As discussed in a previous post in the blog, the U.S. Food and Drug Administration has requested public comment on issues relating to the anticipated introduction of human food products produced from cultured animal cells (“cell-based meat” products), as replacements for traditional meat, poultry or fish or other products of traditional animal agriculture. Then, in a second post, I provided my thoughts on the scientific issues related to this emerging industry sector, including comments in response to the four questions FDA posed in its June 2018 Federal Register notice. In today’s blog entry, I offer my perspective on the regulatory and jurisdictional issues that may arise if the U.S. government decides to institute regulatory oversight over products in this sector.
Although FDA did not explicitly ask for public comment on such issues, I feel it would be appropriate for stakeholders to comment on what would be the best or most optimum regulatory structure in the United States for oversight over cell-based meat. As noted in my first post, battle lines are already being drawn between those preferring FDA to have the lead in such regulation and those preferring that the U.S. Department of Agriculture (USDA), through its Food Safety and Inspection Service (FSIS), have the lead role. I believe that there is a role for both agencies, and that any regulatory regime include participation from both agencies in a collaborative manner, as has been done many times before, in the regulation of biotechnology and other industries.
Specifically, FSIS’s role is to ensure the safety and wholesomeness of the nation’s meat, poultry and egg products through its inspection and labeling programs. Its mission statement is “Protecting the public’s health by ensuring the safety of meat, poultry, and processed egg products.” FSIS regulations under the Federal Meat Inspection Act and the Poultry Products Inspection Act are found in 9 CFR Subchapter E, Parts 412-500, and its regulations for egg product inspections are at 9 CFR Subchapter I, Parts 590-599. Note that FSIS has no authority over fish products, except for catfish, for which FSIS maintains regulatory programs similar to those for meat under 9 CFR Subchapter F, Parts 530-561. FSIS’s regulations include rules governing the safe, sanitary and humane slaughter and processing of food animals, and a robust inspection program under which slaughterhouses and food processing facilities are overseen by federal inspectors and must follow detailed sanitation requirements under 9 CFR Part 416. Part 424 of the regulations contains a lengthy list of ingredients that can be used in meat processing and/or which can appear in meat products. FSIS has also developed test methods for certain food pathogens like the most virulent E. coli strains, and also requires product labels to be approved under 9 CFR Part 412. A good, detailed overview of the system of U.S. regulation of meat and other foods can be found at a North Dakota State University website; another useful site is one posted by Cooperative Extension, focusing on regulation of meat processing.
As effective as this program has been, there are two difficulties in extending this regulatory regime to oversight over cell-based meats. First, the FSIS regulatory program stems from the definition of “meat product” in the Federal Meat Inspection Act (FMIA), which is: “any product capable of use as human food which is made wholly or in part from any meat or other portion of the carcass of any cattle, sheep, swine, or goats, excepting products which contain meat or other portions of such carcasses only in a relatively small proportion or historically have not been considered by consumers as products of the meat food industry …” (emphasis added). Lawyers may long debate whether animal cells that have been grown in culture for multiple generations can be considered to have originated from an “other portion of the carcass”, especially if the cell line was originated with cells from a live animal rather than a dead animal. Based on this language, it would seem likely that regulatory changes, if not an amendment to the legislation, might be needed to unequivocally bring cell-based meat products under the jurisdiction of the FMIA as a “meat product”.
On the other hand, although the definition of “meat product” in the regulations, at 9 CFR 301.2, parallels the definition in the legislation, the regulations also define “meat byproduct” as “Any part capable of use as human food, other than meat, which has been derived from one or more cattle, sheep, swine, or goats …” (emphasis added), without mention of a carcass; and “meat byproduct” is included in the definition of “product” in the regulations. One might therefore argue that cell-based meats could be subject to the FMIA as “meat byproducts”, and that is indeed the position taken by the National Cattlemen’s Beef Association, in a statement issued before FDA’s July 12, 2018 public meeting (although this association’s persistence in calling the new products “fake meat” is frankly not helpful to foster a reasoned public debate). It seems to me that this would be a somewhat tortuous way to achieve regulatory coverage for these products, and manufacturers would not want their products to have to be labeled as “meat byproducts” (although, again, that might satisfy the political goals of the traditional meat industry).
