[Federal Register Volume 87, Number 98 (Friday, May 20, 2022)]
[Notices]
[Pages 30963-30966]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-10698]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-D-0277]


Risk Management Plans To Mitigate the Potential for Drug 
Shortages; Draft Guidance for Industry; Availability; Agency 
Information Collection Activities; Proposed Collection; Comment Request

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or we) is announcing the 
availability of a draft guidance for industry entitled ``Risk 
Management Plans to Mitigate the Potential for Drug Shortages.'' This 
draft guidance is intended to help stakeholders develop, maintain, and 
implement, as appropriate, risk management plans (RMPs) to proactively 
assist in the prevention of human drug product and biological product 
shortages. In March 2020, with the enactment of the Coronavirus Aid, 
Relief, and Economic Security Act (CARES Act), the Federal Food, Drug, 
and Cosmetic Act (FD&C Act) was amended to require certain 
manufacturers to develop, maintain, and implement, as appropriate, a 
``redundancy risk management plan.'' This draft guidance provides 
information about the development and content of RMPs for those 
manufacturers as well as for other stakeholders. This draft guidance 
recommends a framework and factors to consider that stakeholders can 
use to develop RMPs. This draft guidance is relevant for all 
stakeholders, including those with oversight and control 
responsibilities for drug quality and contract establishments, and for 
manufacturers of active pharmaceutical ingredients (APIs), approved or 
licensed drug and biological products, and drug products marketed 
without an application.

DATES: Submit either electronic or written comments on the draft 
guidance by July 19, 2022 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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proposed collection of information in the draft guidance by July 19, 
2022.

[[Page 30964]]


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-2022-D-0277 for ``Risk Management Plans to Mitigate the Potential 
for Drug Shortages.'' 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 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: Karen Takahashi, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 6686, Silver Spring, MD 20993-0002, 301-
796-3191; 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.
    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 ``Risk Management Plans to Mitigate the Potential for Drug 
Shortages.'' This draft guidance is intended to help stakeholders \1\ 
develop, maintain, and implement, as appropriate, RMPs to proactively 
assist in the prevention of human drug product and biological product 
shortages. In March 2020, with the enactment of the CARES Act (Pub. L. 
116-136), Congress added section 506C(j) to the FD&C Act, which 
requires certain manufacturers to develop, maintain, and implement, as 
appropriate, a ``redundancy risk management plan that identifies and 
evaluates risks to the supply of the drug, as applicable, for each 
establishment in which such drug or active pharmaceutical ingredient of 
such drug is manufactured.'' Section 506C(j) of the FD&C Act became 
effective September 23, 2020. This guidance provides information about 
the development and

[[Page 30965]]

content of RMPs for those manufacturers as well as for other 
stakeholders.
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    \1\ For the purposes of this guidance, the term stakeholder 
includes each manufacturer of a drug described in section 506C(a) of 
the FD&C Act (21 U.S.C. 356c(a)) or of any API included in such 
drugs. (See generally section 506C(j) of the FD&C Act.) The term 
stakeholder also broadly includes any person or entity who has 
oversight and control over the manufacture of drugs to ensure 
quality or owns or operates an establishment (as defined in 21 CFR 
207.1 and 600.3) that manufactures a drug or biological product. 
Examples of stakeholders include contract facilities as referenced 
in 21 CFR 200.10(b); applicants with an approved new drug 
application, abbreviated new drug application, or an approved 
biologics license application; manufacturers of drug products 
marketed without an approved application; manufacturers of 
components, including APIs, intended for use in the manufacture of 
drug products; and manufacturers of drug-led, drug-device or 
biologic-led, biologic-device combination products (as defined in 21 
CFR 3.2(e)) regulated by the Center for Drug Evaluation and Research 
or the Center for Biologics Evaluation and Research. This guidance 
references specific stakeholders individually where appropriate 
(e.g., if a specific section of the guidance is relevant to specific 
stakeholders only); otherwise, recommendations that refer to the 
manufacture of drugs are generally relevant to all stakeholders with 
the roles described above with respect to human drug and biological 
products.
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    Drug shortages pose a significant public health threat that can 
delay, and in some cases even deny, critically needed care for 
patients. FDA views RMPs as an important mechanism for stakeholders to 
proactively identify, assess, and mitigate the risks that might lead to 
a disruption in the supply of drug products, thus preemptively reducing 
the probability of a drug shortage, and preserving the private and 
public resources used in resolving the shortage.
    Based on recent publications and reports, the majority of drug 
shortages are associated with quality issues. This guidance proposes a 
framework stakeholders can use to develop RMPs that aligns with 
principles stated in the International Council for Harmonisation 
guidance for industry entitled ``Q9 Quality Risk Management'' 
(available at https://www.fda.gov/media/71543/download). In addition, 
FDA also recommends several factors to consider when developing the 
content of the RMPs. This guidance is relevant for all stakeholders, 
including those with oversight and control responsibilities for drug 
quality and contract establishments, and for manufacturers of APIs, 
approved or licensed drug and biological products, and drug products 
marketed without an application.
    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 ``Risk 
Management Plans to Mitigate the Potential for Drug Shortages.'' 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

