The earlier entries in my blog have described the technical and commercial strategies that are being used to apply the advanced techniques of biotechnology to the production of biofuels, and the companies that are carrying out that research. These approaches are being pursued because of the potential that the newest techniques for genetically modifying microorganisms and plants might enable significant improvements in biofuel production processes, making biofuel manufacture more efficient and less costly, and therefore more competitive with the cost of nonrenewable petroleum-based fuels. However, many of these approaches may become subject to the regulatory framework that exists in the United States and other countries for the regulation of biotechnology and its commercial uses. As I’ll describe, legitimate concerns over the potential environmental and health effects of genetically modified organisms (GMOs) led many national governments, as well as a number of states, provinces and localities, to create regulations governing many commercial uses of GMOs. However, because the earliest debates over biotechnology regulatory and public policy were often contentious or even confrontational, the perception arose that the combination of government regulation and negative public opinion made it impossible to use GMOs in many commercial applications, particularly those in the open environment. This misperception persists in many quarters to this day, and one of my purposes in writing this blog is to try to dispel such beliefs.
In this entry and in the entries to come, I’ll describe the history and the basis for biotechnology regulation in the United States and elsewhere, and describe those regulatory programs that might be applicable to biofuels projects using GMOs. Much of this discussion will focus on the United States, but similar stories have been played out in other countries and regions, and I’ll spend a little bit of time discussing the regulatory situation elsewhere in the world, particularly in Canada and the European Union. Generally speaking, biofuels projects using GMOs might fall under either of two different types of regulatory programs. Those applications in which genetically modified plant species are being developed as novel biofuel feedstocks may be subject to regulations that have governed the agricultural biotechnology industry, and which cover the field testing and eventual commercial use of transgenic plants. In the U.S., these regulations are administered by the U.S. Department of Agriculture under the Federal Plant Protection Act. Certain applications using genetically modified microorganisms or algae may fall subject to other regulations designed to oversee industrial or environmental uses of certain engineered microorganisms; in the U.S. these would be regulations administered by the Environmental Protection Agency under the Toxic Substances Control Act (TSCA). Although these programs differ in many ways, their underlying scientific bases are similar, and in both cases, any needed regulatory approvals can easily be managed and obtained with suitable advance planning.
Biotechnology regulatory frameworks in most countries arose out of the health and safety issues that were initially raised by scientists and eventually debated by the public, shortly after recombinant DNA (rDNA) techniques were first developed in the early to mid 1970s (this early history is well documented by others). The initial concerns were over the potential public health and safety threats that might be posed during laboratory research, if organisms having new traits were inadvertently released outside the laboratory, and this concern led to the adoption of research guidelines, which in some cases had limited applicability (e.g. the U.S. National Institutes of Health rDNA guidelines, binding only of federally-funded research). As the biotechnology industry developed in the 1980s, the focus of the regulatory concern shifted not only to the larger scale uses inherent in commercial application of this new technology, but also to deal with the intention that certain engineered plants, animals and microorganisms would be created for use outside the lab, in the open environment. In fact, the driving force for much of the regulatory action in the 1980s was concern over such “deliberate releases” to the environment, even though most governments instituted frameworks that covered a wider range of commercial products activities.
In the United States, the outcome of several years of public policy discussions was the adoption of a “Coordinated Framework” for biotechnology regulation in 1986. Under this framework, it was decided that the commercial products of biotechnology would be regulated under existing laws and regulations and that it was not necessary to enact a specific law broadly covering all biotechnology activities. Thus, the use of biotechnology to produce drugs, vaccines, diagnostic products, foods and food additives would be regulated by the Food and Drug Administration (FDA), using existing regulatory authority; biotech-derived pesticides would be governed by existing rules of the Environmental Protection Agency (EPA); and most other agricultural products would be regulated by the U.S. Department of Agriculture (USDA). The effect of this decision was that the vast majority of biotech products, especially in the early years of the industry, were to be governed by the existing regulatory programs of the FDA and EPA with little or any regulatory revision; however it was also necessary to create new regulatory structures for some classes of commercial product that could be anticipated to arise from biotechnology. Specifically, although it was decided that existing laws administered by the USDA could be used to regulate genetically engineered (“transgenic”) plants, new regulations under those laws would be needed. In addition, there were a number of potential uses for genetically modified microorganisms that could be regulated under a law used by EPA to regulate the entry of new chemicals into commerce, but here too a set of new rules would be needed to use this law to regulate microbes instead of chemicals. As it happens, these two new regulations are the ones that are the likeliest to affect use of biotechnology in biofuel production in the United States, and these are the ones I’ll discuss in future entries in the blog.
I’ll also spend a little bit of time discussing regulation outside the U.S. Most countries around the world also adopted a similar product-specific approach, and (for example) the entry into the market of biotech-derived drugs is largely regulated in the same manner as conventionally-manufactured drugs. However, approaches to other biotech products differs. For example, Canada wound up adopting a similar framework to that of the U.S., in that uses of transgenic plants are regulated by the Canadian Food Inspection Agency in a manner similar to USDA policies in the U.S.; and various industrial uses of microorganisms are regulated by Environment Canada under a regulatory program resembling the one used for a similar purpose by the U.S. EPA. In Europe, however, the European Union ultimately adopted a series of uniform regulations specifying how national regulatory authorities are to handle the environmental and industrial uses of engineered plants and microorganisms.
