Overview of Legal Regulations of CRISPR-Cas9

By Nora Baty*

CRISPR-Cas9 is a revolutionary gene editing tool first discovered in the 1990s and harnessed for programmable gene editing in 2012.[i] With the introduction of CRISPR-Cas9  genetic editing is cheaper and more readily available than ever before.[ii] CRISPR has the potential to revolutionize the way genetic diseases are treated and make genetically modified organisms (GMO’s) use in agriculture even more widespread.[iii] (GMO’s are defined by the World Health Organization as plants, animals, microorganisms etc. that have genetic material that has been altered in a way that does not occur naturally.[iv] Much of the legal coverage on CRISPR-Cas9 technology has focused on the intellectual property issues surrounding the technology.[v] However, with the ability to edit genomes on such an accessible scale and with such precision comes many regulatory and ethical issues.[vi]

One key regulatory issue is how CRISPR will be treated by regulatory agencies as the technology leaves research and development labs and goes into the real world for use in agriculture and in pharmaceuticals.[vii] This shift is already occurring and some CRISPR products are available such as mushrooms modified to prevent browning.[viii] Currently, three regulatory agencies in the United States have some policy on regulation of biotechnology products that covers gene editing (and therefore CRISPR): the FDA, the USDA, and the EPA.[ix] The FDA by far has the most robust regulatory scheme encompassing veterinary medicine and human gene therapies.[x] Gene edited animals can be subject to the FDA’s review process for new animal drugs.[xi] The USDA, on the other hand, uses looser risk-based principles to determine what kind of regulation applies to the extent that modified organisms deemed low-risk are not subject to its review.[xii] The EPA’s policy on gene-editing remains comparatively unclear.[xiii] The EPA has merely stated that it intends to regulate in a manner consistent with the framework of its approach to pesticide products.[xiv] The EPA regulates pesticide products under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).[xv] Genetically modified organisms that are modified with DNA that is not pesticidal in nature fall outside the scope of the EPA’s regulatory authority.[xvi]

A major ethical issue is the ability to use CRISPR to alter heritable genetic information and alter the genes of future generations.[xvii] On one hand CRISPR potentially allows heritable diseases to be eliminated, however it also risks untended consequences of gene-editing impacting generations to come.[xviii] For example, the first known application of embryonic editing was twins born in China who had a modification made to their genomes to make them HIV resistant. This modification may have also made them more susceptible to the flu and increased their mortality.[xix] Following the first edited embryos scientists called for a global moratorium on germline editing.[xx] The World Health Organization (WHO) has stated that “ it would be irresponsible at this time for anyone to proceed with clinical applications of human germline editing.”[xxi] However, there is no binding worldwide policy or set of rules on gene editing/gene therapy.[xxii]

In the United States, gene therapy technology is regulated by the FDA and treated as a biological drug or device.[xxiii] This regulatory process is part of the FDA’s Investigational New Drug (IND) application.[xxiv] Gene therapy is very tightly controlled in the pre-market stages and development with lots of oversight and safety precautions during clinical trials.[xxv] However, once a gene therapy has been approved the regulatory oversight becomes much more minimal.[xxvi] Even if the therapy was originally approved for one purpose, physicians can use it for another purpose altogether.[xxvii] This is because the FDCA expressly states that “[n]othing in this chapter shall be construed to limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease within a legitimate health care practitioner-patient relationship.”[xxviii] For heritable genetic modification in humans in the United States there is a de facto ban via FDA spending bill but no universal ban.[xxix]

Compare this to China which prior to the worldwide pushback against the rouge scientist who performed gene edits in two young twin girls had almost no national oversight or regulatory and ethics program to address genetic editing/genetic therapy. Now gene editing in any type of cell that will end up in humans, including embryos, requires the Chinese National Health Commissions’ approval.[xxx]

The current patchwork system of regulations for CRISPR gene editing creates needless complication, confusion and potentially unnoticed gaps in a contentious and expanding area of biotechnology.[xxxi] 31  A unified regulatory approach would address many of the problems in the current system. While the International Summit of Human Gene Editing has given its approval to the current FDA regulatory framework for somatic therapies,[xxxii] stronger regulations at least temporarily banning human germline editing are needed in the US. A ban would allow regulators to enforce the scientific consensus that germline editing is irresponsible under current circumstances and give the scientific community time for thoughtful engagement on the ethical issues of germline editing.

*Nora Baty is a Junior Editor on MJEAL. They can be reached via email at nbaty@umich.edu.


[i] See, CRISPR Timeline, Broad Institute, https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/crispr-timeline (last visited Mar. 19, 2020).

[ii] See, Brad Palmer et. al., A Simple guide to CRISPR, one of the biggest scientific stories of the decade, VOX, https://www.vox.com/2018/7/23/17594864/crispr-cas9-gene-editing (Dec. 27, 2018 at 2:45 PM).

[iii] Id.

[iv] Frequently asked questions on genetically modified foods, Food Safety, World Health Organization, (May 2014) https://www.who.int/foodsafety/areas_work/food-technology/faq-genetically-modified-food/en/.

