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The latest version of this guidance issued in June 2006. Below is an earlier version.
This guidance document is being distributed for comment purposes only.
Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit comments to Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.
For questions regarding this draft document contact the Center for Food Safety and Applied Nutrition (CFSAN)
Mary Ditto, Ph.D., (HFS-255)
Office of Food Additive Safety
5100 Paint Branch Parkway
College Park, MD 20740-3835
(301) 436-1165
Submit electronic comments to http://www.fda.gov/dockets/ecomments
Additional copies are available from:
Office of Food Additive Safety
Division of Biotechnology & GRAS Notice Review, HFS-255
Center for Food Safety and Applied Nutrition
Food and Drug Administration
5100 Paint Branch Parkway
College Park, MD20740
(Tel) 301-436-1200
http://www.cfsan.fda.gov/guidance.html
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Food Safety and Applied Nutrition
Center for Veterinary Medicine
November 2004
This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.
This guidance is for developers of new plant varieties that are intended for food(2) use. The guidance describes procedures for the early food safety evaluation of new non-pesticidal(3) proteins(4) produced by such new plant varieties, focusing in particular on such proteins produced in bioengineered plants.(5)
FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in agency guidances means that something is suggested or recommended, but not required.
Consistent with the Coordinated Framework for the Regulation of Biotechnology Products (51 FR 23302, June 26, 1986), the U.S. Office of Science and Technology Policy (OSTP) published a notice in the Federal Register of August 2, 2002 (67 FR 50578), in which it proposed federal actions to update field test requirements and to establish early voluntary food safety evaluations for new proteins produced by bioengineered plants ("the OSTP document"). Rapid developments in genomics are resulting in dramatic changes in the way new plant varieties are developed and commercialized. Scientific advances are expected to accelerate over the next decade, leading to the development and commercialization of a greater number and diversity of bioengineered crops. As the number and diversity of field tests for bioengineered plants increase, the likelihood that cross-pollination due to pollen drift from field tests to commercial fields and commingling of seeds produced during field tests with commercial seeds or grain may also increase. This could result in the inadvertent, intermittent, low-level presence in the food supply of proteins that have not been evaluated through FDA's voluntary consultation process for foods derived from new plant varieties (referred to as a "biotechnology consultation" in the case of bioengineered plants).(6) FDA is issuing this guidance document to address this possibility.
This guidance describes the procedure for early food safety evaluation of new proteins in new plant varieties that are under development. While this guidance is focused on new proteins in bioengineered plants, these procedures may, of course, be used for new proteins in non-bioengineered foods as well. FDA believes that any food safety concern related to such material entering the food supply would be limited to the potential that a new protein in food from the plant variety could cause an allergic reaction in susceptible people or could be a toxin in people or animals.
FDA first addressed the safety evaluation of new proteins in bioengineered plants in its 1992 Statement of Policy: Foods Derived from New Plant Varieties ("1992 policy;" 57 FR 22984, May 29, 1992).(7) The recommendations put forward in this guidance document are consistent with the scientific principles articulated in the 1992 policy for food safety evaluation of a new protein.
Since FDA first issued its 1992 policy, the agency has encouraged developers of new plant varieties, including those varieties developed through biotechnology, to consult with FDA early in the development process to discuss possible scientific and regulatory issues that might arise. This current guidance continues to foster early communication by encouraging developers to submit to FDA their evaluation of the food safety of their new protein. Such communication helps to ensure that any potential food safety issues regarding a new protein in a new bioengineered plant variety are resolved early in development, prior to any possible inadvertent introduction into the food supply of material from that plant variety. Submission of an early food safety evaluation for a new protein is not meant to substitute for a biotechnology consultation with FDA about a food derived from a new bioengineered plant variety. A developer may use the information developed for the early food safety evaluation of a new protein in the biotechnology consultation process.
Consistent with confidentiality requirements, FDA will make submissions of early food safety evaluations for new proteins, and FDA's responses thereto, easily accessible to the public via the Internet. FDA believes this is consistent with the goal, as articulated in the OSTP document, of enhancing public confidence in the regulatory oversight of bioengineered plants.
