[Federal Register Volume 88, Number 66 (Thursday, April 6, 2023)]
[Notices]
[Pages 20526-20530]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-07238]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2020-D-1057]
Notification of a Permanent Discontinuance or Interruption in
Manufacturing Under Section 506C of the Federal Food, Drug, and
Cosmetic Act; Draft Guidance for Industry; Availability; Agency
Information Collection Activities; Proposed Collection; Comment Request
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance for industry entitled ``Notification
of a Permanent Discontinuance or Interruption in Manufacturing Under
Section 506C of the FD&C Act.'' The draft guidance is intended to
assist applicants and manufacturers in providing FDA timely,
informative notifications about changes in the production of certain
finished drugs and biological products as well as certain active
pharmaceutical ingredients (API) that may, in turn, help the Agency in
its efforts to prevent or mitigate shortages. The draft guidance also
explains how FDA communicates information about products in shortage to
the public. This
[[Page 20527]]
draft guidance is not final nor is it in effect at this time.
DATES: Submit either electronic or written comments on the draft
guidance by June 5, 2023 to ensure that the Agency considers your
comment on this draft guidance before it begins work on the final
version of the guidance. Submit electronic or written comments on the
proposed collection of information in the draft guidance by June 5,
2023.
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 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-2020-D-1057 for ``Notification of a Permanent Discontinuance or
Interruption in Manufacturing Under Section 506C of the FD&C Act.''
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, 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.
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 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
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 request or include a fax number to which the draft guidance may be
sent. See the SUPPLEMENTARY INFORMATION section for information on
electronic access to the draft guidance.
FOR FURTHER INFORMATION CONTACT:
With regard to the draft guidance: Jin Ahn, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 6234, Silver Spring, MD 20993-0002, 301-
796-1300; or Diane Maloney, 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.
With regard to the proposed collection of information: Domini Bean,
Office of Operations, Food and Drug Administration, Three White Flint
North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 20852 301-796-
5733, [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Notification of a Permanent Discontinuance or Interruption
in Manufacturing Under Section 506C of the FD&C Act.'' The draft
guidance discusses section 506C of the Federal Food, Drug, and Cosmetic
Act (FD&C Act) (21 U.S.C. 356c), as amended by the Coronavirus Aid,
Relief, and Economic Security (CARES) Act,\1\ and FDA's regulations
which generally require certain applicants and manufacturers to notify
FDA of: (1) a permanent discontinuance in the manufacture of certain
products, (2) an interruption in the manufacture of certain products
that is likely to lead to a meaningful disruption in supply of those
products in the United States, (3) a permanent discontinuance in the
manufacture of API for certain products, or (4) an interruption in the
manufacture of API for certain products that is likely to lead to a
meaningful disruption in the supply of the API for those products. The
draft guidance, when finalized, would recommend that applicants and
manufacturers provide additional details and follow additional
procedures to ensure FDA has the
[[Page 20528]]
specific information it needs to help prevent or mitigate shortages.
The draft guidance also explains how FDA communicates information about
products in shortage to the public.
---------------------------------------------------------------------------
\1\ The CARES Act (Pub. L. 116-136) was enacted on March 27,
2020. The CARES Act amendments to section 506C of the FD&C Act took
effect on September 23, 2020. See section 3112(g) of the CARES Act.
---------------------------------------------------------------------------
While some supply disruptions and product shortages cannot be
predicted or prevented, early communication and detailed notifications
from manufacturers to the Agency play a significant role in decreasing
the incidence, impact, and duration of supply disruptions and product
shortages. Timely notifications that include specific information about
the situation allow the Agency to evaluate the situation and determine
an appropriate course of action. When FDA does not receive timely,
informative notifications, the Agency's ability to respond
appropriately is limited. Therefore, FDA is issuing this guidance to
assist applicants and manufacturers in providing FDA timely,
informative notifications about changes in the production of certain
finished drugs and biological products as well as certain API that may,
in turn, help the Agency in its efforts to prevent and mitigate
shortages. Among other things, the draft guidance, when finalized,
would explain: (1) who must notify FDA and what products are subject to
the notification requirements, (2) when to notify FDA, and (3) what
details to include in notifications that will ensure FDA has
information that would be helpful to assess the potential for a supply
disruption or shortage.
