Download:
pdf |
pdfU.S. Food and Drug Administration
Draft Form FDA 3880:
New Dietary Ingredient Notification (NDIN): Electronic
Submission
See FDA’s website,
http://www.fda.gov/Food/DietarySupplements/NewDietaryIngredientsNotificationProcess/ucm3566
20.htm, for additional information.
1
Submitting a New Dietary Ingredient Notification Electronically
After you have logged in to the FDA Industry Systems (FIS) website, choose the link "New Dietary
Ingredient" from the list of systems available on the FDA’s Unified Registration Listing System (FURLS)
home page. This will take you to the webpage “NDI Home Main Menu” with the banner “75 DAY
PREMARKET NEW DIETARY INGREDIENT (NDI) NOTIFICATION” (Figure 1). Each screen in the NDI
electronic submission process has this banner.
At the top right of each page are the links “FURLS Home”, which will take you to the FIS/FURLS home
page, and "NDI Home," which will take you to the NDI Home Main Menu (Figure 1). Choose the link
“FURLS Home” to log out.
To submit a notification for a new dietary ingredient, select the link “Enter New Notification” from the
page “NDI Home Main Menu” (Figure 1).
Figure 1
2
The screens you will see throughout the NDI online notification process will have the following features:
At the top of every screen is a status bar that will track your progress through each step of the process (for
example, see Figure 2). A "Get Help" link above the menu bar on the right side of the page will provide
page-specific help. For an overview of all the help files available, see the FDA Industry Systems Index of
Help Pages available separately through the “Get Help” link.
In addition, at the bottom of each screen you will see 1, 2 or 3 navigation buttons, depending on the
step in the online notification process (for example, see the bottom of Figure 2). In steps 2 to 5 and step
7, the button on the far left at the bottom of the page labeled “Previous” will take you back one step in
the process to the previous section of the notification. Please note that unsaved information entered
on the form is lost if you press the “Previous” button. In steps 1 to 3, step 6 and step 7, the button
labeled “Save and Exit” on the bottom right saves the data you have entered as a draft, and takes you to
an exit confirmation screen that will provide you with a draft reference ID and a deadline to submit the draft
notification. In steps 1 to 4 and step 6, the button on the bottom right labeled “Next” takes you to the
next screen for entering notification data. In step 5, the button labeled “Save and Upload” on the
bottom far right saves a draft of the notification and navigates away from the electronic submission
portal to the screen called “NDI Document Upload”. After you have uploaded your supporting
documents, you must go back to the NDI Home main menu to retrieve the draft notification and
continue from step 6 to the end to complete and submit the notification. In the last step (step 7), the
button labeled “Submit” on the bottom far right submits the notification to the FDA.
Figure 2
3
Submitting an NDIN Electronically - Step 1
Figures 3, 4, 5, 6 and 7 show the information to be entered in Section 1 of the notification.
Section 1 – Submitter, Notification Owner, and Contact Information
Fields marked with an asterisk (*) in the instructions must be completed to proceed to the next screen. If
any of the required fields are not completed, you will be prompted to enter the missing information
before proceeding to the next screen. If all of the required fields are completed with appropriate data,
the notification will be in compliance with the NDIN regulation, 21 CFR 190.6. If these fields are not filled
in as required, the primary contact designated in the notification will receive an incomplete response
letter from FDA.
Section 1 contains buttons specific to this section. The “Auto fill from Account Information” button on the
far right in the middle of the screen automatically fills the contact fields with relevant information from
your FURLS account (see Figure 4, top right). You will be able to edit the contact fields as necessary. The
button on the right just above the bottom of the screen is labeled “Add Contact”, which stores the contact
information just entered in the “Contact List” table that is located below the instructions on the screen
and above the contact fields (see Figure 3 for the location of the “Contact List” table). The “Clear” button
on the right just above the bottom of the screen clears the contact information entered into the fields
without storing the information in the “Contact List” table (see Figure 4).
4
Figure 3
5
Figure 4
6
Figure 5
7
Please enter the following information about the submitter of the notification in Section 1a and then
press the Add Contact button:
Field
Description
*Type of Submitter
Please select the type of firm or person that is submitting the NDI
notification. Select all that apply.
Select ‘Manufacturer of NDI’ if the notification is being submitted
by the manufacturer of the NDI.
Select ‘Distributor of NDI’ if the notification is being submitted
by the distributor of the NDI.
Select ‘Manufacturer of Dietary Supplement Containing NDI’ if
the notification is being submitted by the manufacturer of a
dietary supplement that contains the NDI.
Select ‘Distributor of Dietary Supplement Containing NDI’ if
the notification is being submitted by the distributor of a
dietary supplement that contains the NDI.
Select ‘Agent/ Attorney/ Consultant’ if the notification is being
submitted by a lawyer, consultant, or other agent on behalf of a
manufacturer or distributor of the NDI or of a dietary supplement
that contains the NDI.
Company Name
If the submitter is a company, enter the full name of the
company.
*Mailing Address Line 1
The street name and number or post office box number for the
submitter’s mailing address.
Mailing Address Line 2
Optional; can be used for building number, suite number, or
other information that doesn’t fit on the first line.
*Country
The country for the submitter’s mailing address. Defaults to
‘United States.’ For foreign addresses, select the appropriate
country from the pull-down menu.
*Zip Code or Postal Code
The zip code for the submitter’s mailing address. For addresses
outside the United States, enter the postal code, if any.
