FDA invites comments on xenotransplantation product regulatory standards ahead of public meeting

This CTGTAC meeting announcement comes after recent technological advancements that have helped facilitate xenotransplantation product development and fueled a renewed interest in xenotransplantation. Most notably, in January 2022, a team of surgeons at University of Maryland Medical Center performed the first successful transplant of a genetically engineered pig heart into a living patient. Unfortunately, the patient died two months after surgery.  The cause is undetermined, but it has been revealed that the pig heart carried porcine cytomegalovirus, a pig virus that is difficult to detect.  In addition, another development garnering interest in xenotransplantation occurred in September 2021, when doctors at New York University Langone Health successfully attached a kidney from a genetically modified pig to the body of a deceased donor.

This announcement suggests the possibility of updates to FDA guidance documents governing xenotransplantation protocols and the development of xenotransplantation products. Over the past 20 years, FDA, the Public Health Service (PHS), and other national authorities have issued guidances to help minimize potential public health risks of xenotransplantation, primarily the transmission of infectious agents of animal origin into the human population. However, these guidances have not been updated to reflect new technological developments. The guidances also impose stringent regulatory requirements on both xenotransplantation product sponsors and recipients of such products, including but not limited to:

• life-long surveillance of product recipients;
• archival of biological specimens obtained from recipients for 50 years beyond the xenotransplantation date; and
• deferral of donation of body fluids such as blood, breast milk, ova and sperm by the recipients and/or close contacts.

These requirements can be unduly burdensome, especially for xenotransplantation products developed from well-characterized animal cell lines, including products for which the initial contact with such animal cell lines during product development was highly attenuated.

FDA appears committed to updating its approach to regulation of xenotransplantation products as scientific knowledge in this area advances. Indeed, in FDA’s Briefing Document, the agency notes the advent of advanced sequencing technology that has permitted for greater sensitivity in quantifying nucleic acid content of both known infectious agents and potentially identifying emerging infectious agents. In light of this, the agency specifically seeks input on the requirement for archiving of xenotransplantation products and patient samples.

The agency also seeks insight from the CTGTAC on:

• infectious disease risks associated with xenotransplantation products;
• prevention of xenotransplant rejection through gene modification of donor animals and immune suppression of human recipients; and
• strategies for meeting regulatory requirements regarding identity, purity, and potency of xenotransplantation products.

Next steps

The CTGTAC will review comments submitted to docket FDA-2022-N-0784 by June 22, 2022. However, comments may generally be submitted to the docket until June 28, 2022. If you wish to submit a comment or have any questions about the opportunities and operational challenges regarding the regulatory requirements for xenotransplantation products, please contact the authors or the Hogan Lovells attorney with whom you regularly work.

Authored by Michael N. Druckman and Yetunde Fadahunsi, with the assistance of summer associate Rebecca Popkin

This article is the seventh in our 2022 series, “Trends in Cell, Tissue, and Gene Therapies,” which aims to help you stay informed about the broad array of legal and regulatory issues affecting companies operating in the regenerative medicine space. From clinical studies, to obtaining patents, to scaling up manufacturing, our global team will discuss novel issues arising in all parts of the world, including unique deal-making, litigation, and inspections concerns for CTGT companies. Ensure you are subscribed to Hogan Lovells Engage to receive these new insights weekly!