Doctor or surgeon with organ transport after organ donation for surgery in front of the clinic in protective clothing.

Pig Hearts for Humans and the FDA

By Jacob Balamut

David Bennett, a man who recently underwent the world’s first successful xenotransplantation organ surgery, died last month after a sudden and as yet unexplained period of rapid deterioration.

Bennett, who was 57 years old, had been suffering from end-stage heart disease. With limited options for treatment, he underwent an experimental emergency procedure to replace his damaged heart with a genetically modified pig’s heart. The pig was genetically modified to limit the likelihood that Bennett’s immune system would reject the heart.

Many researchers and clinicians alike see the potential for genetically modified animal organs to serve as a solution to our organ transplant and supply issues. The Health Resources and Services Administration estimates that 17 people die per day on the candidate waiting list. These deaths are the result of a lack of supply of organs, which has been a longstanding issue within the United States.

However, currently, the U.S. Food and Drug Administration (FDA) has not approved any genetically modified or pure animal organs for xenotransplantation in humans. For the surgery to go forward in Bennett’s case, the team had to submit a request to the FDA seeking to use the pig heart in the emergency procedure (so-called “compassionate use”). The lack of approved xenotransplantation products stems from a lack of safety data and concerns regarding the potential for cross-species infections to occur.

In 2016, the FDA updated previously existing guidance for xenotransplantation. The purpose of the guidance was to inform the industry of how the FDA would be handling xenotransplantation applications and to provide recommendations.  In order for xenotransplantation products to be approved, the following process must occur.

Xenotransplantation Products at the FDA


Generally speaking, when seeking FDA approval, a potential product will first be classified as either a drug or medical device. Drugs and medical devices are broad, overarching categories and establish general requirements for product sponsors. In addition, there are further subcategories such as xenotransplantation, xenograft, and biologics, with each category featuring further requirements relevant to the product.

Section 201(g) of the Federal Food, Drug, and Cosmetic Act, which defines drugs, and Section 201(h), which defines medical devices, are remarkably similar; but one of the primary differences relevant here is that a product cannot be defined as a medical device if it achieves any of its primary purposes through chemical action. A product is considered to achieve a purpose through chemical action where the product interacts with the body on a molecular level.

Any live animal product, such as the pig heart in this context, relies on natural chemical processes in order to function. Consequently, xenotransplantation products are usually classified as drugs, more precisely as biological products under Section 351 of the Public Health Service Act. To be approved, a sponsor of biological products (similar to sponsors of other drugs) must demonstrate that they are safe and effective for their intended purpose.

Approval process for biologics

Within the FDA, the Center for Biologics Evaluation and Research (CBER) specifically contends with applications made for products that are biologics. In the context of biological products, CBER’s process for approval is:

  1. Pre-clinical phase – During the pre-clinical phase, sponsors of biological products gather safety data by testing their products in the laboratory and on animals. For example, in order for a genetically modified pig heart to become an FDA-approved product, it must undergo testing in non-human species to demonstrate that the drug is safe for human trials.
  2. The Investigational New Drug Application (IND): A sponsor submits information regarding the biological product’s composition, the results of pre-clinical tests, and a plan for clinical trials in humans. If the IND application is approved, the sponsor is free to begin clinical trials.
  3. Clinical Trials: Clinical trials consist of three phases. Phase 1 typically employs healthy volunteers to test the safety of the biological product, whereas phases 2 and 3 employ patients to demonstrate the product’s effectiveness for its intended purpose and to observe side effects.
  4. Biologics License Application (BLA): The multi-step process culminates with the submission of an extensive BLA, which includes all the clinical trial data, product labeling, and more.

Challenges to Overcome

This approval framework is implemented by the FDA in order to ensure that biologic products are actually safe and effective for patient use through extensive testing and review. Given this approval framework, it is clear why it will be challenging to get a genetically modified pig heart approved for widespread human transplants.

The first problem for a sponsor of such a product begins with demonstrating, at the end of the pre-clinical stage, that the product is reasonably safe for initial transplantation into humans. Considering the FDA’s concerns regarding the potential for cross-species infection, it would be difficult to demonstrate that the product is safe for transplantation into humans without being able to test on humans. The second major problem occurs during the clinical trial phase — simply gathering enough data to show that the pig heart is safe and effective for widespread use in humans is extremely difficult.

Considering these challenges, it seems unlikely that we will see pig hearts as a regular transplant substitute anytime soon.

Jacob Balamut is a dual degree JD/MPH 3L student at Penn State Dickinson Law and Penn State’s College of Medicine.

The Petrie-Flom Center Staff

The Petrie-Flom Center staff often posts updates, announcements, and guests posts on behalf of others.

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