FDA’s Voluntary Consultation Program for Cultured Meat Products

From time to time on the blog, I’ve commented on the emerging field of foods derived from cultured animal cells, and how these products would be regulated by governments around the world. In today’s post, I’m catching up with some recent developments in the United States, relating to how the U.S. Food and Drug Administration (FDA) is carrying out its roles in oversight over such products.

As I reported back in 2018 in the blog, the FDA and the U.S. Department of Agriculture (USDA) issued a statement on November 16, 2018 to announce that the agencies would work together to develop a regulatory framework for cell-based meats. The statement said:

“Drawing on the expertise of both USDA and FDA, the Agencies are today announcing agreement on a joint regulatory framework wherein FDA oversees cell collection, cell banks, and cell growth and differentiation. A transition from FDA to USDA oversight will occur during the cell harvest stage. USDA will then oversee the production and labeling of food products derived from the cells of livestock and poultry.”

This was followed by a more formal agreement announced in March 2019, setting out agencies’ responsibilities in more detail. Among other responsibilities, it stated that FDA would maintain oversight over the initial processes of cell collection and growth, and in particular that the agency would “conduct premarket consultation processes to evaluate production materials/processes and manufacturing controls, to include oversight of tissue collection, cell lines and banks, and all components and inputs”.

I’m not aware of any subsequent formal announcement from FDA regarding a “premarket consultation process”, but in November 2022 the agency announced that it had reviewed the first product under such a program. In this announcement, the agency referenced the March 2019 USDA agreement, and said “The FDA’s approach to regulating products derived from cultured animal cells involves a thorough pre-market consultation process. While this is not considered an approval process, it concludes when all questions relevant to the consultation are resolved”.

FDA’s voluntary consultation program for human food made from cultured animal cells is described on its website. Although there does not appear to be a more definitive description of how a company would go about requesting voluntary consultation, the web page describes the process as follows:

The FDA’s voluntary pre-market consultation process evaluates the safety of food made from cultured animal cells before it enters the market. The pre-market consultation allows developers to work with the FDA on a product-by-product basis and informs them of issues they must consider to produce safe food that does not violate the Federal Food, Drug and Cosmetic Act’s requirements. As part of the pre-market consultation process, we evaluate the production process and the cultured cell material made by the production process, including the establishment of cell lines and cell banks, manufacturing controls, and all components and inputs. Our goal is to support innovation in food technologies while always maintaining as our priority the production of safe food.

We encourage firms to have conversations with us often and early in their product and process development phase. We are already engaged in discussions with multiple firms about various types of food made from cultured animal cells, including seafood and food destined for animal diets.

As of this date, two products have received “no questions” letters from the FDA under the voluntary consultation program: food products made from cultured chicken cells from UPSIDE Foods (November 2022) and GOOD Meat, Inc. (March 2023).  In both cases, the agency posted on its website the nonconfidential version of the company’s original submission and any amendments, the agency’s “no questions” letter sent to the submitter, and a detailed internal FDA memo summarizing the basis for their finding.

According to FDA’s summary memos, the UPSIDE Foods product consisted of cultured Gallus gallus [chicken] cells, with characteristics of myocytes and fibroblasts, in the form of sheets of cells. The GOOD Meat product also consisted of cultured Gallus gallus cells, in this case derived from a commercially-available chicken cell line UMNSAH/DF1, with characteristics of fibroblasts. Unlike the sheets of cells used in the UPSIDE process, the GOOD Meat process uses a cell paste arising from the harvested cells. In both cases, FDA “evaluated information about the cell lines, the production process (including cell bank establishment), substances used in the production process, and properties of the harvested cell material, including information available in both the disclosable safety assessment as well as supporting, corroborative information in a confidential supplementary appendix”. For each product, FDA concluded that “based on the data and information presented in [the submission], we have no questions at this time about [the company’s] conclusion that foods comprised of, or containing, cultured chicken cell material resulting from the production process defined in [the company’s submission] are as safe as comparable foods produced by other methods”.

FDA’s Inventory page lists only these two submissions that have successfully completed FDA review. The site does not list, or indicate, whether there have been other submissions that are currently undergoing review, but it is reasonable to assume that there have been other submissions. One page on the FDA website says “We are already engaged in discussions with multiple firms about various types of food made from cultured animal cells, including seafood and food destined for animal diets”.

