GAO Report on Cell-Cultured Meat Regulation

In 2018, I wrote several posts about the emerging field of cell-based meats and federal government regulatory issues relating to this new field. Although much of the public and industry debate over this technology has quieted down a bit since that time, there have been some developments since my last post on this topic in December 2018.

As outlined in my previous posts, many observers, particularly in the industry, were concerned that jurisdictional disputes may arise between the two federal agencies having regulatory responsibilities that might apply to meat, poultry and fish products produced by cellular agriculture. These fears were somewhat abated when, in March 2019, the U.S. Department of Agriculture and the Food and Drug Administration entered into a Memorandum of Understanding outlining how they intended to work together to create a workable regulatory framework for cell-based meat products. This MOU, announced on March 7, 2019, applied only to meat and poultry products, and it stated that FDA would retain authority over cell-based fish production (other than catfish, which are currently under USDA jurisdiction). Under the MOU, the agencies agreed that, for the anticipated development of cell-based meat and poultry products, FDA would oversee activities relating to cell collection and proliferation, e.g. cell banks and cell culturing facilities, while USDA would oversee processing, packaging and labeling of cell-based meat products, including facility and product inspection. The MOU further identified areas where the agencies would work together, and it indicated that any emerging regulatory framework would likely rely on existing regulations, but that the agencies would review the possible need for new rules.

The issuance of the MOU seemed to quiet the debate somewhat, and in the months since then there has not been much activity in the public eye regarding an appropriate regulatory framework. To some extent this may be because the technology is still emerging, and aside from the well-publicized (and rapid) growth and public acceptance of plant-based products from companies like Impossible Foods and Beyond Meat, there doesn’t seem that any company is close to wanting to introduce a cell-based meat, poultry or fish product. To my knowledge, there has only been one product in this space which has successfully cleared the U.S. regulatory system, and that is 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.

The latest development in this story came on April 7, 2020, when the U.S. General Accountability Office (GAO) released a report it prepared on federal oversight of cell-cultured meat. The GAO is an independent arm of the government that carries out nonpartisan studies of various topics, generally at the request of Members of Congress or other federal officials. This report, entitled “Food Safety: FDA and USDA Could Strengthen Existing Efforts to Prepare for Oversight of Cell-Cultured Meat” was carried out at the request of Representative Rosa DeLauro, who is the Chairwoman of the Subcommittee on Labor, Health and Human Services, Education, and Related Agencies of the House of Representatives Committee on Appropriations. The full report can be downloaded from this site.

Although this report does not break any new ground or move the public debate forward, it offers a fairly complete current overview of the situation. Much of the report is devoted to a detailed summary of the science behind cell-cultured meats, including a discussion of several areas where technological details are unknown or are still being worked out (e.g. will the process make use of genetically modified cells? What types of materials will be used as the scaffolds to grow animal cells into the desired shape and texture?). And the report summarizes the developments on the federal regulatory front since 2018, including the joint meetings and other activities that preceded the March 2019 MOU. The document reports on one development that I had not previously seen reported publicly, which is that In June 2019, FDA and USDA created three working groups to carry out the terms of the interagency MOU. The working groups are comprised of FDA and USDA officials, and were described in the GAO report as follows:

• Pre-market assessment working group. Led by FDA, this group was created to clarify the process FDA will use for pre-market reviews of cell-cultured meat.
• Labeling working group. Led by USDA, this group will focus on developing joint principles for product labeling and claims.
• Transfer of jurisdiction working group. Co-led by FDA and USDA, this group will develop procedures for the transfer of inspection at harvest, among other things.

The GAO report indicates that the work of these groups is still in the early stages, although two of the working groups held meetings in December 2019.

The main recommendation of the report is that, while the March 2019 MOU represents a good start, and that interagency cooperation is essential, both agencies should better incorporate certain “leading practices to enhance and sustain interagency collaboration”. These are seven principles that the GAO had previously developed to guide federal agencies towards more effective collaboration. I won’t attempt to summarize these here – although they doubtlessly provide important and useful guidance to federal agencies, to the layperson they read like common sense advice for conducting effective collaborations that would also be applicable in the corporate world.

Historically, the GAO and its reports have often proven useful in guiding federal policy and public debate on questions of how best to regulate emerging technologies: this has particularly been true at various critical stages in the early growth of the biotechnology industry. Although this report doesn’t provide any new technological insights or make any substantive recommendations for policy or regulation, it does provide a comprehensive overview of many of the issues that have been discussed to date, and will hopefully serve to continue to move regulatory discussions forward.

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/djglass99and 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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Book chapter published on regulation of bio-based fuels and chemicals

Last year, I was asked to contribute a chapter for a book entitled “Biobased Products and Industries”, being edited by Charis M. Galanakis. This book was published by Elsevier earlier this year.  My chapter, “Government Regulation of Bio-based Fuels and Chemicals”, provides a comprehensive overview of the regulations that might affect the biological production of fuels, chemicals or other specialty products, with emphasis on the U.S. and select other jurisdictions. The chapter covers the following regulatory programs in the U.S., Europe and elsewhere:

• Industrial Chemicals: US regulation under TSCA, EU regulation under REACH.
• Fuel Certification: Standards and registration requirements for civilian, military and aviation fuels in the US and Europe.
• Promotion of Renewable, Bio-Based Products: The US Renewable Fuel Standard and state Low Carbon Fuel Standards, similar programs in Europe.
• Use of Genetically Modified Microorganisms: Regulation of the use of modified microorganisms to produce fuels and chemicals under US EPA TSCA regulations and biosafety regulations elsewhere in the world.
• Use of Genetically Modified Plants as Feedstocks: Regulation of the use of transgenic plants to produce fuels and chemicals under US Department of Agriculture regulations and biosafety regulations elsewhere in the world.
• Other Regulations, including facility registration requirements, use of microbial biomass in animal feed, and others.

