
[Federal Register Volume 84, Number 22 (Friday, February 1, 2019)]
[Notices]
[Pages 1153-1155]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-00676]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-4628]


Risk Evaluation and Mitigation Strategies Assessment: Planning 
and Reporting; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry on the assessment of 
risk evaluation and mitigation strategies (REMS) entitled ``REMS 
Assessment: Planning and Reporting; Draft Guidance for Industry.'' The 
draft guidance is one of several guidance documents being developed to 
fulfill performance goals under the fifth authorization of the 
prescription drug user fee program, the Prescription Drug User Fee Act 
V. This draft guidance describes how to develop a REMS Assessment Plan; 
specifically, how the REMS program goals, objectives, and REMS design 
may impact the selection of metrics and data sources, which will be 
used to assess whether the REMS is meeting its risk mitigation goals.
    The draft guidance recommends assessing the REMS using both process 
measures and outcome measures and provides examples of metrics by 
assessment categories, as well as data sources that may be utilized to 
evaluate the performance of the REMS. The draft guidance also discusses 
considerations for assessing the impact of REMS on patient access to 
the drug or its burden to the healthcare delivery system. Finally, this 
draft guidance provides recommendations on a standardized approach for 
reporting REMS assessment findings to FDA using the REMS Assessment 
Report.

DATES: Submit either electronic or written comments on the draft 
guidance by April 2, 2019 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance 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

[[Page 1154]]

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-2018-D-4628 for ``REMS Assessment: Planning and Reporting.'' 
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 the draft guidance to 
the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10001 New Hampshire Ave., 
Hillandale Bldg., 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 that office in processing 
your requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Doris Auth, Center for Drug Evaluation 
and Research, Food and Drug Administration, 10903 New Hampshire Ave., 
Bldg. 22, Rm. 2480, Silver Spring, MD 20993-0002, 301-796-0487, 
Doris.Auth@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 ``REMS Assessment: Planning and Reporting.'' The Food and Drug 
Administration Amendments Act of 2007 created section 505-1 of the 
Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355-1), 
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.
    REMS elements may include a medication guide, a patient package 
insert, and/or a communication plan. FDA may also require certain 
elements to assure safe use (ETASU) as part of a REMS. 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. 
Certain REMS with ETASU may also include an implementation system 
through which the sponsor is able to monitor and evaluate 
implementation of the ETASU and work to improve their implementation. 
All REMS for drugs approved under a new drug application or a biologics 
license application must include a timetable for submission of 
assessments of the REMS. The timetable for submission of assessments 
must be, at a minimum, by 18 months, 3 years, and in the 7th year after 
the initial approval of the REMS. For additional information about 
REMS, see the guidances for industry ``Format and Content of a REMS 
Document'' (82 FR 47529, October 12, 2017) (available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm18&4128.pdf), FDA's Application of Statutory Factors in 
Determining When a REMS Is Necessary (81 FR 64911, September 21, 2016) 
(available at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM521504.pdf), and 
Risk Evaluation and Mitigation Strategies: Modifications and Revisions 
Guidance for Industry (80 FR 18629, April 7, 2015) (available at 
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM441226.pdf).
    The FD&C Act requires applicants to conduct assessments to evaluate 
the effectiveness of the REMS. The statute specifies that the 
assessment for REMS must include an assessment of the extent to which 
the approved strategy, including each element of the strategy, is 
meeting the goal or whether one or more such goals or such elements 
should be modified (section 505-1(g)(3) of the FD&C Act). The statute 
does not specifically describe how an applicant should conduct 
assessments. Many REMS include a goal related to knowledge, such as to 
inform or educate patients and health care providers about the serious 
risks associated with and safe use of a drug. When knowledge goals are 
part of a REMS, the REMS Assessment Plan generally includes, as 
appropriate, an evaluation of patients' and health care providers' 
understanding of the serious risk(s) associated with, and safe use of, 
the drug. Elsewhere in this issue of the

