Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Financial Disclosure by Clinical Investigators, 7388-7390 [2019-03828]
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Federal Register / Vol. 84, No. 42 / Monday, March 4, 2019 / Notices
consider whether a bulk drug substance
must be used to compound a
vasopressin drug product at
concentrations higher than 20 U/mL. In
sum, FDA finds no basis to conclude
that drug products must be
compounded using a bulk drug
substance rather than the approved drug
product.
IV. Other Issues Raised in Nominations
and Comments
The nominations for nicardipine
hydrochloride and vasopressin and
some comments state that there could be
a benefit in the availability of drug
products containing each of these bulk
drug substances that do not require
dilution prior to administration. We
note first, with respect to nicardipine
hydrochloride, that two ready-to-use
nicardipine drug products are FDAapproved, and the comments do not
identify patients for whom these
products are medically unsuitable. More
broadly, as explained above, when a
bulk drug substance is a component of
an approved drug, FDA asks whether
there is a basis to conclude that an
attribute of each approved drug product
makes each one medically unsuitable to
treat certain patients for their condition,
an interpretation that protects patients
and the integrity of the drug approval
process. The nominations and
comments do not show that the
approved drug product, when not
manufactured in the ready-to-use form,
is medically unsuitable for certain
patients. Nor do the nominations and
comments establish that drug products
in the relevant concentrations,
including ready-to-use products, cannot
be prepared from the approved
nicardipine and vasopressin drug
products.27 Rather, they propose to
compound a ready-to-use product from
bulk drug substances to seek improved
efficiency for prescribers or healthcare
providers, or to address the possibility
that the approved drug might be
mishandled by a medical professional.
That is not clinical need to compound
a drug product using a bulk drug
substance.
The nominations for nicardipine
hydrochloride and vasopressin and
some comments also include statements
that these substances should be added
to the 503B Bulks List because
compounding from the bulk drug
substance could help outsourcing
facilities to address drug shortages and
disruptions in supply of approved drugs
intended for injection. As noted above,
section 503B contains a separate
provision for compounding from bulk
drug substances to address a drug
shortage, and we do not interpret the
other price- and supply-related issues
advanced by the nomination to be
within the meaning of ‘‘clinical need’’
for compounding with a bulk drug
substance.
V. Conclusion
For the reasons stated above, we find
no clinical need for an outsourcing
facility to compound using the bulk
drug substances nicardipine
hydrochloride and vasopressin and,
therefore, we are not including
nicardipine hydrochloride and
vasopressin on the 503B Bulks List.
Dated: February 26, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
[FR Doc. 2019–03810 Filed 3–1–19; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2012–N–0280]
Agency Information Collection
Activities; Submission for Office of
Management and Budget Review;
Comment Request; Financial
Disclosure by Clinical Investigators
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA or Agency) is
announcing that a proposed collection
SUMMARY:
of information has been submitted to the
Office of Management and Budget
(OMB) for review and clearance under
the Paperwork Reduction Act of 1995.
Fax written comments on the
collection of information by April 3,
2019.
DATES:
To ensure that comments on
the information collection are received,
OMB recommends that written
comments be faxed to the Office of
Information and Regulatory Affairs,
OMB, Attn: FDA Desk Officer, Fax: 202–
395–7285, or emailed to oira_
submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910–0396. Also
include the FDA docket number found
in brackets in the heading of this
document.
ADDRESSES:
FOR FURTHER INFORMATION CONTACT:
Amber Sanford, Office of Operations,
Food and Drug Administration, Three
White Flint North, 10A–12M, 11601
Landsdown St., North Bethesda, MD
20852, 301–796–8867, PRAStaff@
fda.hhs.gov.
In
compliance with 44 U.S.C. 3507, FDA
has submitted the following proposed
collection of information to OMB for
review and clearance.
SUPPLEMENTARY INFORMATION:
Financial Disclosure by Clinical
Investigators
OMB Control Number 0910–0396—
Extension
Respondents to this collection are
sponsors of marketing applications that
contain clinical data from studies
covered by the regulations. These
sponsors represent pharmaceutical,
biologic, and medical device firms.
Respondents are also clinical
investigators who provide financial
information to the sponsors of
marketing applications.
Table 1 of this document shows
information that is the basis of the
estimated number of respondents in
tables 2 through 4.
TABLE 1—ESTIMATED NUMBER OF APPLICATIONS, CLINICAL TRIALS, AND INVESTIGATORS SUBJECT TO THE REGULATION
BY TYPE OF APPLICATION 1
Total number
of applications
Application type
Number of
applications
affected
Number of
trials
Number of
investigators
Drugs:
27 With respect to vasopressin specifically, a
comment states that vasopressin cannot be
produced in ready-to-use form because the
approved drug product is labeled with an in-use
time of 18 hours room temperature or 24 hours
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refrigerated once diluted. In contrast, the
commenter says that it could compound a ‘‘prediluted’’ drug product from bulk vasopressin with
a beyond-use-date (BUD) of 60 days. We note that,
in accordance with CGMP provisions, outsourcing
PO 00000
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facilities can conduct stability studies on
vasopressin compounded using the approved drug
product to assign a BUD based on data.
