authorisation/licensing (AT, HU, LI, PT, SE); Authorisation/designation/licence (EL); Authorisation/accreditation/designation/licence (LU). All blood establishments have effectively received a designation, authorisation, accreditation or licence from the competent authorities in 25 Member States (AT, BE, BG, CY, CZ, DE, DK, EE, EL, ES, FI, FR, HR, HU, IE, LT, LU, LV, MT, NL, PL, SE, SI, SK, UK) plus Liechtenstein and Norway. Three Member States were not in a position to confirm that all blood establishments were authorised, licensed, designated or accredited in line with the Directive. They reported the following: IT reported that all blood establishments were authorised according to pre-existing national requirements. The authorisation process of all blood establishments according to the new regulations complying with the EU Directives were expected to be finalised by the end of 2014. By the end of September 2013, 6% of blood establishments had been authorised according to rules set out in EU legislation. The reasons for the delays were: a) lack of homogeneous performance among regions, b) significant demands of the fulfilment of some GMP requirements and c) an excessive number of blood establishments; PT reported that the information on the number of authorised blood establishments was not yet available as some blood establishments were still being evaluated by the new competent authority; RO reported that none of the blood establishments were authorised because the authorisation process had not yet been started, but blood establishments were designated (authorisation to function with a yearly renewal) by Law 282/2005. The reported reasons for the delay were: a) delay in setting up the Government Decision on organisation and functionality of BEs, as set up in Law 282/2005 and b) a need to revise the Order on authorisation of BEs and revise and complete the national standards to ensure the legal basis for verification during inspection. In 2013, an administrative reorganisation was foreseen including of the blood transfusion system.

Inspections, accreditation, authorisation, designation and audit were measures reported by all Member States plus Norway and Liechtenstein to ensure the compliance with the requirements of Article 5(1) of Directive 2002/98/EC. Under Article 5(5), the competent authority or authorities may suspend or revoke the designation/authorisation/accreditation/licence of a blood establishment if it is found to no longer comply with the requirements of the Directives. Revoked authorisations were reported by Greece, Portugal and Liechtenstein: EL reported that authorisations were revoked due to administrative reasons associated with a stepwise centralisation system, starting with the nationwide implementation of NAT testing for HIV, HCV and HBV in September 2008 and followed by the economic crisis and the various structural changes in the national health system (early retirement or suspension of staff, merging of blood services and in certain situations lack of resources delaying procedures); PT mentioned as reasons for revoking authorisations: problems with donor testing, poor compliance with good practices and quality system issues. Comments All Member States fulfil their obligations to have a system of authorisation as laid down in the EU legislation, applied on almost all of the 1,363 reported blood establishments. 2.2.2.Inspections and control measures Inspection Systems Under Article 8(1), Member States must ensure that the competent authority or authorities organise inspections and appropriate control measures in blood establishments. Comprehensive inspection systems were reported to be in place by 27 Member States plus Norway and Liechtenstein. Cyprus explained that the system is not in place due to a lack of trained professionals (four professionals were recently trained under an EU-funded project). In 26 Member States plus Norway these inspections of blood establishments overlap with other inspections schemes as shown in Figure 4. Responsible authorities The following table summarises the competent authorities and departments which are in charge of inspections for each Member State. Country AT BE BG CY CZ CA/ Department Federal Office for Safety in Health Care (BASG) / AGES Austrian Agency for Health and Food Safety Federal agency for medicines and health products FAMHP Executive Director of Bulgarian Drug Agency – inspections direct control CA/Department -“ Control of blood transfusion system”- inspections . Not reported State Institute for Drug Control, Inspection Division, Clinical Practice and Surveillance over Biological Material Processing Country DE DK EE EL ES CA/ Department Regional Competent Authorities and the National Competent Authority – Paul-Ehrlich-Institut (PEI) Sundhedsstyrelsen (Danish Health and Medicines Authority) State Agency of Medicines (SAM), Department of Biologicals For regular inspections National Blood Centre in cooperation with the Regional Health Authorities. Inspections in specific situations and in case of revocation SEYP (Body of Health Inspectors) 1. The Regional Health Authority Inspection Department 2. Accreditation systems - scientific societies (CAT) Country FI FR HR HU IE CA/ Department The Finnish Medicines Agency (Fimea), Supervision and licences -process, Inspectorate -unit. Biological Products Inspection Department and Control Department Ministry of Health Service for blood, tissues and cells inspection National Institute for Quality- and Organizational Development in Healthcare and Medicines National Institute of Pharmacy Inspection department The Compliance Department of the Irish Medicines Board (IMB) Country IT LI LT LU LV CA/ Department Regional health authorities Arzneimittelkontrolle des Amtes für Gesundheit – coordination of inspections delegated to Swissmedic by agreement Special department / unit in charge of inspections and control measures of BEs has not been established. Health Directorate - Inspection Sanitaire State Agency of Medicines. Pharmaceutical activities. Compliance evaluation department Country MT NL NO PL PT CA/ Department The Superintendent of Public Health Health Care Inspectorate Norwegian Board of Health Supervision - Dept of planned inspections and Norwegian Medicines Agency- Dept for inspections and narcotic drugs control Institute of Hematology and Transfusion Medicine (IHTM) – Department of Transfusion Medicine • Direccao Geral de Saude (DGS) -Department of Quality in Health Country RO SE SI SK UK CA/ Department Public Health and Control in Public Health Directorate (PHCPHD)- inspection coordination Public Health County Authority- department of inspection. Health and Social Care Inspectorate: Medical Products Agency: Department of inspection Javna agencija Republike Slovenije za zdravila in medicinske pripomočke (Agency for Medicinal products and Medical Devices of the Republic of Slovenia) Inspection Section of The State Institute for Drug Control. Medicines Inspectorate, Inspection, Enforcement & Standards Division, MRHA

Empowerment The number of full-time inspectors in these competent authorities ranges from 1 to 113. Cyprus, Spain and Lithuania did not provide answers on the number of inspectors. Germany clarified that it was not appropriate to provide the numbers of inspectors since the inspectors typically are based within the regional competent authorities, whereas the Paul Ehrlich Institute, as competent higher federal authority, typically participates with an expert function. Under Article 8(3) of Directive 2002/98/EC, the competent authorities must be empowered to inspect blood establishments, as well as facilities of any third parties on their own territory, take samples for examination and analysis, and examine any documents relating to the object of the inspection. Twenty-five Member States plus Norway reported compliance with this Article. Fig. 5 – Inspector empowerment The answers from Greece and Liechtenstein did not clarify the powers of inspectors. Training and support Member States were asked their views on projects funded by the Commission for training inspectors (Eustite, EUBIS, and CATIE), including participation and usefulness, rating them from 1 (not important) to 5 (essential). Twenty-five Member States, plus Liechtenstein and Norway had sent (or intended to send) their inspectors to the training courses funded by the European Union. The training courses were classified as very good and essential by 21 Member States plus Liechtenstein, and as good by three Member States plus Norway. No Member State considered the training courses as not important and only Austria classified them as sufficient. Denmark justified not sending inspectors for training courses due to lack of human resources, Czech Republic mentioned internal reasons (not specified), France explained difficulties due to ANSM reorganisation (in 2013, one inspector attended one training course) and the United Kingdom cited extensive experience in inspecting blood establishments and third countries since a change in national legislation in 1992. Ten Member States (EE, HR, HU, IE, IT, LV, MT, PL RO and UK) reported international collaboration on inspections with other Member States, such as an inspection of a blood establishment in another Member States, an inspection of a blood establishment in a third country, or responding to requests from other Member States regarding the results and control measures of their own inspections. Twenty-five Member States plus Liechtenstein and Norway use the Council of Europe Guide to the preparation, use and quality assurance of blood components at national level. 18 Member States rated the guide as useful/helpful to excellent. Luxembourg reported that they had plans to use the guide in the future. Comments Whilst overall Member States appear to correctly implement the provisions concerning inspections, a number of Member States reported difficulties related to staffing, which makes it difficult to comply with the required 2-year inspection interval. Many considered that a risk-based approach to inspection scheduling would be more effective and efficient instead of the required 2-year inspection interval. Also there is a need to clarify the basis of an inspection, i.e., desk-based assessments versus on-site inspections. Inspector powers and inspector training were regularly commented upon. The value of international projects, at EU level and co-ordinated by the Council of Europe, are clearly appreciated by most of the competent authorities in order to help maintain an adequate level of training and know-how within the groups of inspectors. 2.2.3.Inspections of blood establishments Inspection Plan

