Contains Nonbinding Recommendations 
Draft-Not for Implementation 
Guidance for Industry 
Providing Regulatory Submissions in 
Electronic or Paper Format to the  
Office of Food Additive Safety  
Draft Guidance 
You may submit written comments regarding this guidance at any time.  Submit written 
comments on the guidance to the Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.  All comments should be 
identified with the title of the guidance document.   
Additional copies are available from: 
Office of Food Additive Safety (HFS-200) 
Center for Food Safety and Applied Nutrition 
Food and Drug Administration 
5001 Campus Drive 
College Park, MD  20740 
(Tel) 301-436-1200 
http://www.fda.gov/FoodGuidances 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Food Safety and Applied Nutrition 
March 2010  Contains Nonbinding Recommendations 
Draft-Not for Implementation 
Table of Contents 
I. Introduction
II. Elements Common to All Regulatory Submissions
A. General
B. Forms
C. Amendments, Updates, and Supplements
D. Table of Contents
E. Information that is Exempt from Disclosure under the Freedom of
Information Act (FOIA)
F. Cover Letter
G. References
III. General Considerations about Regulatory Submissions in
Electronic Format
A. General Information
B. Transmission of a Regulatory Submission in Electronic Format
C. File Formats and Names in an Electronic Regulatory Submission
D. Roadmaps
E. Organization of an Electronic Regulatory Submission
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F.  Preparation of Amendments, Updates, and Supplements in Electronic 
Format 
G.  Electronic Signatures 
IV. Information Specific to Food or Color Additive Petition 
 
Submissions
 
A.  General Information about Petition Submissions 
B.  Petition Submissions in Electronic Format 
C.   Electronic Amendments and Updates to Petition Submissions 
D.  Food and Color Master Files 
V. Information Specific to Food Contact Notification Submissions 
 
and Pre-Notification Consultation Submissions
 
A.  General Information about Food Contact Notification Submissions 
B.  Food Contact Notification Submissions in Electronic Format 
C.  Electronic Amendments to Food Contact Notifications 
D.  Pre-Notification Consultations and Food Master Files for Food Contact 
Substances 
VI. Information Specific to Generally Recognized as Safe Notice 
 
Submissions
 
A.  General Information about Generally Recognized as Safe Notice 
Submissions 
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B.  Generally Recognized as Safe Notice Submissions in Electronic Format 
C.  Electronic Amendments and Supplements to GRAS Notice Submissions 
VII. Information Specific to Biotechnology Final Consultation 
 
Submissions
 
A.  General Information about Biotechnology Final Consultation 
Submissions 
B.  Biotechnology Final Consultation Submissions in Electronic Format 
C.  Electronic Amendments and Supplements to Biotechnology Final 
Consultation Submissions 
VIII.Information Specific to New Protein Consultation Submissions
   
A.  General Information about New Protein Consultation Submissions 
B.  New Protein Consultation Submissions in Electronic Format 
C.  Electronic Amendments and Supplements to New Protein Consultation 
Submissions 
IX. FDA Web Site References
   
A.  Administrative Information Web Site References 
B.  Chemistry Information Web Site References 
C.  Safety Study Information Web Site References 
D.  Environmental Information Web Site References 
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E. Biotechnology Information Web Site References
X. Appendices
5 Contains Nonbinding Recommendations 
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Guidance for Industry1
 
Providing Regulatory Submissions  
to the Office of Food Additive Safety  
in Electronic or Paper Format 
 
 
This guidance, when finalized, will represent the Food and Drug Administrations (FDAs) 
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 telephone number listed on the title page of 
this guidance.  
 
 
I.  Introduction  
This guidance document is intended to assist industry in transmitting regulatory submissions to 
the Office of Food Additive Safety (OFAS) in CFSAN at FDA.  Although the guidance applies 
regardless of whether you transmit the submission in electronic format or in paper format, many 
of the details of this guidance are directed to specific format features associated with transmitting 
a submission in electronic format.  
   
This guidance applies to the following types of regulatory submissions to OFAS:  
  Food Additive Petition (FAP);  
  Color Additive Petition (CAP);  
  Food Master File (FMF);  
  Color Master File (CMF); 
  Food Contact Notification (FCN);  
  Pre-Notification Consultation for a Food Contact Substance (PNC);  
  Generally Recognized As Safe (GRAS) notice;  
  Final Consultation for Food Derived From New Plant Varieties (Biotechnology Final 
Consultation); and 
  Early Food Safety Evaluation of New Non-Pesticidal Proteins Produced by New Plant 
Varieties Intended for Food Use (New Protein Consultation). 
 
                                                 
1 This guidance has been prepared by the Office of Food Additive Safety in the Center for Food Safety and Applied 
Nutrition at the U.S. Food and Drug Administration.  
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OFAS receives other types of submissions in addition to the submissions listed above.  For 
example, OFAS receives Threshold of Regulation submissions in accordance with 21 CFR 
170.39 and Notification for a Food Contact Formulation submissions in accordance with 21 
CFR 170.106.  This document does not provide any specific recommendations regarding these 
submissions because the number of these types of submissions is small.  If you have questions 
about preparing a submission other than those listed above, you should contact us at the 
telephone number provided on the first page of this document.   
FDAs 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.  
II. Elements Common to All Regulatory Submissions
A.  General
1. Where can I find the definitions of the regulatory submissions and terms
covered by this document?
You can find the definitions of the regulatory submissions and terms covered by this guidance in 
Appendix 11. 
2. Do any fees apply to my regulatory submission?
As of the date of this document, fees only apply to the submission of a CAP for the listing of a 
color additive (see 21 CFR 70.19).     
3. Where do I send my regulatory submission?
Send all fully electronic submissions through FDAs Electronic Submission Gateway (ESG).  
For additional information about FDAs ESG, see Section III.B of this document. 
Send a FCN, PNC, or FMF concerning a food contact substance (FCS) that is prepared in paper 
format, or prepared in electronic format but submitted on physical media (e.g., CD-ROM or 
DVD), to: 
Notification Control Assistant 
Office of Food Additive Safety 
HFS-275 
5001 Campus Drive 
College Park, MD 20740-3835  
Send all other regulatory submissions prepared in paper format, or prepared in electronic format 
but submitted on physical media (e.g., CD-ROM or DVD), to: 
7 Contains Nonbinding Recommendations 
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Office of Food Additive Safety 
HFS-200 
5001 Campus Drive 
College Park, MD 20740-3835  
4. May FDA refuse to accept my regulatory submission?
Yes.  FDA may refuse to accept any regulatory submission that is transmitted in electronic 
format, if it is either inaccessible or contaminated with malicious elements such as a computer 
virus.  FDA may also refuse to file a new submission if it is incomplete or if any data are lacking 
or not set forth so as to be readily understood (see, e.g., 21 CFR 71.1(d), 21 CFR 171.1(d), and 
21 CFR 170.104(b)(1)). 
B.  Forms 
5. Should I include a specific form with my regulatory submission?
Yes.  You should include a specific form with any regulatory submission (including any new 
submission and any update, amendment, or supplement to a previous submission), regardless of 
whether you transmit the regulatory submission in electronic format or in paper format.  You 
must use Form FDA 3480 when submitting a FCN (21 CFR 170.101(e)).  If you are sending 
your submission in paper format, place your submission form at the beginning of the entire 
submission.  
6. What is the purpose of the form I include with my regulatory submission?
The form prompts you to include certain elements of the particular type of regulatory submission 
in a standard format.  A form you transmit in electronic format improves the efficiency of our 
administration of your submission, because it provides data and information that our systems can 
extract and upload directly into our databases.  
The form also substitutes for the Dear Sir section of 21 CFR 71.1(c) (for a CAP) and 21 CFR 
171.1(c) (for a FAP).  However, the information on the form is not intended to substitute for the 
complete description of procedures, requirements, or recommendations included in the 
applicable regulation or guidance. 
7. How do I find the correct form and applicable instructions for completing
the form?
Table II-1 identifies the correct form to include with each type of regulatory submission, the 
Appendices where you can find each form, and the Appendices where you can find instructions 
for completing each form. 
Table II-1 
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Where to Find the Correct Form for Your Regulatory Submission 
 
Type of Submission  Form  Where to Find the  Where to Find the Form
No.*  Instructions for Using the 
Form 
FAP, FMF   3503  Appendix 1  Appendix 2 
CAP, CMF  3503  Appendix 1  Appendix 2 
FCN, FMF for FCS,  3480   Appendix 3a  Appendix 4a 
PNC   
Amendment to a FCN,  3480-A  Appendix 3b  Appendix 4b 
PNC, or FMF for a 
FCS 
GRAS Notice  3667  Appendix 5  Appendix 6 
Biotechnology Final  3665  Appendix 7  Appendix 8 
Consultation 
New Protein  3666  Appendix 9  Appendix 10 
Consultation 
* For all original submissions and any additional information to those submissions (except those 
concerning FCS) use the same submission form.  
 
8.  How should I organize a new master file submission?  
You should organize a new master file submission according to the items listed on the applicable 
form (i.e., Form FDA 3503 or Form FDA 3480).  A summary of these items is listed in Table 
IV-1 of this document (for Form FDA 3503) and Table V-1 of this document (for Form FDA 
3480) and described in the applicable instructions for the form (see Appendices 1, 3a and 3b).   
 
C.  Amendments, Updates, and Supplements 
9.  How are the terms amendment, update, and supplement used in the 
context of the regulatory submissions covered by this document? 
The terms amendment, update, and supplement are used as shown in Table II-2. 
 
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Table II-2 
Use of the Terms Amendment, Update, and Supplement 
 
Submission  Amendment  Update  Supplement 
FAP  Any data or information you  Any data or information  N/A* 
submit to a filed FAP in  submitted to a filed FAP 
response to a request from us  on the initiative of the 
for additional information or  submitter (i.e., without a 
clarification   request from FDA) 
CAP  Any data or information you  Any data or information  N/A 
submit to a filed CAP in  submitted to a filed CAP 
response to a request from us  on the initiative of the 
for additional information or  submitter (i.e., without a 
clarification   request from FDA) 
FCN  Any data or information you  N/A  N/A 
submit to an FCN  
PNC  Any data or information you  N/A  N/A 
submit to a PNC 
GRAS notice  Any data or information you  N/A  Any data or information 
submit regarding a filed  you submit regarding a 
GRAS notice before we  GRAS notice after we 
respond to it  respond to it 
Biotechnology  Any data or information you  N/A  Any data or information 
Final  submit regarding a  you submit regarding a 
Consultation  Biotechnology Final  Biotechnology Final 
Consultation before we  Consultation after we 
respond to it  respond to it 
New Protein  Any data or information you  N/A  Any data or information 
Consultation  submit regarding a New  you submit regarding a 
Protein Consultation before  New Protein Consultation 
we respond to it  after we respond to it 
FMF  Any data or information you  Any data or information  N/A 
submit to an FMF  you submit to an FMF 
established for a FCS  established for a 
substance other than a 
FCS 
CMF  N/A   Any data or information  N/A 
you submit to an 
established CMF  
*N/A means Not applicable. 
 
  10 Contains Nonbinding Recommendations 
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D.  Table of Contents 
10. Should I include a Table of Contents with my regulatory submission? 
You should include a Table of Contents: 
  With any submission regarding a GRAS notice, Biotechnology Final Consultation, or 
New Protein Consultation (whether the submission is a new submission or an 
amendment or supplement to a previous submission), regardless of whether the 
submission is transmitted in paper or electronic format;  
  With any other regulatory submission transmitted in paper format; and 
  Within individual Studies submitted as part of a regulatory submission. 
 
11. How should I paginate a regulatory submission in paper format? 
You should paginate a regulatory submission in paper format using continuous pagination.  For 
an example of continuous pagination, see the example Table of Contents in Table II-3 in the next 
question. 
 
12. How should I format the Table of Contents in a regulatory submission I 
transmit in paper format? 
You should format the Table of Contents in a regulatory submission in paper format to show the 
overall page numbers for the entire submission.  When there is more than one volume, the Table 
of Contents should include the volume number.   Below, we provide examples of a Table of 
Contents for a FAP (Table II-3) and a safety study (Table II-4), respectively. 
 
