Regulation of Cell-Based Meats: Scientific Issues

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.

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Cell-Based Meats: Regulatory Issues Facing an Emerging Field

Although a bit off-point from the original scope of this blog (biofuels and bio-based chemicals), I’ve lately been spending some time with the emerging field of cell-based meats, which has in recent months caught the attention of federal regulators here in the U.S. This field, more formally known as “foods produced using animal cell culture” or also as “cellular agriculture,” involves R&D aimed at producing edible substitutes for common human foods through cell culture, rather than through the farming and/or slaughter of live food animals (one early summary of the field can be found here). There are a growing number of companies in the U.S. and elsewhere, as well as numerous academic groups, that are working on such technologies, with the goal of creating beef, pork, poultry or fish products grown from tissue culture. Also under development are products such as egg substitutes comprised of microbially-produced proteins, as well as the “Impossible Burger” where a yeast-produced plant heme protein gives veggie burgers the taste and feel of beef hamburgers.

Although there have been low-key internal discussions within regulatory agencies and individual one-on-one discussions between companies and regulators about the appropriate regulatory pathways for such products, recent events in the first half of 2018 have brought this issue to the forefront. These have included a petition filed in February 2018 by the U.S. Cattleman’s Association asking the U.S. Department of Agriculture (USDA) to block cell-cultured meat products from being labeled as “meat” or “beef” (similar to the unrelated, recently-successful effort to prevent soy- or nut-based products from being labeled as “milk”), a Congressional briefing on the subject of cellular agriculture in June 2018, and a public meeting held by FDA on July 12, 2018 to discuss scientific issues relating to safety and regulatory oversight over such products (see below). Also, although not directly related to the use of tissue culture to produce meat substitute products, in July 2018, the FDA informed Impossible Foods, Inc. that the Agency had no objections to the company’s finding that its microbially-produced soy leghemoglobin was Generally Recognized as Safe for use with its plant-based Impossible Burgers.

FDA’s interest in regulating these products is notable because historically, the regulation of meat products in the U.S. has been under the auspices of the USDA, through the inspection and labeling authorities of its Food Safety and Inspection Service (FSIS). Indeed, the battle lines are beginning to be drawn between those favoring FDA’s having the lead role through its traditional responsibility for reviewing the safety and efficacy of new food additives and ingredients, and those who would prefer to see jurisdiction for meat and poultry to remain with the USDA (cell-based fish products, however, would be on the sidelines of any jurisdictional battle, because USDA has no regulatory or inspection role for any fish products other than, through a legislative quirk, catfish). FDA says that it has been in discussions with USDA about coordination to avoid any possible regulatory overlap, although there are signs that each agency may be pursuing its own plans for regulatory programs.

It was with this backdrop that FDA held its public meeting on July 12, 2018. The stated goal of the session was to “provide the public the opportunity to provide comments related to the production of foods using animal cell culture technology”. The June 18, 2018 Federal Register Notice announcing the meeting listed four topics on which public comments were invited:

  • FDA has evaluated a variety of foods produced by cell culture, including microbial (g.,probiotics), algal (e.g., spirulina), and fungal products (e.g.,mycoprotein). What considerations specific to animal cell culture technology would be appropriate to include in evaluation of food produced by this method of manufacture?
  • FDA has issued guidance on how to assess the effects of significant manufacturing process changes on the safety of a food ingredient. What kinds of variations in manufacturing methods would be relevant to safety for foods produced by animal cell culture technology?
  • FDA has a variety of pre- and postmarket programs for evaluating the safety of substances used in the production and manufacture of foods, including, for example, food additive and color additive regulations and preventive control requirements. 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?
  • 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?

I was not able to attend the meeting myself, and so I can’t summarize the meeting and the nature of the public comments delivered orally at the session. There are several excellent summaries available online, such as reports on the websites of the Food and Drug Law Institute, the Good Food Institute and Ag Funder News. In the public meeting, FDA officials laid out the scientific issues it anticipates being raised by products in this category. In addition to hearing public comments from industry, public interest groups and others, the meeting featured a panel of stakeholders from industry, academia, and the non-profit sector offering their perspective on these issues and the nature of the regulatory regime that might emerge.

Following the meeting, FDA is soliciting public comments through September 25, 2018, which can be submitted online at regulations.gov, or in writing to FDA’s Rockville, MD address.

In follow-up posts, I have offered my thoughts about the scientific questions FDA has posed, and the regulatory and jurisdictional issues that should be addressed to enable the adoption of a rational, science-based regulatory scheme that utilizes all the applicable resources of federal regulatory agencies to assure the public that cell-based foods are safe, without creating an undue burden on the innovative companies developing these 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.