In 17 Member States plus Norway inspections are planned based on a risk-based approach. Number and type of inspections The answers provided by Member States were not detailed enough to perform a complete analysis concerning the number and type of inspections (routine, following serious adverse events or reactions and other) in 2012. However, in 2012, 22 Member States plus Norway reported 775 general system oriented on-site inspections. Cyprus, Hungary, Luxembourg and Liechtenstein reported that no inspections were performed in 2012. Data was not provided by Austria, Belgium and Denmark. Fourteen Member States reported 161 thematic/limited on-site inspections in 2012. Sweden reported 15 desk-based inspections and 79 on-site inspections. Slovenia reported that 15 inspections were performed between 1 January 2008 and 1 December 2012. As set out in the Article 8(4) of Directive 2002/98/EC, the competent authorities must organise inspections and carry out control measures as appropriate in the event of a serious adverse reaction or event (SARE). Nine Member States (BG, DE, EE, FR, HR, IT, LT, PL, RO, SK) reported 21 inspections following a SARE or a suspected SARE. The UK reported that SARE information was considered as a risk indicator when planning and scheduling inspections, but was not necessarily a trigger for an immediate inspection. PL explained that immediate inspections follow every SARE and are analysed by a special team. In 2012, 22 cases were analysed in Poland. Additional information on inspections was provided as follows: BG reported 30 routine and five non-routine (following SARE) inspections in hospitals performing transfusion of blood and blood components as a part of their medical activities; In ES, 24 blood establishments were inspected, of which five were on-site inspections for accreditation and seven for monitoring, 16 ISO Norm 9001 inspections (nine for accreditation and seven for monitoring) and eight “other” without specification; FR reported seven inspections regarding enhancement of the processing of the amotosalen plasma (plasma pathogen reduced/pathogen inactivated), four inspections of haemovigilance organisations and three at mobile collection sessions; LT reported three inspections due to a whistle-blower. Difficulties complying with the required two year intervals when inspecting blood establishments

In the last three years, 559 BEs were inspected at least twice as reported by 20 Member States plus Liechtenstein and Norway. However, CY, EL HR, IT, LU, MT, PT reported that none of their blood establishments were inspected at least twice in the last three years. Half of the reporting countries considered it difficult to comply with the two-year inspection interval required by Article 8(2) of Directive 2002/98/EC. The reasons mentioned by Member States experiencing difficulties were: lack of human resources, current definitions in the EU Blood Directive 2002/98/EC not providing sufficient detail in the description of site activities (e.g. mobile or satellite sites) (Germany) and few results compared to the time and effort invested. Member States who did not report such difficulties quoted a sufficient number of inspectors, inspections performed by more than one competent authority, small numbers of authorised blood establishments and blood banks managed through an accreditation body, and existing adequate resources assigned to inspect the blood establishments. Inspection outcomes Some suspensions of authorisations or closure- of blood establishments were reported in the replies to the survey. No data is available on the number of blood establishments that voluntarily ceased operation or were forced to cease operation for other reasons (e.g. economic). Poland reported the dismissal of one blood establishment director in 2013. Romania reported that four inspections were organised following SARE or the suspicion of SARE. For three of them, it was found that the procedures were compliant with the regulations. For one, administrative measures were imposed due to clerical errors. Four Member States reported having to impose penalties (BG, CZ, LT, SK). It was noted that there is a divergence in criteria for assessment, classification of deficiencies and eventual outcomes of inspections. Comments A move towards a system of risk-based assessment to prioritise establishments to be inspected has been cited as being effective by several Member States. Such systems would be preferred by many instead of, the current legislative requirement to inspect all blood establishments within at most a two-year interval. There is a divergence in criteria for assessment, classification of deficiencies and some Member States called for developing more common definitions of deficiencies and outcomes of inspections. 2.2.4.Other inspections Inspections and control measures of mobile and satellite collection sites Difficulties with inspecting mobile and satellite collection sites every two years, as required by Article 8 of Directive 2002/98/EC, were raised by many Member States, both in the 2013 competent authorities meeting and in response to this survey, due to the high number of existing sites and the definition of ‘mobile site’ not being adequately precise. Some Member States, such as France, the United Kingdom and Belgium, have proposed a risk-based approach to define inspections intervals for these sites and a clarification of the blood establishment definition. France also proposed changes to Article 8 to include specifications regarding mobile site inspections. Inspection approaches for these sites are quite different between Member States. One Member State (Greece) reported having no inspections in place for these sites, while 21 Member States plus Norway reported following a variety of approaches for inspecting mobile/satellite sites: DK, HU, IE, LT, LV, RO, SI, plus NO reported that all mobile sites are inspected every two years although RO clarified that they only inspect fixed sites, not those sites where teams from a blood establishment go with their own equipment;

In AT, at regional level, the sites are inspected based on a risk-based approach; In BE, satellite collection sites are inspected every two years. The mobile collection sites are inspected at a rate of two per province (there are 10 provinces in Belgium plus the region of Brussels); In BG, equipment and documentation are inspected on a regular basis during routine inspections as the mobile team’s staff are considered part of blood establishment personnel. One blood establishment’s satellite site for blood collection was inspected twice in a period of four years, as part of the blood establishment; CZ reported that mobile collection sites are inspected once every four years and satellite collection sites once every two years; DE reported that for satellite collection sites and mobile sites inspection intervals are generally equivalent to routine inspections of the related blood establishments, since the satellite collection sites and the mobile sites are considered to be part of the blood establishment; EE reported that satellite sites have separate authorisations and are inspected at least every two years as blood establishments. Mobile sites are inspected as part of a blood establishment; occasionally on-site inspections are carried out; ES satellite sites are inspected every two years and a sample of the total number of the mobile collection sites is inspected; FI has 18 satellite sites inspected every two years; In FR, the operation and management of the mobile collection site teams and equipment are inspected every two years, as part of the inspection of the reference blood establishment. The premises are inspected as regularly as necessary (less than ten inspected every year); IT reported that the sites are inspected every two years, but a risk-based approach will be introduced; NL reported that mobile sites are inspected randomly without specifying the frequency and intervals; PT reported that the intervals for inspecting those sites are yet to be defined by the new competent authority; SK reported that blood establishments are inspected every two years. Mobile site[s] can be included in this inspection, without clarifying if they are inspected; In the UK, mobile sites are inspected based on a risk-based sampling exercise during the inspection of their associated blood establishment. Plasma establishment inspections In 2012, 253 plasma establishments (a site for the collection of plasma) were inspected in 11 Member States plus Norway. CY, EE, HR, HU, IE, MT, PT, RO and SI reported not having sites for plasma collection. Bulgaria, Spain, Italy and Norway reported that they do not have establishments exclusively performing plasma collection. The United Kingdom reported 16 inspections performed in third countries, as plasma is not collected nationally. Four Member States did not respond. Hospital Blood Bank Inspections Hospital blood banks (HBB) are inspected in 23 Member States plus Liechtenstein and Norway.

In 17 Member States plus Liechtenstein and Norway, the blood national competent authority is involved in the inspections of the HBBs. Ireland clarified that the Irish National Accreditation Board authorises the HBBs with the supervision of the blood competent authority. Comments A significant divergence between national practices emerges as regards the inspection of the 731 mobile units and 534 satellite centres, where an important part of the blood (components) is collected. 2.3.Provisions for Blood Establishments 2.3.1.Responsible person Under Article 9 of Directive 2002/98/EC, blood establishments shall designate a responsible person whose responsibilities and qualifications are defined in paragraphs 1 and 2 of this Article. All Member States plus LI and NO reported having a designated responsible person fulfilling the Article 9 (2) requirements in every blood establishment. In 19 Member States (BE, BG, CY,CZ, DK, EE, ES, FR, HR, IE, LI, LU, LV, NL, PL, RO, SE, SI, SK and UK) plus Norway, the responsible person’s tasks are delegated to other qualified persons where necessary. The competent authorities check the qualifications of the responsible person during inspections. Comments All Member States reported having responsible persons in each blood establishment. The qualifications of the responsible person, and possibly his/her delegates, are verified during inspections. Member States reported the value of Joint Actions and the work of the Council of Europe (CoE) in clarifying common understanding and expectations towards responsible persons, their qualifications and possibilities of delegation, as these can vary between Member States. 2.4.Quality management 2.4.1.Quality System for blood establishments As required by Article 11 (1) of Directive 2002/98/EC and Article 2 (1) of Directive 2005/62/EC, Member States shall take all measures to ensure that each blood establishment and hospital blood bank (Article 6) maintains a quality system based on good practices. All Member States reported that blood establishments and hospital blood banks have a quality system which is verified and strengthened through the following measures: Inspections (AT, BE, BG, CZ, DK, EE, EL, ES, FI, FR, HR, HU, IE, IT, LT, MT, NL, PL, PT, RO, SE, SI, SK, UK plus LI and NO); Audits (IE, LV, PL); Training courses (FR, HR, LV, RO).

