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Document Processing Center (7407)
Office of Pollution Prevention and Toxics
Environmental Protection Agency
Room L-100, 401 M. Street, S.W.
Washington, D.C. 20460
Re: Docket Control Number OPPTS-00049C
The American Society for Microbiology (ASM) is submitting the following comments on the Environmental Protection Agency's (EPA) proposed rule for regulating microbial products of biotechnology under the Toxic Substances Control Act (TSCA) (59 Federal Register 45526-45585).
With a membership of 40,000, the ASM includes scientists from academe, industry and government, who are experts in molecular biology and genetics, environmental microbiology, microbial ecology, medical, agricultural and industrial microbiology. The ASM has a long record of involvement in the development of a coordinated framework for regulation of biotechnology products. The ASM has repeatedly advised government policymakers that biotechnology regulatory policy should be focused on organisms that pose a significant risk to the public health and the environment. The Society endorses the following statement from reports of the National Academy of Sciences: Although genetic modification by molecular methods may be more powerful and capable of producing a wider range of phenotypes, no conceptual distinction exists between genetic modification by classical methods or by molecular methods of modifying DNA...Assessment of an organism should be based on the nature of the organism and the environment into which it will be introduced, not on the methods by which it was produced.
Overall Evaluation of Proposed Rule
Unfortunately, the proposed EPA TSCA regulations for microbial products of biotechnology are not tailored to potential risks. Scientifically sound regulations for biotechnology should be risk based and would regulate phenotype--i.e. what the organism is, rather than process, i.e., how the organism is created. The proposed regulations circumvent scientific underpinnings related to risk. The EPA has proposed regulations under TSCA for biotechnology that represent a practical approach to a difficult problem. We recognize that the proposed regulations will provide a framework for the development and use of microbial products of biotechnology for environmental applications while protecting human health and environmental quality.
The proposed regulations represent an improvement over the current Pre-Manufacturing Notice (PMN) process. The PMN process was originally designed for chemicals, not microorganisms, and requires significant modification for application to biotechnology and the regulation of recombinant microorganisms. Additionally, the PMN system was designed for products ready for commercialization. Use of the PMN system for research and development (R&D) is cumbersome and difficult because the issues related to R&D activities differ greatly from those of full scale manufacturing. The current proposal for a two stage regulatory process--a TSCA Experimental Release Application (TERA) for regulated R&D activities as the first stage and a Microbial Commercial Activity Notice (MCAN) as the second stage--offers the potential to reduce significantly the regulatory burden for products that are still in the R&D phase.
The exemptions provided in the proposed TSCA regulations for microorganisms that are known to be safe to human health and the environment, based upon familiarity derived from extensive investigation and history of safe use, are a significant improvement over previously proposed EPA regulations. The exemption under the proposed TSCA regulations for natural (nonrecombinant) microorganisms, which may be deliberately released in applications such as bioaugmentation to enhance bioremediation, also is aimed at ensuring that the regulation of biotechnology under TSCA is not excessively burdensome. Further safety testing and regulation of these microorganisms and their uses are not needed.
Of particular importance in the proposed regulations is the explicit acceptance by the EPA that the NIH Guidelines for Recombinant DNA Research provide adequate oversight for contained R&D of recombinant DNA technology at institutions required to comply with the NIH Guidelines. Institutions that comply with the NIH Guidelines for contained R&D should be exempt from further regulation. This should include universities receiving federal funding, federal agencies and industry required to comply with the NIH Guidelines, e.g. by lease requirements or by institutional, municipal or state ordinance. Acceptance of the NIH Guidelines as the overriding oversight framework avoids unnecessary new regulations for contained research and, will allow the EPA to focus on products ready for commercialization and for introduction into the environment.
The EPA proposed regulation does not define "commercial purposes" but has signaled that its interpretation of "commercial purposes" will be very broad. We believe that the EPA should focus on commercial products that are intended for intentional introduction into the environment. The EPA should clearly define what is meant by commercial purposes to avoid undue regulation of research. There is no basis for EPA to consider all activities at a nonprofit institution to be commercial because one activity is commercial (page 45537). To do so would result in unnecessary, unwarranted and burdensome reporting requirements for academic research. Clear indices or criteria of commercial purpose should be presented to assist efforts to focus the regulations on commercial products and not on fundamental research. If criteria or clear indices cannot be agreed upon, it may be necessary to require that all intentional testing outside of contained structures be considered commercial.
In keeping with the NIH Guidelines, the EPA should expand its exemption of intergeneric recombinant DNA molecules to include recombinant DNA molecules that consist entirely of DNA segments from species that naturally exchange DNA by known physiological processes. This exemption of natural exchangers would make TSCA regulations of biotechnology consistent with the NIH Guidelines for Recombinant DNA. The NIH Director periodically prepares revised lists of such natural exchangers. For example, at present bacterial intergeneric exchanges between species of the genus Escherichia, the genus Shigella, the genus Salmonella--including Arizona, the genus Enterobacter, the genus Citrobacter--including Levinea, the genus Klebsiella--including K. oxytoca, the genus Erwinia, Pseudomonas aeruginosa, Pseudomonas putida, Pseudomonas fluorescens, Pseudomonas mendocina, Serratia marcescens, and Yersinia enterocolitica are listed in the NIH Guidelines as natural exchangers exempt from Institutional Biosafety Committee (IBC) registration. The ASM is prepared to assist the EPA in identifying a list of additional natural exchangers that would be exempt from regulation. There should be interagency cooperation between NIH and EPA and the EPA list should be forwarded to the NIH for incorporation into the NIH Guidelines.
