What does the future of cultivated meat look like now?

Without doubt, the publication of the FDA’s first pre-market consultation for UPSIDE Foods’ cell-cultured chicken on 16 November 2022 was the most exciting regulatory development to happen last year. But what have we learned, what does the process look like, and what does the future hold?

The US regulatory framework consists of two main phases. The Food and Drug Administration (FDA) Centre for Food Safety and Applied Nutrition (CFSAN) has oversight for cell collection, cell banks, cell amplification and differentiation (and harvesting and production of cells from species not regulated by the USDA – e.g. fish and seafood). Then the US Department of Agriculture (USDA) Food Safety and Inspection Service (FSIS) has oversight for cell harvesting, production and labeling of cells derived from livestock (meat, poultry and Siluriformes).

The pre-market consultation for human food made with cultured animal cells or Cell Culture Consultation (CCC) is voluntary and does not constitute an ‘approval’. This means that a company wishing to sell cultivated meat must prepare a dossier to support the safety of its product, which is submitted to the FDA for review/consultation. If the FDA agrees with the safety conclusion that the company has reached, they issue a ‘No Questions Letter’, same as the Generally Recognized as Safe (GRAS) procedure. The process as we understand it as of today is summarized below:

1. Pre-submission consultation (the FDA encourages food companies to engage with them as early as possible);

2. The food company prepares a comprehensive dossier (similar to a GRAS notice) to support the safety of its product;

3. The dossier is submitted to the FDA where they review the submission and reach out to applicants to inform of issues they must consider and address;

4. They also perform an inspection of the production facility to ensure compliance with the applicable requirements (e.g. current Good Manufacturing Practice, etc);

5. The applicant has the chance to respond and address the FDA’s questions and amend their dossier;

6. Once FDA has completed the pre-market assessment, it issues a No Questions Letter if it agrees with the conclusion of the applicant;

7. The FDA No Questions Letter, scientific memo and a non-confidential version of the dossier are published in the CCC Inventory;

8. Coordination and transition to USDA; USDA-FSIS grant of inspection and labeling review;

9. USDA-FSIS issue mark of inspection;

10. The FDA conducts another inspection once production starts.

FDA intends to issue guidance on the pre-market consultation process, and the draft guidance will be available for public comment. There are no timelines provided but we expect to see the guidance published in 2023.

Hopefully we will see more No Questions Letters issued in 2023, and also see UPSIDE Foods receive the USDA greenlight

FSIS does not intend to establish new regulations for cell-cultured meat or poultry as current regulations are applicable to such products. However, FSIS does intend to publish new labeling regulations. The timelines are not yet clear but there have already been two public consultations on labeling of cell-cultured products that will inform future legislation.

So, what did we learn from the UPSIDE Foods dossier? Well, it took 13 months for the FDA review. This was CCC submission No. 000002, so USPIDE Foods was not the first dossier submitted to the FDA! Confidential information was submitted in a confidential supplementary annex. UPSIDE Foods included two cell lines and one of the cell lines was edited.

All animal-derived raw materials were tested for species-specific adventitious agents that could infect human cells. Demonstration of equivalence with conventional meat was central to the safety narrative. No toxicological studies were performed (e.g. 90-day rat study). Full composition of the cell culture media was provided. Two culture media formulations were submitted – one with serum and one serum-free, and data to support the composition of the final products produced with both types of media were presented. A risk assessment of media ingredients with special consideration to ingredients with no history of safe use in the food chain was submitted to support the safety of the media formulations. The use of recombinant growth factors was justified based on their presence in conventional chicken meat and residue data in the cell-cultured chicken was provided. Cell lines were tested for presence of bacteria, yeasts, molds, Mycoplasma spp., and avian, bovine and porcine viruses of concern – for example, avian viruses that can cross the avian-human species barrier as well as certain mammalian viruses that are capable of infecting avian cells.

What does this mean for the industry? We are waiting for the USDA-FSIS review before UPSIDE Foods can place its product on the market and we are waiting for the USDA to publish new regulations on the labeling of cell-cultured products. Even though we are not there yet, the FDA’s No Questions Letter is a good sign for the industry, and it will only be a matter of time before we see cell-cultured meat on the shelves in the USA.

So, what comes next? Hopefully we will see more No Questions Letters issued in 2023, and also see UPSIDE Foods receive the USDA greenlight. We may see cultivated fish and seafood hit shelves sooner rather than later as these products fall solely under FDA jurisdiction. The pioneering UPSIDE Foods dossier has provided us all with good insights into how the FDA is approaching the risk assessment of cultivated products, but it will be great to have a clear guidance for applicants to follow.

Once we see cultivated chicken hit the shelves, we will get a better understanding of consumer acceptance, which I hope will be positive. However, this in part will be dependent on the future labeling regulation and what the FSIS will allow us to call these products!

Dr Hannah Lester is the CEO & Principle Consultant of Atova Regulatory Consulting and also Head of Regulatory at Gourmey. This article is republished from the January/February 2023 edition of Protein Production Technology International, the industry's leading resource for alternative proteins. To subscribe to all future editions, please click here