Challenges to bringing
cell-based products to market
Natalie E. Rainer
K&L Gates LLP, San Francisco, United States
The burgeoning field of cell-based agriculture is perhaps the most exciting and innovative food technology development in the past century. As a new technology, there remain many unknowns and challenges for cell-based agriculture to become a replacement for animal-derived foods—from government-based legal and regulatory challenges to market-based consumer challenges to industry-based competitive challenges. This article provides an overview of some of the external challenges that the industry faces at this stage, when products are finally starting to enter the market.
Cell-based or cellular agriculture is a technology with the potential to revolutionize food by replacing farming of animals with in vitro methods. The term “cell-based agriculture” generally refers to the growing of animal cells in a bioreactor, rather than the animal itself. Terms such as “in vitro meat,” “lab-grown meat,” “cultured meat”, and “clean meat” refer to cell-based production of animal muscle cells (1). However, the technology is not limited to muscle cell growth; cell-based fats present an interesting option for inclusion in plant-based meat alternatives to create closer flavor parity to traditional meat products.
As a technology that is at the beginning stages of commercialization internationally, the cell-based agriculture industry faces a number of challenges. These challenges range from legal and regulatory to consumer acceptance to potential competitive challenges. These hurdles will influence how quickly the industry grows and whether it can gain purchase as a staple in modern human diets. This article explores some of the obstacles facing this burgeoning industry. As a food regulatory attorney, my perspective is more policy-based than technical. Further, I view the issue more through a U.S.-lens, where concerns like litigation are greater than in most jurisdictions in the world. However, I believe that the majority of the concerns below have relevance to a degree in all jurisdictions.
Cellular agriculture first made international headlines in 2013 when Google co-founder, Sergei Brin, announced that he had sponsored (for upwards of US$300,000) the production of the world’s first “lab-grown” beef burger, dubbed “Frankenburger” in some press outlets (2). Since then, cell-based agriculture companies—producing muscle cells, fats cells, and inputs like cell growth media—have proliferated around the globe.
Today, 10 years since its splashy debut, what do we mean when we refer to “cell-based agriculture”? Briefly, the process involves isolating cells from an animal (e.g., chicken, pork, lobster), immortalizing those cells (3), and culturing them in a bioreactor. During the culturing process, the cells are fed growth media and reproduce. There may be scaffolding on which the cells are grown within the bioreactor, and this scaffolding may be edible or inedible. Once the growth step is complete, the cells are harvested and processed (typically involving blending with other ingredients) into the finished food product.
While cell-based foods are not readily available to consumers anywhere in the world as of yet, the cell-based agriculture industry is now on the verge of reaching the market in a number of jurisdictions. Of course, there is eager anticipation of the first cell-based products to hit the U.S. market, a jurisdiction that has historically been hospitable to new food technologies (4), and on November 16, 2022, U.S. Food and Drug Administration (FDA) announced its first successful “consultation” with Berkeley, California’s UPSIDE Foods Inc. (UPSIDE) on its cell-based chicken product (5). While UPSIDE still needs to complete its review with USDA, the United States is poised to join Singapore as the only jurisdictions to have assessed the safety of cell-based products for human consumption (6).
What are the hurdles that the cell-based agriculture industry faces now, on the verge of anticipated widespread commercialization and production at scale of cell-based products? We consider below three areas: (a) government-based legal and regulatory challenges, (b) market-based consumer acceptance challenges, and (c) industry-based marketing and competitive challenges.
Government-based challenges: Legal and regulatory
The challenge of the legal and regulatory approval of these new foods is that governments and companies are tasked with fully exploring and understanding the potential safety challenges that cell-based products may pose. Such a safety assessment addresses not only the target cells themselves (e.g., from the standpoint of ensuring they are not contaminated with pathogens), but also the safety of each feed media input, potential metabolic byproduct, and material in contact with the cells (e.g., scaffolding, bioreactor liner).
