The donation and transplantation of human organs, tissues and cells is a complex domain that touches on questions of health, law and ethics. These questions are intrinsically connected. Thus, it demands a stringent regulation by public authorities so as to prevent serious health risks and eventual abuses of the consent given by the donor. Furthermore, the increased demand for organs combined with the globalisation has prompted the phenomena of organ trafficking and “transplant tourism”. These phenomena require additional regulation, ideally at global level.

This article provides an overview of the existing international guidelines and international or supra-national law that guide the sector of human organ, cell and tissue transplantation at national level (Part I). Secondly, it presents several national regulatory regimes (Part II), while some improvements.

1. International guidelines and international or supra-national law

World Health Organization (WHO)

The WHO Guiding principles on Human Cell, Tissue and Organ Transplantation have already inspired many legislators around the world and remain a useful tool for regulators in future. The following eleven principles govern the domain of transplantation:

1) The consent of the donor;

2) The physician determining the death of the donor should not be directly involved in the removal of his organs, cells, tissues or the subsequent transplantation procedures;

3) A genuine and well informed choice of the living donor and maintenance of his health condition;

4) General prohibition of removal of minors’ organs, cells and tissues;

5) Principle of free donations and prohibition of sale;

6) Prohibition of advertising of the availability of organs for financial benefits;

7) Health care professionals should ensure that the person consenting to the donation has not been paid, coerced or exploited.

8) Prohibition for the health facilities to make profit from cell, tissue and organ recovery and implantation;

9) The (clinical) criteria for the allocation of organs, cells and tissues should be equitable, externally justified, and transparent;

10) High-quality, safe and efficacious transplantation procedures (traceability); and

11) Transparency of transplantation procedures, while ensuring personal anonymity and privacy of donors.

The Guiding Principles do not apply to the transplantation of gametes, ovarian or testicular tissues, or embryos for reproductive purposes. They do not apply to the transfusion of blood either.

Regulators could equally look into the WHO Aide-Memoire on Key Safety and Quality Requirements providing very precise and concrete guidelines for the human cells and tissues most frequently used for transplantation. The document addresses the procurement, the donor selection and testing, the contamination control, the retrieval and processing, labeling, storage and packaging, all aspects which are also relevant when legislating.

The WHO Aide-Memoire on the Access to Safe and Effective Cells for Transplantation contains a condensed checklist with set of recommendations regarding the safety, quality systems, assessment, education, promotion and clinical use of human cells for transplantation.

The organ trafficking, transplant tourism and transplant commercialism are separately governed by the Declaration of Istanbul, which provides ethical guidelines and principles in the domain.

Council of Europe (CoE)

At regional level, the Convention on Human Rights and Biomedicine and its additional Protocol on Transplantation of Organs and Tissues of Human Origin can serve as a basic reference. Both documents aim to ensure equitable access to the transplantation services, the respect of the donor’s will, the confidentiality of data, the prohibition of financial gain, the cooperation among states, etc.

Furthermore, the Recommendation of the Committee of Ministers of the CoE invites the member states to set up a comprehensive national transplantation system (NTS) for the authorisation, organisation and monitoring of organ/tissue/cell donation and transplantation; but also to clearly define the NTS competences and responsibilities.

European Union (EU)

The so-called acquis (stock of legal provisions) of the EU contains two directives, the Directive 2010/45/EU on standards of quality and safety of human organs for transplantation and the Directive 2004/23/EC governing standards of quality and safety for the donation, storage, distribution, testing and the procurement of human tissues and cells. We understood that a general revision of both legal texts is underway.

When it comes to the organ trafficking, the Directive 2011/36/EU applies. The legal text considers the intentional act of exploitation – via the removal of a human organ – as an extremely serious offense. Under these circumstances, the consent of the “donor” (the victim) is completely irrelevant.

