Contains Nonbinding Recommendations 
Dietary Supplements:  New Dietary 
Ingredient Notification Procedures and 
Timeframes: Guidance for Industry 
 
Additional copies are available from:  
Office of Dietary Supplement Programs, HFS-810  
Center for Food Safety and Applied Nutrition  
Food and Drug Administration 
5001 Campus Drive 
College Park, MD 20740 
(Tel) 240-402-2375 
 
https://www.fda.gov/FoodGuidances 
 
You may submit electronic or written comments regarding this guidance at any time. Submit 
electronic comments to https://www.regulations.gov. Submit written comments to the 
Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852. All comments should be identified with docket number 
FDA-2011-D-0386, listed in the notice of availability that publishes in the Federal Register. 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Food Safety and Applied Nutrition 
  
March 2024  
OMB Control No. 0910-0330 
Current expiration date available at https://www.reginfo.gov/public/do/PRAMain  
See additional PRA statement in Section VI. of this guidance 
 
 
 
 
     
   
Contains Nonbinding Recommendations 
Table of Contents
 
Table of Contents 
I.  Introduction ............................................................................................................................... 3 
II.  Background ............................................................................................................................... 3 
III.  NDIN Procedures and Timeframes ........................................................................................... 5 
A.  Who must submit an NDIN?..................................................................................................... 5 
B.  Can you submit a single NDIN that contains safety data for a range of conditions of use 
and covers multiple products? .......................................................................................... 6 
C.  How should the information in an NDIN be organized and presented? .......................... 6 
D.  How should the NDIN describe the NDI? ....................................................................... 6 
E.  How should the NDIN describe the dietary supplement in which the NDI will be used?7 
F.  Should you explain how the information in the NDIN provides a basis to conclude that 
the dietary supplement in which the NDI will be used will reasonably be expected to be 
safe? ................................................................................................................................. 7 
G.  What information should not be in the NDIN? ................................................................ 8 
H.  When must an NDIN be submitted? ................................................................................ 8 
I.  Does FDA accept NDINs electronically? ........................................................................ 8 
J.  How many copies of an NDIN should be submitted? ...................................................... 8 
K.  Where should an NDIN be submitted? ............................................................................ 9 
L.  How should published literature and other scientific information cited in the NDIN be 
listed? ............................................................................................................................... 9 
M.  Do you have to provide copies of publications cited in the NDIN to FDA? ................... 9 
N.  Can you use material published in languages other than English to support the safe use 
of an NDI? ........................................................................................................................ 9 
O.  How should unpublished scientific work be described in an NDIN? ............................ 10 
P.  Should raw data be provided in an NDIN? .................................................................... 10 
Q.  How should you identify information in an NDIN that you believe is trade secret or 
confidential commercial information (CCI)? ................................................................. 10 
R.  What signature and contact information should you provide in an NDIN? ................... 11 
IV.  What Happens After an NDIN Is Submitted?......................................................................... 11 
A.  When is an NDIN considered to be filed? ..................................................................... 11 
B.  What are examples of omissions that cause an NDIN to be incomplete? ...................... 12 
C.  Will you hear from FDA during the NDIN review period? ........................................... 12 
D.  What type of response may you expect to receive from FDA, and when? .................... 12 
V.  Meetings Between FDA and Notifiers .................................................................................... 13 
VI.  Paperwork Reduction Act of 1995 .......................................................................................... 14 
Document History ............................................................................................................................... 14 
Appendix:  Recommended Template for Organizing an NDIN that is Submitted on Paper .............. 15 
    
 
 
 
 
     
   
Contains Nonbinding Recommendations 
Dietary Supplements:  New Dietary 
Ingredient Notification Procedures and 
Timeframes:  Guidance for Industry1 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or we) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  
You can use an alternative approach if it satisfies the requirements of the applicable statutes and 
regulations.  To discuss an alternative approach, contact the FDA staff responsible for this guidance 
as listed on the title page. 
 
I.  Introduction 
Under section 413(a)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 
350b(a)(2)), the manufacturer or distributor of a new dietary ingredient (NDI) that has not been 
present in the food supply as an article used for food, or of a dietary supplement that contains the 
NDI, must submit a premarket safety notification to FDA at least 75 days before introducing the 
product into interstate commerce.  This guidance is intended to help manufacturers and distributors 
of NDIs and dietary supplements (you) prepare and submit such premarket safety notifications, 
commonly referred to as New Dietary Ingredient Notifications (NDINs).   
This guidance focuses on frequently asked questions about the NDIN submission and review 
process.  We encourage you to consult this guidance when you are ready to submit your NDIN.  
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys 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.   Background 
 
The term dietary supplement is defined in section 201(ff) of the FD&C Act (21 U.S.C. 321(ff)), 
and the term new dietary ingredient in section 413 of the FD&C Act (21 U.S.C. 350b).  Under 
section 413(a)(2) of the FD&C Act, the manufacturer or distributor of an NDI, or of the dietary 
supplement that contains the NDI, must submit a premarket notification to FDA at least 75 days 
before introducing the product into interstate commerce or delivering it for introduction into 
interstate commerce, unless the NDI and any other dietary ingredients in the dietary supplement 
have been present in the food supply as an article used for food in a form in which the food has 
not been chemically altered (21 U.S.C. 350b(a)(1)).  
 
