USDA's Regulation of Genetically Engineered Plants, Microorganisms, and Veterinary Biological Products

Michael Lidsky

Michael Lidsky is a Regulatory Specialist, Biotechnology and Environmental Coordination Staff, in the Animal and Plant Health Inspection Service at the U.S. Department of Agriculture.

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I would like to discuss the regulatory structure and principles of regulation at the U.S. Department of Agriculture USDA).

At USDA, we operate under several regulatory principles. First, we believe that products developed through genetic engineering do not differ fundamentally from those produced by conventional means. Second, we strongly believe that the product and the risk, not the process, should be regulated. Third, we believe that existing statutes are adequate and appropriate for regulating biotechnology.

The USDA has both research and regulatory responsibilities. On the research side, there is an Assistant Secretary for Science and Education. The principal research and education agencies reporting to this secretary are the Agricultural Research Service, the Cooperative State Research Service, and the Extension Service.

The Agricultural Research Service (ARS) administers a basic applied and developmental research program in 1) animal and plant protection; 2) the use and improvement of soil, water, and air; 3) the processing of farm products; and 4) human nutrition. The Cooperative State Research Service participates in the nationwide system of research program planning between states and USDA, and administers grants to state land grant colleges and agricultural experiment stations. The Extension Service helps the public learn about and apply to everyday activities the latest technology developed through research.

USDA's organization is similar to the Department of Health and Human Services, where the research component is headed by the National Institutes of Health (NIH), and the regulatory component is headed primarily by the Food and Drug Administration (FDA).

On the research side of USDA, several regulatory agencies report to the Assistant Secretary for Marketing and Inspection Services. The Food Safety and Inspection Service is responsible for ensuring that meat and poultry products moving in interstate and foreign commerce and intended for human consumption are safe, wholesome, and accurately labeled.

The Agricultural Marketing Service (AMS) administers the Plant Variety Protection Act.¹ That Act protects developers of novel varieties of sexually produced plants, giving them the exclusive right to sell, reproduce, import, or export the plant for a period of up to 18 years. AMS also issues marketing orders setting prices, and develops grade standards for producers.

The Animal and Plant Health Inspection Service (APHIS) conducts regulatory and control programs to protect plant [19 ELR 10501] and animal health. APHIS administers laws to control and eradicate plant diseases and administers the Animal Welfare Act² to ensure humane treatment of animals. Within APHIS, the Biotechnology and Environmental Coordination Staff coordinates implementation of biotechnology and regulatory activities at USDA, and ensures that APHIS complies with the National Environmental Policy Act.³

APHIS is also divided into Veterinary Services (VS) and Plant Protection and Quarantine divisions. Within the VS Division, the VS Biotechnology Committee, composed of representatives from different agencies, reviews environmental assessments and draft regulations.

In general, when a person applies for a permit or license, the application is reviewed by the appropriate regulatory agency, and then a decision is made whether or not to issue that permit or license.

At USDA, when an application for a permit to release a genetically engineered plant comes into APHIS, the Biotechnology and Environmental Coordination Staff notifies the Office of Agricultural Biotechnology (OAB). The OAB functions like the Office of Recombinant DNA Activities at NIH, and also provides staff support to the newly established Agricultural Biotechnology Recombinant DNA Advisory Committee (ABRAC). The ABRAC makes funding decisions for research proposals, and may in the future be reviewing certain significant submissions that APHIS receives, when requested by APHIS.

Another structure within USDA is the Committee on Biotechnology in Agriculture (CBA). The CBA is the policy bridge between the research and regulatory agencies within USDA. The committee is co-chaired by the Assistant Secretary for Science and Education and the Assistant Secretary for Marketing Inspection Services. The CBA members are the administrators of the various research and regulatory agencies within USDA.

As noted, APHIS contains a veterinary services program. With the veterinary service, a veterinary biologics staff administers the Virus-Serum-Toxin Act of 1913.⁴ The VSTA, as amended, regulates the interstate and intrastate shipment and production of veterinary biological products.

