Agency Information Collection Activities; Proposed Collection; Comment Request; General Licensing Provisions: Biologics License Application, Changes to an Approved Application, Labeling, Revocation and Suspension, Postmarketing Studies Status Reports, and Form FDA 356h, 49310-49314 [2019-20328]
Download as PDF
<![CDATA[
49310
Federal Register / Vol. 84, No. 182 / Thursday, September 19, 2019 / Notices
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2013–N–0578]
Agency Information Collection
Activities; Proposed Collection;
Comment Request; General Licensing
Provisions: Biologics License
Application, Changes to an Approved
Application, Labeling, Revocation and
Suspension, Postmarketing Studies
Status Reports, and Form FDA 356h
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA, 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 relating to general licensing
provisions for biologics license
applications (BLAs), changes to an
approved application, labeling,
revocation and suspension,
postmarketing studies status reports,
and Form FDA 356h.
DATES: Submit electronic or written
comments on the collection of
information by November 18, 2019.
ADDRESSES: You may submit comments
as follows: Please note that late,
untimely filed comments will not be
considered. Electronic comments must
be submitted on or before November 18,
2019. The https://www.regulations.gov
electronic filing system will accept
comments until 11:59 p.m. Eastern Time
at the end of November 18, 2019.
Comments received by mail/hand
delivery/courier (for written/paper
submissions) will be considered timely
if they are postmarked or the delivery
service acceptance receipt is on or
before that date.
jbell on DSK3GLQ082PROD with NOTICES
SUMMARY:
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
VerDate Sep<11>2014
17:30 Sep 18, 2019
Jkt 247001
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–
2013–N–0578 for ‘‘General Licensing
Provisions: Biologics License
Application, Changes to an Approved
Application, Labeling, Revocation and
Suspension, Postmarketing Studies
Status Reports, and Form FDA 356h.’’
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.
• 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
PO 00000
Frm 00066
Fmt 4703
Sfmt 4703
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.gpo.gov/
fdsys/pkg/FR-2015-09-18/pdf/201523389.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.
FOR FURTHER INFORMATION CONTACT:
Domini Bean, Office of Operations,
Food and Drug Administration, Three
White Flint North, 10 a.m.–12 p.m.,
11601 Landsdown St., North Bethesda,
MD 20852, 301–796–5733, PRAStaff@
fda.hhs.gov.
SUPPLEMENTARY INFORMATION: Under the
PRA (44 U.S.C. 3501–3520), 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
E:\FR\FM\19SEN1.SGM
19SEN1
Federal Register / Vol. 84, No. 182 / Thursday, September 19, 2019 / Notices
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.
jbell on DSK3GLQ082PROD with NOTICES
General Licensing Provisions: Biologics
License Application, Changes to an
Approved Application, Labeling,
Revocation and Suspension,
Postmarketing Studies Status Reports,
and Form FDA 356h
OMB Control Number 0910–0338—
Extension
Under section 351 of the Public
Health Services Act (PHS Act) (42
U.S.C. 262), manufacturers of biological
products must submit a license
application for FDA review and
approval before marketing a biological
product in interstate commerce.
Licenses may be issued only upon
showing that the establishment and the
products for which a license is desired
meets standards prescribed in
regulations designed to ensure the
continued safety, purity, and potency of
such products. All such licenses are
issued, suspended, and revoked as
prescribed by regulations in part 601 (21
CFR part 601).
Section 130(a) of the Food and Drug
Administration Modernization Act (Pub.
L. 105–115) amended the Federal Food,
Drug, and Cosmetic Act (FD&C Act) by
adding a new provision (section 506B of
the FD&C Act (21 U.S.C. 356b))
requiring reports of postmarketing
studies for approved human drugs and
licensed biological products. Section
506B of the FD&C Act provides FDA
with additional authority to monitor the
progress of postmarketing studies that
applicants have made a commitment to
conduct and requires the Agency to
make publicly available information
that pertains to the status of these
studies. Under section 506B(a) of the
FD&C Act, applicants that have
committed to conduct a postmarketing
study for an approved human drug or
licensed biological product must submit
to FDA a status report of the progress of
the study or the reasons for the failure
of the applicant to conduct the study.
This report must be submitted within 1
year after the U.S. approval of the
VerDate Sep<11>2014
17:30 Sep 18, 2019
Jkt 247001
application and then annually until the
study is completed or terminated.
A summary of the collection of
information requirements follows:
Section 601.2(a) requires a
manufacturer of a biological product to
submit an application on forms
prescribed for such purposes with
accompanying data and information,
including certain labeling information,
to FDA for approval to market a product
in interstate commerce. The container
and package labeling requirements are
provided under §§ 610.60 through
610.65 (21 CFR 610.60 through 610.65).
The estimate for these regulations is
included in the estimate under
§ 601.2(a) in table 1.
Section 601.5(a) requires a
manufacturer to submit to FDA notice of
its intention to discontinue manufacture
of a product or all products. Section
601.6(a) requires the manufacturer to
notify selling agents and distributors
upon suspension of its license, and
provide FDA of such notification.
Section 601.12(a)(2) requires,
generally, that the holder of an
approved BLA must assess the effects of
a manufacturing change before
distributing a biological product made
with the change. Section 601.12(a)(4)
requires, generally, that the applicant
must promptly revise all promotional
labeling and advertising to make it
consistent with any labeling changes
implemented. Section 601.12(a)(5)
requires the applicant to include a list
of all changes contained in the
supplement or annual report; for
supplements, this list must be provided
in the cover letter. The burden estimates
for § 601.12(a)(2) are included in the
estimates for supplements (§§ 601.12(b)
and (c)) and annual reports
(§ 601.12(d)). The burden estimates for
§ 601.12(a)(4) are included in the
estimates under 601.12(f)(4) in table 1.
Sections 601.12(b)(1) and (3), (c)(1),
(3), and (5), and (d)(1) and (3) require
applicants to follow specific procedures
to submit information to FDA of any
changes, in the product, production
process, quality controls, equipment,
facilities, or responsible personnel
established in an approved license
application. The appropriate procedure
depends on the potential for the change
to have a substantial, moderate, or
minimal adverse effect on the identity,
strength, quality, purity, or potency of
the products as they may relate to the
safety or effectiveness of the product.