1 This guidance has been prepared by the Office of Dietary Supplement Programs and the Office of Regulation and 
Policy, both in the Center for Food Safety and Applied Nutrition (CFSAN) at the U.S. Food and Drug Administration.   
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Contains Nonbinding Recommendations 
 
As defined in section 201(ff)(1) of the FD&C Act (21 U.S.C. 321(ff)(1)), a dietary ingredient 
is any one of the following: 
 
  A vitamin; 
  A mineral; 
  An herb or other botanical; 
  An amino acid; 
  A dietary substance for use by man to supplement the diet by increasing the total dietary 
intake; or 
  A concentrate, metabolite, constituent, extract, or combination of any dietary ingredient 
from the preceding categories. 
 
An NDI is defined in section 413(d) of the FD&C Act as a dietary ingredient that was not marketed 
in the United States before October 15, 1994 (21 U.S.C. 350b(d)).  Thus, a substance cannot be a 
new dietary ingredient unless it is also a dietary ingredient.  Dietary ingredients marketed in the 
United States before October 15, 1994 are not NDIs and, therefore, do not require an NDIN.   
 
An NDIN must contain the information, including any citation to published articles, that provides 
the basis on which the manufacturer or distributor of the NDI or dietary supplement (the notifier) 
has concluded that the dietary supplement containing the NDI will reasonably be expected to be 
safe (21 U.S.C. 350b(a)(2)).  If the required premarket notification is not submitted to FDA, 
section 413(a) of the FD&C Act (21 U.S.C. 350b(a)) provides that the dietary supplement 
containing the NDI is deemed to be adulterated under section 402(f) of the FD&C Act (21 U.S.C. 
342(f)).  Even if the notification is submitted as required, the dietary supplement containing the 
NDI is adulterated under section 402(f) of the FD&C Act unless there is a history of use or other 
evidence of safety establishing that the NDI, when used under the conditions recommended or 
suggested in the labeling of the dietary supplement, will reasonably be expected to be safe (21 
U.S.C. 350b(a)).  
 
To help industry comply with the FD&C Acts premarket notification requirements for dietary 
supplements that contain an NDI, FDA issued an NDIN regulation (21 CFR 190.6).  This 
regulation specifies the information the manufacturer or distributor must include in its premarket 
NDIN (see 21 CFR 190.6(b)):  
 
  The name and complete address of the manufacturer or distributor that is submitting the 
notification. 
  The name of the NDI that is the subject of the premarket notification.  For botanicals, the 
Latin binomial name must be given, including the author citation (i.e., the name of the 
scientist who gave the botanical its Latin binomial name). 
  A description of the dietary supplement (or dietary supplements) that contains the NDI, 
including: 
  the level of the NDI in the dietary supplement; and 
  the conditions of use recommended or suggested in the labeling of the dietary 
supplement, or if no conditions of use are recommended or suggested in the 
supplements labeling, the ordinary conditions of use of the supplement. 
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Contains Nonbinding Recommendations 
  The history of use or other evidence of safety establishing that the dietary ingredient, when 
used under the conditions recommended or suggested in the labeling of the dietary 
supplement, will reasonably be expected to be safe. 
  The signature of a person authorized by the manufacturer or distributor to sign the 
notification on its behalf. 
 
In addition to the requirements for the content of NDINs, the NDIN regulation establishes the 
administrative procedures for these notifications.  The NDIN regulation defines the filing date of a 
notification as the date FDA receives it and, consistent with section 413(a)(2) of the FD&C Act, 
prohibits the manufacturer or distributor of the dietary supplement that contains the NDI from 
introducing the product into interstate commerce, or delivering it for introduction into interstate 
commerce, for 75 days after the filing date (see 21 CFR 190.6(c)).  If the manufacturer or 
distributor submits additional substantive information in support of the original NDIN, the date 
FDA receives this supplemental submission becomes the new notification filing date, and the 75-
day period restarts (see 21 CFR 190.6(d)).  FDA will not disclose the existence of, or the 
information contained in, an NDIN for 90 days after the filing date of the notification (see 21 
CFR 190.6(e)).  After the 90th day, the entire notification, except trade secrets and confidential 
commercial information, will be placed on public display (see 21 CFR 190.6(e)).  Finally, the 
regulation provides that FDAs failure to respond to an NDIN does not constitute a finding by us 
that the NDI or the dietary supplement containing the NDI is safe or is not adulterated under 
section 402 of the FD&C Act (21 U.S.C. 342) (see 21 CFR 190.6(f)). 
 