*City
The city for the submitter’s mailing address.
*State or Province
The state, province, or territory for the submitter’s mailing
address. Select a state, province, territory, or “Not applicable”
from the pull-down menu.
8
Please enter the following information about the owner of the notification in Section 1b and then press
the Add Contact button:
Field
Description
Is the owner of the
notification the same as
the submitter?
Answer ‘Yes’ if the owner of the notification is the same as the
submitter of the notification identified in section 1a. Selecting
‘Yes’ will automatically fill the rest of the fields in section 1b with
the information entered for the submitter of the notification in
section 1a. If you select ‘No,’ you must fill in the rest of the
fields in this section.
*Type of Manufacturer or
Distributor
Please select all that apply.
Select ‘Manufacturer of NDI’ if the owner of the notification is
the manufacturer of the NDI.
Select ‘Distributor of NDI’ if the owner of the notification is the
distributor of the NDI.
Select ‘Manufacturer of Dietary Supplement Containing NDI’ if
the owner of the notification is the manufacturer of a dietary
supplement that contains the NDI.
Select ‘Distributor of Dietary Supplement Containing NDI’ if
the owner of the notification is the distributor of a dietary
supplement that contains the NDI.
*Company Name
If the notification owner is a company, enter the full name of the company.
Otherwise, enter the full name of the individual.
*Mailing Address Line 1
The street name and number or post office box number for the notification
owner’s mailing address.
Mailing Address Line 2
Optional; can be used for building number, suite number, or other
information that doesn’t fit on the first line.
*Country
The country for the notification owner’s mailing address. Defaults to
‘United States.’ For foreign addresses, select the appropriate country from
the pull-down menu.
*Zip Code or Postal Code
The zip code for the notification owner’s mailing address. For addresses
outside the United States, enter the postal code, if any.
*City
The city for the notification owner’s mailing address.
*State or Province
The state, province, or territory for the notification owner’s mailing
address. Select a state, province, territory, or “Not applicable” from the
pull-down menu.
9
Figure 6
10
Please specify the primary contact for the notification in Section 1c (see Figure 6). The primary
contact is a person designated to communicate with FDA with regard to matters arising during
FDA’s review of the notification and to be the primary point of contact with the agency. The
primary contact can be an employee or official of the notification owner, the notification
submitter, or a third party (such as a consultant or attorney).
Other contacts authorized to communicate with the FDA during the notification review should
be specified in Section 1d (described below). Additional contacts may also be designated in a
separate letter sent as an amendment to the notification at a later date. FDA reviewers will
communicate only with authorized contacts.
11
Please enter the following information about the primary contact person in Section 1c and then press the
Add Contact button:
Field
Description
*Type of Contact
Select the type of primary contact authorized to communicate with the
FDA during the notification review.
Select ‘Submitter of the notification’ if the contact is an official or
employee of the submitter of the NDIN. Selecting this type will
automatically fill the company name and address fields in section
1c with the information provided for the submitter in section 1a.
Select ‘Owner of the notification’ if the contact is an official or
employee of the owner of the NDIN. Selecting this type will
automatically fill the company name and address fields in section
1c with the information provided for the notification owner in
section 1b.
Select “Agent/Attorney/Consultant” if the contact is an attorney,
consultant, or other agent representing the notification owner.
If none of the other selections applies, select ‘Other’ to specify an
alternative contact type. Describe the contact’s relationship to the
notification owner or submitter in the field provided.
*Name of Contact Person
First and last name of the primary contact person.
Company Name
The name of the primary contact person’s company, if any.
Position
Title of the primary contact person.
* Mailing Address Line 1
The street name and number or post office box number for the primary
contact’s mailing address.
Mailing Address Line 2
Optional; can be used for building number, suite number, or other
information that doesn’t fit on the first line.
*Country
The country for the primary contact’s mailing address. Defaults to ‘United
States.’ For foreign contacts, select the appropriate country from the pulldown menu.
*Zip Code (Postal Code)
The zip code for the primary contact’s mailing address. For addresses
outside the United States, enter the postal code, if any.
*City
The city for the primary contact’s mailing address.
*State or Province
The state, province, or territory for the primary contact’s mailing address.
Select a state, province, territory, or “Not applicable” from the pull-down
menu.
*Telephone Number
The telephone number of the primary contact person.
Fax Number
The telephone number of the primary contact person’s FAX machine.
*Email Address
An electronic mail address for the primary contact person.
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Figure 7
13
Please enter in Section 1d the following information for each additional contact you wish to designate. To
add more than one additional contact, enter the contact information and press the button Add Contact.
Field
Description
Type of Contact
Select the type of contact.
Select ‘Submitter of the notification’ if the contact is an official or
employee of the submitter of the NDIN. Selecting this type will
automatically fill the company name and address fields in section
1c with the information provided for the submitter in section 1a.
Select ‘Owner of the notification’ if the contact is an official or
employee of the owner of the NDIN. Selecting this type will
automatically fill the company name and address fields in section
1c with the information provided for the notification owner in
section 1b.
Select “Agent/Attorney/Consultant” if the contact is an attorney,
consultant, or other agent for the notification owner.
If none of the other selections applies, select ‘Other’ to specify an
alternative contact type. Describe the contact’s relationship to the
notification owner or submitter in the field provided.
Name of Contact Person
First and last name of the contact person.
Company Name
The name of the contact person’s company, if any.
Position
Title of the contact person.