2. National reference legislation

The vast majority of jurisdictions carefully regulate the domain of the transplantation of human organs. They do so in particular due to the possible abuses to the informed consent of a donor and the severe health risks that could occur if unqualified person were to perform the removal and the transplant of an organ. Moreover, the majority of legislations ensure equal and free of charge access to the transplantation services, contain liability provisions and prohibit the flourishing business of human trafficking and commercialisation of organ/tissue transplants. Generally, the jurisdictions regulate the modalities of labeling, transport, storage and concrete eligibility criteria of human transplantation in their secondary legislation or national protocols, as these are highly technical and complex questions.

Whilst there are detailed provisions in so many jurisdictions, some jurisdictions do not dispose of any legislation at all. The Bahamas is an example of a state that still lacks legislation on the transplantation of human organs. However some fundamental principles, e.g. a free and voluntary consent, the social welfare of the donor, the prohibition of commercial dealing, are laid down in its Code of Professional Conduct. Another illustration is the legal framework of Malaysia, which lacks a legal framework on the donation among living donors. Albeit, as the domain requires stringent regulation, we do not recommend following these examples of “extremely light regulation”.

Before we present some good examples of national regulatory practices, it is first to be noted that certain states classify human tissues and cells as “human organs” or regulate them in the general law on transplant products (for ex. Switzerland, Malta, and Nicaragua). Again others (for ex. Singapore, New Zealand) regulate them in a separate legislation.

Secondly, when it comes to the consent to the donation, two systems can be distinguished worldwide. Namely the “opt-in” system, where the consent of a donor is explicitly obtained. This type of system is implemented inter alia in the United Kingdom, US and Germany. Contrary thereto the “opt-out” systems stipulate that the consent is presumed unless there is evidence for the contrary. Spain, Belgium, Singapore, Colombia and Brazil have created “opt-out” systems. Evidently, these “opt-out” systems usually generate higher donation rates among the population. But they also require a clear regulation to avoid any abuse. Finally, it should be noted that regulations worldwide always confer a right to revoke a consent to the donation.

1. Russia has a “light” legislation, regulating the essential aspects of the transplantation of human organs and tissues, e.g. the prohibition of sale, the principle of voluntary donations, and the data protection. Nevertheless, it differs from some other laws, as it also explicitly requires an informed and written consent of the recipient of the donation. Additionally, it expressly confers certain rights to a donor. In particular donors are entitled to receive complete information about the possible complications for his health in connection with the upcoming surgery for the removal of organs/tissues and to receive free treatment, including medication and health services in connection with the surgery.

2. The law of the Philippines disposes of 19 articles and regulates the most important aspects of the organ transplantation. Namely, the legal definition of a “brain death”, a valid consent, the medical acceptability of the organ and training sessions for the personnel. Moreover, the law of the Philippines provides for an empowerment to share tissues and organs with other states’ approved tissue and organ banks. In addition, the Philippines transplant law obliges certain state organisations to inform the public in a joint campaign. Such a clause is rarely found in other legal systems.

Section 15- Information Drive:

“In order that the public will obtain the maximum benefits from this Act, the Department of Health, in cooperation with institutions, such as the National Kidney Institute, civic and non-government health organizations and other health related agencies, involved in the donation and transplantation of human organs, shall undertake a public information program.”

The law of the Philippines allows the removal and the donation of human organs and tissues in three cases:

• by way of a legacy,

• with the consent given by the immediate relative, or

• with the authorisation of the head of the hospital or the physician in charge of the deceased, when the nearest relatives cannot be found.

3. Pakistan regulates jointly the transplantation of human organs and tissues. As many other states, it distinguishes between donations by a living or deceased donor. Only persons older than 17 years may give a valid consent, but there are no age limits among siblings for transplanting regenerative tissue, i.e. stem cells. Other human organs and tissues can be transplanted among non-close blood relatives, only if the “Evaluation Committee” authorises it. The Pakistani law contains an exhaustive provision on the mandatory members and the competences of the Monitoring Authority. In this context and in view of the shortage of human organs, it is envisaged that the xenotransplantation (i.e. the transplantation of organs/tissues from different species) will in future be considered by the Authority. Commercialisation of human organ is sanctioned by 10 years imprisonment.

