CBER Plans Draft Guidance on ‘Sameness’ of Gene Therapies Under Orphan Drug Regulations

The US Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research (CBER) has updated its list of 2019 guidance and added a new draft on interpreting “sameness” of gene therapy products under the orphan drug regulations.

The new draft on sameness, under the category of Tissues and Advanced Therapies, is expected in addition to the finalization of six guidance documents on gene therapies released last July, final guidance from February on expedited programs for regenerative medicines and the evaluation of devices with regenerative medicines, and final guidance from March on CBER’s use of standards in regulatory submissions.

But FDA’s discussion of sameness in the context of gene therapies and orphan exclusivity will be highly anticipated, as about 70% of gene therapies are seeking to treat rare diseases and as the complexity of gene therapies may make it difficult for the agency to set a precedent.

A recent article from Sidley Austin’s Emily Marden and Anna Sims explains how leadership at FDA’s Office of Orphan Products Development (OOPD) said in May 2018 that for “totally different vectors ... [FDA] would look at that as different. Similarly, different transgenes, we would look at that as different. But when you get to serotypes or promoters, we really have to go back and communicate.”

In terms of key product features to be considered when determining if a gene therapy is the same as a predecessor, Marden and Sims point to: “the vector, the transgene, other regulatory elements of transduction and expression, and manufacturing issues, such as those related to target cells.”

Hyman, Phelps & McNamara’s Kurt Karst also noted in the FDA Law Blog in July 2017 that determining the “sameness” of “two genetic components would certainly seem to be an easy issue, as the sequences/compositions of the genetic material can easily be compared. That leaves the vector component. The extent to which the vector component should be considered in an orphan drug ‘sameness’ determination is likely to be the central issue for FDA and OOPD to address and resolve. That is, whether or not the vector is part of the orphan drug, or whether it is merely part of the product ‘formulation’ and serves as a route of delivery for the ‘true’ orphan drug – the genetic component in a gene therapy product.”

CBER Guidance Agenda