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Cell-Cultured Protein: Regulatory Considerations and Opportunities

Cell-Cultured Protein: Regulatory Considerations and Opportunities

Written By: Eve Pelonis, Natalie Rainer, and Connie Potter; Keller and Heckman, LLP

At the forefront of current food innovation and technology is the “cell-cultured protein” sector (also described as “cultured,” “cell-based,” “cultivated,” “lab-grown,” and “in vitro”). Cell-cultured protein technology essentially entails growing protein cells in a growth medium under controlled conditions. Manufacturers across the globe are rushing to culture proteins that have a taste, texture, and nutrition profile that is indistinguishable from their animal-based counterparts. With products ranging from beef to yellowtail to foie gras to lobster, the cell-cultured protein industry has the potential to revolutionize the food and agriculture industries.

While Singapore has taken an early lead in terms of regulatory approvals by becoming the first nation to approve a cell-based protein, the United States is poised to be a fertile ground for the growth of the cell-cultured protein industry. Below we discuss the future regulation of this industry in the U.S., what information will likely be required to seek regulatory approvals from the relevant regulatory agencies, and issues related to the labeling and marketing of cell-cultured proteins in the U.S.

To set the backdrop for the discussion below, we first discuss the basics of cell-based protein technology: biopsy, cell banking, growth, harvest, and food processing. After collecting a tissue sample from an animal in a biopsy, a laboratory team selects the cells with the most desirable traits and adds them to a cell bank. The selected cells are then multiplied using a bioreactor. The bioreactor uses a growth medium and controlled conditions to create an ideal environment for growing cells, which often grow attached to a scaffold or like structure that helps the cells grow in the proper pattern to create a finished product. Once a sufficient number of cells have accumulated, producers harvest the cells from the growth medium and bioreactor, either detaching the cells from the scaffold structure or removing the cells and scaffold together if the scaffold is edible. The cells are then prepared into a finished food product, often by blending the meat cells with a fat to create, for instance, a ground beef patty or meatball. With this background in mind, we discuss the regulatory framework for evaluating this technology, followed by potential labeling issues, below.

Regulatory Status of Cell-Cultured Protein Products in the United States

As the two agencies that oversee the safety of the U.S. food supply, the U.S. Food and Drug Administration (FDA) and Department of Agriculture (USDA) have both asserted regulatory authority over cell-cultured meats. Generally, USDA is responsible for oversight of meat, poultry, processed egg products, and catfish, while FDA oversees virtually all other domestic and imported foods, including all seafood products, sold in the U.S. In 2018, USDA’s Food Safety and Inspection Service (FSIS) and FDA hosted the first of several public meetings on cell-culture technology and discussed potential hazards, oversight considerations, and product labeling.

Following additional public comment periods, the agencies issued a formal interagency agreement in March 2019 that set out their respective roles in the oversight of cell-cultured meat products based on their respective strengths and expertise. Per the formal agreement, FDA will oversee the cell culturing process for meat and poultry products until the harvest stage, including cell collection and the development and maintenance of cell banks, and FDA will retain sole jurisdiction over seafood. Facilities will need to comply with FDA food safety requirements, including food facility registration, hazard analysis and risk-based preventive controls (HARPC), and current Good Manufacturing Practices (GMPs). Following harvest of cells from bioreactors, USDA assumes regulatory authority and is responsible for inspection of the meat cells and finished products derived from livestock and poultry under its authority from the Federal Meat Inspection Act and Poultry Products Inspection Act. FDA and USDA have agreed to collaborate to develop a more detailed joint framework on standard operating procedures, product labeling, and other issues. However, aside from FDA’s issuance of a Request for Information regarding the labeling of foods containing cell-cultured seafood products, as of the date of this publication, neither agency has published further details on these initiatives.

Industry is concerned by the lack of additional action on the part of FDA and USDA. In October 2020, the Alliance for Meat, Poultry, and Seafood Innovation joined the North American Meat Institute in urging FSIS to issue an Advance Notice of Proposed Rulemaking to initiate an

information collection process. The agencies have expressed a great deal of interest in collaborating with cell-cultured meat producers, but companies appear to be reluctant to participate, perhaps given the highly-confidential processes and proprietary information at stake.

