chapter 3 - Chapter 4 - Biological properties of haematopoietic stem cells

*

CHAPTER 3

JACIE & quality management in HSCT

Christian Chabannon, Eoin McGrath

CHAPTER 3 • JACIE & quality management in HSCT

1. Introduction and overview JACIE (Joint Accreditation Committee – ISCT & EBMT) (1) is a non-profit body established for the purposes of assessment and accreditation in the field of haematopoietic stem cell transplantation (HSCT). The Committee was founded in 1998 by the European Group for Blood and Marrow Transplantation (EBMT) and the European branch of the International Society for Cellular Therapy (ISCT), the two leading scientific organisations involved with HSCT in Europe (2). JACIE modelled itself on the US-based Foundation for the Accreditation of Cellular Therapy (FACT) (3, 4), established in 1996 by the ISCT and the American Society for Blood and Marrow Transplantation (ASBMT). JACIE actively collaborates with FACT in establishing standards for the provision of quality medical and laboratory practice in HSCT; the two organisations now issue joint FACT-JACIE standards, which are applicable internationally (5). The primary aim of JACIE is to improve the quality of HSCT in Europe by providing a means whereby transplant centres, collection and processing facilities can demonstrate high quality practice. The need to reinforce quality management (QM) in the practice of highly sophisticated medical procedures such as HSCT was identified partly because of past observations that incidents and adverse events can occur even in experienced transplant centres. It also stems from the increasing use of unrelated donors and international exchanges of cell products, necessitating measures to ensure consistent quality control procedures for these products (6). Improving quality of HSCT is achieved through external inspection of facilities to ensure compliance with the FACT-JACIE standards. An additional and wider aim is to ensure harmonisation between FACT-JACIE standards and other national/international standards, including the EU Tissues & Cells Directive (Directive 2004/23/EC) and the related Commission Directives 2006/17/EC and 2006/86/EC (7–9). JACIE accreditation provides a means whereby transplant facilities can demonstrate that they are working within a QM system covering all aspects of the transplantation process, and thus show compliance with the requirements of national and international regulatory authorities. While JACIE accreditation was initially established as a voluntary process, an increasing number of countries and competent authorities have now included JACIE accreditation as a requisite for authorisation of transplant programmes or for reimbursement of treatment costs by healthcare insurance. These include The Netherlands, Switzerland, France and Italy. The current organisation of JACIE ensures wide consultation, with over 20 European countries now represented on the Board in addition to nursing, paediatrics and cordblood representatives. Officers in the executive committee run day-to-day operations, and together with the President, vice-President, past-President, Medical Director and

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Chair of the Accreditation Committee plan and oversee annual operations, and report to the JACIE board and the EBMT board. The Accreditation Committee reviews all inspection reports and advises the JACIE Board.

2. The FACT-JACIE standards The FACT-JACIE standards (5) cover all aspects of clinical transplant programmes, collection facilities (bone marrow (BM) collection and apheresis collection) and processing of collected cell products. The standards also apply to the use of therapeutic cells (TC) derived from blood or marrow, including donor lymphocytes and mesenchymal stem cells; discussion is ongoing to decide to which extent future versions of the standards should cover the delivery of various form of cell therapies in medical disciplines beyond haematology and oncology (regenerative medicine). Current standards cover the clinical use of Cord Blood Units (CBU) by clinical programmes but not the collection or banking of CBU which are covered by the related Netcord-FACT standards and inspected/accredited by FACT-Netcord (3, 10). Within each subsection of the standards are detailed lists of specific requirements; for example, the standard on donor evaluation and selection contains specific items relating to clinical evaluation, laboratory testing, informed consent etc. The current edition of the standards is the 4th edition, dated 2008 (5). The 5th edition is expected to be released in March 2012. The standards are accompanied by a manual which contains the standards together with detailed guidance on the interpretation and measures required to demonstrate compliance. Each standard is followed by specific questions relating to that standard; these questions form the basis of the inspection checklist, which must be completed prior to inspection by the applicant centre and verified by the inspector during the inspection. The complete standards and the accompanying guidance manual are available on the JACIE website, together with other useful information relating to JACIE organisation, inspection and accreditation (1). 2.1 General aspects of the standards Although the standards are very specific in certain areas, some essential principles apply throughout. The first of these is a requirement for documentation of policies, procedures, actions, requests and so on. This applies to the need to have written policies and procedures, and extends to all aspects of transplant activity. For example, the initial diagnosis of a patient must be documented by source material or reports. A request from the clinical unit to the laboratory for issue of cells must be made in writing. A potential donor must not only be properly evaluated for 42

