[THE STATE OF INTERNATIONAL LEGAL REGULATION OF CADAVERIC DONATION: ON THE PATH TO UNIFICATION (REVIEW)].

The purpose of this study is to assess the current state of international legal regulation of cadaveric donation and determine the possibility of its further unification. Therefore, the subject of the study was the legal regulation of cadaveric donation as a certain part of medicine. In particular, the work examined the norms of international law, as well as the separate provisions of the national legislation of different countries, aimed at regulating relations in the field of cadaveric donation. Also analyzed the results of scientific research on this subject. During the study, different methods of cognition were used. In particular, the historical method allowed to establish trends in the development of legal regulation of cadaveric donation. The comparative-legal method has given an opportunity to highlight the peculiarities of national regulation of relations associated with cadaveric retrieval of organs in some individual countries and correlated them to international legal experience. The statistical method has given an opportunity to establish the effectiveness of the application of a legal construct, its ability to overcome the "deficit" of the bodies and a fair distribution between the recipients. On the basis of the dialectical method, the conclusion was drawn about the possibility of developing common standards for the legal regulation of relations in the area of cadaveric donation. Other methods were used in this work, including: formal-logical, dogmatic, modeling, analysis and synthesis. The result of the study was the conclusion about the need and the possibility of forming a single international standards for the legal regulation of cadaveric donation, and in the context of globalization, there is an urgent need to create a universal Model code on donation and transplantation.

[LEGAL REGULATION OF TRANSPLANTOLOGY AT THE PRESENT STAGE: UKRAINIAN ISSUE AND EXPERIENCE OF FOREIGN STATES].

The objective of the research is to analyze the legal regulation in the transplantology field at the present stage in Ukraine. To address identified challenges, the author investigates the foreign countries experience and suggests ways of improving certain mechanism for legal regulation in the field of organ transplantation and anatomical materials. The empiric material of the study included a wide range of legal instruments regulating this sphere of legal relationships, information regarding the problems of their application, statistics, expert analysis of Ukrainian and foreign researchers. Methodological mechanism of current research includes such methods: systematic, logical and formal, structural-functional, comparative. The research found that the most world's successful model for the organization of transplantation is in Spain. Additionally, the criteria for the reception of such a model are singled out as well as certain aspects of their application in Ukraine are analyzed. Particularly, the most important criteria are: universal and general territorial proliferation of national health systems; relevant economic resources (special attention is paid to the fact that transplantation is not a medicine of luxury, and an adequate compensation to hospitals for transplantation operations should serve as a main economic aspect); an adequate and necessary number of doctors and nurses; the availability of advanced technical options for medical mechanical ventilation (air conditioning of dead bodies). The research led to the following overall findings. Due to the rapid development of medical and biological sciences, there is an urgent need on further investigation of legal, moral and ethical, general medical aspects of transplantation with subsequent proposals for improving legislation in the field of human organs transplantation and other anatomical materials. At the same time, development of appropriate legislation by complex groups of cross-disciplinary specialists and experts (in medicine, biology, law and bioethics) is the key to legal regulation effectiveness.

Chapitre 6. Cells? safety in Europe: Towards an ethical safety.

To encourage and maximise the use of human biological material in Europe, the European Commission instigated a main Directive in 2004 (Directive 2004/23/EC), four technical ones in 2006 (Commission Directives 2006/17/EC and 2006/86/EC) and in 2015 (Commission Directives (EU) 2015/565 and (EU) 2015/566). They encourage the donation of tissues and cells for transplant purposes in the safeguard of public health. Another major aim of Directive 2004/23/EC is to guarantee recipients' safety in transplantation. Hence, measures for accreditation of establishments storing, preparing and distributing tissues and cells are required to be implemented in Members States' jurisdictions. In addition, adequate training is required for the personnel directly involved in such activities. Despite the adoption of a ?full legislation,? the EU legal framework for cells cannot be seen as totally harmonized. In this article we first address the issues posed at the European level by the uses of human cells as therapeutic agent with regards to their qualification: body elements? Medicinal product? We study the ways to address these bioethical dilemmas at an EU level. Then we discuss the impact of this qualification in terms of safety through the definition of safety's measures and their limits regarding the directive's scope. We conclude with the emergence of an ?ethical safety?.