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Where to Go from Here?

Cell-cultured meat products could pose safety concerns unique from those in traditional meat production. In fact, the technology is so new that it remains unclear just how FDA and USDA will approach the specifics of approving cell-cultured foods. The concerns highlighted in an April 2020 report by the Government Accountability Office (GAO) included the potential use of antibiotics at the cell growth stage and potentially new safety issues unique to this new technology (e.g., residues or constituents not seen in conventional meat or other foods). We expect regulators to evaluate the safety of cell-cultured proteins from all angles: microbial contaminants, cell growth media, scaffolding ingredients, bioreactors, etc. All inputs and impurities of potential concern will be explored.

While industry’s hesitation to be among the first in line to approach regulators is understandable, stakeholders should also recognize that there is an opportunity to be among the first to drive the dialogue, to focus regulators on specific issues, and to be the first entrants into the U.S. market. The more the agencies know about the process, the better they can create a regulatory framework that will most accurately capture the way the industry operates. 

Use of the Term “Meat” and Other Labeling Concerns

Another murky legal and regulatory area facing the cell-cultured protein industry is the marketing of cell-cultured protein products and in particular the naming of such products. Some current contenders for naming cell-cultured products include terms like “clean,” which critics argue reflects a bias for or against other products and affect how they are perceived in the market.

While both USDA and FDA are aware of this labeling question, neither entity has proposed a regulatory solution. Various pieces of legislation have been introduced (but have not passed) in Congress that seek to clarify when a “meat,” “milk” or other traditional term can be used, generally restricting such term to products from traditionally-raised livestock or requiring that non-traditional products use the term “imitation” in their product identity statement. 

Perhaps because of the lack of action by Congress or federal agencies, several states—including Arkansas, Arizona, Louisiana, Mississippi, Missouri, Oklahoma, Nebraska, North Dakota, South Dakota, Texas, and Wyoming—have passed laws restricting use of the term “meat” on cell-cultured meat or plant-based meat alternative products. Many of these laws have been challenged in court by companies in the meat-alternative space that argue the laws violate the First Amendment by limiting speech and are not necessary to protect the public from potentially misleading information in addition to being overbroad and impeding competition in the marketplace. Results of the suits have varied, with some successes for the meat alternative industry. For example, while an Arkansas federal district court granted a preliminary injunction preventing enforcement of a state law that restricted the use of meat claims on plant-based products in 2019—finding that the plaintiffs were likely to prevail on their First Amendment claims, a federal district court in Oklahoma upheld a similar challenge to a state law that required a disclaimer on plant-based foods using a meat term in the product identity statement. 

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Cell-cultured products will be ready to enter the market soon, and USDA and FDA will need to act quickly to create a framework that manufacturers can work with if they want to assert leadership in this space. Even if cell-cultured meat products can overcome regulatory hurdles and enter the market, several recently-published studies show consumers may not yet be willing to embrace cell-cultured meat as an alternative to traditional meat products because of concerns over taste, food safety, and lack of knowledge about the process. Manufacturers will need to focus on consumer outreach and launch education initiatives to garner an understanding of their products to be successful.

(1) Cultured Meat: Shaping the Future of Foods, Keller and Heckman LLP (Feb. 1, 2021), https://www.khlaw.com/insights/cultured-meat-shaping-future-foods. Cell-culturing technology could be an intriguing option for countries like Singapore with limited capabilities for livestock production that seek to produce more food domestically. Other countries have frameworks in place to review cell-cultured products but have not yet approved any. In the European Union, cell-cultured meat products must be assessed as a novel food by the European Food Safety Authority under Regulation (EU) 2015/2283. Australia and New Zealand’s food regulatory agency, Food Standards Australia New Zealand, has a premarket approval system in place that would similarly encompass new cell-cultured products. Cell Based Meat, Food Standards Australia New Zealand https://www.foodstandards.gov.au/consumer/generalissues/Pages/Cell-based-meat.aspx (last visited Feb. 14, 2020).

