[Federal Register Volume 63, Number 173 (Tuesday, September 8, 1998)]
[Notices]
[Pages 47505-47506]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-24072]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 98D-0340]


Draft Guidance for Industry: Use of Antibiotic Resistance Marker 
Genes in Transgenic Plants; Report and Guidance for Industry; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance entitled ``Use of Antibiotic 
Resistance Marker Genes in Transgenic Plants: Guidance for Industry'' 
(the draft guidance) and report entitled ``Report on Consultations 
Regarding Use of Antibiotic Resistance Marker Genes In Transgenic 
Plants.'' The report summarizes FDA's recent consultations with outside 
experts on the use of antibiotic resistance marker genes in transgenic 
plants. The draft guidance is intended to provide information to crop 
developers that will assist them on the use of antibiotic resistance 
marker genes in the development of transgenic plants. In accordance 
with FDA's good guidance practices (GGP's) for Level 1 guidance, the 
agency is making the draft guidance available for public comment. The 
agency is also making the report available for public comment.

DATES: Written comments by December 7, 1998.
ADDRESSES: Submit written comments on the draft guidance and report to 
the Dockets Management Branch (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit written 
requests for single copies of the draft guidance and report to the 
Division of Product Policy (HFS-206), Center for Food Safety and 
Applied Nutrition, Food and Drug Administration, 200 C St. SW., 
Washington, DC 20204. Send two self-addressed adhesive labels to assist 
that office in processing your requests. Requests and comments should 
be identified with the docket number found in brackets in the heading 
of this document. The draft guidance, report, and received comments are 
available for public examination in the Dockets Management Branch 
between 9 a.m. and 4 p.m., Monday through Friday.
FOR FURTHER INFORMATION CONTACT:
    Regarding human food issues: Nega Beru, Center for Food Safety and 
Applied Nutrition (HFS-206), Food and Drug Administration, 200 C St. 
SW., Washington, DC 20204, 202-418-3097.
    Regarding animal feed issues: William D. Price, Center for 
Veterinary Medicine (HFV-200), Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855, 301-827-6652.

SUPPLEMENTARY INFORMATION: In the Federal Register of May 29, 1992 (57 
FR 22984), FDA published a notice on a policy statement (the 1992 
policy) regarding foods derived from new plant varieties, including 
those derived using genetic engineering techniques. In the 1992 policy 
statement, FDA specifically discussed antibiotic resistance selectable 
marker genes and noted that both the antibiotic resistance gene and the 
enzyme encoded by the gene, unless removed, are expected to be present 
in foods derived from plants developed using the markers. The agency 
acknowledged that, when present in food, enzymes that are encoded by 
selectable marker genes and that inactivate certain clinically useful 
antibiotics theoretically might reduce the therapeutic efficacy of 
antibiotics administered orally. Accordingly, FDA believes that it is 
important to evaluate such concerns with respect to commercial use of 
antibiotic resistance marker genes in food, especially those marker 
genes that will be widely used. In addition, the agency also believes 
that it is important to consider the possibility that resistance to 
antibiotics in microorganisms has the potential to spread through 
horizontal transfer of antibiotic resistance marker genes from plants 
(59 FR 26700, May 23, 1994). This second consideration was reflected in 
FDA's evaluation of the safety of the use of the kanamycin resistance 
(kanr) gene product, aminoglycoside 3'-phosphotransferase II 
(APH(3')II, also known as neomycin phosphotransferase II or nptII) when 
the agency amended the food additive regulations to permit the use of 
APH(3')II in the development of transgenic tomato, cotton, and oilseed 
rape.
    FDA received several comments from the public regarding the use of 
antibiotic resistance marker genes in transgenic plants in response to 
the 1992 policy, and in response to the agency's solicitation for 
comment regarding the request of Calgene, Inc., for an advisory opinion 
on the use of the kanr gene as a selectable marker in the 
development of transgenic tomatoes (56 FR 20004, May 1, 1991). FDA 
responded to these comments when it issued the final rule permitting 
the use of APH(3')II in the development of transgenic tomatoes, oilseed 
rape, and cotton (59 FR 26700 at 26706).
    Since FDA's decision approving the use of the APH(3')II in the 
development of transgenic tomatoes, cotton, and oilseed rape, the 
agency has continued to receive inquiries from crop developers as well 
as from the public regarding the safety and regulatory status of 
antibiotic resistance marker genes. Therefore, FDA sought to develop 
sound scientific principles regarding the safety of the use of 
antibiotic resistance marker genes in the development of transgenic 
plants intended for food use so as to provide sound scientific guidance 
to crop developers regarding the safe use of antibiotic resistance 
marker genes. Toward this end, FDA undertook several consultations with 
outside experts having expertise in relevant fields including gene 
transfer and antibiotic resistance. The purpose of the consultations 
was to determine whether circumstances exist under which FDA should 
recommend that a given antibiotic resistance gene not be used in crops 
intended for food use, and if so, to delineate the nature of those 
circumstances.
    A team of scientists from FDA's Center for Food Safety and Applied 
Nutrition, Center for Veterinary Medicine, and Center for Drug 
Evaluation and Research held separate consultations with each expert. 
Following completion of all of the consultations, FDA prepared a report 
summarizing the discussions in each consultation. The report is 
entitled ``Report on Consultations Regarding Use of Antibiotic 
Resistance Marker Genes In Transgenic Plants.'' The agency is by this 
notice making this report available for comment.
    In order to facilitate the consultations, the agency developed 
several questions to form the basis of the discussions with the outside 
experts. These questions, enumerated in the report, were not intended 
to be exhaustive but rather to initiate the discussions with the 
experts. The agency is aware that there may be relevant issues not 
covered by these questions, e.g., the likelihood of a mutation in a 
given antibiotic resistance gene giving rise to resistance to another 
antibiotic. In commenting on the draft guidance and report, the agency 
encourages comments on issues that may have not been covered.
    With this notice, FDA is announcing the availability of the draft 
guidance. The draft guidance represents the agency's current thinking 
on the use of antibiotic resistance marker genes in transgenic plants. 
It does not create or confer any rights for or on any person and does 
not operate to bind FDA or the

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public. An alternative approach may be used if such an approach 
satisfies the requirements of the applicable statute, regulations, or 
both. The draft guidance is being distributed for comment purposes in 
accordance with FDA's GGP's (62 FR 8961, February 27, 1997); the draft 
guidance has been designated as Level 1 guidance.
    Interested persons may, on or before December 7, 1998, submit 
written comments regarding the draft guidance and report to the Dockets 
Management Branch (address above). Two copies of any comments are to be 
submitted, except that individuals may submit one copy. Comments and 
requests for copies are to be identified with the docket number found 
in brackets in the heading of this document. A copy of the draft 
guidance, report, and received comments may be seen in the office above 
between 9 a.m. and 4 p.m., Monday through Friday. After consideration 
of any comments received in response to this notice, FDA will revise 
the draft guidance as appropriate and will announce its availability in 
the Federal Register.
    An electronic version of the draft guidance and report are 
available on the Internet using the World Wide Web (WWW) at http://
vm.cfsan.fda.gov under the heading ``Biotechnology.''

    Dated: August 28, 1998.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 98-24072 Filed 9-4-98; 8:45 am]
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