FDA recommends that sponsors and developers of new plant varieties intended for food use consult with FDA about their evaluation of the food safety of any new proteins produced in these plants prior to the stage of development where the new proteins might inadvertently enter the food supply. Thus, the safety evaluation recommended by this guidance is termed an "early" food safety evaluation of new proteins. If a protein has been evaluated in an early food safety evaluation and no safety concerns are identified, we would not expect an additional early food safety evaluation to be submitted if the same protein is introduced into another plant species. Also, if a protein has previously been reviewed as part of a biotechnology consultation and there were no safety concerns identified, we would not expect you to submit an early food safety evaluation for such a protein. This guidance does not apply to plant-incorporated protectants (PIPs), which are regulated by EPA.(8)
This guidance provides a scientific framework in which to evaluate the food safety of new proteins, and provides recommendations about communicating with us about your scientific evaluation. We recommend that you evaluate the food safety of new proteins early in the development process for your bioengineered plant.
As well, this document provides guidance about the format of a submission for the early food safety evaluation of a new protein.
When would I send a food safety evaluation for a new protein to FDA?
We encourage you to submit to us your food safety evaluation of a new protein prior to the time you have concerns that the new protein could enter the food supply, for example via pollen flow or commingling as you increase the size or extent of field testing.
How can I obtain information that will help me in preparing a food safety evaluation of my new protein?
You can obtain current guidance regarding the preparation of your safety evaluation by writing to the Office of Food Additive Safety (OFAS) at the address listed previously or by looking on OFAS's home page on the Internet (http://www.cfsan.fda.gov/~lrd/foodadd.html). You may also contact OFAS to schedule a meeting to discuss issues specific to your safety evaluation.
Does FDA recommend that I still participate in FDA's biotechnology consultation process, i.e., submit a BNF, even if I have communicated with FDA about the food safety of a new protein?
Yes, we recommend that you participate in FDA's biotechnology consultation process even if you have submitted to us and completed the early food safety evaluation of the new protein in your bioengineered plant. You may use the information developed for your food safety evaluation of a new protein in the biotechnology consultation process. The biotechnology consultation process evaluates the full complement of food safety and regulatory issues based on the characteristics of the food, including potential unintended changes in the composition of the food.
You should consider whether the new protein is an allergen, or a toxin.
While the 1992 policy addresses the full food safety evaluation of bioengineered foods, general considerations for conducting a food safety evaluation of a new protein, as well as flow charts diagramming specific questions relevant to such an evaluation, may also be found in the 1992 policy(7).
We also encourage you to refer to the approach that is discussed in the Codex Alimentarius "Guideline for the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants" (Codex Plant Guideline, see footnote 2) (CAC/GL 45-2003) Paragraphs 34-43 under Expressed Substances (non-nucleic acid substances) and the Codex Allergenicity Annex available at ftp://ftp.fao.org/es/esn/food/guide_plants_en.pdf.
Do I need to have a meeting with FDA?
It is not necessary to have a meeting with us to communicate about your early food safety evaluation of your new protein. If, however, you think a discussion with us would be useful to address issues that have arisen in your safety evaluation, we recommend that you request a meeting.
Where do I send my safety evaluation?
Send your safety evaluation to OFAS at the address listed previously. CFSAN will coordinate FDA's evaluation of your request with CVM.
May I send my safety evaluation as an electronic file?
Yes, you may send your safety evaluation as an electronic file plus one paper copy. Please contact OFAS before sending an electronic file to obtain specific guidance on electronic submission.(9)
If I choose to send a paper copy of my safety evaluation, how many copies do I send?
A single copy of your safety evaluation is sufficient.
What if I am sending confidential commercial information?
FDA will handle information submitted as part of a food safety evaluation of a new protein in accord with the requirements of the FOIA, other applicable statutes, and FDA's regulations at 21 CFR Part 20.
May I submit any data or other information, such as a reprint of a published scientific article, in a foreign language?
If you submit any material in a foreign language, we request that you provide an accurate and complete English translation.
May I incorporate data or other information that are already retained in FDA's files by referring to them?
If you previously submitted information to us, you may incorporate that information by referring to it.
