Document ID: FDA-2016-D-2730-0001
Agency: fda
Document Type: Notice
Title: Food and Drug Administration’s Application of Statutory Factors in
Determining When a Risk Evaluation and Mitigation Strategy Is Necessary; Draft Guidance for Industry; Availability
Posted Date: 2016-09-21T04:00Z

[Federal Register Volume 81, Number 183 (Wednesday, September 21, 2016)]
[Notices]
[Pages 64911-64913]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-22689]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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

Food and Drug Administration's Application of Statutory Factors 
in Determining When a Risk Evaluation and Mitigation Strategy Is 
Necessary; Draft Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a draft guidance for industry entitled ``FDA's 
Application of Statutory Factors in Determining When a REMS Is 
Necessary.'' This draft guidance is intended to clarify how FDA applies 
the factors set forth in the Federal Food, Drug, and Cosmetic Act (the 
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 being developed to 
fulfill performance goals that FDA agreed to satisfy in the context of 
the fifth reauthorization of the prescription drug user fee program 
(the Prescription Drug User Fee Act V).

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that the Agency considers your comment on this 
draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by November 21, 2016.

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,

[[Page 64912]]

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 the ``FDA's Application of Statutory Factors in 
Determining When a REMS Is Necessary; Draft Guidance for Industry.'' 
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.
    Submit written requests for single copies of the draft 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 assist the office in processing 
your requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Aaron Sherman, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6366, Silver Spring, MD 20993, 240-402-
0493, Aaron.Sherman@fda.hhs.gov; 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.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``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). A REMS is a required risk management strategy that can 
include one or more elements to ensure that the benefits of a drug 
outweigh its risks (see section 505-1(e) of the FD&C Act). A REMS may 
consist of a Medication Guide, a patient package insert, and/or a 
communication plan (section 505-1(e)(2) to (e)(3) of the FD&C Act). FDA 
may also require certain elements to assure safe use (ETASU) as part of 
a REMS for a drug (see section 505-1(f) of the FD&C Act). (The ETASU 
can include, for example, requirements that health care providers who 
prescribe the drug have particular training or experience, that 
patients using the drug be monitored, or that the drug be dispensed to 
patients with evidence or other documentation of safe use conditions 
(Id.). The ETASU may also include an implementation system through 
which the sponsor is able to monitor, evaluate, and improve 
implementation of the ETASU (see section 505-1(f)(4) of the FD&C Act).) 
Finally, REMS generally must have a timetable for submission of 
assessments of the strategy (see section 505-1(d) 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).
---------------------------------------------------------------------------

    \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) of the FD&C Act and to applications submitted or 
approved 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).
---------------------------------------------------------------------------

    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. In conducting this 
analysis, FDA considers whether (based on premarketing or postmarketing 
risk assessments) there is a particular risk associated with the use of 
the drug that, on balance, outweighs its benefits and whether 
additional interventions beyond FDA-approved labeling are necessary to 
ensure that the drug's benefits outweigh its risks.
    If FDA determines that additional interventions are necessary to 
ensure that the benefits of a drug outweigh its risks, FDA considers 
what the goals of a proposed REMS to address these risks would be and 
what specific elements could help meet those goals. If a REMS can be 
designed that FDA expects will meet the relevant goals and not unduly 
impede patient access to the drug, then FDA will generally approve the 
drug with a REMS (or, if the drug is already being marketed, require 
that a REMS be imposed for the drug). If FDA believes that the drug's 
risks would exceed its benefits even if FDA were to require a REMS for 
the drug, FDA will not approve the drug or may consider seeking 
withdrawal of the drug if it is already being marketed.
    FDAAA requires FDA to consider the following six factors \2\ in 
making a

[[Page 64913]]

decision about whether to require a REMS:
---------------------------------------------------------------------------

    \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.
---------------------------------------------------------------------------

     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
     The estimated size of the population likely to use the 
drug

These six factors influence FDA's decisions with respect to both 
whether a REMS is required for a particular drug and what type of REMS 
might be necessary (i.e., what specific elements/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. No single factor, by itself, is determinative as to 
whether a REMS is necessary to ensure that the benefits of a drug 
outweigh its risks. This guidance describes how FDA considers each of 
these factors in conducting its REMS analysis.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the current thinking of FDA on how the Agency 
applies 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.

II. Electronic Access

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

    Dated: September 15, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-22689 Filed 9-20-16; 8:45 am]
 BILLING CODE 4164-01-P