Cord blood beyond transplantation: can we use the experience to advance all cell therapies?

Unrelated cord blood (CB) units, already manufactured, fully tested and stored, are high-quality products for haematopoietic stem cell transplantation and cell therapies, as well as an optimal starting material for cell expansion, cell engineering or cell re-programming technologies. CB banks have been pioneers in the development and implementation of Current Good Manufacturing Practices for cell-therapy products. Sharing their technological and regulatory experience will help advance all cell therapies, CB-derived or not, particularly as they transition from autologous, individually manufactured products to stored, 'off-the shelf' treatments. Such strategies will allow broader patient access and wide product utilisation.

[Structural or functional relationship between immunohematology and distribution - Which elements for controlling risks?] / Lien immunohématologie-délivrance structurel ou fonctionnel ­ Quels éléments pour la maîtrise des risques ?

OBJECTIVE: Transfusion safety is based on the availability of safe and compatible blood products at the right time and to the right patient, and requires close monitoring in order to detect possible incidents. The decree of June 20th 2018, which establishes the national blood transfusion's guiding plan, states that the organization that prevails throughout the national territory is built around an inseparable link between the implementation of erythrocyte immunohematology and the labile blood products delivery by authorised structures. METHOD: The article describes the two types of the link's organization, structural or functional, used to develop the comparative risk-benefit analysis. RESULTS: The structural link, which has fewer interfaces, reduces risk situations that lead to delays in release by default of a compatible product. The cases in which a functional link may have a greater benefit than the risks generated are those related to a geographical distance between the delivery site and the patient's place of care. In these cases, a functional link is possible provided that certain organizational points are mastered. CONCLUSION: The comparative analysis shows that the structural link is to be favoured since that the coherence of the patient's care and his care path is ensured. In certain situations, mainly geographical, the functional link can have a benefit that offsets the risks generated by the new interfaces; provided that the system is secured by a real tripartite collaboration between health care institution, biology laboratory and delivery site.

Banking feces: a new frontier for public blood banks?

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection and is potentially beneficial in other microbiota-related disorders. The provision of FMT in routine clinical practice requires an extensive infrastructure that is reliant on voluntary donors. Alongside an increasing demand for FMT, the logistic barriers of a large-scale donor-dependent operation and the difficulties among health authorities to regulate FMT limit the dissemination of sustainable FMT services. Blood centers are large organizations that handle a multitude of donor-dependent operations on a daily basis. Blood and feces share many of the same dependencies, and feces may present a new opportunity for the blood services to handle. In this paper, we describe how an FMT service may be established and embedded within the blood service infrastructure, and we explain the benefits of using blood donors as feces donors. We further explore the current indications of FMT, the challenges related to the lack of legislation, and the future perspectives for blood banks to meet a new and increasing demand.

Developing Induced Pluripotent Stem Cell-Based Therapy for the Masses.

The discovery of induced pluripotent stem cells and the ability to manufacture them using clinically compliant protocols has the potential to revolutionize the field of regenerative medicine. However, realizing this potential requires the development of processes that are reliable, reproducible, and cost-effective and that at the same time do not compromise the safety of the individuals receiving this therapy. In the present report, we discuss how cost reductions can be obtained using our experience with obtaining approval of biologic agents, autologous therapy, and the recent approval of cord blood banks. Significance: For therapy to be widely available, the cost of manufacturing stem cells must be reduced. The steps proposed in the present report, when implemented, have the potential to reduce these costs significantly.

[Why is it necessary to review the December 15th 2003 circular relative to the transfusion act?]. / Pourquoi réviser la circulaire du 15 Décembre 2003, relative à l'acte transfusionnel?

Blood transfusion is currently a delegated medical act in patient care services. Following severe adverse events, hemovigilance now disposes of a dense regulation. Data collection and analysis in the national hemovigilance "e-FIT" database allow detection of errors or malfunctions in the transfusion act. Blood transfusion safety depends on the strict respect of processes from the prescription of blood products and required patient immuno-hematology exams to the administration of blood products and follow-up of the patient. In the circular relative to the transfusion act, many steps of the transfusion process, less explicit, can be interpreted differently by health care professionals and thus lead to errors or severe adverse events. Standardization of procedures for the transfusion act and its surveillance would increase their safety and avoid potential risks for the patient.

Research using autologous cord blood - time for a policy change.

