Food and Drug Administration Guidance on Design of Clinical Trials for Gene Therapy Products with Potential for Genome Integration or Genome Editing and Associated Long-Term Follow-Up of Research Subjects

Abstract

Introduction: With the burgeoning growth of the gene therapy industry, the Food and Drug Administration (FDA) has produced various guidance documents intended to help gene therapy manufacturers design their preclinical testing and clinical trials to facilitate the process of obtaining marketing approval.

Discussion: Biosafety professionals and institutional biosafety committees (IBCs) with oversight of clinical trials or biopharmaceutical manufacturing stand to benefit from understanding how these guidance documents set the standard for writing the clinical research protocols that are reviewed by IBCs. Although the FDA guidance documents are typically meant for manufacturers (either pharmaceutical companies serving as research sponsors or investigators at academic institutions), much of the content is useful for biosafety professionals and IBCs during the IBC review process.

Conclusion: This article specifically addresses guidance documents pertaining to gene therapy vectors capable of genomic integration, testing for replication competent retrovirus, genome editing, and long-term follow-up of research subjects.

Keywords: FDA guidance; clinical trials; gene editing; gene therapy; long-term follow-up; replication competent retrovirus.

Figure 1.

Framework to assess the risk of GT-related delayed adverse events and need for LTFU. The decision tree outlines the FDA's risk assessment process for determining whether a GT product may result in delayed adverse events. LTFU is indicated for GT products deemed to pose a risk of delayed adverse events. Adapted from the FDA guidance, “Long-Term Follow-Up After Administration of Human Gene Therapy Protocols: Guidance for Industry.” FDA, Food and Drug Administration; GT, gene therapy; LTFU, long-term follow-up.