2.4.2.Record keeping Under Articles 13 and 14 (3) of Directive 2002/98/EC, Member States must ensure that blood establishments maintain records of the information required in Annexes II and IV. Moreover Articles 14 (3) of Directive 2002/98/EC and 4 of Directive 2005/61/EC require that blood establishments, hospital blood banks or facilities keep data to ensure full traceability for a minimum of 30 years in an appropriate and readable storage medium. As reported, compliance with this requirement is verified through inspections and legal provisions to verify compliance: CY reported that requirements are fulfilled under the responsibility of the responsible person. Nonetheless it was not clear how this is checked by the competent authority; EL replied that for BEs and HBBs without a computerised system, this requirement cannot be fully respected; it is therefore not certain if these requirements are fulfilled in all Greek BEs and HBBs; ES mentioned specific computer systems; UK reported that this is ensured by IT systems, data retention policies and a disposal schedule. The required mediums to store records are paper and electronic forms in 26 Member States, while only electronic forms are required in 2 Member States plus Norway. Liechtenstein requires only paper forms. All countries, except Romania and Norway, considered 30 years an adequate timeframe for data storage. Romania considered this period to be too long due to difficulties foreseen in ensuring archiving space and document management. Comments All Member States report to have quality systems in blood establishments, as well as in hospital blood banks. These are verified during inspections or audits. Member States mentioned the work of the Council of Europe (CoE), which organises regular training on quality management systems, to be helpful to keep these systems in line with legislation and state of the art practice in the sector. While the 30 year data retention period is questioned by some Member States, this time window is in line with general data retention periods in the medical sector. Some Member States do, however, call for a clarification and limitation of what data should be retained. 2.5.Haemovigilance 2.5.1.Traceability - Donor identification system Under Article 14 (1) of Directive 2002/98/EC, Member States must ensure that all blood and blood components, collected, tested, processed, stored, released and/or distributed on their territory can be traced from the donor to the recipient and vice versa. In this regard, Member States are required to implement a donor identification system for each donation and single blood unit and component. Twenty-seven Member States plus Norway reported that a donor identification system was implemented in their countries. There is one national coding system in 18 Member States plus Norway, and multiple systems in nine Member States. Liechtenstein has no system implemented, as they only have autologous pre-deposit donations. All Member States reported that the same rules on traceability apply to blood establishments as well as to hospital blood banks. Member States reported the following policies and donor identification systems: A national donor identification system is in place in CY, CZ, EE, EL, FI, FR, HR, HU, IE, IT, LU, MT, NL, NO, PL, RO, SE, SI, SK, UK;

AT, BE, BG, DE, DK, ES, LT, LV, PT have more than one system implemented. The donor identification systems used are: ISBT 128 (in 16 Member States plus Norway: AT, CY, DE, DK, EE, ES, FI, IE, LT, LV, MT, NL, PL, PT, SE, UK), Codabar (in 2 Member States: Hungary, Slovenia), Codabar plus ISBT 128 (IE) and Eurocode plus ISBT 128 (Germany). Spain reported that 76%, and Belgium that 96%, of blood establishments use the ISBT 128 system. The use of international coding systems by Member States for labelling different blood components is listed in the following figure: Some Member States specified which are the “other” labelled components: granulocytes (DE, HU, IE, PL, SE, SI), cryoprecipitate (Estonia, Poland, United Kingdom), buffy coat (Norway, United Kingdom), neonatal components (Ireland, Poland). Denmark, Portugal and the United Kingdom reported that all blood components are labelled using international codes. Comments The great majority of Member States have implemented international standards for the identification and labelling of blood and blood components. 2.5.2.Notification of serious adverse events and reactions Under Article 15(1), Member States must ensure the notification to the competent authority of any serious adverse events which may influence the quality and safety of blood and blood components and which may be attributed to the collection, testing, processing, storage and distribution of blood and blood components, as well as serious adverse reactions observed during or after transfusion which may be linked to the quality and safety of blood and blood components. The procedures for notifying serious adverse events and reactions are laid down in Commission Directive 2005/61/EC. National vigilance system All Member States except for Hungary reported having a national vigilance system in place. In co-operation with Member States, templates, and practical guidance for their compilation, have been developed by the Commission for annual reporting of serious adverse events and reactions (Directive 2005/61/EC, Articles 5 and 6). This guidance is also used at national level in 24 Member States (AT, BE, CY, CZ, DK, EE, EL, ES, FI, HR, HU, IE, IT, LT, LU, LV, MT, NL, PL, PT, RO, SE, SI, SK, UK) plus Liechtenstein. Bulgaria and Norway reported using national regulations. In 24 Member States (AT, BE, CY, CZ, DK, EE, EL, ES, FI, HR, HU, IE, IT, LI, LT, LU, LV, MT, PL, PT, RO, SE, SI, SK) plus Liechtenstein, the European templates are also used at national level. BG, DE, FR, NL and NO use national templates. In 21 Member States plus Liechtenstein and Norway, there is a dedicated vigilance officer at national level. Member States without an appointed officer gave different reasons for this. Germany explained that each competent authority has a responsible person and there is cooperation between the federal competent authority and the regional competent authorities of the Laender. In Estonia, the same specialist is responsible for haemovigilance, licensing and inspecting blood establishments. In the United Kingdom, there is a team of two haemovigilance officers. Blood establishments reporting SARE in 2012 In 2012, SARE reports were provided by 100% of blood establishments in 19 Member States plus Liechtenstein and Norway, 70-99% of blood establishments in eight Member States and 50-60% of blood establishments in one Member State.