Several Latin American countries dispose of easily comprehensible legislation at the same level of “middle” complexity. Honduras, Peru and Colombia regulate on the consent (e.g. 21 years as minimum age for a valid consent in Honduras). They distinguish between a transplantation from a living or a deceased donor, regulate on organ and tissue banks and establish penal provisions. More specifically, they prohibit the transplantation of organs from children and from the aborted foetus. As Colombia disposes of an “opt-out” system, it also contains a provision on the objection to the legal presumption to be a donor.

4. The legislation of Queensland (Australia) thoroughly regulates both human organs and tissues. It confers a big part of its provisions to the donor’s consent. The requirements for a valid consent distinguish between:

• regenerative or non-regenerative tissues;

• deceased donors who died inside and those who died outside the hospital;

• children capable or incapable of understanding the issue of donation. In the latter case the presence of designated officer is required. Generally, the age of 18 years, a sound mind and a furnished medical advice are required.

Additionally, the law contains provision on the examination after death. In the Part 7 of the law, well elaborated penal provisions can be observed. Giving false or misleading information and taking reprisal are defined as offenses. Notwithstanding the prohibition to sell the organs/tissues, the owner of a tissue bank can charge certain fees covering expenses when it comes to the (a) removing, evaluating, processing, storing or distributing donated tissue; or (b) sell, agree to sell, offer to sell or hold himself or herself out as being willing to sell donated tissue for a “cost-recovery amount”. Finally, Queensland foresees the adoption of regulations to further govern more technical aspects, e.g. the conditions, the precautions, and the premises, where the transplantation can take place.

5. The legislation of New Zealand regulates the transplantation of human organs, tissues and cells explicitly. The law is very detailed but not overly complex, while defining the meaning of the expressions used under each section. The conditions and the process for an informed consent, an informed objection and an overriding objection are exhaustively described. Interestingly, New Zealand considers a 16-year old person capable of giving a valid consent to the donation. Besides, it contains penal provisions, e.g. on trading and advertisement of tissues, where corporate and individual liability is foreseen. But even this detailed legislation requires the adoption of ever more detailed regulations to govern the concrete aspects of quality and safety of the collection, import and export of human tissues.

6. Switzerland disposes of the most complete law as it governs the transplantation of organs, tissues and cells from both human and animal origin. Among the initial provisions, the prohibition of human organ/ tissue trade and non-commercialisation of donation are instituted, with the exception of a subsequent symbolic gesture of gratitude, which is allowed. The Swiss law equally permits the preparatory medical measures to preserve organs from a living donor, if (s)he has been informed comprehensively and has freely given the consent. When it comes to the criteria for allocation of organs, the principle of non-discrimination shall be respected. In particular, the following criteria shall be observed:

a. the medical urgency of a transplantation;

b. the medical benefit of a transplantation;

c. the waiting time.

When allocating organs, an effort must be made to ensure that patients who, because of their physiological characteristics, are likely to have to wait a very long time have the same probability of being allocated an organ as patients without these characteristics.

In addition, the National Organ Allocation Office shall document each decision on the allocation of organs and keep the record for 10 years. The Swiss law governs the waiting lists and authorises the storage of organs/tissues, if the necessary technical and operative requirements have been fulfilled and a suitable quality assurance system is in place. Equally, the due diligence needs to be performed by mandatory testing the donor for pathogenic agents. The Swiss legislation can also be commended as it governs the mandatory labeling, documentation, traceability and archiving of important documents (20 years). Additionally, the xenotransplantation, clinical trials, the stem cell register and handling of embryonic and foetal human tissues and cells are thoroughly regulated. Moreover, a right to appeal is foreseen and the law can be submitted to an eventual referendum. Furthermore, the law contains varied enforcement provisions, unfortunately without protection of “whistle-blowers”. Albeit, we can commend to take as a reference the Swiss law. It is very complete, easily comprehensible and not too lengthy.

To conclude, Switzerland recently opened a public consultation to modify certain aspects of its transplant law. Namely, Switzerland considers to further define the unauthorised medical measures before the transplantation from a living donor, to financially protect the living donors and to ensure their medical follow-up.