In July 2011, we published a draft guidance entitled Guidance for Industry:  Dietary Supplements:  
New Dietary Ingredient Notifications and Related Issues, in compliance with our statutory 
requirements under section 113(b) of the FDA Food Safety Modernization Act (Pub. L. 111-353).  
This draft guidance discussed FDAs views and recommendations on when an ingredient intended 
for use in a dietary supplement is an NDI, when the requirement to submit an NDIN to FDA 
applies, the types of data and information that manufacturers and distributors should consider when 
they evaluate the safety of a dietary supplement containing an NDI, what to include in an NDIN 
(including recommendations about identity and safety information), and the procedures for 
submitting an NDIN.  In 2016, we replaced the 2011 draft guidance with a revised draft guidance, a 
portion of which is being finalized in this document.  We understand the importance of finalizing 
other parts of the 2016 revised draft guidance, and we plan to finalize other individual sections as 
we complete our review and analysis of those sections.  
 
 
III.  NDIN Procedures and Timeframes 
  
A.  Who must submit an NDIN? 
 
Either the manufacturer or distributor of a dietary supplement that contains an NDI, or the 
manufacturer or distributor of the NDI, must notify FDA at least 75 days before marketing the 
article in the United States, unless the NDI has been present in the food supply as an article used 
for food in a form in which the food has not been chemically altered (see 21 CFR 190.6(a)).  
Although FDA does review NDINs from manufacturers and distributors of NDIs, notifications 
from ingredient manufacturers do not eliminate the requirement for a NDIN from the manufacturer 
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or distributor of the dietary supplement in which the NDI will be used unless the prior notification 
for the NDI included information about the dietary supplement, specifically:  (1) a description of 
the dietary supplement that contains the information required by 21 CFR 190.6(b)(3); and (2) the 
history of use or other evidence of safety that formed the basis of the notifiers conclusion that the 
dietary supplement would reasonably be expected to be safe under its labeled conditions of use.  
(For more information, see the response to question B in this section.) 
 
B. Can you submit a single NDIN that contains safety data for a range of 
conditions of use and covers multiple products? 
 
Yes.  We accept NDINs that cover multiple dietary supplements and include safety data for a range 
of doses, daily intake levels, or other variations in conditions of use (e.g., serving size, duration of 
use, frequency of intake, target population, dosage form).  We recommend you submit safety data 
up to and including the highest dose and daily intake level at which the NDI may be marketed, 
indicate any lower daily intake levels at which the NDI may be marketed, and include research that 
evaluates statistically relevant data points, such as a range of daily intake levels, to strengthen the 
safety analysis.  FDA has received a number of NDINs that cover a range of doses and daily intake 
levels.  These NDINs are publicly available in the NDIN docket on www.regulations.gov (see 
question IV.D. in this guidance for more information on this docket).2  Contact FDAs Office of 
Dietary Supplement Programs by email at NDIN@fda.hhs.gov for more information.   
 
C. How should the information in an NDIN be organized and presented?  
   
The NDIN should be well organized to facilitate an efficient and timely FDA review.  If you file 
electronically, the system organizes the NDIN for you.  We encourage electronic submission to 
help ensure that you submit a complete NDIN and to enhance FDAs ability to process and review 
your NDIN efficiently (see the responses to questions I and J in this section for more information 
on electronic submission).   
 
Instead of electronic submission, you may submit a paper NDIN for us to review.  We recommend 
that the paper NDIN be organized by sections, with continuous and consecutive pagination 
throughout the notification.  The page number should appear in the same location on every page.  
In addition, each subject area should begin with a new page to facilitate division of the NDIN 
among reviewers.  FDA encourages those who wish to submit NDINs on paper to consult 
Appendix A of this guidance, which contains a recommended template for organizing a paper 
NDIN.   
 