Under § 601.12(b)(4), an applicant may
ask FDA to expedite its review of a
supplement for public health reasons or
if a delay in making the change
described in it would impose an
extraordinary hardship of the applicant.
PO 00000
Frm 00067
Fmt 4703
Sfmt 4703
49311
The burden estimate for § 601.12(b)(4) is
minimal and included in the estimate
under § 601.12(b)(1) and (3) in table 1.
Section 601.12(e) requires applicants
to submit a protocol, or change to a
protocol, as a supplement requiring
FDA approval before distributing the
product. Section 601.12(f)(1) through (3)
requires applicants to follow specific
procedures to report certain labeling
changes to FDA. Section 601.12(f)(4)
requires applicants to report to FDA
advertising and promotional labeling
and any changes.
Under § 601.14, the content of
labeling required in 21 CFR
201.100(d)(3) must be in electronic
format and in a form that FDA can
process, review, and archive. This
requirement is in addition to the
provisions of §§ 601.2(a) and 601.12(f).
The burden estimate for § 601.14 is
minimal and included in the estimate
under §§ 601.2(a) (BLAs) and
601.12(f)(1) through (3) (labeling
supplements and annual reports) in
table 1.
Section 601.45 requires applicants of
biological products for serious or lifethreatening illnesses to submit to the
Agency for consideration, during the
preapproval review period, copies of all
promotional materials, including
promotional labeling as well as
advertisements.
In addition to §§ 601.2 and 601.12,
there are other regulations in 21 CFR
parts 640, 660, and 680 that relate to
information to be submitted in a license
application or supplement for certain
blood or allergenic products as follows:
§§ 640.6; 640.17; 640.21(c); 640.22(c);
640.25(c); 640.56(c); 640.64(c); 640.74(a)
and (b)(2); 660.51(a)(4); and
680.1(b)(2)(iii) and (d).
In table 1, the burden associated with
the information collection requirements
in the applicable regulations is included
in the burden estimate for §§ 601.2 and/
or 601.12. A regulation may be listed
under more than one subsection of
§ 601.12 due to the type of category
under which a change to an approved
application may be submitted.
There are also additional container
and/or package labeling requirements
for certain licensed biological products
including: § 640.74(b)(3) and (4) for
Source Plasma Liquid; § 640.84(a) and
(c) for Albumin; § 640.94(a) for Plasma
Protein Fraction; § 660.2(c) for Antibody
to Hepatitis B Surface Antigen;
§ 660.28(a), (b), and (c) for Blood
Grouping Reagent; § 660.35(a) through
(d) for Reagent Red Blood Cells; § 660.45
for Hepatitis B Surface Antigen; and
§ 660.55(a) and (b) for Anti-Human
Globulin. The burden associated with
the additional labeling requirements for
E:\FR\FM\19SEN1.SGM
19SEN1
jbell on DSK3GLQ082PROD with NOTICES
49312
Federal Register / Vol. 84, No. 182 / Thursday, September 19, 2019 / Notices
submission of a license application for
these certain biological products is
minimal because the majority of the
burden is associated with the
requirements under §§ 610.60 through
610.65 or 21 CFR 809.10. Therefore, the
burden estimates for these regulations
are included in the estimate under
§§ 610.60 through 610.65 in table 1. The
burden estimates associated with
§ 809.10 are approved under OMB
control number 0910–0485.
Section 601.27(a) requires that
applications for new biological products
contain data that are adequate to assess
the safety and effectiveness of the
biological product for the claimed
indications in pediatric subpopulations,
and to support dosing and
administration information. Section
601.27(b) provides that an applicant
may request a deferred submission of
some or all assessments of safety and
effectiveness required under § 601.27(a)
until after licensing the product for use
in adults. Section 601.27(c) provides
that an applicant may request a full or
partial waiver of the requirements under
§ 601.27(a) with adequate justification.
The burden estimates for § 601.27(a) are
included in the burden estimate under
§ 601.2(a) in table 1 since these
regulations deal with information to be
provided in an application.
Section 601.28 requires sponsors of
licensed biological products to submit
the information in § 601.28(a)–(c) to the
Center for Biologics Evaluation and
Research (CBER) or to the Center for
Drug Evaluation and Research (CDER)
each year, within 60 days of the
anniversary date of approval of the
license. Section 601.28(a) requires
sponsors to submit to FDA a brief
summary stating whether labeling
supplements for pediatric use have been
submitted and whether new studies in
the pediatric population to support
appropriate labeling for the pediatric
population have been initiated. Section
601.28(b) requires sponsors to submit to
FDA an analysis of available safety and
efficacy data in the pediatric population
and changes proposed in the labeling
based on this information. Section
601.28(c) requires sponsors to submit to
FDA a statement on the current status of
any postmarketing studies in the
pediatric population performed by, on
or behalf of, the applicant. If the
postmarketing studies were required or
agreed to, the status of these studies is
to be reported under § 601.70 rather
than under this section.
Sections 601.33 through 601.35 clarify
the information to be submitted in an
application to FDA to evaluate the
safety and effectiveness of
radiopharmaceuticals intended for in
VerDate Sep<11>2014
17:30 Sep 18, 2019
Jkt 247001
vivo administration for diagnostic and
monitoring use. The burden estimates
for §§ 601.33 through 601.35 are
included in the burden estimate under
§ 601.2(a) in table 1 since these
regulations deal with information to be
provided in an application.
Section 601.70 (b) requires each
applicant of a licensed biological
product to submit annually a report to
FDA on the status of postmarketing
studies for each approved product
application. Each annual postmarketing
status report must be accompanied by a
completed transmittal Form FDA 2252
(Form FDA 2252 approved under OMB
control number 0910–0001). Under
§ 601.70(d), two copies of the annual
report shall be submitted to FDA.
