Draft Guidance for Industry: Regulatory Submissions to OFAS, Part V Food Contact Substance Submissions March 2010
Not for implementation. Contains non-binding recommendations.
Contains Nonbinding Recommendations
Draft — Not for Implementation
Table of Contents and Introduction (Part I)
Information for all regulatory submissions
- Part I: Introduction
- Part II: Common Elements
- Part III: General Considerations - Electronic Format
- Part IX: FDA References
- Part X: Appendices
- Quick Links to Forms, Instructions and Downloadable Folders
Regulatory submissions for program areas
- Part IV: Food or Color Additive Submissions
- Part V: Food Contact Substance Submissions
- Part VI: GRAS Notices
- Part VII: Biotechnology Final Consultations
- Part VIII: New Protein Consultations
All parts [Printable PDF Version]
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a food additive petition proposing the approval of the FCS for the use in your FCN, we will consider that you have withdrawn your FCN on the date we receive your petition.
- General Information about Food Contact Notification Submissions
- Food Contact Notification Submissions in Electronic Format
- Electronic Amendments to Food Contact Notifications
- Pre-Notification Consultations and Food Master Files for Food Contact Substances
A. General Information about Food Contact Notification Submissions
- 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.
- 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.
- 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.
- 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.
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
- 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.
- 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).
- 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
- How should I organize an electronic FCN submission?
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.
Outline Representing the FCN Submission Roadmap
- Main directory
- Confidential Environmental Information
- Chemical Name 1*
- Genetic Toxicity Studies
- 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 or Combined Chronic
Toxicity/Carcinogenicity Studies Rodents
- Carcinogenicity Studies Rodents
- Reproduction Studies
- Developmental Toxicity Studies
- Immunotoxicity Studies
- Metabolism and Pharmacokinetic Studies
- Neurotoxicity Studies
- Chemical Name 2*
- Chemical Name 1*
* 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.
- Main directory
- 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.
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 Applicable Subfolders Any time you transmit chemistry data or information, regardless of whether you are transmitting a new submission or an amendment Environmental Folder and Applicable Subfolders Any time you transmit environmental data or information, regardless of whether you are transmitting a new submission or an amendment Safety Folder and Applicable Subfolders Any time you transmit safety data or information, regardless of 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).
- 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..
- 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.
Files in the “Administrative” Folder of a FCN Submission
File Name Information in File Applicable Regulatory Citation and Guidance Form3480_..._YYYY-MM-DD.pdf Some specific information in the submission and a list of documents included 21 CFR 170.101 5 CoverLetter_..._YYYY-MM-DD.pdf Letter accompanying the submission if you choose to send a letter in addition to Form FDA 3480 N/A* DesignationOfNondisclosableInformation _..._YYYY-MM-DD.pdf A document describing the data or information in your submission that you view as nondisclosable (see Section II.E of this document) 21 CFR 20.61(d) ProposedLanguageForFCNListing_..._ YYYY-MM-DD.pdf Proposed Language for your FCN listing 21 CFR 170.101(b) RedactedBySubmitter_..._YYYY-MM-DD.pdf Copy(ies) of one or more files in 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
* N/A means “Not applicable.”
- 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.
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 chemical formula(s), structure(s) and molecular weight(s) Form FDA 3480 II.A.5 (Description) Ref. 10 Structure_..._YYYY-MM-DD.mol A structure for the FCS and for substances that may migrate into food from use of the FCS (see Part III.C of this guidance for file formats) Form FDA 3480 II.A.5 (Description) Ref. 10 IR_..._YYYY-MM-DD.pdf NMR_..._YYYY-MM-DD.pdf MassSpec_..._YYYY-MM-DD.pdf Spectroscopic data characterizing the FCS Form FDA 3480 II.A.6 (Characterization) Ref. 10 ManufacturingProcess_..._ YYYY-MM-DD.pdf A complete description of the manufacturing process Form FDA 3480 II.B.1 (Manufacturing Process) Ref. 10 RawMaterialSpecs_..._ YYYY-MM-DD.pdf Specifications for reagents, solvents, catalysts, purification aids, etc., used in the manufacturing process Ref. 10 Impurities_…_YYYY-MM-DD.PDF Supporting data used to arrive at the levels of impurities reported on Form FDA 3480, and/or information supporting that no migration to food is expected Form FDA 3480 II.C.1 (Impurities) Ref. 10 Specifications_…_YYYY-MM-DD.pdf Physical and chemical specifications for the FCS Form FDA 3480 II.C.2 (Specifications) Ref. 10 MolWeightProfile_..._YYYY-MM-DD.pdf The maximum percentage of oligomeric species (not including residual monomers, reactants, or solvents) below 1000 Daltons and supporting data and analytical methods Form FDA 3480 II.A.7 (Molecular Weight Profile) Ref. 10 IntendedUse_..._ YYYY-MM-DD.pdf Use level of the FCS, the types of food contact articles in which it may be used, types of food, conditions of use, etc. Form FDA 3480 II.D.1,2 (Intended Use) Ref. 10 TechnicalEffect_..._ YYYY-MM-DD.pdf A description of the intended technical effect of the FCS; summary of data showing the FCS will achieve the intended technical effect and that the proposed use level is the minimum level required to accomplish the intended technical effect Form FDA 3480 II.D.3 (Intended Technical Effect) Ref. 10 Stability_..._YYYY-MM-DD.pdf Description of any 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** Form FDA 3480 II.E (Stability of the FCS) Ref. 10 MigrationCalculation_..._YYYY-MM-DD.pdf A description of the mathematical approach used in estimating migration levels of the FCS to food and/or any of its constituents. Form FDA 3480 II.F.2 (Migration Calculation Option) Ref. 10 ExposureCalculation_..._ YYYY-MM-DD.pdf Representative calculations for the dietary concentration (DC) and estimated daily intake (EDI) for all substances migrating to food as a result of the intended use of the FCS Form FDA 3480 II.G (Estimated Daily Intake) 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).
