Bergeson & Campbell, P.C.

The DNA of the U.S. Regulatory System: Are We Getting It Right For Synthetic Biology?


U.S. regulatory oversight of synthetic biology across the board needs to be modernized to reflect and address the promising technologies routinely entering the market. From a statutory perspective, the pertinent laws appear sufficiently broad to empower federal agencies to address potential risks and promote the potential benefits of synthetic biology. The regulatory infrastructure, however, is ill-suited to address all the regulatory implications of new products derived from synthetic biology.

Improvements that are urgently needed include:

  • Increased funding to federal agencies, including “embedded” new technology stewards in each office of all relevant federal agencies to monitor and coordinate topics of emerging technologies and share information with other agency offices
  • Dedicated centers of technological excellence in pertinent federal offices to stay abreast of new developments
  • Regular routine intervention by industry and academic innovators to brief government agencies on trends, developments, and challenges
  • Implementation of an ongoing process to demystify synthetic biology and its products so that they are more clearly and accurately understood by federal decision-makers and the public
  • Developing a long-range, governmentwide strategy to assure that, going forward, the regulation of synthetic biology encourages innovation while timely identifying and addressing risks through a science-based, transparent process that encourages public confidence

Some of these recommendations are reflected in a July 2, 2015, memorandum issued by the White House Office of Science and Technology Policy that directs the Environmental Protection Agency (EPA), Food and Drug Administration (FDA), and the Department of Agriculture (USDA) to update the 1986 Coordinated Framework for Regulation of Biotechnology, under which these agencies have proceeded for nearly three decades. The directive to revise the Coordinated Framework is long overdue. Developments in synthetic biology will not halt during the overhaul of the Coordinated Framework. Improvements in regulatory oversight can and should be put into place, even while the updating of the Coordinated Framework is in progress.

Report Summary
As highlighted in this report, especially in the illustrative case studies, competing and sometimes conflicting jurisdictional issues confound, if not frustrate, prompt and effective government oversight of synthetic biology. The novelty of some technologies challenges even government staff in sorting out which agency has primary jurisdiction over a particular product or new technology or which office within an agency should be exercising regulatory oversight.

The Oxitec case study highlights the threshold regulatory issues that can arise within a single agency – in this case, the FDA -- in the synthetic biology context. Oxitec has developed a genetically engineered mosquito that is highly effective in decreasing the population of disease-carrying A. aegypti mosquitos through breeding after the engineered mosquito is released into the wild. But the Oxitec mosquito does not fit cleanly into any FDA regulatory category; eventually it was determined to assess it as an animal drug by one office of the FDA rather than by another FDA office as a human drug though its ultimate goal is to reduce yellow fever and allied diseases in human beings -- and hence to act as a human drug. Uncertainty is expensive. Without a reliably defined regulatory assessment pathway, innovation is discouraged. For Oxitec, a threshold question even had arisen whether the USDA, rather than FDA, should be in charge if the engineered mosquito could be described as a pest control technology.

Where the synthetic biology product is a cosmetic ingredient, uncertainties are magnified because cosmetics, in most cases, are not subject to pre-market review by FDA, which typically relies on enforcement authorities it can deploy against improperly labeled cosmetics already on the market. Accuracy in labeling is a slippery slope when it comes to synthetic biology, as described in the case study on squalene, an emollient in lotions. The best source of natural squalene is shark oil, but with some shark species deemed endangered and plant sources often uneconomical, the biotechnology firm Amyris has developed and is marketing synthetic squalene, apparently through the engineering of proprietary yeast strains, for cosmetic use. This poses the question whether synthetically derived squalene is the same for regulatory/ labeling purposes as squalene from fish oil or plant oil sources. Consumers are entitled to accuracy in labeling, but neither consumers nor product developers are well served if the regulatory agency in charge has not addressed and clarified the issue ahead of the launch of the cosmetic product in the commercial market.

The fundamental issue of which regulatory statute applies to a synthetic biology product can be unexpectedly complex, as depicted by the PBAN case study. PBAN is a naturally occurring substance that encourages female insects to produce pheromones to attract males for mating; researchers have developed a genetically modified strain of E. coli that yields a synthetic PBAN used in an innovative process for moth control. Mixed with a sugar solution, the synthetic PBAN is placed in a trap as food for female moths, inducing them to produce pheromones, which in turn attracts male moths into the trap. The use of a biopesticide in a trap for purposes of mitigating a pest typically requires registration under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), despite a FIFRA exemption for pheromones; synthetic PBAN, while inducing pheromone production, is not itself a pheromone. Thus PBAN is subject to FIFRA although it is a more benign approach to pest control than is a conventional pesticide. As the case study notes, if synthetic PBAN had obtained the benefit of the FIFRA exemption, it still might be subject to the Toxic Substances Control Act (TSCA) or other authorities. Depending on its use, and on whether other substances would be placed in the trap along with it, other regulatory scenarios could be triggered. The process of deciding whether and how to regulate a synthetic biology product may well require as much effort as the regulatory process itself.

In some instances, synthetic biology products go without regulatory oversight because the relevant statute, as read by the implementing agency, does not cover them. The Plant Protection Act (PPA) extends only to “plant pests,” a defined term that USDA’s Animal and Plant Health Inspection Service (APHIS), in a reading affirmed by a federal appeals court, construes the term to exclude genetically engineered plants from regulation unless the plants themselves, the genetic material, or the engineering method involve plant pests. For this reason, APHIS declined to take jurisdiction over either “BioGlow” or the “Glowing Plant” as the case study illustrates. The former now commercialized and the latter, an open-source technology funded through a Kickstarter campaign. Seeds of the glowing plant were made available to consumers as supporter bonuses and in Do-It-Yourself (DIY) kits where individuals can make the genetic transformation themselves. Synthetic biology was far in the future when the original legislation that became the PPA was enacted – and it shows.

Not only is the underlying legislation often ill-equipped to address the challenge of commercialized synthetic biology, the problem is exacerbated at the implementing agency level. Given the extreme and growing shortages in government staff and funding throughout the federal agencies, including those whose regulatory reach extends to synthetic biology, technological literacy remains a critical problem. Government personnel with institutional know-how and expertise are retiring from the workforce and not always being replaced, and those who are added are not being provided with opportunities to understand fully new synthetic biology technologies entering the commercial space. In addition to the recommendations outlined above, better, more systematic, and routine communication and coordination between and among federal agencies is also urgently needed. The deeply-embedded stove piping confounds communication and coordination within and among government offices and blunts opportunities for more efficient, informed reviews of new products moving to market.

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