Sections 601.91 through 601.94
concern biological products for which
human efficacy studies are not ethical or
feasible. Section 601.91(b)(2) requires,
in certain circumstances, such
postmarking restrictions as are needed
to ensure the safe use of the biological
product. Section 601.91(b)(3) requires
applicants to prepare and provide
labeling with relevant information to
patients or potential patients for
biological products approved under part
601, subpart H, when human efficacy
studies are not ethical or feasible (or
based on evidence of effectiveness from
studies in animals). Section 601.93
provides that biological products
approved under subpart H are subject to
the postmarketing recordkeeping and
safety reporting applicable to all
approved biological products. Section
601.94 requires applicants under
subpart H to submit to the Agency for
consideration during preapproval
review period copies of all promotional
materials including promotional
labeling as well as advertisements.
Under §§ 601.91(b)(2) and 601.93, any
potential postmarketing reports and/or
recordkeeping burdens would be
included under the adverse experience
reporting (AER) requirements under 21
CFR part 600 (OMB control number
0910–0308). Therefore, any burdens
associated with these requirements
would be reported under the AER
information collection requirements
(OMB control number 0910–0308). The
burden estimate for § 601.91(b)(3) is
included in the estimate under
§§ 610.60 through 610.65.
Section 610.9(a) requires the
applicant to present certain information,
in the form of a license application or
supplement to the application, for a
modification of any particular test
method or manufacturing process or the
conditions which it is conducted under
the biologics regulations. The burden
estimate for § 610.9(a) is included in the
PO 00000
Frm 00068
Fmt 4703
Sfmt 4703
estimate under §§ 601.2(a) and 601.12(b)
and (c) in table 1.
Under § 610.15(d), the Director of
CBER or the Director of CDER may
approve, as appropriate, a
manufacturer’s request for exceptions or
alternatives to the regulation for
constituent materials. Manufacturers
seeking approval of an exception or
alternative must submit a request in
writing with a brief statement describing
the basis for the request and the
supporting data.
Section 640.120 requires licensed
establishments to submit a request for
an exception or alternative to any
requirement in the biologics regulations
regarding blood, blood components, or
blood products. For licensed
establishments, a request for an
exception or alternative must be
submitted in accordance with § 601.12;
therefore, the burden estimate for
§ 640.120 is included in the estimate
under § 601.12(b) in table 1.
Section 680.1(c) requires
manufacturers to update annually their
license file with the list of source
materials and the suppliers of the
materials. Section 680.1(b)(3)(iv)
requires manufacturers to notify FDA
when certain diseases are detected in
source materials.
Sections 600.15(b) and 610.53(b)
require the submission of a request for
an exemption or modification regarding
the temperature requirements during
shipment and from dating periods,
respectively, for certain biological
products. Section 606.110(b) (21 CFR
606.110(b)) requires the submission of a
request for approval to perform
plasmapheresis of donors who do not
meet certain donor requirements for the
collection of plasma containing rare
antibodies. Under §§ 600.15(b),
610.53(b), and 606.110(b), a request for
an exemption or modification to the
requirements would be submitted as a
supplement. Therefore, the burden
hours for any submissions under
§§ 600.15(b), 610.53(d), and 606.110(b)
are included in the estimates under
§ 601.12(b) in table 1.
Form FDA 356h, ‘‘Application to
Market a New or Abbreviated New Drug
or Biologic for Human Use,’’ is used for
the applicable submissions to both
CBER and CDER. The application form
serves primarily as a checklist for firms
to gather and submit certain information
to FDA and helps to ensure that the
application is complete and contains all
the necessary information, so that
delays due to lack of information may
be eliminated. In addition, the form
provides key information to FDA for
efficient handling and distribution to
the appropriate staff for review. FDA
E:\FR\FM\19SEN1.SGM
19SEN1
Federal Register / Vol. 84, No. 182 / Thursday, September 19, 2019 / Notices
estimates an average of 24 hours to
complete the application form which is
included in the average burden per
response. The estimated burden hours
for nonbiological product submissions
to CDER using FDA Form 356h are
approved under OMB control number
0910–0001 (an estimated 16,650
submissions × 24 hours = 399,600
hours).
For advertisements and promotional
labeling (e.g., circulars, package labels,
container labels, etc.) and labeling
changes, manufacturers of licensed
biological products may submit to CBER
or CDER Form FDA 2253. Form FDA
2253 can also be submitted
electronically. Form FDA 2253 is
approved under OMB control number
0910–0001.
Respondents to this collection of
information are manufacturers of
biological products. Under table 1, the
numbers of respondents are based on
the estimated annual number of
manufacturers that submitted the
required information to FDA or the
number of submissions FDA received in
fiscal year 2018. Based on information
obtained from FDA’s database systems,
there are an estimated 424 licensed
biologics manufacturers. The total
annual responses are based on the
estimated 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 information provided by industry
and past FDA experience with the
various submissions or notifications.
The hours per response include the time
estimated to prepare the various
submissions or notifications to FDA,
and, as applicable, the time required to
fill out the appropriate form and collate
the documentation. Additional
information regarding these estimates is
provided below as necessary.
Under §§ 601.2 and 601.12, the
estimated hours per response are based
on the average number of hours to
submit the various submissions. The
estimated average number of hours is
based on the range of hours to complete
a very basic application or supplement
and a complex application or
supplement.
Under section 601.6(a), the total
annual responses are based on FDA
estimates that establishments may notify
an average of 20 selling agents and
distributors of such suspension, and
provide FDA of such notification. The
number of respondents is based on the
estimated annual number of
suspensions of a biologic license. In
table 1, FDA is estimating one in case
a suspension occurs.
Under §§ 601.12(f)(4) and 601.45,
manufacturers of biological products
may use Form FDA 2253 to submit
49313
advertising and promotional labeling
(which can include multiple pieces).
Based on information obtained from
FDA’s database system, the estimate is
based on the number of submissions
received using Form FDA 2253 for
advertising and promotional labeling.
Under §§ 601.28 and 601.70(b), FDA
estimates that it takes an applicant
approximately 24 hours (8 hours per
study × 3 studies) annually to gather,
complete, and submit the appropriate
information for each postmarketing
status report (approximately 2 to 4
studies per report) and the accompanied
transmittal Form FDA 2252. Included in
these 24 hours is the time necessary to
prepare and submit two copies of the
annual progress report of postmarketing
studies to FDA under § 601.70(d).