In general, the VSTA prohibits shipping a veterinary biological product, or delivering it for shipment, if the product is worthless, contaminated, dangerous, or harmful. Veterinary biological products must be prepared in a USDA-licensed establishment and each product must be individually licensed. The Food Security Act of 1985⁵ gives USDA regulatory authority over the export of veterinary biological products. USDA's authority to regulate importation of veterinary biological products was included in the VSTA.

Veterinary biological products are broadly defined to encompass all viruses, serums, toxins, and analogous products, of natural or synthetic origin. This includes diagnostics, antitoxins, vaccines, live microorganisms, killed microorganisms, and the antigenic or immunizing components of microorganisms intended for use in the diagnosis, treatment, or prevention of diseases in animals.⁶

Under the Veterinary Biologics Program, USDA has developed a scheme for categorizing hybridomas and recombinant DNA-derived animal biologics. This scheme is based on the biological properties of these organisms, and on the safety concerns that they present.

Organisms are classified in one of three categories. Class I products are inactivated recombinant DNA-derived viral vaccines, inactivated recombinant DNA-derived bacterial products, viral bacterial or other sub-unit products, or monoclonal antibodies. In general, one can say that these nonviable or kill products present no new or unusual safety concerns.

Class II products are vaccines containing live organisms modified by gene insertion or deletion. So far, three pseudorabies vaccines have been licensed under the Class II guidelines. The USDA believes that precautions must be taken with Class II products, to ensure that the addition or deletion of specific generic information does not impart or increase virulence, pathogenicity, or survival advantages in the modified organisms. In other words, Class II organisms should not present any greater risk than natural or wild-type forms. Modifications to these organisms must not impart new or increased invasion factors or colonization properties. The genetic information added to or deleted from these organisms must consist of well-characterized DNA segments.

Class III products are vaccines using live vectors to carry recombinant DNA-derived foreign genes. For Class III products, safety and transmission characteristics must be thoroughly examined before a decision can be made with respect to environmental release or product licensing. USDA has received an application from the Wistar Institute for field testing of a Class III vaccine under 9 C.F.R. § 103.3. The application is not yet complete; USDA will require additional information before deciding whether or not this product can be field-tested. Of course, we will also have to prepare a thorough environmental assessment.

APHIS has issued a rule on permits for importation, movement in interstate commerce, or environmental release of genetically engineered organisms. This rule, codified in 7 C.F.R. part 340, is administered by the Plant Protection and Quarantine Division of APHIS. The rule was originally proposed as part of the Coordinated Framework for Regulation of Biotechnology, which was published by the President's Office of Science and Technology Policy (OSTP) on June 26, 1986.⁷ After receiving approximately 190 comments, USDA published the final rule in June, 1987, effective July 16, 1987.⁸

The final rule and the permit program are based on USDA's existing statutory authority — the Plant Quarantine Act (PQA)⁹ and the Federal Plant Pest Act (FPPA)¹⁰ — as well as the existing administrative structure within APHIS. Permits for environmental release or movement of genetically engineered organisms are administered by a group within the biological assessment support staff of APHIS.

The regulation is not process-based, since it is predicated on the reasonable belief that a genetically engineered organism may be a plant pest, or the agency's determination that the organism is a plant pest. The regulation is flexible: the final rule allows the list of plant pest organisms to be amended readily, through a petition process.

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Further, the regulation encourages collaboration with other agencies. USDA specifically solicits comments from state agencies within 30 days of receiving a permit application. Public participation is encouraged through the petition process, through public notices of permit applications received, and through public notice of the availability of environmental assessments.

To highlight the major provisions of the rule: first, in section 340.0 there are general restrictions on the introduction of a regulated article; a permit is required for introduction of a regulated article in the United States. Introduction is defined to include importation, interstate movement, or release into the environment.

Section 340.1 of the regulation contains key definitions, among them the definition of genetic engineering. This rule uses the NIH definition of genetic engineering: "the genetic modification of organisms by recombinant DNA techniques."

