CFSAN/Office of Food Additive Safety
Center for Veterinary Medicine
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
For questions regarding this guidance, please contact: Mary Ditto, Center for Food Safety and Applied Nutrition, 301-436-1165
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Food Safety and Applied Nutrition
Center for Veterinary Medicine
Issued June 2006
OMB Control No. 0910-0583
Expiration Date: 04/30/2009
See additional PRA statement in Section VIII of this guidance
TABLE OF CONTENTS
This guidance represents 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 use. The guidance describes procedures for the early food safety evaluation of new non-pesticidal proteins produced by such new plant varieties, including for example such proteins produced in bioengineered plants.
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. The U.S. Department of Agriculture/Animal and Plant Health Inspection Service (USDA/APHIS) oversees the field testing of new varieties of bioengineered plants and requires developers to follow procedures that minimize the chance of inadvertent introduction of material from these new varieties to agriculture, the environment, and the food supply. As the number and diversity of field tests for bioengineered plants increase however, the likelihood that cross-pollination due to pollen drift from field tests to commercial fields and commingling of seeds produced under 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). 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 for food use. In most cases, the proteins expected to become components of food, whether as a result of the use of traditional or modern biotechnology methods, will be the same or quite similar to proteins commonly found in food. 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). 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 plant variety are resolved early in development, prior to any 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. If a developer decides to commercialize a new bioengineered plant variety, FDA expects that the developer will participate in the consultation process. 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.
This guidance provides a scientific framework in which to evaluate the food safety of new proteins prior to the stage of development where the new proteins might inadvertently enter the food supply, and provides recommendations about communicating with us about your scientific evaluation.
As well, this document provides guidance about the format of a submission for the early food safety evaluation of a new protein.
We encourage you to submit to us your food safety evaluation of a new protein prior to the stage of development at which a new protein might inadvertently enter the food supply, for example, via pollen flow or commingling as you increase the size or extent of field testing.
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.
Yes, we recommend that if you decide to commercialize your new plant variety 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 foods derived from new plant varieties, 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 (see footnote 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 5) (CAC/GL 45-2003) Paragraphs 34-43 under Expressed Substances (non-nucleic acid substances) and the Codex Allergenicity Annex (see footnote 5).
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.
Send your safety evaluation to OFAS at the address listed previously. CFSAN will coordinate FDA's evaluation of your request with CVM.
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.
A single copy of your safety evaluation is sufficient.
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.
If you submit any material in a foreign language, we request that you provide an accurate and complete English translation.
If you previously submitted information to us, you may incorporate that information by reference.
If someone else previously submitted information to us, the procedure to be used to incorporate that information by reference 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 reference.
If the information is not publicly available, you may incorporate that information by reference 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.
If you choose to incorporate information by reference, you should describe the information in such a way that we can readily locate it.
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".
Consistent with confidentiality requirements, FDA will make the following information easily accessible to the public via the Internet:
We suggest that your submission consist of two parts. If any information requested in Part II 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 and your conclusions about potential food safety concerns if your protein inadvertently entered the food supply. 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 could potentially cause an allergic reaction in susceptible people or could be a toxin in people or animals, 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.
In general, FDA plans to respond as follows:
This guidance contains information collection provisions that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).
The time required to complete this information collection is estimated to average 20 hours per response, including the time to review instructions, search existing data resources, gather the data needed, and complete and review the information collection. Send comments regarding this burden estimate or suggestions for reducing this burden to: 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, MD 20740.
An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. The OMB control number for this information collection is 0910-0583 (expires 04/30/2009).
 This guidance has been prepared by the 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.
 In this document, food refers to both human food and animal feed, unless otherwise specifically stated.
 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.
 In this document we refer to such proteins as "new proteins."
 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.
 See the OSTP document for a discussion of proposed actions by EPA regarding EPA regulation of PIPs.
 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 (see footnote 5).
 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 above guidance document supercedes the previous version dated November 2004.