The difficulty of the path toward legal and regulatory clearance of cell-based products is interestingly political. That is, jurisdictions more concerned with food sovereignty or that have limited arable land (e.g., Singapore, United Arab Emirates, Israel) may be more welcoming and faster to grant clearances than jurisdictions that do not face such concerns (e.g., the European Union (EU)). Singapore, for example, a nation-state with insufficient land to feed its growing population, currently relies heavily on food imports. With this in mind, it is not entirely surprising that Singapore was the first jurisdiction in the world to clear cell-based products for use in human food (7). Cell-based agriculture offers Singapore and similarly situated countries independence from other countries for a highly critical resource. On the other hand, the EU, which follows the “precautionary principle” in assessing new foods, has typically been slow to adopt new food technologies and will be handling cell-based foods through its cumbersome and often opaque novel food and genetically modified food petition processes, which is likely to take years to navigate.
A happy medium perhaps—and a jurisdiction that other countries may imitate—is the approach in the United States. In the United States, there is a memorandum of understanding in which two regulatory agencies will share regulatory jurisdiction over cell-based products (8). The U.S. Food and Drug Administration (FDA) will exercise jurisdiction until the harvest stage. FDA will apply its expertise in addressing novel food safety issues to conduct a thorough science-based assessment. At harvest, the U.S. Department of Agriculture (USDA) will assume authority and will ensure the appropriate handling of such products, as well as approve labeling.
To date only UPSIDE has successfully completed the first stage of the U.S. regulatory review framework, with FDA issuing a press release on November 16, 2022, that UPSIDE had successfully undergone “consultation” with FDA to assess the safety of its cell-based chicken product (9). The FDA assessment—not an “approval”—considered the safety of UPSIDE’s product following a framework akin to the Hazard Analysis and Risk-Based Preventive Controls framework. The consultation process apparently spanned 13 months after the submission of UPSIDE’s safety assessment to the FDA and addressed issues including: (a) potential contamination of the cell-lines from reagents or the environment; (b) the safety of inputs such as cell growth media, antibiotics, and antimycotics; (c) the safety of the genetic modification to immortalize the chicken cells; and (d) potential contamination from equipment, environment, and media components at the various stages of the manufacturing process (i.e., proliferation, differentiation, and harvest). Not surprisingly, the assessment focused attention not on the safety of the chicken cells per se (which are nearly identical to conventional chicken), but on how the processing aids (growth media), environmental contaminants (viruses, bacteria), food-contact materials, and other aspects of the manufacturing process could compromise the purity and safety of those cells. Next UPSIDE will presumably work with the USDA to focus on safety post-harvest, as well as labeling issues.
Vastly different regulatory frameworks are developing around the globe to regulate these food products. The extent to which these frameworks present challenges, versus opportunities, is country-specific and is expected to evolve substantially over the next five to 10 years.
A second type of legal and regulatory challenge facing the industry is legislation limiting the use of “meat” terms for cell-based products (10). For example, France has issued legislation both limiting the use of terms (e.g., “steak,” “fillet,” “bacon”) that can be used for plant-based products (11) and has set maximum levels of plant-based protein that can be present in various meat products (e.g., products described as “bacon,” “ham,” “sausage” and the like) (12). It is possible that similar initiatives will seek to limit the use of traditional animal-based meat terms in the context of cell-cultured products. As with the potential political influence on legal and regulatory premarket approvals of cell-based agriculture, jurisdictions with strong animal farming lobbies may encounter legislation that limits the ability to use certain terms in marketing cell-based products, whereas countries without such industries may be less burdened by these types of laws.
Market-based challenges: Consumer acceptance
Over the past two decades, there has been an overwhelming public interest in and demand for “natural” products. Cell-based agriculture, while from a natural source, would be hard-pressed to fit the current definition of “natural”. It is not clear whether consumers—many of whom are mistrustful of technologies like genetic modification—will be able to accept cell-based foods and ingredients in the current environment that prizes a low-technology approach to food.
