[Federal Register Volume 88, Number 34 (Tuesday, February 21, 2023)]
[Notices]
[Pages 10520-10522]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-03508]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2022-N-2440]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Biologics License 
Applications Procedures and Requirements

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Submit written comments (including recommendations) on the 
collection of information by March 23, 2023.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be submitted to https://www.reginfo.gov/public/do/PRAMain. Find this particular information 
collection by selecting ``Currently under Review--Open for Public 
Comments'' or by using the search function. The OMB control number for 
this information collection is 0910-0338. Also include the FDA docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: 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: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

Biologics License Applications (BLAs) Procedures and Requirements

OMB Control Number 0910-0338--Extension

    This information collection supports Agency regulations and 
recommendations found in associated guidance pertaining to BLA 
procedures and requirements. A BLA is a request for permission to 
introduce, or deliver for introduction, a biological product into 
interstate commerce (Sec.  601.2 (21 CFR 601.2)). BLAs are regulated 
under parts 600 through 680 (21 CFR parts 600 through 680). A BLA is 
submitted by any legal person or entity who is engaged in manufacture 
or an applicant for a license who takes responsibility for compliance 
with product and establishment standards. Interested persons may visit 
https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/biologics-license-applications-bla-process-cber for 
additional information, including available Agency resources.
    Regulations in part 601 set forth applicable procedures for the 
submission of license application information, including content and 
format elements. The regulations also explain requirements for 
suspension, revocation, and reissuance of BLAs and communicate 
procedures for requesting a hearing. Additionally, the information 
collection includes the submission of manufacturing change information 
governed by section 506A of the Federal Food, Drug, and Cosmetic Act 
(FD&C Act) (21 U.S.C. 356a), as well as postmarketing reports for 
approved human drugs and licensed biological products governed by 
section 506B of the FD&C Act (21 U.S.C. 356b). Finally, regulations in 
parts 610 through 680 establish both general and specific biological 
product standards.
    To implement these provisions, we have developed the following 
collection instruments:
1. Forms
    Form FDA 356h, Application to Market a New or Abbreviated New Drug 
or Biologic for Human Use, provides a uniform format for submitting 
BLAs. Form FDA 356h is a fillable PDF form that may be submitted 
through our Electronic Submission Gateway (ESG), for which respondents 
must create and maintain a user account. Utilizing Form FDA 356h helps 
to ensure that an application is complete and contains all the 
necessary information, so that delays due to lack of information may be 
avoided. In addition, the form provides key information to FDA for 
efficient handling and distribution to the appropriate staff for 
review. We have recently made minor updates to Form FDA 356h resulting 
from the October 3, 2022, reauthorization of the Prescription Drug User 
Fee Act. In this collection we account for BLAs submitted using Form 
FDA 356h.
    Form FDA 2252, Transmittal of Annual Report for Drugs and Biologics 
for Human Use, is used by an applicant of a licensed biological product 
to submit annual reports required by Sec.  601.70(b) (21 CFR 
601.70(b)). Form FDA 2252 is also a fillable PDF form and approved in 
OMB control number 0910-0001; however, in this information collection 
we account for submissions pertaining to biological products.
    Form FDA 2253, Transmittal of Advertisements and Promotional 
Labeling for Drugs and Biologics for Human Use, was developed for use 
by respondents to transmit specimens of advertisements and promotional 
labeling (e.g., circulars, package labels, container labels, etc.), as 
well as labeling changes. The submission of this information is 
required by Sec.  601.12 (21 CFR 601.12) for biological products and by 
21 CFR 314.81 for drug products. Form FDA 2253 is a fillable PDF form 
and is approved for use in OMB control number 0910-0001; however, in 
this information collection we account for submissions pertaining to 
biological products.
    Form FDA 3674, Certificate of Compliance Under 42 U.S.C. 
282(j)(5)(B), with Requirements of ClinicalTrials.gov Data Bank, was 
developed for use by respondents to certify submissions as required by 
section 402(j)(5)(B) of the Public Health Service (PHS) Act and is 
submitted through our ESG. Form FDA 3674 is a fillable PDF form and is 
approved for use in OMB control number 0910-0616; however, in this 
information collection we account for submissions pertaining to 
biological products.
2. Cover Sheets
    As provided for under Sec.  601.2(a), we also utilize cover sheets, 
so denoted for purposes of identifying specific content information 
within a given application.
3. Guidance Documents
    The guidance document ``Cooperative Manufacturing Arrangements for 
Licensed Biologics,'' (November 2008), available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cooperative-manufacturing-arrangements-licensed-biologics, discusses 
strategies for meeting an increased need for flexible manufacturing 
arrangements. Since cooperative manufacturing arrangements can take a 
considerable amount of time to develop, the guidance is intended to be 
useful for planning purposes in the early phases of product 
development. Many companies that perform only limited aspects of 
manufacturing processes are interested in sharing or contracting parts 
of manufacturing to facilitate product development and manufacturing 
flexibility. The guidance discusses recommended communication between