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eligibility, but the programme must have clear written criteria for what constitutes an eligible donor and must clearly document whether the donor meets these criteria. The second is a requirement that personnel must not only be appropriately qualified, they must be trained in the procedures they regularly perform and their competency to perform the task after training must be assessed and documented. Similarly there is a requirement for validation of all equipment and procedures. Validation is a term used to describe the activity required to prove that any procedure, process, equipment, material, activity or system actually leads to the expected results. For example a new apheresis machine must be shown to produce the expected results in terms of cell yields. Also important is the requirement for close cooperation and interaction between the different parts of the programme, especially important where a clinical programme may use a distant collection and/or processing facility. Mechanisms for transfer of information must be clearly established. 2.2 Quality management (QM) An active quality management programme (QMP) is essential to ensure that all aspects of the programme run effectively. A QMP is a mechanism to ensure that procedures are being carried out by all staff members in line with agreed standards. In a transplant programme, this ensures that the clinical, collection and laboratory units are all working together to achieve good communication, effective common work practices and increased guarantees for patients. It is a means of rapidly identifying errors or accidents and resolving them so that the possibility of repetition is minimised. It assists in training and clearly identifies the roles and responsibilities of all staff. Once the required level of quality has been achieved, the remaining challenge is to maintain this standard of practice. With a working QMP in place and adequate resources, the fundamental elements necessary to sustain the programme are continued staff commitment and vigilance. The culture and systems for QM are well-established in laboratories but are relatively new in clinical units; many programmes have experienced difficulty setting up a QMP to cover the clinical programme and collection facility. It is recommended that a programme should have a dedicated quality manager, ideally with specific training in QM, not only to develop the QMP and meet the initial requirements for accreditation but to ensure continued adherence to standards. To assist centres in developing a QMP JACIE has published “A practical guide to implementing quality management in a stem cell transplantation (SCT) programme” (1). Within a programme there can be one QM system covering all areas, i.e. clinical,


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collection and processing, or the laboratory may have a separate system, and other combinations are possible. When there is more than one system, there should be a clear mechanism for interaction between them. 2.3 Policies and procedures There are specific requirements for how policies and procedures should be written, to ensure that all essential aspects are covered. Procedures necessary to perform a given procedure should be easily available to staff. Electronic access is acceptable but there must be at least one hard copy available at all times and staff must know where to access this. For each section – clinical, collection and processing – there is a list of specific policies and procedures that must be covered. All Standard Operating Procedures (SOPs) must be reviewed no more than every two years or earlier if changes are introduced in a procedure between the scheduled review dates. 2.4 Clinical programme, collection facility and processing facility standards The following paragraphs will comment on some particular aspects of the standards, but for full details the reader should refer to the standards and manual. 2.4.1 Definition of a programme The standards define a Clinical Transplantation Programme as an integrated medical team housed in geographically contiguous or proximate space with a single Programme Director and common staff training programs, protocols, and QMP. Programmes that include non-contiguous institutions in the same area must share common protocols, staff training procedures, QMP, and review of clinical results and evidence of regular interaction. This means that two separate units should not combine together for the purposes of JACIE accreditation unless they are truly working together in everyday practice. Where two separate clinical transplantation units are working together, they must be within one hour travelling time to ensure close and regular interaction. Centres may apply for accreditation as complete programmes comprising clinical programme, collection facility and a processing laboratory or as a single collection or processing facility which may serve a number of clinical programmes. Clinical units must be using collection and processing facilities that meet the FACT-JACIE standards. 2.4.2 Clinical programme activity To ensure continuing proficiency in a transplant programme, a minimum volume of patients must be treated per year. The current minimum activity requirements for each 12-month period are as follows: 44