A consumer acceptance challenge remains in creating products that consumers enjoy. Mimicking animal products in terms of taste, texture, structure, and even color (before and after cooking) remains a challenge. In terms of different cell-based products entering the market, cell-based fat presents a perhaps easier point of entry than a complex steak-type product. Plant-based meat alternatives currently lacking in flavor may achieve much closer taste to traditional meat products simply with the addition cell-based fat, so this may be one of the first types of products we see employing cell-based ingredients. However, this type of product has a limited audience. Reaching a wider swath of the market is likely to require advances in producing complex structures in which muscle, fat, and connective tissue grow in a way that is similar to conventional whole-cut products. Producing a steak-type product, with layers of differentiated cells, poses distinct challenges. Aleph Farms took a step toward more complex cell-based foods when it announced in 2021 that it had 3D printed a “ribeye steak” (13). However, at this stage, most cell-based muscle products are currently better suited to be blended and to produce burger-type products.
Lastly, cell-based products are entering the market at a time when there are many different diets that are of interest to consumers: vegan (strictly no animal-based ingredients), vegetarian (may accommodate non-meat ingredients, such as eggs and cheese), whole food (unprocessed or minimally processed, “natural”) paleo (meat-based), and keto (high in protein and fat, low in carbohydrates). The motivations to choose these diets can range from health to weight loss to the environment to animal welfare and to some or all of these factors. How will cell-based products fit into these competing diets? Are vegetarians interested in plant-based products with cell-based animal ingredients? Will meat-eaters tolerate a less-than-perfect substitute for steak if there is an environmental benefit? What if the cost is significantly higher (14)? Should we be seeking cell-based alternatives to traditional meat, or should we be changing our tastes to prefer plant-based diets? These and similar questions will affect how popular cell-based products are and how widespread their adoption will be.
Industry-based challenges: Competitive claims
In promoting cell-based products in comparison to traditional animal products, companies will draw a high level of scrutiny from the animal agriculture industry. For example, benefits to the environment are often touted as a reason for supporting cell-based agriculture (e.g., citing the high carbon emissions, waste production, water use, and deforestation associated with traditional animal agriculture and the potential for cell-based technologies to improve upon these metrics) (15). However, it will take a significant amount of research to substantiate environmental claims comparing environmental impacts of specific cell-based and animal-based products. Such claims will be examined closely and are expected to be vigorously challenged if overly broad or misleading in any regard. Environmental claims may also need to be reassessed fairly frequently as cellular agriculture evolves to larger scales that perhaps will require different processing techniques and inputs and have potentially different environmental impacts.
Similarly, marketing terms such as “clean meat” are likely to draw challenges. Many cell-based products continue to rely on costly and complex feed media such as fetal bovine serum, a mixture containing potentially thousands of constituents that is harvested from the fetuses of slaughtered cows (16). Use of inputs that consumers may find undesirable presents potential risk to companies making “clean” or similar claims implying that cell-based products are superior to traditional meat products.
Cell-based agriculture is still in its infancy, and many hurdles will need to be overcome before it becomes a viable food source globally. While the past 10 years of technical advances have brought market accessibility much closer to fruition, the external challenges described above will certainly impact how widely and how quickly consumers in different markets get access to cell-based foods.
References and notes
References and notes
- In a paper by Keri Szejda of the Good Food Institute (published in 2018 and updated in 2020), research evaluated the consumer acceptance of 74 different names for cellular agriculture products. See Keri Szejda, Cellular Agriculture Nomenclature: Optimizing Consumer Acceptance, the Good Food Institute, (January 2020), Jan-2020-Updated-2018-Cellular-Agriculture-Nomenclature-Report.pdf (gfi.org).
- Josh Schonwald, The Frankenburger Is Coming Sooner Than You Think Thanks to Google, Time, (August 15, 2014), https://time.com/3118571/lab-grown-meat-frankenburger-google/.