The following items are responses to requests for comments made on the pages indicated of the proposed rule as published in the Federal Register notice.
C. Statutory Framework, b. Plants and animals are not subject to this proposed rule. In the last sentence of this section, EPA reserves the authority to regulate transgenic plants and animals under TSCA in the future. Since adequate regulations for transgenic plants and animals have already been promulgated by USDA, additional regulations by EPA under TSCA are not needed and will cause overlapping jurisdiction with other federal agencies.
2. Application of TSCA, Section 5. Since "any type of production" is considered 'manufactured,' all types of microbial growth, from test tubes to fermentors are 'covered.' This seems excessive unless exemptions are made for all activities in contained structures.
b. Definition of "new." request for comment on mobile genetic elements (MGEs): The MGE inclusion for assessing 'new' is reasonable except for natural exchangers as discussed above.
e. Exemptions from the section 5 notification process. While EPA oversight at the R&D level may satisfy public concern, it is difficult to justify the time and expense for EPA TERAs. If IBCs are in place, a better alternative would be for the company/institution to forward the proposed experiment to the EPA with a 30-day period for review. This would constitute a combination of notification and review for those microorganisms unlikely to pose substantial or unreasonable risk.
Requests for comment on approaches and alternatives: Although cumbersome, this assessment of whether or not reporting is needed seems reasonable, except for the concern about natural exchangers.
b. State coordination. We believe it is a disincentive for R&D to be required to provide evidence for having notified state authorities of planned activities. This should only be applicable, if at all, to environmental, i.e. noncontained R&D.
2. MCAN submission and review process--a MCAN submission process. The prospective EPA "review that considers all (emphasis added) the reasonable ascertainable information on...effects" can be interpreted as open ended and subject to challenge both by submitters and opponents to biotechnology. It would be better to review only that information likely to be pertinent to the change in the phenotype of the organism.
Figure 1. Tier 1 and Tier II should be added.
3. Requirements necessary for eligibility for exemptions from TERA reporting A. The contained structures exemption (ii) R&D not subject to another agency. An "authorized official" should include the possibility of using an IBC chair to prevent creating an additional layer of bureaucracy for an institution/business.
p. 45536 & 45537
5. Options for oversight of R&D activities. EPA claims a process of oversight commensurate with the level of risk, yet prejudices the science by assuming all genetically modified organisms are a greater risk than unmodified organisms. This assumption is unwarranted. The EPA should explicitly state that the proposed regulations under TSCA for microorganisms are not risk based.
p. 45536 & 45537
Requests for comments on options for R&D activities and alternatives approach. The options for R&D appear flexible and reasonable for work in contained structures. The R&D option of specific alternative exemptions for low-risk field tests is endorsed.
We draw EPA's attention to the following publications on the field-testing of microorganisms: the USDA's ABRAC document (Guidelines for Research Involving Planned Introduction into the Environment of Genetically-Modified Organisms) in which risk categories were specifically addressed, OECD documents, and the book, "Microbial Ecology: Principles, Methods, and Applications," edited by M. A. Levin, R. J. Siedler, and M. Rogul, McGraw Hill, 1992.
Since the TERA burden is structured to be minimal, the value of exemptions will rely primarily on the response time by EPA to exemption requests. Long delays in granting exemptions could negate the benefits of the exemption process and favor use of the TERA process which has mandated a 60-day review period (alternatively, 120 days if EPA extends the period for good reason).
B. Exemption for Research in Contained Structures 2. Difficulties in ensuring that microorganisms used for R&D will not increase beyond small quantities. It is erroneous to presume that a non-replicating chemical cannot do localized or even wide-spread damage. It depends on the chemical's reactivity and potency. Conversely, it is erroneous to assume that self-sustaining or multiplying populations of microorganisms will do damage; they may actually be beneficial.
It is erroneous to presume that the microorganisms used in small-scale field tests will establish themselves permanently in the environment. For example, even known deleterious organisms, such as plant pathogens are used annually in hundreds of tests without unreasonable adverse environmental effects.
Request for comment on exemption from TERA reporting. We support the proposed exemptions for Bradyrhizobium japonicum and Rhizobium meliloti. Since these exemptions are limited to modifications originating from the same species, it is difficult to see how they could constitute an unreasonable risk. If it is necessary or desirable to have an EPA notification procedure it could be managed efficiently by IBCs or the PIs using electronic mail. We believe it would be prudent to limit recipient strains to be introduced into the environment to those that do not produce rhizobitoxine. This toxin, in combination with susceptible cultivars of soybeans, can cause chlorosis (yellows) and subsequent yield loss. If toxin-producing strains were to be used, a TERA should be filed.