(2) U.S. Gov’t Accountability Off., GAO-20-325, Food Safety: FDA and USDA Could Strengthen Existing Efforts to Prepare for Oversight of Cell-Cultured Meat 9–11 (2020), https://www.gao.gov/assets/710/705768.pdf.

(3) Technology is still improving to create more structured meat products, such as a filet. Aleph Farms, an Israeli start-up, recently announced it had developed a ribeye steak using bioprinting technology. Aleph Farms and The Technion Reveal World’s First Cultivated Ribeye Steak, Cision PR Newswire (Feb. 9, 2021), https://www.prnewswire.com/news-releases/aleph-farms-and-the-technion-reveal-worlds-first-cultivated-ribeye-steak-301224800.html. 

(4) Recordings of each USDA-FDA Joint Public Meetings are linked at FDA’s Food Made with Cultured Animal Cells page, https://www.fda.gov/food/food-ingredients-packaging/food-made-cultured-animal-cells.

(5) Formal Agreement Between FDA and USDA Regarding Oversight of Human Food Produced Using Animal Cell Technology Derived from Cell Lines of USDA-amenable Species, FDA (March 7, 2019), https://www.fda.gov/food/domestic-interagency-agreements-food/formal-agreement-between-fda-and-usda-regarding-oversight-human-food-produced-using-animal-cell.

(6) See FDA Seeks Input on Labeling of Food Made with Cultured Seafood Cells, FDA (Oct. 6, 2020), https://www.fda.gov/food/cfsan-constituent-updates/fda-seeks-input-labeling-food-made-cultured-seafood-cells. The Senate has twice introduced bills aimed at moving the regulatory process forward by formalizing the USDA/FDA formal agreement and prescribing a timeline for the agencies to promulgate regulations. See Food Safety Modernization for Innovative Technologies Act, S. 3053, 116th Cong. (2019), https://www.congress.gov/bill/116th-congress/senate-bill/3053 (codifying the division of authority for cell-cultured products between USDA and FDA as set forth in their 2019 formal agreement, providing guidelines for inspection of cell-cultured meat production facilities, and creating labeling guidelines specific to cell-cultured meat products); Cell-Cultured Meat and Poultry Regulation Act of 2019, S. 1056, 116th Cong. (2019), https://www.congress.gov/bill/116th-congress/senate-bill/1056 (codifying the USDA/FDA 2019 formal agreement and giving the agencies eighteen months to promulgate regulations regarding inspection frequency of relevant facilities and labeling guidelines).

(7) Meat Institute and AMPS Innovation Send Joint Letter to USDA on Mandatory Labeling for Cell-Based/Cultured Meat & Poultry Products, North American Meat Institute (Oct. 19, 2020), https://www.meatinstitute.org/ht/display/ReleaseDetails/i/180624/pid/287.

(8) U.S. Gov’t Accountability Off., supra note 2, at 8.

(9) See id.

(10) The U.S. Cattlemen’s Association submitted a petition to USDA in February 2018 requesting the agency limit the term “beef” to products from traditionally-harvested livestock, and the petition received over 6000 comments, but USDA has not moved on the issue to date. See Petition for the Imposition of Beef and Meat Labeling Requirements: To Exclude Products Not Derived Directly from Animals Raised and Slaughtered from the Definition of “Beef” and “Meat”, U.S. Cattlemen’s Association (Feb. 9, 2018), https://www.fsis.usda.gov/wps/wcm/connect/e4749f95-e79a-4ba5-883b-394c8bdc97a3/18-01-Petition-US-Cattlement-Association020918.pdf?MOD=AJPERES.

(11) See, e.g., Food Safety Modernization for Innovative Technologies Act, supra note 6; Cell-Cultured Meat and Poultry Regulation Act, supra note 6; Real Marketing Edible Artificials Truthfully Act of 2019, H.R. 4881, 116th Cong., https://www.congress.gov/bill/116th-congress/house-bill/4881/all-info.

(12) Elaine Watson, ‘Highly disingenuous…’ Plant-based labeling battle heats up as more states challenge use of meat, dairy terms, Food Navigator-USA (Feb. 3, 2021), https://www.foodnavigator-usa.com/Article/2021/02/03/Highly-disingenuous-Plant-based-labeling-battle-heats-up-as-more-states-challenge-use-of-meat-dairy-terms?utm_source=newsletter_daily&utm_medium=email&utm_campaign=03-Feb-2021.

