June 21, 2014

NIH: Recombinant DNA Advisory Committee Review No Longer Necessary for Gene Therapy Trials

In a move that signals the maturity of the gene therapy field, the National Institutes of Health (NIH) has announced that it will no longer subject all applications for gene therapy trials to automatic review by the Recombinant DNA Advisory Committee (RAC). Gene therapy is defined as: 
the transfer of genetic material into humans with the goal of replacing or compensating for the function of abnormal genes, or to enhance the immune system’s ability to attack cancer cells.
RAC occupies a singular place in the history of government oversight of new technologies. The committee was established in 1974, following increasing concern by scientists in the then-emerging field of molecular biology as the techniques involving recombinant DNA were developed and disseminated. The Asilomar conference of 1975 originated with scientIsts, and led to the publication of physical and biological containment strategies to limit the risk of working with recombinant organisms (e.g., bacteria, viruses). RAC issued the first Recombinant DNA Research Guidelines in 1976, and these were the precursor to later guidelines for the gene therapy applications that were first submitted to RAC in the late 1980's. Now, following a study from the Institute of Medicine that called for streamlining the review process for gene therapy (removing redundancies in the review process), the NIH has acceded to their recommendation that RAC reviews of gene therapy be reserved for exceptional cases where both of these conditions exist: 
1. The protocol review could not be adequately performed by other regulatory and oversight processes (for example, the institutional review boards, institutional biosafety committees, and the FDA).

2. One or more of the following criteria are satisfied: 

Protocol uses a new vector, genetic material, or delivery method that represents a first-in-human experience, thus representing unknown risk.

Protocol relies on preclinical safety data that were obtained using a new preclinical model system of unknown and unconfirmed value.

Proposed vector, gene construct, or method of delivery is associated with possible toxicities that are not widely known and that may render it difficult for local and federal regulatory bodies to evaluate the protocol rigorously.
In reviewing the history of RAC oversight for the gene therapy field, the IOM stated
When recombinant DNA technology was new, and the many risks concerning individual clinical trial protocols were uncertain, the public, scientists, and policy makers raised important questions about potential dangers—such as whether this technology could harm patients, create new infectious organisms, or make genetic alterations that could be passed down to future human generations. In its report, the IOM committee finds that the major concerns about recombinant DNA from 40 years ago do not raise the same level of concern today, as hundreds of gene therapy clinical trials have evaluated the technique’s safety and effectiveness. 
The RAC committee stands as a model of a technology-specific review body set up to augment existing regulatory processes in the case where a novel technology has emerged with potential risks to health and safety. This recent move now becomes a model for partial deregulation of a maturing technology. Gene therapy protocols will continue to be reviewed by the FDA and institutional oversight panels. The IOM report recognizes that this model of regulatory layering still has relevance for current emerging technologies, and specifically cites the field of nanotechnology as a candidate for a future RAC-like review body to consider its specific applications in medicine.

No comments: