[Federal Register Volume 84, Number 132 (Wednesday, July 10, 2019)]
[Notices]
[Pages 32928-32929]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-14663]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2014-D-1747]


Risk Evaluation and Mitigation Strategies: Modifications and 
Revisions; Guidance for Industry; 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 final guidance for industry entitled ``Risk 
Evaluation and Mitigation Strategies: Modifications and Revisions.'' 
This guidance provides information on how FDA will define and process 
submissions for modifications and revisions of risk evaluation and 
mitigation strategies (REMS), as well as information on what types of 
changes to approved REMS will be considered modifications or revisions 
of the REMS. The guidance also provides instructions to application 
holders related to procedures for submission of REMS modifications and 
revisions to FDA as well as different timeframes for FDA's review of 
and action on such changes. The definitions of REMS modifications and 
revisions apply to all types of REMS. This guidance updates the 
guidance of the same name, issued April 7, 2015, including finalizing 
the portion that sets forth the submission procedures for REMS 
revisions.

DATES: The announcement of the guidance is published in the Federal 
Register on July 10, 2019.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://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 https://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): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, 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-2014-D-1747 for ``Risk Evaluation and Mitigation Strategies: 
Modifications and Revisions.'' Received comments will be placed in the 
docket and, except for those submitted as ``Confidential Submissions,'' 
publicly viewable at https://www.regulations.gov or at the Dockets 
Management Staff 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 https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. 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: https://www.gpo.gov/fdsys/pkg/FR2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://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 Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    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, or the Office of 
Communication, Outreach, and Development, Center for Biologics 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, 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: Vaishali Jarral, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 6480, Silver Spring, MD 20993-0002, 301-
796-4248; or Stephen Ripley, Center for

[[Page 32929]]

Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 
240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Risk Evaluation and Mitigation Strategies: Modifications and 
Revisions.'' This guidance provides information on what types of 
changes to approved REMS will be considered modifications of the REMS 
and what types of changes will be considered revisions. (See section 
505-1(h) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 
U.S.C. 355-1(h)).) This guidance also provides information on how REMS 
modifications and revisions should be submitted to FDA and how FDA 
intends to review and act on these submissions.
    If FDA determines that a REMS is necessary to ensure that the 
benefits of a drug outweigh its risks, FDA is authorized to require a 
REMS for such drugs under section 505-1 of the FD&C Act.\1\ Section 
505-1(g) and (h) of the FD&C Act include provisions for the assessment 
and modification of an approved REMS. Section 505-1(h) of the FD&C Act 
requires FDA to review and act on proposed minor modifications, as 
defined in guidance, within 60 days.\2\ It also requires FDA to 
establish, through guidance, that ``certain modifications'' can be 
implemented following notification to FDA. (See section 505-
1(h)(2)(A)(iv) of the FD&C Act.) In addition, FDA is required to review 
and act on REMS modifications to conform the REMS to approved safety 
labeling changes, or to a safety labeling change that FDA has directed 
the application holder to make pursuant to section 505(o)(4) of the 
FD&C Act within 60 days. (See section 505-1(h)(2)(A)(iii) of the FD&C 
Act.) Finally, section 505-1(g)(4)(A) of the FD&C Act specifies that 
proposed REMS modifications no longer require submission of a REMS 
assessment; instead, proposed modifications must include an adequate 
rationale for the proposed changes.
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    \1\ Section 505-1 of the FD&C Act applies to applications for 
prescription drugs submitted under subsection 505(b) (i.e., new drug 
applications) or (j) (i.e., abbreviated new drug applications) of 
the FD&C Act (21 U.S.C. 355(b) or (j), respectively) and 
applications under section 351 of the Public Health Service Act 
(i.e., biologics license applications).
    \2\ See section 505-1(h)(2)(A)(ii) of the FD&C Act. Section 
1132(c) of the Food and Drug Administration Safety and Innovation 
Act also provides that FDA will issue guidance that, for purposes of 
section 505-1(h)(2)(A) of the FD&C Act, describes the types of 
modifications to approved risk evaluation and mitigation strategies 
that are considered to be minor modifications of such strategies.
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    This guidance updates the guidance of the same name, issued April 
7, 2015 (80 FR 18629), and finalizes the portion that sets forth the 
submission procedures for REMS revisions. FDA carefully considered all 
comments received, including comments on the submission procedures 
portion, and revised the guidance as appropriate.
    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 ``Risk Evaluation and Mitigation Strategies: 
Modifications and Revisions.'' 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. This guidance is not subject to Executive 
Order 12866.

II. Paperwork Reduction Act of 1995

    This final guidance refers to previously approved collections of 
information found in FDA regulations. These collections of information 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). REMS 
modifications are submitted to FDA as supplements to approved new drug 
applications (NDAs) under 21 CFR 314.70 and for abbreviated new drug 
applications (ANDAs) under 21 CFR 314.97, and for approved biologics 
license applications (BLAs) under 21 CFR 601.12. Burden hours for NDAs 
and ANDAs are approved by OMB under control number 0910-0001, and for 
BLAs under control number 0910-0338. REMS revisions are submitted to 
FDA as application correspondence and are also approved by OMB under 
control numbers 0910-0001 and 0910-0338.

III. Electronic Access

    Persons with access to the internet may obtain the guidance at 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, or 
https://www.regulations.gov.

    Dated: July 3, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-14663 Filed 7-9-19; 8:45 am]
 BILLING CODE 4164-01-P