(13) Turtle Island Foods SPC v. Soman, 424 F. Supp. 3d 552, 571 (E.D. Ark. 2019) (finding a state law that prohibits plant-based meat alternative products from using terms such as “burger,” “sausage,” and “roast,” even if the product identity statement contains a disclaimer phrase such as “plant-based” or “veggie”).

(14) Upton’s Naturals Co. v. Stitt, No. CIV-20-938-F, slip op. at (W.D. Ok. Nov. 19, 2020) (finding that a law requiring disclaimer terms on plant-based meat alternatives to be at least as equally prominent in size and color as the product name was not unduly burdensome and justified in preventing consumer confusion).

(15) In study published by the University of Sydney and Curtin University, 72% of the 227 surveyed Australian customers in “Generation Z” (born between 1995 and 2010) reported perceptions of uneasiness and discomfort with cultured meat products, even if they thought the product might be a more sustainable food option than traditionally farmed meat. Diana Bogueva & Dora Marinova, Cultured Meat and Australia’s Generation Z, Frontiers in Nutrition, Sept. 2020, at 6, https://doi.org/10.3389/fnut.2020.00148. See also Jo Anderson & Chris Bryant, Messages to Overcome Naturalness Concerns in Clean Meat Acceptance: Primary Findings, Faunalytics, July 2018, Clean-Meat-Acceptance-Primary-Findings.pdf (faunalytics.org) (surveying 1,185 American adults in 2018 and finding that while the majority of those surveyed had not heard of a cell-cultured meat product before, 66% of those surveyed would be willing to try it, but using biased terminology such as “clean meat” that would have legal risk if used in the market); Nearly One in Three Consumers Willing to Eat Lab-Grown Meat, According to New Research, Surveygoo (Jan. 2018), https://surveygoo.com/portfolio/cultured-meat-survey/ (surveying 1,000 U.S. and U.K. consumers and finding 29% would be willing to eat a cell-cultured meat product described as “cultured meat”). 4839-4212-9116, v. 4

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Safety – Organic food health benefits have been hard to assess, but that could change

Grapes harvest. Farmers hands with freshly harvested black grapes.

 

Written by: Cynthia Curl, Assistant Professor, Boise State University
Originally published in The Conversation
16 August 2019

 

“Organic” is more than just a passing fad. Organic food sales totaled a record US$45.2 billion in 2017, making it one of the fastest-growing segments of American agriculture. While a small number of studies have shown associations between organic food consumption and decreased incidence of disease, no studies to date have been designed to answer the question of whether organic food consumption causes an improvement in health.

 

I’m an environmental health scientist who has spent over 20 years studying pesticide exposures in human populations. Last month, my research group published a small study that I believe suggests a path forward to answering the question of whether eating organic food actually improves health.

 

What we don’t know

 

According to the USDA, the organic label does not imply anything about health. In 2015, Miles McEvoy, then chief of the National Organic Program for USDA, refused to speculate about any health benefits of organic food, saying the question wasn’t “relevant” to the National Organic Program. Instead, the USDA’s definition of organic is intended to indicate production methods that “foster cycling of resources, promote ecological balance, and conserve biodiversity.”

 

While some organic consumers may base their purchasing decisions on factors like resource cycling and biodiversity, most report choosing organic because they think it’s healthier.

 

Sixteen years ago, I was part of the first study to look at the potential for an organic diet to reduce pesticide exposure. This study focused on a group of pesticides called organophosphates, which have consistently been associated with negative effects on children’s brain development. We found that children who ate conventional diets had nine times higher exposure to these pesticides than children who ate organic diets.

 

Our study got a lot of attention. But while our results were novel, they didn’t answer the big question. As I told The New York Times in 2003, “People want to know, what does this really mean in terms of the safety of my kid? But we don’t know. Nobody does.” Maybe not my most elegant quote, but it was true then, and it’s still true now.