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licensed manufacturers and contract manufacturers regarding changes to 
production and facilities, results of tests and investigations 
regarding the product, types of products manufactured in the contract 
facility, and standard operating procedures. We believe that the 
information collection provisions in the guidance do not create a new 
burden for respondents. We believe the reporting and recordkeeping 
provisions are part of usual and customary business practices.
    All Agency guidance documents issued are consistent with our good 
guidance practice regulations in 21 CFR 10.115, which provide for 
public comment at any time. We maintain a searchable database of our 
guidance documents at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
    Respondents to this collection of information are licensed 
manufacturers of biological products. Based on the number of 2021 
fiscal year application submissions, we estimate there are 371 such 
respondents. The total annual responses are based on the number of 
submissions (i.e., license applications, labeling and other 
supplements, protocols, advertising and promotional labeling, 
notifications) for a particular product received annually by FDA. The 
hours per response are based on informal communications with industry 
and our experience with the information collection.
    In the Federal Register of November 1, 2022 (87 FR 65776) we 
published a 60-day notice soliciting comment on the proposed collection 
of information. No comments were received.
    We estimate the burden of this collection of information as 
follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
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                                                                           Number of
   21 CFR section or other citation;     Form FDA No.      Number of     responses per   Total annual     Average  burden per  response     Total hours
               activity                                   respondents     respondent       responses                                            \2\
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601.2(a) and 610.60 through 610.65;               356h              51           1.078              55  860.............................          47,300
 Application for biologics license
 (includes labeling).
601.5(a); Requirement to notify FDA of              NA              17          1.0589              18  0.33 (20 minutes)...............               6
 intention to discontinue manufacture
 of a product or all products.
601.6(a); Requirement to provide FDA                NA               1               1               1  0.33 (20 minutes)...............               1
 with copy of notification to selling
 agents and distributors upon
 suspension of its license.
601.12(a)(5); Requirement to inform                 NA             327          10.263           3,356  1...............................           3,356
 FDA of changes to an approved
 application.
601.12(b)(1), (b)(3), and (e);                    356h             195           5.795           1,130  80..............................          90,400
 Requirement to inform FDA of changes
 to an approved application.
601.12(c)(1) and (3); Requirement to              356h             153          4.6536             712  50..............................          35,600
 inform FDA of changes to an approved
 application.
601.12(c)(5); Requirement to inform               356h              73           2.740             200  50..............................          10,000
 FDA of changes to an approved
 application.
601.12(d)(1), (d)(3), and (f)(3);                 356h             279           3.398             948  24..............................          22,752
 Requirement to inform FDA of changes
 to an approved application.
601.12(f)(1); Requirement to inform               2253              64            2.75             176  40..............................           7,040
 FDA of changes to an approved
 application.
601.12(f)(2); Requirement to inform               2253              66           1.758             116  20..............................           2,320
 FDA of changes to an approved
 application.
601.12(f)(4) and 601.45; Requirement              2253             173         340.416          58,892  10..............................         588,920
 to inform FDA of changes to an
 approved application.
601.27(b); Request for deferred                     NA               9           1.778              16  24..............................             384
 submission of some or all safety and
 effectiveness assessments.
601.27(c); Request for full or partial              NA               8               1               8  8...............................              64
 waiver of safety and effectiveness
 assessments.
601.70(b) and (d), and 601.28; Annual             2252             101            1.84             186  24..............................           4,464
 progress reports of postmarketing
 studies.
610.15(d); Request for exceptions or                NA               1               1               1  1...............................               1
 alternatives to the regulation for
 constituent materials.
680.1(c); Requirement to annually                   NA               9               1               9  2...............................              18
 update a license file with the list
 of source materials and the suppliers
 of the materials.

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680.1(b)(3)(iv); Requirement to notify              NA               1               1               1  2...............................               2
 FDA when certain diseases are
 detected in source materials.
601.12; Amendments/Resubmissions......            356h             170          27.888            4741  20..............................          94,820
Section 402(j)(5)(B) of the PHS Act;              3674           1,291               1           1,291  0.28 (17 minutes)...............             358
 Certification to accompany biological
 product applications.
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    Total.............................  ..............  ..............  ..............  ..............  ................................         907,806
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ The numbers in this column have been rounded to the nearest whole number.


                                               Table 2--Estimated Annual Third-Party Disclosure Burden \1\
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                                                                   Number of
           21 CFR section; activity                Number of      disclosures    Total annual       Average  burden per  disclosures        Total hours
                                                  respondents   per respondent    disclosures                                                   \2\
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601.6(a); Requirement to notify selling agents               1              20              20  0.33 (20 minutes).......................               7
 and distributors upon suspension of license.
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ The number in this column has been rounded to the nearest whole number.

    Our estimated burden for the information collection reflects an 
overall increase of 467,907 hours and a corresponding increase in 
responses. Most of our adjustment reflects an increase in the number of 
annual submissions that we have received under Sec. Sec.  601.12(b)(1) 
and (3), (e), and (f)(4), and 601.45 over the last few years. We 
attribute the remaining increase (358 hours) to submissions of Form FDA 
3674.

    Dated: February 15, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-03508 Filed 2-17-23; 8:45 am]
BILLING CODE 4164-01-P