We, FDA, are providing you, a sponsor who is developing a human gene therapy product (GT Product),  recommendations regarding the design of long term follow-up studies (LTFU observations) for the collection of data on delayed adverse events following administration of a GT product.  Often, GT products are designed to achieve therapeutic effect through permanent or long-acting changes in the human body.  As a result of long term exposure to an investigational GT product, study subjects may be at increased risk of undesirable and unpredictable outcomes that may present as delayed adverse event(s).  To understand and mitigate the risk of a delayed adverse event, subjects in gene therapy trials may be monitored for an extended period of time, which is commonly referred to as the “long term follow-up” (LTFU) period (of a clinical study).  LTFU observations are extended assessments that continue some of the scheduled observations of a clinical trial past the active follow-up period, and are an integral portion of the study of some investigational GT products.  LTFU observations are important to monitor long term safety of GT products.  For GT products that present long term risks to subjects, LTFU/surveillance plan(s) should also be put in place post-licensure for monitoring of delayed adverse events (for details we refer you to section VI. of this document).  Not all GT products will require LTFU observations; a risk assessment should be performed by a sponsor based on several factors as outlined in this guidance.

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