D. How should the NDIN describe the NDI?  
 
Your NDIN should: (1) specify which of the dietary ingredient categories in section 201(ff)(1) of 
the FD&C Act the NDI belongs to and explain the basis for your conclusion; (2) describe the 
manufacturing process used to make the NDI, including process controls; (3) describe the physical 
properties and chemical or molecular composition and structure of the NDI; and (4) include a 
 
2 Information on how to access redacted copies of FDAs response letters to NDINs is available at 
https://www.fda.gov/food/new-dietary-ingredients-ndi-notification-process/submitted-75-day-premarket-notifications-
new-dietary-ingredients. 
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specification sheet (preferably in table form) that describes the critical identity and safety attributes 
of the NDI, including the purity and strength of the NDI and the identities and levels of any 
impurities and contaminants.  
 
NDIs should be described in a way that accurately communicates their basic nature and 
characterizing ingredients or components, as appropriate.  For example, bacteria should be 
described by Latin binomial name and strain designation. 
 
If your NDI is an herb or other botanical, the name must include the Latin binomial name, 
including the author citation (21 CFR 190.6(b)(2)).  Because different parts of the same botanical 
often have different chemical and physical properties, an NDIN for a botanical or botanically 
derived ingredient should also specify the part of the botanical that is the source of the NDI (e.g., 
leaf, bark, root).  Unusual forms of botanicals should be identified (e.g., immature apples or malted 
barley).  In addition, botanicals grown under controlled, specific conditions to concentrate or 
increase specific constituents should be identified.  
 
If the NDI was the subject of a previous NDIN submitted by you or your supplier (the 
manufacturer or distributor from which you obtain the NDI), please include the NDIN number, 
which you can find in your FDA response letter or in the NDIN's docket file at 
www.regulations.gov. 
 
E. How should the NDIN describe the dietary supplement in which the NDI will 
be used? 
 
The NDIN should contain a description of the dietary supplement in which the NDI will be used, 
including: (1) the level of the NDI in the dietary supplement per serving; (2) the identity and level 
of any other dietary ingredients and non-dietary ingredients (e.g., binders and fillers) in the dietary 
supplement per serving; (3) a description of the manufacturing process of the dietary supplement, 
including process controls; (4) a specification sheet for the dietary supplement that describes its 
critical safety attributes; and (5) the conditions of use recommended or suggested in the labeling of 
the dietary supplement, or if no conditions of use are recommended or suggested in the labeling of 
the dietary supplement, a discussion of the ordinary conditions of use of the dietary supplement.  
 
The conditions of use include the serving form (e.g., tablet, capsule, powder, liquid), serving size 
(e.g., weight or volumetric measure per serving), frequency of use (e.g., number of servings per 
day and interval between servings), duration of use, instructions for use, target population, 
excluded populations (if any), and any other restrictions on use.  For purposes of FDAs review, 
daily lifetime use by all age groups and other populations at the highest described serving size and 
number of servings will be assumed, unless the notification specifies that the labeling will contain 
restrictions on conditions of use.    
 
F.  Should you explain how the information in the NDIN provides a basis to 
conclude that the dietary supplement in which the NDI will be used will 
reasonably be expected to be safe? 
 
Yes.  Your NDIN should include a dietary supplement safety narrative containing your objective 
evaluation of the history of use or other evidence of safety cited in the notification, along with an 
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explanation of how the evidence of safety provides a basis to conclude that the dietary supplement 
containing the NDI, when used under the conditions described in the NDIN, will reasonably be 
expected to be safe.  
 
G.  What information should not be in the NDIN?  
 
Your NDIN should contain only data or information that identifies your NDI or the dietary 
supplement containing the NDI, or that helps provide a basis for the safety of the NDI or the dietary 
supplement.  An NDIN should not contain general or extraneous information.  For example, data or 
information that is used primarily to substantiate a claim about the efficacy of the ingredient or 
supplement is not useful unless it also contains information that pertains to identity or safety.  An 
NDIN should not include published review articles about other products, or publications and 
websites that promote other products, unless the information in the articles or websites can be 
specifically linked to the NDI or dietary supplement that is the subject of the notification.  An 
NDIN also should not include data or information intended to satisfy other regulatory requirements.  
For example, the requirement to notify FDA within 30 days after marketing a dietary supplement 
with a labeling claim described in section 403(r)(6) of the FD&C Act cannot be met by submitting 
the required information in a premarket NDIN.3   
 
H. When must an NDIN be submitted? 
 
You must submit your NDIN at least 75 days before the dietary supplement containing the NDI is 
introduced into interstate commerce or delivered for introduction into interstate commerce.  (21 
U.S.C. 350b(a); 21 CFR 190.6(a)).   
 
I.  Does FDA accept NDINs electronically? 
 
Yes.  We encourage you to submit your NDIN electronically through FDAs CFSAN Online 
Submission Module (COSM).  COSMs data validation helps prevent incomplete notifications by 
ensuring that all required fields are completed before the NDIN is submitted.  For more information 
about how to submit electronic NDINs, see the New Dietary Ingredients Notification Process page 
on the FDA website.4   
 
Firms that prefer to submit a paper NDINs still have the option to do so.  Please see the 
recommended template for the format and content of a paper NDIN in Appendix A.  To avoid 
delays, we recommend using the template in Appendix A to ensure the notification is complete 
before submission.   
 