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- For allogeneic transplantation: At least 10 new patients - For autologous transplantation only: At least 5 new patients - For centres performing both allogeneic and autologous transplantation there is no minimum requirement for autograft numbers, provided that the minimum number of allografts is met - For combined adult and paediatric programmes, a minimum of 5 new adult patients and 5 new paediatric patients - For programs utilising more than one clinical site for transplantation, a minimum of 5 new patients must be transplanted at each site. 2.4.3 Donor evaluation This section covers information, consent, and requirements for evaluation including medical history and testing for infectious disease markers. The medical history for allogeneic donors must include a number of specific items relating to possible transmission of infections and non-infections disease. The use of a standard donor history questionnaire is recommended. Testing for infectious diseases must conform to national and international regulations. The complete list of mandatory markers differs for autologous and allogenic transplantation. A positive result may result in the definitive rejection of a donor (i.e HIV), or in the decision to proceed with the use of a positive donor, following a careful risk-benefit evaluation and possibly specific measures for the recipient; such deviations must be notified to and accepted by the recipient. In some instances such as West Nile Virus and Trypanosoma Cruzi risk assessment should be performed in accordance with governmental regulations. The tests must be performed within 30 days prior to collection of cells. If more than one collection is performed the tests will need to be repeated if they are out of this time period. Other required tests include at least: ABO group and Rh type and pregnancy assessment for all female donors of childbearing potential. For allogeneic donors HLA-A, -B, -DR typing must be performed and HLA-C testing for unrelated donors and related donors other than siblings, in all cases by an EFI-accredited laboratory. 2.4.4 Data collection The programme must collect all the data necessary to complete in the EBMT MEDA forms. Prior to inspection the team must submit records of this data for 10 consecutive patients and on the day of inspection the inspectors verify the data against the source material. It is important to have records of the tests used to confirm the original diagnosis as well as of all the peri-transplant data.


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2.4.5 Bone marrow collection If a programme regularly uses BM, this must be collected in a facility that meets the FACT-JACIE standards. This means that the BM collection facility must also be inspected and accredited. The minimum activity required to apply for accreditation is an average of 1 collection in the year preceding application for accreditation, and has been decreased as a consequence of the reduced activity in this field by most adult transplant programmes. Even where only one harvest is performed per year, all requirements of the standards must be met, e.g. relevant SOPs must be in place and regularly reviewed, with evidence of continued training of staff and review of procedures. 2.4.6 Apheresis collection The minimum activity requirement for an apheresis collection facility (CF) is an average of 10 procedures per year during each accreditation cycle. A CF must have a Director and a Medical Director. These can be the same person, but the Director does not have to be medically qualified. 2.4.7 Processing facility standards A processing facility must have a Director and a Medical Director. These can be the same person, but the Director does not have to be medically qualified. There must be appropriate and validated assays and test procedures for the evaluation of cellular therapy products. Procedures must be demonstrated to result in acceptable target cell viability and recovery. Where processing includes exposure to the environment this must take place in an environment with specified air quality and cleanliness, as established through appropriate validation and testing. The FACT-JACIE standards do not specify any defined level of air quality. However in EU member states the laboratory must comply with the requirements of the EU Directive on air quality.

3. The inspection and accreditation process 3.1 Initial application The centre implements measures as described in the JACIE accreditation manual, then applies for inspection by submitting the application form containing basic information about the programme/facility and a number of supporting documents including a self-assessment checklist. The application information and checklist must be submitted in English but all other documentation, including SOPs is accepted in the language of the centre where the inspectors assigned are able to read and speak the language of the centre. 46

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3.2 Inspection An on-site visit is carried out by a team of trained inspectors, usually one per facility (clinical/collection/processing). Inspectors are medical, scientific or other professional persons working in HSCT, with specific qualifications and experience for inspecting clinical, collection and/or processing facilities (1). Inspectors must attend a JACIE-sponsored training course and pass an examination. Where a clinical programme performs adult and paediatric transplants, an adult and a paediatric inspector will attend. Inspectors may also be from another country but should be either native or fluent speakers of the relevant language. In countries where it is not possible to assign an inspector who speaks the language, a local expert is requested to assist with translation of interviews and documents as necessary. An inspection visit generally lasts between 1 and 2 days and involves meeting with staff during their work, review of documents/records and completion of a detailed checklist relating to the standards. The inspectors prepare their report in English, noting any areas of non-compliance with the standards. The report is reviewed by the Inspection Report Assessors and presented to the Accreditation Committee for discussion and recommendations for actions. 3.3 Report and correction phase Based on the inspectors’ findings, a summary report is prepared making specific recommendations for corrections and improvements. Between 3 and 9 months is allowed for the centre to correct deficiencies, depending on the amount of work required. The centre must indicate acceptance of the findings and then in due course submit documentary evidence to confirm corrections or amendments. The original inspectors review the documentation. In some cases a limited revisit may be the best way to show that deficiencies have been remedied. The inspectors confirm to JACIE that all necessary corrections have been made or indicate that there are still outstanding areas for completion. 3.4 Accreditation The Accreditation Committee reviews all the reports and relevant documentation and if satisfied that all previous deficiencies have been corrected, awards accreditation, subject to an annual report from the centre noting any significant changes in personnel or procedures and including annual activity figures. At the end of year 2 of accreditation, a short interim audit is performed to ensure that the programme has maintained its quality management system functioning. Reaccreditation follows the same process as the initial accreditation.