 
Table II-3 
Example of a Table of Contents for a FAP Submitted in Paper Format 
 
Title  Volume  Page No. 
Proposed Regulation  I  1-2 
Chemistry Information  I - VII  3-2560 
  Identity  I  3-203 
  Use and Technical Effect  I - III  204-1342 
  Labeling  III  1343-1350 
  Manufacturing Method  III  1351-1377 
  Specifications  III  1378-1379 
  Stability Studies  III -  IV  1380 - 1753 
  Studies Regarding Intended Effect  IV - V  1754 -2109 
  Analytical Methods  V - VI  2110 -2531 
  Chemistry References  VI  2532 -2560 
Safety Information  VI - XXXI  2561-11671 
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Title  Volume  Page No. 
  Toxicology Narrative   VI  2561-2575 
  Genetic Toxicity Tests   VI  2576-2848 
  Short Term Toxicity Studies in Rodents  VII  2849-3120 
  Short Term Toxicity Studies in Non-Rodents  VII - VIII  3121-3170 
  Subchronic Toxicity Studies in Rodents  VIII - IX  3171- 3552 
  Subchronic Toxicity Studies in Non-Rodents  IX  3553-3853 
  One Year Toxicity Studies in Non-Rodents  X  3854 - 4104 
  Combined Chronic Toxicity/Carcinogenicity  X - XIX  4105-9948  
Studies in Rodents 
  Multi-Generation Reproduction Study  XIX - XXX  9949-10970 
  Immunotoxicity Studies  XXX  10971-11021 
  Neurotoxicity Studies  XXX  11022-11202 
  Metabolism and Pharmacokinetic Studies  XXX - XXXI  11203-11673 
  Safety References  XXXI  11674-11678 
Environmental Assessment  XXXI  11679-11792 
 
 
Table II-4 
Example of a Table of Contents for a One Year Toxicity Study in Non-Rodents Submitted 
in Paper Format 
 
Title  Volume  Page No.  
Authentication   X  1 
Quality Assurance  X  2-3 
Summary and Conclusions  X  4-10 
Study Organization  X  11-13 
Information on the Test and Control Article  X  14-18 
Experimental Procedure  X  19-29 
Evaluation of Data  X  30 - 40 
Archives  X  41-43 
Schedule of the Study  X  44-48 
Comments and Deviations from The Original Protocol  X  49- 51 
and Amendments 
Results  X  52-200 
Tables of Mean Values  X  201-225 
Appendices (individual results)  X  226 -245 
Addenda  X  246 -249 
Statement of Compliance  X  250 
 
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E. Information that is Exempt from Disclosure under the Freedom
of Information Act (FOIA)
13.Should I designate in my regulatory submission information that I view as
exempt from disclosure under the Freedom of Information Act?
Yes.  We recommend that you designate information that you consider exempt from disclosure 
in writing (21 CFR 20.61(d)).  However, if we disagree that the designated information satisfies 
the criteria for exemption from disclosure (see 21 CFR 20.27 and 21 CFR Part 20 Subparts D 
and E), the procedures in 21 CFR 20.61(e) will apply.   
14.How should I designate information that I consider exempt from
disclosure?
You should designate this information in a manner that will unambiguously communicate your 
view.   
We recommend that you: 
 Describe the information that you consider exempt from disclosure in a separate 
document (for the purposes of this guidance we are calling this document Designation of 
Nondisclosable Information).  For example, the Designation of Nondisclosable 
Information included with a FAP could identify a particular quantitative formula you 
view as exempt from disclosure within the meaning of 21 CFR 171.1(h)(2)(iii).  This 
would ensure that we know your view on this quantitative formula each and every time it 
appears.  Such a separate document could, for example, both identify a quantitative 
formula you view as confidential and provide a list of places in the submission where the 
formula occurs. 
 Identify information as exempt from disclosure at the place where it occurs in a 
submission (e.g., by highlighting).  You may mark an entire page or set of pages as 
confidential (e.g., by a stamp at the top of each page) when you consider entire pages or 
multi-page documents as trade secret or confidential information (e.g., when describing a 
manufacturing process in a food additive petition).  You should not mark an entire page 
or set of pages as confidential when the page or pages contain both confidential and non-
confidential information.  If you are unable to mark information on the electronic 
submission form as confidential (e.g., by highlighting), you should describe the 
information entered on the form you consider nondisclosable in a Designation of 
Nondisclosable Information document, as described above.
15.May I provide a redacted copy of some or all of my regulatory submission?
Yes.  You may provide a redacted copy of your complete submission, or a redacted copy of only 
those parts of your submission containing information you view exempt from disclosure.  If you 
provide a redacted copy of some or all of your regulatory submission, we nonetheless 
recommend that you also designate information exempt from disclosure as described above.  
This will help to ensure that we are aware of your view if, for example, you inadvertently did not 
redact all nondisclosable information. 
13 Contains Nonbinding Recommendations 
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16. Will FDA use my redacted copy when FDA responds to a request, under 
the FOIA, for a disclosable copy of my submission? 
FDA may or may not use your redacted copy depending on whether the redacted copy satisfies 
the criteria for exemption under FOIA (see 21 CFR Part 20 at 20.27 and Subparts D and E) and 
on whether using your redacted copy will be the most efficient means for us to respond to FOIA 
requests (e.g., because of formatting issues). 
 
17. Are the data and information in a master file submission available for 
public disclosure? 
Whether the data and information in a master file submission are available for public disclosure 
is a case-by-case determination that we make in accordance with our regulations in 21 CFR part 
20 and (when applicable) in submission-specific regulations such as 21 CFR 171.1(h).  Whether 
specific data and information are exempt from disclosure depends on circumstances and, thus, 
may change as circumstances change.   
 
F.  Cover Letter 
18. Should I include a cover letter with my regulatory submission?  
We do not ask you to include a cover letter if you use the applicable form for the regulatory 
submission.  If you choose not to use the applicable form, you should include a cover letter 
regardless of whether you transmit the submission in electronic format or in paper format and 
regardless of whether your submission is a new submission or an amendment, update, or 
supplement to an existing submission. 
 
19. What should a cover letter include? 
A cover letter should include the administrative information that would have been included with 
the applicable form.  For FCN submissions, this information can be found in Part I of Forms 
3480 and 3480-A.  For all other regulatory submissions, this information can be found in Parts I, 
II, and III of the applicable form. 
 
Examples of this administrative information include:  
  The type of regulatory submission (e.g., FAP, New Protein Consultation); 
  Whether the submission is a new submission or an amendment, update or supplement to a 
previous submission; 
  The applicable regulation or guidance associated with the submission (e.g., a FAP is 
submitted in accordance with 21 CFR 171.1 and a New Protein Consultation is submitted 
in accordance with our Guidance to Industry entitled Recommendations for the Early 
Food Safety Evaluation of New Non-Pesticidal Proteins Produced by New Plant Varieties 
Intended for Food Use (Ref. 22));  
  14 Contains Nonbinding Recommendations 
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  The format and mode of transmission (e.g., electronic format transmitted on physical 
media) and the number of any enclosed physical media (e.g., three CD-ROMs); and 
  A statement that any electronic files have been checked and found to be virus-free.   
 
In addition, when your submission is a CAP or a FAP, the cover letter should include the 
elements specified in the opening of 21 CFR 71.1(c) (for a CAP) or 21 CFR 171.1(c) (for a 
FAP).   
 
G.  References 
20. How should I provide the Web site address when I refer to information 
available on the Internet?  
You should provide the Web site address for information available on the Internet by including it 
in a list of references or web-based documents.  For additional information on providing Web 
site addresses in electronic submissions, see Section III.E in this document. 
 
III.  General Considerations about Regulatory Submissions in 
Electronic Format    
A.  General Information 
1.  Should I use a password to protect a regulatory submission in electronic 
format? 
No.  Our internal security and archival processes will maintain the integrity of the files received. 
 
2.  Should I check a regulatory submission in electronic format for computer 
viruses? 
Yes.  The forms provide a checkbox prompting you to confirm that the submitted files have been 
checked and are free of computer viruses. If you are sending a cover letter refer to Section II.F 
above. 
 
3.  What is the size limit of electronic files I submit? 
The size limit of electronic files you submit is 50 Megabytes (MB).  You should divide any files 
larger than 50 MB into multiple files.   
 
B.  Transmission of a Regulatory Submission in Electronic Format 
4.  What is the FDA Electronic Submission Gateway (FDA ESG)? 
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The FDA ESG is an agency-wide portal mechanism for receiving submissions in electronic 
format.  The FDA ESG enables the secure submission of regulatory information for review and 
provides for the receipt of a document. 
 
5.  How do I use the FDA ESG? 
Complete instructions for use of the FDA ESG are available in FDAs Web site (Ref. 1). 
 
6.  Is the FDA ESG the only mechanism available for me to transmit my 
regulatory submission in electronic format? 
No.  You also may transmit a regulatory submission in electronic format by providing your 
electronic files on physical media (e.g., CD-ROM or DVD) and transmitting these physical 
media by means such as mail or a courier service. 
 
7.  What recommendations apply when I use physical media (such as CD-
ROMs or DVDs) to transmit my regulatory submission in electronic 
format?   
A regulatory submission transmitted in electronic format on physical media should be 
accompanied by a paper copy of any form or cover letter that you sign.  At this time, we are not 
able to accept an electronic signature in documents transmitted on physical media. 
 
You may zip files to provide as much information as possible on a single disc (or other 
physical medium).  If you need to use more than one disc (or other physical medium), you 
should label each item (e.g., Disc 1 of 4, Disc 2 of 4, etc.).   
 
C.  File Formats and Names in an Electronic Regulatory Submission 
8.  What file formats should I use for my regulatory submission?   
The type of file format to use depends on the type of data or information you are submitting.  
Table III-1 lists the file formats we recommend you use for the most common types of data and 
information.  We generally are able to access formats listed in Table III-1 and data sets that are 
compatible with XML (extensible markup language) format.  We recommend that you contact us 
before submitting data or information in any file format not listed in Table III-1.  Doing so 
should minimize problems with your electronic submission. 
 
The different Centers in FDA are in varying stages of implementing a pilot program for 
accessing files in Standard for Exchange of Nonclinical Data (SEND) and Study Data Tabulation 
Model (SDTM) (Ref. 14).  The likelihood that OFAS will be able to receive files in SEND or 
SDTM increases as time goes on.  Therefore, we recommend that you contact us before 
submitting files in SEND or SDTM formats.  We can also receive files containing study data in 
XML format. 
 
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Additional information relevant to the use of electronic collection of clinical trial data is 
available in the Guidance to Industry - Computerized Systems Used in Clinical Investigations 
(Ref. 12). 
 
Table III-1 
Recommended File Formats 
 
Type of Data or Information  Recommended File Format 
General text   Portable Document Format (PDF) 
Primary data or summary data (e.g.,  Both PDF and, if available, spreadsheet format 
toxicological study reports)  for tabular data (e.g., .xls).   
Chemical structures  Molfiles (.mol) (preferred); or 
ChemDraw files (.cdx); or 
Structure & data files (.sdf) 
(Chemical structures may also be provided as 
images within PDF files) 
Animal Study Data  In addition to PDF for full study reports, use 
templates when available and transmit the 
information in the completed template in PDF 
(Ref. 13); OR 
Use Standard for Exchange of Nonclinical 
Data (Ref. 14) 
Clinical Trial Data Generated by Computerized  Study Data Tabulation Model (SDTM) (Ref. 
Systems  14) 
References  PDF 
 
 
9.  What recommendations apply to files prepared in PDF format?   
We recommend that you create PDF files directly from electronic source documents (rather than 
from scanned images) whenever possible.  Such files require less memory space than scanned 
image files.  Such files also help assure access to, and accurate searching of, text, tabular data 
and graphical objects.  
 
If you scan a document to create a PDF file, we recommend that you capture text by optical 
character recognition (OCR) software so that the text of the resulting electronic documents is 
reasonably accessible and searchable. 
 
10. How should I name files in a regulatory submission transmitted in 
electronic format? 
You should name a file in a way that will help us to see what is in the file and when the file was 
prepared or submitted.  Doing so will help us to store the file in our database in a way that our 
reviewers can easily find it and will improve the efficiency of our review.   
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In general, you should name a file using both generic elements (which relate to the type of 
information in the file, such as a toxicity study) and specific elements (which relate to your 
particular submission, such as the name of the substance that is the subject of the submission).  
The specific recommended conventions for naming files vary depending on factors such as: 
  The type of data or information;  
  Whether the data or information is transmitted in a new regulatory submission or in an 
amendment, update or supplement to a previous regulatory submission; and 
  Whether the document that is the subject of the file exceeds 50 megabytes and, thus, is 
broken into more than one file. 
 
You should refer to Appendix 12 and the detailed guidance for each type of regulatory 
submission (in Sections IV through VIII of this document) for more complete recommendations 
for naming files and for examples.   
 
D.  Roadmaps 
11. What is an electronic submission roadmap? 
An electronic submission roadmap is an organized grouping of electronic folders that you can 
download and use to structure an electronic submission. 
 
12. Do different types of regulatory submissions have different roadmaps? 
Yes. 
 
13. Should I include a roadmap with each electronic regulatory submission I 
make? 
Yes.  You should include the applicable roadmap with each electronic regulatory submission 
(including a new submission and any update, amendment, or supplement to a previous 
submission).  You should download a new roadmap each time you transmit an amendment, 
update or supplement to an existing submission.  This will help us to distinguish the newly 
submitted information from the information in your original submission. 
 
14. Where can I find the roadmaps for use in structuring regulatory 
submissions?  
The roadmaps are available in Appendix 15.  
 
15. Where can I find examples of representative roadmaps for the submissions 
described in this document? 
 
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Figures IV-1, V-1, VI-1, VII-1, and VIII-1 of this document (see Sections IV, V, VI, VII, and 
VIII of this document), which are submission outlines, depict examples of representative 
roadmaps for the submissions described in this document.   
 
16. What would a roadmap look like when displayed on my computer? 
Figures III-1 and III-2 provide examples of a roadmap as seen on your computer (Microsoft 
Windows).  Figure III-1 shows a foldering structure and Figure III-2 shows files included within 
a particular folder.  The information presented in this diagram depicts a set of folders in a food 
additive petition; an alternative presentation of Figure III-1 (in text format) is in Figure IV-1.  
 