Mailing Address Line 1
The street name and number or post office box number for the contact’s
mailing address.
Mailing Address Line 2
Optional; can be used for building number, suite number, or other
information that doesn’t fit on the first line.
Country
The country for the other contact’s mailing address. Defaults to ‘United
States.’ For foreign contacts, select the appropriate country from the pulldown menu.
Zip Code (Postal Code)
The zip code for the contact’s mailing address. For addresses outside the
United States, enter the postal code, if any.
City
The city for the contact’s mailing address.
State or Province
The state, province, or territory for the contact’s mailing address. Select a
state, province, territory, or “Not applicable” from the pull-down menu.
Telephone Number
The telephone number of the contact person.
Fax Number
The telephone number of the contact person’s FAX machine.
Email Address
An electronic mail address for the contact person.
14
Submitting an NDIN Electronically - Step 2
Section 2 – General Administrative Information
The form for section 2 is shown in Figure 8.
Figure 8
15
Please enter in Section 2 the following information about the new dietary ingredient notification. In the
instructions below, the fields marked with an asterisk (*) must be completed to proceed to the next
screen.
Field
Description
1: Name of New Dietary
Ingredient
Enter the name of the new dietary ingredient that is the subject of the
notification. Please note that for an NDI notification that concerns an NDI
that is a combination of two or more NDIs, the NDI notification should
include safety information for each component NDI as part of the safety
information for the combination NDI.
*2: Have you designated
information in your
notification that you view
as a trade secret or
confidential commercial
information? (Check one)
Select ‘Yes, see attached designation of confidential information’ if there
are trade secrets or confidential commercial information in the notification
and you are providing an attachment detailing the information you view as
confidential. This attachment should be uploaded in Section 5.
Select ‘Yes, information is designated at the place where it occurs in the
notification’ if you have marked certain material as confidential within the
notification.
Select ‘No’ if you do not consider any of the information in the notification
to be a trade secret or confidential commercial information.
*3: Are you providing a
redacted copy of some or
all of the notification?
(Check one)
Select ‘Yes’ if you are including a redacted copy of your notification. The
redacted copy should be uploaded as an attachment in Section 5.
Select ‘No’ if you are not including a redacted copy of your notification.
*4: Are all citations to
published information
accompanied by reprints
or full photostatic copies
of the publication? (Check
one)
Select ‘Yes’ if the notification includes reprints or photocopies of all
publications cited.
Select ‘No’ if the notification cites publications and does not include
reprints or photocopies of all publications cited. If you select ‘No,” your
notification will be incomplete and you will not be able to transmit it to
FDA.
*5: Are the notification
and all publications
submitted in English or
accompanied by a
complete and accurate
English translation? (Check
one)
Select ‘Yes’ if the entire notification, including any supporting publications,
is in English or if the notification includes a complete and accurate English
translation of any foreign language materials submitted.
Select ‘No’ if any part of the notification, including supporting publications,
is being submitted in a foreign language without a complete and accurate
English translation. If you select ‘No,” your notification will be incomplete
and you will not be able to transmit it to FDA.
16
Submitting an NDIN Electronically - Step 3
Section 3 – Description of New Dietary Ingredient and Dietary Supplement
Please describe the new dietary ingredient and the dietary supplement containing the new dietary
ingredient by answering the questions in Section 3 (shown in Figures 9 & 10).
Figure 9
17
Figure 10
18
Please enter in Section 3 the following information about the new dietary ingredient. In the instructions
below, the fields marked with an asterisk (*) must be completed to proceed to the next screen.
Field
Description
1. New Dietary Ingredient
Type
(Check all that apply)
Select the dietary ingredient type to which the new dietary ingredient
that you wish to introduce belongs, using the categories provided.
More than one category may apply; e.g., for vanilla extract you would
check the “herb or other botanical, “dietary substance,” and
“concentrate, metabolite, constituent, extract, or combination” boxes.
2: New dietary ingredient name
and related information
Enter the maximum level of the NDI (including units of
measurement) in a serving of the dietary supplement, if your
notification applies to a specific dietary supplement. If you are a
bulk supplier or if your notification is intended to cover dietary
supplements at a range of doses, enter the maximum level of the
NDI (including units of measurement) per serving that you have
concluded will reasonably be expected to be safe under the
conditions of use described in the notification.
The NDI name you entered in section 2 will be filled in for you in
the first field below the maximum serving level.
Next, list the trade name of the NDI and any synonyms for the NDI
(other names under which the NDI is known) that should be used
to search the scientific literature about the safety of the NDI.
For botanical and microbial NDIs, enter the following additional
pieces of information:
•
•
•
The plant part and plant strain from which the NDI is taken.
(For microbial NDIs, enter the microbial strain.)
The Latin binomial name.
The author of the Latin binomial name (if applicable).
*3: Dietary supplement serving
form (Check all that apply)
Select the form of the dietary supplement containing the NDI. If the NDI
will be an ingredient of dietary supplements in more than one form,
select all forms that apply. If the form of your dietary supplement is not
listed, select ‘Other’ and describe the form in the text box provided. If
you are a bulk ingredient supplier, select ‘Other’, enter “Bulk Ingredient
Supplier” in the text box, and check serving forms you recommend. If
the serving form you recommend is not listed, describe the form in the
text box after “bulk ingredient supplier.”
*4: Description of dietary
supplement (Include level of
the NDI and all other
ingredients in one unit of the
dietary supplement)
List the names and levels of all ingredients in each dietary supplement
that contains the new dietary ingredient. Provide the level per unit of
the dietary supplement, not per serving of the dietary supplement. The
level should correspond to the level in a specified serving form in
question 3. You should list both dietary ingredients and other
19
Field
Description
ingredients for each supplement.
If the notification concerns an NDI that is a combination of two or more
other NDIs, you should provide the following information for each
component NDI: Synonyms, Trade Name, and NDI type (using categories
from Question 1). Where relevant, you should also include the following
additional information for each component NDI: Plant Part, Strain, Latin
Binomial Name, Author of Latin Binomial Name, CAS registry number,
Unusual form (e.g., malted barley or immature apples), Type of
manufacture (e.g., >99% purity, 50:1 dry leaf extract, or fermentation
product).
If you are a bulk ingredient supplier, provide the requested information
about NDI level, other ingredients, form, and type of manufacture based
on the conditions of use that you recommend for your NDI and for
which you have a reasonable expectation of safety based on history of
use or other evidence.
If the notification is intended to cover more than one dietary
supplement containing the NDI, enter the description of the first dietary
supplement here, and enter the descriptions of the remaining dietary
supplements in the safety information attachment you will download
and complete in Section 4.
5: Conditions of Use of the
Dietary Supplement
Provide information on the conditions of use for each dietary supplement
containing the NDI.
If you are a bulk ingredient supplier, provide the conditions of use you
recommend for dietary supplements containing the NDI.
If the notification is intended to cover more than one dietary
supplement containing the NDI, enter the conditions of use for the first
dietary supplement here, and enter the conditions of use for the
remaining dietary supplements in the safety information attachment
you will download and complete in Section 4.
*5a: Serving Instructions (e.g.,
“take with food,” “take before
bed,” “dissolve in a glass of
water,” etc.)
Provide information on the serving instructions (directions for use) for
each dietary supplement containing the NDI.
*5b: Dietary supplement
serving size (weight or
volumetric measure), serving
frequency (# of servings/day,
interval between servings),
For each dietary supplement containing the NDI, provide information on
the dietary supplement serving size (weight or volumetric measure of
one serving of the dietary supplement), serving frequency (number of
servings per day, length of time between servings), duration of use, and
maximum daily intake level (weight or volumetric measure) of the 20
Field
Description
duration of use and maximum
total daily intake level
dietary supplement when taken as suggested in its labeling.
*5c: Target populations/
excluded populations/other
restrictions
For each dietary supplement containing the NDI, provide information on
the population groups for which the product is intended and on any
population groups that should not take the product. For example, you
may want to state that the dietary supplement should not be taken by
pregnant and lactating women or by individuals with certain medical
conditions (e.g., diabetics or individuals unable to metabolize
phenylalanine.) Also provide information on any other use restrictions
that may apply. For example, if the intake of the NDI or one of the other
dietary ingredients in the supplement needs to be limited for safety
reasons, you may want to state that the dietary supplement should not
be taken in combination with other dietary supplements that contain
the same dietary ingredient.
6: Other
Please provide any additional information describing the NDI and the
dietary supplement(s) containing the NDI. This field can also be used as
additional space to enter information on the answers to the questions in
this section.
21
Submitting an NDIN Electronically - Step 4
This section must be completed to proceed to the next screen.
Section 4 –Safety Information Attachment
In this section, you will download and fill in a safety information template describing the scientific
information on which you base your conclusion that the dietary supplement(s) containing the NDI will
reasonably be expected to be safe. Safety information means, among other things, information showing
that the NDI is identical or related to substances documented as having a history of use as food and/or to
test articles used in safety studies. In addition, safety information means documentation of history of use
as food, and the results of safety studies, including genetic toxicology studies, pharmacokinetic studies,
animal toxicology studies and human clinical studies. The template asks for details about the identity of
the NDI, verification of that identity, information about history of use as food, and/or other evidence
relevant to the safety of the NDI and the dietary supplement. The template also asks for reprints or
photostatic copies of all cited studies. After filling in the template, you will attach the completed safety
information template file and files containing the scientific publications cited in your notification.
22
Figure 11
To download the template file for entering your safety information, click on the blue link in the sentence
“Click here to download the Safety information template file” (see Figure 11). After you have downloaded
the template file, fill out the various sections in the template with the requested information about your
NDI and the dietary supplement(s) containing the NDI, and save the completed template to your
computer in one of the supported file formats (.doc, .docx, .rtf, or .pdf). You will be prompted to upload
attachments pertinent to sections 4 and 5 in subsequent screens. You may wish to combine the
completed safety information template file and the files containing cited studies in one file, and upload
this one file in the section called Safety Information Attachment. Alternatively, you may attach the files
containing cited studies separately by combining these files into one file each for identity, history of use,
and other evidence of safety, and attach these three files in the optional section called Additional
Attachments (see section 5).
23
Submitting an NDIN Electronically - Step 5
This is an optional section.
Section 5 – Additional Attachments
Additional attachments to the NDI notification are explained in Section 5 (shown in Figure
12). Uploading labeling for the dietary supplement containing the NDI will help FDA
evaluate what conditions of use are being recommended or suggested. If you are the
manufacturer or distributor of the NDI and do not have access to labeling for the dietary
supplement(s) in which the NDI will be used, please upload the labeling of the bulk NDI.
Figure 12
24
Attachments to be uploaded may include the following: Product labels (label for dietary supplement
containing the NDI or NDI bulk label, if dietary supplement label is not available), letter designating
additional contacts authorized to communicate with the FDA during the notification review, additional
safety information provided as an amendment to the notification, redacted copy of the notification, or
list of information you believe is trade secret or confidential commercial information. You should clearly
identify the attachments with appropriate descriptive file names (for example, first author, year, and
title or paraphrase of title for publications). You should number the pages in each attachment
consecutively. Buttons are provided for adding, editing and deleting attachments. If you need to correct
an attachment or add a new attachment after the notification has been submitted, contact FDA at
CFSAN-NDIN-submissions@fda.hhs.gov and we will send you a link that will allow you to upload
additional attachments. Although you cannot change an attachment once your notification has been
submitted to the FDA, you can upload an amendment that explains what information needs to be
changed.
Pressing the button “Save and Upload,” located on the far right on the bottom of the screen, saves a
draft of the notification in preparation for uploading your attachments. The next screen is the
confirmation screen, which provides you with a draft reference ID and a deadline to submit the draft
notification (see Figure 13). Click on the blue link in the sentence “Click here to begin your upload” at the
bottom of the screen, and you will be directed to the “NDI Document Upload” module to begin selecting
files to upload.
Figure 13
25
Submitting an NDIN Electronically - NDI Document Upload:
Figures 14, 15, and 16 illustrate the screens you will see next as you navigate away from the electronic
submission portal to the “NDI Document Upload” module. The first screen of NDI Document Upload has
the description of the Safety Information Attachment section of the notification on the top half of the
screen (see Figure 14) and the description of the Additional Attachments section of the notification on the
bottom half of the screen (see Figure 15). Under the “Safety Information Attachment” heading, you will
see a box captioned “Add Attachment.” Click on the Browse button in the box to locate the safety
information file with the completed template on your computer and select it, and then click Upload.
Then go down to the “Additional Attachments” heading and locate the box captioned “Add
Attachment(s)” below it. Click on the Browse button in the box to locate any additional attachments (e.g.,
publications you are submitting in support of your notification) on your computer, select them, and then
click Upload. Click the Submit button at the bottom of the screen to attach the uploaded documents to
your draft notification. The next screen (shown in Figure 16) confirms that the attachments have been
uploaded, and explains the next step to complete the notification. After you have uploaded the
attachments to your notification, click on the blue link in the sentence “Click here to go to FURLS Home”
at the bottom of the screen, and you will be directed to the screen “FURLS Home” to retrieve the draft
notification from the NDI Home main menu and continue with the electronic submission at step 6. In step
6, you will be given the opportunity to review the information you have entered and make changes before
submitting the notification to FDA.
26
Figure 14
27
Figure 15
28
Figure 16
29
Submitting an NDIN Electronically - Step 6
This section must be completed to proceed to the next screen.
Review Page
The NDIN review page is provided in Step 6 (shown in Figures 17, 18, 19, 20 and 21). Please review the
information in your notification, correct any errors, and fill in any missing information.
Figure 17
30
Figure 18
31
Figure 19
32
Figure 20
33
Figure 21
Review your NDIN information before submitting it to FDA. Selecting the EDIT button for a section brings
up the corresponding data entry form, where you can edit and save changes.
34
Submitting an NDIN Electronically - Step 7
Section 6 – Certification
Please read the certification statement, check the certification box, and enter your name and title in Section
6 (shown in Figure 22) to identify yourself as submitter. By checking the box and submitting the notification,
you certify that the information in the notification is true and accurate and that you are authorized to
submit the notification to FDA. This section must be completed to submit your notification and receive a
confirmation.
Figure 22
35
After you submit the notification, you will be directed to a confirmation screen similar to the one shown in
Figure 23.
Figure 23
36
FDA New Dietary Ingredient Notification Safety Information
NEW DIETARY INGREDIENT (NDI)
SAFETY INFORMATION
Enter your company name
Enter today’s date
1
FDA New Dietary Ingredient Notification Safety Information
Instructions
In this template, which supplements the data entry screens in the NDI notification electronic
submission portal, you will describe the scientific information on which you base your
conclusion that the dietary supplement containing the NDI will reasonably be expected to be
safe. Safety information includes, among other things, (1) information showing that the NDI
is identical or related to substances documented as having a history of use as food; (2)
information showing that the NDI is identical or related to test articles used in safety studies;
(3) information showing that a substance or product has a history of use as food; and (4)
safety data, including the results of genetic toxicology studies, pharmacokinetic studies,
animal toxicology studies and human clinical studies. This template asks for details about
the identity of the NDI, verification of that identity, information about history of use as food,
and any other evidence relevant to the safety of the NDI under its proposed conditions of use
in the dietary supplement. After filling in the template, you will upload the completed
template as an attachment to your online NDI notification and attach files containing the
scientific publications cited in your notification.
For a notification that concerns the use of an NDI in a dietary supplement that contains no
other ingredients, the safety of the NDI and the dietary supplement would be synonymous.