All countries, except United Kingdom and Cyprus, reported having a mandatory procedure for hospital blood banks when reporting SARE to the blood establishments which distributed the blood and blood components, as required by Article 5 (1) of Directive 2005/61/EC. In Cyprus, the hospital blood banks report directly to the Ministry of Health. Root cause analysis of SARE A root cause analysis of SARE is performed in 23 Member States (AT, BE, BG, DE, DK, EE, EL, ES, FI, FR, HR, HU, IT, LT, LU, LV, MT, NL, PL, PT, RO, SI, SK) plus Norway. Cyprus and Liechtenstein explained that they had not performed root cause analyses because no SARE cases had been reported so far. In Czech Republic, Spain and Sweden mentioned that root cause analyses are performed by blood establishments and hospital blood banks. In Ireland, root cause analyses are performed by the National Haemovigilance Office in association with the competent authority. Feedback to blood establishments of SARE reported at EU level Feedback to the blood establishments regarding SARE reported at EU level is given by 23 Member States (BE, BG, CY, CZ, DE, EE, EL, FI, FR, HR, HU, IE, IT, LT, LU, MT, NL, PL, PT, RO, SE, SK, UK) plus Norway. Spain and Norway waited for the publication of the European Commission summary report to share with their establishments. Denmark issue a national yearly Recall procedures Article 15(1) of Directive 2002/98/EC requires blood establishments to have an efficient and verifiable procedure to withdraw distributed blood and blood components associated with the notification of SARE. All Member States plus Liechtenstein and Norway reported to have this in place. In 2012, 1,867 recalls were reported by a total of 14 Member States. Austria and the United Kingdom reported that data was unavailable, Spain reported that data was only available at regional level and Italy reported that recall reporting is not mandatory. Post donation information on donor health which could affect the quality and safety of blood and blood components was a common cause for recalls reported: Country Causes BE In 26 cases, microbiological testing of platelets had been negative at the time of distribution but the samples subsequently became positive resulting in recall. CZ 135 (vast majority - look back procedure for plasma fractionation) EL 1 unit in-date RBCs was recalled, in the case of whole blood platelets transfusion severe WNV encephalitis transmission. The FFP derived from the same blood unit was already transfused in to another patient (who remained WNV asymptomatic). FI 246 recalls in 2012 because of defective product (3), reclamation (complaints?) (164), look back/trace back (9) or deviation in transport temperature (70); over 90% of which were red cells. FR 4 recalls of blood derived medical products were performed as a precautionary measure following the onset of a CJD (sporadic form) in a donor. HU 11 events related with donor. Lyme risk 4 cases, tuberculosis 1 case of acute leukaemia, all cases detected after blood collection. 2 minipools HCV contamination detected by PCR technique by plasma fractionation company, but the infections were not evident in the patients. IE 159 (69.4%) recalls due to post donation information (including abnormal full blood count); 29 (13%) recalls due to suspected bacterial contamination; 33 (14.4%) recalls due to suspected adverse reaction to product; 8 (3.5%) repeated reactive virology test; 3 (1.3%) platelet aggregates; 2 (1%) air in line; 6 (2.6%) others. NL 394 recalls mostly because of withdrawn donations and positive BactAlerts (bacterial contamination suspected) PL Storage – 66 Distribution – 13 Transport – 3 Other (no specify) – 52 PT 122 Total: positive bacterial - 91 blood components; post donation information - 21 blood components; TRALI - 5 blood components; HIV positive - 1 blood component; other - 4 blood component Rapid alerts and blood establishment notification by competent authorities All Member States plus Norway and Liechtenstein reported having a system or procedure to notify blood establishments in case of a rapid alert either at national or at European level via the rapid alert system for blood. Member States were asked to provide information on their systems or procedures (Table 4). Country AT BE BG CY CZ Alert System Information by mail Information note to the BEs by email In July 2011 has been created team (directors and responsible persons from all big blood establishments) for crisis management associated with transmissible infections (WNVD) which reacts in case of a national rapid alert. Information by fax, emails and via telephone to blood centre and blood banks Information on web page of State Institute for Drug Control, and distributed via Medical Society Country DE DK EE EL ES Alert System PEI informs by e-mail the responsible regional CAs of the “Laender” and the graduated scheme officer/ qualified person. Graduated scheme officers are responsible to set up and manage a pharmacovigilance system and to collect and evaluate notifications on medicinal product risks and to co-ordinate the measures A blood establishment contact list is available if it is necessary. State Agency of Medicines(SAM) is responsible to notify all the BEs about the national rapid alert. All BEs have 24 hour phone number to be contacted by SAM .Information send by e mails as written confirmation. Coordinating Haemovigilance Centre (Skae) of the Hellenic Center for Disease Control and Prevention is sending classified mails to BEs. A system similar to RAB is now under construction NCA and the BEs’ responsible person are in touch by e-mail and phone. A mail distribution list is continually updated. An alert system called e-Room, similar to the CIRCA BC platform under development Country FI FR HR HU IE Alert System The national rapid alert procedure secures the transmission of information e.g. between the Finnish Medicines Agency and blood establishments when urgent remedial or precautionary action is needed due to a serious public health threat. Rapid alert system of the EU (CIRCA) for communication with the Commission and Member States -National emailing ,fax and phone calls - If necessary, a national crisis management team (CMT) is activated Blood establishments are notified through network of CA’s inspectors and responsible persons of blood establishments (by mail and fax). The contact person - quality director- get the information from EU, countryside and it will be analysed with the clinical director of the service and coordinates the process. Due to small number of BEs and BBs in Ireland, it is possible for the CA to communicate national rapid alerts via email to all relevant personnel and through use of CA website where required. Country IT LI LT LU LV Alert System Rapid alert is part of the web-based HV system, performed by automated launch of emails to involved parties. Information by fax and phone Information notified via emails and phone calls Direct information from NCA to BE Information not provided Country MT NL NO PL PT Alert System The CA Haemovigilance Unit is responsible for alerting and forwarding both National alerts to the Blood Establishment and other stakeholders establishments on relevant alerts at an EU level received through the CIRCABC system Only one blood establishment in the Netherlands, contacted by CA regularly. There is a standard operating procedure for notifying rapid alerts, and an updated mailing list of contact persons in all BEs. Information on any new focus of infection is reported by the National IHR Focal Point or Main Sanitary Inspectorate to CA. CA informs BEs. email communication send to the responsible persons of blood establishments Country RO SE SI SK UK Alert System Information sent by MoH or Centre for transmissible Diseases (depending on the case) to the NITH and from there to the BEs. If it is the case, BEs inform hospitals in their region. Swedish National Board of Health and Welfare has a 24-hours service, receives all alerts and informs all CA. CAs inform responsible CA as BE/hospital blood banks by e mail and public website. A blood establishment contact list is available to the coordinators at IVO. Ad hoc meeting on BTCS, the short description of alert and actions send to BE. In cases of SARE, CA is informed. Information is reported to State Institute for Drug Control and Ministry of Health. Inspectors of State Institute for Drug Control conduct non- routine inspection and warn Head expert for Transfusion. MHRA would issue alerts by email Alert notification to and from other national vigilance/alert systems Member States were asked if the national blood system notifies, or receives alerts from, other national vigilance or alert systems (e.g., pharmaceuticals or tissues & cells). Cyprus, Estonia, and Latvia reported no notification to or from other national vigilance/alert systems. Slovakia reported not receiving alerts from other national vigilance/alert systems. In Liechtenstein, there is only one national vigilance/alert system. The systems with which information is exchanged by Member States are shown in Figure 21.

Additional questions on traceability and SAR/E reporting Member States were asked for additional questions/ on traceability and SARE reporting. Poland suggested having a more precise and legally binding SAE definition: 'SAE – as only an event which is a real threat as result of improper component being issued for transfusion and SAE – as any event that might have endangered the recipient’s health, even though identified and eliminated according to internal control procedures'. Poland considered that the definition of “serious adverse events” should also include events that had taken place in a hospital laboratory, on a hospital ward or during the transfusion procedure. Simplification of the imputability table related to serious adverse events was suggested as follows: Transfusion-related imputability level: 0 - not assessable; 1 - no relation – there is evidence for attributing the adverse reaction to alternative causes, and; 2 - relation assessed – evidence includes results of diagnostic tests. Comments The relatively large number of blood establishments that do not report SARE requires particular attention. The number of non-reporters leads to the conclusion that annual SARE reporting activities are an underestimate of the real number of SARE, and national efforts should be further scaled up. During the annual presentations of SARE data during the competent authority meetings, national authorities have expressed their interest in further developing the root cause analyses of SARE, which can lead to valuable lessons learned for professionals and possible reductions in SARE numbers. There was a call for common definitions to further harmonise the SARE reporting exercise. Additional questions were brought up on how to involve hospitals in SARE reporting and how to involve local actors in root cause analyses. Competent authorities in this respect welcome the work by the CoE work on guidance and training. Competent authorities also highlight that the current legislation requires reporting of serious adverse reactions in recipients only; even a donor death is not reportable (Directive 2002/98/EC, Article 15). This is despite the definition of a serious adverse reaction in the same Directive (Article 3) that gives equal importance to adverse reactions in donors and in recipients. Many consider that donor protection is to be strengthened through strong legal protection given to living donors, in line with the requirements in the field of organs laid down in Directive 2010/53/EC (Article 15). The national link to the EU rapid alert system for blood and blood components (RAB), set up in 2013, is now well established. 2.5.3.Import/export Member State import rules and regulations Under Article 21, Member States shall ensure that imported blood and blood components intended for use or distribution in the Union are tested in conformity with the Directive’s requirements. In addition, Member Sates shall ensure there is a quality system or equivalent in the stages preceding import (Article 2(3) of Directive 2005/62/EC), as well as a traceability system or equivalent as required under Directive 2005/61/EC. Twenty-two Member States (BE, BG, CZ, DE, EE, EL, FI, FR, HR, HU, IE, IT, LT, LU, LV, MT, NL, PL, RO, SE, SI and SK) plus Liechtenstein and Norway reported having rules in place for authorisation and control of blood and blood components for transfusion, coming from other (EU and third) countries. These rules define the conditions under which such import can take place, or in some cases prohibit such imports. Austria and Denmark reported they have no rules or conditions. Cyprus, Spain and Portugal replied that blood components are not imported for transfusion. The existence of rules to authorise and control import of blood and blood components for fractionation was reported by 17 Member States (AT, BE, BG, CZ, DE, EL, ES, FI, FR, HU, IT, LU, LV, PL, RO, SE and UK). Importation of blood components for transfusion Twenty Member States (BG, CY, CZ, DE, EE, EL, ES, FI, FR, HR, HU, IE, IT, LT, LU, NL, PT, RO, SI, SK) plus Norway reported having data regarding blood components imported for transfusion from third countries (outside the EU). However, only Greece and Ireland reported the import from third countries in 2012: 25,200 red cell concentrates from the Swiss Red Cross Blood Centre to Greece and two red cell concentrates from the USA to Ireland. Importation of plasma for fractionation