Figure III-1 shows a Main directory with five first level folders (Administrative, 
Administrative Technical, Chemistry, Safety and Environmental).  The Administrative folder has 
three second level folders (Designation of Nondisclosable Information, Redacted Document and 
Incoming Correspondence).  The Chemistry folder has two second level folders (Methods and 
References).  The Safety folder has two second level folders (Studies and References).  The 
Environmental folder has three second level folders (Confidential Environmental Info, Studies 
and References).  The second level folders Incoming Correspondence, Chemistry, Safety and 
Environmental also contain third level folders.  The third level Studies folder under the Safety 
folder has many fourth level folders. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  19 Contains Nonbinding Recommendations 
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Figure III-1 Example of the Main Directory of a FAP Submission Roadmap  
 
 
 
Figure III-2 Example of the Contents of the Administrative Subfolder  
in a FCN Submission Roadmap 
 
Figure III-2 has two panels. The left panel of Figure III-2 shows a Main directory with four 
first level folders (i.e., Administrative, Chemistry, Environmental, and Safety folders).  A 
plus sign precedes three folders (i.e., Chemistry, Safety, and Environmental folders), 
indicating that these folders contain second level folders.   
 
The administrative folder in the left panel of Figure III-2 is highlighted to show that its contents 
are presented in the right panel of Figure III-2.  The right panel of Figure III-2 contains three 
  20 Contains Nonbinding Recommendations 
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PDF files (i.e.., for Designation of Nondisclosable Information, Form 3480, and Proposed 
Language for the FCN Listing for a food contact substance). 
 
 
 
E.  Organization of an Electronic Regulatory Submission 
17. What format features should I include in the Table of Contents in a PDF 
file included in an electronic regulatory submission? 
You should format the Table of Contents in a PDF file using bookmarks designed to help the 
reader navigate through the document efficiently. 
 
18. How should I paginate the individual files in a regulatory submission in 
electronic format? 
You should paginate each individual file transmitted in the regulatory submission.  In most cases, 
you should paginate each submitted file so that it begins on page 1  i.e., you should not 
incorporate any type of continuous pagination.  This recommendation is in contrast to our 
recommendation for pagination of paper submissions, where continuous pagination is 
appropriate (see Section II.D of this document).  See the next question for an exception 
associated with studies that are so large that you submit them in multiple files that use 
continuous pagination.   
 
19. How should I organize information in large studies? 
You should organize information in large studies as follows: 
  Include a Table of Contents at the beginning of each study; 
  Separate files by sections of the study rather than breaking in the middle of a section; and  
  Preserve the pagination of a large study with each PDF file continuing the pagination 
where the previous PDF file left off.   
 
For example, consider a study file with 2000 pages.  If you split the file at the end of page 1500, 
the next file should start at page 1501.  (See Appendix 12 for additional information on naming 
these files.) 
 
  21 Contains Nonbinding Recommendations 
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20. How should I format the Web site addresses included in a reference list 
submitted in electronic format? 
You should format Web site addresses in a reference list as hyperlinks and include the applicable 
Web site address as of the date when you accessed the reference from the Web site. 
 
F.  Preparation of Amendments, Updates, and Supplements in 
Electronic Format 
21. What special recommendations apply to the submission of amendments, 
updates, or supplements in an electronic regulatory submission? 
The following recommendations apply to amendments, updates, and supplements for all 
regulatory submissions prepared in electronic format.  
  Use the applicable form. 
  Download a new Roadmap and change the name of the Main directory to the number 
we assigned to your submission type (e.g., FCN 009999 or FAP 9A9999).    
  Organize the information in the submission into one or more individual files as described 
in the specific guidance for your regulatory submission.  (For example, an amendment or 
update to a FAP would include a separate file directed to each topic addressed in the 
amendment or update, whereas an amendment or supplement to a GRAS notice would 
include a single file regardless of the number of topics addressed in the amendment or 
supplement.)  
  Begin each filename with the date (YYYY-MM-DD) the amendment, update or 
supplement is submitted.   
  Place the files in appropriate folders according to the applicable roadmap.  
  Do not include files already submitted.   
 
Additional recommendations for amendments, updates or supplements are available in the 
specific guidance for each submission type as follows:  
  FAPs/CAPs:  Section IV.C;  
  FCNs: Section V.C;  
  GRAS notices: Section VI.C;  
  Biotechnology Final Consultations: Section VII.C; and  
  New Protein Consultation Submissions: Section VIII.C.   
 
Following these recommendations will help us to store the data and information in the 
amendment, update or supplement in our database in a way that our reviewers can easily find it. 
 
G.  Electronic Signatures 
22. Where can I find information about electronic signatures in a regulatory 
submission? 
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Information about electronic signatures in regulatory submissions to FDA is available in 21 CFR 
11.200 and at the ESG (Ref. 1).  For further information on the current status of electronic 
signatures, contact OFAS at 301-436-1200. 
 
  23 Contains Nonbinding Recommendations 
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IV.  Information Specific to Food or Color Additive Petition 
Submissions 
Section IV of this document addresses FAP and CAP submissions (petition submissions).  You 
must submit an FAP in accordance with 21 CFR 171.1 and a CAP in accordance with 21 CFR 
71.1.  We assign a number (FAP No. or CAP No., respectively) to your submission and review 
your submission to determine whether to establish a regulation for the use of a food additive or 
list a color additive in Title 21 of the Code of Federal Regulations.   
 
A.  General Information about Petition Submissions  
1.  How do the Parts on Form FDA 3503 relate to the elements of FAPs and 
CAPs? 
Table IV-1 shows the elements of FAPs and CAPs and links each element to the applicable part 
of Form FDA 3503.   
 
Table IV-1 
Elements of FAPs and CAPs as Shown on Form FDA 3503 
 
Element of FAPs and CAPs  Applicable Part on Form FDA 3503 
Introductory information about the  I 
submission 
Information about the petitioner (and any  II 
attorney or agent acting on behalf of the 
petitioner) 
General administrative information   III 
Information specific to Food Additive  IV.A 
Petitions 
Information (including fees) specific to  IV.B 
Color Additive Petitions 
Identity  V  
Administrative  VI 
Administrative Technical   VI 
Chemistry  VI 
Safety  VI 
Environmental  VI 
Signature  VII 
N/A  VIII (List of Attachments) 
 
 
  24 Contains Nonbinding Recommendations 
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2. How should I organize a new petition submission?
You should organize a new petition submission as a series of documents presenting the elements 
of a petition in an order corresponding to that of the elements listed on Form FDA 3503.  A 
summary of these elements is listed in Table IV-1 of this document and described in the 
instructions for Form FDA 3503 (see Appendix 1).  If you include any data or information not 
identified as an element on Form FDA 3503, you should place these data or information in a 
logical place in your submission based on the type of information. 
3. Am I required to include a proposed regulation with my petition
submission?
You must include a proposed regulation if your petition would alter an existing food additive 
regulation or color additive listing (see 21 CFR 171.1(c)G and 21 CFR 71.1(c)H).  If your 
petition is for a new food additive regulation or color additive listing, you may include a 
proposed regulation (see 21 CFR 171.1(c)F and 21 CFR 71.1(c)F). 
4. Am I required to include a proposed tolerance with my petition
submission?
You must include a proposed tolerance with your petition if a tolerance is required to ensure 
safety (see 21 CFR 171.1(c)F and 21 CFR 71.1(c)F).    
B. Petition Submissions in Electronic Format
General Questions and Answers about Petition Submissions in Electronic Format 
5. How should I organize an electronic FAP or CAP submission?
You should organize an electronic FAP or CAP submission using the foldering structure 
available in a downloadable Petition Submission Roadmap (see instructions in Appendix 1 and 
the roadmap in Appendix 15).  The entire Petition Submission Roadmap is organized under the 
folder entitled Main directory.  The Main directory includes six first-level folders, and 
several of these first-level folders include second-level and third-level subfolders.  We show 
these folders and subfolders, using an outline format, in Figure IV-1, below. 
Figure IV-1 
Outline Representing the Folders and Subfolders in a Petition Submission Roadmap 
(Main directory) 
 Main directory
o Administrative
 Designation of Nondisclosable Information
 Redacted Document
 Incoming Correspondence
 Amendment
25 Contains Nonbinding Recommendations 
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 Update
o Administrative Technical
o Chemistry
 Studies
 Stability
 Technical Effect
 Migration
 Other
 Methods
 References
o Safety
 Studies
 Genetic Toxicity Tests
 Short Term Toxicity Studies Rodents
 Short Term Toxicity Studies Non-Rodents
 Subchronic Toxicity Studies Rodents
 Subchronic Toxicity Studies Non-Rodents
 One Year Toxicity Studies Non-Rodents
 Chronic Toxicity Studies Rodents
 Combined Chronic Toxicity/Carcinogenicity Studies Rodents
 Carcinogenicity Studies Rodents
 In Utero Exposure Phase for Addition to Carcinogenicity Studies 
Rodents
 Reproduction Studies
 Developmental Toxicity Studies
 Immunotoxicity Studies
 Metabolism and Pharmacokinetic Studies
 Neurotoxicity Studies
 Ocular Studies
 Dermal Studies
 Human Studies
 Other Studies
 References
 Literature Publications
 Other
o Environmental
 Confidential Environmental Information
 Studies
 References
o Other
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6.  When should I use the specific folders and subfolders in the Petition 
Submission Roadmap (Main directory)? 
 
You should use the specific folders and subfolders as shown in Table IV-2.  You should not 
place any specific files directly in Main directory, which refers to the entire submission 
organized in the foldering structure (refer to Figure III-1 and Figure IV-1). Main directory only 
contains folders.   
 
 
Table IV-2 
When to Use Specific Folders and Subfolders in the Main Directory of a Petition 
Submission Roadmap*  
 
 
Folder/Subfolder      When to Use it 
Administrative folder  Any time you transmit a new submission, a file relating to fees 
associated with a CAP, or a redacted electronic file(s) 
Designation of  Any time you transmit data or information that satisfies the 
Nondisclosable Information  criteria for exemption from disclosure 
folder 
Redacted Folder  Any time you submit a redacted copy, place it in the redacted 
subfolder under the Administrative folder, regardless of whether 
you are transmitting a new submission, an amendment, or an 
update 
Incoming Correspondence  You should not place any specific files directly in the Incoming 
folder  Correspondence folder. The Incoming Correspondence folder 
only contains subfolders 
Incoming  Any time you transmit an amendment or update to your petition 
Correspondence/Submission 
Form Subfolder 
Incoming Correspondence/  Only when the data or information you transmit to a filed 
Amendment Subfolder  submission in response to correspondence from us do not fall 
within the scope of any other folder, such as Chemistry, Safety, or 
Environmental 
Incoming Correspondence/  Only when the data or information you transmit to a filed 
Update Subfolder  submission on your own initiative (i.e., not in response to 
correspondence from us) do not fall within the scope of any other 
folder, such as Chemistry, Safety, or Environmental 
Administrative Technical  Any time you transmit a proposed regulation, proposed tolerance, 
Folder  or information regarding exemption from batch certification for a 
color additive, regardless of whether you are transmitting a new 
submission, an amendment, or an update 
  27 Contains Nonbinding Recommendations 
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Folder/Subfolder      When to Use it 
Chemistry Folder and  Any time you transmit chemistry data or information, regardless 
Applicable Subfolders  of whether you are transmitting a new submission, an amendment, 
or an update 
Safety Folder and  Any time you transmit safety data or information, regardless of 
Applicable Subfolders  whether you are transmitting a new submission, an amendment, or 
an update 
Environmental Folder and  Any time you transmit environmental data or information, 
Applicable Subfolders  regardless of whether you are transmitting a new submission, an 
amendment, or an update 
Other Folder  Any time you transmit data or information in an original 
submission that does not fall within the scope of any other folders 
or subfolders 
*If you are transmitting an amendment or update to your submission, you should rename Main 
directory to reflect the submission designation we assigned to it (i.e., FAP9A9999 or CAP 
9C9999). 
 
7.  How should I name files in an electronic petition submission? 
You should name each file using both generic and specific elements as described in Section III.C 
and Appendix 12 of this document.  Generic elements in the file names specific to petition 
submissions are included in the examples in Tables IV-3 through IV-11 (below).  
 
Questions and Answers about Files in the Administrative and Administrative Technical 
Folders in the original Petition Submissions 
8.  What subfolders and files should I place in the Administrative folder?  
Table IV-3 shows the subfolders and files you should place in the Administrative folder.  
 
Table IV-3 
Subfolders and Files in the Administrative Folder of a Petition 
 
 
Folder/subfolder  File Name  Information in  Applicable 
File  Regulatory 
Citation  
Administrative  Form3503_..._YYYY-MM-DD.pdf   Some specific  N/A 
information in the 
submission and a 
list of documents 
included 
  28 Contains Nonbinding Recommendations 
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Folder/subfolder  File Name  Information in  Applicable 
File  Regulatory 
Citation  
Administrative  CoverLetter_..._YYYY-MM-DD.pdf   Letter  21 CFR 71.1 
accompanying the  21 CFR 
submission if you  171.1 
choose to send a 
letter in addition to 
Form FDA 3503 
Administrative/  DesignationOfConfidentialInformation_ A description of  21 CFR 
Designation of  ..._YYYY-MM-DD.pdf  the data or  20.61(d) 
Confidential  information in 
Information  your submission 
that you 
designated as 
nondisclosable 
information. 
Administrative/  RedactedBySubmitter_..._YYYY-MM- Data or  N/A* 
Redacted  DD.pdf  information copied 
from one or more 
files in your 
submission and 
then modified by 
deletion of data or 
information you 
designated as 
nondisclosable 
information. 
*N/A means Not applicable. 
 