Requirements for Clinical Trials with Gene Therapy and Transplant Products in Switzerland.

This chapter aims to describe and summarize the regulation of gene and cell therapy products in Switzerland and its legal basis. Product types are briefly described, as are Swiss-specific terminologies such as the term "transplant product," which means products manufactured from cells, tissues, or even whole organs. Although some parts of this chapter may show a guideline character, they are not legally binding, but represent the current thinking of Swissmedic, the Swiss Agency for Therapeutic Products. As so far the experience with marketing approval of gene therapy and cell therapy products in Switzerland is limited, this chapter focuses on the regulation of clinical trials conducted with these products. Quality, nonclinical, and clinical aspects are summarized separately for gene therapy products and transplant products.

Faecal microbiota transplantation: a sui generis biological drug, not a tissue.

Responding to Smith et al. (Nature, 2014), this paper argues that for medical use, faecal microbiota transplantation (FMT) should be considered a sui generis biological drug, rather than a tissue. Smith and colleagues' thesis is based on possible undesirable economic consequences of this designation--not on its scientific and conceptual basis. The faecal transplant (including gut microbiota, metabolites, mucus, human cells, viruses, fungi, etc.) is not a tissue; it is of topographic--not cellular--human origin. We consider the donor a bioreactor, producing the faecal substrate of therapeutic interest. The debate is of singular importance as the FDA considers FMT a drug and released a new guidance for public consultation in February 2014, whereas to date the European Medicines Agency has not promulgated its position. The UK's National Institute for Heath and Care Excellence does not consider FMT to involve the transplantation of body tissue, and in March 2014 the French regulatory agency ANSM expressly declared it to be a drug. As FM is a complex and highly variable admixture, its components cannot be completely characterized, and to date, compositional quality cannot be assessed. We consider FMT to be a sui generis biologic drug, albeit one prepared with unconventional raw material under microbiologic control. The possibility of associating identified bacterial species with particular diseases and cultivating selected bacteria of therapeutic interest would certainly define a second generation of microbiome therapeutics, but is still speculative.

[Report on notifications according to section 8d of the German Transplantation Act (TPG) for the years 2009-2011]. / Bericht zur Meldung nach § 8d Transplantationsgesetz (TPG) für die Jahre 2009 bis 2011.

In Germany, the Tissue Act came into effect on 1 August 2007. Since then, every tissue establishment is legally obligated to keep a record of its activities according to section 8d subsection 3 of the Transplantation Act (TPG). An annual report must be submitted to the Paul Ehrlich Institute once a year up to 1 March of the subsequent year. The report should include the types and quantities of tissues procured, conditioned, processed, stored, distributed or otherwise disposed of, imported, and exported. The report should be made on a TPG-based notification form published on the Internet by the Paul Ehrlich Institute. The present report according to section 8d subsection 3 of the TPG is based on data of the reporting years 2009-2011. Six years after implementation of the TPG's reporting obligation for tissue establishments, the number of tissue establishments known by the Paul Ehrlich Institute has increased from 349 in 2007 to 949 in 2011. In the course of continuous optimization of the notification forms, including tissue-specific glossaries, the reported data of most of the tissues and tissue preparations have become more conclusive.

Organ procurement and transplantation network. Final rule.

: HHS is issuing this final rule (herein referred to as ``this rule'') to add vascularized composite allografts (VCAs) as specified herein to the definition of organs covered by the rules governing the operation of the Organ Procurement and Transplantation Network (OPTN) (herein referred to as the OPTN final rule). When it enacted the National Organ Transplant Act in 1984, Congress included a definition of the term organ and authorized the Secretary to expand this definition by regulation. The Secretary has previously exercised this authority and expanded the statutory definition of organ. Prior to this rule, the OPTN final rule defined covered organs as ``a human kidney, liver, heart, lung, or pancreas, or intestine (including the esophagus, stomach, small and/or large intestine, or any portion of the gastrointestinal tract). Blood vessels recovered from an organ donor during the recovery of such organ(s) are considered part of an organ with which they are procured for purposes of this part if the vessels are intended for use in organ transplantation and labeled `For use in organ transplantation only.' '' This rule also includes a corresponding change to the definition of human organs covered by section 301 of the National Organ Transplant Act of 1984, as amended (NOTA).

