Source Animal, Product, Preclinical, and Clinical Issues Concerning the Use of Xenotransplantation Products in Humans

Status: Final

Date: April 2003

Target Audience:

Sponsors of clinical trials, clinical investigators, source animal facility staff, and laboratory personnel involved in protocol development and regulatory submissions to the FDA, such as Investigational New Drug Applications (IND) and Biologics License Applications (BLA)

Laws and Regulations:

  1. 21 CFR Part 312- regulates INDs for drugs and biologics for human use
  2. Public Health Services Act (42 U.S.C. 262), section 351- regulates xenotransplantation products, including cellular therapies, as biologic products
  3. 21 CFR Part 812- regulates investigational device exemptions (IDE) for xenotransplantation products that are a combination of medical devices and biologic material
  4. 21 CFR Part 3- regulates combination products and assignment for premarket review of them

A shortage of transplantation material from humans, such as hearts, kidneys, and tissue from the pancreas, has led researchers to consider using material from non-human animals for transplantation and implantation in humans. This process is called xenotransplantation. However, transplanting tissues, organs, and cells from animals comes with risk of infection from viruses, bacteria, and other infectious agents from the animal donor to the human recipient. The final guidance addresses safety, clinical, and practical issues related to the production, testing, and evaluation of non-human animal material to be transplanted into humans. The goal of the guidance is to suggest methods that improve the safety of patients and researchers before, during, and after clinical trials involving xenotransplantation.

Using animal-derived material in clinical trials presents a risk of transmission of disease from the donor animal to the human subject. Animals with some diseases do not show symptoms of the disease. In the worst cases, some diseases cannot be detected in the host animal without rigorous testing. In order to improve safety during clinical trials using animal-derived material, the animal’s provenance should be well documented and the animal material should be tested for a variety of pathogens, parasites, and diseases such as porcine endogenous retrovirus (PERV).

In order to improve safety, animal sources should be well documented and from US-based herds that are all from the same farm. The animals should be well supervised and not raised as free-range animals. Tissue should not come from slaughterhouses, either. At the time that material is harvested from the animal, samples should be archived for later testing, if necessary.

All xenotransplantation products should be tested for safety, identity, purity, and potency. Assay tests should be performed for bacteria, fungi, microplasma, viruses, and endotoxins. In cases where infectious agents are found, they should be inactivated or removed, or the animal material should not be used and should be disposed of properly.

When the product to be used in a clinical trial is a combination of animal material and medical device, the product should be tested preclinically for bioreactivity and biocompatibility.

When designing clinical trials using animal-derived material, sponsors and individuals involved in developing protocols should address where animal-derived material comes from, how it is tested for infectious agents, and how the safety of clinical trial subjects, laboratory personnel, and healthcare workers will be ensured.

For more information on this issue, contact the Kulkarni Law Firm.