J.  How many copies of an NDIN should be submitted?  
 
If you are submitting on paper, you must submit an original and two copies of your NDIN (see 21 
CFR 190.6(a)).  If the NDIN is submitted through COSM, you need not submit any duplicate 
 
3 The regulation governing these notifications is 21 CFR 101.93.  Please refer to 21 CFR 101.93(a)-(e) for instructions 
on how to submit a notification of a dietary supplement labeling claim under 21 U.S.C. 343(r)(6).  Notifications for 
labeling claims are not reviewed by the same staff who review NDINs.  
4 FDAs New Dietary Ingredients Notification Process page may be accessed at https://www.fda.gov/food/new-dietary-
ingredients-ndi-notification-process/how-submit-notifications-new-dietary-ingredient.     
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copies.    
 
K. Where should an NDIN be submitted?  
 
If you are submitting your NDIN electronically, you may do so via COSM at https://cfsan-
onlinesubmissions.fda.gov.  FDAs website provides details on how to use COSM.5 
 
If you are submitting a paper NDIN, send it to: 
 
Office of Dietary Supplement Programs (HFS-810) 
Center for Food Safety and Applied Nutrition 
Food and Drug Administration 
5001 Campus Drive 
College Park, MD 20740-3835   
 
L.  How should published literature and other scientific information cited in the 
NDIN be listed?   
 
If you are submitting your NDIN electronically, COSM provides instructions for listing your 
references.  For paper NDINs, we recommend listing your references in a reference section at the 
end of the notification (see suggested format in Appendix A to this guidance).  The list of 
references for both paper and electronic NDINs should include full citations to all published and 
unpublished sources cited or relied upon in the notification.  Furthermore, the list of references 
should include the reference number or short descriptor used to cite to each study or publication in 
the body of the NDIN.   
 
M. Do you have to provide copies of publications cited in the NDIN to FDA?    
 
Yes.  Whether submitting electronically or on paper, all references to published information offered 
in support of the NDIN must be accompanied by reprints or photocopies of such references (see 21 
CFR 190.6(b)(4)).  That means submitting a photocopy or reprint of the full text of each reference.  
Submitting only the abstract or bibliographic citation of a publication is not sufficient for FDA to 
evaluate whether the study supports the assertions in your NDIN.  In addition, we do not 
recommend submitting abstracts that are the only published report of a scholarly or scientific work.  
Because abstracts do not contain sufficient information to judge the reliability of the scientific 
conclusions drawn in the study and generally do not undergo the rigorous review and editing used 
to evaluate full-length publications, they do not provide data that are useful in evaluating the safety 
of an NDI.  
 
N. Can you use material published in languages other than English to support 
the safe use of an NDI?    
 
Yes.  Material written in a foreign language may be used as part of the basis for a conclusion that 
the NDI will reasonably be expected to be safe under the conditions of its intended use in the 
dietary supplement; however, the material must be accompanied by an accurate and complete 
 
5 FDAs New Dietary Ingredients Notification Process page may be accessed at https://www.fda.gov/food/new-dietary-
ingredients-ndi-notification-process/how-submit-notifications-new-dietary-ingredient. 
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English translation (21 CFR 190.6(b)(4)). 
 
O. How should unpublished scientific work be described in an NDIN?   
 
In your NDIN, you should provide a complete description of the data and methods used in an 
unpublished scientific work.  Without such a description, FDA reviewers may not be able to 
evaluate whether the data and methods support the safe use of the dietary supplement containing 
the NDI.  Abstracts or summaries of data (e.g., a 90-day study in five rats failed to show any 
toxicity) do not provide enough detail to make a safety determination. 
 
P.  Should raw data be provided in an NDIN?    
 
In some cases, yes.  It depends on how important the data in question are to the notifiers 
conclusion of safety and whether the data suggest a safety problem.  Although data summaries 
(e.g., a table containing the average value and range or standard deviation for each parameter 
measured in a safety study or the peaks in a spectrum or chromatogram) are often sufficient, raw 
data are sometimes necessary for a thorough safety review.  The more critical the data are to the 
overall safety evaluation, the more likely it is that more detail is needed.   
 
During review of the NDIN, FDA may request submission of raw data or other additional 
information.  If the additional information is a substantive amendment, FDA will reset the filing 
date and start a new 75-day review period (see 21 CFR 190.6(d); see also question IV.C in this 
guidance, which discusses when FDA expects to contact the notifier during NDIN review). 
 