If someone else previously submitted information to us, the procedure to be used to incorporate that information into your submission depends on whether the information is publicly available (e.g., the information is in an electronic reading room or is otherwise available under FOIA). If the information is publicly available, you may incorporate that information by referring FDA to it.
If the information is not publicly available, you may incorporate that information by referring FDA to it only if the person who submitted the information authorizes you to do so in a signed statement and you include that signed statement in your safety evaluation.
May I withdraw my safety evaluation from FDA's consideration?
At any time during our evaluation of your submission, you may request that we cease to evaluate it. Your request would not preclude you from sending a revised submission, nor prejudice a new submission about the same new protein at a later date. If you request that we cease to evaluate your submission, we will retain your submission in our files and classify your submission as "withdrawn.''
What information about my submission and FDA's response will be available on the agency's Internet site?
Consistent with confidentiality requirements, FDA will make the following information easily accessible to the public via the Internet:
We suggest that your submission have two parts. If the information requested in a part does not apply, please explain why it does not apply.
Part I is your cover letter informing FDA that you are submitting your early evaluation of the food safety of a new protein. In your cover letter please include your name, position or title, address, telephone number, and electronic address.
Part II of your submission is where you explain your scientific evaluation of the food safety of your new protein by providing a synopsis of the safety data and information about the new protein. These data and information should focus on whether the new protein is an allergen, or a toxin. They should include:
When data or information from 1-7 indicate that the new protein is a toxin in humans or animals, or is an allergen in humans, further evaluation is necessary. For other information that may be helpful in resolving these issues, you may refer to the Codex Plant Guideline, Paragraphs 34-43 under Expressed Substances (non-nucleic acid substances) and the Codex Allergenicity Annex for additional guidance. You may also consult with OFAS regarding these issues. When the source of the introduced genetic material is wheat, rye, barley, oats, or related cereal grains, the new protein may have the potential to elicit gluten-sensitive enteropathy in sensitive individuals. For additional guidance that may be helpful in resolving this issue, you may consult with OFAS.
(1) This guidance has been prepared by the Division of Biotechnology and GRAS Notice Review, Center for Food Safety and Applied Nutrition (CFSAN) in cooperation with the Center for Veterinary Medicine (CVM) at the U.S. Food and Drug Administration.
(2) In this document, food refers to both human food and animal feed, unless otherwise specifically stated.
(3) The Environmental Protection Agency (EPA) is responsible for evaluating the safety of pesticides, including plant-incorporated protectants. As such, these proteins are not subject to FDA review and are not the subject of this guidance.
(4) In this document we refer to such proteins as "new proteins."
(5) Bioengineered plants are also referred to as "biotechnology-derived plants" in the Office of Science and Technology Policy Federal Register notice (67 FR 50578, Aug. 2, 2002), and as "recombinant-DNA plants" by the Codex Alimentarius, in "Guideline for the Conduct of Food Safety Assessment of Foods Derived from Recombinant-DNA Plants" (CAC/GL 45-2003), available at ftp://ftp.fao.org/es/esn/food/guide_plants_en.pdf.
(6) Guidance on Consultation Procedures: Foods Derived from New Plant Varieties can be found at http://www.cfsan.fda.gov/~lrd/consulpr.html.
(7) The 1992 policy can be found at http://www.cfsan.fda.gov/~acrobat/fr920529.pdf.
(8) See the OSTP document for a discussion of proposed actions by EPA regarding EPA regulation of PIPs.
(9) You may also consult "Providing Regulatory Submissions in Electronic Format- General Considerations," available at http://www.cfsan.fda.gov/~dms/guidance.html .
(10) For additional guidance on this issue, you may refer to the Codex Plant Guideline, Paragraph 38 under Expressed Substances (non-nucleic acid substances) and the Annex to the Codex Plant Guideline: Assessment of Possible Allergenicity (Codex Allergenicity Annex), Section 3.2, available at ftp://ftp.fao.org/es/esn/food/guide_plants_en.pdf.
(11) For additional guidance on this issue, you may refer to the Codex Plant Guideline, Paragraph 38 under Expressed Substances (non-nucleic acid substances) and the Codex Allergenicity Annex, Section 3.3.
The latest version of this guidance issued in June 2006.