In other situations, however, that may not be the case. For example, when an NDI is used in
a dietary supplement with one or more other NDIs, the safety of the dietary supplement may
not be the sum of the safety of the individual NDIs. In such circumstances, you should
document your basis for concluding that the dietary supplement will reasonably be expected
to be safe and explain why that conclusion is reasonable. For example, if two botanical
extracts have separate histories of use in traditional medicine, but no history of being used
together, the safety of the combination may not be clear from the safety information
pertaining to the individual NDIs. On the other hand, if an extract of a medicinal herb is
combined with an extract of a material that has a long history of safe use as food, then it may
be reasonable to conclude that the combination is safe based on information about the safety
of the individual NDIs. If you wish to submit a notification for the use of an NDI in a dietary
supplement with other NDIs, the FDA recommends that you confer with a member of the
New Dietary Ingredient Review Team in FDA’s Division of Dietary Supplement Programs
about how to proceed. If you have any questions concerning this matter please contact the
New Dietary Ingredients Review Team, which can be reached on (240) 402-1756 or by email
at fred.hines@fda.hhs.gov.
If a section or subsection is not applicable to your notification, mark “N/A” in your response.
Sections marked as “Required” in the template’s section headings must have complete
responses in all subsections for which you have data. If you leave a “Required” section
blank or respond “N/A,” FDA will consider your notification incomplete for failure to
comply with 21 CFR 190.6(b). An incomplete notification does not satisfy the requirement
to submit an NDI notification. You may not introduce your NDI or a dietary supplement
containing the NDI into interstate commerce, or deliver the NDI or dietary supplement for
2
FDA New Dietary Ingredient Notification Safety Information
introduction into interstate commerce, until at least 75 days after you have submitted a
complete notification to FDA.
Please include full citations for all published and unpublished sources cited or relied on in
your notification in the Reference List (Section 5). You will be prompted to attach e-copies
of these sources when you return to the electronic submission portal after filling in this
template.
The template includes some sections identified as “Recommended.” These sections solicit
information that FDA considers helpful in evaluating NDI notifications. You are encouraged
but not required to respond to template sections that are identified as “Recommended.”
However, if you leave a “Recommended” section blank or respond “N/A” and FDA
determines that the information is needed to establish safety, your notification may be
considered inadequate to conclude that the NDI will reasonably be expected to be safe under
its proposed conditions of use in the dietary supplement.
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FDA New Dietary Ingredient Notification Safety Information
Table of Contents
1.
2.
3.
New Dietary Ingredient Identity Information (Recommended) ............................................. 6
1.1
Description of the identity of the NDI ............................................................................. 6
1.2
Description of the evidence verifying the identity of the NDI......................................... 6
1.3
NDI manufacture .............................................................................................................. 6
1.3.1
Raw materials............................................................................................................ 6
1.3.2
Formulation ingredients ............................................................................................ 6
1.3.3
Manufacturing process .............................................................................................. 6
1.3.4
NDI specifications .................................................................................................... 7
1.3.5
Methods of analysis .................................................................................................. 7
1.3.6
Analysis of potentially toxic processes ..................................................................... 7
1.3.7
Disintegration and dissolution profile....................................................................... 7
1.3.8
Shelf-life and conditions of storage .......................................................................... 7
Dietary Supplement Manufacture (Recommended) ............................................................... 7
2.1.
Raw materials ................................................................................................................... 7
2.2.
Formulation ingredients other than the NDI .................................................................... 8
2.3.
Manufacturing process ..................................................................................................... 8
2.4.
Product specifications ...................................................................................................... 8
2.5.
Methods of analysis .......................................................................................................... 8
2.6.
Analysis of potentially toxic processes ............................................................................ 8
2.7.
Disintegration and dissolution profile .............................................................................. 8
2.8.
Shelf-life and conditions of storage ................................................................................. 8
History Of Use Or Other Evidence Of Safety (Required) ...................................................... 9
3.1
History of use ................................................................................................................... 9
3.1.1
Description of the relationship between the historically consumed material and the
NDI or dietary supplement containing the NDI...................................................................... 9
3.1.2
Describe identity information verifying the relationship between the historically
consumed material and the NDI or dietary supplement containing the NDI .......................... 9
3.1.3
Historical conditions of use and cumulative exposure estimate for the historically
consumed material .................................................................................................................. 9
3.1.4
Adverse events associated with historically consumed material ............................ 10
3.1.5
Alternative rationale for reasonable expectation of safety based on history of use 10
3.2
Other evidence of safety................................................................................................. 10
3.2.1
Safety study type ..................................................................................................... 10
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FDA New Dietary Ingredient Notification Safety Information
3.2.2
Safety study title, if any .......................................................................................... 10
3.2.3
Citation for the safety study (either public or non-public), if any .......................... 10
3.2.4
Identity information verifying the relationship between the test article and the NDI
or the dietary supplement ...................................................................................................... 10
3.2.5
Route of administration, serving size, frequency of use, interval between servings,
and duration of use of the test article .................................................................................... 11
3.2.6
Study design and safety metrics .............................................................................. 11
3.2.7
Discussion of toxicity and conclusion .................................................................... 11
3.2.8
Alternative rationale for reasonable expectation of safety based on other evidence
of safety................................................................................................................................. 11
4. Basis For Concluding That the New Dietary Ingredient Will Reasonably Be Expected To
Be Safe For Use in the Dietary Supplement (Required) ............................................................... 11
4.1 Determination of the No-Observed-Adverse-Effect-Level (NOAEL) or LowestObserved Adverse Effect Level (LOAEL) ............................................................................... 12
4.2
Determination of safety factor........................................................................................ 12
4.3
Determination of the Acceptable Daily Intake (ADI) .................................................... 12
4.4
Determination of Estimated Daily Intake (EDI) and the EDI/ADI Ratio ...................... 12
4.5
Determination of margin of safety ................................................................................. 12
4.6
Safety narrative and conclusion ..................................................................................... 12
4.7
Alternative basis for reasonable expectation of safety ................................................... 12
5.
