As discussed in the 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. The following are my thoughts on the scientific issues related to this emerging industry sector, including responses to the four questions FDA posed in its June 2018 Federal Register notice,
FDA’s questions largely asked commenters for input as to whether the anticipated production methods for cell-based meats would raise safety concerns, and in particular whether they might raise concerns different from those applicable to traditional meat products. In fact, some of the questions, notably the fourth, can be viewed as suggesting that commenters provide evidence for why the new methods might be safer than existing practice, rather than riskier. There is some overlap between their questions, and so I first offer the following general comments, which may be applicable to more than one of FDA’s questions. These comments assume that, as a result of this public comment process, FDA will put in place some form of premarket review for cell-based meat products, although that is far from a certainty, and my comments should not necessarily be construed as favoring such an outcome.
- Production of foods from animal cell culture has the potential to be more reproducible and predictable than manufacturing meat products by growing and slaughtering animals. Once each producer develops and optimizes its production method, it is expected that the methods will be carried out under suitable Good Manufacturing Processes, including Standard Operating Procedures and appropriate QA/QC methods. Companies would use food-grade ingredients (e.g. the components of cell growth media) that are well-studied and known to be safe. Production would take place under well-understood protocols where temperature and sanitary conditions could be better controlled; and the need for aseptic techniques would minimize the possibility of contamination by pathogens.
- There is a long history of use of animal tissue culture cells in research and for commercial purposes such as pharmaceutical production. Although such activity has been carried out for purposes different from food production, this experience provides basic guidance for how animal cell culture work can be carried out safely, to avoid adverse occupational health effects, other public health concerns, and any possible environmental risks. There are several articles in the literature dealing with the safety aspects of animal tissue culture research. One example is a recent review (Herman and Pauwels, 2015), which describes the potential health and safety risks to consider when working with animal cell culture (e.g. the potential for microbial contamination) as well as the types of procedures and practices that can be used to minimize such risks. Presumably commenters will bring these and other references to FDA’s attention during the comment period.
- In many cases, production of meat products via cell culture would avoid contamination that is currently possible from environmental or other inputs: e.g., meat products would not require the massive use of antibiotics now common in animal agriculture, and fish products would be free from contamination from mercury, plastics and other potentially-hazardous materials present in oceanic or river environments.
- In the case of fish, cell-based methods would eliminate the need for fish flesh to be maintained on ice for hours or days from the time of fish catch to the time of processing.
To address FDA’s specific questions (paraphrased or excerpted):
What considerations specific to animal cell culture technology would be appropriate to include in evaluation of food produced by this method of manufacture?
Although the focus of regulation should be on the end product, and in particular its comparison to traditional meat products, it is appropriate for FDA to review manufacturing information as part of any premarket assessment it may institute. Such information might include the identity, the original source, and characterization of the cell lines used, the methods and growth conditions used for cell culture, the components of the culture media used to grow the cells, and any downstream processing steps. Manufacturers should ascertain that cell lines and the resulting product are free of viruses or any contaminating microorganisms, as well as any other contaminants.
What kinds of variations in manufacturing methods would be relevant to safety for foods produced by animal cell culture technology?
To some extent, an answer to this question is the same as for the first question. However, a response to this question could be that cell culture manufacturing methods hold the potential to be more predictable, more reproducible, more sanitary and therefore safer than traditional methods involving the slaughter of animals, for the reasons discussed above. Use of cell culture as a manufacturing method would not necessarily create new potential risks, but could in fact reduce or eliminate risks of existing food processing. In addition, any regulatory scheme should provide an expedited path to market when minor manufacturing changes are proposed for products already reviewed and cleared for human consumption.
What kinds of substances would be used in the manufacture of foods produced using animal cell culture technology and what considerations would be appropriate in evaluating the safety of these uses?
Detailed responses to this question would need to be addressed by each individual manufacturer, but FDA’s assessment should be no different than current practice in evaluating foods or food additives produced by biological processes like microbial fermentation. In such assessments, FDA requests information on the components of fermentation media and other inputs into the process, and generally requires that all such substances be food-grade and of suitable purity. Specific ingredients in animal cell culture may require some additional scrutiny or require efforts from industry to develop or source food-grade replacements. Any ingredients that are not food-grade may need to be replaced. That being said, the focus should be on the final, finished product, and whether the substances used in processing are present in the product, and if so, whether such presence poses any health or safety risks.
Are the hazards associated with production of foods using animal cell culture technology different from those associated with traditional food production/processing (such as, for example, insanitary conditions, improper temperature controls, or control of contaminants)? Is there a need for unique control measures to address the hazards associated with production of foods using animal cell culture technology?
This question is addressed by the general comments above. It is very likely that fewer potential risks would arise from producing foods using cell culture compared to traditional methods. The control measures that might be needed for cell-based manufacture would be similar to those commonly used in the microbial fermentation industry, but would likely need to be different from those now imposed on traditional meat production (e.g. under USDA’s sanitation regulations).
I am planning to use this blog post as the starting point to draft and submit my comments to FDA by the September 25, 2018 due date, as requested at the docket for this matter at regulations.gov, but I welcome any feedback or comments anyone may have on these issues.
In the post that follows, I’ll offer some comments on what might be an appropriate regulatory scheme for cell-based meat 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/djglass99 and 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.