Document ID: FDA-2023-N-0573-0002
Agency: fda
Document Type: Notice
Title: Changes to Third-Party Vendors for Risk Evaluation and Mitigation Strategies; Establishment of a Public
Docket; Request for Comments
Posted Date: 2023-03-23T04:00Z

[Federal Register Volume 88, Number 56 (Thursday, March 23, 2023)]
[Notices]
[Pages 17578-17579]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-05962]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2023-N-0573]

Changes to Third-Party Vendors for Risk Evaluation and Mitigation 
Strategies; Establishment of a Public Docket; Request for Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; establishment of a public docket; request for comments.

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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is 
announcing the establishment of a docket to solicit comments on factors 
that generally should be considered by the Secretary of Health and 
Human Services (Secretary) when reviewing modification requests from 
sponsors of drugs subject to risk evaluation and mitigation strategies 
(REMS) related to changes in third-party vendors engaged by sponsors to 
aid in implementation and management of the strategies.

DATES: Submit either electronic or written comments by July 21, 2023. 
See the SUPPLEMENTARY INFORMATION section for registration date and 
information.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of July 21, 2023. Comments received 
by mail/hand delivery/courier (for written/paper submissions) will be 
considered timely if they are received on or before that date.

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-2023-N-0573 for ``Proposed Changes to Third-Party Vendors 
Establishment of a Public Docket; Request for Comments.'' Received 
comments, those filed in a timely manner (see ADDRESSES), 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, 240-402-7500.
     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.govinfo.gov/content/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, 240-402-7500.

FOR FURTHER INFORMATION CONTACT: Marcus Cato, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 4475, 301-796-2380, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    Section 505-1 of the Federal Food, Drug, and Cosmetic Act (FD&C 
Act) (21 U.S.C. 355-1), authorizes FDA to require a REMS if FDA 
determines that a REMS is necessary to ensure that the benefits of the 
drug outweigh its risks. A REMS is a required risk management strategy 
that employs tools beyond prescribing information to ensure that the 
benefits of a drug outweigh its risks. A REMS may require a Medication 
Guide (or patient package insert) to provide risk information to 
patients, a communication plan to disseminate risk information to 
healthcare providers, and certain packaging and safe disposal systems 
for drugs that pose a serious risk of abuse or overdose. FDA may also 
require certain elements to assure safe use (ETASU) when such elements 
are necessary to mitigate a specific serious risk listed in the 
labeling of the drug. ETASU may include, for example, requirements that 
healthcare 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 applicant is able to monitor 
and evaluate implementation of the ETASU

[[Page 17579]]

and work to improve their implementation. Finally, REMS generally must 
have a timetable for submission of assessments of the strategy.
    FDA can require a REMS before initial approval of a new drug 
application (NDA) or biologics license application (BLA) or after the 
drug has been approved if FDA becomes aware of new safety information 
about a drug and determines that a REMS is necessary to ensure that the 
benefits of the drug outweigh its risks. Under section 505-1(i)(1) of 
the FD&C Act, a drug that is approved under an abbreviated new drug 
application (ANDA) is only required to have certain elements of a REMS 
if these elements are required for the applicable listed drug: a 
Medication Guide or patient package insert, a packaging or disposal 
requirement, ETASU, and an implementation system.
    When applicants develop REMS with ETASU, particularly those ETASU 
that require verification of certain conditions before the drug is 
dispensed, they often hire third-party vendors to design operational 
components to help implement and manage the program requirements. These 
third-party vendors, often referred to as REMS administrators, may 
perform a variety of functions for the REMS program, including building 
and operating a centralized database or repository for patient 
enrollment, prescriber and pharmacy certifications, and wholesaler 
enrollments. They often host a website or web portal that participants, 
such as patients, prescribers, pharmacies, and wholesalers, use to 
enroll in the program, and they provide the technological means for 
pharmacies and other dispensers to perform the necessary verifications 
at the point of dispensing. These operational components are often 
referred to collectively as the ``REMS system.'' In many cases, 
therefore, the REMS administrator performs critical functions in the 
daily operations of a REMS which directly impact patient access to the 
drug.
    Applicants may submit modifications to their REMS at any time after 
approval which propose the addition, modification, or removal of any 
goal or element of the approved strategy. While FDA does not approve 
REMS administrators or changes in REMS administrators per se, an 
applicant's decision to change a REMS administrator may affect the REMS 
system, prompting an applicant to propose a REMS modification. 
Implementing such a change has the potential to cause significant 
disruptions in the operations of the program, including the ability for 
stakeholders to interact with the tools necessary to fulfill the 
various REMS requirements. These disruptions can impact patients' 
ability to access the drug.
    The Consolidated Appropriations Act, 2023, signed into law on 
December 29, 2022, specified that ``[n]ot later than 90 days after the 
date of enactment of this Act, the Secretary shall open a single public 
docket to solicit comments on factors that generally should be 
considered by the Secretary when reviewing requests from sponsors of 
drugs subject to [REMS] to change third-party vendors engaged by 
sponsors to aid in implementation and management of the strategies. . . 
. Such factors include the potential effects of changes in third-party 
vendors on--(A) patient access; and (B) prescribing and administration 
of the drugs by healthcare providers.''

II. Request for Comments

    FDA is soliciting comments from stakeholders regarding the factors 
that FDA should consider when it reviews a proposed REMS modification 
that is prompted by or related to a change in a REMS administrator for 
a REMS with ETASU. In addition to general factors, such as effect of 
the modification on patient access and prescribing and administration 
by healthcare providers, FDA is interested in comments on the following 
topics:
    1. Comment on any stakeholder input that the applicant and/or REMS 
administrator should obtain prior to developing and implementing a new 
REMS system, including the extent and timing of stakeholder input.
    2. Comment on whether the sponsor and/or REMS administrator should 
conduct testing of the changes to the operation of the REMS system 
prior to full implementation including:
     User acceptance testing with stakeholders and evaluation 
of any unexpected impact on stakeholder workflow
     An assessment of REMS data flows, including whether REMS 
data from the existing REMS system can be timely and successfully 
transferred to a new REMS system.
    3. Comment on the amount of time needed to transition stakeholders 
from one REMS system to another REMS system (e.g., enrollment or 
recertification), and the factors that go into that time frame.
    4. Comment on whether the sponsor and/or the REMS administrator 
should conduct a failure modes and effects analysis to identify and 
plan for system failures. This includes providing for adequate support 
services in the event that the system fails to work as intended 
following full implementation of the new REMS system.
    5. Comment on the metrics that the sponsor should capture to 
evaluate whether the REMS system was successfully and efficiently 
implemented.

    Dated: March 20, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-05962 Filed 3-22-23; 8:45 am]
BILLING CODE 4164-01-P