International Regulation of Microorganisms for Biofuel or Chemical Production: North and South America and Africa

In two blog entries in 2010, I described the possible regulatory regimes that might affect the use of genetically modified microorganisms or plants in the production of biofuels or bio-based chemicals, focusing on Canada and Europe.  In today’s entry, I’d like to update that information and extend it to a broader group of countries.

As explained in my 2010 posts, biotechnology regulations might apply to either of two strategies for the use of advanced biotechnology in biofuel or chemical production, that is, the development either of genetically modified microorganisms or modified plants.  In either case, some government review or permitting will likely be needed, and in many countries such oversight would be governed by the provisions of a single law. As I described in a previous post, many countries in the world that have adopted a biotechnology regulatory framework have done so to conform with the provisions of the Cartagena Biosafety Protocol under the Convention on Biological Diversity. National laws that are based on the Cartagena Protocol often feature unified provisions for government review of any biotechnology proposal, although in most cases the driving force for the creation of such rules was the desire for adequate oversight over agricultural and food uses of modified crop species.

The use of genetically modified microorganisms (GMOs) in manufacturing will likely face a fairly straightforward regulatory process in most countries, because such “contained” uses will generally pose far fewer hypothetical concerns about environmental or public health impacts. In contrast, the use of genetically modified plants as improved biofuel feedstocks will entail the field testing and ultimately the outdoor cultivation of modified plants, and may trigger a more rigorous review of potential environmental impacts.  In many cases, national biotechnology laws cover both potential applications, but in today’s post I’ll focus on the regulation of modified microorganisms for the manufacture of biofuels or bio-based chemicals. I won’t explicitly the discuss regulation of transgenic plants in today’s post, although I hope to eventually do so in a subsequent post on the blog.

The following are brief summaries of several countries in North America, South America and Africa having explicit biotechnology laws with reasonably clear applicability to uses of GMO microbes in contained manufacturing ( “contained use” or “confined use”).  I’ll cover countries elsewhere in the world in a subsequent post.

North America

Mexico is a signatory to the Cartagena Protocol and has a Bio-Safety Law adopted in 2005. The Bio-Safety Law assigned primary responsibility for biotechnology regulation to three agencies: the Secretariat of Agriculture, Livestock, Rural Development, Fisheries and Food (SAGARPA), the Secretariat of Environment and Natural Resources (SEMARNAT), and the Secretariat of Health (SALUD), and specified each agency’s jurisdiction. The Inter-Ministerial Commission on Biosecurity and Genetically Modified Organisms (CIBIOGEM) coordinates Mexico’s biotechnology oversight activities. The government has issued regulations (known by the Spanish title Reglamento) under the Bio-Safety Law, with the most recent version being issued in March 2008. The Reglamento provides detailed requirements for the use of GMOs outside containment, or for food use, human use, or bioremediation.

The Reglamento ostensibly also provided for a notification scheme for contained uses, but this does not appear to have been fully fleshed out until April 2011, when the government published notice of an agreement between SAGARPA and SEMARNAT regarding a unified approach to notifications for confined uses of GMOs. This notice is available here, apparently only in Spanish. Part of this notice is a lengthy “Annex” containing the proposed unified format for notifications. This notification form requires submission of a good deal of information describing the GMO, how it is proposed to be used, as well as information pertaining to a risk assessment for the proposed use. The amount and type of information required is of a similar scope to what would be required in the U.S. (e.g. in a Microbial Commercial Activity Notice under EPA regulations), but the information would of course need to be submitted in Spanish (EPA’s data requirements are discussed in my previous blog entries from 2010). The form can be a little difficult to understand, in that it specifies that different sections are to be completed for each of several different permit types, and so advance consultation with the relevant regulatory agency would be recommended.

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 existing federal laws. 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, and which are meant to cover biotechnology products or microorganisms 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 or bio-based chemical production, or for manufacture of enzymes for use in biofuel production. My 2010 post described these regulations in detail, but the following is a brief summary and update.

EC considers microorganisms as being potentially subject to these “New Substance Notification” (NSN) regulations if they meet the definition of “new substance”.  The law defines a “new substance” as one intended for introduction into commerce that is not on the Domestic Substance List (DSL) as having been used in commerce between January 1, 1984 and December 31, 1986. The DSL for microorganisms includes about 70 naturally-occurring species, identified by ATCC accession numbers. Thus, if a microorganism on this list was used in commerce from 1984-86 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. The required information is generally similar to the information the U.S. EPA requests in MCAN submissions under its TSCA regulations  (EPA’s requirements are discussed in my previous blog entries from 2010). Information on the Canadian biotechnology rule is available at the biotechnology home page, and the New Substance regulations themselves can be found here. A Guidelines document that is similar to EPA’s “Points to Consider document” can be accessed here. CEPA published a fact sheet specific for biofuels, which is accessible here.

CEPA has reviewed and approved a number of notifications for industrial uses of new microorganisms. These have been described in my 2010 blog post on the Canadian regulations, which includes links to the various decision documents. There do not appear to have been any published decision documents or risk assessments in the time since my earlier blog post.