When finalized, this guidance will replace the March 2020 guidance
entitled ``Notifying FDA of a Permanent Discontinuance or Interruption
in Manufacturing Under Section 506C of the FD&C Act.''
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 notifying FDA
of a discontinuance or interruption in manufacturing of finished
products or API under section 506C of the FD&C Act. 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. Paperwork Reduction Act of 1995
This draft guidance contains information collection provisions that
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521).
Under the PRA, Federal Agencies must obtain approval from OMB for each
collection of information they conduct or sponsor. ``Collection of
information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and
includes Agency requests or requirements that members of the public
submit reports, keep records, or provide information to a third party.
Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) requires
Federal Agencies to provide a 60-day notice in the Federal Register
concerning each proposed collection of information before submitting
the collection to OMB for approval. To comply with this requirement,
FDA is publishing notice of the proposed collection of information set
forth in this document.
With respect to the following collection of information, FDA
invites 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.
This draft guidance refers to previously approved collections of
information found in FDA regulations. These collections of information
in Sec. Sec. 310.306, 314.81, and 600.82 (21 CFR 310.306,
314.81(b)(3)(iii), and 600.82) have been approved under OMB control
number 0910-0001. The draft guidance describes the requirements in
these regulations for applicants or manufacturers of certain drugs and
biological products to notify FDA of a permanent discontinuance in the
manufacture of certain finished products or an interruption in
manufacture of certain finished products that is likely to lead to a
meaningful disruption in the supply of such products in the United
States.
In addition, the draft guidance refers to notification requirements
added to section 506C of the FD&C Act by the CARES Act and, when
finalized, would describe additional recommendations for the submission
of information that have not been previously approved by OMB under the
PRA.
Section III.B of the draft guidance refers to requirements for when
notifications must be submitted to FDA under section 506C of the FD&C
Act and FDA regulations, but also requests that manufacturers submit
notifications to FDA in specific circumstances when notification is not
required. For example, if a manufacturer is considering taking an
action that may lead to a meaningful disruption in the supply of a
product (e.g., holding production to investigate a quality issue or
transfer of ownership), the draft guidance requests that the
manufacturer notify FDA immediately. The draft guidance also requests
that manufacturers notify FDA when they are unable to meet demand for
certain products covered by the notification requirement under section
506C of the FD&C Act, even in the absence of an interruption in
manufacturing, for example, when there is a sudden, unexpected spike in
demand.
Section III.C of the draft guidance refers to requirements for
information that must be included in notifications under section
506C(a) of the FD&C Act concerning permanent discontinuances or
interruptions in manufacturing of covered finished products, but also
recommends that additional information be included in such
notifications. For example, the draft guidance states that under
section 506C(a) of the FD&C Act notifications must include:
If an API is a reason for, or risk factor in, the
discontinuation or interruption in manufacturing of a covered finished
product, the source of the API and any alternative sources for the API
known by the manufacturer and
Whether any associated device used for preparation or
administration included in the product is a reason for, or risk factor
in, the discontinuation or interruption in manufacturing of the covered
finished product.
In addition, the draft guidance recommends that notifications
provide certain additional information beyond what is required under
section 506C of the FD&C Act and FDA's regulations. The following are
examples of additional information that FDA recommends be included in
notifications of a permanent discontinuance or interruption in
manufacturing concerning a covered finished product:
The anticipated time frame for all existing product (on
hand and in distribution channels) to be exhausted if the notification
is for a permanent discontinuance;
The estimated market share for the product and whether the
entire market share is affected by this issue;
Amount of current inventory of product at the
manufacturing facility or warehouse; and
Whether a proposal is available for FDA to review to
expedite availability of
[[Page 20529]]
the product or suggestions for FDA actions that may help prevent or
mitigate a supply disruption or shortage.
Section III.D of the draft guidance describes what information to
include in notifications about permanent discontinuances or
interruptions in manufacturing of API for covered finished products.
Similar to section III.C, the draft guidance in section III.D refers to
requirements for what information must be included in notifications
under section 506C(a) of the FD&C Act concerning permanent
discontinuances or interruptions in manufacturing of APIs for covered
finished products but also recommends that additional information be
included in such notifications.