Under § 610.15(d), FDA has received
no submissions since the
implementation of the final rule in April
2011. Therefore, FDA is estimating one
respondent and one annual request to
account for a possible submission to
CBER or CDER of a request for an
exception or alternative for constituent
materials under § 610.15(d).
There were a total of 3,398
amendments to an unapproved
application or supplement and
resubmissions submitted using Form
FDA 356h.
We estimate the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1
Number of
respondents
Number of
responses per
respondent
Total annual
responses
Average burden
per response
Form FDA No.
601.2(a),2 610.60 through 610.65 3
601.5(a) ...........................................
601.6(a) ...........................................
601.12(a)(5) .....................................
601.12(b)(1)/(b)(3)/(e) 4 ...................
601.12(c)(1)/(c)(3) 5 .........................
601.12(c)(5) .....................................
601.12(d)(1)/(d)(3) 6/(f)(3) 8 ..............
601.12(f)(1) 7 ....................................
601.12(f)(2) 7 ....................................
601.12(f)(4)/601.45 9 ........................
601.27(b) .........................................
601.27(c) .........................................
601.70(b) and (d)/601.28 ................
610.15(d) .........................................
680.1(c) ...........................................
680.1(b)(3)(iv) ..................................
Amendments/Resubmissions ..........
356h ...................
NA ......................
NA ......................
NA ......................
356h 2 .................
356h 2 .................
356h 2 .................
356h 2 .................
2253 ...................
2253 ...................
2253 ...................
NA ......................
NA ......................
2252 ...................
NA ......................
NA ......................
NA ......................
356h ...................
36
8
1
430
166
149
7
245
65
43
134
12
2
65
1
9
1
136
1.28
1.13
1
4.158
4.843
4.58
1.14
3.575
3.169
2.05
145.86
1.08
1
3.169
1
1
1
24.985
46
9
1
1,788
804
682
8
876
206
88
19,545
13
2
206
1
9
1
3,398
860 .....................
0.33 (20 minutes)
0.33 (20 minutes)
1 .........................
80 .......................
50 .......................
50 .......................
24 .......................
40 .......................
20 .......................
10 .......................
24 .......................
8 .........................
24 .......................
1 .........................
2 .........................
2 .........................
20 .......................
39,560
3
1
1,788
64,320
34,100
400
21,024
8,240
1,760
195,450
312
16
4,944
1
18
2
67,960
Total .........................................
............................
........................
........................
........................
............................
439,899
1 There
jbell on DSK3GLQ082PROD with NOTICES
Total hours 10
21 CFR section
are no capital costs or operating and maintenance costs associated with this collection of information.
2 The reporting requirements under §§ 601.14, 601.27(a), 601.33, 601.34, 601.35, 610.9(a), 640.17, 640.25(c), 640.56(c), 640.74(b)(2),
660.51(a)(4), and 680.1(b)(2)(iii) are included in the estimate under § 601.2(a).
3 The reporting requirements under §§ 601.93(b)(3), 640.74(b)(3) and (4), 640.84(a) and (c), 640.94(a), 660.2(c), 660.28(a), (b), and (c),
660.35(a) through (d), 660.45, and 660.55(a) and (b) are included under §§ 610.60 through 610.65.
4 The reporting requirements under §§ 601.12(a)(2) and (b)(4), 600.15(b), 610.9(a), 610.53(b), 606.110(b), 640.6, 640.17, 640.21(c), 640.22(c),
640.25(c), 640.56(c), 640.64(c), 640.74(a) and (b)(2), 640.120, and 680.1(d) are included in the estimate under § 601.12(b).
5 The reporting requirements under §§ 601.12(a)(2), 610.9(a), 640.17, 640.25(c), 640.56(c), and 640.74(b)(2) are included in the estimate under
§ 601.12(c).
VerDate Sep<11>2014
17:30 Sep 18, 2019
Jkt 247001
PO 00000
Frm 00069
Fmt 4703
Sfmt 4703
E:\FR\FM\19SEN1.SGM
19SEN1
49314
Federal Register / Vol. 84, No. 182 / Thursday, September 19, 2019 / Notices
6 The
reporting requirement under § 601.12(a)(2) is included in the estimate under § 601.12(d).
reporting requirement under § 601.14 is included in the estimate under § 601.12(f)(1) and (2).
reporting requirement under §§ 601.12(a)(4) and 601.14 is included in the estimate under § 601.12(f)(3).
9 The reporting requirement under § 601.94 is included in the estimate under § 601.45.
10 The numbers in this column have been rounded to the nearest whole number.
7 The
8 The
TABLE 2—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1
Annual
disclosures
per
respondent
Number of
respondents
21 CFR section
601.6(a) ..................................................
1
Total annual
disclosures
20
20
Average burden per disclosure
Total hours 2
0.33 (20 minutes) ........................
7
1 There
2 The
are no capital costs or operating and maintenance costs associated with this collection of information.
number is this column have been rounded to the nearest whole number.
Our estimated burden for the
information collection reflects an
overall increase of 105,948 hours and a
corresponding decrease of 2,671
responses. We attribute this adjustment
in the total hours to an increase in the
number of submissions we have
received under §§ 601.12(f)(4) and
601.45 and §§ 601.12(b)(1), (b)(3), and
(e) over the last few years. We attribute
the decrease in total annual responses to
a decrease in responses received under
§§ 601.12(a)(5) and 601.27(b) over the
last few years.
Dated: September 10, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019–20328 Filed 9–18–19; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2019–N–3277]
Revocation of Authorization of
Emergency Use of an In Vitro
Diagnostic Device for Detection and/or
Diagnosis of Zika Virus
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing the
revocation of the Emergency Use
Authorization (EUA) (the Authorization)
issued to Luminex Corp., for the xMAP
MultiFLEX Zika RNA Assay. FDA
revoked this Authorization on July 3,
2019, under the Federal Food, Drug, and
Cosmetic Act (FD&C Act), as requested
by Luminex Corp. by a letter dated June
jbell on DSK3GLQ082PROD with NOTICES
SUMMARY:
VerDate Sep<11>2014
17:30 Sep 18, 2019
Jkt 247001
18, 2019. The revocation, which
includes an explanation of the reasons
for revocation, is reprinted in this
document.
DATES: The Authorization is revoked as
of July 3, 2019.