9.  What files should I place in the Administrative Technical subfolder?  
Table IV-4 shows the files you should place in the Administrative Technical folder.  
 
Table IV-4 
Files in the Administrative Technical Folder of a Petition Submission 
 
File Name  Information in File  Applicable 
Regulatory 
Citation 
ProposedRegulation_..._YYYY- Your proposed text for the food additive  21 CFR 71.1(c) H 
MM-DD.pdf  regulation or color additive listing.    21 CFR 171.1(c) G
  29 Contains Nonbinding Recommendations 
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File Name  Information in File  Applicable 
Regulatory 
Citation 
ProposedTolerance_..._YYYY- Your proposed text for the tolerance  21 CFR 71.1(c) F 
MM-DD.pdf  provision of the food additive regulation  21 CFR 171.1(c) F 
or color additive listing, if a tolerance is 
required to ensure safety.   
ExemptCertification_..._YYYY- The reasons why batch certification for a  21 CFR 71.1(c) G 
MM-DD.pdf (CAP only)  color additive is not necessary, including   
supporting data to establish the safety of 
the intended use (when applicable)  
 
 
Questions and Answers about Files in the Chemistry, Safety and Environmental Folders 
of a Petition Submission 
10. What files should I place directly in the Chemistry folder (rather than 
under any Chemistry subfolders)?  
Table IV-5 shows the files you should place directly in the Chemistry folder.  
 
Table IV-5 
Files in the Chemistry Folder of a Petition Submission 
 
File Name  Information in File  Applicable 
Regulatory 
Citation or 
Guidance 
Identity_..._YYYY-MM- The physical, chemical, and biological  21 CFR 71.1(c) A 
DD.pdf  properties of the additive, as well as any  21 CFR 171.1(c) A 
information about the chemical identity 
and composition of the additive not 
included on Form FDA 3503 
UseAndTechnicalEffect_..._  Information about the foods in which the  21 CFR 71.1(c) B 
YYYY-MM-DD.pdf  additive will be used, the levels of use in  21 CFR 171.1(c) B 
such foods, and the purpose for which the  21 CFR 170.3(n) 
additive will be used, and all directions,  21 CFR 170.3(o) 
recommendations, and suggestions 
regarding the proposed use 
  30 Contains Nonbinding Recommendations 
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File Name  Information in File  Applicable 
Regulatory 
Citation or 
Guidance 
Labeling_..._ YYYY-MM-   CAP: Specimens of the labeling  21 CFR 71.1(c) B 
DD.pdf  proposed for the additive   21 CFR 171.1(c) B 
  FAP: Specimens of the labeling 
proposed for the additive and any 
labeling that will be required by 
applicable provisions of the Act on the 
finished food by reason of the use of 
the additive  
ManufacturingMethod_..._  Information about the manufacturing  21 CFR 71.1(c) A 
YYYY-MM-DD.pdf  process and any person other than the  21 CFR 171.1(c) A 
petitioner who performs any  21 CFR 171.1(j) 
manufacturing, processing, and packing   
operations for the additive 
Residues_..._ YYYY-MM- How residues of the additive may occur in  21 CFR 71.1(c) B 
DD.pdf  food when the additive would be used in  21 CFR 171.1(c) B 
packaging and what residues may 
reasonably be anticipated  
Specifications_..._ YYYY-   CAP: Specifications prescribing the  21 CFR 71.1(c) A 
MM-DD.pdf  additives component(s) and  21 CFR 171.1(c) A 
identifying and limiting the reaction  Ref. 7 
byproducts and other impurities.   Ref. 8  
  FAP: Specifications prescribing the 
minimum content of the desired 
component(s) and identifying and 
limiting the reaction byproducts and 
other impurities. Where such 
information is not available, you 
should include a statement as to the 
reasons why. 
  31 Contains Nonbinding Recommendations 
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File Name  Information in File  Applicable 
Regulatory 
Citation or 
Guidance 
ExposureEstimates_..._    The basis for any alternative approach,  21 CFR 71.1(c) E 
YYYY-MM-DD.pdf  other than the approach described in  Ref. 7  
Refs. 7 and 9, that a petitioner wishes  Ref. 9  
OFAS to use in estimating daily 
intake. 
  CAP: Complete data to allow us to 
consider the probable consumption of, 
and/or other relevant exposure from 
the additive and of any substance 
formed in or on food, drugs, or 
cosmetics because of such additive; 
and the cumulative effect, if any, of 
such additive in the diet of man or 
animals. 
 
 
11. What files should I place in the Chemistry Studies subfolders?  
Table IV-6 shows the subfolders and files you should place in the Studies subfolder of the 
Chemistry folder.  
 
Table IV-6 
Subfolders and Files in the Studies Subfolder of the Chemistry Folder of a Petition 
 
Folder/  File Name  Information in the File  Applicable 
Subfolder  Regulatory 
Citation or 
Guidance 
Chemistry/  StabilityData_..._  Stability data and, when needed, the  21 CFR 71.1(c) A 
Studies/  YYYY-MM-DD.pdf  expiration period.  A CAP also must  21 CFR 171.1(c) A 
Stability  include any packaging and labeling  Ref. 7 
precautions needed to preserve  Ref. 8  
stability.   
  32 Contains Nonbinding Recommendations 
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Folder/  File Name  Information in the File  Applicable 
Subfolder  Regulatory 
Citation or 
Guidance 
Chemistry/  IntendedEffect_..._  FAP Only: Data establishing that the  21 CFR 171.1(c) C 
Studies/  YYYY-MM-DD.pdf  food additive will have the intended  Ref. 7 
Intended  physical or other technical effect or   
Effect  that it may reasonably be expected to   
become a component, or to affect the 
characteristics, directly or indirectly, 
of food and the amount necessary to 
accomplish this. These data should 
include information in sufficient 
detail to permit evaluation with 
control data. 
Chemistry/  MigrationData_..._  Information sufficient to permit  21 CFR 171.1(c) B 
Studies/  YYYY-MM-DD.pdf  estimation of consumer exposure to a  Ref. 7 
Migration  food additive.   
 
Chemistry/  [Sweetness Potency   Study of Sweetness Potency  N/A 
Studies/  ]_..._ YYYY-MM-
Other   DD.pdf 
 
 
12. What files should I place in the Chemistry Methods and References 
subfolders?  
Table IV-7 shows the files you should place in the Chemistry Methods and References 
subfolders.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  33 Contains Nonbinding Recommendations 
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Table IV-7 
Files in the Chemistry Methods and References Subfolders of a Petition Submission 
 
Folder/  File Name  Information in the File  Applicable 
Subfolder  Regulatory 
Citation or 
Guidance 
Chemistry/  AnalyticalMethod_..._  FAP and CAP: A description of  21 CFR 71.1(c) C 
Methods  YYYY-MM-DD.pdf  practicable methods to determine  21 CFR 171.1(c) D
the amount of the additive in the  Ref. 7 
raw, processed, and/or finished food  Ref. 8  
and of any substance formed in or   
on such food because of its use. 
CAP: A description of practicable 
methods to determine the pure color 
and all intermediates, subsidiary 
colors, and other components of the 
color additive. 
Chemistry/  See Appendix 12 Any references to the scientific  Ref. 7 
 
References  literature   Ref. 8  
Ref. 10 
Ref. 2
 
 
 
13. What files should I place directly in the Safety folder (rather than under 
any Safety subfolders)?  
Table IV-8 shows the files you should place in the Safety folder.  
 
Table IV-8 
Files in the Safety Folder of a Petition Submission 
 
File Name  Information in File  Applicable 
Regulatory 
Citation or 
Guidance 
ToxicologyNarrative_..._  A summary of the results of, and  Ref. 2 
YYYY-MM-DD.pdf  conclusions from, safety studies included   
in your petition submission and relevant 
safety studies in the scientific literature.   
 
 
  34 Contains Nonbinding Recommendations 
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14. What files should I place in the Safety Studies subfolders?  
Table IV-9 shows examples of the files you should place in the Studies subfolders.  
 
 
 
Table IV-9 
Folders and Files in the Studies Subfolder of the Safety Folder of a Petition 
Submission 
 
Subfolder  Examples of File Names  Applicable 
Regulatory 
Citation or 
Guidance 
Safety/Studies/  Ames_..._YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
GeneticToxicityStudies  21 CFR 171.1(c) E 
Ref. 15 
Ref. 16
 
Safety/Studies/  ShortTermToxicity_..._YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
ShortTermToxicity  21 CFR 171.1(c) E 
StudiesRodents  Ref. 15 
Ref. 16
 
Safety/Studies/  ShortTermToxicity_..._YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
ShortTermToxicity  21 CFR 171.1(c) E 
StudiesNon-Rodents  Ref. 15 
Ref. 16
 
Safety/Studies/  SubchronicToxicity_..._YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
SubchronicToxicity  21 CFR 171.1(c) E 
StudiesRodents  Ref. 15 
Ref. 16
 
Safety/Studies/  SubchronicToxicity_..._YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
SubchronicToxicity  21 CFR 171.1(c) E 
StudiesNon-Rodents  Ref. 15 
Ref. 16
 
Safety/Studies/  ChronicToxicity_..._YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
OneYearToxicity  21 CFR 171.1(c) E 
StudiesNon-Rodents  Ref. 15 
Ref. 16
 
Safety/Studies/  ChronicToxicity_..._YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
ChronicToxicityOr  21 CFR 171.1(c) E 
CombinedChronic  Ref. 15 
Toxicity/Carcinogenicity  Ref. 16
 
StudiesRodents 
  35 Contains Nonbinding Recommendations 
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Subfolder  Examples of File Names  Applicable 
Regulatory 
Citation or 
Guidance 
Safety/Studies/  Carcinogenicity_..._YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
CarcinogenicityStudies  21 CFR 171.1(c) E 
Rodents  Ref. 15 
Ref. 16
 
Safety/Studies/  ReproductiveToxicity_..._YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
ReproductionStudies  21 CFR 171.1(c) E 
Ref. 15 
Ref. 16
 
Safety/Studies/  ReproductiveToxicityTeratology_..._YYYY-MM- 21 CFR 71.1(c) D 
DevelopmentalToxicity  DD.pdf  21 CFR 171.1(c) E 
Studies  Ref. 15 
Ref. 16
 
Safety/Studies/  Immunotoxicity_..._YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
ImmunotoxicityStudies  21 CFR 171.1(c) E 
Ref. 15 
Ref. 16
 
Safety/Studies/  PharmacokineticRats_..._YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
MetabolismAnd  21 CFR 171.1(c) E 
PharmacokineticStudies  Ref. 15 
Ref. 16
 
Safety/Studies/  Neurotoxicity_..._MMMM-MM-DD.pdf  21 CFR 71.1(c) D 
NeurotoxicityStudies  21 CFR 171.1(c) E 
Ref. 15 
Ref. 16
 
Safety/Studies/  HumanClinical_..._ YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
HumanClinicalStudies    21 CFR 171.1(c) E 
Ref. 15 
Ref. 16
 
Safety/Studies/  Epidemiology_..._YYYY-MM-DD.pdf  Ref. 15 
EpidemiologyStudies  Ref. 16
 
Safety/Studies/  OcularIrritation_..._YYYY-MM-DD.pdf  Ref. 17
 
OcularStudies 
Safety/Studies/  Dermal_..._YYYY-MM-DD.pdf  Ref. 17
 
DermalStudies 
Safety/Studies/  [DescriptiveName]_..._YYYY-MM-DD.pdf  21 CFR 71.1(c) D 
OtherStudies  21 CFR 171.1(c) E 
 
 
 
 
  36 Contains Nonbinding Recommendations 
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15. What files should I place in the Environmental folder of a petition?  
Table IV-10 shows the files you should place in the Environmental folder.  
 
 
 
Table IV-10 
Folders and Files in the Environmental Folder of a Petition Submission Roadmap 
 
Folder/  File Name  Information in the File  Applicable 
Subfolder  Regulatory 
Citation or 
Guidance 
Environmental  EA_ ..._YYYY-MM- Concise public document that  21 CFR 71.1(c) J 
DD.pdf  provides sufficient evidence and  21 CFR 171.1(c) H 
analysis for FDA to determine  21 CFR 25.40 
whether to prepare an  Ref. 19
 
Environmental Impact 
Statement (EIS) or a Finding of 
No Significant Impact (FONSI) 
Environmental  ClaimCategorical  (1) The section of the CFR  21 CFR 71.1(c) J 
Exclusion_..._YYYY- under which the categorical  21 CFR 171.1(c) H 
MM-DD.pdf  exclusion is claimed;   21 CFR 25.15 
(2) A statement of compliance  21 CFR 25.30 
with the categorical exclusion  21 CFR 25.32 
criteria; and   Ref. 19
 
(3) A statement that, to the 
submitter's knowledge, no 
extraordinary circumstances 
exist that require submission of 
an Environmental Assessment. 
Environmental/  MarketVolume_  Data and information that are  21 CFR 25.51 
Confidential  ..._YYYY-MM- protected from disclosure under  Ref. 19
 
Environmental  DD.pdf  18 U.S.C. 1905, 21 U.S.C. 
Information  331(j) or 360j(c) 
Environmental/ ..._YYYY-MM- Study reports of environmental  Ref. 19
 
Studies  DD.pdf  fates or effects studies 
Environmental/ ..._YYYY-MM- Environmental literature  Ref. 19
 
References  DD.pdf  references (published studies, 
excerpts) 
 
 
 
  37 Contains Nonbinding Recommendations 
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C. Electronic Amendments and Updates to Petition Submissions 
16. What recommendations apply to amendments and updates to petition 
submissions? 
You should refer to Section III.F of this document for general recommendations applying to 
amendments and updates in electronic format.   
 