• Type 1 diabetes results from the loss of normal immunological self-tolerance, which may be attributable to the failure of Foxp3+ regulatory T cells (Tregs). Umbilical cord blood is rich in Tregs and therefore has the potential to prevent or delay the onset of type 1 diabetes. A pilot trial is currently underway in Australia to examine whether infusion of autologous cord blood can prevent type 1 diabetes in high-risk children with serum antibodies to multiple ß-cell antigens. • A number of other potential therapeutic indications for autologous cord blood have been proposed, including cerebral palsy and hypoxic-ischaemic encephalopathy. • Recruitment to clinical trials using cord blood is influenced by divergent public and private cord blood banking policy in Australia. The burgeoning consumer demand for storage of cord blood highlights the need for regulatory bodies to develop and adapt policies to facilitate research that may extend the use of cord blood beyond currently recognised indications. • Consumers, researchers and policymakers must also recognise specific ethical issues associated with collection and storage of cord blood, including storage in public and private banks, informed consent, ownership, access and the principle of beneficence.

Ethical and legal issues raised by cord blood banking - the challenges of the new bioeconomy.

• Cord blood banking raises ethical and legal issues which highlight the need for careful regulatory approaches to the emerging bioeconomy. • Consent processes for both private and public banking should be inclusive and representative of the different familial interests in the cord blood. • Property law is a potentially useful way of understanding the mechanisms for donation to both public and private banks. • Increasing tensions between public and private models of banking may require the adoption of hybrid forms of banking.

Institutional incentives for altruism: gifting blood in China.

BACKGROUND: In mainland China, the motivation behind voluntary blood donation is a relatively new and understudied behavior. In recent times provincial governments in China have implemented various institutional incentive measures. However, little is known regarding the effectiveness of such measures. This qualitative study investigated the nature and outcomes of some identified institutionalized mechanisms, in particular how these were created and distributed in the form of incentives for voluntary blood donation. METHODS: Participatory observations were conducted at two blood donation stations and four blood collecting vehicles in Changsha city, China. In-depth interviews were conducted with 17 staff and 58 blood donors at the aforementioned venues from May to October 2008 in Changsha. RESULTS: Thematic analysis revealed the operation of four primary type incentives: policy-driven, symbolic, information feedback and role models, which constituted the system of institutional incentives. The current blood reimbursement system was not the primary motivation for blood donation; instead this system was a subtheme of future assurance for emergency blood needs. It was evident that symbolic incentives stressed the meaning and value of blood donation. Furthermore, post-donation information services and the inherent mechanisms of communication, enhanced by some public role models, served to draw the public to donate blood. CONCLUSIONS: At the institutional level, blood donation was not only informed by altruism, but also carried a system of benefit and reward for the donors and their family members. We would recommend that such arrangements, if accommodated effectively into China's health promotion strategies, would increase the likelihood of blood donation.

High acceptance rate of hybrid allogeneic-autologous umbilical cord blood banking among actual and potential Swiss donors.

BACKGROUND: Two competitive concepts of umbilical cord blood (UCB) banking are currently available: either allogeneic UCB is donated to a public bank or autologous cells are stored in a private bank. Allogeneic-autologous hybrid banking is a new concept that combines these two approaches. However, acceptance of hybrid UCB banking among potential donors is unknown to date. STUDY DESIGN AND METHODS: In a prospective survey, we aimed to establish the acceptance of the hybrid banking model among actual and potential UCB donors in Switzerland. The study groups consisted of parents and pregnant women with or without children. As control group, women at reproductive ages were investigated. RESULTS: The majority of participants agreed fundamentally with UCB donation, and overall acceptance of private banking was 47%. If a possibility for hybrid banking were to be made available, 49% would opt for such a public-private model and only 13% would choose private banking alone. Among the proponents of hybrid banking, a majority of participants chose donor cell splitting over the sequential banking mode. Fifty-six percent of responders wished prior notification before the release of their donated UCB to a foreign recipient. CONCLUSIONS: This is the first study which compared the acceptance of allogeneic, autologous, and hybrid allogeneic-autologous UCB banking in different target groups. We demonstrated that hybrid cord blood banking is the preferred model of banking among actual and potential UCB donors. With increasing demand for UCB in the future, health care providers should therefore consider offering hybrid banking as a viable storage option.

Umbilical cord blood banks. Ethical aspects. Public versus private banks.

The creation of umbilical cord blood (UCB) banks raises interesting medical, social, economic and ethical issues. This paper reviews the ethical problems specifically. In this respect, it evaluates: a) whether there are advantages to the use of UCB compared to bone marrow, b) whether or not it is ethical to create UCB banks, c) whether their creation is ethically acceptable in terms of their clinical usefulness or d) the use made of them for therapeutic purposes, and finally e) whether their creation is ethically justified from a cost/profitability point of view. We focus primarily on evaluating the ethical controversy between public and private banks, particularly on whether it is ethical to bank autologous blood in private UCB banks, on the basis of its limited possibilities for use by the cord blood donor. We can conclude that, from an ethical point of view, autologous blood banks have limited acceptance among specialised researchers, scientific societies and other public institutions. Therefore, we believe that it is ethically more acceptable to support the creation of public UCB banks for medical and social reasons and, above all, based on the principle of justice and human solidarity. Nevertheless, there is no definitive ethical argument why a couple, according to their autonomy and freedom, cannot bank their child's UCB in a private bank. An equally acceptable solution could be the creation of mixed banks, such as that proposed by the Virgin Health Bank or like the Spanish system where autologous samples can be stored in public banks but with the proviso that if at any time the stored sample is required by any person other than the donor, it would have to be given to them.

