Previous entries in this blog have focused on U.S. government biotechnology regulations that might affect the use of genetically modified organisms in biofuel production. In this entry and the next I’ll focus on regulations outside the U.S. In this entry, I’ll briefly discuss the regulatory framework in Canada which may affect such proposed industrial applications, and I’ll discuss the handful of proposals which have, to date, been subject to these regulations. The next entry will discuss applicable European Union regulations.
Canadian regulation of microorganisms used for industrial purposes
Canada’s regulatory approach resembles that of the U.S., in that existing laws and regulations are used to regulate biotechnology in a product-specific way. Therefore, many products of biotechnology would be regulated in Canada under federal laws such as the Pest Control Products Act (pesticides), the Seeds Act (plants) and the Fertilizers Act (nitrogen fixing microbes). In November 1997, Environment Canada (EC) issued biotechnology regulations under the Canadian Environmental Protection Act (CEPA), that are similar in scope and approach to the U.S. EPA’s TSCA biotechnology regulations. EC has been using CEPA to conduct risk assessments of certain biotechnology products that are new to commerce in Canada and which are not regulated by other federal agencies. Among products that could fall under this law’s scope would be microbial strains used for biofuel production, or for manufacture of enzymes for use in biofuel production.
EC considers microorganisms as being potentially subject to these “New Substance Notification” (NSN) regulations if they meet the definition of “new substance”. Unlike, the U.S. EPA, however, EC did not create a specific definition of “new microorganism” using scientific criteria, but instead is relying on the definition in the law that a “new substance” is one intended for introduction into commerce that is not on the Domestic Substance List as having been used in commerce between January 1, 1984 and December 31, 1986. Thus, if a microorganism was used in commerce in this time period in a way such that “its entry into the environment was unrestricted”, it is exempt from reporting; but all other microorganisms, regardless of make-up, are subject to reporting. In this way, the Canadian CEPA regulations are broader than those of the U.S. EPA, in subjecting a larger class of microorganisms to regulation, and it is important to note that the regulations are broad enough to include naturally occurring or classically mutated strains, if such strains had never previously been used in commerce.
Under the NSN regulations, any person who manufactures or imports substances subject to notification must provide a notification package to EC, which contains certain information specified in the regulations. EC uses this information to conduct a risk assessment prior to entry into commerce. These requirements are generally similar to those used by the U.S. EPA, which I’ve discussed in previous blog entries. Information on the Canadian biotechnology rule is available at the biotechnology home page, and the New Substance regulations themselves can be found at http://www.gazette.gc.ca/archives/p2/2005/2005-09-21/html/sor-dors248-eng.html. A Guidelines document that is similar to EPA’s “Points to Consider document” can be accessed at http://www.ec.gc.ca/subsnouvelles-newsubs/default.asp?lang=En&xml=42A1CC66-BCCA-CF00-5C87-C57E1D9D25B0.
According to the EC website, the following New Substance Notifications have been received and risk assessment decisions made for new microorganisms since the regulations were put into place:
- EAU-313: Carnobacterium maltaromaticum strain CB1
- EAU-308, 309, 310, 311, 312: Rotavirus strains W179-9 (G1), SC2-9 (G2), 178-9 (G3), BrB-9 (G4), 179-4 (P1)
- EAU-288: Saccharomyces cerevisiae strain ECMo01
- EAU-224: Saccharomyces cerevisiae strain ML01
- NSN 11017: Trichoderma reesei 1391A IOGEN
- NSN 10642: Pseudomonas putida CR30RNSLL(pADPTel)
- NSN 6823: Trichoderma longibrachiatum RM4-100
- NSN # 11909: Trichoderma reesei P59G
- NSN # 12961: Trichoderma reesei P210A
- NSN # 13912: Trichoderma reesei P345A
Interestingly, although not related to biofuels use, the two notifications for novel S. cerevisiae strains (third and fourth bullet points) are the same modified yeast strains that have been reviewed by the U.S. FDA for GRAS status for use in wine-making (see the blog entry immediately preceding this one for more information). Of these ten risk assessments, five have involved modified microbial strains for the manufacture of enzymes for use in biofuels, and these have all been submitted by the Canadian company Iogen Corporation. More information about these five notifications are as follows (note that the hyperlinks provided have all been obtained from the EC website, but as of today’s writing some or all of these links may not be operational).
- NSN #6823: Commercial production of a novel thermophilic xylanase enzyme by the genetically engineered strain Trichoderma longibrachiatum RM4-100.