Based on FDA's extensive experience receiving notifications
required under Sec. Sec. 310.306, 314.81(b)(3)(iii), and 600.82 and
working closely with manufacturers to prevent and mitigate shortages,
we estimate that 10 percent of the 75 respondents currently covered by
OMB control number 0910-0001 \2\ (``number of respondents'' in table 1,
row 1) will submit 1 additional notification concerning covered
finished products annually (``number of responses per respondent'' in
table 1, row 1) for certain circumstances that are not required by
section 506C of the FD&C Act and FDA regulations, such as an inability
to meet demand even with no interruption in manufacturing. This would
lead to an additional 7.5 responses annually (``total annual
responses'' in table 1, row 1). We estimate that each new response will
take approximately 2.75 hours to prepare (2 hours per response as
currently approved in OMB control number 0910-0001 and an additional
0.75 hours, as described below) (``hours per response'' in table 1, row
1).
---------------------------------------------------------------------------
\2\ The respondents are applicants of approved new drug
applications (NDAs), abbreviated new drug applications (ANDAs), and
biologic license applications (BLAs), as well as manufacturers of
prescription drugs marketed without an approved ANDA or NDA if the
product is life-supporting, life-sustaining, or intended for use in
the prevention or treatment of a debilitating disease or condition,
including use in emergency medical care or during surgery, and is
not a radiopharmaceutical product. BLA applicants of blood or blood
components are respondents if they manufacture a significant
percentage of the nation's Blood supply. We note that the CARES Act
clarified that products that are ``intended for use in the
prevention or treatment of a debilitating disease or condition''
includes ``any . . . [product] that is critical to the public health
during a public health emergency declared by the Secretary under
section 319 of the Public Health Service Act.'' This clarification
does not affect the estimated number of respondents because it does
not change the products or manufacturers covered by the notification
requirement; it merely clarifies that manufacturers of products
critical to the public health during a public health emergency
declared by the Secretary under section 319 of the Public Health
Service Act are covered.
---------------------------------------------------------------------------
Also based on our experience receiving notifications and working
closely with manufacturers to prevent and mitigate shortages, we
estimate that the new information that the CARES Act amended section
506C of the FD&C Act to require in notifications, as well as
information that FDA recommends in the draft guidance that respondents
provide beyond what is required under section 506C would lead to
respondents spending an additional 0.75 hours per response (``hours per
response'' in table 1, row 2). We anticipate that the additional 0.75
hours will provide sufficient time for respondents to gather and
compile the required and voluntary information for submission to FDA.
Currently, under OMB control number 0910-0001, it is estimated that FDA
receives 352.5 responses annually, and the additional 0.75 hours would
apply to each response.
For the new category of notifications required regarding
discontinuances and interruptions in manufacturing of API of covered
finished products, the respondents remain the same as those currently
covered by OMB control number 0910-0001 (subject to the requirements in
Sec. Sec. 310.306, 314.81(b)(3)(iii), and 600.82). However, based on
our understanding of the frequency of API manufacturing issues and
disruptions in API supply, we anticipate that 50 percent of the 75
respondents currently covered by OMB control number 0910-0001 (``number
of respondents'' in table 1, row 3) will submit 1 notification related
to API annually. This would lead to 37.5 responses annually (``total
annual responses'' in table 1, row 3). In light of anticipated
coordination between the applicant or finished product manufacturer and
the API supplier, we estimate a burden of 2 hours per response.
FDA estimates the additional burden of this collection of
information as follows:
Permanent Discontinuance or Interruption in Manufacturing of Certain
Drug or Biological Products OMB Control Number 0910-0001--Revision
Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
Guidance on notification of a
permanent discontinuance or Number of
interruption in manufacturing Number of responses per Total annual Average burden Total hours
under section 506C of the FD&C respondents respondent responses per response
Act
----------------------------------------------------------------------------------------------------------------
Voluntary Notifications of 75 0.1 7.5 2.75 20.63
Circumstances Where Supply May
Not Meet Demand for Finished
Products (described in section
III.B).........................
Additional Information on the 75 4.7 352.5 0.75 264.38
Discontinuance or Interruption
in Manufacturing of Finished
Products (described in section
III.C).........................
Notifications Regarding 75 0.5 37.5 2 75
Discontinuances and
Interruptions in Manufacturing
of API.........................
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 360
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this information collection.
[[Page 20530]]
III. Electronic Access
Persons with access to the internet may obtain an electronic
version of the draft guidance at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.
Dated: April 3, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-07238 Filed 4-5-23; 8:45 am]
BILLING CODE 4164-01-P