Guidance for Human Somatic Cell Therapy and Gene Therapy – FDA

Definitions of Somatic Cell Therapy and Gene Therapy

Recently, various innovative therapies involving the ex vivo manipulation and subsequent reintroduction of somatic cells into humans have been used or proposed. Somatic cell therapy is the administration to humans of autologous, allogeneic, or xenogeneic living cells which have been manipulated or processed ex vivo. Manufacture of products for somatic cell therapy involves the ex vivo propagation, expansion, selection (see: "A Proposed Approach to the Regulation of Cellular and Tissue-based Products", Feb. 28, 1997, (62 FR 9721)), or pharmacologic treatment of cells, or other alteration of their biological characteristics. Such cellular products might also be used for diagnostic or preventive purposes. Manufacturers should review policy and regulations to determine how a particular somatic cell therapy or gene therapy product is regulated.

Recently, various innovative therapies involving the introduction of somatic cells into humans have been used or proposed. For the purpose of this Guidance, the term somatic cell therapy refers to the administration to humans of autologous, allogeneic, or xenogeneic living non-germline cells, other than transfusable blood products, for therapeutic, diagnostic, or preventive purposes.

Gene therapy is a medical intervention based on modification of the genetic material of living cells. Cells may be modified ex vivo for subsequent administration to humans, or may be altered in vivo by gene therapy given directly to the subject. When the genetic manipulation is performed ex vivo on cells which are then administered to the patient, this is also a form of somatic cell therapy. The genetic manipulation may be intended to have a therapeutic or prophylactic effect, or may provide a way of marking cells for later identification. Recombinant DNA materials used to transfer genetic material for such therapy are considered components of gene therapy and as such are subject to regulatory oversight.

This document does not discuss genetic manipulation aimed at the modification of germ cells.

Examples of somatic cell therapies include implantation of cells as an in vivo source of a molecular species such as an enzyme, cytokine or coagulation factor; infusion of activated lymphoid cells such as lymphokine activated killer cells and tumor-infiltrating lymphocytes (addressed in a separate Points to Consider document: see below); and implantation of manipulated cell populations, such as hepatocytes, myoblasts, or pancreatic islet cells, intended to perform a complex biological function.

Initial approaches to gene therapy have involved the alteration and administration of somatic cells. However, additional approaches such as the direct administration to patients of retroviral vectors or other forms of genetic material have been used. The concerns described below apply regardless of the method used, though the applicable tests may be different.

Cells for therapeutic purposes may be delivered in various ways. For example, they may be infused, injected at various sites or surgically implanted in aggregated form or along with solid supports or encapsulating materials. Any matrices, fibers, beads, or other materials which are used in addition to the cells may be categorized as excipients, additional active components, or medical devices.

Because of the complexities of potential interactions with the cells and other constituents, additional components should be considered as part of the final biological product for purposes of preclinical evaluation.

Regulatory Considerations

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Guidance for Human Somatic Cell Therapy and Gene Therapy - FDA