International Regulation of Microorganisms for Biofuel or Chemical Production: Europe, Asia and Australia

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 a post last week, I briefly summarized 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”). In today’s entry, I’ll describe regulatory regimes for contained uses of modified microorganisms in Europe and Australia, and in selected countries in Asia.

As explained in the earlier 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. Many countries in the world that have adopted a biotechnology regulatory framework that conforms with the provisions of the Cartagena Biosafety Protocol under the Convention on Biological Diversity, and such regulations may often cover proposed uses of either engineered microorganisms or transgenic plants. Under such regulatory schemes, the use of GMO microorganisms in contained manufacturing will likely face a fairly straightforward regulatory process, because using a GMO in “contained” conditions in a manufacturing process will generally pose far fewer hypothetical concerns about environmental or public health impacts. 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, although I hope to eventually do so in a subsequent post on the blog.

Europe

The European Union has adopted a directive governing the “contained uses” of GMOs (Directive 2009/41/EC). Briefly, this directive would require applicants to assign a risk level to its organisms, to adopt containment measures appropriate for that risk level, and to notify a designated national agency before beginning operations. However, specific requirements in any given EU nation would be governed by national legislation or regulation adopted in conformance with the EU directive, so that national requirements in any given country may differ from, and may even exceed, the requirements of the EU directive.

The definition of “contained use” in Article 2 of Directive 2009/41/EC reads as follows:

‘contained use’ means any activity in which micro-organisms are genetically modified or in which such GMMs [genetically modified microorganisms] are cultured, stored, transported, destroyed, disposed of or used in any other way, and for which specific containment measures are used to limit their contact with, and to provide a high level of safety for, the general population and the environment.

This definition appears to give an applicant proposing to use a GMM in Europe (called a “user” in the directive) would have a fair amount of leeway in determining that a system or process is “contained”, and what level of containment measures are called for.

Article 4 of the directive requires the user to carry out a risk assessment of the GMM, using considerations set forth in Annex III of the directive. As a result of this assessment, the user would determine which of four containment levels is appropriate for the organism, after which the user would have the requirement to adopt appropriate containment measures in accordance with Annex IV of the directive. These requirements are similar to the U.S. NIH Guidelines and other international biosafety guidelines, and most microorganisms used for fuel or chemical production would qualify to be included within the lowest level of containment, “Containment Level 1”.

Article 6 of the directive requires users to notify the “competent” national authority (i.e., the government agency designated in national legislation as having jurisdiction to enforce the contained use directive) before a facility is to be used with GMMs for the first time. Annex V specifies the information required to be submitted with such notifications, and for Class 1 organisms, the necessary information is fairly minimal.

The EU Contained Use Directive should be viewed as providing general guidance and baseline requirements for member state governments to adopt national regulations for oversight There is at least one recent (and very comprehensive) summary of national legislation under this directive available online – it is a report published in January 2011 by the Netherlands Commission on Genetic Modification – it can be downloaded from this site. One example of a national law adopted in conformance with the EU Contained Use Directive is the law adopted in the United Kingdom, described in the portal site accessible here. Briefly, the UK law requires advance notice to the relevant agency before any work with modified microorganisms is to begin, as well as the submission of a risk assessment for the agency’s review.

Asia

Indonesia has ratified the Cartagena Protocol, and adopted Law Number 21 of 2004, followed by Government Regulation Number 21 of 2005 to implement its responsibilities under the Protocol. These regulations, although largely focusing on agricultural uses of GMOs, appear to require an environmental risk assessment for the importation of any GMO, even for contained use. The gist of the regulations is that any GMO either created in the country or imported into Indonesia must undergo a risk assessment to ascertain environmental safety, food safety, or animal feed safety.  The Ministry of Environment appears to be the main contact for GMOs, and is listed with the Cartagena Protocol as the “Competent National Authority”.

In addition, Law 21 required the formation of a Biosafety Commission of Genetically Engineered Products (Indonesian acronym KKH), and this was apparently not established until 2010. The commission is under the responsibility of the President of Indonesia and is assigned to assist relevant agencies in giving recommendations about biosafety, in conducting control over importation and use of genetically engineered products, as well as in the scientific evaluation of applications and reports. The commission has the authority to assign the Biosafety Technical Team for Genetic Engineered Product in the conduct of evaluation and technical assessment of biosafety of GMO products.