Regarding plasma imported for fractionation, 15 Member States (BG, CY, CZ, DE, EE, FI, FR, HR, LT, LU, NL, PT, RO, SE, SI,) plus Norway reported having data on plasma imported for fractionation from third countries. See Annex 2 for information reported on plasma fractionation facilities in Member States. Thirteen Member States (AT, CZ, DK, EE, IE, LT, LU, LV, MT, NL, PT, SI, SK) plus Liechtenstein and Norway do not report having data on imported plasma for fractionation or they do not import it. The national standards in place for verifying the equivalent quality and safety of blood components imported from third countries are listed Figure 22. Regarding “others”, Belgium and the United Kingdom mentioned inspections as the verification method applied. Germany, France, Italy and the United Kingdom reported that equivalent standards to national standards are required. In Sweden, compliance with the Plasma Master File is a requirement in addition to equivalent standards of the Directive 2002/98/EC. Latvia reported that import is not allowed. Testing requirements for import of blood and blood components from third countries going beyond the minimum requirements provided in Annex IV to Directive 2002/98/EC are applied by 15 Member States (BE, CZ, DE, EL, ES, FR, HR, IE, IT, LI, NL, PL, PT, RO, SI, SK) plus Liechtenstein. These include the tests shown in Figure 23. Ireland reported “possibly NAT and perhaps West Nile virus testing” and considered that the issue needs to be discussed with the European blood establishments and ECDC. Export In 2012, only Finland, France and Italy reported export of blood components for transfusion from their Member State to third countries (outside the EU): FI 2 units red blood cells, leucocyte depleted in additive solution Norway FR 200 units of therapeutic lyophilized plasma USA IT 126 red blood cell units Congo, Paediatric Hospital of Kimbondo, for humanitarian aid 70 red blood cell units Republic of San Marino according to bilateral agreement. A majority of Member States reported that they have data on the export of plasma for fractionation in third countries or in other EU Member States. Just six Member States reported data on the export of plasma for fractionation: DE 3,399,419 L Third countries (not specified) DK 214,576 (60,9 metric tons) Switzerland EE 34,196 ‘doses’ of plasma Countries not specified SK 3063 L Ukraine Member States reported the following rules for the authorisation and control of the export of blood and blood components for fractionation to EU Member States or third countries: CY, EL, ES, FR, HR, HU, IE, MT, NL, PT and UK do not export blood components for fractionation; BG limits export to humanitarian aid and production of drugs for their national needs; NL clarified that plasma is only collected for fractionation in the country and is not exported; AT referred to GMP Annex 14;

DE, DK, RO and SK referred to national laws; CZ reported that requirements to export depend on the partner and export is under a MoH export licence; In FI and NO, there are no special rules for the export of blood and blood components for fractionation; In IT, national plasma can only be sent to EU Member States for contract fractionation purposes. This is authorised and controlled by the competent authority (the National Medicines Agency (Agenzia Italiana del Farmaco - AIFA). Commercialisation is strictly prohibited; LI has authorised blood collection by the Austrian Red Cross, section Vorarlberg; LT reported following the requirements of the blood Directives and European Pharmacopoeia (Ph. Eur.) monographs on human plasma-derived products; LV requires a manufacturing licence for the manufacture of medicinal products in another Member State; SI reported that a contract and quality assurance agreement is required; All BEs in SE, that are releasing plasma for fractionation abroad, are inspected and authorised according the same national legislation as applies for use of the plasma in Sweden. Member States reported the following rules for the authorisation and control of the export of blood and blood components for transfusion to EU Member States or third countries: Blood components are not exported for transfusion in AT, CY, EL, ES, HR, HU, LI, LU, MT, PT, SE, UK; Export is limited to emergency situations in BG, IE, DK and SI which allows export to neighbouring countries for immunised patients or for humanitarian assistance; In FI, LT, NO, and PL there are no specific rules; In FR, there is a legislative rule for export of blood components, but no mandatory authorisation procedure. Export is carried out by the civil National Blood Service (EFS), which notifies the competent authority (ANSM); IT reported a national legally binding specific procedure to export blood components for transfusion, which must fulfil national quality and safety requirements and be authorised by the Ministry of Health; NL reported that only authorised blood establishments could export blood or components for transfusion. The Military Blood Bank supplies the Dutch troops in third countries; RO and SK referred to national provisions which have to be followed. Comments While it is clear that there is limited movement of blood and blood components for transfusion between Member States and to and from third countries, it is difficult to draw conclusions on the volumes of plasma for fractionation that are imported or exported in the absence of a harmonised data collection system. There is a not always clear distinction between import/export from/to third countries and distribution from/to other EU Member States. 2.5.4.Shortages and surplus of blood and blood components

In this survey, regular shortages of blood components for transfusion were reported by six Member States: BG reported red cell and platelet shortages once per year, most commonly seasonally, often after long summer holidays, less frequently there is a shortage of a particular blood group; Shortages of red cells and platelets were reported by CY and SE; EL reported red cell and platelet shortages during summer holidays, intensified by WNV outbreaks; HU reported shortages of platelets, plasma, red blood cells and whole blood; PT reported having a shortage of red cells during the first semester of 2012, which does not occur frequently. A surplus of blood and blood components was reported by five Member States: platelets, plasma and red blood cells reported by Germany, red blood cells by Italy, plasma by Lithuania, Romania and Sweden. In Romania and Italy, surplus plasma is discarded. In Sweden it is sold to pharmaceutical companies. BG, CY, EL and HU expressed interest in concluding bilateral agreements with other Member States and in establishing short-term/ad-hoc mechanisms for addressing shortages, while Italy, Liechtenstein and Romania expressed interest in such agreements to address blood component surpluses. Greece has taken the lead on an initiative to draft a model for such agreements within the group of national competent authorities. Comments The existence of national surpluses, shortages and cross-border donations suggests the potential benefits of closer collaboration between Member States. 2.5.5.Cross-border movement of Donors Thirteen Member States (EL, SK, EE, DE, IE, FR, NL, HU, SI, LU, CZ, PL, UK) reported that they have cross-border movement of donors to/from their countries. Fifteen other Member States (AT, HR, IT, DK, SE, LV, CY, RO, MT, FI, BE, PT, LT, BG, ES) plus Liechtenstein and Norway reported that they do not observe this practice. Comments Close to half of the Member States report cross-border movements of donors, making donation outside their country of origin/residence. Due to its relationship to the compensation or incentives offered to donors, this topic is covered more extensively in the Staff Working Document on the implementation of the principle of voluntary unpaid donation. 2.6.Quality and safety of blood and blood components 2.6.1.Provision of information to prospective donors Under Article 16 of Directive 2002/98/EC, Member States must ensure that blood establishments provide prospective donors of blood or blood components with the information set out in Part A of Annex II to Directive 2004/33/EC. All 28 Member States plus Norway and Liechtenstein replied that they have measures in place to ensure only trained personnel provide the required information to donors. Twenty-seven Member States plus Norway and Liechtenstein mentioned that the information for donors is standardised at national/regional level to ensure the requirements of Article 2 of Directive 2004/33/EC are fulfilled. Eight Member States (CY, FR, IE, IT, RO, SI, SK, UK) plus Liechtenstein indicated other measures.