Second, FSIS has not, historically, maintained any program of premanufacture review of the safety of meat or its ingredients. Its regulatory oversight is based on the assumption that as long as meat is obtained from healthy animals and is processed under the appropriate sanitary conditions and is appropriately labeled, meat products are safe to eat. It is not clear whether USDA FSIS has the required staff or expertise to conduct science-based premarket reviews of the safety of new meat products in a timely manner.
FDA, on the other hand, has long had as part of its mission the requirement to review the safety of proposed new food ingredients, although I should note that U.S. law does not require premarket approval of “foods” per se. Companies can introduce and sell new food products without oversight, as long as they are not “adulterated” or do not include new ingredients not already approved for use in food: such new ingredients would be regulated as food additives unless they can be shown to be Generally Recognized as Safe (GRAS). I have previously described FDA’s GRAS Notice program and the 2016 Final Rule that established this program in previous posts on the blog, most recently in January 2018; with more information available on FDA’s website. Under this rule and its predecessor interim policy, FDA has reviewed hundreds of new food ingredients in a timely and professional manner. .
To the extent that premarket review for cell-based meat products is deemed to be needed or desirable, I suggest an approach along the following lines. FDA’s Center for Food Safety and Nutrition (CFSAN) should be responsible for premarket review, under its existing GRAS Notice program or a by creating a new parallel (but similar) process. Manufacturers would submit dossiers to FDA supporting the safety of their product, and I suggest that the main focus of FDA’s review should be to assess the equivalence of the product to traditional meat products from a nutritional and safety perspective, while also assessing the safety of the manufacturing process and the ingredients used in food production. In other words, the developer of a product produced from animal cell culture should not have to demonstrate safety de novo, i.e. through extensive toxicology or other testing, but instead should be able to show that the product has equivalent nutritional value to traditional products, has no unwanted impurities or byproducts as a result of its production method, and is chemically or compositionally equivalent to the comparable existing product. Manufacturers should also be required to follow Good Manufacturing Practices and other procedures as mandated under current food safety law (e.g. the Food Safety Modernization Act). My preference would be a program like the GRAS Notice program, where FDA review is encouraged but not mandatory; or if mandatory that provision be made for expedited review of follow-on products having only minor differences from originally-approved products.
In establishing such a program, FDA should make use of available scientific expertise, including from academia, industry and importantly also from within the USDA, particularly within FSIS, to ensure that the best and most appropriate technical knowledge is applied to premarket safety assessments. Then, once a product is approved for marketing or otherwise clears FDA’s review process, the traditional inspection and oversight authority of FSIS could come into play. New procedures would need to be established for oversight, inspection and registration of cellular production facilities, analogously to existing oversight of meat processing plants, and this might require revisions to FSIS regulations, for example, to define revised sanitary and other procedures and safeguards applicable to cell culture, and possibly also to provide for the inspection of final products and their labeling. USDA should retain its labeling authority under the FMIA regulations; but I won’t comment on the important question of whether these products should or should not be labeled as “meat”.
Whenever a new technology emerges that may lead to novel, paradigm-breaking products, it is inevitable that regulatory turf wars will arise or loom on the horizon. It’s also inevitable that the existing industries that are threatened by the new products close ranks and, where possible, use existing regulatory barriers to make life difficult for what they see as upstart competitors. In fact this is far from the first time in the history of the biotech industry that battles over regulatory jurisdiction have occurred, most notably for oversight over pest-resistant GMO crop plants and certain other agricultural products, but these disputes have always been satisfactorily resolved. I hope that FDA and USDA are able to amicably work together to establish a reasonable regulatory framework that assures the public that these new products are safe and nutritious to eat, without imposing an unnecessary burden or punitive regulatory barriers on the innovative companies developing such products.
D. Glass Associates, Inc.is a consulting company specializing in government and regulatory affairs support for renewable fuels, industrial biotechnology and related field. David Glass, Ph.D. is a veteran of over thirty years in the biotechnology industry, with expertise in industrial biotechnology regulatory affairs, U.S. and international renewable fuels regulation, patents, technology licensing, and market and technology assessments. More information on D. Glass Associates’ regulatory affairs consulting capabilities, and copies of some of Dr. Glass’s prior presentations on biofuels and biotechnology regulation, are available at www.slideshare.net/djglass99and at www.dglassassociates.com. The views expressed in this blog are those of Dr. Glass and D. Glass Associates and do not represent the views of any other organization with which Dr. Glass is affiliated.
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