It appears that importation of a GMO into Indonesia, even for a contained use, requires government review. For example, Article 13 of Government Regulation 21 reads: “Any person who imports any [GMO] of the same type from abroad for the first time, shall submit an application to the competent Minister or Head of Non-Departmental Agency”, and goes on to say that the application must include a risk assessment document attesting to environmental, food, and animal feed safety. The regulation and other background documents provide some guidance as to what information must be submitted. Presumably, applications for production of fuels or chemicals would be submitted to the Ministry of the Environment, but would be reviewed by the Biosafety Commission.  Advance consultation with the Ministry would certainly seem prudent.

Japan is a signatory to the Cartagena Protocol, and it has adopted Law 97 of 2003, entitled “Law Concerning the Conservation and Sustainable Use of Biological Diversity through Regulations on the Use of Living Modified Organisms,” to place Japanese law in conformance with the Protocol. (Note: this law and other documents referenced here can be downloaded in English from the Japan Biosafety Clearing House website). Law 97 forms the basis for Japan’s biotechnology regulatory regime. Among the defined terms of Law 97 are definitions of two categories of use of Living Modified Organisms (LMOs). “Type 1” Uses correspond to what is typically called “deliberate releases”, while “Type 2” Uses are “contained uses”, which are both defined in Article 2 of the Law as follows:

5. In this Law, “Type 1 Use” shall mean use not subject to taking the measures provided for in the following paragraph.

6. In this Law, “Type 2 Use” shall mean use undertaken with the intention of preventing the dispersal of living modified organisms into the air, water or soil outside facilities, equipment or other structures (hereinafter “Facilities”) in accordance with measures specifying this fact or other measures stipulated in the ordinance of the competent ministries.

The provisions governing Type 2 Uses are covered in Chapter 2, Section 2 (Articles 12-15) of Law No. 97. These articles contain general provisions specifying that appropriate containment procedures must be put in place, and specifying procedures to be implemented in the event of an accidental release of an organism.

To implement Law 97, the government adopted “Regulations related to the Enforcement of the Law concerning the Conservation and Sustainable Use of Biological Diversity through Regulations on the Use of Living Modified Organisms”. Article 40(3) of these Regulations  specify which “competent ministers” have responsibility for Type 2 Uses, either for R&D or commercial purposes. Jurisdiction for R&D is more clear: under subparagraph (i) of this Article, either the Minister of Education, Science and Technology or the Minister of the Environment would have jurisdiction over Type 2 R&D Uses. Subparagraph (ii) of this Article covers activities other than R&D, and specifies that the competent minister depends on who “has jurisdiction over the undertakings performed by persons who make of the Type 2 Use, along with the Minister of the Environment”. Presumably this means that the Minister with jurisdiction would be the Minister ordinarily responsible for the type of commercial activity to which biotechnology is to be applied, with additional responsibility assigned to the Minister of the Environment.

Japanese regulatory law is structured via a series of hierarchical regulations, such that the procedures applicable to commercial Type 2 Uses are further governed by another document, “The Ministerial Ordinance Providing Containment Measures to Be Taken in the Industrial Use of Type 2 Use of Living Modified Organisms” (there is also an equivalent document for Type 2 R&D Uses). The “Ministerial Ordinance” goes into more specific detail about appropriate containment provisions for microorganisms, plants and animals. For microorganisms, the procedures required for the lowest risk category generally correspond to Good Industrial Large Scale Practice (GILSP). The Ministerial Ordinance also includes the application form needed to be submitted to the competent minister. This is “Form 1”, which asks for information about the LMO and its properties and the measures to be adopted to ensure containment. These data provisions appear to be equivalent to those in place in other countries around the world.

It is not clear whether there have been any Type 2 Use applications in Japan for commercial activities outside of the pharmaceutical field. While the applicable procedures and data requirements appear straightforward, given the intricacies of the Japanese legal and regulatory system, it would naturally be advisable for foreign companies to work with a Japanese partner and/or attorney, and to hold early discussions with the applicable regulatory agencies in advance of any submission.