    Under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-
3521), Federal Agencies must obtain approval from the Office of 
Management and Budget (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, 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.

Discontinuance or Interruption in the Production of Life-Saving Drugs

OMB Control Number 0910-0045--Revision

    This information collection helps support implementation of 
requirements under section 506C(j) of the FD&C Act. Section 506C(j) of 
the FD&C Act requires manufacturers of drug products described in 
section 506C(a) of the FD&C Act or of any active pharmaceutical 
ingredient or any associated medical devices used for preparation or 
administration included in the drug to develop, maintain, and 
implement, as appropriate, a redundancy RMP that identifies and 
evaluates risks to the supply of the drug, as applicable, for each 
establishment in which such drug or active pharmaceutical ingredient of 
such drug is manufactured.
    For purposes of this analysis, respondents are those identified in 
the draft guidance, section III.A., Stakeholders in the Manufacturing 
Supply Chain. A primary stakeholders is generally the entity that 
determines which materials and services are necessary to produce a drug 
product. Secondary stakeholders are entities that are expected to have 
more detailed insight into specific segments of the supply chain for a 
drug product but may not have an understanding of its entirety. 
Finally, other stakeholders, such as inactive ingredient manufacturers, 
packagers, and distributors, are involved in other segments of the 
supply chain. In the draft guidance, section IV., RMP Framework and 
Development Strategy, we discuss specific recommendations regarding the 
RMP.
    We estimate the burden of this collection of information as 
follows:

                                                   Table 1--Estimated Annual Recordkeeping Burden \1\
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                                                            Number of
    Section 506C(j) of the FD&C Act;        Number of      records per    Total records       Average burden per  recordkeeping \2\         Total hours
         recordkeeping activity           recordkeepers   recordkeeper
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Developing an RMP; Guidance for                   2,600               1           2,600  29.32 (range 25 to 250)........................          76,250
 Industry section IV.B.
Updating an RMP........................           5,200               1           5,200  2.93 (range 2.5 to 25).........................          15,250
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    Total..............................  ..............  ..............  ..............  ...............................................          91,500
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\1\ There are no capital costs or operating and maintenance costs associated with this information collection.
\2\ Figure has been rounded.

    We assume a total of 2,600 respondents will incur an initial burden 
associated with developing an RMP based on recommendations described in 
the draft guidance. This figure is comprised of 50 primary 
stakeholders; 1,125 secondary stakeholders; and 1,425 other 
stakeholders, and represents half the total number of respondents we 
identify for each of the three respective categories.
    For burden associated with updating an RMP, we include all 
respondents in the respective three categories, for a total of 5,200.
    We believe the overall burden for collecting information and 
preparing

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RMPs depends on the stakeholder type (primary, secondary, or other 
stakeholder) and its operation.
    We anticipate that stakeholders will be able to leverage 
information across products, but we understand that the actual burden 
for a given stakeholder will depend on the portfolio of covered 
products and the complexity of their operations. Our estimate reflects 
what we believe is the average burden among all respondents.
    This draft guidance also refers to previously approved FDA 
collections of information found in FDA regulations. The collections of 
information found in 21 CFR 310.306, 314.81(b)(3)(iii), and 600.82 on 
notifying FDA of a permanent discontinuance or an interruption in 
manufacturing of certain drugs or biological products, and 21 CFR part 
314 new drug and abbreviated new drug applications, and 21 CFR part 600 
biologics license applications have been approved under OMB control 
numbers 0910-0001 and 0910-0338, respectively; the collections of 
information in 21 CFR parts 210 and 211 on current good manufacturing 
practice have been approved under OMB control number 0910-0139.

III. Electronic Access

    Persons with access to the internet may obtain an electronic 
version of the draft guidance at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.

    Dated: May 13, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-10698 Filed 5-19-22; 8:45 am]
BILLING CODE 4164-01-P