- 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.
Files in the “Studies” and “References” Subfolders of the “Chemistry” Folder of a FCN Submission Roadmap
Folder/ Subfolder File Name Information in the File Applicable Item on Form FDA 3480 and Guidance* Chemistry/ Studies StabilityStudy_..._YYYY-MM-DD.pdf A study on the stability of the FCS ** Form FDA 3480 II.E (Stability of the FCS) Ref. 10 Chemistry/ Studies MigrationStudy_..._YYYY-MM-DD.pdf A study determining the expected levels of migration of the FCS or its components to food Form FDA 3480 II.F.1 (Migration Testing Option) Ref. 10 Chemistry/ References See Appendix 12 Any references to the scientific literature Ref. 10
* 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).
- 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.
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_..._ YYYY-MM-DD.pdf A summary describing the scientific basis of your determination that the food contact substance (FCS) is safe under the conditions of use Form FDA 3480 III.1 (Safety Narrative) Ref. 18
- 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.
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 Toxicology Profile (CTP), for the specific chemical, including detailed study summaries Form FDA 3480 III.2 Ref. 18 Safety/ChemicalName1 LiteratureSearch_..._.pdf Data or information that the notifier relies upon to prepare the CTP Ref. 18
* The applicable section of the regulation is 21 CFR 170.101(a).
- 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.
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
Subfolder Examples of File Names Applicable Regulatory Citation, Part on Form FDA 3480, and Guidance Safety/ ChemicalName1/Studies/ GeneticToxicityStudies Ames_..._YYYY-MM-DD.pdf Form FDA 3480 III.3 Ref. 18 Ref. 16 Safety/ChemicalName1/References (Titles of the reference, citation,…) See Appendix 12 Ref. 18 Ref. 16
- 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.
Folders and Files in the "Environmental" Folder of an FCN Submission
Folder/ Subfolder File Name Information in the File Applicable Regulatory Citation, Part on Form FDA 3480, and Guidance Environmental EA…-YYYY-MM-DD.pdf Concise public document that provides sufficient evidence and analysis for FDA to determine whether to prepare an Environmental Impact Statement (EIS) or a Finding of No Significant Impact (FONSI) 21 CFR 170.101(d) Form FDA 3480 Part IV 21 CFR 25.40 Ref. 19 Environmental FIFRA Label_..._ YYYY-MM-DD .pdf (1) A copy of the current FIFRA registration label for the substance that has the same use requested in the submission; and (2) The proposed FIFRA registration label that includes the food contact use for which the sponsor intends to request an amendment from EPA. 21 CFR 170.101(d) Form FDA 3480 IV 21 CFR 25.32(q) Ref. Ref. 19 Environmental/ Confidential Environmental Information MarketVolume…-YYYY-MM-DD.pdf Data and information that are protected from disclosure under 18 U.S.C. 1905, 21 U.S.C. 331(j) or 360j(c) 21 CFR 170.101(d) Form FDA 3480 IV Ref. Ref. 19 Environmental/Studies …YYYY-MM-DD.pdf Study reports of environmental fates or effects studies Ref. Ref. 19 Environmental/References …YYYY-MM-DD.pdf Environmental literature references (published studies, excerpts) Ref. Ref. 19
C. Electronic Amendments to Food Contact Notifications
- 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.)
- 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
- 2006-12-07_Form FDA 3480-A_InResponseToFDA2006-11-20 Letter.pdf
- 2006-12-07_ResponsesToFDA2006-11-20ChemistryQuestions_(Impurities_MigrationStudy_ …).pdf
- 2006-12-07_ImpuritiesBatchData(TIPA, 34901-14-9, catalyst)_Chromatograms&Calculations.pdf
- 2006-12-07_EA_Revised_HPNH_ InPolypropylene.pdf
- 3-AP-PEG (34901-14-9)
- ·2006-12-07_Response to FDA2006-06-20Question-Toxicity of 3-AP-PEG
- 3-AP-PEG (34901-14-9)
- FCN 009999
D. Pre-Notification Consultations and Food Master Files for Food Contact Substances
- 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.
Elements of PNCs and FMFs as Shown on Form FDA 3480
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
- 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.
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