[Federal Register Volume 84, Number 66 (Friday, April 5, 2019)]
[Notices]
[Pages 13668-13669]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-06663]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-D-2730]


Risk Evaluation and Mitigation Strategy: The Food and Drug 
Administration's Application of Statutory Factors in Determining When a 
Risk Evaluation and Mitigation Strategy Is Necessary; 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 Strategy: FDA's Application of Statutory 
Factors in Determining When a Risk Evaluation and Mitigation Strategy 
Is Necessary.'' This guidance is intended to clarify how FDA applies 
the factors set forth in the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) in determining whether a risk evaluation and mitigation strategy 
(REMS) is necessary to ensure that the benefits of a drug outweigh its 
risks. This guidance is one of several developed to fulfill performance 
goals that FDA agreed to satisfy in the reauthorization of the 
prescription drug user fee program (the Prescription Drug User Fee Act 
(PDUFA) V). This guidance finalizes the draft guidance entitled ``FDA's 
Application of Statutory Factors in Determining When a REMS Is 
Necessary,'' issued September 21, 2016.

DATES: The announcement of the guidance is published in the Federal 
Register on April 5, 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-2016-D-2730 for ``REMS: FDA's Application of Statutory Factors in 
Determining When a REMS Is Necessary.'' 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/FR-2015-09-18/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 to 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

[[Page 13669]]

assist that office in processing your requests. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Jason Bunting, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6366, Silver Spring, MD 20993, 301-796-
1292, [email protected]; or Stephen Ripley, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 
240-402-7911, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``REMS: FDA's Application of Statutory Factors in Determining 
When a REMS Is Necessary.'' The Food and Drug Administration Amendments 
Act of 2007 (FDAAA) (Pub. L. 110-85) created section 505-1 of the FD&C 
Act (21 U.S.C. 355-1),\1\ which authorizes FDA to require a REMS for 
certain drugs if FDA determines that a REMS is necessary to ensure that 
the benefits of the drug outweigh its risks (see section 505-1(a) of 
the FD&C Act). FDA can require a REMS before initial approval of a new 
drug application or, should FDA become aware of ``new safety 
information'' (as defined in section 505-1(b)(3) of the FD&C Act) about 
a drug and determine that a REMS is necessary to ensure that the 
benefits of the drug outweigh its risks, after the drug has been 
approved (see section 505-1(a)(2) of the FD&C Act).
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    \1\ Section 505-1 of the FD&C Act applies to applications for 
prescription drugs submitted or approved under subsections 505(b) 
(i.e., new drug applications) or (j) (i.e., abbreviated new drug 
applications) (21 U.S.C. 355(b) or (j)) of the FD&C Act and to 
applications submitted or licensed under section 351 (i.e., 
biologics license applications) of the Public Health Service Act (42 
U.S.C. 262). In this document, unless otherwise specified, the term 
``drug'' refers to drug and biological products (or biologics).
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    FDA's determination as to whether a REMS is necessary for a 
particular drug is a complex, drug specific inquiry, reflecting an 
analysis of multiple, interrelated factors. Section 505-1(a) of the 
FD&C Act, as added by FDAAA, requires FDA to consider the following six 
factors \2\ in making a decision about whether to require a REMS:
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    \2\ Section 505-1(a)(1) of the FD&C Act requires the Agency to 
consider these factors in determining whether a REMS is necessary 
for a new drug. FDA also generally considers these factors in 
determining whether (based on new safety information), a REMS is 
necessary for a drug that is the subject of an approved application.
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     The seriousness of any known or potential adverse events 
that may be related to the drug and the background incidence of such 
events in the population likely to use the drug;
     The expected benefit of the drug with respect to the 
disease or condition;
     The seriousness of the disease or condition that is to be 
treated with the drug;
     Whether the drug is a new molecular entity;
     The expected or actual duration of treatment with the 
drug; and
     The estimated size of the population likely to use the 
drug.
    These six factors influence FDA's decisions with respect to whether 
a REMS is required for a particular drug and what type of REMS might be 
necessary (i.e., what specific elements or tools should be included as 
part of the REMS). FDA makes decisions about requiring a REMS as part 
of a benefit-risk determination for a drug after an evaluation that 
includes integrated consideration of each of the statutory factors. All 
six factors are considered together to inform FDA's REMS decision 
making process and no single factor is determinative as to whether a 
REMS is necessary. The relative importance or weight of each factor is 
a case specific inquiry. This guidance describes how FDA considers each 
of these factors in conducting its REMS analysis.
    This guidance finalizes the draft guidance entitled ``FDA's 
Application of Statutory Factors in Determining When a REMS Is 
Necessary,'' issued September 21, 2016 (81 FR 64911). Interested 
persons were invited to comment by November 21, 2016. FDA received 
comments related to how we weigh the six factors when determining if a 
REMS is necessary, minor clarifying comments on how we apply the six 
factors, and comments suggesting that FDA expand on which REMS elements 
or tools should be used when it is determined that a REMS is necessary. 
FDA has considered all of the public comments received in finalizing 
this guidance. Clarifying edits were made to address the comments as 
appropriate. Additionally, edits were made to streamline the guidance, 
extraneous background information was removed, and the title was 
modified for clarity.
    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 ``REMS: FDA's Application of Statutory 
Factors in Determining When a REMS Is Necessary.'' 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. Electronic Access

    Persons with access to the internet may obtain the guidance at 
either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or 
https://www.regulations.gov.

    Dated: April 1, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-06663 Filed 4-4-19; 8:45 am]
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