0759 SSA Perm Discontinuation 2018 Ext

United States Food and Drug Administration
Permanent Discontinuance or Interruption in Manufacturing of
Certain Drug or Biological Products
OMB Control No. 0910-0759
SUPPORTING STATEMENT Part A: Justification
1. Circumstances Making the Collection of Information Necessary
This information collection supports Food and Drug Administration (FDA, us or we) regulations.
As amended by the Food and Drug Administration Safety and Innovation Act (FDASIA), (Pub.
Law 112-144), the Federal Food, Drug, and Cosmetic Act (FD&C Act) requires all
manufacturers of certain drugs to notify FDA of a permanent discontinuance or an interruption in
manufacturing of these drugs 6 months in advance of the permanent discontinuance or
interruption in manufacturing, or as soon as practicable. FDASIA also added section 506E to the
FD&C Act (21 U.S.C. 356e), requiring FDA to maintain a current list of drugs that are
determined by FDA to be in shortage in the United States and to include on that public list
certain information about those shortages. Finally, FDASIA permits FDA to apply section 506C
to biological products by regulation and implement certain drug shortages provisions.
Accordingly we established regulations in 21 CFR Parts 310.306, 314.81, and 600.82 to
implement these provisions. Under the regulations, applicants with an approved new drug
application (NDA) or abbreviated new drug application (ANDA) for a covered drug product,
manufacturers of a covered drug product marketed without an approved application, and
applicants with an approved biologics license application (BLA) for a covered biological product
(including certain applications of blood or blood components) must notify FDA in writing of a
permanent discontinuance of the manufacture of the drug or biological product or an interruption
in manufacturing of the drug or biological product that is likely to lead to a meaningful
disruption in the applicant's supply (or a significant disruption for blood or blood components) of
that product. The notification is required if the drug or biological 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 if the drug or
biological product is not a radiopharmaceutical drug product.
The regulations prescribe the collection of the following information: (1) The name of the drug
or biological product subject to the notification, including the NDC (or, for a biological product
that does not have an NDC, an alternative standard for identification and labeling that has been
recognized as acceptable by the Center Director); (2) the name of each applicant of the drug or
biological product; (3) whether the notification relates to a permanent discontinuance of the drug
or biological product or an interruption in manufacturing of the product; (4) a description of the
reason for the permanent discontinuance or interruption in manufacturing; and (5) the estimated
duration of the interruption in manufacturing.

As previously stated, notifications must be submitted to FDA electronically at least 6 months
prior to the date of the permanent discontinuance or interruption in manufacturing. If 6 months'
advance notice is not possible because the permanent discontinuance or interruption in
manufacturing was unanticipated 6 months in advance, the applicant must notify FDA as soon as
practicable, but in no case later than 5 business days after the permanent discontinuance or
interruption in manufacturing occurs.
We therefore request OMB approval of the information collection provisions found in the
following regulations:
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21 CFR 310.306 – notification of a permanent discontinuance or an interruption in
manufacturing of marketed prescription drugs for human use without approved new drug
applications;
21 CFR 314.81(b)(3)(iii) – permanent discontinuance or interruption in manufacturing of
approved prescription drugs; and
21 CFR 600.82 – permanent discontinuance or interruption in manufacturing of
prescription biological products.

2. Purpose and Use of the Information Collection
Respondents to the information collection are applicants of approved NDAs, ANDAs, and
BLAs, as well as manufacturers of prescription drug products marketed without an approved
ANDA or NDA if the product is life supporting, life sustaining, or intended for use in the
prevention or treatments of a debilitating disease or condition, including use in emergency
medical care or during surgery, and is not a radiopharmaceutical product. Finally, BLA
applicants of blood or blood components manufacturing a significant percentage of the Nation’s
blood supply are also subject to the applicable regulations. The information collection was
established to help prevent and reduce current and future disruptions in the supply of lifesaving
medicines, as well as to ensure that both FDA and the public receive adequate advance notice of
shortages whenever possible. Shortages can involve critical drugs used to treat cancer, to
provide required parenteral nutrition, or to address other serious medical conditions and can
delay or deny needed care for patients. Shortages can also result in providers prescribing
second-line alternatives, which may be less effective or higher risk than first-line therapies.
Early notifications of potential shortages enables us to work with manufacturers and other
stakeholders to help prevent such shortages.
3. Use of Improved Information Technology and Burden Reduction
Sections 310.306, 314.81(b)(3)(iii), and 600.82 provide that the notifications must be provided to
FDA electronically, in a format that FDA can process, review, and archive. We anticipate that
manufacturers will email us the submissions.