Q. How should you identify information in an NDIN that you believe is trade 
secret or confidential commercial information (CCI)?  
 
For the first 90 days after the filing date of an NDIN, FDA will not disclose the existence or 
content of the notification.  After the 90th day, all information in the NDIN will be placed on 
public display, except for any information that is trade secret or CCI (see 21 U.S.C. 350b(a); 21 
CFR 190.6(e)). 
 
We recommend that you clearly identify any information in the NDIN that you believe is trade 
secret or CCIeither by marking the information where it appears in the notification or by 
identifying this information in a separate document that accompanies the notificationand that 
you explain the basis for this belief.  Likewise, if you believe there are no trade secrets or CCI 
contained in the NDIN, we request that you state this in your notification. 
 
Trade secret information may consist of any commercially valuable plan, formula, process, or 
device that is used for the making, preparing, compounding, or processing of trade commodities 
and that can be said to be the end product of either innovation or substantial effort (21 CFR 
20.61(a)).  There must be a direct relationship between the trade secret and the productive process; 
for example, information relating to the manufacturing process (see 21 CFR 20.61(a)).  Examples 
of trade secret information might include manufacturing methods and product composition (if 
different from what is declared on the label), product specifications needed to protect proprietary 
composition information (including proprietary analytical methods used to evaluate the product), 
and certificates of analysis. 
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CCI covers information that is confidential6 and used in a business (21 CFR 20.61(b)).  Examples 
of CCI might include sales statistics, dollar volume, amount or source of income (e.g., a companys 
list of customers), profits or losses, expenditures (of any person, firm, partnership, corporation, or 
association), names of suppliers or subcontractors, or brand of equipment.  
 
The following data and information contained in or related to a notification are generally not trade 
secrets or CCI and, therefore, would be available for public disclosure after the 90th day after the 
NDINs filing date: 
 
  Information about history of use or other safety information related to the NDI or the 
dietary supplement, which is generally based on published studies7; and   
  Correspondence and written summaries of oral discussions relating to the notification, 
except specific information that is exempt from disclosure under 21 CFR 20.61. 
 
R. What signature and contact information should you provide in an NDIN? 
 
FDA regulations require an NDIN to be signed by the person designated by the manufacturer or 
distributor of the dietary supplement that contains the NDI (see 21 CFR 190.6(b)(5)).  This person 
should be the primary contact, who represents the notifier in any discussions with FDA about the 
NDIN and who designates any additional contact persons in the notification or in subsequent 
correspondence.  Based on our experience, FDA has found that it is helpful for the notifier to 
designate additional contact persons to help ensure a timely response to FDAs questions. Contact 
persons can be agents, employees, officers, consultants, or attorneys for the notifier. 
 
If you are submitting your NDIN on paper, the typed or printed name, title, address, telephone 
number and, if available, email address of the primary contact person should be listed at the end 
of the cover letter that accompanies the notification (see suggested notification format in 
Appendix A of this guidance) so that FDA can reach them when necessary.  The typed or printed 
names, titles, addresses, telephone numbers and, if available, email addresses of additional 
contact persons for the NDIN should be listed after the contact information for the primary 
contact.   
 
IV.  What Happens After an NDIN Is Submitted? 
 
A. When is an NDIN considered to be filed?  
 
The date when FDA receives a complete NDIN is the date of that notifications filing.  A 
complete NDIN is a notification that contains all the information required by 21 CFR 190.6.  
The date of filing is the start of the 75-day premarket review period during which the 
manufacturer or distributor of a dietary supplement containing an NDI may not market the 
dietary supplement (21 U.S.C. 350b(a)(2); 21 CFR 190.6(c)).  
 
6 Food Marketing Institute v. Argus Leader Media, 139 S. Ct. 2356 (2019). 
7 On occasion, FDA gets questions regarding the posting of unpublished and published studies on 
www.regulations.gov.  As a general matter, FDA does not post these studies in the NDIN docket on 
www.regulations.gov.   
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B.  What are examples of omissions that cause an NDIN to be incomplete?  
 
An incomplete NDIN is one that does not contain all the information required by 21 CFR 190.6.  If 
we find that your NDIN is incomplete, we will inform you via COSM or in writing by U.S. mail or 
a courier service.  FDA does not evaluate safety or identity information in incomplete NDINs.   
 
Examples of omissions that can cause an NDIN to be incomplete include:   
 
  Material in a language other than English that is either not translated or is translated 
inaccurately or incompletely. 
  Citations to published literature for which a full copy of the publication is not provided. 
  An NDIN that is not signed, or contact information that is inaccurate and does not permit 
FDA to establish contact with the notifier. 
  Failure to provide the Latin binomial name, including the author citation, for any ingredient 
that is a botanical or derived from a botanical.   
  