Although there does not appear to be any specific guidance for companies regarding how to prepare a dossier for consideration under this program, the agency’s website says that for questions about the pre-market consultation process for human food, companies should contact the agency’s Center for Food Safety and Applied Nutrition, Office of Food Additive Safety at AnimalCellCultureFoods@fda.hhs.gov. For cultured animal cell food products, or any of the byproducts generated during the production of process, intended for use in animal food, firms should contact the Center for Veterinary Medicine, Division of Animal Food Ingredients, at Animalfood-premarket@fda.hhs.gov.

D. Glass Associates, Inc. is a consulting company specializing in government and regulatory affairs support for renewable fuels and industrial biotechnology. David Glass, Ph.D. is a veteran of over thirty-five 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. In addition to his work as a consultant assisting industrial biotechnology companies prepare for and comply with government regulations, he has served as Director of Regulatory Affairs for Joule Unlimited Technologies and Vice President of Government and Regulatory Affairs for BioTechnica International. Dr. Glass has extensive experience with the biotechnology regulations of the U.S. EPA and other agencies, and has coordinated or assisted in the preparation and submission of 18 successful Microbial Commercial Activity Notices and several other biotechnology submissions in the U.S. and other countries. Dr. Glass holds a B.S. in Biological Sciences from Cornell University and a Ph.D. in Biochemical Sciences from Princeton University.

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FAO Report on Safety Aspects of Cell-Based Foods

The Food and Agriculture Organization (FAO) of the United Nations has published a new report that comprehensively summarizes the state of the emerging field of cell-based or cultured food. The 146 page report, entitled “Food safety aspects of cell-based food” was issued by the FAO, in collaboration with the World Health Organization (WHO) in March 2023. This follows a 2020 report from the U.S. General Accounting Office on the regulatory framework for cell-cultured meat, which I described in an earlier post on the blog.

According to the FAO’s announcement, the new document “includes a literature synthesis of relevant terminology issues, principles of cell-based food production processes and the global landscape of regulatory frameworks for cell-based food production”. The document also focuses on potential hazards arising from the technology, based on an expert consultation to comprehensively identify possible food safety hazards.

The report devotes an introductory chapter to a description of the technologies used in the development and production of cell-based foods, along with a survey of applicable regulations in about a dozen countries or jurisdictions. The next chapter presents case studies of product development, commercialization and regulation in three countries: Israel, Qatar and Singapore. After a chapter discussing the possible safety hazards that could arise from the technology, the report concludes with a summary of its conclusions and recommendations for a path forward. The conclusions stress the need for application of the appropriate scientific knowledge, including correct terminology, and the need for hazard identification, in order for governments to conduct risk assessments of new products in this field, and the report calls for cooperation among countries to share knowledge and expertise as the field develops.

I’ve only begun to review the report by focusing on the sections dealing with international regulation of cell-based foods. The report summarizes the applicable regulatory frameworks in important jurisdictions like the U.S., Europe, Australia and New Zealand, Japan and other countries, concluding that, in most cases, existing laws and regulations such as those governing “novel foods” would be applicable to the market introduction of cell-based foods in these jurisdictions. I would note, however, that the findings of the report address the state of the industry up to March 1, 2022, and so some of the regulatory descriptions are not fully up to date. In particular, the section on the U.S. framework does not discuss FDA’s voluntary consultation program for human food made from cultured animal cells, under which two products have received “no questions” letters from the FDA in recent months: food products made from cultured chicken cells from UPSIDE Foods (November 2022) and GOOD Meat, Inc. (March 2023) (I plan to discuss this program and these approvals in an upcoming blog post). Strangely, the report also does not address the fact that several related products have been reviewed by FDA under their GRAS Notice program, including the GRAS Notice submitted by Impossible Foods for the soy leghemoglobin from genetically modified microorganisms that it uses to provide texture to its plant-based meat products, which received FDA’s “no questions” letter in July 2018.

I hope to be able to review the FAO report in more detail in the coming weeks, and to post additional comments here on the blog.

