Document ID: FDA-2010-D-0503-0075
Agency: fda
Document Type: Notice
Title: Investigational New Drug Applications--Determining Whether Human 
Research Studies Can Be Conducted Without an Investigational New Drug Application; Guidance for Clinical Investigators, Sponsors, and 
Institutional Review Boards; Partial Stay and Republication of Guidance
Posted Date: 2015-10-30T04:00Z

[Federal Register Volume 80, Number 210 (Friday, October 30, 2015)]
[Notices]
[Pages 66907-66909]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-27729]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-D-0503]

Investigational New Drug Applications--Determining Whether Human 
Research Studies Can Be Conducted Without an Investigational New Drug 
Application; Guidance for Clinical Investigators, Sponsors, and 
Institutional Review Boards; Partial Stay and Republication of Guidance

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of administrative stay of action.

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SUMMARY: The Food and Drug Administration (FDA or we) is announcing a 
stay of portions of the final guidance for clinical investigators, 
sponsors, and institutional review boards (IRBs) entitled 
``Investigational New Drug Applications--Determining Whether Human 
Research Studies Can Be Conducted Without an IND.'' We are republishing 
the guidance with the portions that are being stayed clearly identified 
so readers can distinguish parts of the guidance that remain in effect 
from parts that are subject to this stay.

DATES: This stay is effective October 30, 2015 Submit either electronic 
or written comments on FDA guidances at any time.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2010-D-0503 for ``Investigational New Drug Applications--
Determining Whether Human Research Studies Can Be Conducted Without an 
Investigational New Drug Application; Guidance for Clinical 
Investigators, Sponsors, and Institutional Review Boards; Partial Stay 
and Republication of Guidance.'' Received comments will be placed in 
the docket and, except for those submitted as ``Confidential 
Submissions,'' publicly viewable at http://www.regulations.gov or at 
the Division of Dockets Management between 9 a.m. and 4 p.m., Monday 
through Friday.
     Confidential Submissions--To submit a comment with 
confidential

[[Page 66908]]

information that you do not wish to be made publicly available, submit 
your comments only as a written/paper submission. You should submit two 
copies total. One copy will include the information you claim to be 
confidential with a heading or cover note that states ``THIS DOCUMENT 
CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will review this copy, 
including the claimed confidential information, in its consideration of 
comments. The second copy, which will have the claimed confidential 
information redacted/blacked out, will be available for public viewing 
and posted on http://www.regulations.gov. Submit both copies to the 
Division of Dockets Management. If you do not wish your name and 
contact information to be made publicly available, you can provide this 
information on the cover sheet and not in the body of your comments and 
you must identify this information as ``confidential.'' Any information 
marked as ``confidential'' will not be disclosed except in accordance 
with 21 CFR 10.20 and other applicable disclosure law. For more 
information about FDA's posting of comments to public dockets, see 80 
FR 56469, September 18, 2015, or access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Philip L. Chao, Center for Food Safety 
and Applied Nutrition (HFS-024), Food and Drug Administration, 5100 
Paint Branch Pkwy., College Park, MD 20740, 240-402-2112, email: 
philip.chao@fda.hhs.gov; or Ebla Ali-Ibrahim, Center for Drug 
Evaluation and Research (HFD-160), Food and Drug Administration, 10903 
New Hampshire Ave., Silver Spring, MD 20993, 301-796-3691; or Stephen 
Ripley, Center for Biologics Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 71, Rm. 7301, Silver 
Spring, MD 20993, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of October 14, 2010 (75 FR 63189), we 
announced the availability of a draft guidance entitled ``Guidance for 
Industry: Investigational New Drug Applications (INDs)--Determining 
Whether Human Research Studies can be Conducted without an IND'' (``the 
draft guidance''). In the Federal Register of September 10, 2013 (78 FR 
55262), we published a document announcing the availability of the 
final version of the guidance, now entitled ``Guidance for Clinical 
Investigators, Sponsors, and Institutional Review Boards (IRBs) on 
Investigational New Drug Applications--Determining Whether Human 
Research Studies Can Be Conducted Without an IND'' (``the final 
guidance''). We received multiple comments asking for a further 
opportunity to comment on subsections VI.C and VI.D of the final 
guidance, which discuss when an IND is needed for studies involving 
products marketed as cosmetics or foods, respectively. Accordingly, on 
February 6, 2014, we issued a document reopening the comment period on 
only those subsections of the final guidance that address the 
applicability of the IND regulations to clinical research studies 
involving products marketed as cosmetics or foods (including dietary 
supplements) (79 FR 7204) (``notice to reopen''). The comment period 
closed on April 7, 2014. We received comments from trade organizations, 
individual companies, scientific associations, public interest 
organizations, and individuals in response to our notice to reopen. 
These comments raised questions about application of the IND 
requirement to certain clinical studies of conventional foods, dietary 
supplements, and cosmetics being investigated for uses covered by the 
drug definition in section 201(g)(1)(B) or (C) of the Federal Food, 
Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 321(g)(1)(B) or (C)).

