
[Federal Register Volume 80, Number 208 (Wednesday, October 28, 2015)]
[Notices]
[Pages 66013-66014]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-27418]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-D-0142]


Nonclinical Safety Evaluation of Reformulated Drug Products and 
Products Intended for Administration by an Alternate Route; Guidance 
for Industry and Review Staff; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a guidance for industry and review staff entitled 
``Nonclinical Safety Evaluation of Reformulated Drug Products and 
Products Intended for Administration by an Alternate Route.'' The 
guidance provides recommendations concerning the evaluation of the 
nonclinical safety of reformulated drug products or products being used 
by an alternate route. It is intended for use by interested individuals 
in industry and reviewers within the Center for Drug Evaluation and 
Research (CDER). The goals of this guidance are to foster and expedite 
the development of reformulated drug products or the use of previously 
approved drugs by alternate routes, communicate to industry current 
CDER thoughts pertaining to safety data needed to support these drug 
products, and increase uniformity within CDER on expectations for the 
nonclinical development of reformulated drug products or products being 
used by an alternate route. This guidance finalizes the draft guidance 
of the same name published on March 7, 2008.

DATES: Submit either electronic or written comments on Agency 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-2008-D-0142 for ``Nonclinical Safety Evaluation of Reformulated 
Drug Products and Products Intended for Administration by an Alternate 
Route; Guidance for Industry and Review Staff.'' 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 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.

[[Page 66014]]

    Submit written requests for single copies of this guidance to the 
Division of Drug Information, Center for Drug Evaluation and Research, 
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale 
Building, 4th Floor, Silver Spring, MD 20993-0002. Send one self-
addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Paul C. Brown, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg., 22, Rm. 6472, Silver Spring, MD 20993-0002, 301-
796-0856.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry and 
review staff entitled ``Nonclinical Safety Evaluation of Reformulated 
Drug Products and Products Intended for Administration by an Alternate 
Route.'' This guidance provides recommendations regarding the 
nonclinical evaluation of a new formulation containing a previously 
approved drug substance and of a product proposed for use by an 
alternate route of administration for which the product was not 
previously approved.
    Generally, nonclinical data support use of a drug product by a 
particular route and also reflect the planned duration of use. Much of 
the available nonclinical information used to support approval of the 
initial formulation can be used to support the safety of additional 
formulations assuming all legal rights to the information are met. 
Information used to support an initial formulation, however, may not 
always be sufficient to support such additional approvals because 
changes in the formulation could produce a new toxicity. This is 
particularly true if the drug product's route of administration is 
different or the duration of use changes markedly. Therefore, 
additional nonclinical studies might be recommended to ensure that the 
toxicity of a new formulation is fully characterized.
    This guidance provides general nonclinical considerations for all 
reformulations or new routes of use and several route-specific 
considerations. The considerations in this guidance can also be applied 
to routes not specifically mentioned in the guidance.
    This guidance finalizes the draft guidance of the same name 
published on March 7, 2008. Changes to the guidance include the 
addition of a recommendation that toxicology studies be conducted under 
good laboratory practices, clarification that histopathology can be 
limited in some cases to locally exposed tissues, the addition of a 
reference to the International Conference on Harmonisation guidance for 
industry entitled ``S10 Photosafety Evaluation of Pharmaceuticals,'' 
and other clarifications to the studies recommended for specific routes 
such as dermal, ocular, and intranasal.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
current thinking of FDA on nonclinical safety evaluation of 
reformulated drug products and products intended for administration by 
an alternate route. 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.

II. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.

    Dated: October 21, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-27418 Filed 10-27-15; 8:45 am]
 BILLING CODE 4164-01-P