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4. Outcome of inspections 4.1 Inspections to date To date, 235 facilities have formally applied for accreditation at least once. Of these, 135 centres applied for accreditation for a combination of clinical, collection and processing facilities; 16 centres applied for clinical and collection only; 18 centres applied for collection and processing only; 37 for the clinical programme only; 2 for clinical and processing only; 1 for BM collection only; 8 for apheresis collection only and 18 for processing only. Since 2000, 223 inspections have been performed. Of these, 177 were first-time inspections and 46 were reaccreditation inspections. Almost all centres were found to be functioning at a high level of excellence (11). However some deficiencies in compliance were found in all programmes inspected so far, varying from minor non-compliances, e.g. in formatting of SOPs, to major deficiencies e.g. lack of reliable alarm systems for products stored in liquid nitrogen. In almost all cases correction of deficiencies was verified by submission of documentation by the centre. The median time taken for correction of deficiencies is just over 5 months. In a very small number of cases a limited re-inspection was required to demonstrate correction of deficiencies. At the time of writing, 145 inspected centres have achieved accreditation at least once and 32 centres have achieved re-accreditation. These centres are listed on the JACIE website (1). 4.2 Common deficiencies The four most common deficiencies are in QMP, documentation, labelling and donor management (11, 12). This is consistent with the experience of the FACT accreditation programme in the United States (13). Deficiencies in QMP were by far the most common cause of failure of compliance with the standards, including problems with policies and procedures (SOPs). They can only be corrected by maintaining resource and efforts over several accreditation cycles, thus contributing to improving the knowledge of QM by all professionals participating in the programme. Similarly building and maintaining comprehensive documentation that covers all aspects of the activity requires a long-standing commitment of the entire team. Documentation of key aspects of patient and donor management must be improved for an accurate evaluation of the risk-benefit ratio of the proposed transplantation. JACIE standards for labelling of components require that essential information is shown including a unique alphanumeric identifier, name of the product and the 48

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recipient’s name. The label must be securely attached, of a size that allows the contents of the pack to be inspected and clearly labelled using indelible ink. In the majority of centres it was found that labelling of products during collection and processing was not compliant with the standards in a variety of ways, and a common problem in designing JACIE-compliant labels was identified. This has been addressed by an international collaboration – the Cellular Therapy Coding and Labelling Advisory Group (CTCLAG) – which has designed HSC and TC component labels and standardised terminology based on the ISBT 128 system for stem cell component identification (14, 15). Adoption of ISBT 128 labels must be en route in the 4th and 5th edition of the standards, and it is expected that complete implementation will be requested by the 6th edition. Further information is available at: http://www.iccbba.org/subject-area/cellular-therapy. 4.3 Experience of centres implementing JACIE It was anticipated that implementation of the JACIE standards would pose some difficulties for applicant centres, particularly in relation to establishing a QMP. It was also anticipated that there would be resource implications in terms of staff time because of the amount of detailed documentation that is required to demonstrate compliance with the standards. The most difficult part of preparation was implementing the QM system, adverse event reporting system and other documentation. Lack of a culture of QM has been cited as an important problem; there is an important need for training of clinical staff (doctors and nurses) in QM. Where extra personnel were required, these were frequently quality managers and data managers; many programmes testified that part of the challenge was to maintain these individuals in the programme, once JACIE accreditation was granted. In ongoing surveys, centres indicated that they had benefited from implementing the JACIE standards. The areas of greatest perceived benefit are in procedures and practices, staff motivation, control of adverse events, and co-ordination between different areas of the programme. Significant benefits have also been perceived in facilities, patient care and safety and training of new and existing staff. Improvements clearly depend on the level of existing services, so that failure to demonstrate improvement may reflect good pre-existing resources. In other areas procedures were only set up as part of implementing JACIE, so that it is difficult to monitor improvements without an established baseline for comparison. Indeed implementation of JACIE may have the paradoxical effect of seeming to increase adverse events because these were not previously adequately reported. More importantly, EBMT recently conducted a retrospective registry analysis on more than 100.000 transplants, looking to see whether preparation and obtaining of JACIE


