[Federal Register Volume 87, Number 210 (Tuesday, November 1, 2022)]
[Notices]
[Pages 65776-65779]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-23728]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Agency Information Collection Activities; Proposed Collection; 
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 or Agency or we) is 
announcing an opportunity for public comment on the proposed collection 
of certain information by the Agency. Under the Paperwork Reduction Act 
of 1995 (PRA), Federal Agencies are required to publish notice in the 
Federal Register concerning each proposed collection of information, 
including each proposed extension of an existing collection of 
information, and to allow 60 days for public comment in response to the 
notice. This notice solicits comments on the collection of information 
associated with biologics license application (BLA) procedures and 
requirements.

DATES: Either electronic or written comments on the collection of 
information must be submitted by January 3, 2023.

ADDRESSES: You may submit comments as follows. Please note that late, 
untimely filed comments will not be considered. The https://www.regulations.gov electronic filing system will accept comments until 
11:59 p.m. Eastern Time at the end of January 3, 2023. Comments 
received by mail/hand delivery/courier (for written/paper submissions) 
will be considered timely if they are received on or before that date.

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-N-2440 for ``Biologics License Applications Procedures and 
Requirements.'' Received comments, those filed in a timely manner (see 
ADDRESSES), 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.

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: Under the 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, including 
each proposed extension of an existing 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

[[Page 65777]]

of automated collection techniques, when appropriate, and other forms 
of information technology.

Biologics License Applications 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 (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 (PDUFA). 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 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 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 part 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 
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.
    We estimate the burden of this collection of information as 
follows:

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                                                     Table 1--Estimated Annual Reporting Burden \1\
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                                                                               Number of
21 CFR section or other citation; activity   Form FDA No.      Number of     responses per   Total annual    Average burden per response    Total hours
                                                              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 with               NA               1               1               1  0.33 (20 minutes)...........               1
 copy of notification to selling agents
 and distributors upon suspension of its
 license.
601.12(a)(5); Requirement to inform FDA of              NA             327          10.263           3,356  1...........................           3,356
 changes to an approved application.
601.12(b)(1), (b)(3), and (e); Requirement            356h             195           5.795           1,130  80..........................          90,400
 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 FDA of            356h              73           2.740             200  50..........................          10,000
 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 FDA of            2253              64            2.75             176  40..........................           7,040
 changes to an approved application.
601.12(f)(2); Requirement to inform FDA of            2253              66           1.758             116  20..........................           2,320
 changes to an approved application.
601.12(f)(4) and 601.45; Requirement to               2253             173         340.416          58,892  10..........................         588,920
 inform FDA of changes to an approved
 application.
601.27(b); Request for deferred submission              NA               9           1.778              16  24..........................             384
 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 update a              NA               9               1               9  2...........................              18
 license file with the list of source
 materials and the suppliers of the
 materials.
680.1(b)(3)(iv); Requirement to notify FDA              NA               1               1               1  2...........................               2
 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    Total
                                    respondents   per respondent    disclosures        disclosure      hours \2\
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601.6(a); Requirement to notify                1              20              20  0.33 (20 minutes)..          7
 selling agents 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.


[[Page 65779]]

    Our estimated burden for the information collection reflects an 
overall increase of 467,907 hours and a corresponding increase in 
responses. We attribute part of this adjustment in the total hours to 
an increase in the number of submissions that we have received under 
601.12(b)(1) and (3), (e), and (f)(4), and 601.45 over the last few 
years, which accounts for an increase of 467,549 hours. An additional 
increase of 358 hours is associated with certifications on Form FDA 
3674.

    Dated: October 27, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-23728 Filed 10-31-22; 8:45 am]
BILLING CODE 4164-01-P