The blood directives do not require the existence of a system for self-exclusion by a donor. Nevertheless, 19 Member States reported to have such a system in place, including post-donation cards with a bar code (Belgium); a section with questions for self-exclusion in the blood establishment website (Ireland), information in the pre-donation material (Czech Republic, France, Italy); phone calls (Netherlands, Slovenia) and boxes available for posting self-exclusion forms (Slovakia). Given the widespread adoption of self-exclusion systems, which often lead to effective recalls of donated blood (components), competent authorities suggested that it might be valuable to reflect on measures to improve further adoption of these systems by EU Member States. Comments All Member States reported having measures to inform prospective donors through interview by trained staff. Many Member States report good experiences with donor self-exclusion systems which are one of the main triggers for recalls. 2.6.2.Information required from blood donors and examination of blood donors Blood donor information is collected through a personal interview by a healthcare professional, who may or may not be a medical doctor, through a standardised questionnaire, in 22 Member States. In some Member States, there is a mixed situation, as shown in the following figures. There have been numerous discussions in the competent authority meetings related to the differences in the questions asked on the national, regional or local forms. An exercise comparing questions and streamlining national questionnaires was suggested for consideration. Germany specified that a national standardised form to collect blood donor information does exist but blood establishments may also use forms not standardised at the national level, as long as requirements as set by national law (i.e. Transfusion law) and relevant guidelines (e.g. haemotherapy guidelines) are taken into account. Comments The personal donor interview by a healthcare professional is an essential step to help ensure that a planned donation is safe for the donor as well as for the future recipient(s). While the questionnaires are standardised within many Member States, they do however vary between Member States. 2.6.3.Eligibility criteria for donors of whole blood and blood components Article 18 of Directive 2002/98/EC requires that the evaluation of blood and blood component donors should be assured by blood establishments in compliance with criteria defined in the Annex III to Directive 2004/33/EC. Relevance of eligibility criteria

In response to the question on the most relevant acceptance/deferral criteria provided in Annex III, nine Member States (AT, BE, EE, FR, LV, NL, PL, PT, SK) plus Norway and Liechtenstein consider all criteria equally relevant. The United Kingdom considered that the criteria as a minimum standard are too broad, i.e. not specific enough. The criteria associated with higher risk of disease transmission, and pre-donation haemoglobin levels were considered the criteria most relevant to protect recipients and donors, respectively. Difficulties in implementing and verifying the eligibility criteria Sexual behaviour was considered by 19 Member States the most difficult or the least reliable criterion to implement while Germany, Poland and Norway expressed no difficulties in verifying the eligibility criteria. Changes in eligibility criteria Asked about the need to change the current age acceptance criteria considering an ageing EU population, seven Member States answered as follows: In BE, in 2012, the age of acceptance was raised from 65 to 71; In CY, donors older than 65 are accepted if a good health medical certificate is provided; DE proposed that upper age limits should be decided by the physician in charge of donor selection when deciding on deferral or admission for donation; FI has proposed that an annual permission for 66-70 year old donors could be given by a qualified healthcare professional (by a physician) to maintain self-sufficiency in Finland. The Finnish Medicines Agency (Fimea) proposed a revision of donor age limits based on a risk assessment regarding donors and recipients, and a survey of the practice of annual permission for donors over 65 years old in EU countries; In LU, since August 2012, the maximum age is 70 years; NL replied that the size of the donor population could be increased if the age criteria were replaced with medical condition criteria; In PL, a lower age limit is being considered if it does not conflict with other Polish regulations. Persons over 65 can donate blood if there are no contraindications.

Fourteen Member States considered that other eligibility criteria as laid down in Annex III to Directive 2004/33/EC need to be changed: Belgium proposed a change to the 28 day West Nile virus (WNV) deferral period (28 days after leaving an area with ongoing transmission of WNV to humans) by accepting donations when a molecular genomic test is negative or if the blood component is treated with a pathogen inactivation method (validated for inactivation of WNV). This has been partly addressed in a recent amendment in the implementing legislation and development of a related preparedness plan by ECDC. Moreover, Belgium proposed that for particular epidemiological situations (e.g. disease outbreaks) notification should be done by the competent authority of the Member States concerned to the European Commission, with a view to EU-level action. Finland proposed a survey of EU Member State practices and a risk assessment of the impacts of raising upper age limits on both donors and recipients. In addition, they proposed discussion on the following changes: Minor dental treatment - no deferral; Malignancy with complete recovery - temporary deferral; permanent only for haematological malignancies; Endoscopic examination performed in EU- no deferral; Acupuncture performed with sterile single-use needles - no deferral; Malaria - criteria for deferral should be re-assessed. France also proposed revisions of: The West Nile virus (and arbovirus) deferral period (analysis of the appropriateness of a deferral period of 120 days), genomic testing and definition of West Nile Virus “affected area” as adopted by ECDC; The minimum level of donor haemoglobin: Member States may however adopt requirements for minimum haemoglobin levels down to 120 g/l for females and 130 g/l for males on the basis of the results of studies carried out on their specific population; Chikungunya and dengue: Analysis of the opportunity to introduce clinical criteria for donors at risk of exposure; Analysis of risk and the measures to be taken regarding donors who have travelled. Croatia proposed an extension and more specific point 2.3 of 2004/33/EC for particular epidemiological situations in affected areas (e.g. WNV, Malaria, Dengue, HEV). Italy proposed changes on hepatitis B: except for HBsAg-negative persons who are “demonstrated to be immune", it should be clarified what is intended by "demonstrated to be immune", considering that persons testing anti-HBs positive with (or even without) anti-HBc may test HBV DNA positive, thus resulting in OBI (Occult HBV Infection) carriers. Lithuania proposed that the behaviours at risk of acquiring infectious diseases that could be transmitted by blood should be listed. Malta proposed a change on haemoglobin levels in general. Changes proposed by the Netherlands included:

That if HBV-NAT screening is performed, HBsAg screening can be cancelled; WNV-NAT instead of temporary deferral after visit to affected area; An update on criteria for Malaria, Q-fever. Poland proposed the following changes: Donors under 17 years of age may donate blood in exceptional circumstances (for instance: Donation of HLA–compatible blood components for family members); Donor weight and haemoglobin concentration definition in case of two unit red cell apheresis; Coagulopathy and bleeding tendency should be clarified; “metabolic disease” and endocrine disorders (e.g. hypothyroidism) should be mentioned separately; Diabetes should be mentioned under donors on oral medication; Body temperature criteria should be included; Borreliosis (Lyme disease) should be included and deferral for chronic Q disease should be more precise; An update on criteria for Malaria and West Nile virus; Point 2.2.2, in right column of the first row should be revised to include HIV and hepatitis B, and in the left column to include hepatitis B carriers, hepatitis C and HIV; Deferral period extension after hepatitis B vaccination; Precise deferral period following “exposure” to tick born encephalitis and after recovery from tick born encephalitis; Guidelines for deferral during breastfeeding; Coherence and precision on permanent and temporary deferral regarding ”persons whose behaviour or activity places them at risk of acquiring infectious diseases that may be transmitted by blood” ; Discussion and recommendations on accepting donations from persons detained in juvenile correctional institutions (homes). The following changes were proposed by Romania: Additional temporary deferral criteria: leucocytosis (leucocytes over 11000/mmc- 12000);

Evaluation of iron status at least in particular situation in donors having borderline Hb value, based on physician decision. A general concern that is expressed regularly by the competent authorities is the absence of legal requirements focused on the protection of the living donor. Assessment of sexual behaviours implying risk According to Annex III to Directive 2004/33/EC persons whose sexual behaviour puts them at high risk of acquiring severe infectious diseases that can be transmitted by blood and blood components or derivatives should be permanently deferred for allogeneic blood donation. 18 Member States plus Norway and Liechtenstein reported existing national guidelines for the assessment of risk associated with sexual behaviour. The main exclusion criteria for sexual risk behaviour listed by the reporting countries were men having sex with men, being paid for sex with drugs or money, having sex with someone who injects drugs or is paid for sex, having sex with someone who is from an area of high prevalence of HIV, having multiple sexual partners or a new partner. Assessment of variant Creutzfeldt Jacob disease (vCJD) Annex III to Directive 2004/33/EC foresees precautionary measures regarding vCJD. Seventeen Member States plus Norway and Liechtenstein reported existing national guidelines to assess vCJD risk. Main causes leading to deferrals Twenty-one Member States reported having a centralised system to collect data on blood donor deferral (either a national IT system or annual reports). The main causes leading to deferrals reported by Member States that collect this data nationally were: low haemoglobin levels, risk of transmission of infectious diseases, risk behaviours, travel, medication and other medical reasons. The “other medical reasons” included abnormal blood pressure (CY, HR, LT, MT, SI and UK).

