So you’ve made a new product by genetically engineering a living organism, and are eager to sell it in the United States. Before it gets to market, however, you’ll need to answer a critical question: Which U.S. agency has to sign off on its safety? The U.S. Food and Drug Administration (FDA), Department of Agriculture (USDA), and Environmental Protection Agency (EPA) might all lay claim to a product made through synthetic biology, depending on the method of production and its intended use. But many new technologies don’t fit neatly into the purview of one office, concludes a report released today.
In the report, penned by the Synthetic Biology Project at the Woodrow Wilson International Center for Scholars, a Washington, D.C.–based think tank, a team of regulatory experts describe just how tortuous the path to market could be for new biotech products. It serves as a warning to startup companies that they’ll likely need to visit multiple agencies early in the development process, says Todd Kuiken, the Synthetic Biology Project’s principle investigator.
This summer, the White House acknowledged that the legal framework evaluating biotech products, last updated in 1992, has become outdated. It announced plans to modernize the rules, will begin discussions at a public meeting later this month, and is accepting public comment through 13 November. The new report lays out a series of cases—some theoretical, others already on regulators’ desks—where the current framework leads to perplexing and unpredictable results.
Here is a quartet of examples that promise regulatory mayhem:
The Oxitec mosquito
- What does it do? Genetically altered Aedes aegypti mosquitos developed by the biotech firm Oxitec carry a lethal gene that prevents their female offspring from maturing. The company hopes to limit the spread of mosquito-borne diseases such as Chikungunya virus and Dengue fever by releasing engineered mosquitos that will produce inviable offspring and shrink the population. Oxitec has already conducted field trials in Malaysia and on the Caribbean island of Grand Cayman. It’s now planning a trial in the Florida Keys.
- Why the uncertainty? Genetically altered insects are usually regulated by the USDA’s Animal and Plant Health Inspection Service (APHIS) because they are intended to control plant pests. But these mosquitos aren’t plant pests; they are a new strategy to prevent human disease, leading some to argue that they should be treated like other anti-infective medications and reviewed as a new drug by FDA’s Center for Drug Evaluation and Research (CDER).
- Who regulates it? The Oxitec mosquito was instead deemed a “new animal drug,” and is being evaluated by another FDA office, the Center for Veterinary Medicine. It is the same office that evaluates other technologies to sterilize animals for population control. The decision has prompted concerns that the FDA office is less equipped than USDA to carry out an assessment of the mosquito’s environmental impact. (Meanwhile the company’s new genetically modified diamondback moth, which uses the same basic strategy but targets a scourge on vegetable crops, has been evaluated and cleared for field trials by USDA.)
- What does it do? Squalene is an organic compound used as an emollient in lotions. It’s abundant in shark liver oil and other fish oils, and is also found in some plant oils. The biotech company Amyris engineered specialized yeast strains that can produce the molecule from sugar.
- Why the uncertainty? Ingredients like squalene in cosmetics raise an issue that FDA has yet to address: whether products made through synthetic biology should be labeled differently from naturally occurring substances, and whether their makers risk breaking rules on the accurate labeling of product ingredients (set by the Federal Food, Drug, and Cosmetic Act, or FFDCA).
- Who regulates it? Cosmetic ingredients don’t require FDA approval before they can be sold, and synthetic squalene is already on the market. The new report warns that both FDA and the Federal Trade Commission may be compelled to take a closer look at how synthetic ingredients are described on labels.
The PBAN moth trap
- What does it do? Pheromone Biosynthesis Activating Neuropeptide (PBAN) offers an alternative to insect pheromones, which are often used as bait in traps for agricultural pests, but can be expensive and difficult to produce. Students in a 2014 undergraduate student synthetic biology competition run by the International Genetically Engineered Machine (iGEM) Foundation devised a PBAN-laced bait. When eaten by female moths in the trap, PBAN induces them to produce their own pheromones and lure in males. The students at the National Chiao Tung University in Taiwan created genetically modified bacteria to produce PBAN, which they mixed with a moth-enticing sugar solution.
- Why the uncertainty? A product placed in a trap to interfere with the growth or mating of pests would normally be subject to EPA regulation under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the new report explains. But FIFRA exempts pheromones, which are considered to pose less of an environmental risk than traditional pesticides. If a company sought to market PBAN traps, however, it’s not clear whether they would enjoy the same exemption: PBAN is not technically a pheromone but a hormone that prompts moths to produce a pheromone themselves.
- Who regulates it? If such a product slipped past EPA on the pheromone exemption, the report’s analysts suggest PBAN could still be subject to EPA’s Toxic Substances Control Act, or even the FFDC, depending on its application.
- What does it do? Ornamental cress plants designed by Glowing Plant, Inc. contain firefly and jellyfish genes that cause them to glow green in the dark.
- Why the uncertainty? Genetically modified plants typically fall under USDA’s jurisdiction because they rely on a gene transfer technique that uses agrobacterium—a plant pest. But the Glowing Plant prototypes use a newer technique known as a gene gun to blast gene-carrying particles into plant cells.
- Who regulates it? In December of 2014, APHIS informed Glowing Plant, Inc. that its product doesn’t fall under its jurisdiction; no agency has formally assessed its potential environmental risks. According to the company’s Kickstarter page, which accepts preorders for both plants and seeds, the company is “in the final phase of getting the plant ready for shipping.” But the company has also advertised a DIY kit for those who want to genetically modify the seeds themselves. And because this kit relies on agrobacterium, the report says, an individual customer could be legally obligated to seek a permit from APHIS.