BRUSSELS, Belgium - The challenges posed by tissue transplantation, particularly now that biotechnological techniques are widening its scope dramatically, are receiving increasing attention from regulators and international organizations - a development with obvious implications for the biotech industry.
Elettra Ronchi, head of biotechnology projects at the Paris-based Organisation for Economic Cooperation and Development (OECD), called for urgent international action to develop standards for risk assessment, assist database management, and agree on sharing of information. And a high-level European Union advisory group has just delivered a series of tough recommendations for new ethical and safety rules on human tissue banking.
Ronchi locates the OECD call for action against a background in which biotechnology is revolutionizing transplantation. Novel immunosuppressive regimes, alongside progressive knowledge of the immune system and its role in organ rejection, have rekindled interest in xenotransplantation. Meanwhile, advances in biotechnology and transgenic technology have led to new methods to prevent or reduce xenograft rejection. At the same time, cloning has permitted new approaches to cell and tissue sourcing.
“It seems that xenotransplantation technology is on the way in,“ Ronchi said. “The British biotechnology company Imutran [of Cambridge], for instance, has announced that unless there is evidence of infection in the samples of the 150 patients treated to date with living pig tissues, it will go ahead with a program of experiments which, pending approval from the U.K. government, could lead within five years to the first kidney transplant from its genetically engineered pigs.“
And, among the 29 countries of the OECD, a common conclusion of the many national working documents and discussion papers now under development is that xenotransplantation from pigs is ethically acceptable in principle, Ronchi said.
But the OECD is conscious of widely varying national views on the implications of such advances. “In Europe, there have been some calls for a hold on clinical trials until further research demonstrates that the technology is safe and offers unarguable benefits,“ Ronchi said. Key concerns are the the possibility of new pathogens spreading to humans; the definition of acceptable risk for the human population; and animal welfare issues.
An OECD workshop on transplantation biotechnology earlier this year revealed “a substantial divergence of opinion“ between countries, requiring international dialogue and cooperation on norms for evaluation and management, an agreed research agenda, as well as work on international databases, registries and archives. The latter might be based on the OECD Biotrack system, shared by member governments, which lists field trials of genetically modified organisms and their related commercial applications and product approvals.
The World Health Organization is already consulting on a first working document for the prevention and management of xenozoonoses, as infectious agents transmitted by xenografts are known, but Ronchi insisted that “to make cooperation work, governments will have to involve industry, where most of the research and development is carried out.“ It will also be necessary “to find ways of getting the public involved in the debate,“ Ronchi said.
Tissues 'Subject To Ethical Requirements'
Meanwhile, the European group on ethics in science and new technologies, which advises the European Commission, delivered an opinion on the ethical aspects of human tissue banking in late July. This too recognizes the recent rapid shifts in potential as a result of biotechnology - for instance, by explicitly extending its scope to include not only “constituent parts of the human body,“ but also “cells intended for grafting (in particular for somatic gene therapy and cell therapy), cell lines from cell cultures, as well as cells used to produce proteins and other substances (e.g., monoclonal antibodies).“ Products can “now be obtained by increasingly sophisticated techniques which enable certain properties of the tissues to be modified,“ the group remarked.
Such tissues, it stressed, regardless of how they are obtained and whether they are used for diagnostic, therapeutic or research purposes, “are subject to ethical requirements intended to safeguard respect for human beings, for their dignity and autonomy, and for the common good,“ and to the need for safety for all involved. The opinion examined some of the areas of controversy - such as the problem of commercialization of human tissues, especially those processed and prepared for therapeutic purposes. While recognizing that “some commentators“ argue for non-profit operation only, the group noted that “others hold that the processing and conversion of tissues involves costs which they believe justify their commercial sale,“ with the “added advantage“ of encouraging industry to invest. This is an argument “most often advanced with regard to 'engineered' tissues requiring sophisticated industrial processing techniques,“ it noted.
But the group drew attention to some deficiencies. “At present, we cannot be sure that the health safety of tissues is properly ensured throughout the European Union,“ it concluded, “due to the shortcomings of the existing national rules.“ In addition, there is “insufficient information on tissue storage and distribution conditions across Europe, as no general inventory of human tissue banks has been made“ - although the opinion noted “some of them have been set up by private industries, particularly for the production of engineered tissues.“
The opinion therefore made specific recommendations, “in view of the urgent need to regulate the conditions under which human tissues circulate in the European market. Safety rules must be uniform throughout the European Union.“ The recommendations cover minimum requirements to assess donor and tissue safety, including licensing, staffing and supervision rules, and an obligation that banks not accept tissues which are inadequately procured.
It also came out in favor of tissue banks being “in principle“ reserved to non-profit institutions - although it accepts that “it is difficult to exclude“ commercial organizations, particularly for “'engineered' products requiring the use of sophisticated medical techniques.“ Nonetheless, the opinion insisted that “tissue banks set up by industry should be subject to the same licensing and monitoring requirements as non-commercial operators.“ And tissue imports or exports, it said, should be licensed by public authorities. *