[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Cosmetic Act; Draft Guidance for Industry; Availability; Agency 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availability of a draft guidance for industry entitled ``Notification 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 The draft guidance is intended to 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 The draft guidance also 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draft guidance is not final nor is it in effect at this time.

DATES: Submit either electronic or written comments on the draft 
guidance by June 5, 2023 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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proposed collection of information in the draft guidance by June 5, 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