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Federal Register, FDA is announcing the availability of a draft 
guidance entitled ``Survey Methodologies to Assess REMS Goals That 
Relate to Knowledge,'' which addresses the use of surveys to address 
the knowledge goal.
    In addition to knowledge-related goals, REMS may include goals and 
objectives related to the outcomes the REMS is intended to mitigate; 
therefore, REMS assessments should also include elements that would 
indicate whether these goals and objectives are being met. REMS 
assessments can also include elements to assess the burden of REMS on 
the health care delivery system and any unintended barriers to patient 
access of the drug.
    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 ``REMS 
Assessment: Planning and Reporting.'' 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 draft guidance refers to collections of information that 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). The title, 
description, and respondent description of the information collection 
are given under this section with an estimate of the annual reporting 
burden. Included in the estimate is the time for reviewing 
instructions, searching existing data sources, and gathering and 
maintaining the data needed.
    We invite comments on these topics: (1) Whether the proposed 
collection of information is necessary for the proper performance of 
FDA's functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.
    Title: REMS Assessment: Planning and Reporting--OMB Control Number 
0910-NEW.
    Description: This draft guidance provides instruction on submitting 
REMS Assessments to FDA. These instructions recommend that application 
holders submitting REMS Assessments should include the following 
information in each submission: (1) A cover page that includes the 
reporting time point, the date of the REMS Assessment Report, and the 
assessment reporting period. The cover page should be followed by (2) a 
table of contents; (3) an executive summary of the findings and 
conclusions; (4) an introduction section; (5) a background section, 
which includes the REMS goals and objectives, requirements, and 
materials that were in place during the assessment reporting period, a 
REMS history, and any pending supplements; (6) a summary of the REMS 
Assessment Plan as an overview in tabular format (or other format 
outline) and details of the assessment plan including any study 
protocols submitted with the assessment or references to protocols 
submitted prior to the REMS Assessment Report and methodology used to 
support REMS assessment (e.g., survey, other methodology); (7) a 
summary of the previous assessments, including the key results and the 
overall conclusions; (8) the results or summary of findings of each 
assessment metric, including a written summary of the data that was 
analyzed, key results and a description of any limitations. When 
appropriate, the data should be reported for the reporting period and 
cumulatively, and trends in performance compared to previous periods 
should be reported and discussed; (9) a discussion including the 
overall assessment of whether the REMS is meeting its goals and 
objectives, including the basis for that conclusion, and for REMS with 
ETASU, whether the burden on the healthcare delivery system is being 
minimized to the extent practicable, whether the ETASU are unduly 
burdensome on patient access to medication, and an explanation for 
these conclusions; (10) any proposed modifications to the REMS (e.g., 
to address REMS compliance issues, reduce burdens, overcome barriers to 
patient access, improve efficiencies) as well as the basis for the 
proposed modifications; and (11) any proposed revisions to the REMS 
Assessment Plan if additional information is needed to make a 
determination that the goal of the REMS is being met, or if there are 
aspects of the REMS that are no longer necessary to assess.
    We estimate the burden of the information collection as follows:

                                                      Table 1--Estimated Annual Reporting Burden 1
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                                                                                         Number of                       Average burden
  Guidance for industry on REMS assessment: Planning and reporting      Number of      responses per     Total annual     per response     Total hours
                                                                       respondents       respondent       responses         (hours)
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REMS Assessments Submissions.......................................              47                1               47            162.5            7,638
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1 There are no capital costs or operating and maintenance costs associated with this collection of information.

    There are currently 76 approved REMS programs. Based on a current 
review of REMS assessment submission data and anticipating a similar 
number of future submissions, we estimate that there will be 47 REMS 
Assessment submissions annually. We also estimate that it will take an 
application holder 162.5 hours to prepare and submit each REMS 
Assessment (``Average Burden per Response'' in table 1) in accordance 
with recommendations found in the guidance.

III. Electronic Access

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

    Dated: January 16, 2019.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2019-00676 Filed 1-31-19; 8:45 am]
 BILLING CODE 4164-01-P