Vascularized composite allotransplantation: a member of the transplant family?

The definition of vascularized composite allograft (VCA) and the nomenclature require further attention and interaction with the competent authorities. When compared with solid organ transplantation, VCA donation and allocation imply additional elements such as donor identification, race, and bone constitution, which need to be worked into a scheme for VCA allocation. Furthermore, retrieval of limbs, faces, and possibly other body parts demands algorithms for the sequence of steps during the donor operation. Relevant aspects and criteria for any VCA allocation concept are addressed in this article.

Allocation of vascularized composite allografts: what is it?

To date, there are more than 80 reports of vascularized composite allografts (VCAs; a.k.a. composite tissue allotransplantation). However, the classification of this type of transplantation for oversight purposes has not been clarified. From a biological and regulatory perspective, we propose that VCA retrieval and transplantation is akin to organ transplantation and should be incorporated into the organ oversight structure. As VCA becomes more of a clinical reality, the need for a methodical approach to allocation and access to more donors will develop. Such an allocation system will likely incorporate parameters that deviate from those used for organ transplantation. To develop an effective and balanced system, the use of existing regulatory agencies that oversee solid organs should provide the maximum benefit to the patients and the society.

[Report on notifications according to Section 8d of the German Transplantation Act (TPG) for the year 2008]. / Bericht zur Meldung nach § 8d Transplantationsgesetz (TPG) für das Jahr 2008.

In Germany, the tissue law came into effect on 1 August 2007. The law implemented the requirements of EC directives on quality and safety of human tissues and cells in the German Transplantation Act ("Transplantationsgesetz," TPG) and in the German Medicinal Products Act. Accordingly, tissue establishments are obligated to keep a record of their activities and to submit an annual report to the Paul-Ehrlich-Institut (PEI). The report shall include the types and quantities of tissues procured, conditioned, processed, stored, and distributed, or otherwise disposed of, imported and exported. For this purpose, the PEI published TPG-based notification forms in the Bundesanzeiger and in the Internet. The data provided by tissue establishments have been anonymized and compiled in a general report. The analysis revealed inconclusive data, which can be due to a number of different causes. To achieve better consistency of data provided in the future, the explanations for completing the notification forms will be amended. Thus far, compiled data are not appropriate to draw conclusions on the availability of tissues and tissue preparations in Germany, but the data can serve as reference points.

[The issues of normative regulation of organs and tissues transplantation in WHO documents].

The article deals with the issues of WHO activities in the area of normative regulation of transplantological medical care. The focus is made on the elaboration of normative legal documentation, organization of theoretical and practical discussions, analysis of theory and practice of transplantology of human organs and tissues.

[The 2009 performance report of the German cornea banks]. / Leistungsbericht der Deutschen Hornhautbanken 2009.

BACKGROUND: In Germany, human tissue for corneal and amniotic transplantation is supplied by 27 cornea banks. METHODS: The Section for Tissue Transplantation and Biotechnology of the German Ophthalmological Society records the cornea banks' activities by means of an annual questionnaire. RESULTS: In 2009, a total of 4,818 corneal grafts were processed by 21 responding cornea banks, and 57% were deemed suitable for transplantation. This ratio is slightly higher than the European average. In addition, German cornea banks released 1,257 amniotic grafts in 2009. DISCUSSION: German cornea banks are currently facing new regulatory issues due to updated legislation regarding tissue transplantation. Recent updates in European law have limited the cutoff time for postmortem blood sampling to 24 h, and this regulation may lead to a significant reduction in potential donors.

The regenerative medicine laboratory: facilitating stem cell therapy for equine disease.

This article focuses on the emerging field of equine regenerative medicine with an emphasis on the use of mesenchymal stem cells (MSCs) for orthopedic diseases. We detail laboratory procedures and protocols for tissue handling and MSC isolation, characterization, expansion, and cryopreservation from bone marrow, fat, and placental tissues. We provide an overview of current clinical uses for equine MSCs and how MSCs function to heal tissues. Current laboratory practices in equine regenerative medicine mirror those in the human field. However, the translational use of autologous and allogeneic MSCs for patient therapy far exceeds what is currently permitted in human medicine.

Coding and traceability in Iran.