When transmitting any amendment or update to a petition submission, you should organize your 
submission into individual files addressed to specific topic areas (administrative, chemistry, 
safety, or environmental), even if an amendment responds to multiple questions we sent you in a 
single letter.  You then should place these files in appropriate folders/subfolders according to the 
Petition Submission Roadmap.   
 
For example, an amendment to a FAP could include two Chemistry files (one to revise 
specifications and another to revise an analytical method), a Safety file responding to our 
questions about a subchronic toxicity study conducted in dogs, and a file containing a revised 
Environmental Assessment.  In this example, you would: 
  Place the file containing revised specifications directly in the Chemistry folder;  
  Place the file containing the revised analytical method in the Chemistry/Methods 
subfolder;  
  Place the file containing the response to our questions about the toxicology study in the 
Safety/Studies/Subchronic Toxicity Non-Rodents subfolder; and  
  Place the revised Environmental Assessment in the Environmental Assessment folder. 
 
17. What files should I place in the Incoming Correspondence subfolder?  
Table IV-11 shows the files you should place in the two subfolders of the Incoming 
Correspondence folder.  
 
Table IV-11 
Files in the Additional Information/Incoming Correspondence Subfolder for a Petition 
Submission 
 
Subfolder  File Name  Information in the File 
IncomingCorrespondence/  YYYY-MM-DD_  Form with responsive material 
Amendment   Form3503_....pdf   completed for an amendment. 
   
 
YYYY-MM- An amendment that does not fit in 
DD_Amendment_...pdf  any of the other folders (e.g. 
Chemistry, Safety, 
Environmental,etc) 
IncomingCorrespondence/  YYYY-MM-DD_  Form with responsive material 
Update  Form3503_....pdf   completed for an update. 
  38 Contains Nonbinding Recommendations 
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Subfolder File Name Information in the File 
YYYY-MM- An update that does not fit in any of 
DD_Update_...pdf  the other folders (e.g. Chemistry, 
Safety, Environmental, etc) 
18.Where can I find an example of a foldering structure with an amendment
for a FAP?
Below is an example of an amendment to an existing, fictional FAP (FAP 0A9999), arranged in 
the standard roadmap.  Folder names are in bold and file names are in italics; for clarity, we 
omitted empty folders.  In this example, the amendment responds to an FDA letter dated 11-20-
2006, which requested further information.  Note that each file name begins with the date the 
amendment is submitted (see Section III.C and Appendix 12 of this document for file naming 
conventions).  We would place these amendment documents in the corresponding folders in our 
database file for FAP 0A9999, alongside documents previously submitted.  (You should not re-
submit any previously submitted documents.) 
 FAP 0A9999
o Administrative
 Incoming Correspondence
 Amendment
o 2006-12-07_Form FDA 3503_InResponseToFDA2006-11- 
20 Letter.pdf
o Chemistry
 Methods
 2006-12-07_ResponsesToFDA2006-11- 
20ChemistryQuestions_(AnalyticalMethod_ ...).pdf
o Safety
 Studies
 SubchronicToxicityStudies
o 2006-12-07_SubchronicToxicity_Study5567_ 
EmulsifierX_Rats_OralGavage_ 2000-11-08.pdf
o Environmental
 2006-12-07_EA_Revised_EmulsifierX.pdf
o Food and Color Master Files
19.How do the parts on Form FDA 3503 relate to the elements of FMFs and 
CMFs?
Table IV-12 shows the elements of FMFs and CMFs and links each element to the applicable 
part of Form FDA 3503.   
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Table IV-12 
Elements of FMFs and CMFs as Shown on Form FDA 3503 
 
Element of FMFs and CMFs  Applicable Part on Form FDA 3503 
Introductory information about the  I 
submission 
Information about the company  II 
responsible for the master file (and any 
attorney or agent acting on behalf of that 
company) 
General administrative information   III 
Information specific to Food or Color  IV.C 
Master Files 
Identity  V  
Administrative Technical (when a  VI 
submission is in advance of a planned 
FAP or CAP) 
Chemistry  VI 
Safety  VI 
Environmental  VI 
Signature  VII 
N/A  VIII (List of Attachments) 
 
 
20. How should I organize an electronic master file submission prepared 
according to the elements on Form FDA 3503? 
You should organize an electronic master file submission prepared according to the elements on 
Form FDA 3503 using the foldering structure available in a downloadable Petition Roadmap (see 
instructions in Appendix 1 and the roadmap in Appendix 15).  In general, you should follow the 
recommendations in Sections III and IV.B of this document for more detailed information about 
organizing an electronic master file submission according to the elements of Form FDA 3503. 
 
  40 Contains Nonbinding Recommendations 
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V.  Information Specific to Food Contact Notification Submissions 
and Pre-Notification Consultation Submissions 
 
Section V of this document addresses FCN and PNC submissions for food contact substances.  
You must submit an FCN in accordance with 21 CFR 170.101.  You voluntarily submit a PNC 
prior to submitting a FCN to facilitate your preparation of a FCN.  We assign a file number 
(FCN No. or PNC No., respectively) to your submission and review your submission.  If we do 
not object to your FCN within 120 days, your FCN becomes effective.  If we object to your 
FCN, we will send you an FCN objection letter; if we do so within 120 days, your FCN will not 
become effective.  If we and you agree that you may submit a food additive petition proposing 
the approval of the FCS for the use in your FCN, we will consider that you have withdrawn your 
FCN on the date we receive your petition. 
 
A.  General Information about Food Contact Notification 
Submissions  
1.  When do I use Form FDA 3480? 
You must use Form FDA 3480 when transmitting an original FCN submission (21 CFR 
101.101). 
 
You should use Form FDA 3480 when transmitting: 
  A PNC as described in Ref. 5; and  
  A FMF regarding a food contact substance. 
 
2.  When should I use Form FDA 3480-A? 
You should use Form FDA 3480-A when transmitting an amendment to a previously submitted 
FCN, PNC, or FMF regarding a FCS.  Form FDA 3480-A is much shorter than Form FDA 3480. 
 
3.  How do I determine whether to send FDA a Pre-Notification Consultation 
for a FCS or a Food Master File for a FCS? 
You should send us a PNC if your reason for providing us with information relevant to a FCS is 
to consult with us to facilitate preparation of a complete FCN in the future (Ref. 5).  
 
You should send us a FMF if your reason for providing us with information relevant to a FCS is 
outside the context of your own preparation of a complete FCN.  For example, you would submit 
a FMF submission for a FCS if you are providing confidential data or information in support of a 
FCN submitted to us by a manufacturer who does not have access to these confidential data or 
information.   
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4.  How do the parts on Form FDA 3480 relate to the elements of a FCN? 
Table V-1 shows the elements of FCNs and links each element to the applicable part of Form 
FDA 3480.   
 
Table V-1 
Elements of FCNs as Shown on Form FDA 3480 
 
 
Element of FCNs  Applicable Part on Form FDA 3480 
General information   I 
Chemistry information   II 
Safety information   III 
Environmental  IV 
Certification  V 
List of Attachments   VI 
 
5.  How should I organize a new FCN submission?  
You should organize a new FCN submission as a series of documents presented in an order 
corresponding to that presented on Form FDA 3480.  If you include any data or information not 
identified on Form FDA 3480 (e.g., raw material specifications and technical bulletins), you 
should place these data or information in a logical place in your submission based on the type of 
information.   
 
6.  What should I include for the proposed language for the FCN listing? 
You should include the language that you propose for your FCN in our Inventory of Effective 
Food Contact Substance (FCS) Notifications (the Inventory), including the FCS identity, 
notifier, manufacturer/supplier(s), and limitations and specifications.  See the Inventory for 
examples (Ref. 3).   
 
7.  Why should I include proposed language for the FCN listing? 
Including proposed language for the FCN listing will help to ensure that we understand the 
conditions of use that are the subject of your FCN.  Under 21 CFR 170.101(b), your FCN must 
include all data and other information that form the basis of the determination that the FCS is 
safe under the intended conditions of use.   
 
B.  Food Contact Notification Submissions in Electronic Format  
8.  How should I organize an electronic FCN submission? 
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You should organize an electronic FCN submission using the foldering structure called the FCN 
Submission Roadmap (see instructions in Appendix 3a and the roadmap in Appendix 15).  The 
entire FCN Submission Roadmap is organized under the folder entitled Main directory.  The 
Main directory includes four first-level folders.  Three of these first-level folders include 
second-level subfolders, and one of these folders (i.e., the Safety folder) includes third-level and 
fourth-level subfolders.  We show the FCN Submission Roadmap, using an outline format, in 
Figure V-1, below.  In the various subfolders, Figure V-1 uses the convention [Etc] to mean 
that there are more folders in the FCN Roadmap (not shown in the outline) that continue the 
pattern of the outline. 
Figure V-1 
Outline Representing the FCN Submission Roadmap 
 Main directory
o Administrative
o Chemistry
 Studies
 References
o Environmental
 Confidential Environmental Information
 Studies
 References
o Safety
 Chemical Name 1*
 References
 Studies
o Genetic Toxicity Studies
o Short Term Toxicity Studies Rodents
o Short Term Toxicity Studies Non-Rodents
o Subchronic Toxicity Studies Rodents
o Subchronic Toxicity Studies Non-Rodents
o One Year Toxicity Studies Non-Rodents
o Chronic Toxicity or Combined Chronic
          Toxicity/Carcinogenicity Studies Rodents 
o Carcinogenicity Studies Rodents
o Reproduction Studies
o Developmental Toxicity Studies
o Immunotoxicity Studies
o Metabolism and Pharmacokinetic Studies
o Neurotoxicity Studies
 Chemical Name 2*
 References
 Studies
o [Etc]
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 [Etc]
* The original FCN Submission Roadmap includes 10 Chemical Name # folders.  You would
rename the Chemical Name 1, Chemical Name 2, etc. folders to specific chemical names of
substances (e.g., the FCS or impurities) for which you have included safety studies (see
Conventions for Naming Files in Appendix 12).  You may delete or ignore remaining Chemical
Name # folders that you do not use.  Our system will not import empty folders.
9. When should I use the specific folders and subfolders in the FCN
Submission?
You should use these folders and subfolders as shown in Table V-2.  You should not place any 
specific files directly in Main directory. Main directory only contains folders.   
Table V-2 
When to Use Specific Folders and Subfolders in the Main Directory of a FCN 
Submission Roadmap*  
Folder/Subfolder  When to Use it 
Administrative folder  Any time you transmit a new submission, an amendment, or a 
redacted electronic file(s)  
Chemistry Folder and  Any time you transmit chemistry data or information, 
Applicable Subfolders  regardless of whether you are transmitting a new submission 
or an amendment 
Environmental Folder and  Any time you transmit environmental data or information, 
Applicable Subfolders  regardless of whether you are transmitting a new submission 
or an amendment 
Safety Folder and Applicable  Any time you transmit safety data or information, regardless of 
Subfolders  whether you are transmitting a new submission or an 
amendment 
*If you are transmitting an amendment to your submission, you should re-name the Main
directory to the file number we assigned to it (e.g. FCN000999).
10.How should I name files in an electronic FCN submission?
You should name each file using both generic and specific elements as described in Section III.C 
and Appendix 12 of this document.  Generic elements in the file names specific to FCN 
submissions are included in Tables V-3 through V-9 (below).  See Appendix 12 for examples of 
complete file names..    
11.What files should I place in the Administrative folder of a FCN
submission?
Table V-3 shows the files you should place in the Administrative folder.  
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Table V-3 
Files in the Administrative Folder of a FCN Submission 
 
  Information in File  Applicable 
File Name  Regulatory 
Citation and 
Guidance 
Form3480_..._YYYY-MM-DD.pdf   Some specific information in the  21 CFR 170.101 
submission and a list of  Ref.5
 
documents included 
CoverLetter_..._YYYY-MM-DD.pdf   Letter accompanying the  N/A* 
submission if you choose to send 
a letter in addition to Form FDA 
3480 
DesignationOfNondisclosableInformation A document describing the data  21 CFR 20.61(d)
_..._YYYY-MM-DD.pdf  or information in your 
submission that you view as 
nondisclosable (see Section II.E 
of this document) 
ProposedLanguageForFCNListing_..._  Proposed Language for your  21 CFR 
YYYY-MM-DD.pdf  FCN listing  170.101(b) 
RedactedBySubmitter_..._YYYY-MM- Copy(ies) of one or more files in  N/A 
DD.pdf  your submission modified by 
deletion of data or information 
you view as trade secret or 
confidential information, if you 
choose to include these 
* N/A means Not applicable. 
 
12.  What files should I place directly in the Chemistry folder (rather than in 
any Chemistry subfolders)?  
Table V-4 shows the files you should place directly in the Chemistry folder.  
 