Section 340.2 of the regulation lists the groups of organisms deemed to be plant pests. The Section 340.2 list is very broad; within the list some organisms are plant pests and others are not. For taxonomic reasons, we found it nearly impossible to develop a definitive, all-inclusive list of organisms that are plant pests. Instead, we listed broad families of organisms. If an organism falls within a family on the list, a determination has to be made whether or not it is a plant pest.

Section 340.3 outlines the different types of permits that USDA can issue under this rule. There are four types: 1) a permit for release into the environment, 2) a limited permit for interstate movement, 3) a limited permit for importation, and 4) a courtesy permit. Applicants can seek a courtesy permit if they want to import an organism and believe that its movement might be impeded because of its similarity to a regulated article. The applicant must demonstrate that, based on the organism's biology, it is not a regulated article.

Section 340.4 contains the petition process for amending the Section 340.2 list of organisms. Section 340.5 dictates how a regulated article is to be marked during shipment. Section 340.6 sets container requirements for shipment of regulated articles.

It is worth taking a moment to read the definition of "plant pest,"¹¹ because it is so broad. Plant pests include "any living stage (including active and dormant forms) of insects, mites, nematodes, slugs, snails, protozoa, or other invertebrate animals, bacteria, fungi, other parasitic plants or reproductive parts thereof; viruses; or any organisms similar to or allied with any of the foregoing; or any infectious agents or substances, which can directly or indirectly injure or cause damage in or to any plants or parts thereof or any processed, manufactured, or other products of plants."

An organism has to meet three conditions before a permit will be required under this rule. First, the organism must be genetically engineered using recombinant DNA techniques. Second, it must be on the list of regulated organisms, and the organism in fact has to be a plant pest. Third, the organism must be introduced — that is, imported, moved interstate, or released into the environment.

The Federal Plant Pest Act and the Plant Quarantine Act traditionally have been used to regulate importation and interstate movement. In the proposed rule, USDA argued that it was consistent with congressional intent to use these statutes to regulate the introduction of organisms that are new to the United States, where there is reason to believe that the organism could be a plant pest. We find it reasonable to construe these statutes to allow USDA to regulate release of regulated articles from containment into the environment and have crafted the regulation accordingly.

As noted, this regulation contains provisions for state notification and review. Within 30 days of receiving an application, USDA sends the state a letter indicating its preliminary findings. We send a notice to the state when we receive an application for the importation or interstate movement of regulated articles into a state, but the most detailed analysis is given to organisms that will be released into the environment. USDA then solicits comments from the state, requesting information on the site where the organism is to be released, and requesting concurrence with our initial assessment.

A standard form, PPQ Form 1001, is used to apply for all four types of permits. In general, USDA processes a permit for release within 120 days. Permits for interstate movement or importation, and courtesy permits, are processed within 60 days.

The USDA and EPA undertake joint review of applications that may be regulated by the Federal Fungicide, Insecticide and Rodenticide Act¹² and the Toxic Substances Control Act¹³ as well as the FPPA. Most recently, we have been involved with EPA in reviewing an application submitted by Crop Genetics International for a microorganism to be used as a microbial pesticide. In this case, USDA has participated with EPA in their biotechnology science advisory committee meetings. We have asked the company for a single set of data that we believe will meet our needs as well as EPA's. This process ensures comparable rigor in the review of the application while minimizing duplication of effort by the applicant and the agencies.

The Section 340.4 petition process can be used to add or remove a genus, species, or subspecies from the Section 340.2 list of regulated organisms. The petitioner is asked to explain, on factual grounds, why the organism is or is not a plant pest. The petitioner is required to include copies of literature and copies of unpublished studies or test data, including any unfavorable information on the organism.

Once a petition is complete, USDA will publish a proposed rule in the Federal Register to amend the Section 340.2 list of exempt organisms. After public comment, we determine within 180 days whether to amend the list.

DISCUSSION

MARGARET G. MELLON: Is the Federal Plant Pest Act the only statute available to regulate plants?

