Information and Recommendations for Physicians Involved in the Co-Culture of Human Embryos with Non-Human Animal Cells

The U.S. Food and Drug Administration (FDA) wants you to know that the co-culture of human embryos with nonhuman animal cells raises health concerns for the recipients of such embryos, the offspring resulting from such embryos, and the general public. The use of nonhuman animal cells, tissues or organs in the treatment of human medical conditions is called xenotransplantation. The United States Public Health Service (USPHS) and the FDA define xenotransplantation as "any procedure that involves the transplantation, implantation, or infusion into a human recipient of either (a) live cells, tissues, or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues, or organs that have had ex vivo contact with live nonhuman animal cells, tissues, or organs."

Co-culture of human embryos with nonhuman animal cells fits the second part of this definition. During co-culturing, human embryos and nonhuman animal cells are maintained together outside the body, in ex vivo contact. Thus, the woman into whom the co-cultured embryos are transferred is a recipient of a xenotransplantation product.

A serious concern regarding the clinical use of xenotransplantation is the potential for the transmission of infectious disease from nonhuman animals to humans. Scientists believe that the potential for transmission of an infectious disease from the animal source to a human is of concern either when live nonhuman animal cells, tissues or organs are implanted directly into a human, or when human cells are exposed to live nonhuman animal cells by ex vivo contact. Experience with organ allotransplantation has shown that diseases such as human immunodeficiency virus (HIV) infection, Creutzfeldt-Jakob disease, hepatitis B virus infection and hepatitis C virus infection can be transmitted from the human donor to the recipient. Similarly, xenotransplantation poses concerns for infection with recognized, or as yet unrecognized, infectious agents from nonhuman animals. These concerns may extend beyond the recipient to the general public because of the potential for subsequent transmission of an infectious agent to the recipient's contacts and to the general population. Infections originating from animals that have been known to infect and be transmitted from human to human include, for example, HIV and swine influenza.Many viruses exhibit latency, so that the lack of symptoms at the time of the embryo transfer, or in the short term, does not alleviate all concern.

The U.S. Public Health Service has published guidelines on infectious disease issues in xenotransplantation.  These guidelines, as well as FDA guidance documents, can be found at the website http://www.fda.gov/cber/xap/xap.htm, or obtained from FDA.  They recommend, for example, that:

• You should inform recipients of xenotransplantation products that they and their intimate contacts should defer from donation of blood and other tissues.
• You should inform patients that they have been treated with a xenotransplantation product and of the risks involved.
• You should archive patient samples, such as blood, to allow future monitoring for potential infections.
• You should follow patients for their lifetimes and counsel them to be alert to any unusual symptoms.
• You should archive samples of the xenotransplantation product. In this case, the nonhuman animal cells used for the co-culture process should be archived.

We would be happy to discuss any questions you might have about these recommendations. The nature and level of our concerns may vary depending on the species of nonhuman animal used in the co-culture technique and the source of the culture cells. We plan to have further public discussion of this topic with an appropriate federal advisory committee. At this time, FDA plans to enforce investigational new drug application (IND) requirements for investigations involving further production of embryos co-cultured with live nonhuman animal cells. However, currently it is not our intent to take enforcement action based on the transfer of already existing embryos created by co-culture with live nonhuman animal cells.