II. The Stay

    FDA is staying part of the final guidance to allow for further 
consideration of issues raised by the comments submitted in response to 
the notice to reopen. Specifically, we are staying portions of 
subsection VI.D.2, ``Conventional Food,'' and all of subsection VI.D.3, 
``Studies Intended to Support a Health Claim,'' except as to studies 
intended to evaluate whether a food substance reduces the risk of a 
disease in individuals less than 12 months old, those with altered 
immune systems, and those with serious or life-threatening medical 
conditions. Subsections VI.D.2 and VI.D.3 discuss, respectively, 
conventional food studies generally and studies intended to support a 
health claim for a conventional food or dietary supplement. The 
portions of subsection VI.D.2 that are being stayed are the third 
paragraph (which pertains to clinical studies intended to evaluate a 
food's effect on the structure or function of the body) and a sentence 
in the fourth paragraph concerning clinical studies intended to 
evaluate a non-nutritional effect on the structure or function of the 
body. In subsection VI.D.3, a text box inserted below the subsection 
heading explains that clinical investigations intended to evaluate 
whether a food substance may reduce the risk of a disease in three 
categories of medically vulnerable subjects (individuals less than 12 
months old, those with altered immune systems, and those with serious 
or life-threatening medical conditions) are excluded from the stay, and 
that subsection VI.D.3 is in effect for such investigations.
    The stay of portions of subsection VI.D.2 and all of subsection 
VI.D.3 (subject to the exclusion for studies in the medically 
vulnerable populations described in this document) of the final 
guidance is effective immediately. All other parts of the final 
guidance remain in effect. We are republishing the guidance with the 
stayed material clearly identified so readers can distinguish parts of 
the guidance that remain in effect from parts that are subject to the 
stay.
    FDA generally does not intend to seek INDs for studies in the 
stayed categories while the stay is in effect. This stay does not, 
however, preclude enforcement of any provision of the FD&C Act or other 
relevant Federal statutes or regulations other than IND requirements 
(e.g., human subject protection laws and regulations). This stay does 
not affect investigations of conventional foods or dietary supplements 
studied for use in the diagnosis, cure, mitigation, treatment, or 
prevention of disease. Products intended for such uses meet the 
definition of a ``drug'' at section 201(g)(1)(B) of the FD&C Act; such 
investigations will continue to be subject to IND requirements. For 
example, dietary supplements containing bacteria have been given to 
infants born prematurely for prevention of necrotizing enterocolitis. 
The investigation of such use, and similar uses of conventional foods 
or dietary supplements to diagnose, cure, mitigate, treat, or prevent a 
disease, continues to require an IND.
    In summary, while the partial stay of the final guidance is in 
effect, FDA does not consider clinical investigators or study sponsors 
to be under any

[[Page 66909]]

obligation to obtain an IND for the following types of studies 
evaluating the effects of a product marketed as a conventional food or 
dietary supplement:
    For conventional foods:
     Clinical studies designed to evaluate whether a 
conventional food may reduce the risk of a disease, intended to support 
a new or expanded health claim, and conducted in a population that does 
not include individuals less than 12 months old, those with altered 
immune systems, or those with serious or life-threatening medical 
conditions;
     Clinical studies designed to evaluate a non-nutritional 
effect of a conventional food on the structure or function of the body.
    For dietary supplements:
     Clinical studies designed to evaluate whether a dietary 
supplement may reduce the risk of a disease, intended to support a new 
or expanded health claim, and conducted in a population that does not 
include individuals less than 12 months old, those with altered immune 
systems, or those with serious or life-threatening medical conditions.
    Further, as noted in the final guidance itself, no IND is required 
for clinical studies designed to evaluate the nutritional effects of a 
conventional food, clinical studies designed to evaluate a dietary 
supplement's effects on the structure or function of the body, or 
clinical studies designed to evaluate the relationship between a 
conventional food or dietary supplement and reduced risk of a disease, 
if there is already an authorized health claim for the substance-
disease relationship.
    The following types of studies do continue to require an IND for 
the reasons explained in the final guidance:
    For conventional foods:
     Clinical studies designed to evaluate a conventional 
food's ability to diagnose, cure, mitigate, treat, or prevent a 
disease, except for studies designed to evaluate whether a conventional 
food reduces the risk of a disease, intended to support a health claim, 
and conducted in a population that does not include individuals less 
than 12 months old, those with altered immune systems, or those with 
serious or life-threatening medical conditions;
     Clinical studies designed to evaluate whether a food 
substance reduces the risk of a disease, intended to support a new or 
expanded health claim, and conducted in a population that includes 
individuals less than 12 months old, those with altered immune systems, 
or those with serious or life-threatening medical conditions.
    For dietary supplements:
     Clinical studies designed to evaluate a dietary 
supplement's ability to diagnose, cure, mitigate, treat, or prevent a 
disease, except for studies designed to evaluate whether a dietary 
supplement reduces the risk of a disease, intended to support a health 
claim, and conducted in a population that does not include individuals 
less than 12 months old, those with altered immune systems, or those 
with serious or life-threatening medical conditions;
     Clinical studies designed to evaluate whether a dietary 
supplement reduces the risk of a disease, intended to support a new or 
expanded health claim, and conducted in a population that includes 
individuals less than 12 months old, those with altered immune systems, 
or those with serious or life-threatening medical conditions.
    For cosmetics:
     Clinical studies designed to evaluate a cosmetic's effect 
on the structure or function of the body or its ability to diagnose, 
cure, mitigate, treat, or prevent a disease.

    Dated: October 26, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-27729 Filed 10-29-15; 8:45 am]
BILLING CODE 4164-01-P