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4. Efforts to Identify Duplication and Use of Similar Information
This is the first extension request of an information collection established through agency
rulemaking (0910-AG88). Now that regulatory requirements have been codified and the
effective date realized, we intend to consolidate the information collection elements into existing
and approved collections as appropriate. Specifically, we believe burden attributed under this
collection may be accounted for under related collections (see OMB Control Nos. 0910-0308,
0910-0230, and 0910-0645), and we are therefore reviewing our inventory. Upon ensuring that
information collection requirements associated with the permanent discontinuance or
interruption in manufacturing of certain drug or biological products as prescribed under 21 CFR
§§ 310.306, 314.81(b)(3)(iii), and 600.82 are included elsewhere in our inventory, we will
discontinue this information collection.
5. Impact on Small Businesses or Other Small Entities
While new drug and biological product development is typically an activity completed by large
multinational drug firms, we do not believe the information collection poses undue burden on
small entities. At the same time, we provide assistance to small businesses in complying with
our regulations. We offer assistance from both scientific and administrative staffs within the
agency and have provided a Small Business Guide on our website at
http://www.fda.gov/ForIndustry/SmallBusinessAssistance/default.htm.
6. Consequences of Collecting the Information Less Frequently
The regulations implement a statutory 6-month notification period before permanent
discontinuance or interruption in manufacturing of applicable products, or, if that is not possible,
as soon as practicable thereafter. We believe this information collection schedule is necessary to
help prevent and reduce current and future disruptions in the supply of lifesaving medicines.
7. Special Circumstances Relating to the Guidelines of 5 CFR § 1320.5
There are no special circumstances for this collection of information.
8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the
Agency
In accordance with 5 CFR 1320.8(d), we published a notice in the Federal Register of April 13,
2018 (83 FR 16108) soliciting public comment on the information collection. No comments
were received in response to the notice.
9. Explanation of Any Payment or Gift to Respondents
No payments or gifs are provided to respondents to the information collection.

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10. Assurance of Confidentiality Provided to Respondents
Confidentiality of the information submitted under drug approval applications is protected under
21 CFR 314.430 and under 21 CFR part 20. The unauthorized use or disclosure of trade secrets
required in applications is specifically prohibited under Section 310(j) of the FD&C Act. In
addition, information is protected under §§ 314.81(b)(3)(iii)(d), and 600.82(d).
11. Justification for Sensitive Questions
There are no questions of a sensitive nature associated with the information collection.
12. Estimates of Annualized Burden Hours and Costs
12a. Annualized Hour Burden Estimate
We estimate the burden of the information collection as follows:
21 CFR Section

Table 1.--Estimated Reporting Burden1
No. of
No. of
Total
Respondents Responses per
Annual
Respondent
Responses
75
4.7
352.5

Average
Burden per
Response

Total
Hours

Notifications required under
2
705
§§ 310.306 (unapproved drugs),
314.81(b)(3)(iii) (products approved
under an NDA or ANDA), and 600.82
(products approved under a BLA)
1
There are no capital costs or operating and maintenance costs associated with this collection of information.

Based on the number of drug and biological product shortage related notifications we have
received in the past 12 months, we estimate that annually 75 respondents (“No. of Respondents”
in table 1) will notify us of a permanent discontinuance of the manufacture of a drug or
biological product or an interruption in manufacturing of a drug or biological product that is
likely to lead to a meaningful disruption in the respondent’s supply of that product.
Cumulatively we estimate these respondents will submit 352.5 notifications annually as required
under §§ 310.306, 314.81(b)(3)(iii), and 600.82. We estimate 4.7 notifications per respondent,
because a respondent may experience multiple discontinuances or interruptions in manufacturing
in a year that require notification (“No. of Responses per Respondent” in table 1). We also
estimate that preparing and submitting these notifications to FDA will take approximately 2
hours per respondent (“Average Burden per Response” in table 1).
12b. Annualized Cost Burden Estimate
Based on previous analysis in support of agency rulemaking (0910-AG88), we retain an
estimated annual cost to respondents of $16,827. This estimate assumes industry costs
associated with the reporting requirements as prescribed in the regulations.

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13. Estimates of Other Total Annual Costs to Respondents and/or Recordkeepers/Capital Costs
There are no capital costs, start-up, operating or maintenance costs associated with this
information collection.
14. Annualized Cost to the Federal Government
Based on FTE allocations for review of information submitted and associated administrative
activities, we estimate a cost of $441,000 annually to the Federal government.
15. Explanation for Program Changes or Adjustments
This information collection reflects adjustments since the previous OMB approval. The current
burden is based on the number of actual new notifications received including notifications that
were counted previously under the OMB approval for the interim final rule entitled “Permanent
Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products” (80
FR 38915, July 8, 2015) (OMB control number 0910-0699). This results in an increase of 128
responses and 255 burden hours.
16. Plans for Tabulation and Publication and Project Time Schedule
There are no tabulated results to publish for this information collection.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
FDA is not seeking approval to exempt display of the expiration date of OMB approval.
18. Exception to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.

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