2. Specific provisions

Many jurisdictions define the brain death which is evidently the primary criterion for the donation of organs from a deceased person. E.g., the legislation of Chile defines the “brain death” by three criteria which must be met cumulatively:

• no voluntary movement can be observed for one hour,

• breathing stopped three minutes after the lung ventilator has been removed, and

• there is absence of brain stem reflexes.

Ontario (Canada) and New Zealand have set up a specific provision regarding the consent to the donation, which is obtained through the driving license procedure. The driving license can only obtained once the driver has declared whether or not s/he consents to the donation of his organs/tissues in case of death. Thereby citizens are obliged to take a position as to whether they wish to consent to the donation or not. Evidently, the basic idea of obliging citizens to take a position could be pursued by other means as well.

Singapore provides for the protection of “whistle-blowers” in Article 15J. Additionally, the legislation contains a special provision requiring the coroner’s consent, when the manner and the cause of the death are being investigated.

The legislation of Taiwan recently prohibited the transplant tourism and imposed high penalties.

Hong Kong contains an elaborate provision regarding the commercial dealings in human organs, e.g. dealings that make, receive, initiate, negotiate or seek to find offers to supply human organs against payment. 50,000 $ and imprisonment up to 1 year are foreseen as sanctions. These sanctions are significantly lower than the Taiwanese provisions.

The transplant law of India has a wide liability provision, on top of the usual responsibility of the director of a company. Under the Indian law, any secretary or other officer of the company with whose consent or connivance the offense was committed, or when the offence is attributable to any neglect on their part is held responsible.

Sri Lanka has set up a provision that allows removal of any organ or tissue from a prisoner, who died inside the prison.

Norway has set up a range of conditions to attain appropriate and timely transport of organs. More specifically, the transport container should be labeled with the following information: name, address and telephone number of both the institute from where it was removed and where the organ will be transplanted; text “Human organs”, the specification of the organ and sign “Gently”; type of transport, temperature and location conditions.

Interestingly, Israel gives certain incentives to donors, i.e. free access to national parks and natural reserves. In addition, it is possible to designate the recipient of the donation. However, this is subject to the decision of the “Evaluation Board”. This Board is composed of a specialised physician not performing transplants, a psychiatrist, an attorney, a social worker and a representative of the public. Moreover, the Israeli legislation provides that the donor and the recipient should undergo a medical, psychological and possibly, a social examination.

South Africa disposes of a separate and very elaborate secondary legislation related to the import and export of human tissue, cells, embryos, etc., stem cells banks, tissue banks, and general control of human body, tissue and organ for transplantation. Equally, Tunisia (available only in French and Arabic) could be commended as it contains specific but clear provisions on the removal, storage, transport and transplantation of the organ. Furthermore, the obligatory screening of organs for diseases is foreseen, however not enlisting exactly the diseases that need to be checked. In this regard India is more precise. The Indian Ministry of Health adopted Rules containing detailed provisions on the obligatory medical tests, i.e. screening for diseases of the organ. Regarding the verification of eligibility of living donors, it requires for ex. supplying a proof of marriage, such as old photographs for unrelated donors in order to prevent commercial dealings.

Australia has recently adopted concrete clinical guidelines on the recipient and donor eligibility.

Regarding the labeling of tissue products, one could take as example the guidelines adopted by the UK Transplantation Professional Advisory Committee.

2. Missing elements or weaknesses

1. Enforcement

The enforcement of a regulation is the essential step in ensuring the effective implementation and contains many aspects. Too often, regulators focus solely on penal provisions, while disregarding other incentives for compliance and other enforcement measures (see the list of incentives of Section 2.3.3 and the Chapter 7 of the Handbook “How to regulate?”).

The legislation of Switzerland is to some extent an exception. It prescribes the adoption of measures necessary to enforce the act, e.g. suspend or revoke authorisations or approvals. The Swiss legislation also provides for a periodic compliance monitoring. The Act shall even be scientifically evaluated as to its influence on the behavior of both the population and medical personnel.