Transplantation has a long history in Iran. Cornea was the first tissue transplantation in 1935. The Central Eye Bank of Iran was established in 1991 and the Iranian Tissue Bank (ITB) in 1994. Now, there are also some private cell and tissue banks in the country, that produce different tissue grafts such as homograft heart valves, musculoskeletal tissues, soft tissues, cartilages, pericardium, amniotic membrane and some cell based products. There is not a separate legislation for tissue transplantation but the legal framework for tissue donation is based on the "Deceased or Brain dead patient organ transplantation" act (passed on April 6, 2000). For tissue banking there is no regulatory oversight by the national health authority. To increase the level of safety and considering the importance of effective traceability, each tissue bank has its own policy and terminology for coding and documentation without any correlation to others. In some cases tissue banks have implemented ISO based standards (i.e., ISO 9001) as a basic quality management system.

Composite tissue allotransplantation in Europe. Logistics and infrastructure of a centre.

BACKGROUND: Composite Tissue Allotransplantation (CTA) is a new medical field of growing importance. This paper focuses on the infrastructure and organisation of European CTA centres and discusses the differences between national health systems. MATERIAL/METHODS: Eight European centres (Valencia, Innsbruck, Munich, Lyon, Amiens, Creteil, Wroclaw, Monza) were sent with a specially-designed, standardized, 20-item questionnaire. RESULTS: Five of the eight centres returned our questionnaire: Munich, Innsbruck, Lyon, Amiens, Wroclaw. Since 1998, CTA has been performed at these centres. In both French centres and the Polish centre public funding is available in addition to the coverage provided by health insurers. In Munich the costs for a double upper-arm transplantation were Euro 150,000 with an additional Euro 50,000-70,000 per year. In Lyon the costs for a singular hand transplantation were Euro 70,000 per year and in Wroclaw (Poland) the costs for a hand or upper arm transplantation were Euro 20,000-30,000. As many as 17 different medical professions are involved in the CTA at the different centres. CONCLUSIONS: CTA is an innovative promising therapeutic tool that is based on the experiences of solid organ transplantation and profound microsurgical skills. Due to the complexity of the infrastructure, sourcing and the organisation CTA can only be successfully performed at specialized centres. A European network with an international European waiting list and a central coordination for CTA should be established. In order to advance CTA as an important tool in reconstructive surgery we must turn our attention to how the costs will be met, the legal environment for procurement of adequate donors and open ethical questions.

Practical experience in post-mortem tissue donation in consideration of the European tissue law.

In consequence of the European guidelines of safety and quality standards for the donation, retrieval, storing and distribution of human tissues and cells the purpose of tissue transplantation was implemented into German legislation in May 2007. The law came into effect on August 1st 2007 considering of the European rules. The Institutes for Legal Medicine of the University of Frankfurt/Main and the University Medical Center Hamburg-Eppendorf developed a model for tissue retrieval. The Institute of Legal Medicine (I.f.R.) at the University Medical Center Hamburg cooperates with the German Institute of Cell and Tissue Replacement (Deutsches Institut für Zell--und Gewebeersatz DIZG). Potential post-mortem tissue donors (PMTD) among the deceased are selected by standardized sets of defined criteria. The procedure is guided by the intended exclusion criteria of the tissue regulation draft (German Transplant Law TPG GewV) in accordance with the European Guideline (2006/17/EC). Following the identification of the donor and subsequent removal of tissue, the retrieved samples were sent to the DIZG, a non-profit tissue bank according to the tissue regulation. Here the final processing into transplantable tissue grafts takes place, which then results in the allocation of tissue to hospitals in Germany and other European countries. The Center of Legal Medicine at the Johann Wolfgang Goethe-University Medical Center Frankfurt/Main cooperates since 2000 with Tutogen, a pharmaceutical company. Harvesting of musculoskeletal tissues follows corresponding regulations. To verify the outcome of PMTD at the I.f.R. Hamburg, two-statistic analysis over 12 and 4 months have been implemented. Our results have shown an increasing number of potential appropriate PMTD within the second inquiry interval but a relatively small and unvaryingly rate of successful post-mortem tissue retrievals similar to the first examination period. Thus, the aim of the model developed by the I.f.R. is to increase the number of PMTD retrievals and, furthermore, to avoid any conflict of interest between organ and tissue donation.