Gene Therapy Oversight: Lessons for Nanobiotechnology

Abstract

Oversight of human gene transfer research ("gene therapy") presents an important model with potential application to oversight of nanobiology research on human participants. Gene therapy oversight adds centralized federal review at the National Institutes of Health's Office of Biotechnology Activities and its Recombinant DNA Advisory Committee to standard oversight of human subjects research at the researcher's institution (by the Institutional Review Board and, for some research, the Institutional Biosafety Committee) and at the federal level by the Office for Human Research Protections. The Food and Drug Administration's Center for Biologics Evaluation and Research oversees human gene transfer research in parallel, including approval of protocols and regulation of products. This article traces the evolution of this dual oversight system; describes how the system is already addressing nanobiotechnology in gene transfer: evaluates gene therapy oversight based on public opinion, the literature, and preliminary expert elicitation; and offers lessons of the gene therapy oversight experience for oversight of nanobiotechnology.

Clinical Translation and Regulations of Theranostics

“…Additional oversight measures have been proposed by Susan Wolfe and members of two work groups convened to evalulate potential oversight models for nanostructures and nanosystems [9,16]. The first, in 2009, proposed an oversight structure similar to the one now in place for gene therapy, including oversight by the FDA, Office of Human Research Protection (OHRP), NIH, and local institutional and Institutional Review Board (IRB) review.…”

“…Federal regulation requires posting of clinical trial results, and the NIH review of gene therapy protocols is available to the public. A take-away message from this work is that the regulatory process does force an exchange of information that, despite the work of scientific consortiums, is lacking at this point [16]. There is a need for a clear definition of the field and development of a standardized approach to reference materials, research protocols, analysis, and reporting [14,17].…”

“…This phase of research helps to identify appropriate endpoints for use in later trials [33]. Serious and unexpected mortality and morbidity associated with FIH trials have resulted in greater scrutiny by regulators, ethics boards, and the general public and will impact the study design and monitoring of FIH trials [16,34]. The safety of research participants is of paramount importance in these studies and close collaboration with FDA and study designs that assure adequate oversight are critical to this phase of translational research.…”

“…The gene therapy oversight model has responded effectively to safety events and has protected patients, staff, and environment. However, concern was expressed about the appropriateness of this model in a scientific environment that is generating new therapies at nanospeed [16].…”

Ocular gene transfer in the spotlight: implications of newspaper content for clinical communications

“…Historical abuses, including non-disclosure of serious adverse events and highly publicized conflicts-of-interest, have damaged its reputation [1-3], eroded public trust, and presented significant setbacks for its clinical development [4,5]. …”