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CFSAN/Office of Food Additive Safety
September 2003
The latest version of this guidance issued April 2006. Below is an earlier version.
Whom do I contact to determine if I need to submit a petition to the Office of Food Additive Safety?
After I submit a petition, who is the point of contact for my petition?
How do I prepare the scientific documentation to support the safe use of my proposed food additive?
What are the basic elements of a safety assessment for a food additive?
What is meant by the administrative record for a food additive?
What are the essential elements of a good petition?
How do I prepare a petition that contains the appropriate chemistry information?
How do I prepare an adequate environmental assessment?
How do I determine the type of toxicological information necessary to support the safety of my proposed food additive?
How do I design toxicological studies that will provide the information necessary to establish safety?
What other factors can help to make my submission of toxicological information successful?
How should the results of the toxicity studies be presented and discussed?
What are some factors to consider when assessing the significance of treatment-related effects in toxicity studies?
Can you give a very simplified overview of the process a petition undergoes after it is filed?
What are some characteristics of the food additive approval process?
After a notice of filing is published, how long does it usually take until a final regulation is published in the Federal Register?
Obtaining Information through the Office of Food Additive Safety
A Consumer Safety Officer (CSO) is assigned to each petition
The CSO is the point of contact for consultation with FDA technical experts
The CSO arranges meetings
The CSO provides information about the status and progress of a petition's review
To contact a CSO, write, call, FAX or e-mail:
FDA/Center for Food Safety and Applied Nutrition
HFS-200
5100 Paint Branch Parkway
College Park, MD 20740-3835
TEL: (301) 436-1200
FAX: (301) 436-2973
premarkt@cfsan.fda.gov
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Technical Guidelines for Scientific Documentation
Toxicology guidelines: Redbook I, Redbook II and Redbook 2000
Chemistry guidelines for direct additives, indirect additives, (specific subtypes)
Environmental guidance (specific subtypes)
Guidelines vs. regulations*
*Note: Regulations are requirements defined by law in the U.S. code of Federal Regulations (CFR). The format required for a food additive petition is outlined in 21CFR 171.1 and it must be followed exactly because it is a regulation. Guidance documents are neither requirements nor are they binding by law, but are agency documents that provide assistance to the petitioner in preparing information for scientific review. These documents provide information that helps the petitioner submit information in a consistent and appropriate manner.
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Elements of Safety Assessment
Identity
Estimated daily intake (EDI)
Acceptable daily intake (ADI)
Limitations of conditions of use (may be necessary to ensure safe use)
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Administrative Record for a Food Additive
Data are submitted by the petitioner
There is communication between FDA and the petitioner
FDA reviews the data as clarified by the communication, and prepares memoranda
FDA prepares a final administrative memorandum summarizing its findings
FDA publishes a final regulation, which
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Food Additive Petition Required Content
The identity and composition of the additive
The proposed use in food
The amount to be added to food
Data establishing the intended effect
Quantitative detection methods in food
Full reports of all safety studies
Proposed tolerances (if needed)
Environmental information (for NEPA*)
*As required by the National Environmental Policy Act, as revised (62 FR 40570; July 29, 1997)
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Chemistry Information
Read and study the Chemistry Guidance Documents
Guidelines are NOT requirements, BUT
Consult with the Office of Food Additive Safety (OFAS) for protocol review BEFORE initiating any studies to ensure:
Submit all supporting raw data, including that for:
Submit all other relevent information, for example:
Discuss the results:
Ensure that consistent information is presented throughout all sections of the petition, including those pertaining to:
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Environmental Information
The draft guidance listed below is intended to assist submitters in the preparation of claims of categorical exclusion and environmental assessments (EA). The draft guidance recommends the types of information that would be helpful to the agency's review of environmental submissions and refers to the National Environmental Policy Act (NEPA) implementing regulations in 21 CFR Part 25 that were revised in July 29, 1997.
Preparing a Claim of Categorical Exclusion or an Environmental Assessment for Submission to the Center for Food Safety and Applied Nutrition.