One final, general comment about biotech regulation, as it applies to the environmental and industrial uses of engineered organisms. The need for these regulations is based on legitimate scientific concerns about the potential environmental effects of organisms having novel traits, particularly the concern that a new organism might have some competitive advantage over naturally occurring organisms, so that it could establish itself in the environment to detrimental effect. Some of these concerns are not unique to engineered organisms, and many observers would have similar concerns about large-scale releases of any novel organism, whether recombinant or not. Where most responsible observers in the industry have differed from critics in environmental groups and the general public is the overall perception of how significant the risk may be: while some in the general public fear that engineered microorganisms and plants inherently have potentially serious environmental risks, many scientists and industry officials feel that whatever risks may exist are easily assessable and manageable, and in any event do not differ in degree from the risks posed by similar uses of naturally-occurring organisms.
Applicability to Biofuels
These are the regulatory programs that will affect the use of genetically modified organisms in biofuel production that I’ll discuss in the next several entries of the blog.
Regulation of engineered microorganisms by U.S. EPA. Under regulations adopted under the Toxic Substances Control Act (TSCA) in 1997, EPA has the authority to regulate the use of certain “new microorganism” when proposed to be used for specific industrial, environmental or agricultural purposes. TSCA itself was enacted in 1976 to allow EPA to regulate the manufacture of new chemicals that are not already in commerce, for purposes not subject to regulation as a pesticide or under the food and drug laws. When the federal government was developing its coordinated interagency approach to biotechnology regulation in the 1980s, EPA decided to use TSCA in this same “gap-filling” way, to capture those microorganisms used in commerce that were not regulated by other federal agencies. The use of a microbe in a biofuel production process, or to produce an enzyme used in biofuel production would be one of the industrial applications falling under TSCA jurisdiction, but in order to be regulated, the microorganism must be considered to be “new”. Under the regulations, new organisms are defined as “intergeneric”, meaning that they include coding DNA sequences that have arisen from a taxonomic genus different than that of the host organism. Commercial use of a “new microorganism” in a covered industrial application would require reporting to EPA. However, the biotechnology rules under TSCA cover only commercial uses, and most R&D uses, probably including pilot plants, would be exempt from EPA reporting. Several modified microorganisms intended for biofuel use, as well as a number of microbes engineered to manufacture industrial enzymes for biofuel production, have already been cleared by EPA under these regulations.
Regulation of transgenic plants by USDA. The Agriculture Department adopted regulations in 1987 under which the outdoor growth or interstate movement of certain genetically modified plants or agricultural microorganisms require permits. These regulations, administered by USDA’s Animal and Plant Health Inspection Service (APHIS), have overseen the growth of the U.S. agricultural biotechnology industry. Technically, these regulations do not cover all genetically engineered plants, and instead cover only those plants engineered to contain sequences from certain microbial genera that contain species that are potential plant pests. In practice, because most plant transformation procedures use DNA from the microbe Agrobacterium tumefaciens, which appears on the “plant pest” list, these regulations have covered the vast majority of transgenic plants that have been developed. Today, after a series of regulatory revisions over the years, most transgenic plant field tests can take place merely upon notification to the agency, but most industrial uses of transgenic plants, likely including most field uses of engineered biofuel feedstock plants, would require permits under these regulations. The regulations also feature a “delisting” process by which specific transgenic varieties are cleared for commercial sale. Engineered biofuel “energy crops” have been field tested under these regulations for at least the last 3-4 years, and one engineered corn variety is awaiting USDA approval for commercial use. However, USDA has been contemplating revisions to these regulations for the past several years, which might affect how transgenic biofuel crops are regulated.
Regulations governing disposal or reuse of spent biomass from microbial fermentations. One common issue facing companies running fermentation processes using microorganisms is how to dispose of, or reuse, the microbial biomass that remains after the production process. These microorganisms are typically sterilized or inactivated in some way after the fermentation is completed (e.g. as required under regulations like the EPA TSCA regulations), but something needs to be done with these cells after they are killed. I’ll discuss some of the regulatory issues pertaining to the possible disposal of inactivated cell biomass into wastewater streams or the application of the biomass to the land, either in landfilling or as a soil supplement. I’ll also discuss the regulations that may govern the use of spent, inactivated biomass in animal feed – something that has been common for many years in conventional fermentation processes, particularly where the biomass is yeast. Here, the U.S. Food and Drug Administration might get involved, under regulations proposed in 1997 (which are being implemented as an interim policy) that offer a streamlined procedure under which applicants can notify FDA of new substances which are believed to be “Generally Recognized as Safe”(GRAS) for use in food or animal feed.
Regulations outside the U.S. I’ll also describe regulatory frameworks that have evolved outside the U.S. for the regulation of engineered microorganisms or plants as they may apply to biofuel production. As mentioned above, a framework similar to that of the U.S. exists in Canada, and the European Union has adopted a uniform approach to all biotechnology products that is standardized across the EU but which differs in many ways from the U.S. process. I’ll also discuss the possible impact of international understandings such as the Convention on Biological Diversity.
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.