Temporary derogations during a potential crisis In 2009, in view of a potential H1N1 pandemic, Commission Directive 2009/135/EC was adopted to allow Member States to invoke temporary derogations to accept donors with lower haemoglobin levels, to ensure blood supply during times of potential crisis. Those temporary derogations were considered the most efficient measure to maintain blood supply in case of future crises by 22 Member States (BE, BG, CY, CZ, DK, EE, EL, FR, HR, HU, IE, IT, LT, LU, LV, MT, NL, PL, PT, SI, SK, UK) plus Norway and Liechtenstein. Temporary derogations were applied by eight Member States (BE, BG, CY, EL, LU, LV, SK, UK). As additional measures, only Finland suggested that the donor upper age limit could be raised and that the competent authorities should be empowered to decide on temporary derogations. Germany explained that the situation may be very different for some types of crises such as severe disasters. Overall, such temporary measures were considered useful. Comments The main causes for donor deferral are the risk of transmission of infectious diseases, low haemoglobin levels, risk behaviours, travel history and other medical reasons, such as high blood pressure. Other eligibility criteria relate to age limits, to temporary deferrals in case of crises and to the assessment of risk associated with sexual behaviour. Several Member States also emphasised the need for more donor protection measures. 2.6.4.Testing of Donations Under Directive 2002/98/EC, every blood and blood component donation should be tested by qualified laboratories, which have been accredited, designated, authorised or licensed (Article 5, (1)) in conformity with the requirements of Annex IV (Article 21, (1)). Laboratory inspections In compliance with Article 5(1) of Directive 2002/98/EC, 27 Member States plus Norway and Liechtenstein inspect laboratories to ensure that the tests required for donors are carried out only by qualified laboratories that have been accredited, designated, authorised or licensed. The methods by which competent authorities ensure compliance with this requirement are shown in the figure below: Cyprus reported that all laboratories performing tests for donors are designated by the Ministry of Health. However, these laboratories are not inspected as an inspection system is not in place. In Finland, one blood establishment has activities relating to the testing of human blood and blood components. However, some activities relating to donor testing may be performed externally (i.e. rare tests for donors) under a written contract which is checked routinely during blood establishment inspections, though the testing activities might not be inspected on-site every two years. Poland and Slovakia reported that laboratories are audited as well as blood establishments. Nucleic acid amplification testing (NAT) The competent authorities were also asked to provide data/information regarding use of NAT technology for routine testing of blood or blood components. NAT is not required by Annex IV to Directive 2002/98/EC, but it is used in some Member States to test donor blood samples. Twenty Member States (AT, BE, DE, DK, EE, EL, ES, FI, FR, HR, IE, IT, LT, LU, LV, NL, PL, PT, SI, UK) reported the use of NAT technology for routine testing of every donation. In most countries it is used for HIV, hepatitis B and C although in some of these Member States (Germany and France) it is not mandatory to use it for hepatitis B. It is also used much less frequently for West Nile virus (WNV), hepatitis A and Parvovirus B19 testing. NAT technology is not used in SE, SK, CY, RO, MT, HU, CZ, BG, plus Liechtenstein and Norway. The reasons mentioned for this were financial constraints (BG, CY, CZ, MT, NO, RO, SK), minimal benefits (CZ, MT, NO, SK) and lack of a legal obligation (Sweden and Liechtenstein). In Greece and Italy, NAT for WNV is only used seasonally (in the summer period), to ensure safety of the blood supply within the affected areas. In Germany, NAT is mandatory as routine screening for HIV-1 (10.000mIU/ml) and HCV- (5.000 IU/ml), and for confirmatory testing for HIV-1, HCV, HBV. NAT for HBV, HAV and Parvovirus B19 is not mandatory, but used for routine screening by many blood establishments, mainly those also delivering plasma for fractionation.

A centralised system to collect positive/abnormal test results was reported by 27 Member States (BE, BG, BI, CY, CZ, DE, DK, EE, EL, ES, FI, FR, HR, HU, IE, IT, LT, LU, LV, MT, NL, PL, PT, RO, SI, SK, UK) and Norway. The number of positive test results in 2012 (on donations between 1/1/2012 and 31/12/2012) for HIV, hepatitis B, C and other agents were provided (see Annex 3). During meetings of the competent authorities, it was suggested that gathering nationally centralised test results and comparing them at EU level would be beneficial. Additional tests performed on a routine basis All countries except Spain, Liechtenstein and Latvia reported having additional tests to those required in Annex IV to Directive 2002/98/EC. See the previous point for NAT tests for Hepatitis B, C and HIV. Country AT BE BG CY CZ Additional tests For whole blood donations: unspecific immune reaction marker (Neopterin, CRP) Syphilis testing and NAT for HIV1, HBV and HCV. Syphilis and irregular antibodies. They are mandatory under national legislation for each whole blood donation. Syphilis (Treponema pallidum) HIV p24 antigen, syphilis antibodies Country DE DK EE EL ES Additional tests Mandatory for whole blood donations and apheresis donations for transfusion are " Blood grouping: " Rh details (C,c,D,E,e), Kell criterion, serum blood group antibodies on the occasion of first and second whole blood donation. Infectious disease markers: " Anti-HBc antibodies " HCV Genom (NAT) " HIV-1 Genom (NAT) " Anti-Treponema pallidum antibodies ID NAT for HIV; HBV and HCV Some of them are mandatory. HBV NAT test is not mandatory, but all the BE-s are using it in addition to HBsAg. No additional tests reported No additional tests reported Country FI FR HR HU IE Additional tests NAT for HIV-1–, HCV- and HBV are mandatory for whole blood donations. B19-DNA and HAV-RNA tests are done but not mandatory for whole blood donations Screening tests for all donations: HIV NAT, HCV NAT, HBV NAT, Anti-HTLV I/II, Syphilis. NAT for HBV is not mandatory. Screening test for Malaria, Chagas disease: If necessary. Screening test for hepatitis E virus NAT since December 2012 for FFP-SD NAT (pool of 96 samples), - by the CTSA in the earlier of 2013 for plasma lyophilized pools. HIV 1p24 antigen, HCV core, TP antibody (Syphilis) anti-HBc, TP antibody (Syphilis) NAT PCR performed on all allogeneic donations but not mandatory Country IT LI LT LU LV Additional tests NAT testing for HBV, HCV and HIV at each donation. HCV NAT mandatory since 2002, HBV and HIV NAT since 2008 No additional tests reported HIV NAT, HBV NAT and HCV NAT Law only says that additional tests can be required No additional tests reported Country MT NL NO PL PT Additional tests Anti HBc testing is performed Not mandatory. Ant- HBc when > 6 months since last donation All donations are tested for HBV DNA, RNA HCV and RNA HIV (mandatory). NAT for HIV, HCV and HBV; EiA IgM and IgG testing for Syphilis - All blood donations EiA HTLV 1 e HTLV 2 - First Time donations Malaria Country RO SE SI SK UK Additional tests Yes, MoH Order no. 1226/2007 updated by Order 650/2012 anti-HTLV- I o II Treponema Pallidum Test for syphilis is required: not required for autologous donations. anti- HB core (total) and ALT are mandatory Syphilis, HTLV, and HCV Member States were asked about additional tests for plasma donations but reported no additional information. Additional tests required by Member States are usually justified for local reasons, e.g. the increased prevalence of certain infectious diseases. These criteria might however also limit the sharing of blood and blood components between Member States. Members States authorities therefore expressed interest in having a transparent perspective on the additional tests implemented in each of the Member States. Additional information on testing Some Member States provided additional information on testing: BG reported that testing laboratories, as a part of blood establishments, participate in the Proficiency Testing Scheme organised by EDQM. The national system for external control of transmissible infections for testing laboratories in blood establishments is organised by the National Centre of Infectious and Parasitic Diseases (NCIPD); HR: An international accreditation system for testing laboratories is foreseen to be implemented in renewed legislation; IT: European Proficiency Testing Studies, as already performed by EDQM, should be enhanced; UK: All labs perform NEQAS (Scotland) (an external quality control program). Changes in basic testing requirements Eight Member States (CY, DE, EL, HR, IT, LT, NL, RO) considered changes are needed to the mandatory testing requirements for donations as specified in Annex IV to Directive 2002/98/EC: CY and RO proposed including testing for syphilis as a minimum requirement; DE replied that a general answer cannot be given as it depends on national strategies, e.g. in relation to the specific epidemiology of a given country, the use of pathogen-inactivated blood components etc; EL, HR, IT and LT proposed mandatory NAT; IT proposed that WNV NAT should be regulated as an option to screen donors living in affected areas and to screen potentially exposed donors; An additional sentence was proposed by NL: "Additional tests or alternative combinations of tests may be required for ..." This will allow the listed tests to be omitted if another test or combination of tests makes the listed test redundant.