If extraordinary circumstances indicate that the proposed action might have significant environmental impacts, the agency will require the preparation of an EA for any normally excluded action. Examples of extraordinary circumstances are listed under Council on Environmental Quality regulations (40 CFR 1508.27) at http://ceq.eh.doe.gov/nepa/regs/ceq/1508.htm. In most instances, a categorical exclusion can be determined or confirmed by review of other information in the submission. In limited instances, CFSAN will recommend additional information to establish that the criteria for a categorical exclusion have been met, particularly for exclusions claimed under 21 CFR 25.32(i) and (q).
When testing is necessary, consult the Environmental Assessment Technical Assistance Handbook.
Please contact the Environmental Review Group at ERG@CFSAN.FDA.GOV for assistance in preparing a claim of categorical exclusion or an EA and before doing environmental fate and effects testing. If an EA is necessary, we recommend that you:
Completely and accurately address all format items in the specific guidance document.
Ensure that the environmental assessment (EA) is consistent with earlier sections of the petition:
Support all conclusions with data, calculations, or information from the scientific literature.
Include appropriate references (in English).
Place any confidential information in an appendix to the petition.
Further suggestions:
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Toxicology Information
Read FDA's Toxicology Guidelines (1982 Redbook, 1993 draft Redbook and Redbook 2000).
Additional Toxicology Guidelines may be useful:
FDA's Good Laboratory Practice (GLP) Guidelines.
FDA's Good Clinical Practice (GCP) Guidelines.
Guidelines are NOT requirements:
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Toxicology Information
Consult with FDA/CFSAN/OFAS! Contact the Consumer Safety Officer (CSO) assigned to the petition:
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Toxicology Information
Provide an inventory of studies and an overview of the toxicology data.
Submit all toxicity studies on the petitioned substance.
Uniquely identify each toxicity study.
Provide English language copies of studies or literature cited.
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Toxicology Information
Include data that will allow the reviewer to independently verify the results claimed. For example:
Discuss results. For example:
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Toxicology Information
When assessing treatment-related effects, these are some of the factors to consider when determining the significance of differences between treated and control groups:
From: Principles and Methods of Toxicology, Third Edition (1994), Chapter 17, page 668.
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The Food Additive Petition Review Process
The schematic below represents an extremely simplified picture of some of the elements that contribute to the food additive petition review process. This is an iterative process in which some steps may be repeated several times until there is an agency consensus that there is a reasonable certainty of no harm from the use of the petitioned additive.
A new food additive petition is received |
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The Consumer Safety Officer distributes appropriate parts of the petition to experts for evaluation: |
Chemistry Review | Health Effects Evaluation | Environ- mental Review |
Evaluation by Other Govern- ment Experts |
Evaluation by "Outside" Experts |
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The identity, functionality, manufacturing process and specifications are verified. | Toxicology and Nutrition studies are verified. A toxicity NOEL is established. | Enviromental data are evaluated. | As needed on a case-by-case basis | As needed on a case-by-case basis |
An EDI is calculated. | An ADI is calculated. | An Environmental Review is prepared. | A report is prepared. | A report is prepared. |
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The final agency review is completed. |
The final regulation is published in the Federal Register. |
The regulation appears in the Code of Federal Regulations. |
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Some Characteristics of the Food Additives Approval Process
Regulations issued are "generic" and are not "licenses" in the drug/device sense:
Approvals are safety-based only:
Direct food additives are not very toxic in comparison to "industrial chemicals"; effects of concern are ordinarily subtle and chronic.
Food additives are consumed for a lifetime by all segments of the population.
The statute requires that a food additive cannot be used until a regulation is published in the Federal Register:
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Time to Final Rule
Type of Submission | Average Time Between Submission Until a Final Rule is Published |
Threshold of Regulation (1) | 4 months |
Indirect Additive Petition (1) | 13 - 18 months |
Color Additive Petition | 6 - 72 months |
Direct Additive Petition | 24 months |
GRAS Petition (2) | N/A |
1. Many Food Contact Substances should be covered by the new Premarket Notification Program.
2. The Agency has proposed a GRAS notification process and has accepted a number of GRAS notifications.
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