[v] See, e.g., Diana Kwon, A Brief Guide to the Current CRISPR Landscape, TheScientist (Jul 15, 2019) https://www.the-scientist.com/news-opinion/a-brief-guide-to-the-current-crispr-landscape–66128. E.g., Knut J Egelie et. al., The emerging patent landscape of CRISPR-Cas gene editing technology, 34 Nature Biotechnology 1025 (2016).

[vi]  CRISPR- a challenge for policy makers and regulators, Allen & Overy, https://www.allenovery.com/en-gb/global/news-and-insights/crispr/crispr-a-challenge-for-policy-makers-and-regulators (last visited Mar. 19, 2020). See also, What are the Ethical Concern of Genome Editing, National Human Genome Research Institute, https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/ethical-concerns (last visited Mar. 21, 2020).

[vii] CRISPR- a challenge for policy makers and regulators, Allen & Overy, https://www.allenovery.com/en-gb/global/news-and-insights/crispr/crispr-a-challenge-for-policy-makers-and-regulators (last visited Mar. 19, 2020).

[viii] CRISPR in Agriculture: An Era of Food Evolution, SYNTHEGO (Mar. 28, 2019) https://www.synthego.com/blog/crispr-agriculture-foods.

[ix] Coordinated Framework for Regulation of Biotechnology, 51 Fed. Reg. 23,302 (Jun. 26, 1986).

[x] FDA, Draft Guidance for Industry, Regulation of Intentionally Altered Genomic DNA in Animals (Jan. 2017), https://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM113903.pdf. See also FDA, Information About Self-Administration of Gene Therapy (Nov. 21, 2017), https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/information-about-self-administration-gene-therapy.

[xi] FDA, Draft Guidance for Industry, Regulation of Intentionally Altered Genomic DNA in Animals (Jan. 2017), https://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM113903.pdf.

[xii] USDA, Proposed Rule, Importation, Interstate Movement, and Environmental Release of Certain Genetically Engineered Organisms, 82 Fed. Reg. 7008 (Jan. 19, 2017), available at: https://www.regulations.gov/docket?D=APHIS-2015-0057.

[xiii] Executive Office of the President, National Strategy for Modernizing the Regulatory System for Biotechnology Products, 17 (Sept. 2016), available at: https://www.epa.gov/sites/production/files/2016-12/documents/biotech_national_strategy_final.pdf.

[xiv] Id.

[xv] Pesticide Registration, EPA, https://www.epa.gov/pesticide-registration/about-pesticide-registration (Last visited Mar. 20, 2020).

[xvi] EPA’s Regulation of Biotechnology for Use in Pest Management, EPA, https://www.epa.gov/regulation-biotechnology-under-tsca-and-fifra/epas-regulation-biotechnology-use-pest-management#role (Last visited Mar. 21, 2020).

[xvii] What are the Ethical Concern of Genome Editing, National Human Genome Research Institute, https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/ethical-concerns (last visited Mar. 21, 2020).

[xviii] Id.

[xix] Rob Stein, 2 Chinese Babied with Edited Genes May Face Higher Risk of Premature Death, NPR (Jun. 3, 2019, 11:49 AM), https://www.npr.org/sections/health-shots/2019/06/03/727957768/2-chinese-babies-with-edited-genes-may-face-higher-risk-of-premature-death.

[xx] Eric Lander et. al., Adopt a moratorium on heritable genome editing, 567 Nature 165 (2019).

[xxi] Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing, Report of the First Meeting, WHO, 3 (Jul. 26, 2019), available at: https://www.who.int/ethics/topics/human-genome-editing/GenomeEditing-FirstMeetingReport-FINAL.pdf?ua=1.

[xxii] National Academies of Sciences, Engineering, and Medicine; National Academy of Medicine; National Academy of Sciences; Committee on Human Gene Editing: Scientific, Medical, and Ethical Considerations. Human Genome Editing: Science, Ethics, and Governance. Washington (DC): National Academies Press (US); 2017 Feb 14. B, International Research Oversight and Regulations. Available from: https://www.ncbi.nlm.nih.gov/books/NBK447261/.

[xxiii] FDA, Guidance for Industry, Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs), 2 (Jan. 2020), https://www.fda.gov/media/113760/download.

[xxiv] Id.

[xxv] 21 C.F.R. § 312.21 (2019).

[xxvi] R. Alta Charo, The Legal and Regulatory Context for Human Gene Editing, Issues in Science and Technology, (Spring 2016).

[xxvii] 21 U.S.C. § 396 (West 2016).

[xxviii] Id.

[xxix] Jocelyn Kaiser, Update: House spending panel restore U.S. ban on gene-edited babies, Science (Jun. 4, 2019 at 1:45 PM), available at: https://www.sciencemag.org/news/2019/06/update-house-spending-panel-restores-us-ban-gene-edited-babies.

[xxx] David Cyranoski, Chine to tighten rules on gene editing in humans, Nature (Mar. 6, 2019).

[xxxi] Supra Charo.

[xxxii] Organizing Committee for the International Summit of Human Gene Editing, On Human Gene Editing: International Summit Statement, National Academies (Dec. 3, 2015).

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