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.