  45 Contains Nonbinding Recommendations 
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Table V-4 
Files in the Chemistry Folder of a FCN Submission 
 
File Name  Information in File  Applicable Item 
on Form FDA 
3480 and 
Guidance*   
Identity_..._YYYY-MM-DD.pdf  A description of the FCS, including  Form FDA 3480 
chemical formula(s), structure(s) and  II.A.5 
molecular weight(s)  (Description) 
Ref. 10
 
Structure_..._YYYY-MM- A structure for the FCS and for  Form FDA 3480 
DD.mol  substances that may migrate into food  II.A.5 
from use of the FCS (see Part III.C of  (Description) 
this guidance for file formats)  Ref. 10
 
IR_..._YYYY-MM-DD.pdf  Spectroscopic data characterizing the  Form FDA 3480 
NMR_..._YYYY-MM-DD.pdf  FCS  II.A.6 
MassSpec_..._YYYY-MM- (Characterization) 
DD.pdf  Ref. 10
 
ManufacturingProcess_..._  A complete description of the  Form FDA 3480 
YYYY-MM-DD.pdf  manufacturing process   II.B.1 
(Manufacturing 
Process) 
Ref. 10
 
RawMaterialSpecs_..._ YYYY- Specifications for reagents, solvents,  Ref. 10
 
MM-DD.pdf  catalysts, purification aids, etc., used in 
the manufacturing process 
Impurities_..._YYYY-MM- Supporting data used to arrive at the  Form FDA 3480 
DD.PDF  levels of impurities reported on Form  II.C.1 
FDA 3480, and/or information  (Impurities) 
supporting that no migration to food is  Ref. 10
 
expected 
  46 Contains Nonbinding Recommendations 
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File Name  Information in File  Applicable Item 
on Form FDA 
3480 and 
Guidance*   
Specifications_..._YYYY-MM- Physical and chemical specifications for  Form FDA 3480 
DD.pdf  the FCS  II.C.2 
(Specifications) 
Ref. 10
 
MolWeightProfile_..._YYYY- The maximum percentage of oligomeric  Form FDA 3480 
MM-DD.pdf  species (not including residual  II.A.7 
monomers, reactants, or solvents) below  (Molecular Weight 
1000 Daltons and supporting data and  Profile) 
analytical methods  Ref. 10
 
IntendedUse_..._ YYYY-MM- Use level of the FCS, the types of food  Form FDA 3480 
DD.pdf  contact articles in which it may be used,  II.D.1,2 
types of food, conditions of use, etc.  (Intended Use) 
Ref. 10
 
TechnicalEffect_..._ YYYY-MM- A description of the intended technical  Form FDA 3480 
DD.pdf  effect of the FCS; summary of data  II.D.3 (Intended 
showing the FCS will achieve the  Technical Effect) 
intended technical effect and that the  Ref. 10
 
proposed use level is the minimum level 
required to accomplish the intended 
technical effect 
Stability_..._YYYY-MM-DD.pdf  Description of any chemical breakdown  Form FDA 3480 
process that the FCS may undergo  II.E 
during either its intended use in the  (Stability of the 
manufacture of a food contact article or  FCS) 
during migration testing**  Ref. 10
 
MigrationCalculation_..._YYYY- A description of the mathematical  Form FDA 3480 
MM-DD.pdf  approach used in estimating migration  II.F.2 
levels of the FCS to food and/or any of  (Migration 
its constituents.  Calculation 
Option) 
Ref. 10
 
ExposureCalculation_..._ YYYY- Representative calculations for the  Form FDA 3480 
MM-DD.pdf  dietary concentration (DC) and  II.G 
estimated daily intake (EDI) for all  (Estimated Daily 
substances migrating to food as a result  Intake) 
of the intended use of the FCS  Ref. 10
 
* The applicable section of the regulation is 21 CFR 170.101(b). 
** When applicable, a study on the stability of the FCS is placed in the Studies subfolder of 
the Chemistry folder (see Table V-5). 
 
  47 Contains Nonbinding Recommendations 
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13. What files should I place in the Studies and References subfolders of 
the Chemistry folder of a FCN submission?  
Table V-5 shows the files you should place in the Studies and References subfolders of the 
Chemistry folder.  
 
Table V-5 
Files in the Studies and References Subfolders of the Chemistry Folder of a FCN 
Submission Roadmap 
 
Folder/  File Name  Information in the File  Applicable Item 
Subfolder  on Form FDA 
3480 and 
Guidance*   
Chemistry/  StabilityStudy_..._YYYY- A study on the stability of the  Form FDA 3480 
Studies  MM-DD.pdf  FCS **  II.E 
  (Stability of the 
FCS) 
Ref. 10
 
Chemistry/  MigrationStudy_..._YYYY- A study determining the  Form FDA 3480 
Studies  MM-DD.pdf  expected levels of migration of  II.F.1 
  the FCS or its components to  (Migration 
food  Testing Option) 
Ref. 10
 
Chemistry/  See Appendix 12 Any references to the scientific  Ref. 10
   
References  literature  
* The applicable section of the regulation is 21 CFR 170.101(b). 
** When applicable, a narrative description of a chemical breakdown process that the FCS may 
undergo during either its intended use in the manufacture of a food contact article or during 
migration testing is placed directly in the Chemistry folder (see Table V-4). 
 
14. What file should I place directly in the Safety folder of a FCN submission 
(rather than in any Safety subfolders)?   
Table V-6 shows the file you should place directly in the Safety folder. 
 
Table V-6 
Files in the Safety Folder of a FCN Submission 
 
 
Folder/Subfolder  File Name  Information in File  Applicable Item on 
Form FDA 3480 and 
Guidance 
Safety  SafetyNarrative_..._  A summary  Form FDA 3480 III.1 
YYYY-MM-DD.pdf  describing the  (Safety Narrative) 
  48 Contains Nonbinding Recommendations 
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scientific basis of   
your determination  Ref. 18
 
that the food contact 
substance (FCS) is 
safe under the 
conditions of use 
 
15. What files should I place directly in the subfolder for a specific chemical in 
the Safety folder of a FCN submission (rather than in any subfolder for 
that chemical)?  
Table V-7 shows the files you should place directly in the subfolder for a specific chemical in the 
Safety folder.  
 
Table V-7 
Files in the Subfolder for a Specific Chemical in the Safety Folder of a FCN Submission 
Roadmap 
 
Folder/Subfolder  File Name  Information in File  Applicable 
Item on Form 
FDA 3480 
and 
Guidance* 
Safety/ChemicalName1  CTP_..._.pdf  A Comprehensive  Form FDA 
Toxicology Profile (CTP),  3480 III.2 
for the specific chemical,  Ref. 18
 
including detailed study 
summaries  
Safety/ChemicalName1  LiteratureSearch_..._.pdf Data or information that  Ref. 18
 
the notifier relies upon to 
prepare the CTP 
* The applicable section of the regulation is 21 CFR 170.101(a). 
 
16. What files should I place in the Studies and References subfolders for a 
specific chemical in the Safety folder?  
Table V-8 shows the files you should place in the subfolders of the Studies subfolder of the 
Safety subfolder for a given chemical.   
 
 
Table V-8 
Example Subfolder and File in the Safety/Chemical Name 1/ Studies Subfolder and files 
in the Safety/Chemical Name 1/ References subfolder of an FCN Submission 
 
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Subfolder  Examples of File Names  Applicable 
Regulatory 
Citation, Part on 
Form FDA 3480, 
and Guidance 
Safety/ ChemicalName1/Studies/  Ames_..._YYYY-MM-DD.pdf  Form FDA 3480 
GeneticToxicityStudies  III.3 
Ref. 18 
Ref. 16
 
Safety/ChemicalName1/References  (Titles of the reference, citation,...)   Ref. 18 
See Appendix 12 Ref. 16
   
 
 
17. What files should I place in the Environmental folder of a FCN 
submission?  
Table V-9 shows the files you should place in the Environmental folder, and in the 
Confidential Environmental Information, References and Studies subfolders.     
 
Table V-9 
Folders and Files in the Environmental Folder of a FCN Submission 
 
Folder/  File Name  Information in the File  Applicable 
Subfolder  Regulatory 
Citation, Part on 
Form FDA 3480, 
and Guidance 
Environmental  EA...-YYYY-MM- Concise public document that  21 CFR 170.101(d) 
DD.pdf  provides sufficient evidence and  Form FDA 3480 
analysis for FDA to determine  Part IV 
whether to prepare an  21 CFR 25.40 
Environmental Impact  Ref. 19
 
Statement (EIS) or a Finding of 
No Significant Impact (FONSI) 
Environmental   FIFRA Label_..._  (1) A copy of the current FIFRA  21 CFR 170.101(d) 
YYYY-MM-DD .pdf  registration label for the  Form FDA 3480 IV 
  substance that has the same use  21 CFR 25.32(q) 
requested in the submission; and  Ref. 19 
(2) The proposed FIFRA   
registration label that includes 
the food contact use for which 
the sponsor intends to request an 
amendment from EPA. 
  50 Contains Nonbinding Recommendations 
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Folder/  File Name  Information in the File  Applicable 
Subfolder  Regulatory 
Citation, Part on 
Form FDA 3480, 
and Guidance 
Environmental/  MarketVolume...- Data and information that are  21 CFR 170.101(d) 
Confidential  YYYY-MM-DD.pdf  protected from disclosure under  Form FDA 3480 IV 
Environmental  18 U.S.C. 1905, 21 U.S.C.  Ref. 19
 
Information  331(j) or 360j(c) 
Environmental/ ...YYYY-MM-DD.pdf  Study reports of environmental  Ref. 19
 
Studies  fates or effects studies 
Environmental/ ...YYYY-MM-DD.pdf  Environmental literature  Ref. 19
 
References  references (published studies, 
excerpts) 
 
 C.  Electronic Amendments to Food Contact Notifications 
18. What recommendations apply to electronic amendments to FCN 
submissions? 
You should first refer to Section III.F of this document for general recommendations applying to 
amendments in electronic format.   
 
You should use Form FDA 3480-A (rather than Form FDA 3480) when transmitting an 
amendment to a FCN.  Form FDA 3480-A is much shorter than Form FDA 3480. 
 
When transmitting any amendment to a FCN submission, you should organize your submission 
into individual files, each addressed to specific topic areas (administrative, chemistry, safety, or 
environmental), even if your amendment responds to multiple questions we sent you in a single 
letter.  You then should place these files in the appropriate folders/subfolders (according to the 
content of the file) in the FCN Submission Roadmap.   
 
For example, an amendment to a FCN might include two Chemistry files (one to revise 
specifications and another to revise a migration study), a Safety file responding to our questions 
about the toxicity of an impurity, known as 3-AP-PEG (CAS Reg. No. 34901-14-9), and a file 
containing a revised Environmental Assessment.  In this example, you would: 
  Place the file containing revised specifications directly in the Chemistry folder;  
  Place the file containing the migration study revisions in the Chemistry/Studies 
subfolder;  
  Place the file containing the response to our questions about the toxicity of 3-AP-PEG in 
the Safety/3-AP-PEG (34901-14-9) subfolder ; and  
  Place the revised Environmental Assessment in the Environmental folder. 
 
(See the file structure for this example under the next question.) 
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19. May I see  an example of the file structure for  a complete amendment to a 
FCN? 
The outline  below is an example of an amendment  to an existing, hypothetical FCN (FCN 
009999), arranged in the standard submission roadmap.  Folder names are in bold and file names 
are  in italics;  for  clarity, we  omitted empty folders.  In this example, the amendment responds to 
an FDA letter dated 11-20-06, which requested further information.  Note that each file name  
begins with the date the amendment is submitted  (i.e., the  date entered on page  1 of Form FDA  
3480-A) (see  Section III.C and Appendix 12 of this document for recommendations for  naming 
files).  FDA would place these amendment documents in the corresponding folders  in our 
database  file for FCN 009999, alongside  documents previously submitted.  (You should not re-
submit any previously submitted documents.)  
  FCN 009999 
o  Administrative 
2006-12-07_Form FDA 3480-A_InResponseToFDA2006-11-20 Letter.pdf 
 
o  Chemistry 
2006-12-07_ResponsesToFDA2006-11-
 
20ChemistryQuestions_(Impurities_MigrationStudy_ ...).pdf 
2006-12-07_ImpuritiesBatchData(TIPA, 34901-14-9, 
 
catalyst)_Chromatograms&Calculations.pdf 
o  Studies 
2006-12-07_MigrationStudy_RevisedChromatograms_....pdf 
 
o  Environmental 
2006-12-07_EA_Revised_HPNH_ InPolypropylene.pdf 
 
o  Safety 
3-AP-PEG (34901-14-9) 
 
  2006-12-07_Response to FDA2006-06-20Question-Toxicity of 3-
AP-PEG 
D.  Pre-Notification Consultations and Food Master Files for Food 
Contact Substances 
20. How do the parts on Form FDA 3480 relate to the elements of PNCs and 
FMFs for  FCSs? 
Table V-10 shows the potential elements of PNCs and links each element to the applicable part  
of Form FDA 3480.  PNCs and FMFs sometimes contain only a subset of the information (e.g., 
specific  chemistry information) that would be  included in a  FCN for a FCS. 
Table V-10 
Elements of PNCs and FMFs  as Shown  on Form FDA 3480 
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Element of PNCs and FMFs  Applicable Part on Form FDA 3480 
General information   I 
Chemistry information   II 
Safety information   III 
Environmental  IV 
Certification  V 
List of Attachments   VI 
 
21. How should I organize an electronic PNC submission? 
You should organize an electronic PNC submission using the foldering structure available in a 
downloadable FCN Submission Roadmap (see instructions in Appendix 3a and the roadmap in 
Appendix 15).  In general, you should follow the recommendations in Sections III and V.B of 
this document for more detailed information about organizing an electronic PNC submission. 
 
