Global regulatory requirements for xenotransplantation clinical trials

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  • The views expressed in this paper are the responsibility of the author and not necessarily of WHO.

Progress registered by xenotransplantation research in pre-clinical studies, year after year, continues to justify hopes in clinical applications that could solve current therapeutic limitations and perhaps result in a breakthrough. Yet, there are few current ongoing clinical trials. Prudence in the conception and conduct of xenotransplantation trials follows the requirements of the Changsha Communiqué resulting from the First WHO Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials in Changsha, China, 19–21 November 2008.

The article on “Xenotransplantation-associated infectious risk” by Jay A. Fishman, Linda Scobie, and Yasuhiro Takeuchi in this issue was written as a background document for the Second Global Consultation on the same theme that took place on 17–19 October 2011 in Geneva. The International Xenotransplantation Association and The Transplantation Society must be acknowledged for their support without which the consultation could not have taken place. The consultation brought together 23 experts in xenotransplantation from 14 countries, 13 designated by their national authorities, and seven of them representatives of national regulatory authorities.

Even if progress has been made in the prevention and detection of some of the risks of xenozoonosis transmission, human xenotransplantation must remain under careful scrutiny. Yet, the global heterogeneity allows unregulated xenotransplantation activities to continue in countries with regulatory loopholes or weak health authorities. Some promoters of xenotransplantation clinical trials have moved their activities from continent to continent, sometimes evidently taking advantage of weaknesses in the regulatory oversight. Vulnerable patients are lured into paying hefty sums for therapies with unproven efficacy and unknown risks.

The second consultation stressed the need for transparency in the co'nduct of any xenotransplantation activities, including (but not limited to) the design of the trials, as well as in the development of national policies and procedures to regulate them. Transparency acknowledges patient’s privacy rights and commercial confidential information but shares justifications for the trial as well as measures taken to minimize risks. Transparency includes full publication of data and encourages independent experts’ advice, as well as allowing timely independent data review. In case of suspicion of a transmitted xenozoonosis in one recipient, global expertise and resources, for instance for testing, must be available to ensure optimal safety. It is expected that WHO should facilitate the creation of a collaborative group of public/ academic xeno-related infectious disease reference laboratories and appropriate Health Authorities’ resources to support assay development, validation, and standardization. In general, WHO is to be a catalyst bringing together regular (annual or biennial) interaction between regulator and xenotransplantation subject matter experts, as appropriate to the level of contemporary xenotransplantation activity. This global consultation would discuss planned or ongoing xenotransplantation clinical activities and provide a framework for exchanges identifying needs for advice and collaborations.

The necessity to create a global governance of xenotransplantation was underlined by the Fifty-seventh World Health Assembly in Resolution WHA57.18. Mindful of the infectious risk associated with xenogeneic transplantation, the Assembly requested the Director-General to facilitate communication and international collaboration among health authorities. Likewise, Member States were urged to harmonize global practices. It is hoped that all stakeholders will contribute to establish this global communication and complementary cross reliance.

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