India has an existing regulatory framework, although it is based on a 27-year-old law that the government has been trying to update. This law is the Environmental Protection Act of 1986, whose provisions are implemented by the 1989 “Rules for the Manufacture, Use/Import/Export and Storage of Hazardous Microorganisms/Genetically Engineered Organisms and Cells” (both the law and the rules can be downloaded from the government’s biotechnology website. The two primary regulatory bodies under this regime are the Department of Biotechnology (DBT) within the Ministry of Science and Technology and the Genetic Engineering Approval Committee (GEAC) within the Ministry of Environment and Forestry. The DBT has developed recombinant DNA guidelines, and the GEAC has developed guidelines for field testing and food use of GMOs. Under the Act and the Rules, all uses of genetically engineered organisms, including “production in which genetically engineered organisms or cells or micro-organisms are generated or used” require advance approval of the GEAC (although the final section of the Rules gives the Environment Ministry the power to grant exemptions from this requirement). In relying on a single regulatory committee with representatives from various government agencies, the Indian system embodies a regulatory regime that is better suited for R&D applications than for commercial uses, but which reflects the prevailing practice at the time the law was adopted.

The Indian government has been trying to revise these regulations to create a stronger framework since 2007. Under a National Biotechnology Strategy issued in that year, the Ministry of Science and Technology and the DBT have created drafts of a proposed “Biotechnology Regulatory Authority of India Bill”. The first version of this bill was proposed in 2008, with a subsequent version proposed in 2012 following inter-agency consultations and stakeholder feedback. The bill would create a unified National Biotechnology Regulatory Authority, with individual branches having responsibility for different commercial and R&D uses of biotechnology: for example, under the original 2008 proposal, the “Industrial and Environmental Applications Branch” would have responsibility for “application[s] in industrial production or manufacturing processes”, and so if this regime is implemented, that Branch would presumably have responsibility for review of uses of engineered microorganisms in fuel production.

It appears from online sources that the government has not made much progress in passing this new legislation, and that it has engendered opposition from many fronts. Not least of the opposition has come from India’s state governments, which are concerned that the new law might pre-empt authority they currently maintain to play a significant role in regulating certain biotechnology products. There has been opposition from segments of the public as well. At this writing it does not look likely that this law will be implemented in the near future, and so the status quo under the 1986 Act and 1989 Rules remains in effect. Although not an ideal regulatory regime, it has the advantage of providing applicants with fairly straightforward requirements. Companies seeking to use genetically modified microorganisms for fuel or chemical production would likely need to gain approval from the GEAC.

Australia

 Australia has a Gene Technology Act of 2000, implemented by the Gene Technology Regulations of 2011, which would dictate whether the use of modified microorganisms for biofuel production would require a license. The Act and regulations established  the Gene Technology Regulator (GTR) as the central office that administers the Act. The GTR plays the key role in assessing, regulating and licensing GMOs and enforcing license conditions. The Gene Technology Act defines gene technology as any technique for the modification of genes or other genetic material, although there is an exception for “homologous recombination” that appears quite narrow.

The most important features of the Gene Technology Regulations are the clarification of procedures for licensing certain uses of GMOs (activities involving GMOs are referred to by the term “Dealings”). Of the dealings requiring a license, a distinction is made between those involving a deliberate release of a GMO into the environment, and those that do not, with the latter being referred to as a DNIR (“dealing not involving release”).  Applicants for either type of license are required to submit certain information to the GTR, which is then used to prepare a risk assessment and risk management plan, which forms the basis for the GTR’s decision.

Procedures for DNIR license applications are similar to those for deliberate releases, except that the time period for the government’s decision is shorter for DNIRs (90 working days as opposed to 150-255 working days for release applications), and that public involvement may not be required for DNIR applications as they are for deliberate releases.  Another feature of all license applications is that they must first be reviewed and approved by an Institutional Biosafety Committee (IBC). The law and regulations specify requirements for such committees, and it appears that to meet such requirements, applicants would need to use an IBC in Australia.

It appears that any proposed use of a modified microorganism in contained manufacturing of a fuel or chemical would require a permit from the GTR. The GTR website has links to the application forms, and the form for application for a DNIR license can be downloaded here. The application form is quite detailed, although the scientific information it requires is similar to the information that would be submitted to the U.S. EPA in a Microbial Commercial Activity Notice, which were summarized in one of my 2010 posts.

I’ll admit that the two posts in this series represent a somewhat arbitrary selection of countries, particularly in South America and Asia. I’d be happy to answer questions about regulations in other countries not mentioned in either post, either through Comments on this post, or by contacting me offline.

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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