VI.  Information Specific to Generally Recognized as Safe Notice 
Submissions 
 
Section VI of this document addresses submission of GRAS notices.  The GRAS notification 
procedure2 is a voluntary procedure in which you inform us of your view that a particular use of 
a substance is exempt from the premarket approval requirements of the Act based on your 
determination that such use is GRAS in accordance with 21 CFR 170.30.  We assign a file 
number (GRAS Notice No. (GRN)) to your submission and respond to you by letter.  
A.  General Information about Generally Recognized as Safe Notice 
Submissions  
1.  How do the parts on Form FDA 3667 relate to the elements of a GRAS 
notice? 
Table VI-1 shows the elements of a GRAS notice and links each element to the applicable part of 
Form FDA 3667.   
 
Table VI-1 
Elements of a GRAS Notice as Shown on Form FDA 3667 
 
Element of a GRAS Notice  Applicable Part on Form FDA 3667 
Introductory information about the submission  I 
                                                 
2 We have issued a proposed rule that would establish this procedure in 21 CFR 170.36 (Federal Register of April 
17, 1997; 62 FR 18938).  As of the date of this guidance publication we have not yet issued a final rule based on that 
proposed rule. 
 
  53 Contains Nonbinding Recommendations 
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Element of a GRAS Notice  Applicable Part on Form FDA 3667 
Information about the notifier (and any attorney  II 
or agent acting on behalf of the notifier) 
General administrative information   III 
Intended use  IV 
Identity  V and VI 
Method of manufacture   VI 
Specifications VI
Dietary exposure  VI 
Self-limiting levels of use  VI 
Common use in food before 1958 (if applicable)  VI 
Comprehensive discussion of the basis for the  VI 
GRAS determination 
Bibliography VI
Signature VII
N/A  VIII (List of Attachments) 
2. How should I organize a new GRAS notice submission?
You should organize a new GRAS notice as a document presenting the elements of a GRAS 
notice in an order corresponding to that of the elements listed on Form FDA 3667.  A summary 
of these elements is listed in Table VI-1 of this document and described in the instructions for 
Form FDA 3667 (see Appendix 5).  If you include any data or information not identified on 
Form FDA 3667, you should place these data or information in a logical place in your 
submission based on the type of information.   
B. Generally Recognized as Safe Notice Submissions in Electronic
Format
3. How should I organize an electronic GRAS notice submission?
You should organize an electronic GRAS notice submission using the foldering structure 
available in a downloadable GRAS Notice Submission Roadmap (see instructions in Appendix 5 
and the roadmap in Appendix 15).  The entire GRAS Notice Submission Roadmap is organized 
under the folder entitled Main directory.  The Main directory includes three first-level 
folders, entitled Administrative, GRAS Notice, and Incoming Correspondence.  The 
Incoming Correspondence folder includes three second-level subfolders entitled Submission 
Form, Amendment and Supplement.  We show these folders and subfolders, using an 
outline format, in Figure VI-1, below. 
Figure VI-1 
Outline Representing the Folders and Subfolders in the Main directory of a GRAS 
Notice Submission Roadmap 
 Main directory
54 Contains Nonbinding Recommendations 
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o Administrative
o GRAS Notice
o Incoming Correspondence
 Submission Form
 Amendment
 Supplement
4. When should I use the specific folders and subfolders in the GRAS Notice 
Submission Roadmap?
You should use these folders and subfolders as shown in Table VI-2. You should not place any 
specific files directly in Main directory. Main directory only contains folders.   
Table VI-2 
When to Use Specific Folders and Subfolders 
in the Main Directory of a GRAS Notice Submission Roadmap* 
Folder/Subfolder  When to Use it 
Administrative  Any time you transmit a new GRAS notice and submission form 
or a redacted electronic file(s) 
GRASNotice  Only when you transmit a new GRAS notice 
IncomingCorrespondence  You should not place any specific files directly in the Incoming 
Correspondence folder. The Incoming Correspondence folder 
only contains subfolders. 
Incoming  Any time you transmit information while we are reviewing your 
Correspondence/Submission  GRAS notice or after we have responded to your GRAS notice 
Form 
IncomingCorrespondence/  Any time you transmit information while we are reviewing your 
Amendment  GRAS notice 
IncomingCorrespondence/  Any time you transmit information after we have responded to 
Supplement  your GRAS notice 
*If you are transmitting an amendment or supplement to your GRAS notice, you should re-name
Main directoryto reflect the file number we assigned to your notice.
5. How should I name files in an electronic GRAS notice submission?
You should name each file using both generic and specific elements as described in Section III.C 
and Appendix 12 of this document.  Generic elements in the file names specific to GRAS notice 
submissions are included in the examples in Table VI-3 (below).   
6. What files should I place in each folder and subfolder?
Table VI-3 shows the files you should place in each folder and subfolder.  
55 Contains Nonbinding Recommendations 
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Table VI-3 
Placement of Files in the GRAS Notice Submission Roadmap 
 
Folder/Subfolder  File Name  Information in File 
Administrative  Form3667_..._YYYY-MM-DD.pdf  Form FDA 3667 with responsive 
material completed 
Administrative  CoverLetter_..._YYYY-MM- Letter accompanying the submission 
DD.pdf  if you choose to send a letter in 
addition to Form FDA 3667 
Administrative  DesignationOfConfidential  A description of the data or 
Information_..._YYYY-MM- information in your submission that 
DD.pdf  you designated as nondisclosable 
information (21CFR 20 Subpart D) 
Administrative  RedactedBySubmitter_..._YYYY- Copy(ies) of one or more files in your 
MM-DD.pdf  submission modified by deletion of 
data or information you designated as 
nondisclosable information 
GRASNotice  GRASNotice_..._YYYY-MM- File containing the following 
DD.pdf  information not placed on the form:  
  Table of Contents  
  Any additional information 
about identity not covered in 
Part V of Form FDA 3667 
  Method of manufacture 
  Specifications for food-grade 
material 
  Dietary exposure 
  Self-limiting levels of use 
  Common use in food before 
1958 (if applicable) 
  Comprehensive discussion of 
the basis for the determination 
of GRAS status 
  Bibliography  
  Other Information  
GRASNotice  [Miscellaneous]_..._YYYY-MM- One or more files containing 
DD.pdf  miscellaneous information you ask 
FDA to consider in evaluating your 
GRAS notice (e.g., technical 
bulletins) 
IncomingCorrespondence/  YYYY-MM-DD-  Form FDA 3667 with responsive 
Submission Form  Form3667_..._.pdf  material completed 
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Folder/Subfolder  File Name  Information in File 
IncomingCorrespondence/  YYYY-MM- When applicable, file(s) containing 
Amendment  DD_Amendment_....pdf  the information you submit to us 
  during our review of your GRAS 
notice.  An amendment addressing 
more than one topic should include a 
Table of Contents. 
IncomingCorrespondence/  YYYY-MM- When applicable, file containing the 
Supplement  DD_Supplement_....pdf  information you submit to us after we 
  respond to your GRAS notice.  A 
supplement addressing more than one 
topic should include a Table of 
Contents. 
 
 
C.  Electronic Amendments and Supplements to GRAS Notice 
Submissions 
7.  What recommendations apply to amendments and supplements to GRAS 
notice submissions? 
You should refer to Section III.F of this document for general recommendations applying to 
amendments and supplements in electronic format.   
 
When transmitting any amendment or supplement to a GRAS notice, you should organize your 
submission as a single file.  If an amendment or supplement addresses more than one topic, the 
file should include a Table of Contents with bookmarks to aid in navigating through the 
submission.  You then should place this file in the Incoming Correspondence/Amendment or 
Incoming Correspondence/Supplement subfolder in the GRAS Notice Submission. 
 
VII.  Information Specific to Biotechnology Final Consultation 
Submissions  
Section VII of this document addresses Biotechnology Final Consultation submissions,  A 
Biotechnology Final Consultation is a voluntary procedure for foods derived from new plant 
varieties.  Information about that consultation procedure is available in our guidance entitled 
Guidance on Consultation Procedures. Foods Derived From New Plant Varieties (the 
consultation procedures) (Ref. 20).  We assign a file number (Biotechnology Notification File 
No. (BNF)) to your submission and respond to you by letter. 
    
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A.  General Information about Biotechnology Final Consultation 
Submissions  
1.  How do the parts on Form FDA 3665 relate to the elements of a 
Biotechnology Final Consultation? 
Table VII-1 shows the elements of a Biotechnology Final Consultation and links each element to 
the applicable part of Form FDA 3665.   
 
Table VII-1 
Elements of a Biotechnology Final Consultation as Shown on Form FDA 3665 
 
Element of a Biotechnology Final Consultation  Applicable Part on Form FDA 3665 
Introductory information about the submission  I 
Information about the person responsible for the  II 
submission (and any attorney or agent acting on 
behalf of that person) 
General administrative information   III 
Information about the food and the new plant  IV 
variety from which it is derived 
Identity of new substances in the new plant  V 
variety  
Summary of safety and nutritional assessment  VI  
Signature  VII 
N/A  VIII (List of Attachments) 
 
 
2.  How should I organize a Biotechnology Final Consultation?  
You should organize a new Biotechnology Final Consultation as a document presenting the 
elements of a Biotechnology Final Consultation in an order corresponding to that of the elements 
listed on Form FDA 3665.  These elements are also listed in Table VII-1 of this document and 
described in the instructions for Form FDA 3665 (see Appendix 7).  If you include any data or 
information not identified as an element on Form FDA 3665, you should place these data or 
information in a logical place in your submission based on the type of information. 
   
 
B.  Biotechnology Final Consultation Submissions in Electronic 
Format  
3.  How should I organize an electronic Biotechnology Final Consultation 
submission? 
  58 Contains Nonbinding Recommendations 
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You should organize an electronic Biotechnology Final Consultation submission using the 
foldering structure available in the downloadable Biotechnology Final Consultation Submission 
Roadmap (see instructions in Appendix 7 and the roadmap in Appendix 15).  The entire 
Biotechnology Final Consultation Submission Roadmap is organized under the folder entitled 
Main directory in the Biotechnology Final Consultation Submission Roadmap.  The Main 
directory contains three first-level folders, entitled Administrative, Submission, and 
Incoming Correspondence.  The Incoming Correspondence folder includes three second-
level subfolders entitled Submission Form, Amendment and Supplement.  We show these 
folders and subfolders, using an outline format, in Figure VII-1, below. 
Figure VII-1 
Outline Representing the Folders and Subfolders in the Main directory of a 
Biotechnology Final Consultation Submission Roadmap 
 Main directory
o Administrative
o Submission
o Incoming Correspondence
 Submission Form
 Amendment
 Supplement
4. When should I use the specific folders and subfolders in the Biotechnology 
Final Consultation Submission Roadmap?
You should use these folders and subfolders as shown in Table VII-2. You should not place any 
specific files directly in Main directory. Main directory only contains folders.   
Table VII-2 
When to Use Specific Folders and Subfolders in the Main Directory of a Biotechnology 
Final Consultation Submission Roadmap* 
.   
Folder/Subfolder  When to Use it 
Administrative  Any time you transmit a new Biotechnology Final Consultation 
and submission form or a redacted copy(s) 
Submission  Only when you transmit a new Biotechnology Final Consultation 
IncomingCorrespondence  You should not place any specific files directly in the Incoming 
Correspondence folder. The Incoming Correspondence folder 
only contains subfolders. 
59 Contains Nonbinding Recommendations 
Draft-Not for Implementation 
 
Folder/Subfolder  When to Use it 
Incoming  Any time you transmit information while we are reviewing your 
Correspondence/Submission  Biotechnology Final Consultation or after we have responded to 
Form  your Biotechnology Final Consultation 
Incoming Correspondence/  Any time you transmit information while we are reviewing your 
Amendment  Biotechnology Final Consultation 
Incoming Correspondence/  Any time you transmit information after we have responded to 
Supplement  your Biotechnology Final Consultation 
*If you are transmitting an amendment or supplement to your Biotechnology Final Consultation, 
you should re-name the Main directory to reflect the file number we assigned to your 
submission. 
 
5.  How should I name files in an electronic Biotechnology Final Consultation 
submission? 
You should name each file using both generic and specific elements as described in Section III.C 
and Appendix 12 of this document.  Generic elements in the file names specific to Biotechnology 
Final Consultation submissions are included in Table VII-3 (below).   
 
6.  What files should I place in each folder of the Main directory?  
Table VII-3 shows the files you should place in each folder and subfolder..  
 