- NSN# 11017: Trichoderma reesei 1391A, expressing of a novel xylanase II enzyme with enhanced thermal stability and a selectable marker.
- NSN # 11909: Commercial production of a β-glucosidase enzyme by genetically engineered Trichoderma reesei P59G.
- NSN # 12961: Commercial production of a novel thermophilic and alkalophilic xylanase II (xln2) enzyme by genetically engineered Trichoderma reesei P210A.
- NSN # 13912: Commercial production of a thermophilic/ alkalophilic xylanase II enzyme by genetically engineered strain Trichoderma reesei P345A.
Canadian regulation of microorganisms used for animal feed
Canadian regulation of genetically modified plants
Canada’s CFIA maintains regulations governing the field testing (“confined release”) and commercialization (“unconfined release”) of plants with novel traits (“PNTs”). These regulations are conceptually similar to the regulations of the U.S. Department of Agriculture. According to the Agency’s website, a PNT is “a plant that contains a trait which is both new to the Canadian environment and has the potential to affect the specific use and safety of the plant with respect to the environment and human health, … [which has been] introduced using biotechnology, mutagenesis, or conventional breeding techniques”. CFIA is responsible for regulating the environmental release of PNTs, including the approval of unconfined release of PNTs, the approval and inspection of confined research field trials of PNTs, the assessment of import applications for PNTs, the development of domestic regulatory policies related to the environmental release of PNTs, and the development of internationally aligned regulatory policies through participation in various international forums.
The regulations administered by CFIA, “Regulations Respecting the Quality of Seeds Including Seed Potatoes, and the Testing, Inspection, and Sale Thereof (C.R.C., c. 1400)”, were created under the authority of the Seeds Act, and it is Part V of these regulations that specifically govern the field use and commercialization of PNTs. The regulations require applicants to notify CFIA prior to carrying out a field test of a PNT, and to provide information of a similar nature to that required under the USDA regulations in the U.S., and CFIA approval is needed before the field test can begin. PNTs approved for confined release cannot be used in food or livestock feed. A separate process is required to have a PNT approved for unconfined use, including possible use in food or livestock feed. CFIA has developed a guidance document for applications to conduct field tests of plants with novel traits, known as “Directive Dir2000-07: Conducting Confined Research Field Trials of Plant with Novel Traits in Canada”.
The CFIA website includes a listing of PNTs that have been cleared in recent years for confined field trials. This list can be accessed at http://www.inspection.gc.ca/english/plaveg/bio/confine.shtml. This database listing is not as convenient to search as are the databases available for U.S. field tests, but it appears that only two companies have conducted field tests of transgenic plants intended for biofuel use. Agrisoma conducted its first field tests in 2009 of engineered Brassica and soybean that have been improved in oil quality, content and seed size. And for at least the past several years, Targeted Growth has field tested engineered Camelina and soybean varieties at numerous locations in Canada, including varieties modified for improved performance as biofuel feedstocks.
There is one transgenic biofuel crop that has been approved for unconfined release and commercial use in Canada, and that is Syngenta Seeds’s Event 3272 corn, engineered to express a thermostable alpha-amylase (described in more detail in a previous blog entry). On March 11, 2008, in Decision Document DD2008-70, CFIA approved this variety for “production of grain for use in the dry-grind ethanol process”, and to allow by-products of the dry-grind ethanol process to be used as livestock feed. As I’ve noted in my previous blog entry, this corn variety has been awaiting approval by the U.S. Department of Agriculture for several years.
In summary, the situation in Canada resembles that of the United States, both in the nature of the regulatory framework and also in the overall tenor of the political and public relations climate. Although pockets of opposition to GMOs remain in both the U.S. and Canada, for the most part these countries are both reasonably hospitable to biotechnology innovations, particularly industrial applications, and particularly for applications not involving any proposed food use of the modified organism.
D. Glass Associates, Inc. is a consulting company specializing in several fields of biotechnology. David Glass, Ph.D. is a veteran of nearly thirty years in the biotech industry, with expertise in industrial biotechnology regulatory affairs, patents, technology licensing, and market and technology assessments. This blog provides back-up and expanded content to complement a presentation Dr. Glass made at the EUEC 2010 conference on February 2, 2010 entitled “Prospects for the Use of Genetic Engineering in Biofuel Production.” The slides from that presentation, along with more information on D. Glass Associates’ regulatory affairs consulting capabilities, are available at www.slideshare.net/djglass99.