A description of the book along with a Table of Contents and other information can be accessed here. I would be happy to answer any questions you may have on this chapter or the topics discussed.

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/djglass99and 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.

EPA revises TSCA biotechnology rule to expand the list of microorganisms eligible for tiered exemptions

EPA recently issued a Final Rule that is the first major amendment or revision to its biotechnology regulations under the Toxic Substances Control Act (TSCA) since the rules were first issued in 1997. These regulations, found at 40 CFR Part 725, cover certain commercial uses of microorganisms that have been modified to contain coding nucleic acid sequences from more than one taxonomic genus (so-called “intergeneric” microorganisms). The new Final Rule, issued on March 10, 2020, adds two species of microorganism to the list of host (“recipient”) microorganisms that are eligible to qualify for the tiered exemptions from commercial reporting under the biotechnology rule.

As previously reported in this blog, EPA published a Proposed Rule back in 2012 in which it proposed adding these two microbial species, Trichoderma reesei and Bacillus amyloliquefaciens subspecies amyloliquefaciens, to the list of microorganisms in 40 CFR 725.420 that may qualify for the Tier I and Tier II exemptions from full notification and reporting. Under the biotechnology regulations, companies planning commercial use or importation of an intergeneric microorganism, other than for purposes regulated as pesticides or by the Food and Drug Administration, must file a Microbial Commercial Activity Notice (MCAN) at least 90 days in advance of the proposed use or importation. The regulations provide several exemptions from MCAN reporting, particularly these tiered exemptions that may be available for those intergeneric microorganisms where well-characterized genetic changes have been made to one of several starting species of recipient organism. These exemptions were described in detail in one of my 2010 blog posts, and the list of the original ten eligible recipient species was included in another 2010 post. Briefly, if the company can certify that it can use a qualifying organism at a particular location in conformance with certain equipment, facilities and procedural requirements specified in the regulations to minimize potential release of the organism from the production facility, it can proceed under the Tier I exemption without prior EPA review, merely upon 10 days advance notice to EPA. If instead the company wishes to use the organism under different containment conditions that it considers to be equivalent or appropriate for the proposed use, it can submit a Tier II exemption application to EPA at least 45 days before commercial use, but must wait for EPA approval before proceeding.

The Part 725 biotechnology rule provides a process by which interested parties could file petitions proposing that additional microorganisms be added to the list of species eligible for the tiered exemptions. In response to two such petitions, on September 5, 2012, EPA published a notice in the Federal Register announcing the issuance of a Proposed Rule that would add two microbial species to the list of recipient organisms potentially eligible for the tiered exemptions. Trichoderma reesei and Bacillus amyloliquefaciens are both well-studied species that have historically been used quite frequently in industrial fermentations and which have been used to produce biofuel-processing enzymes or for production of industrial enzymes. The March 2020 action issuing the Final Rule represents the final stage of this process,  so that, effective April 9, 2020, the following two species have been added to the list of qualifying organisms in 40 CFR Part 725.420.

(k) Trichoderma reesei strain QM6a and its derivatives used only in submerged standard industrial fermentation operations as defined at 40 CFR 725.3.

(l) Bacillus amyloliquefaciens subsp. amyloliquefaciens.

The eventual final rule followed the proposed rule closely, except that, in response to comments on the proposed rule submitted by industry trade groups, EPA decided to modify the qualifying language for T. reesei strains, to read as shown above. In the Federal Register notice announcing the new rule, EPA noted that it “has reviewed 48 MCANs involving intergeneric T. reesei production organisms used to manufacture a number of industrial enzymes, including amylases, glucosidases, proteases, phytase, laccase, and numerous cellulolytic enzyme preparations”. The notice did not indicate how many MCANs EPA had received for B. amylolquefaciens, but noted that the species has been widely studied and used for many years in a variety of commercial fermentations and production processes.  The March 10 Federal Register notice included a detailed summary of the scientific risk assessment EPA carried out to support this final rulemaking.

The direct impact of this ruling will largely be limited to the small number of companies that have submitted MCANs for production of industrial enzymes or other products using these microorganisms. And it is curious that it took EPA over 7 years to finalize the proposed rule, although I’d note that the TSCA biotechnology team has always been understaffed, and in recent years has had to deal with an increasing number of MCAN and other submissions, so this rulemaking may not have been a major priority for the agency. It is, however, a good sign that EPA is willing to learn from its 20-plus years of experience under the biotech rule to consider ways in which the regulations can be revised and the burden on the regulated community eased in specific ways, supported by appropriate science.

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/djglass99and 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.