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accreditation may contribute to improve HSCT outcome. The statistical analysis took into account confounding criteria related to both transplanted patients and transplant programme/centre characteristics, such as the year HSCT was performed, centre size, gross national income for the country in which HSCT was performed, the EBMT risk score for patients who underwent HSCT and other factors, and concluded that there is stepwise improvement in the outcome of HSCT performed in a centre that engaged in preparing and eventually obtaining JACIE accreditation (16). Although this will need further and careful evaluation, this is nevertheless initial evidence that introduction of a QMP can improve the results of a medical procedure, together with the introduction of new drugs and regimens, and other organisational aspects of HSCT activities (17–19). This is also an incentive for hospitals and clinics to devote the necessary resource for obtaining and maintaining JACIE accreditation (20), in addition to obtaining the mandatory authorisations for their activities in this field.

5. Conclusion The JACIE accreditation system is now firmly established in Europe and the experience of centres that have been inspected is that implementation of the JACIE standards has led to significant improvements in different aspects of their transplant programmes. Key points are shown below. JACIE has further assisted with a number of training courses and tools for preparing centres for accreditation. JACIE has also developed a close working relationship with other organisations involved in cellular therapy, which will form the basis for a new global approach to harmonisation of standards and accreditation systems worldwide. This collaboration represents an innovative and proactive approach to solving the problems of international exchange of tissues and cells. The future of JACIE will depend on how globally the system can develop. Most accredited centres are located in Western Europe, while transplant programmes located in Eastern Europe have so far only minimally engaged in the process. Recently, a few Eastern Mediterranean transplant programmes have expressed interest in JACIE, and indeed the first one of these centres was granted accreditation in 2010. In addition to the well-established partnership with FACT, JACIE maintains contacts with investigators in the Asian-Pacific area. The future of JACIE will also depend on major changes arising in the regulatory field; JACIE has been conceived for programmes that use grafts produced in mostly academic facilities, and these are differently regulated than pharmaceutical companies; the recently released European regulation on Advanced Therapy Medicinal Products (ATMPs) (21) is not currently applicable to “historical” HSCT, but will undoubtedly affect our practices in the midand long-term; JACIE will have to consider its role and mission in this evolving context. 50

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Key points Promoting excellence in haematopoietic stem cell transplantation Promoting harmonisation in haematopoietic stem cell transplantation Standards Definition of a programme for haematopoietic stem cell transplantation On-site inspection Implementation of quality management Documentation of deviations Training of personnel Donor screening and validation ISBT 128 labeling system

Acknowledgements

The authors wish to express their appreciation to Derwood Pamphilon currently serving as Medical Director, Alessandro Rambaldi currently serving as vice-President, Jane Apperley currently serving as past-President, Christiane Vermylen currently Chair of the Accreditation Committee, and to all past and present members of the executive office, the accreditation committee, the board, as well as to all inspectors and all personnel involved in preparing or obtaining JACIE accreditation for their centres, for their invaluable help in establishing JACIE as a key component in improving safety and quality of care for patients who undergo HSCT at European centres.

References 1. 2. 3. 4. 5. 6. 7.

JACIE. www.jacie.org. Kvalheim G, Berli M. EBMT and ISHAGE-Europe create a foundation for inspection and accreditation in Europe. Cytotherapy 1999; 1: 363–364. FACT. www.factwebsite.org Warkentin PI. Voluntary accreditation of cellular therapies: Foundation for the Accreditation of Cellular Therapy (FACT). Cytotherapy 2003; 5: 299–305. FACT-JACIE. FACT-JACIE International Standards For Cellular Therapy Product Collection, Processing, and Administration. 4th edition, 2008. Gratwohl A, Baldomero H. Trends of hematopoietic stem cell transplantation in the third millennium. Curr Opin Hematol 2009; 16: 420–426. Directive 2004/23/EC of the European Parliament and of the Council of 31 march 2004 on setting standards of quality and safety for the donation, procurement, testing,


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8. 9.