D. Glass Associates, Inc. is a consulting company specializing in government and regulatory affairs support for renewable fuels and industrial biotechnology. David Glass, Ph.D. is a veteran of over thirty-five 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. In addition to his work as a consultant assisting industrial biotechnology companies prepare for and comply with government regulations, he has served as Director of Regulatory Affairs for Joule Unlimited Technologies and Vice President of Government and Regulatory Affairs for BioTechnica International. Dr. Glass has extensive experience with the biotechnology regulations of the U.S. EPA and other agencies, and has coordinated or assisted in the preparation and submission of 18 successful Microbial Commercial Activity Notices and several other biotechnology submissions in the U.S. and other countries. Dr. Glass holds a B.S. in Biological Sciences from Cornell University and a Ph.D. in Biochemical Sciences from Princeton University.

Recently-Approved MCANs

From time to time, I’ve posted analyses of recent Microbial Commercial Activity Notices (MCANs) reviewed and received by the U.S. Environmental Protection Agency (EPA) under its biotechnology regulations (40 CFR Part 725). Since the 2016 enactment of the Lautenberg Amendments to the law on which these regulations are based, the Toxic Substances Control Act, or TSCA, EPA has changed the way approved MCANs are posted on the agency’s website. Some of these changes are for the better – approvals are posted much more quickly after the approval date, as opposed to the old system where approval lists were often many months out of date. However, the new format of the approval listings has made it a bit harder to learn much of any value regarding the microorganisms covered by the MCANs and their company applicants.

One page on the EPA website is an “MCAN Table”, which is dedicated to the biotechnology program and which lists in one place all the MCANs approved since the June 2016 amendments, with 200 entries as of April 10, 2023. However, this page does not show any information other than the submission and approval dates, and in particular does not identify the applicant (where that is not confidential) or provide the generic (non-confidential) names of the organisms. A more informative page is the “Chemicals Determined Not Likely to Present an Unreasonable Risk” page, which includes biotechnology submissions along with all other submissions for chemical substances under Section 5 of TSCA, and includes 547 entries as of April 10 submitted since June 2016. This page is searchable, and by searching for the MCAN prefix “J”, it’s possible to develop a list of MCANs approved since 2016. Although this list does not identify the applicants, working from this listing is advantageous because each entry includes the generic name of the microorganism with a link to EPA’s decision document for each MCAN. Although the decision documents rarely contain any information specific to the organism that is the subject of the MCAN, this table provides more information than the “MCAN Table” mentioned above.

The latter table allows the following to be said regarding approved MCANs submitted during Fiscal Years 2021, 2022 and 2023 to date (i.e. submitted since October 1, 2020). As of April 10, 2023, of those MCANs submitted in this time period, 50 were approved (note that when consolidated MCANs are filed, each of the strains is assigned its own MCAN number, so these 50 assigned MCAN numbers correspond to about 24 discrete submissions). Of the fifty, 23 were identified in the generic organism name as covering genetically modified Saccharomyces cerevisiae, while the other 27 were for other microbial species or were for MCANs for which the identity of the species was claimed as confidential (although several of these were for “modified yeast” strains, some of which may also be S. cerevisiae). The listings include a “generic use” for the organisms, and among the uses cited were biofuel production, production of chemicals, enzymes or other proteins, nucleic acids, or agricultural products. (For full disclosure, I should add that I prepared or assisted in the preparation of 10 of these 24 submissions on behalf of several clients).

There isn’t much more that can be said about these MCANs without obtaining the nonconfidential copies of the filings from EPA’s public information offices. However it is interesting that these figures show that EPA is receiving and approving approximately 20 or more MCANs per year, which is perhaps a bit below the historical peak, but is still a decent size workload. It’s also interesting that many of the S. cerevisiae MCANs specifically reference the production of biofuels, at a time when industry interests are shifting towards production of bio-based chemicals with less emphasis on products like biofuels that generally have lower profit margins.

D. Glass Associates, Inc. is a consulting company specializing in government and regulatory affairs support for renewable fuels and industrial biotechnology. David Glass, Ph.D. is a veteran of over thirty-five 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. In addition to his work as a consultant assisting industrial biotechnology companies prepare for and comply with government regulations, he has served as Director of Regulatory Affairs for Joule Unlimited Technologies and Vice President of Government and Regulatory Affairs for BioTechnica International. Dr. Glass has extensive experience with the biotechnology regulations of the U.S. EPA and other agencies, and has coordinated or assisted in the preparation and submission of 18 successful Microbial Commercial Activity Notices and several other biotechnology submissions in the U.S. and other countries. Dr. Glass holds a B.S. in Biological Sciences from Cornell University and a Ph.D. in Biochemical Sciences from Princeton University.