- An excellent discussion of cell immortalization is available in Immortalizing Cells for Human Consumption. Emily Soice and Jeremiah Johnston, Immortalizing Cells for Human Consumption, International Journal of Molecular Sciences (October 28, 2021), http://dx.doi.org/10.3390/ijms222111660.
- The “Generally Recognized As Safe” or GRAS Notice program in the U.S. demonstrates the FDA’s openness to new technologies. See, e.g., FDA, GRAS Notice (GRN) No.863, (March 29, 2019), https://www.fda.gov/media/137104/download.
- FDA, FDA Completes First Pre-Market Consultation for Human Food Made Using Animal Cell Culture Technology (November 16, 2022), https://www.fda.gov/food/cfsan-constituent-updates/fda-completes-first-pre-market-consultation-human-food-made-using-animal-cell-culture-technology, and UPSIDE Foods, Inc., Premarket Notice for Integral Tissue Cultured Poultry Meat (Oct. 1, 2021), https://www.fda.gov/media/163262/download.
- Singapore Health Services Authority, Regulatory overview of cell, tissue or gene therapy products, (June 16, 2021), https://www.hsa.gov.sg/ctgtp/regulatory-overview.
- Amy Woodyatt and Danielle Wiener-Bronner, Singapore becomes first country to approve lab-grown meat, CNN (December 2, 2020), https://edition.cnn.com/2020/12/02/business/lab-grown-chicken-intl-scli-scn/index.html.
- FDA and USDA, Formal Agreement Between FDA and USDA Regarding Oversight of Human Food Produced Using Animal Cell Technology Derived from Cell Lines of USDA-amenable Species, (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.
- FDA, Letter to UPSIDE Foods, Inc. on Cell Culture Consultation Notification File: CCC000002 (November 16, 2022), https://www.fda.gov/media/163260/download.
- Júlia de Paula Soares Valente, Rodrigo Alonso Fiedler, Marina Sucha Heidemann, and Carla Forte Maiolino Molento, First glimpse on attitudes of highly educated consumers towards cell-based meat and related issues in Brazil, PLoS ONE (August 30, 2019), https://doi.org/10.1371/journal.pone.0221129.
- Balance of trade relations in the agri-food sector (EGALIM) (No. 627) Amendment No. CE2044 - National Assembly, https://www.assemblee-nationale.fr/dyn/15/amendements/0627/CION-ECO/CE2044.
- Decree No. 2022-947 of 29 June 2022 on the use of certain names used to designate foodstuffs containing vegetable proteins, https://www.legifrance.gouv.fr/jorf/id/JORFTEXT000045978360.
- Lana Bandoim, World’s First 3D Bioprinted and Cultivated Ribeye Steak Is Revealed, Forbes, (Feb. 12, 2021), https://www.forbes.com/sites/lanabandoim/2021/02/12/worlds-first-3d-bioprinted-and-cultivated-ribeye-steak-is-revealed/?sh=395626af4781.
- In a paper published in Biotechnology and Bioengineering, author David Humbird’s analysis indicates that, even after accounting for enhancement of metabolic efficiency and lowering the cost of cell media, the minimum cost of cell-based meat (i.e., nugget and ground meat-style products) will be on the order of $50 per kilogram. David Humbird, Scale‐up economics for cultured meat, Biotechnology Bioengineering, (June 7, 2021), https://doi.org/10.1002/bit.27848.
- The Good Food Institute, Growing Meat Sustainably: The Cultivated Meat Revolution, https://gfi.org/wp-content/uploads/2021/01/sustainability_cultivated_meat.pdf.
- For more information on the composition and use of fetal bovine serum in cell culturing, see The Good Food Institute’s excellent Deep dive: Cultivated meat cell culture media at https://gfi.org/science/the-science-of-cultivated-meat/deep-dive-cultivated-meat-cell-culture-media/.