LIDSKY: The FPPA and the Plant Quarantine Act are both available to regulate genetically engineered plants.

MELLON: Does the FPPA exclude nonparasitic plants and vertebrate animals by definition?

LIDSKY: Yes, it does.

MELLON: So, if a plant or an organism presents a risk but is not a plant pest risk, isn't it outside of USDA's purview? In essence, isn't USDA's policy that there are no risks of concern other than the risk that these organisms will be plant pests?

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LIDSKY: As I indicated earlier, we believe that products should be regulated by risk rather than by their production process. The statutory authorities with which we are armed are the FPPA and the PQA. The FPPA defines plant pests very broadly, making the statute adequate to regulate the risks presented by biotechnology. We do not want to regulate something merely because it is genetically engineered.

MELLON: But there are large groups of plants and animals which could not be considered plant pests under any conditions, but which do pose risks of environmental disruption. There are also secondary and tertiary effects. For example, if a plant is herbicide-tolerant, its widespread use might have the secondary effect of increasing the use of herbicides without itself posing a risk as plant pest.

Does USDA have any authority that would allow it to bring those organisms into its regulatory system in order to assess their secondary effects? Also, has USDA received any applications for forestry products, garden products, or horticultural products?

LIDSKY: To date, USDA has not received any applications for those types of products. We do prepare thorough environmental assessments when we issue a permit.

MELLON: If you have the organism in your system, you can perform an assessment.

LIDSKY: Yes, with the qualification that the organism has to be reasonably believed to be a plant pest, although plant pest is very broadly defined.

MELLON: Do you think that forest products such as trees will fit in under the definition of plant pest?

LIDSKY: They could, depending on how the genetically engineered organism is made.

EDWARD LEE ROGERS: Are environmental assessments available to the public by notice in the Federal Register?

LIDSKY: Yes.

ROGERS: Is this after the final agency action, or is there a 30-day comment period for the environmental assessment?

LIDSKY: I believe we have been issuing the environmental assessments prior to making a determination on field testing for veterinary biologics. For plants, we have been issuing the notices of availability just around the time the permit is issued. But we have also been publishing a notice of receipt of permit applications, to let people know what has been received. They can then obtain copies of the applications and comment on them before a permit is issued.

ROGERS: Is a comment provision included in those notices? Will it be USDA's consistent practice to issue those notices of receipt?

LIDSKY: Yes.

ROGERS: When was this policy implemented?

LIDSKY: Beginning in March 1988. We want to increase public participation by letting people know what applications we are reviewing.

ROGERS: Does USDA perform an environmental assessment for every deliberate release into the environment, or only for products in the second and third categories?

LIDSKY: Only for products in the second and third categories. USDA believes that the first category of products-killed products — do not present undue risks. We will be proposing NEPA regulations this summer to exclude this category.

1. 7 U.S.C. 2321.

2. 7 U.S.C. §§ 2131-2157.

3. 42 U.S.C. §§ 4321-4370a, ELR STAT. NEPA 001.

4. 21 U.S.C. §§ 151-158.

5. P.L. No. 99-138, 99 STAT. 1354 (1985).

6. 9 C.F.R. § 101.2(w).

7. Office of Science and Technology Policy, Coordinated Framework for Regulation of Biotechnology, 51 Fed. Reg. 23,302 et seq. (June 26, 1986).

8. Department of Agriculture, 7 CFR Parts 330 and 340, Introduction of Organisms and Products Altered or Produced Through Genetic Engineering Which Are Plant Pests or Which There is Reason to Believe Are Plant Pests, 52 Fed. Reg. 22,892 et seq. (June 16, 1987).

9. 7 U.S.C. § 151-164a, 166-167.

10. 7 U.S.C. § 147a, 150aa-jj.

11. 7 C.F.R. § 340.1

12. 7 U.S.C. §§ 136-136y, ELR STAT. FIFRA 001.

13. 15 U.S.C. §§ 2601-2654, ELR STAT. TSCA 001.