ADDRESSES: Submit written requests for
single copies of the revocation to the
Office of Counterterrorism and
Emerging Threats, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 1, Rm. 4338, Silver Spring,
MD 20993–0002. Send one selfaddressed adhesive label to assist that
office in processing your request or
include a Fax number to which the
revocation may be sent. See the
SUPPLEMENTARY INFORMATION section for
electronic access to the revocation.
FOR FURTHER INFORMATION CONTACT:
Jennifer J. Ross, Office of
Counterterrorism and Emerging Threats,
Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 1, Rm.
4332, Silver Spring, MD 20993–0002,
240–402–8155 (this is not a toll-free
number).
SUPPLEMENTARY INFORMATION:
I. Background
Section 564 of the FD&C Act (21
U.S.C. 360bbb–3), as amended by the
Project BioShield Act of 2004 (Pub. L.
108–276), and the Pandemic and AllHazards Preparedness Reauthorization
Act of 2013 (Pub. L. 113–5) allows FDA
to strengthen the public health
protections against biological, chemical,
nuclear, and radiological agents. Among
other things, section 564 of the FD&C
Act allows FDA to authorize the use of
an unapproved medical product or an
unapproved use of an approved medical
product in certain situations. On August
4, 2016, FDA issued an EUA to Luminex
PO 00000
Frm 00070
Fmt 4703
Sfmt 4703
Corp. for the xMAP MultiFLEX Zika
RNA Assay, subject to the terms of the
Authorization. Notice of the issuance of
the Authorization was published in the
Federal Register on October 28, 2016
(81 FR 75092), as required by section
564(h)(1) of the FD&C Act. In response
to requests from Luminex Corp., the
EUA was amended on January 7, 2017,
and May 19, 2017. Under section
564(g)(2) of the FD&C Act, the Secretary
of HHS may revoke an EUA if, among
other things, the criteria for issuance are
no longer met or other circumstances
make such revocation appropriate to
protect the public health or safety.
II. EUA Revocation Request for an In
Vitro Diagnostic Device for Detection of
the Zika Virus
On June 18, 2019, Luminex Corp.
requested, and on July 3, 2019, FDA
revoked, the EUA for the xMAP
MultiFLEX Zika RNA Assay because the
product will no longer be marketed, and
these circumstances make revocation
appropriate to protect the public health
or safety.
III. Electronic Access
An electronic version of this
document and the full text of the
revocation are available on the internet
at https://www.regulations.gov/.
IV. The Revocation
Having concluded that the criteria for
revocation of the Authorization under
section 564(g) of the FD&C Act are met,
FDA has revoked the EUA for Luminex
Corp.’s xMAP MultiFLEX Zika RNA
Assay. The revocation in its entirety
follows and provides an explanation of
the reasons for revocation, as required
by section 564(h)(1) of the FD&C Act.
E:\FR\FM\19SEN1.SGM
19SEN1
]]>Agencies
[Federal Register Volume 84, Number 182 (Thursday, September 19, 2019)]
[Notices]
[Pages 49310-49314]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-20328]
[[Page 49310]]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2013-N-0578]
Agency Information Collection Activities; Proposed Collection;
Comment Request; General Licensing Provisions: Biologics License
Application, Changes to an Approved Application, Labeling, Revocation
and Suspension, Postmarketing Studies Status Reports, and Form FDA 356h
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA, 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
relating to general licensing provisions for biologics license
applications (BLAs), changes to an approved application, labeling,
revocation and suspension, postmarketing studies status reports, and
Form FDA 356h.
DATES: Submit electronic or written comments on the collection of
information by November 18, 2019.
ADDRESSES: You may submit comments as follows: Please note that late,
untimely filed comments will not be considered. Electronic comments
must be submitted on or before November 18, 2019. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of November 18, 2019. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are postmarked or the delivery
service acceptance receipt is 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-2013-N-0578 for ``General Licensing Provisions: Biologics License
Application, Changes to an Approved Application, Labeling, Revocation
and Suspension, Postmarketing Studies Status Reports, and Form FDA
356h.'' 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.
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.gpo.gov/fdsys/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.
FOR FURTHER INFORMATION CONTACT: Domini Bean, Office of Operations,
Food and Drug Administration, Three White Flint North, 10 a.m.-12 p.m.,
11601 Landsdown St., North Bethesda, MD 20852, 301-796-5733,
[email protected].
SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), 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
[[Page 49311]]
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.
General Licensing Provisions: Biologics License Application, Changes to
an Approved Application, Labeling, Revocation and Suspension,
Postmarketing Studies Status Reports, and Form FDA 356h
OMB Control Number 0910-0338--Extension
Under section 351 of the Public Health Services Act (PHS Act) (42
U.S.C. 262), manufacturers of biological products must submit a license
application for FDA review and approval before marketing a biological
product in interstate commerce. Licenses may be issued only upon
showing that the establishment and the products for which a license is
desired meets standards prescribed in regulations designed to ensure
the continued safety, purity, and potency of such products. All such
licenses are issued, suspended, and revoked as prescribed by
regulations in part 601 (21 CFR part 601).
Section 130(a) of the Food and Drug Administration Modernization
Act (Pub. L. 105-115) amended the Federal Food, Drug, and Cosmetic Act
(FD&C Act) by adding a new provision (section 506B of the FD&C Act (21
U.S.C. 356b)) requiring reports of postmarketing studies for approved
human drugs and licensed biological products. Section 506B of the FD&C
Act provides FDA with additional authority to monitor the progress of
postmarketing studies that applicants have made a commitment to conduct
and requires the Agency to make publicly available information that
pertains to the status of these studies. Under section 506B(a) of the
FD&C Act, applicants that have committed to conduct a postmarketing
study for an approved human drug or licensed biological product must
submit to FDA a status report of the progress of the study or the
reasons for the failure of the applicant to conduct the study. This
report must be submitted within 1 year after the U.S. approval of the
application and then annually until the study is completed or
terminated.
A summary of the collection of information requirements follows:
Section 601.2(a) requires a manufacturer of a biological product to
submit an application on forms prescribed for such purposes with
accompanying data and information, including certain labeling
information, to FDA for approval to market a product in interstate
commerce. The container and package labeling requirements are provided
under Sec. Sec. 610.60 through 610.65 (21 CFR 610.60 through 610.65).
