The US Food and Drug Administration (FDA) issued a draft guidance to help companies developing gene therapies determine whether their therapy is the same as another product when aiming to apply for orphan drug designation and orphan drug exclusivity. The agency states that when a gene therapy shares the same “principal molecular structural features” as another gene therapy with orphan drug status, it cannot be approved by the FDA for the same condition (albeit with certain exceptions, such as when a second product is clinically superior). The “molecular structural features” refer to the transgene and vector of a gene therapy, and thus the FDA will consider two gene therapies different if they express different transgenes and/or use different vectors, such as a retrovirus vector or an adeno-associated virus (AAV). If vectors from the same viral class are used (such as different AAV subtypes), then the FDA will determine on a case-by-case basis whether the gene therapies are the same. The FDA notes that additional features, such as regulatory elements or the cell type transduced, might be taken into account when determining sameness. As a consequence, even when two gene therapies share the same transgene and vector, they might not be considered the same. But questions remain before the guidelines can be put into practice. “Would a gene editing tool be considered a principal molecular structure in a manner analogous to a vector?” says Emily Marden, counsel at Sidley Austin, Palo Alto, California. Nevertheless, having the FDA’s views in guideline format is useful. “By explaining some of FDA’s thinking, the guidance helps companies better formulate questions for discussion with the agency,” says Philip Katz, partner at Hogan Lovells, Washington, DC. The draft guidelines are open for comments until 29 April.