An incomplete NDIN does not satisfy the notification requirement found in section 413(a)(2) of the 
FD&C Act (21 U.S.C. 350b(a)(2)).  Therefore, if the dietary supplement containing the NDI is 
marketed in reliance on an incomplete NDIN, it is deemed to be adulterated under section 402(f) of 
the FD&C Act (21 U.S.C. 342(f)).   
 
C. Will you hear from FDA during the NDIN review period?  
 
If we have questions during the NDIN review process, we will contact you.  For example, we 
may request that you submit more information.  Note that after reviewing a submission of 
additional information, FDA may determine that the submission is a substantive amendment and 
reset the filing date (see 21 CFR 190.6(d)).  Should we make this determination, we will notify 
you that the 75-day review period is being reset and provide the new filing date, which will be 
the date of receipt by FDA of the information that constitutes the substantive amendment (see 21 
CFR 190.6(d)).  
 
D. What type of response may you expect to receive from FDA, and when?  
 
After receiving an NDIN, FDA sends an acknowledgement of receipt to the notifier stating the date 
of receipt of the notification (see 21 CFR 190.6(c)) and provides the NDIN number assigned to the 
notification.  The date of the NDINs receipt is also the filing date on which the 75-day prohibition 
on introducing the NDI-containing dietary supplement into interstate commerce begins (21 CFR 
190.6(c)).  We may use electronic communication to send the acknowledgement of receipt.  In this 
communication, we will also state that we intend to send a detailed response letter within 75 days 
of the filing date.   
 
After finishing our review, FDA will send the response letter to the notifier.  Examples of the types 
of response FDA commonly sends include:   
 
  Letter of acknowledgement without objection;  
  Letter listing deficiencies that make the NDIN incomplete under 21 CFR 190.6;  
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  Objection letter raising concerns with the adequacy of the identity information or safety 
information (e.g., identifying gaps in the history of use or that the safety information on the 
NDI does not support the conditions of use); and  
  Letter raising other regulatory issues with the ingredient or product (e.g., the ingredient is 
not a dietary ingredient under 21 U.S.C. 321(ff)(1), or the product does not satisfy all parts 
of the dietary supplement definition under 21 U.S.C. 321(ff)).  
 
Note that receiving an acknowledgement letter without objection means that FDAs review of the 
NDIN did not find any reason to object to the notifiers basis for concluding that the NDI and the 
dietary supplement containing the NDI will reasonably be expected to be safe.  However, such a 
letter does not constitute an independent finding by FDA that the NDI and the dietary supplement 
that contains the NDI are safe, or that they are not adulterated under section 402(f) of the FD&C 
Act.  FDA is not precluded from taking action in the future against a dietary supplement containing 
your NDI if it is adulterated, misbranded, or if its distribution in interstate commerce otherwise 
violates the FD&C Act. 
    
The NDIN and the response letter sent at the end of FDAs review will be kept confidential for 
90 days after the filing date, as required by our regulation at 21 CFR 190.6(e).  After the 90-day 
date, the NDIN and the response letter will be placed on public display at www.regulations.gov, 
except for any information that is trade secret or CCI (see 21 CFR 190.6(e)).8  We recommend 
that you  clearly identify any information in the notification that you believe is trade secret or 
CCIeither by marking the information where it appears in the notification or by identifying 
this information in a separate document that accompanies the NDINand that you explain the 
basis for this belief.  Likewise, if you believe there are no trade secrets or CCI contained in the 
NDIN, we request that you state this in the notification. 
 
 
V.  Meetings Between FDA and Notifiers   
Some firms request meetings with FDA to ask questions and get preliminary and non-binding 
feedback from FDA regarding planned or potential NDINs.  For example, some notifiers find it 
useful to obtain information regarding identity, safety, or how to submit before submitting an 
NDIN.   Others have questions on submitting a new NDIN that is related to a previously reviewed 
submission.  For example, they may wish to obtain clarification about what information could be 
useful to address concerns raised in a prior related FDA response letter.  It is entirely voluntary to 
request feedback on a potential or planned NDIN.  However, should you wish to do so, you may 
email FDA at NDITEAM@fda.hhs.gov, using the subject line [Firm Name] Pre-NDIN Meeting 
Request.  Note that a request for a meeting may be denied, although this is a rare occurrence.  For 
example, we may deny a meeting request if a previous meeting for the same purpose has already 
been held and no significantly new information has become available, or if the subject matter is not 
appropriate for a meeting with FDA.    
Meeting requesters should be aware that meeting materials, like other agency records, may be 
 
8 Redacted copies of FDAs response letters are publicly available on www.regulations.gov.  Information on how to 
access them is available at https://www.fda.gov/food/new-dietary-ingredients-ndi-notification-process/submitted-75-
day-premarket-notifications-new-dietary-ingredients.   
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requested under the Freedom of Information Act9 (FOIA) and, unless the information being 
requested is classified as trade secret, CCI, or is otherwise exempt from disclosure under the FOIA, 
it will be released to requesters. 
 