Table VII-3 
Placement of Files in the Biotechnology Final Consultation Submission Roadmap 
 
Folder/Subfolder  File Name  Information in File 
Administrative  Form3665_..._YYYY-MM-DD.pdf  Form FDA 3665 with responsive 
material completed 
Administrative  CoverLetter_..._YYYY-MM-DD.pdf  Letter accompanying the 
submission if you choose to send a 
letter in addition to Form FDA 
3665 
Administrative  DesignationOfConfidentialInformation A description of the data or 
_..._YYYY-MM-DD.pdf  information in your submission 
that you designated as 
nondisclosable information 
(21CFR 20 Subpart D). 
Administrative  RedactedBySubmitter_..._YYYY-MM- Copy(ies) of one or more files in 
DD.pdf  your submission modified by 
deletion of data or information you 
designated as nondisclosable 
information. 
  60 Contains Nonbinding Recommendations 
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Folder/Subfolder  File Name  Information in File 
Submission  Submission_..._YYYY-MM-DD.pdf  File containing the following 
information not placed on the form 
  Table of Contents 
  Summary of Safety and 
Nutritional Assessment 
  Other Information  
Incoming  YYYY-MM-DD_ Form3665_..._.pdf  Form FDA 3665 with responsive 
Correspondence/  material completed 
SubmissionForm 
Incoming  YYYY-MM-DD_Amendment_....pdf  When applicable, file containing 
Correspondence/    the information you submit to us 
Amendment  during our review of your 
Biotechnology Final Consultation. 
An amendment addressing more 
than one topic may include a Table 
of Contents. 
Incoming  YYYY-MM-DD_Supplement_....pdf  When applicable, file containing 
Correspondence/    the information you submit to us 
Supplement  after we respond to your 
Biotechnology Final Consultation.  
A supplement addressing more 
than one topic may include a Table 
of Contents. 
  
C.  Electronic Amendments and Supplements to Biotechnology Final 
Consultation Submissions 
7.  What recommendations apply to amendments and supplements to 
Biotechnology Final Consultation submissions? 
You should refer to Section III.F of this document for general recommendations applying to 
amendments and supplements in electronic format.   
 
When transmitting any amendment or supplement to a Biotechnology Final Consultation, you 
should organize your submission as a single file.  If an amendment or supplement addresses 
more than one topic, the file may include a Table of Contents with bookmarks to aid in 
navigating through the submission.  You then should place this file in the Incoming 
Correspondence/Amendment or Incoming Correspondence/Supplement subfolder in the 
Biotechnology Final Consultation Submission Roadmap. 
 
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VIII.  Information Specific to New Protein Consultation 
Submissions 
Section VIII of this document addresses submissions about the early food safety evaluation of a 
new non-pesticidal protein produced by a new plant variety (New Protein Consultation).  The 
New Protein Consultation is a voluntary procedure for proteins derived from a new plant variety.  
Information about the consultation procedure is available in our guidance entitled 
Recommendations for the Early Food Safety Evaluation of New Non-Pesticidal Proteins 
Produced by New Plant Varieties Intended for Food Use (Ref.22).  We assign a file number (the 
NPC number) to your submission and respond to you by letter.   
 
A.  General Information about New Protein Consultation 
Submissions  
1.  How do the parts on Form FDA 3666 relate to the elements of a New 
Protein Consultation? 
Table VIII-1 shows the elements of a New Protein Consultation and links each element to the 
applicable part of Form FDA 3666.   
 
 
Table VIII-1 
Elements of a New Protein Consultation as Shown on Form FDA 3666 
 
Element of a New Protein Consultation  Applicable Part on Form FDA 3666 
Introductory information about the submission  I 
Information about the person responsible for the  II 
submission (and any attorney or agent acting on 
behalf of that person) 
General administrative information   III 
Information about the new protein  IV 
Information about genetic material  V 
Scientific evaluation of the food safety of the  VI 
new protein 
Other pertinent information  VI 
Signature  VII 
N/A  VIII (List of Attachments) 
 
 
2.  How should I organize a New Protein Consultation?  
You should organize a New Protein Consultation as a document presenting the elements of a 
New Protein Consultation in an order corresponding to that of the elements listed on Form FDA 
3666.  These items are also listed in Table VII-1 of this document and described in the 
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instructions for Form FDA 3666 (see Appendix 9).  If you include any data or information not 
identified as an element on Form FDA 3666, you should place these data or information in a 
logical place in your submission based on the type of information. 
B. New Protein Consultation Submissions in Electronic Format
3. How should I organize an electronic New Protein Consultation submission?
You should organize an electronic New Protein Consultation submission using the foldering 
structure available in a downloadable New Protein Consultation Submission Roadmap (see 
instructions in Appendix 9 and the roadmap in Appendix 15).  The entire New Protein 
Consultation Submission Roadmap is organized under the folder entitled Main directory.  The 
Main directory contains three first-level folders, entitled Administrative, Submission, and 
Incoming Correspondence.  The Incoming Correspondence folder includes three second-
level subfolders entitled Submission Form, Amendment and Supplement.  We show these 
folders and subfolders, using an outline format, in Figure VIII-1, below. 
Figure VIII-1 
Outline Representing the Folders and Subfolders in the Main directory of a New Protein 
Consultation Submission Roadmap 
 Main directory
o Administrative
o Submission
o Incoming Correspondence
 Submission Form
 Amendment
 Supplement
4. When should I use the specific folders and subfolders in the New Protein
Consultation Submission Roadmap?
You should use these folders and subfolders as shown in Table VIII-2.You should not place any 
specific files directly in Main directory. Main directory only contains folders.   
Table VIII-2 
When to Use Specific Folders and Subfolders 
in the Main Directory of a New Protein Consultation Submission Roadmap* 
Folder/Subfolder  When to Use it 
Administrative  Any time you transmit a (new) New Protein Consultation and 
submission form or a redacted copy(s) 
Submission  Only when you transmit a (new) New Protein Consultation 
63 Contains Nonbinding Recommendations 
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Folder/Subfolder  When to Use it 
IncomingCorrespondence  You should not place any specific files directly in the Incoming 
Correspondence folder. The Incoming Correspondence folder 
only contains subfolders. 
Incoming  Any time you transmit information while we are reviewing your 
Correspondence/Submission  New Protein Consultation or after we have responded to your 
Form  New Protein Consultation 
IncomingCorrespondence/  Any time you transmit information while we are reviewing your 
Amendment  New Protein Consultation 
IncomingCorrespondence/  Any time you transmit information after we have responded to 
Supplement  your New Protein Consultation 
*If you are transmitting an amendment or supplement to your New Protein Consultation, you 
should re-name the Main directory to reflect the file number we assigned to your submission. 
 
5.  How should I name files in an electronic New Protein Consultation 
submission? 
You should name each file using both generic and specific elements as described in Section III.C 
and Appendix 12 of this document.  Generic elements in the file names specific to New Protein 
Consultation submissions are included in the examples in Table VIII-3 (below).   
 
6.  What files should I place in each folder of the Main directory?  
Table VIII-3 shows the files you should place in each folder and subfolder of the Main 
directory.   
 
Table VIII-3 
Placement of Files in the New Protein Consultation Submission Roadmap 
 
 
Folder/Subfolder  File Name  Information in File 
Administrative  Form3666_..._YYYY-MM-DD.pdf  Form FDA 3666 with responsive 
material completed 
Administrative  CoverLetter_..._YYYY-MM-DD.pdf  Letter accompanying the 
submission if you choose to send a 
letter in addition to Form FDA 
3666 
Administrative  DesignationOfConfidentialInformation A description of the data or 
_..._YYYY-MM-DD.pdf  information in your submission 
that you designated as 
nondisclosable information 
(21CFR 20 Subpart D). 
  64 Contains Nonbinding Recommendations 
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Folder/Subfolder  File Name  Information in File 
Administrative  RedactedBySubmitter_..._YYYY-MM- Copy(ies) of one or more files in 
DD.pdf  your submission modified by 
deletion of data or information you 
designated as nondisclosable 
information. 
Submission  Submission_..._YYYY-MM-DD.pdf  File containing  
  Table of Contents  
  Scientific evaluation of the 
food safety of the new 
protein 
  Other pertinent information 
Incoming  YYYY-MM-DD_Form3666_..._.pdf  Form FDA 3666 with responsive 
Correspondence/  material completed 
SubmissionForm 
Incoming  YYYY-MM-DD_Amendment_....pdf  When applicable, file containing 
Correspondence/    the information you submit to us 
Amendment  during our review of your New 
Protein Consultation. An 
amendment addressing more than 
one topic may include a Table of 
Contents. 
Incoming  YYYY-MM-DD_Supplement_....pdf  When applicable, file containing 
Correspondence/    the information you submit to us 
Supplement  after we respond to your New 
Protein Consultation.  A 
supplement addressing more than 
one topic may include a Table of 
Contents. 
  
C.  Electronic Amendments and Supplements to New Protein 
Consultation Submissions 
7.  What recommendations apply to amendments and supplements to New 
Protein Consultation submissions? 
You should refer to Section III.F of this document for general recommendations applying to 
amendments and supplements in electronic format.   
 
When transmitting any amendment or supplement to a New Protein Consultation, you should 
organize your submission as a single file.  If an amendment or supplement addresses more than 
one topic, the file may include a Table of Contents with bookmarks to aid in navigating through 
the submission.  You then should place this file in the Incoming Correspondence/Amendment or 
  65 Contains Nonbinding Recommendations 
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Incoming Correspondence/Supplement subfolder in the New Protein Consultation Submission 
Roadmap. 
 
IX.  FDA Web Site References  
As of January 28, 2010, FDA had verified the Web site addresses for the references it makes 
available as hyperlinks from the Internet copy of this guidance.  
A.  Administrative Information Web Site References 
1. FDA Electronic Submissions Gateway (ESG). Information on setting up an FDA ESG 
Account (Webtrader and AS2). 
 2. Guidance for Industry - Questions and Answers About the Petition Process. 
3. Inventory of Effective Food Contact Substance (FCS) Notifications. 
4. Definitions of Food Types and Conditions of Use for Food Contact Substances. 
5. Guidance for Industry - Preparation of Food Contact Notifications: Administrative. 
6. Guidance for Industry - Frequently Asked Questions About GRAS. 
B.  Chemistry Information Web Site References 
7. Guidance for Industry - Recommendations for Submission of Chemical and Technological 
Data for Direct Food Additive Petitions. 
8. Guidance for Industry - Color Additive Petitions. FDA Recommendations For Submission Of 
Chemical And Technological Data On Color Additives For Food, Drugs, Cosmetics or 
Medical Devices. 
9. Guidance for Industry - Estimating Dietary Intake of Substances in Food. 
10. Guidance for Industry - Preparation of Premarket Submissions for Food Contact Substances: 
Chemistry Recommendations. 
11. Enzyme Preparations: Chemistry Recommendations For Food Additive And Gras   
Affirmation Petitions. 
C.  Safety Study Information Web Site References 
12. Guidance to Industry - Computerized Systems Used in Clinical Investigations. 
13. Guidance for Industry: Templates for Reporting Toxicology Data. 
14. Standard for Exchange of Non-Clinical Data. 
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15. Guidance for Industry - Summary Table of Recommended Toxicological Testing for 
Additives Used in Food. 
16. Guidance for Industry and Other Stakeholders - Toxicological Principles for the Safety 
Assessment of Food Ingredients. Redbook 2000. 
17. Appendix E - Color Additives For Medical Devices. 
18. Preparation of Food Contact Notifications for Food Contact Substances: Toxicology 
Recommendations. 
D.  Environmental Information Web Site References 
19. Guidance for Industry - Preparing a Claim of Categorical Exclusion or an Environmental 
Assessment for Submission to the Center for Food Safety and Applied Nutrition. 
E.  Biotechnology Information Web Site References 
20. Guidance on Consultation Procedures. Foods Derived From New Plant Varieties. 
21. Statement of Policy: Foods Derived From New Plant Varieties. 
22. Guidance for Industry - Recommendations for the Early Food Safety Evaluation of New 
Non-Pesticidal Proteins Produced by New Plant Varieties Intended for Food Use. 
 
X.  Appendices  
Appendix 1: Instructions for Completing Form FDA 3503 Food/ Color Additives and Master 
Files   
Appendix 2: Food and Color Additive Petition and Master File Form FDA 3503 (available in 
PDF)  
Appendix 3a: Instructions for Completing Food Contact Substance  Form FDA 3480 
Appendix 3b: Instructions for Completing Food Contact Substance Form FDA 3480-A for 
Amendments  
Appendix 4a: Notification for New Use of a Food Contact Substance under Premarket 
Notification submission Form FDA 3480: (available in PDF) 
Appendix 4b: Notification for New Use of a Food Contact Substance under Premarket 
Notification submission Form FDA 3480-A for amendments (available in PDF) 
Appendix 5: Instructions for Completing GRAS Notice Form FDA 3667    
Appendix 6: GRAS Notice Form FDA 3667 (available in PDF) 
Appendix 7: Instructions for Completing Biotechnology Notification FORM FDA 3665  
Appendix 8: Biotechnology Final Consultation Form FDA 3665 (available in PDF) 
Appendix 9: Instructions for Completing New Protein Consultation Form FDA 3666 
Appendix 10: New Protein Consultation Form FDA 3666 (available in PDF) 
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Appendix 11: Definition of Regulatory Submissions and Terms 
Appendix 12: Conventions for Naming Files and Folders in an Electronic Submission 
Appendix 13: List of Abbreviations and Acronyms 
Appendix 14: Creating Reference Hyperlinks in E-submission Documents 
Appendix 15: Links to Downloadable Foldering Structures 
68