Reference List (Required) ..................................................................................................... 13
6.
Comments ............................................................................................................................. 13
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FDA New Dietary Ingredient Notification Safety Information
1. New Dietary Ingredient Identity Information (Recommended)
1.1 Description of the identity of the NDI
(Please identify and describe each source you rely on for information on the identity of the
NDI, including its composition where relevant. Please provide information on the regulatory
status of any excipients present in the NDI, including citations to any regulations that apply.)
1.2 Description of the evidence verifying the identity of the NDI
(Please identify and describe each source you rely on to verify the identity of the NDI. FDA
uses this information to determine whether the NDI is the same as or similar to the material
that is the subject of the studies and history of use documentation that the notification relies
on as evidence of safety.)
1.3 NDI manufacture
Please note: In a typical NDI notification, the description of the NDI’s manufacture contains
trade secrets (TS) and/or confidential commercial information (CCI). You may indicate to
FDA your designation of information as TS or CCI in Section 2 of the NDI portal. You also
may indicate in that section whether you are attaching a redacted copy of some or all of the
notification. If you provide a redacted copy of the notification or a list of information that
you believe to be TS or CCI, you should upload and attach it in Section 5 of the NDI portal.
1.3.1 Raw materials
(Please list and describe the raw materials used to manufacture the NDI.)
1.3.2 Formulation ingredients
(Please list and describe all ingredients used to manufacture the NDI.)
1.3.3 Manufacturing process
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FDA New Dietary Ingredient Notification Safety Information
(Please describe the process used to manufacture the NDI, and provide the process
flowchart.)
1.3.4 NDI specifications
(Please provide the specifications for the NDI.)
1.3.5 Methods of analysis
(Please provide the specification methods of analysis and other methods of analysis used
to establish the identity of the NDI.)
1.3.6 Analysis of potentially toxic processes
(Please describe your analysis of any potentially toxic process involved in the
manufacture of the NDI, including any analysis of impurities or external contaminants.)
1.3.7 Disintegration and dissolution profile
(Where relevant, please provide information on the disintegration and dissolution of the
NDI and describe any other processes relevant to the nature of the ingredient.)
1.3.8 Shelf-life and conditions of storage
(Please provide the shelf-life of the NDI, explain how the shelf-life was determined, and
describe the NDI’s conditions of storage. Please include any process workflows
involved.)
2. Dietary Supplement Manufacture (Recommended)
2.1.
Raw materials
(Please list and describe the raw materials used to manufacture the dietary supplement.)
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FDA New Dietary Ingredient Notification Safety Information
2.2.
Formulation ingredients other than the NDI
(Please list and describe all ingredients that are used to manufacture the dietary supplement,
including both dietary ingredients (other than the NDI) and non-dietary ingredients.)
2.3.
Manufacturing process
(Please describe the process used to manufacture the dietary supplement, and include the
process flowchart.)
2.4.
Product specifications
(Please provide the specifications for the dietary supplement.)
2.5.
Methods of analysis
(Please provide the specification methods of analysis and other methods of analysis used to
establish the identity of the dietary supplement.)
2.6.
Analysis of potentially toxic processes
(Please describe your analysis of any potentially toxic process involved in the manufacture of
the dietary supplement, including any analysis of impurities or external contaminants.)
2.7.
Disintegration and dissolution profile
(Where relevant, please provide information on the disintegration and dissolution of the
dietary supplement and describe any other processes relevant to the nature of the product.)
2.8.
Shelf-life and conditions of storage
(Please provide the shelf-life of the dietary supplement, explain how the shelf-life was
determined, and describe the product’s conditions of storage. Please include any process
workflows involved.)
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FDA New Dietary Ingredient Notification Safety Information
3. History Of Use Or Other Evidence Of Safety (Required)
3.1 History of use
If you are providing history of use as evidence of safety, then for each instance of history of
use you must either provide the information requested in Subsections 3.1.1 to 3.1.4, when
applicable, or discuss in Subsection 3.1.5 how the history of use evidence supports a
conclusion that the NDI will reasonably be expected to be safe under the conditions
recommended or suggested in the labeling of the dietary supplement.
3.1.1
Description of the relationship between the historically consumed
material and the NDI or dietary supplement containing the NDI
(Please describe the relationship between the historically consumed material and your
product(s). For example, if your NDI is an omega-3 fatty acid, how is it chemically
identical to the fish oil omega 3 fatty acids normally consumed by people?)
3.1.2
Describe identity information verifying the relationship between the
historically consumed material and the NDI or dietary supplement
containing the NDI
(Please describe the information verifying the relationship between each historically
consumed material and the NDI or dietary supplement.)
3.1.3
Historical conditions of use and cumulative exposure estimate for the
historically consumed material
(Please summarize the history of use data about the serving size, frequency of intake,
duration of use, and other relevant conditions of use of the historically consumed
material; provide your estimate of cumulative exposure to the historically consumed
material; explain how you calculated the estimate based on supporting history of use
data cited in your notification; and discuss how estimated consumer exposure to the
historically consumed material compares to the estimated consumer exposure to your
NDI under its proposed conditions of use in the dietary supplement. If the proposed
exposure of your NDI is above the levels for which a history of safe use in human food
has been documented, describe any other evidence of safety (such as animal testing or
human clinical trials) that you relied on to conclude that the NDI will reasonably be
expected to be safe under the conditions recommended or suggested in the labeling of the
dietary supplement.