The estimate for these regulations is included in the estimate under
Sec. 601.2(a) in table 1.
Section 601.5(a) requires a manufacturer to submit to FDA notice of
its intention to discontinue manufacture of a product or all products.
Section 601.6(a) requires the manufacturer to notify selling agents and
distributors upon suspension of its license, and provide FDA of such
notification.
Section 601.12(a)(2) requires, generally, that the holder of an
approved BLA must assess the effects of a manufacturing change before
distributing a biological product made with the change. Section
601.12(a)(4) requires, generally, that the applicant must promptly
revise all promotional labeling and advertising to make it consistent
with any labeling changes implemented. Section 601.12(a)(5) requires
the applicant to include a list of all changes contained in the
supplement or annual report; for supplements, this list must be
provided in the cover letter. The burden estimates for Sec.
601.12(a)(2) are included in the estimates for supplements (Sec. Sec.
601.12(b) and (c)) and annual reports (Sec. 601.12(d)). The burden
estimates for Sec. 601.12(a)(4) are included in the estimates under
601.12(f)(4) in table 1.
Sections 601.12(b)(1) and (3), (c)(1), (3), and (5), and (d)(1) and
(3) require applicants to follow specific procedures to submit
information to FDA of any changes, in the product, production process,
quality controls, equipment, facilities, or responsible personnel
established in an approved license application. The appropriate
procedure depends on the potential for the change to have a
substantial, moderate, or minimal adverse effect on the identity,
strength, quality, purity, or potency of the products as they may
relate to the safety or effectiveness of the product. Under Sec.
601.12(b)(4), an applicant may ask FDA to expedite its review of a
supplement for public health reasons or if a delay in making the change
described in it would impose an extraordinary hardship of the
applicant. The burden estimate for Sec. 601.12(b)(4) is minimal and
included in the estimate under Sec. 601.12(b)(1) and (3) in table 1.
Section 601.12(e) requires applicants to submit a protocol, or
change to a protocol, as a supplement requiring FDA approval before
distributing the product. Section 601.12(f)(1) through (3) requires
applicants to follow specific procedures to report certain labeling
changes to FDA. Section 601.12(f)(4) requires applicants to report to
FDA advertising and promotional labeling and any changes.
Under Sec. 601.14, the content of labeling required in 21 CFR
201.100(d)(3) must be in electronic format and in a form that FDA can
process, review, and archive. This requirement is in addition to the
provisions of Sec. Sec. 601.2(a) and 601.12(f). The burden estimate
for Sec. 601.14 is minimal and included in the estimate under
Sec. Sec. 601.2(a) (BLAs) and 601.12(f)(1) through (3) (labeling
supplements and annual reports) in table 1.
Section 601.45 requires applicants of biological products for
serious or life-threatening illnesses to submit to the Agency for
consideration, during the preapproval review period, copies of all
promotional materials, including promotional labeling as well as
advertisements.
In addition to Sec. Sec. 601.2 and 601.12, there are other
regulations in 21 CFR parts 640, 660, and 680 that relate to
information to be submitted in a license application or supplement for
certain blood or allergenic products as follows: Sec. Sec. 640.6;
640.17; 640.21(c); 640.22(c); 640.25(c); 640.56(c); 640.64(c);
640.74(a) and (b)(2); 660.51(a)(4); and 680.1(b)(2)(iii) and (d).
In table 1, the burden associated with the information collection
requirements in the applicable regulations is included in the burden
estimate for Sec. Sec. 601.2 and/or 601.12. A regulation may be listed
under more than one subsection of Sec. 601.12 due to the type of
category under which a change to an approved application may be
submitted.
There are also additional container and/or package labeling
requirements for certain licensed biological products including: Sec.
640.74(b)(3) and (4) for Source Plasma Liquid; Sec. 640.84(a) and (c)
for Albumin; Sec. 640.94(a) for Plasma Protein Fraction; Sec.
660.2(c) for Antibody to Hepatitis B Surface Antigen; Sec. 660.28(a),
(b), and (c) for Blood Grouping Reagent; Sec. 660.35(a) through (d)
for Reagent Red Blood Cells; Sec. 660.45 for Hepatitis B Surface
Antigen; and Sec. 660.55(a) and (b) for Anti-Human Globulin. The
burden associated with the additional labeling requirements for
[[Page 49312]]
submission of a license application for these certain biological
products is minimal because the majority of the burden is associated
with the requirements under Sec. Sec. 610.60 through 610.65 or 21 CFR
809.10. Therefore, the burden estimates for these regulations are
included in the estimate under Sec. Sec. 610.60 through 610.65 in
table 1. The burden estimates associated with Sec. 809.10 are approved
under OMB control number 0910-0485.
Section 601.27(a) requires that applications for new biological
products contain data that are adequate to assess the safety and
effectiveness of the biological product for the claimed indications in
pediatric subpopulations, and to support dosing and administration
information. Section 601.27(b) provides that an applicant may request a
deferred submission of some or all assessments of safety and
effectiveness required under Sec. 601.27(a) until after licensing the
product for use in adults. Section 601.27(c) provides that an applicant
may request a full or partial waiver of the requirements under Sec.
601.27(a) with adequate justification. The burden estimates for Sec.
601.27(a) are included in the burden estimate under Sec. 601.2(a) in
table 1 since these regulations deal with information to be provided in
an application.
Section 601.28 requires sponsors of licensed biological products to
submit the information in Sec. 601.28(a)-(c) to the Center for
Biologics Evaluation and Research (CBER) or to the Center for Drug
Evaluation and Research (CDER) each year, within 60 days of the
anniversary date of approval of the license. Section 601.28(a) requires
sponsors to submit to FDA a brief summary stating whether labeling
supplements for pediatric use have been submitted and whether new
studies in the pediatric population to support appropriate labeling for
the pediatric population have been initiated. Section 601.28(b)
requires sponsors to submit to FDA an analysis of available safety and
efficacy data in the pediatric population and changes proposed in the
labeling based on this information. Section 601.28(c) requires sponsors
to submit to FDA a statement on the current status of any postmarketing
studies in the pediatric population performed by, on or behalf of, the
applicant. If the postmarketing studies were required or agreed to, the
status of these studies is to be reported under Sec. 601.70 rather
than under this section.