Events at blood collection area due to nonconforming blood bags and plateletpheresis kits: need for timely corrective and preventive actions.

BACKGROUND: Good blood banking practice requires that every effort should be made to detect any deviation or defect in blood bank products and to identify any potential risk to blood donor or recipient(s). We report the findings of an exercise that provide an insight into why feedback from the user side is crucial. STUDY DESIGN AND METHODS: Various events involving blood bags and plateletpheresis kits and the corresponding appropriate actions instituted for remedial measures were recorded. These scattered events were recorded for 6 months following the use of a new batch of improved blood bags with add-on features. Several events related to plateletpheresis kits from three different manufacturers were also recorded for 1 year. RESULTS: The affected blood bags were utilized with no untoward incident. The complaint was closed following satisfactory response from the blood bag manufacturing company that acted in a timely manner in addressing the root causes of the problems. However, corrective and preventive actions (CAPA) could not be implemented for plateletpheresis kits. The rate of undesirable events was higher with plateletpheresis kits as compared with whole blood bags (1.75% vs. 0.06%). CONCLUSION: As defects or deviations that trigger the need for CAPA can stem from numerous sources, it is important to clearly identify and document the problems and level of risk so that appropriate investigations can be instituted and remedial actions can be taken in a timely manner. This study demonstrates the usefulness of a quality initiative to collate and analyze blood product faults in conjunction with blood product manufacturers.

Blood bank regulations in India.

Successful blood services depend on legally empowered regulatory services. Blood transfusion services are important constituents of national health services. Blood transfusion services in India are regulated by the Drugs and Cosmetics Act, 1940 and its subsequent amendments. The Drugs and Cosmetics Act, 1940 specifies about accommodation, manpower, equipment, supplies and reagents, good manufacturing practices, and process control to be followed in Indian blood transfusion services.Regulatory affairs in the Indian blood banking system are controlled by central and provincial Drug Control authority under Drug Controller General of India. National AIDS Control Organization (NACO) acts as a facilitator to Indian blood transfusion services on behalf of the Ministry of Health and Family Welfare, Government of India,especially to the government sector. The National Blood Policy was published by the Government of India in 2002 and it provides objectives to provide safe, adequate quantity of blood, blood components, and products.

Biobanks between common good and private interest: the example of umbilical cord blood private biobanks.

Storage of human biological samples and personal data associated with them is organised in Biobanks. In spite of expectation given by biobanks in medicine, their management involved some ethical questions, for example, the need for policies to regulate economic interests, potential commercial use of data (including patents), private sector financing, ownership of samples and benefit sharing. In the context of contributing to the general public interest, we can consider the act of giving biological material to biobanks as a donation, in which the donation constitutes part of a generalised form of reciprocity in which the act of donation contributes to society's common good. Starting from this perspective, we move into a different situation represented by the biobanking of umbilical cord blood for personal use. We used the example of the private biobanking of umbilical cords to demonstrate the restrictive utility of the collection and preservation of cord blood for personal use in private biobanks, in the context of society's common good. In summary, a system based on solidarity seems to be able to guarantee necessary levels of supply for the donation of biological material to biobanks.

Creación de la red de servicios de medicina transfusional y bancos de sangre del Ministerio de Salud Pública y Asistencia Social, para su regionalización y categorización: acuerdo ministerial No. 529-2011 / Creation of the network of transfusion medicine services and blood banks of the Ministry of Public Health and Social Assistance, for its regionalization and categorization: ministerial agreement No. 529-2011

El objetivo de crear esta red, es la de integrar todos los servicios de la medicina transfusional y los bancos de sangre. En el documento se establecen las funciones de la mencionada red. Incluye las definiciones de los conceptos relacionados al tema principal, además de la infraestructura que deberá tener cada centro, incluidos el equipo y recurso humano y técnico. Enumera la ubicación de los distintos centros de medicina transfusional y los bancos de sangre, destacando como de "referencia" los de los hospitales San Juan de Dios y Roosevelt, los mismos cuentan con los dos bancos principales de sangre del país. Hace la diferencia entre un banco de sangre regional y un centro de trasfusión, detallando igualmente la infraestructura, características, servicios y personal de estos últimos.

