Dear Members,

I have been asked to take on the IXA Newsletter and Communications on behalf of the IXA Council in place of Rita Bottino who has provided expert leadership over recent years and who has taken on the role of Secretary-Treasurer of IXA. On behalf of the Society, many thanks to Rita for her hard work!

The IXA Newsletter should reflect the interests of the membership – and serve to invite new members from the many clinicians and scientists involved in xenotransplantation, notably as clinical trials emerge. As we think about new ways to communicate the excitement surrounding xenotransplantation, I invite our members to offer advice and content for future newsletters (fishman.jay@mgh.harvard.edu). We will be reaching out via podcasts and other social media in the future. Many thanks for your participation!

Best wishes for 2022!

As preclinical and clinical studies advance, as well as generation of swine as potential source animals for clinical xenotransplantation, the US Food and Drug Administration (FDA) has issued a revised PHS Guideline on Infectious Disease Issues in Xenotransplantation (Docket No. FDA-2012-N-0559) for comments by the public (Public Health Service (PHS) Guideline on Infectious Disease Issues in Xenotransplantation). These proposed guidelines have raised a series of thoughtful considerations regarding the safety challenges posed by clinical xenotransplantation. As is generally understood, the risk for infection will be related to the intensity and duration of immunosuppression deployed in a specific xenotransplantation regimen that will be defined for each specific protocol. This proposed guideline discusses (1) The development of xenotransplantation clinical protocols; (2) the preparation of submissions to FDA; and (3) the conduct of xenotransplantation clinical trials. Under the proposal, record-keeping/clinical data would be maintained in a cross-referenced system that links the relevant records of the xenotransplantation product recipient, xenotransplantation product, source animal(s), animal procurement center, and significant nosocomial exposures. These records and blood and tissue samples would be maintained for 50 years. The PHS guideline also describes an occupational health service program for the protection of health care workers involved in xenotransplantation procedures, caring for xenotransplantation product recipients, and performing associated laboratory testing. The duration of maintenance of clinical records and samples is extrapolated from experience with Human immunodeficiency virus (HIV) and Human T-lymphotropic virus (HTLV) and hepatitis C virus – which may have prolonged latency. It may be worth noting that such exogenous human viruses have a much shorter latency in immunosuppressed allotransplant recipients and that for HIV and HCV, antiviral therapies have emerged that impact the course of infection. The likelihood of infection by comparable endogenous retroviruses of swine (or unknow porcine viruses) remains unknown.

The guideline poses some important practical questions:

1. Who are the best candidates for initial trials of clinical xenotransplantation? And who might be excluded by virtue (e.g.,) of preexisting immune deficiency in the recipient or their social contacts? How might children be considered as candidates?
2. How should infectious disease surveillance be performed for recipients and clinical staff involved in organ procurement, transplantation, and clinical care? How should infectious disease surveillance be performed for source animal caretakers? Assuming universal and contact precautions are deployed, how would needlestick or laceration injuries be handled?
3. Which samples (blood cells, sera) should be stored against future epidemiological investigations? And from who?
4. Who has access to such data and samples? And which tests are performed routinely and for “cause”?
5. Who should develop and maintain a central database to catalog samples and patient data for up to 50 years (when most of the clinical sponsors, patients and clinical staff may no longer be available)?

Many of these questions will merit discussion among investigators on an international basis – as was done under the auspices of the World Health Organization in the past. The IXA will continue to be engaged in these discussions as clinical application of xenotransplantation develops.