From Alzheimer’s to Zebrafish: Eclectic Science and Regulatory Stories 158
Regulatory Compliance
The growth of zebrafish as a model organism has so far greatly outpaced regulatory
oversight governing its care and use in research. However, it is likely the same levels of
regulation that characterize the set of traditional mammalian models will be extended to
zebrafish. The challenge for both the zebrafish research community and regulatory agents
is to ensure emerging guidelines are sensible and serve to promote quality science and the
highest standards of animal care.16
Currently, the US Food and Drug Administration (FDA) is willing to discuss alter-
native methods of toxicity and biocompatibility testing. The alternative methods, i.e.,
zebrafish embryos, should be capable of detecting the same endpoints with the same
specificity and sensitivity as currently provided by traditional methods. Any company
planning to use zebrafish models should contact the appropriate review division or
branch for complete feedback to ensure any changes introduced by the new model can
be addressed prior to conducting the test. This should certainly be considered as part of
the pre-Investigational Device Exemption (IDE) process. At that time, it would be wise to
make sure the documentation supports the equivalence of the traditional and alternative
approaches.
Fortunately, FDA’s National Center for Toxicological Research has established a
zebrafish facility to provide adult fish and/or embryos for high throughput toxicity
assessments. According to the center, zebrafish-based assays are increasingly utilized by
industry to screen for drug/toxicant effects.17 This information should facilitate personnel
at the device branch to willingly accept less traditional models.
Final Thoughts
Microtest, a major testing laboratory, announced that its zebrafish embryo assay has better
sensitivity and generates more scientific data than the small animal tests currently recom-
mended by FDA. The method can also save time and money because embryos develop
in 24 hours. The laboratory believes that the assay will reduce or eliminate the current
animal testing required for all medical devices.18
Zebrafish embryos are also being used in new nanotechnology test methods for drug
studies. It would be ironic if, 30 years after publication of George Streisinger’s seminal
paper, the next decade in genetic, drug and medical device research becomes “the age of
the zebrafish.” Stranger things have happened.
References
1. Zebrafish. Published by Mary Ann Liebert, Inc.
2. Vogel G. “How zebrafish mend a broken heart.” Science Now. 24 March 2010.
3. Vogel G. “Thalidomide’s partner in crime.” Science Now. 11 March 2010.
4. Mione M, et al. “Disease modeling in zebrafish: cancer and immune responses.” Zebrafish. 2009 6(4):445–9.
5. Ibid.
6. University of Oregon. Zebrafish FAQs. www.neuro.uoregon.edu/k12/FAQs.html. Accessed 28 August 2011.
7. Streisinger G, et al. “Production of clones of homozygous diploid zebrafish (Brachydanio rerio).” Nature.
1981 293–6.
8. Op cit 6.
9. University of Sheffield. Why are zebrafish used for scientific research? http://www.fishforscience.com/
model-organisms/why-zebrafish. Accessed 28 August 11.
10. Fishman MC. “Zebrafish—the canonical vertebrate.” Science. 2001 294:1290–1.
11. Thisse C, Zon LI: “Organogenesis–heart and blood formation from the zebrafish point of view.” Science. 2002
295:457–62.
12. Rihel J, et al. “Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation.”
Science. 2010 327:348–51.
13. Op cit 2.
14. Begeman G. “Literature review and commentary.” Zebrafish. 2010 7(4):379–82.
15. Animal Research Info. Zebrafish. www.animalresearch.info/en/science/animalsused/zebrafish. Accessed 28
August 2011.
Regulatory Compliance
The growth of zebrafish as a model organism has so far greatly outpaced regulatory
oversight governing its care and use in research. However, it is likely the same levels of
regulation that characterize the set of traditional mammalian models will be extended to
zebrafish. The challenge for both the zebrafish research community and regulatory agents
is to ensure emerging guidelines are sensible and serve to promote quality science and the
highest standards of animal care.16
Currently, the US Food and Drug Administration (FDA) is willing to discuss alter-
native methods of toxicity and biocompatibility testing. The alternative methods, i.e.,
zebrafish embryos, should be capable of detecting the same endpoints with the same
specificity and sensitivity as currently provided by traditional methods. Any company
planning to use zebrafish models should contact the appropriate review division or
branch for complete feedback to ensure any changes introduced by the new model can
be addressed prior to conducting the test. This should certainly be considered as part of
the pre-Investigational Device Exemption (IDE) process. At that time, it would be wise to
make sure the documentation supports the equivalence of the traditional and alternative
approaches.
Fortunately, FDA’s National Center for Toxicological Research has established a
zebrafish facility to provide adult fish and/or embryos for high throughput toxicity
assessments. According to the center, zebrafish-based assays are increasingly utilized by
industry to screen for drug/toxicant effects.17 This information should facilitate personnel
at the device branch to willingly accept less traditional models.
Final Thoughts
Microtest, a major testing laboratory, announced that its zebrafish embryo assay has better
sensitivity and generates more scientific data than the small animal tests currently recom-
mended by FDA. The method can also save time and money because embryos develop
in 24 hours. The laboratory believes that the assay will reduce or eliminate the current
animal testing required for all medical devices.18
Zebrafish embryos are also being used in new nanotechnology test methods for drug
studies. It would be ironic if, 30 years after publication of George Streisinger’s seminal
paper, the next decade in genetic, drug and medical device research becomes “the age of
the zebrafish.” Stranger things have happened.
References
1. Zebrafish. Published by Mary Ann Liebert, Inc.
2. Vogel G. “How zebrafish mend a broken heart.” Science Now. 24 March 2010.
3. Vogel G. “Thalidomide’s partner in crime.” Science Now. 11 March 2010.
4. Mione M, et al. “Disease modeling in zebrafish: cancer and immune responses.” Zebrafish. 2009 6(4):445–9.
5. Ibid.
6. University of Oregon. Zebrafish FAQs. www.neuro.uoregon.edu/k12/FAQs.html. Accessed 28 August 2011.
7. Streisinger G, et al. “Production of clones of homozygous diploid zebrafish (Brachydanio rerio).” Nature.
1981 293–6.
8. Op cit 6.
9. University of Sheffield. Why are zebrafish used for scientific research? http://www.fishforscience.com/
model-organisms/why-zebrafish. Accessed 28 August 11.
10. Fishman MC. “Zebrafish—the canonical vertebrate.” Science. 2001 294:1290–1.
11. Thisse C, Zon LI: “Organogenesis–heart and blood formation from the zebrafish point of view.” Science. 2002
295:457–62.
12. Rihel J, et al. “Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation.”
Science. 2010 327:348–51.
13. Op cit 2.
14. Begeman G. “Literature review and commentary.” Zebrafish. 2010 7(4):379–82.
15. Animal Research Info. Zebrafish. www.animalresearch.info/en/science/animalsused/zebrafish. Accessed 28
August 2011.