VI.  Paperwork Reduction Act of 1995 
This guidance contains information collections that are subject to review by the Office of 
Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501- 
3521). 
 
The time required to complete this information collection is estimated to average one (1) hour per 
submission, including the time to review instructions, search existing data resources, gather the data 
needed, and complete and review the information collection. Send comments regarding this burden 
estimate or suggestions for reducing this burden to: 
 
Office of Dietary Supplement Products (HFS-810)  
Center for Food Safety and Applied Nutrition  
Food and Drug Administration 
5001 Campus Drive  
College Park, MD 20740  
 
An agency may not conduct or sponsor, and a person is not required to respond to, a 
collection of information unless it displays a currently valid OMB control number. The 
OMB control number for this information collection is 0910-0330 (To find the current 
expiration date, search for this OMB control no. available at 
https://www.reginfo.gov/public/do/PRAMain). 
 
 
Document History 
  July 2011  Original version of the draft guidance was issued. 
  August 2016  2016 Revised Draft Guidance was issued. 
  March 2024  Final guidance issued. 
   
 
9 5 U.S.C. 552. 
 
 
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Appendix:  Recommended Template for Organizing an NDIN that is 
Submitted on Paper  
 
Note:  Parenthetical references to question numbers in this template refer to questions in the 
body of the guidance. 
 
I.  Cover Letter 
Consumer Safety Officer 
Office of Dietary Supplement Programs (HFS-810)  
Center for Food Safety and Applied Nutrition 
Food and Drug Administration 
5001 Campus Drive 
College Park, MD 20740  
 
DEAR [Name]: 
 
The undersigned, ___________________________________, (Name of the primary contact 
person designated by the manufacturer or distributor that is submitting the notification) 
submits this NDIN under section 413(a)(2) of the Federal Food, Drug, and Cosmetic Act with 
respect to ___________________________________(Name of the dietary supplement 
containing the NDI), which contains the following new dietary 
ingredient:___________________________________.   
 
 
_____________________________________ 
(Signature of the contact person designated by the manufacturer or distributor)  
 
 
Primary Contact: (see question III.R) 
(Typed or printed name, title, address, telephone number and, if available, email address of the 
primary contact person.) 
 
Additional Contacts: (see question III.R) 
(Typed or printed name, title, address, telephone number and, if available, email address of 
each additional contact person.) 
 
II.  Table of Contents 
The table of contents should consist of a listing of the sections of the NDIN in the order in 
which they appear, along with the beginning page number of each section.  Each section of 
the notification should begin on a new page (see question III.C). 
 
III.   Body of the Notification 
 
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A.  Administrative 
1.  Description of the NDI, the dietary supplement containing the NDI, and the 
conditions of use of the dietary supplement (see questions III.D  III.E).   
2.  Identification of information believed to be trade secret or confidential 
commercial information, including the basis for identifying the information as 
such (see question III.Q). 
3.  Safety narrative for the dietary supplement. 
 
B.  Attachments used to establish identity 
[Provide only the information that identifies your NDI and dietary supplement (see question 
III.G).] 
 
1.  Detailed description of the identity of the NDI and the dietary supplement. 
2.  Manufacturing methods and practices to establish identity and safety. 
3.  Specifications to identify dietary ingredients, other ingredients, and contaminants, 
including the analytical methods used to determine each. 
4.  Identity References 
[This subsection should contain reprints or photocopies of the full text of all 
published and unpublished identity references that have not already been included 
in other subsections of the Identity section.] 
 
C.  Safety and Toxicology Attachments 
[Provide only the information that formed the basis for your conclusion that the dietary 
supplement containing the new dietary ingredient is reasonably expected to be safe (see 
question III.G).] 
 
1.  Safety Narrative for the NDI 
2.  Toxicology Studies 
3.  Human Studies 
4.  Other Studies 
5.  History of Use 
6.  Other Evidence of Safety 
7.  Other Safety and Toxicology References 
[This subsection should contain reprints or photocopies of the full text of all 
published and unpublished safety and toxicology references that have not already 
been included in other subsections of the Safety and Toxicology section.] 
 
IV.   Complete List of References 
 
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