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FDA New Dietary Ingredient Notification Safety Information
3.1.4
Adverse events associated with historically consumed material
(Please provide information on any adverse events associated with the historically
consumed material and whether any monitoring for adverse events was conducted.)
3.1.5
Alternative rationale for reasonable expectation of safety based on
history of use
(Provide any alternative or additional rationale for concluding that the history of use
evidence cited in your notification supports a conclusion that the NDI will reasonably be
expected to be safe under its proposed conditions of use in the dietary supplement.)
3.2 Other evidence of safety
If you relied on other evidence of safety in addition to or instead of history of use, you must
either provide the information requested in Subsections 3.2.1 to 3.2.7 for each safety study
cited in your notification, or explain in Subsection 3.2.8 how the safety data and information
in your notification support a conclusion that the NDI will reasonably be expected to be safe
under the conditions recommended or suggested in the labeling of the dietary supplement.
3.2.1
Safety study type
(Examples of relevant study types:
●Absorption, distribution, metabolism
and excretion (ADME) studies
●Acute toxicity studies
●Dose range-finding studies
●Subchronic (90 day) or chronic studies
●Reproductive or developmental studies
●Genetic toxicology studies
● Allergenicity studies
●Human clinical studies
●Adverse event reports and monitoring,
●Any other relevant studies for safety
assessment (please describe))
3.2.2
Safety study title, if any
3.2.3
Citation for the safety study (either public or non-public), if any
3.2.4
Identity information verifying the relationship between the test article
and the NDI or the dietary supplement
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FDA New Dietary Ingredient Notification Safety Information
3.2.5
Route of administration, serving size, frequency of use, interval
between servings, and duration of use of the test article
3.2.6
Study design and safety metrics
(Describe the route of administration, animal model, or, for clinical studies, the criteria
for selecting and screening human subjects. Include complete information on
observational endpoints (e.g., clinical chemistry, hematology, histopathology, etc),
methods used to determine and quantify these endpoints, frequency of data collection
(endpoint monitoring), and quality control procedures.
3.2.7
Discussion of toxicity and conclusion
(Discussion should include key study findings and biological relevance of any
statistically significant finding, calculation of the margin of safety using the estimated
No-Observed-Adverse-Effect-Level (NOAEL), Acceptable Daily Intake (ADI), Estimated
Daily Intake (EDI), and background exposure versus history of use, and how the data
from the study factor into your conclusion that the NDI will reasonably be expected to be
safe under its proposed condition of use in the dietary supplement.)
3.2.8
Alternative rationale for reasonable expectation of safety based on
other evidence of safety
(Provide any alternative or additional rationale for concluding that the other evidence of
safety cited in your notification supports a conclusion that the NDI will reasonably be
expected to be safe under its proposed conditions of use in the dietary supplement.)
4. Basis For Concluding That the New Dietary Ingredient Will
Reasonably Be Expected To Be Safe For Use in the Dietary
Supplement (Required)
(You must either provide the information requested in Subsections 4.1 to 4.6, when
applicable, or explain in Subsection 4.7 your alternative rationale for concluding, based on
the totality of the scientific evidence, that the NDI will reasonably be expected to be safe
under its proposed conditions of use in the dietary supplement.)
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FDA New Dietary Ingredient Notification Safety Information
4.1 Determination of the No-Observed-Adverse-Effect-Level (NOAEL) or
Lowest-Observed Adverse Effect Level (LOAEL)
(Please provide information to determine the NOAEL or the LOAEL for the NDI or dietary
supplement containing the NDI.)
4.2 Determination of safety factor
(Please state the safety factor that should be used to calculate the acceptable daily intake
(ADI) of the NDI or dietary supplement, and explain how you determined what safety factor
was appropriate.)
4.3 Determination of the Acceptable Daily Intake (ADI)
(Please explain how you determined the ADI for the NDI or dietary supplement.)
4.4 Determination of Estimated Daily Intake (EDI) and the EDI/ADI Ratio
(Please explain how you determined the EDI for the NDI or dietary supplement and provide
the daily intake ratio (EDI/ADI).)
4.5 Determination of margin of safety
(Please describe how you calculated the margin of safety for the NDI or dietary supplement
based on the studies cited in your notification.)
4.6 Safety narrative and conclusion
(Please summarize the safety evidence and describe how this body of evidence, considered as
a whole, provides a basis to conclude that the NDI will reasonably be expected to be safe
under its proposed conditions of use in the dietary supplement.)
4.7 Alternative basis for reasonable expectation of safety
(Provide any alternative or additional rationale for concluding, based on the evidence of
safety cited in your notification, that the NDI will reasonably be expected to be safe under its
proposed conditions of use in the dietary supplement.)
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FDA New Dietary Ingredient Notification Safety Information
5. Reference List (Required)
(List all published articles and other evidence of safety (published or unpublished) cited or relied
on in your notification here.)
6. Comments
(You have the option to provide any additional information about the NDI or the dietary
supplement that you believe will assist FDA in processing your notification.)
13
| File Type | application/pdf |
| Author | Santhanam, Swapna * |
| File Modified | 2014-10-01 |
| File Created | 2014-10-01 |