Sections 601.33 through 601.35 clarify the information to be
submitted in an application to FDA to evaluate the safety and
effectiveness of radiopharmaceuticals intended for in vivo
administration for diagnostic and monitoring use. The burden estimates
for Sec. Sec. 601.33 through 601.35 are included in the burden
estimate under Sec. 601.2(a) in table 1 since these regulations deal
with information to be provided in an application.
Section 601.70 (b) requires each applicant of a licensed biological
product to submit annually a report to FDA on the status of
postmarketing studies for each approved product application. Each
annual postmarketing status report must be accompanied by a completed
transmittal Form FDA 2252 (Form FDA 2252 approved under OMB control
number 0910-0001). Under Sec. 601.70(d), two copies of the annual
report shall be submitted to FDA.
Sections 601.91 through 601.94 concern biological products for
which human efficacy studies are not ethical or feasible. Section
601.91(b)(2) requires, in certain circumstances, such postmarking
restrictions as are needed to ensure the safe use of the biological
product. Section 601.91(b)(3) requires applicants to prepare and
provide labeling with relevant information to patients or potential
patients for biological products approved under part 601, subpart H,
when human efficacy studies are not ethical or feasible (or based on
evidence of effectiveness from studies in animals). Section 601.93
provides that biological products approved under subpart H are subject
to the postmarketing recordkeeping and safety reporting applicable to
all approved biological products. Section 601.94 requires applicants
under subpart H to submit to the Agency for consideration during
preapproval review period copies of all promotional materials including
promotional labeling as well as advertisements. Under Sec. Sec.
601.91(b)(2) and 601.93, any potential postmarketing reports and/or
recordkeeping burdens would be included under the adverse experience
reporting (AER) requirements under 21 CFR part 600 (OMB control number
0910-0308). Therefore, any burdens associated with these requirements
would be reported under the AER information collection requirements
(OMB control number 0910-0308). The burden estimate for Sec.
601.91(b)(3) is included in the estimate under Sec. Sec. 610.60
through 610.65.
Section 610.9(a) requires the applicant to present certain
information, in the form of a license application or supplement to the
application, for a modification of any particular test method or
manufacturing process or the conditions which it is conducted under the
biologics regulations. The burden estimate for Sec. 610.9(a) is
included in the estimate under Sec. Sec. 601.2(a) and 601.12(b) and
(c) in table 1.
Under Sec. 610.15(d), the Director of CBER or the Director of CDER
may approve, as appropriate, a manufacturer's request for exceptions or
alternatives to the regulation for constituent materials. Manufacturers
seeking approval of an exception or alternative must submit a request
in writing with a brief statement describing the basis for the request
and the supporting data.
Section 640.120 requires licensed establishments to submit a
request for an exception or alternative to any requirement in the
biologics regulations regarding blood, blood components, or blood
products. For licensed establishments, a request for an exception or
alternative must be submitted in accordance with Sec. 601.12;
therefore, the burden estimate for Sec. 640.120 is included in the
estimate under Sec. 601.12(b) in table 1.
Section 680.1(c) requires manufacturers to update annually their
license file with the list of source materials and the suppliers of the
materials. Section 680.1(b)(3)(iv) requires manufacturers to notify FDA
when certain diseases are detected in source materials.
Sections 600.15(b) and 610.53(b) require the submission of a
request for an exemption or modification regarding the temperature
requirements during shipment and from dating periods, respectively, for
certain biological products. Section 606.110(b) (21 CFR 606.110(b))
requires the submission of a request for approval to perform
plasmapheresis of donors who do not meet certain donor requirements for
the collection of plasma containing rare antibodies. Under Sec. Sec.
600.15(b), 610.53(b), and 606.110(b), a request for an exemption or
modification to the requirements would be submitted as a supplement.
Therefore, the burden hours for any submissions under Sec. Sec.
600.15(b), 610.53(d), and 606.110(b) are included in the estimates
under Sec. 601.12(b) in table 1.
Form FDA 356h, ``Application to Market a New or Abbreviated New
Drug or Biologic for Human Use,'' is used for the applicable
submissions to both CBER and CDER. The application form serves
primarily as a checklist for firms to gather and submit certain
information to FDA and helps to ensure that the application is complete
and contains all the necessary information, so that delays due to lack
of information may be eliminated. In addition, the form provides key
information to FDA for efficient handling and distribution to the
appropriate staff for review. FDA
[[Page 49313]]
estimates an average of 24 hours to complete the application form which
is included in the average burden per response. The estimated burden
hours for nonbiological product submissions to CDER using FDA Form 356h
are approved under OMB control number 0910-0001 (an estimated 16,650
submissions x 24 hours = 399,600 hours).
For advertisements and promotional labeling (e.g., circulars,
package labels, container labels, etc.) and labeling changes,
manufacturers of licensed biological products may submit to CBER or
CDER Form FDA 2253. Form FDA 2253 can also be submitted electronically.
Form FDA 2253 is approved under OMB control number 0910-0001.
Respondents to this collection of information are manufacturers of
biological products. Under table 1, the numbers of respondents are
based on the estimated annual number of manufacturers that submitted
the required information to FDA or the number of submissions FDA
received in fiscal year 2018. Based on information obtained from FDA's
database systems, there are an estimated 424 licensed biologics
manufacturers. The total annual responses are based on the estimated
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 information provided by industry and
past FDA experience with the various submissions or notifications. The
hours per response include the time estimated to prepare the various
submissions or notifications to FDA, and, as applicable, the time
required to fill out the appropriate form and collate the
documentation. Additional information regarding these estimates is
provided below as necessary.
Under Sec. Sec. 601.2 and 601.12, the estimated hours per response
are based on the average number of hours to submit the various
submissions. The estimated average number of hours is based on the
range of hours to complete a very basic application or supplement and a
complex application or supplement.
Under section 601.6(a), the total annual responses are based on FDA
estimates that establishments may notify an average of 20 selling
agents and distributors of such suspension, and provide FDA of such
notification. The number of respondents is based on the estimated
annual number of suspensions of a biologic license. In table 1, FDA is
estimating one in case a suspension occurs.
