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FDA comments on phase I clinical trials without vector biodistribution data

Nature Genetics volume 22, page 326 (1999)Cite this article

In the June issue of Nature Genetics, Haig Kazazian discussed calculations presented at a Recombinant DNA Advisory Committee (RAC) meeting held on 12 March 1999 on inadvertent germline alteration1. He mentioned a proposed safety limit on genetic insertions, which was attributed to the Food and Drug Adminstration (FDA). We would like to clarify the FDA's policy. Rather than a specific limit, policy decisions about risks of genetic insertion are based on disease severity, age, life expectancy and reproductive status, as well as vector biology and animal safety data.

The FDA agrees with Kazazian that the natural rate of insertional mutations should be considered when developing regulations, and his presentation at the meeting was a key factor enabling a decision on policy to be reached. There are also other relevant factors to consider. Public reaction to a harmful germline mutation caused, even inadvertently, by gene therapy might differ from reaction to insertional mutations in nature. In addition, expression of therapeutic genes in inappropriate tissues or stages of development may have harmful consequences.

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References

  1. Kazazian, H. Nature Genet. 22, 130 (1999).

    Article  CAS  Google Scholar 

  2. Splicing Life, Report of President's Commission on gene therapy, cited in Capron, A.M. Hum. Gene Ther. 1, 69–71 (1990).

    Article  CAS  Google Scholar 

  3. The Revised "Points to Consider" Document, 1989, reprinted in Hum. Gene Ther. 1, 93–103 (1990).

  4. Wadman, M. Nature 392, 317 (1998).

    PubMed  Google Scholar 

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Acknowledgements

We thank E. Max, J. Kassis and J. Siegel for helpful comments.

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Authors and Affiliations

  1. Division of Cellular and Gene therapies, CBER, FDA, 1401 Rockville Pike, HFM-521, Rockville, 20852-1448, Maryland, USA

    Suzanne Epstein, Steven Bauer, Andra Miller, Anne Pilaro & Philip Noguchi

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  1. Suzanne Epstein
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  2. Steven Bauer
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  5. Philip Noguchi
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Epstein, S., Bauer, S., Miller, A. et al. FDA comments on phase I clinical trials without vector biodistribution data. Nat Genet 22, 326 (1999). https://doi.org/10.1038/11895

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