Follow-up: FDA responds to gene editing questions
Last month, WLJ ran a cover story on a move by the Food and Drug Administration (FDA) to regulate gene editing. The focus of the article was FDA’s Draft Guidance for Industry #187 (GFI 187). The topic raised numerous questions best put to the FDA that went unanswered by press time.
Since then, WLJ has had a drawn out correspondence with the FDA regarding those questions. This is presented below so that readers may get a better idea of the agency’s perspective on the matter. Both questions and answers as presented have been edited for flow, relevance and brevity.
The language in GFI 187 seems to contradict itself on whether or not it is a regulation with the force of law; can you clarify?
Guidance documents represent the FDA’s current thinking on a topic. The guidance document itself does not establish requirements, however, it may refer to requirements that are established by statute or regulation.
In this case, the guidance is intended to clarify and explain how the law and its implementing regulations apply to intentionally altered genomic DNA in animals.
The draft guidance explains that intentionally altered genomic DNA in an animal meets the statutory definition of a drug under the provisions of the Food, Drug, and Cosmetic Act (FD&C Act). That means that requirements for new animal drugs in the statute and regulations apply, unless otherwise excluded. The draft guidance document references those requirements and explains how they apply in this context; it did not create those requirements.
Is GFI 187’s focus on the intention of gene-editors——rather than the editing process or the results of that editing—— new or unusual for government guidances or regulations?
As described in GFI 187, FDA regulates products that meet the drug definition and not the processes by which such products are created.
The definition of “drug” in the FD&C Act has always focused on “intent.” An article is a “drug” if it is “intended” to do certain things.
Thus, for decades, the “intended use” of a product has been critical to determining whether a product is subject to FDA requirements pertaining to human or animal drugs.
We can’t comment directly on other agencies’ regulatory processes. As a general matter we note that other statutes also focus on the “intent” of the product in determining jurisdiction. For example, the definition of “pesticide” in the Federal Insecticide, Fungicide, and Rodenticide Act is “any substance or mixture of substances intended for…”
Why is “random mutagenesis followed by phenotypic selection”—a common practice among plant breeders whereby plants are exposed to chemicals or radiation to induce genetic mutations—pointedly excluded from the “modern molecular technologies” being addressed in GFI 187?
Mutagenesis is not considered a modern molecular technology so it does not fall within the scope of that term. We also note that we are unaware of the use of chemical- or radiation-induced mutagenesis being used in animal agriculture in a manner similar to plant-based agriculture.
Draft Guidance 187 focuses on intentionally altered genomic DNA in animals, which is an issue handled by the Center for Veterinary Medicine. If you are interested in food derived from genetically engineered plants, that is a matter handled by the Center for Food Safety and Applied Nutrition.
The agency is currently accepting public comment to help inform its regulatory approach to human and animal foods derived from plants developed using genome editing. Readers can go here and submit comments, which will be accepted through April 19.
Scientists working with gene-edited food animals have expressed concern that GFI 187 could make gene-edited food animals reaching the market impractical due to excessive regulation; can you comment on this concern?
The FDA Center for Veterinary Medicine’s mission is to protect human and animal health. To further this mission, CVM applies its regulatory authority to ensure animal drugs are safe and effective. CVM evaluates new animal drug applications as expeditiously as possible and has been able to approve some applications related to genetically engineered (GE) animals quickly, such as a GE goat and a GE chicken that produce human medical products.
In addition, as stated in the guidance, based upon risk, FDA has modified its regulatory approach in the past and is willing to do so with regard to genome-edited animals as well. For example, FDA has exercised enforcement discretion over approval requirements for animals that pose minimal risk such as the GloFish, a GE aquarium fish, and has exercised enforcement discretion over a large animal model of human disease.
In the notice accompanying the draft guidance, we asked for comment on whether there are categories of genome-edited animals that pose minimal risk.
We made this request because we are willing to modify our approach based on an analysis of hazard and risk, but, as a science-based agency, we cannot do so in the absence of data or information that demonstrates empirically that certain alterations pose a minimal risk. — Kerry Halladay, WLJ Editor