Proceedings of a consensus conference: Risk-Based Decision Making for Blood Safety.

Blood safety decision making has become increasingly complex, and a framework for risk-based decision making is, thus, needed. The purpose of this consensus conference was to bring together international experts in an effort to develop the foundations for such a framework. These proceedings are described with a view to making available to the transfusion medicine community the considerable amount of information and insight that was presented and that emerged through debate by the experts, panel members, and delegates.

Family-directed umbilical cord blood banking.

Umbilical cord blood transplantation from HLA-identical siblings provides good results in children. These results support targeted efforts to bank family cord blood units that can be used for a sibling diagnosed with a disease which can be cured by allogeneic hematopoietic stem cell transplantation or for research that investigates the use of allogeneic or autologous cord blood cells. Over 500 patients transplanted with related cord blood units have been reported to the Eurocord registry with a 4-year overall survival of 91% for patients with non-malignant diseases and 56% for patients with malignant diseases. Main hematologic indications in children are leukemia, hemoglobinopathies or inherited hematologic, immunological or metabolic disorders. However, family-directed cord blood banking is not widely promoted; many cord blood units used in sibling transplantation have been obtained from private banks that do not meet the necessary criteria required to store these units. Marketing by private banks who predominantly store autologous cord blood units has created public confusion. There are very few current validated indications for autologous storage but some new indications might appear in the future. Little effort is devoted to provide unbiased information and to educate the public as to the distinction between the different types of banking, economic models and standards involved in such programs. In order to provide a better service for families in need, directed-family cord blood banking activities should be encouraged and closely monitored with common standards, and better information on current and future indications should be made available.

Blood, AIDS, and bureaucracy: the crisis and the tragedy.

The politics of health were never tested more than when AIDS surfaced at the beginning of the 1980s in the industrialized nations. In those countries, it became the most important medical crisis of the last half of the 20th century. Today, the significance of AIDS remains as not only an unrelenting disease but also as a disease that continues to affect social and political life throughout the entire world. The connection between blood transfusion and AIDS is now under control in the industrialized countries but only because of lessons that took too long to learn over the past 25 years. That process had different roots and effects depending on the various national blood programs and policies in different countries. That is illustrated by comparing events in France, Japan, Canada, and the United States that differed in donor and patient populations and on decisions made and secrets kept. Some of the problems persist to this day in parts of the world. Overall, the lessons learned from what happened with blood early in the AIDS epidemic apply to other aspects of human disease and could help in facing the new problems that are sure to appear in the future.

[Seventeen years of haemovigilance in France: assessment and outlook]. / Dix-sept ans d'hémovigilance en France: bilan, perspectives.

Since 1994, the French haemovigilance network has not stopped evolving. Based initially on the reporting of informations and incidents related to recipients, it quickly became interested in the procedures and other activities related to blood component transfusion, in order to improve blood safety. Despite some failures (under reporting, heavy declarative management), the French haemovigilance network is going to continue working on improving blood safety, both at the level of the recipients and the donors, and participate to the global improvement of quality of care.

[European Blood Alliance (EBA) and EuroNet TMS: what challenges for the transfusion of tomorrow?]. / European Blood Alliance (EBA) et EuroNet TMS: quels enjeux pour la transfusion de demain?

The primary mission of the European Blood Alliance (EBA) is to contribute to the safety and efficiency of the supply of blood products, cells and tissues, in developing an active network of blood establishments in Europe (25 countries). Its strategic objectives are to improve performance (through working groups and projects funded by the European Union), to engage in regulatory affairs (particularly at the European Commission level) to promote best practices and to facilitate a network to collect and share knowledge and experiences. The main objective of EuroNet TMS, combining the blood scientific societies from more than 30 countries in Europe, is to update and publish regularly, intended for policymakers, a White Book on the transfusion chain from donor to patient and probable or possible changes in the coming 5 years. Since 2008, EBA and EuroNet TMS actively collaborate on the drafting of the 2nd edition to be published in 2011. The two presidents jointly drafted the final chapter outlining the major issues of transfusion for tomorrow, summarized thereafter. Transfusion will still be useful for a long time and for reasons of safety and ethics the voluntary and unpaid donations, with non-profit blood establishments, will remain, the cornerstone of the supply of blood products. This renders crucial the continuous improvement of donor management and optimal blood use. On the regulatory side, after 5 years of implementation, EU directives must be independently evaluated and the Blood Guide of the Council of Europe should gradually become a regulatory standard. Finally, if a competition should be introduced for the blood products, it should be strictly regulated to prevent any threat to the security of their supply and quality for patients.