 

Studies only hint at potential health benefits

 

Health-conscious people want to buy organic for its health benefits, but it’s not yet clear whether such benefits exist.Goran Bogicevic/Shutterstock.com

 

 

 

Since 2003, several researchers have looked at whether a short-term switch from a conventional to an organic diet affects pesticide exposure. These studies have lasted one to two weeks and have repeatedly shown that “going organic” can quickly lead to dramatic reductions in exposure to several different classes of pesticides.

 

Still, scientists can’t directly translate these lower exposures to meaningful conclusions about health. The dose makes the poison, and organic diet intervention studies to date have not looked at health outcomes. The same is true for the other purported benefits of organic food. Organic milk has higher levels of healthy omega fatty acids and organic crops have higher antioxidant activity than conventional crops. But are these differences substantial enough to meaningfully impact health? We don’t know. Nobody does.

 

Some epidemiologic research has been directed at this question. Epidemiology is the study of the causes of health and disease in human populations, as opposed to in specific people. Most epidemiologic studies are observational, meaning that researchers look at a group of people with a certain characteristic or behavior, and compare their health to that of a group without that characteristic or behavior. In the case of organic food, that means comparing the health of people who choose to eat organic to those who do not.

 

Several observational studies have shown that people who eat organic food are healthier than those who eat conventional diets. A recent French study followed 70,000 adults for five years and found that those who frequently ate organic developed 25% fewer cancers than those who never ate organic. Other observational studies have shown organic food consumption to be associated with lower risk of diabetes, metabolic syndrome, pre-eclampsia and genital birth defects.

 

The problem with drawing firm conclusions from these studies is something epidemiologists call “uncontrolled confounding.” This is the idea that there may be differences between groups that researchers cannot account for. In this case, people who eat organic food are more highly educated, less likely to be overweight or obese, and eat overall healthier diets than conventional consumers. While good observational studies take into account things like education and diet quality, there remains the possibility that some other uncaptured difference between the two groups – beyond the decision to consume organic food – may be responsible for any health differences observed.

 

What next?

 

Often, new medical and health knowledge comes from carefully designed clinical trials, but no such trial has been conducted for organic food. Anyaivanova/Shutterstock.com

 

When clinical researchers want to figure out whether a drug works, they don’t do observational studies. They conduct randomized trials, where they randomly assign some people to take the drug and others to receive placebos or standard care. By randomly assigning people to groups, there’s less potential for uncontrolled confounding.

 

My research group’s recently published study shows how we could feasibly use randomized trial methods to investigate the potential for organic food consumption to affect health.

 

We recruited a small group of pregnant women during their first trimesters. We randomly assigned them to receive weekly deliveries of either organic or conventional produce throughout their second and third trimesters. We then collected a series of urine samples to assess pesticide exposure. We found that those women who received organic produce had significantly lower exposure to certain pesticides (specifically, pyrethroid insecticides) than those who received conventional produce.

 

On the surface, this seems like old news but this study was different in three important ways. First, to our knowledge, it was the longest organic diet intervention to date – by far. It was also the first to occur in pregnant women. Fetal development is potentially the most sensitive period for exposures to neurotoxic agents like pesticides. Finally, in previous organic diet intervention studies, researchers typically changed participants’ entire diets – swapping a fully conventional diet for a fully organic one. In our study, we asked participants to supplement their existing diets with either organic or conventional produce. This is more consistent with the actual dietary habits of most people who eat organic food – occasionally, but not always.

 

Even with just a partial dietary change, we observed a significant difference in pesticide exposure between the two groups. We believe that this study shows that a long-term organic diet intervention can be executed in a way that is effective, realistic and feasible.

 

The next step is to do this same study but in a larger population. We would then want to assess whether there were any resulting differences in the health of the children as they grew older, by measuring neurological outcomes like IQ, memory and incidence of attention-deficit disorders. By randomly assigning women to the organic and conventional groups, we could be sure any differences observed in their children’s health really were due to diet, rather than other factors common among people who consume organic food.

 

The public is sufficiently interested in this question, the organic market is large enough, and the observational studies suggestive enough to justify such a study. Right now, we don’t know if an organic diet improves health, but based on our recent research, I believe we can find out.