15 June 2018

FDA regulation and the CRISPR Zoo

‘A Menagerie of Moral Hazards: Regulating Genetically Modified Animals’ by Sarah Polcz and Anna C.F. Lewis in (2018) 40 The Journal of Law, Medicine and Ethics  180-184 comments
Dairy cattle naturally grow long and dangerous horns. So as a protective measure, farmers permanently remove calves’ small horns through a painful procedure. Recently, scientists have used modern genetic editing techniques to create dairy cattle that never develop horns, and so never need to be “dehorned.” The regulatory fate of these genetically dehorned cattle may be bound up with numerous more controversial cases from the same rapidly diversifying field: the genetic editing of animals. Or, at least so it could be under draft Food and Drug Administration (FDA) guidance which closed for public commentary in June 2017. The FDA’s challenge is to chart a flexible regulatory course. One which will support the potential of gene-editing technology, while staking out the boundaries of acceptable risks — i.e. the ethical boundaries — of the looming “CRISPR zoo.” Here we review the background to the draft guidance, as well as the scathing comments it received from disparate interest groups. The comments show that to foster public trust in how gene-editing technologies are used, it is imperative that the FDA re-engage with all stakeholders, including the public at large. 
In its draft guidance, the FDA proposed to regulate “intentionally altered genomic DNA” of animals as a drug being evaluated for use in animals. The original altered animal and all its progeny would be subject to the animal drug regulations. The FDA invited comments on these proposed amendments. As we discuss here, a mere handful of the 151 comments received were supportive,4 and most were extremely critical, including those from the National Association of State Departments of Agriculture (NASDA). We argue that the FDA’s proposals are unsatisfactory and should be withdrawn.
The authors conclude
 We agree that the product should be the subject of regulation, and not the process that created it. A focus on product would force the FDA to clarify its regulatory intent, increas- ing transparency not just for product developers, but also for the public. It would elevate the importance of understanding risk, a view that was shared by a broad cross section of commenters. By contrast, a focus on process bunches diverse applications under one umbrella, from curing inherited diseases to adding in genes from distant species, from food to de- extinction of animals. And it divides products that should be considered together. In contrast, the USDA excluded from its proposed regulations any genetically modified organ- ism that could have been produced using traditional breeding techniques because “[s]uch organisms are essentially identical, despite the method of creation.” 
Moreover, history has shown that biotech regulations focusing on process have a frustratingly short shelf life. Regulation introduced in 2009 focused on process, calling out recombinant DNA. Just a few years later, new technologies arrived that are not covered by that regulation. Updating guidance with updated technologies repeats the original error. Already technology is outpacing proposals: mice have had their epigenomes successfully edited, and as these terms are currently understood they would not qualify as having “intentionally altered genomic DNA”. 
A focus on process has allowed the FDA to avoid answering tough product questions. This needs to change. The approach proposed by the NAS in its report concerning the future products of biotechnology, in our opinion represents a sound core for a revised approach: a single cross-agency entry point for the risk based appraisal of new products. In the context of technology designed to affect animals, an additional concern should be for animal welfare. Technology such as gene editing has huge potential to not only improve animal welfare, but also to decrease it. 
The lack of consistency across different agencies concerning geneti- cally altered organisms is not only confusing within the U.S., it makes it almost impossible for other coun- tries to follow the U.S.’s lead. The aim should be internal consistency within the U.S. as part of a cohesive international approach for these international issues: protection from large-scale risk while helping provide for the food security and better health of humanity. 
Finally, the FDA received a similar number and spread of comments as the USDA received in reaction to its proposals. The same arguments cited by the USDA in withdrawing its own proposals apply equally to the FDA. In both cases, the propos- als clearly fail to attract even minimal support from a broad range of commenters. Moreover, as the USDA noted, the publication of the proposed rules constrained its ability to explore alternatives with stakeholders. The withdrawal opened up the opportunity for “a more open and robust policy dialogue.” Given the opposition to the proposals, it would be consistent for the FDA to likewise withdraw them as a first step towards a cohesive framework. Then we can start the much needed dialog to build a risk-based approach, both for gene-editing and for the biotechnologies to come.