South America

Colombia is a signatory to the Cartagena Protocol, and has adopted laws and regulations to ensure compliance. These include Act 740 of 2002 and Decree 4525 of 2005, which implements Act 740, and establishes which agencies would have authority for which types of activities (note: these links will lead to the original Spanish versions of these documents). These agencies are: the Ministry of Agriculture and Rural Development, with responsibility for agricultural, livestock, fisheries, forest plantations and agribusiness; the Ministry of Environment, Housing and Territorial Development, with responsibility for organisms intended solely for use in the environment; and the Ministry of Social Protection, with responsibilities for uses in health or foods. Decree 4525 appears to require at least a notification to the appropriate government agency prior to any intent to import a GMO into Colombia for use in contained R&D, accompanied by a suitable risk assessment of the proposed use. The law and the implementing regulations do not explicitly state the requirements for commercial use of a GMO in contained manufacturing, and so consultation with the government, likely the Ministry of the Environment, would be advised.

Chile has signed the Cartagena Protocol, but it has not been ratified, with no set timetable for ratification. The country has no national biosafety law, but the National Commission of the Environment (CONAMA) worked with the United Nations Environmental Project (UNEP) in 2005 to develop a document that proposed the fundamentals for a national biosafety framework for Chile that would be consistent with the Cartagena Protocol, but no action on such a proposal has yet taken place. In spite of the lack of a national law, the government has reviewed requests for field use of transgenic plants under existing agricultural regulations. Responsibility for such reviews within the Ministry of Agriculture was given to the Advisory Committee for the Release of Transgenes (known by the Spanish acronym CALT), which has reviewed and approved a large number of applications for field growth of transgenic plants since 1992. On the microorganism side, there are guidelines for laboratory use of GMOs but apparently no laws that would clearly cover proposed uses such as use of a GMO in a contained manufacturing process. It is probably advisable for companies planning activities in Chile to consult either with the Ministry of the Environment or with the CALT committee. 

Brazil has ratified the Cartagena Protocol and has been active in oversight over agricultural and industrial biotechnology. Brazil has a national biosafety law (Law No. 11,105 of March 24, 2005, available here in either English or Portuguese). The law creates a national regulatory framework administered by the Biosafety National Technical Committee (Comissão Técnica Nacional de Biossegurança, known by its Portuguese acronym CTNBio), and the National Biosafety Council (CNBS), with the involvement of the Ministries of Health, Environment and Agriculture, the Special Secretariat of Agriculture and Fishery, and other agencies. The CTNBio website, in Portuguese but with some links to English pages, can be found here. The Law and its regulations require that companies wishing to conduct commercial activities using GMOs or to test or use GM plants in the environment must seek the approval of CTNBio. Specifically, the Law requires approval for any activities involving the “cultivation, production, handling, transport, transfer, commercialization, import, export, storage, consumption, release and disposal of GMOs and their derivatives for commercial purposes.” Thus, unlike some national regulatory frameworks that are largely restricted to covering outdoor use of GMO plants, it is clear that the Law covers not only contained manufacturing but also the importation of GMO strains into Brazil.

There are precedents in Brazil for prior approvals for industrial biotechnology activities. These are two applications that were filed by Amyris for the use of genetically modified strains of S. cerevisiae (yeast) for the production of farnesene for fuel and chemical use. These applications appear to have been approved by CTNBio within a review period of several months, following submission by the company of a fairly detailed dossier describing the organisms, their construction and proposed use, and a risk assessment of the proposed commercial application.

Africa

South Africa adopted the Genetically Modified Organisms Act of 1997, which was amended in 2006 after the country ratified the Cartagena Protocol. The regulations and any required permit applications would be administered by the Ministry of Agriculture. Regulations were first established in 1999, but apparently implementation of these regulations was problematic with regard to permit applications and public access to decision-making documents, so there was pressure to revise the regulations. An Amendment to the Genetically Modified Organisms Act was adopted in 2006, in part to overcome these problems, and this version is in effect at this time. There is a website that is the gateway to downloading permit applications, and from the list of applications shown on this site, it appears that the following three applications might need to be submitted for a proposed biofuel or bio-based chemical plant which uses GMOs.

  • Application for authorization to import GMOs into South Africa that are destined for contained use
  • Application for contained use of GMOs
  • Application to register a facility for activities involving genetic modification

The “contained use” application generally asks for the sorts of information one would expect, including a description of the organism, the facility, and the process, and is guided by a list of issues to address. The contained use application also requires submission of a risk assessment in a format set out in an appendix to the application, which is similar to, but not identical to, the risk assessment format set out in the Cartagena Protocol: it appears that the South Africa form is longer and asks for more data than the risk assessment format that is contained in Annex III of the Protocol.

D. Glass Associates, Inc. is a consulting company specializing in government and regulatory affairs support for renewable fuels and industrial biotechnology. 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. Dr. Glass also serves as director of regulatory affairs for Joule Unlimited Technologies, Inc. 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 Joule Unlimited Technologies, Inc. or any other organization with which Dr. Glass is affiliated. Please visit our other blog, Biofuel Policy Watch. 

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