Several of the testing requirements have been subject to discussion in the bi-annual competent authority meetings. Their relevance/value and use/feasibility should be continuously assessed in order to keep the tests aligned with the changes in the underlying risks that they need to help address. It was noted in the discussions at the competent authority meetings that, while the theoretical value of testing can be high, the effective value depends largely on the implementation and validation of these tests and their introduction can have a major impact on the local availability of blood and blood components. Testing can therefore not be considered as the single pillar for safety of blood and blood components but must be combined with deferral criteria and, where appropriate, inactivation techniques. It is through a combination of these strategies that safety risks are reduced to a minimum. Techniques for pathogen reduction/inactivation Techniques for pathogen reduction/inactivation are used in 16 Member States (AT, BE, CZ, DE, EL, ES, FR, IT, LT, LU, NL, NO, PL, PT, SE, SI, UK) plus Norway. Methylene blue, amotosalen (riboflavin), and solvent detergent are examples of pathogen reduction/inactivation techniques used, as summarised in Table 8. Country AT BE CZ DE Pathogen inactivation techniques Plasma (Methylene blue / Intercept / Mirasol) Platelets, RBCs (Radiation) Plasma for transfusion: pathogen inactivation mandatory techniques used - methylene blue, solvent detergent, amotosalen. Platelets: pathogen inactivation techniques used- amotosalen, (riboflavin) Platelets: very few units (dozens), amotosoralen a) Therapeutic frozen MB plasma: methylene blue and light followed by absorption of methylene blue and its photo derivatives by blueflex filter. b) Therapeutic frozen SD plasma: plasma pooled and tested according to Ph.Eur. monograph Human Plasma for Fractionation; treatment with solvent and detergent and removal of these additives according to Ph.Eur. monograph Human Plasma (pooled and treated for virus inactivation c) Therapeutic frozen Intercept Plasma: plasma obtained from whole blood or apheresis donations treated with amotosalen-HCl and UVA b) Intercept-PC: platelet concentrates from pooled buffy coats or from apheresis donations suspended in plasma and additive solution, treated with amotosalen-HCl and UVA. Country EL ES FR IT Pathogen inactivation techniques Photo-inactivation of Plasma with Methylene blue Methylene-blue inactivation for plasma (transfusion) Amotosalen with UVA light exposure used for Platelets (platelets apheresis leucocyte-depleted and platelets recovered pooled leucocyte-depleted) pathogen. For plasma fresh-frozen leucocyte-depleted pathogen reduction/inactivation: Solvent-detergent, Amotosalen with light exposure. Blood Component pathogen reduction/inactivation is not mandatory. Pathogen inactivation techniques are applied to a minor percentage of fresh frozen plasma for transfusion (riboflavin/UV, amotosalen/UVA, methylene blue, solvent detergent) and platelets (riboflavin/UV, amotosalen/UVA). Two specific full Health Technology Assessment studies, respectively on FFP and PLT pathogen inactivation, are in progress at the National Blood Centre, in order to make adequate data and information available for eventual national regulatory decision-making. Country LT LU NL NO PL Pathogen inactivation techniques Mirasol technology is used for approx. 3 % of platelets. Only for FFP, solvent detergent plasma is used Irradiation: plasma Washing: all products Solvent Detergent: plasma Solvent Detergent for all plasma units. Pathogen Reduction of 11 % of platelet concentrates (Intercept and Mirasol) Mirasol PRT for platelets and plasma for clinical use and Macopharma Macotronic system for plasma for clinical use. Country PT SE SI UK Pathogen inactivation techniques Inactivation of pathogens by Amotosalen UVA (Intercept) in 1 BE Some of the blood establishments in Sweden are using pathogen inactivation techniques for platelets but it is not mandatory and the blood establishment itself has to consider if they want to use that technology. Amotosoralen + UV radiation (Intracept) for Platelets Methylene blue treatment of plasma (England, Northern Ireland) Pathogen inactivation techniques are mainly used for plasma and not for other blood components. It was noted in the discussions at the competent authority meetings that, while the theoretical value of pathogen inactivation techniques can be high, the effective value depends largely on the implementation and validation of these techniques. Pathogen inactivation techniques can therefore not be considered as the single pillar for safety of blood and blood components but are to be combined with deferral criteria and testing. It is through a combination of these strategies that safety risks are reduced to a minimum. Comments In all Member States tests are performed by laboratories authorised by the blood competent authority or other competent authorities. Competent authorities also recognise the role of international accreditation programmes for these laboratories. While the EU legislation requires minimum testing for Hepatitis B, C and HIV (1/2), Member States reported additional routine tests mainly for syphilis, malaria, hepatitis A, hepatitis E and Parvovirus B19. Introduction of mandatory NAT testing for HIV and hepatitis, and where appropriate pathogen inactivation techniques, were highlighted as important issues that need further reflection, particularly regarding cost-benefit assessments. In that respect, a general point mentioned was the need for a common assessment mechanism to understand the impact of changes in deferral criteria, testing or other measures on safety, quality, cost and supply. The role of common assessments by ECDC and the Commission was recognised, e.g. the development of a preparedness plan to address the seasonal outbreaks of West Nile Virus in some Southern EU countries. Competent authorities reiterated also the value of consolidating nationally centralised test result data. 2.6.5.Storage, transport and distribution conditions The storage, transport and distribution conditions of blood and blood components in blood establishments and in hospital blood banks must comply with Article 22 of Directive 2002/98/EC, and Article 5 and Annex IV to Directive 2004/33/EC. To comply with these requirements, 23 Member States plus NO reported existing legislation and regulations: CY reported existing national guidelines; HR, LI and NL mentioned their blood establishments’ standard operating procedures (SOPs); ES reported existing specific computer systems; The reply from HU was unclear as it only mentioned refrigerator validation by the quality assurance department; 13 Member States (BE, EL, FI, FR, IE, IT, MT, NL, NO, PL, PT, RO, SE and UK) plus NO ensure the compliance with these requirements by inspections; LU reported that quality management is ensured by SOPs;

LV reported control measures as visits to blood establishments and hospital blood banks and audits of documentation. Comments Many Member States report that they verify compliance with these EU provisions during inspection. Standard operating procedures, computer systems and audits were also mentioned as tools to verify or strengthen compliance. 2.6.6.More stringent measures More stringent measures to ensure safety and quality, with respect to those foreseen under the Directive, were introduced or were maintained by 10 Member States. These measures included: NAT testing for hepatitis B (HBV NAT), hepatitis C (HCV NAT), and HIV 1/2 (HIV 1 NAT) for whole blood and apheresis donations; NAT testing for WNV (EL); Dengue fever testing (PT); Pathogen inactivation techniques of plasma (EL); Requiring the responsible person to be a licensed physician, specialist in transfusion medicine or equivalent discipline, with at least 5 years of post-graduate full-time service in a blood establishment (IT); Additional eligibility/deferral criteria (RO); Mandatory inspection for hospital blood banks (RO); Registration and reporting of all incidents and adverse reactions, including the activity performed at clinical service level (RO); Penalties applicable to violations occurring at the clinical level - before, during or after transfusion, import or export of blood or blood components (BG). Comments Member States implement additional national safety and quality measures, in some cases because of increased risk e.g. the increased local prevalence of a certain disease.

2.7.Exchange of information, reports and penalties 2.7.1.Penalties Under Article 27 of Directive 2002/98/EC Member States must lay down rules on penalties applicable to infringements of the national provisions, and take all measures necessary to ensure that they are implemented and notified to the Commission. Twenty-five Member States have adopted national provisions laying down rules on penalties for infringements. Four Member States reported to have imposed penalties: BG, CZ, LT and SK. The main reasons were related to the clinical use of blood and blood components (Bulgaria - five financial penalties), the change of legal entity of blood establishments which was not announced in advance (Czech Republic - one financial penalty), non-compliance with testing documentation requirements (Lithaunia - one licence revoked), and major shortcomings which were not eliminated after inspection (Slovakia – one authorisation suspension). The penalties foreseen in national legislations, their criteria for implementation and their effective implementation can differ significantly between Member States. In order to ensure mutual trust between Member States, in particular where blood (components) are exchanged, it was suggested that further collaboration and coordination could be envisaged, potentially in a dedicated EU initiative related to inspections and authorisations. 2.7.2.Difficulties in transposition or implementation Asked about difficulties they may have encountered when transposing or implementing the EU Blood Directives, Member State