Even in the quite detailed Swiss regulation, the protection of and incentives for “whistle-blowers” are missing. We found elements of whistle-blower protection in the legislation of Singapore, however the incentives for “whistle-blowers” are not foreseen there either. Some examples of whistle-blower protection can be found in Section 7.11.2 of the Handbook “How to regulate?”.

Furthermore potential “whistle-blowers” need to know where to blow the whistle. Central complaint portals, managed by an independent investigation authority, are a useful tool even for jurisdictions which do not wish to go as far as protecting whistle-blowers and giving them incentives. To find examples in other regulatory sectors, see Sections 7.11.2 and 8.6 of the Handbook “How to regulate?”.

[We stress this aspect of whistle-blowing and complaints so much because the attribution of organs is in so many jurisdictions subject to favoritism and non-application of officially foreseen criteria. How can an infringement of the law be better detected than not by an “insider” daring to whistle-blow? Detection by insiders might not only be necessary in certain transplant centres, but sometimes also in certain hospitals. According to press reports, hospital doctors in various countries have worsened the medical diagnosis in order to increase the likelihood of obtaining organs for their patients. Evidently, we cannot assess the frequency of these manipulations and thus the size of the problem.]

2. Information

Providing information to the general public and to those applying the law is an essential preliminary step for the proper application of the law. In the case of donations of organs and tissues information is even essential to make the entire system work. Nonetheless, we could only find few and still incomplete provisions on information, namely in the regulation of the Philippines (explicitly), Singapore (the permitted disclosure of information as a way to enforce the regulation), Israel (conducting public information/education activities to encourage the lawful donation of organs) and Switzerland (informing the public on the transplant medicine).

3. Responding to risks

Despite the notable health risks linked to the transplantation of organs/tissues, very few of the observed legal systems govern the risks extensively already at the legislative level. Thus, states prefer to adopt more detailed regulatory acts due to the high technicality and complexity of the domain. Nevertheless, we believe that at least the following risks should be dealt with already at the level of the primary legislation, given the importance thereof and given the importance of the legislator determining basic risk management principles:

• Risk of spreading disease by use of human and animal tissues (e.g. the law of Switzerland requires a low probability to allow the transplantation);

• In the context of xenotransplantation, the risk of uncontrolled proliferation of tissues but also viruses, sponges and bacteria.

These and other risks can be dealt with in application of the principle of optimised risk reduction, the “full safety principle” (for certain fully controllable risks) and the principle of “risk-benefit analysis”, as explained under Chapter 3 of the Handbook “How to regulate?” .

 

4. Process control

Transplantation centres and hospitals involved in transplantation have to follow complex procedures. Where there is complexity in procedures, there is risk of errors. Hence it would be conceivable to set up legal requirements regarding process control. More and more regulatory sectors have set up such requirements, a movement that started from the sector of aviation. and there is no particular reason why such process control should not be appropriate in the field of transplantation. The risk of favoritism and inappropriate application of criteria, one of the main weak points of the transplantation centres and hospitals, can also partly be mitigated by internal and external process control.

Process control can be executed with different degrees of intensity, up to the level of comprehensive quality management systems (see for examples the end of Section 3.16 of the Handbook “How to regulate?”). Process control shall always be internal, but may be external in addition to add another level of control and verification. External process control is also a tool of enforcement.

5. Incentives for donors

The prohibition of sale and free donation are two fundamental principles, when it comes to the transplantation of organs/tissues. Hence, it is not evident to introduce financial incentives for organ donations in the regulatory frameworks. Nevertheless, in view of the shortage of organs worldwide, it might be pertinent to reconsider the issue. In addition, non-financial incentives, e.g. public recognition of the donor, preferential access for donors to donated organs under the reciprocity system¹ should become operational tools. The few examples of incentives listed above are certainly not the only incentives that could be thought of; see the comprehensive list of incentives in Section 2.3.3 of the Handbook “How to regulate?”. However, evidently the ethical and factual consequences of these incentives have to be carefully examined.

2. Additional information

Global data on the donations and transplantation, country per country and international registers can be accessed on the following link: http://www.transplant-observatory.org/

This article has been written by Ajda Mihelčič, M.A.S., on behalf of the Regulatory Institute, Brussels.