Under Sec. Sec. 601.12(f)(4) and 601.45, manufacturers of
biological products may use Form FDA 2253 to submit advertising and
promotional labeling (which can include multiple pieces). Based on
information obtained from FDA's database system, the estimate is based
on the number of submissions received using Form FDA 2253 for
advertising and promotional labeling.
Under Sec. Sec. 601.28 and 601.70(b), FDA estimates that it takes
an applicant approximately 24 hours (8 hours per study x 3 studies)
annually to gather, complete, and submit the appropriate information
for each postmarketing status report (approximately 2 to 4 studies per
report) and the accompanied transmittal Form FDA 2252. Included in
these 24 hours is the time necessary to prepare and submit two copies
of the annual progress report of postmarketing studies to FDA under
Sec. 601.70(d).
Under Sec. 610.15(d), FDA has received no submissions since the
implementation of the final rule in April 2011. Therefore, FDA is
estimating one respondent and one annual request to account for a
possible submission to CBER or CDER of a request for an exception or
alternative for constituent materials under Sec. 610.15(d).
There were a total of 3,398 amendments to an unapproved application
or supplement and resubmissions submitted using Form FDA 356h.
We estimate the burden of this collection of information as
follows:
Table 1--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of
21 CFR section Form FDA No. Number of responses per Total annual Average burden per Total hours
respondents respondent responses response \10\
--------------------------------------------------------------------------------------------------------------------------------------------------------
601.2(a),\2\ 610.60 through 610.65 356h.................... 36 1.28 46 860.................... 39,560
\3\.
601.5(a)............................. NA...................... 8 1.13 9 0.33 (20 minutes)...... 3
601.6(a)............................. NA...................... 1 1 1 0.33 (20 minutes)...... 1
601.12(a)(5)......................... NA...................... 430 4.158 1,788 1...................... 1,788
601.12(b)(1)/(b)(3)/(e) \4\.......... 356h \2\................ 166 4.843 804 80..................... 64,320
601.12(c)(1)/(c)(3) \5\.............. 356h \2\................ 149 4.58 682 50..................... 34,100
601.12(c)(5)......................... 356h \2\................ 7 1.14 8 50..................... 400
601.12(d)(1)/(d)(3) \6\/(f)(3) \8\... 356h \2\................ 245 3.575 876 24..................... 21,024
601.12(f)(1) \7\..................... 2253.................... 65 3.169 206 40..................... 8,240
601.12(f)(2) \7\..................... 2253.................... 43 2.05 88 20..................... 1,760
601.12(f)(4)/601.45 \9\.............. 2253.................... 134 145.86 19,545 10..................... 195,450
601.27(b)............................ NA...................... 12 1.08 13 24..................... 312
601.27(c)............................ NA...................... 2 1 2 8...................... 16
601.70(b) and (d)/601.28............. 2252.................... 65 3.169 206 24..................... 4,944
610.15(d)............................ NA...................... 1 1 1 1...................... 1
680.1(c)............................. NA...................... 9 1 9 2...................... 18
680.1(b)(3)(iv)...................... NA...................... 1 1 1 2...................... 2
Amendments/Resubmissions............. 356h.................... 136 24.985 3,398 20..................... 67,960
----------------------------------------------------------------------------------------
Total............................ ........................ .............. .............. .............. ....................... 439,899
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ The reporting requirements under Sec. Sec. 601.14, 601.27(a), 601.33, 601.34, 601.35, 610.9(a), 640.17, 640.25(c), 640.56(c), 640.74(b)(2),
660.51(a)(4), and 680.1(b)(2)(iii) are included in the estimate under Sec. 601.2(a).
\3\ The reporting requirements under Sec. Sec. 601.93(b)(3), 640.74(b)(3) and (4), 640.84(a) and (c), 640.94(a), 660.2(c), 660.28(a), (b), and (c),
660.35(a) through (d), 660.45, and 660.55(a) and (b) are included under Sec. Sec. 610.60 through 610.65.
\4\ The reporting requirements under Sec. Sec. 601.12(a)(2) and (b)(4), 600.15(b), 610.9(a), 610.53(b), 606.110(b), 640.6, 640.17, 640.21(c),
640.22(c), 640.25(c), 640.56(c), 640.64(c), 640.74(a) and (b)(2), 640.120, and 680.1(d) are included in the estimate under Sec. 601.12(b).
\5\ The reporting requirements under Sec. Sec. 601.12(a)(2), 610.9(a), 640.17, 640.25(c), 640.56(c), and 640.74(b)(2) are included in the estimate
under Sec. 601.12(c).
[[Page 49314]]
\6\ The reporting requirement under Sec. 601.12(a)(2) is included in the estimate under Sec. 601.12(d).
\7\ The reporting requirement under Sec. 601.14 is included in the estimate under Sec. 601.12(f)(1) and (2).
\8\ The reporting requirement under Sec. Sec. 601.12(a)(4) and 601.14 is included in the estimate under Sec. 601.12(f)(3).
\9\ The reporting requirement under Sec. 601.94 is included in the estimate under Sec. 601.45.
\10\ The numbers in this column have been rounded to the nearest whole number.
Table 2--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
Annual
21 CFR section Number of disclosures Total annual Average burden Total hours
respondents per respondent disclosures per disclosure \2\
----------------------------------------------------------------------------------------------------------------
601.6(a)...................... 1 20 20 0.33 (20 7
minutes).
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ The number is this column have been rounded to the nearest whole number.
Our estimated burden for the information collection reflects an
overall increase of 105,948 hours and a corresponding decrease of 2,671
responses. We attribute this adjustment in the total hours to an
increase in the number of submissions we have received under Sec. Sec.
601.12(f)(4) and 601.45 and Sec. Sec. 601.12(b)(1), (b)(3), and (e)
over the last few years. We attribute the decrease in total annual
responses to a decrease in responses received under Sec. Sec.
601.12(a)(5) and 601.27(b) over the last few years.
Dated: September 10, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-20328 Filed 9-18-19; 8:45 am]
BILLING CODE 4164-01-P