10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21.

processing, preservation, storage and distribution of human tissues and cells. Commission Directive 2006/17/EC implementing Directive 2004/23/EC of the European Parliament and of the Council as regards certain technical requirements for the donation, procurement and testing of human tissues and cells. Commission Directive 2006/86/EC implementing Directive 2004/23/EC of the European Parliament and of the Council as regards traceability requirements, notification of serious adverse reactions and events and certain technical requirements for the coding, processing, preservation, storage and distribution of human tissues and cells. Netcord. www.Netcord.org. Samson D, Slaper-Cortenbach I, Pamphilon D et al. Current status of JACIE accreditation in Europe: A special report from the Joint Accreditation Committee of the ISCT and the EBMT (JACIE). Bone Marrow Transplant 2007; 39: 133–141. Pamphilon D, Apperley JF, Samson D et al. JACIE Accreditation in 2008: Demonstrating excellence in stem cell transplantation. Hematol Oncol Stem Cell Ther 2009; 2: 311–319. Warkentin PI, Nick L, Shpall EJ. FAHCT accreditation: Common deficiencies during onsite inspections. Cytotherapy 2000; 2: 213–220. Ashford P, Distler P, Gee A et al. Terminology and labeling of cellular products: 1. Standards. Bone Marrow Transplant 2007; 40: 1075–1083. Slaper-Cortenbach I. ISBT 128 coding and labeling for cellular therapy products. Cell Tissue Bank 2010; 11: 375–378. Gratwohl A, Brand R, Niederwieser D et al. Introduction of a quality management system and outcome after hematopoietic stem-cell transplantation. J Clin Oncol 2011; 29: 1980–1986. Loberiza FR Jr., Zhang MJ, Lee SJ et al. Association of transplant center and physician factors on mortality after hematopoietic stem cell transplantation in the United States. Blood 2005; 105: 2979–2987. Horan JT, Logan BR, Agovi-Johnson MA et al. Reducing the risk for transplantation-related mortality after allogeneic hematopoietic cell transplantation: How much progress has been made? J Clin Oncol 2010; 29: 805–813. Gooley TA, Chien JW, Pergam SA et al. Reduced mortality after allogeneic hematopoieticcell transplantation. N Engl J Med 363: 2091–2101. Apperley J. Just another cost increasing exercise (JACIE)? Bone Marrow Transplant 2004; 34: 835–838. Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004.

Multiple Choice Questionnaire To find the correct answer, go to http://www.esh.org/online-training/handbook/ 1. Which of the following statements about JACIE accreditation is correct: 52

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a) The 3rd version of FACT-JACIE standards is in use . . . . . . . . . . . . . . . . . . . . . . . . . . . b) JACIE accreditation is mandatory in all European member states . . . . . . . . . c) Transplantation of related CBU does not fall in the scope of JACIE . . . . . . . d) Inspectors are professionals in the field of stem cell transplantation, collection or processing, who have received prior training for inspection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Which of the following statements about quality management is correct: a) Quality management is the last step to achieve, once all medical and technical issues have been dealt with . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . b) Deficiencies related to quality management are among the most frequent noted during document reviews and on-site inspections . . . . . . . . c) Personnel training is necessary only in programs that perform either paediatric transplantations, or innovative forms of stem cell transplantation that are evaluated in the context of clinical research . . . . d) Document control is necessary only when requested by national regulations, which is usually the case for collection and processing. . . . . . 3. Which of the following statements about clinical activity is correct: a) Access to an ICU must be secured in advance, in case transplanted patients develop complications and need to be transferred . . . . . . . . . . . . . . . b) Quality management is not mandatory for the clinical activity, but only for collection and processing activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . c) Consent must be obtained from donor and recipient, only when they are solicited to participate in a clinical research study in the context of stem cell transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . d) A program performing only autologous transplantation in children cannot receive JACIE accreditation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Which of the following statements about JACIE accreditation is correct: a) At the end of the inspection, the inspector team leader will decide whether or not to accredit the applicant program . . . . . . . . . . . . . . . . . . . . . . . . . . b) Accreditation is valid for four years . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .


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c) The main objective of JACIE is to ensure that all transplant performed in Europe comply with European directives on cell and tissue procurement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . d) ISBT 128 is a system that allow for the exchange of information relating to donor consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. Which of the following statements about donor evaluation is correct: a) JACIE has accurately defined and regularly updates which testing is to be performed on donors for transmittable diseases. JACIE prescriptions prevail over national or international regulations . . . . . . . . . . . . . . . . . . . . . . . . . . b) Criteria for donor evaluation must be flexible, in order to adapt for the variable and more or less urgent need of transplantation in recipients diagnosed with different diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . c) In case of donor positive or incomplete testing for transmittable disease, the recipient physician must be informed . . . . . . . . . . . . . . . . . . . . . . . . . d) A biohazard label must be affixed to all collected, processed and distributed cell products because these contain cells of human origin . . .

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