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Federal Register / Vol. 84, No. 42 / Monday, March 4, 2019 / Notices
TABLE 1—ESTIMATED NUMBER OF APPLICATIONS, CLINICAL TRIALS, AND INVESTIGATORS SUBJECT TO THE REGULATION
BY TYPE OF APPLICATION 1—Continued
New drug application (NDA), new molecular entity (NME) .....................
NDA nonNME:
NDA efficacy supplement .................................................................
Abbreviated new drug application (ANDA) .......................................
ANDA supplement ............................................................................
Biologics:
Biologics license application (BLA) ..........................................................
BLA efficacy supplement .........................................................................
Medical Devices:
Premarket approval (PMA) ......................................................................
PMA supplement ......................................................................................
Reclassification devices ...........................................................................
510(k) .......................................................................................................
1 Source:
Number of
applications
affected
Total number
of applications
Application type
Number of
trials
Number of
investigators
35
26
3 to 10 ...........
3 to 100.
173
1,152
6,774
86
250
383
1 to 3 .............
1.1 ..................
1 .....................
10 to 30.
2.
2.
22
16
19
14
3 to 10 ...........
1 to 3 .............
3 to 100.
10 to 30.
48
23
3
4,000
48
23
1
200
1
1
1
1
10 to 20.
3 to 10.
3 to 10.
3 to 10.
to 3 .............
to 3 .............
.....................
.....................
Agency estimates.
In the Federal Register of September
27, 2018 (83 FR 48819), FDA published
a 60-day notice requesting public
comment on the proposed collection of
information. FDA received one
comment, however, it was not
responsive to the four collection of
information topics solicited and
therefore this comment will not be
discussed in this document.
FDA estimates the burden of this
collection of information as follows:
Reporting Burden
Under § 54.4(a) (21 CFR 54.4(a)),
applicants submitting an application
that relies on clinical studies must
submit a complete list of clinical
investigators who participated in a
covered clinical study, and must either
certify to the absence of certain financial
arrangements with clinical investigators
(Form FDA 3454) or, under § 54.4(a)(3),
disclose to FDA the nature of those
arrangements and the steps taken by the
applicant or sponsor to minimize the
potential for bias (Form FDA 3455).
FDA estimates that almost all
applicants submit a certification
statement under § 54.4(a)(1) and (a)(2).
Preparation of the statement using Form
FDA 3454 should require no more than
1 hour per study. The number of
respondents is based on the estimated
number of affected applications.
When certification is not possible and
disclosure is made using Form FDA
3455, the applicant must describe,
under § 54.4(a)(3), the financial
arrangements or interests and the steps
that were taken to minimize the
potential for bias in the affected study.
As the applicant would be fully aware
of those arrangements and the steps
taken to address them, describing them
will be straightforward. The Agency
estimates that it will take about 5 hours
to prepare this narrative. Based on our
experience with this collection, FDA
estimates that approximately 10 percent
of the respondents with affected
applications will submit disclosure
statements.
TABLE 2—ESTIMATED ANNUAL REPORTING BURDEN 1
Number of
respondents
21 CFR section
Number of
responses per
respondent
Average
burden per
response
Total annual
responses
Total hours
Certification—54.4(a)(1) and (a)(2)—Form FDA 3454 ........
Disclosure—54.4(a)(3)—Form FDA 3455 ...........................
1,050
105
1
1
1,050
105
1
5
1,050
525
Total ..............................................................................
........................
........................
........................
........................
1,575
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
Recordkeeping Burden
Under § 54.6, the sponsors of covered
studies must maintain complete records
of compensation agreements with any
compensation paid to nonemployee
clinical investigators, including
information showing any financial
interests held by the clinical
investigator, for 2 years after the date of
approval of the applications. Sponsors
of covered studies maintain many
records regarding clinical investigators,
including protocol agreements and
investigator resumes or curriculum
vitae. FDA estimates that an average of
15 minutes will be required for each
recordkeeper to add this record to the
clinical investigator’s file.
TABLE 3—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
21 CFR section
Number of
recordkeepers
Number of
records per
recordkeeper
Total annual
records
Average
burden per
recordkeeping
Total hours 2
Recordkeeping—54.6 ..........................................................
1,050
1
1,050
0.25
263
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
have been rounded.
2 Numbers
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Federal Register / Vol. 84, No. 42 / Monday, March 4, 2019 / Notices
Third-Party Disclosure Burden
Under § 54.4(b), clinical investigators
supply to the sponsor of a covered study
financial information sufficient to allow
the sponsor to submit complete and
accurate certification or disclosure
statements. Clinical investigators are
accustomed to supplying such
information when applying for research
grants. Also, most people know the
financial holdings of their immediate
family and records of such interests are
generally accessible because they are
needed for preparing tax records. For
these reasons, FDA estimates that the
time required for this task may range
from 5 to 15 minutes; we used the mean,
10 minutes, for the average burden per
disclosure. The number of respondents
is the sum of the number of affected
applications multiplied by the mean of
the estimated number of investigators
for each application type (rounded) (see
table 1 of this document).
TABLE 4—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1
21 CFR section
Number of
respondents
Number of
disclosures
per
respondent
Total annual
disclosures
Average
burden per
disclosure
Total hours 2
54.4(b)—Clinical Investigators .............................................
7,894
1
7,894
0.17
1,342
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
have been rounded.
2 Numbers
Our estimated burden for the
information collection reflects an
overall increase of 222 hours and a
corresponding increase of 893
responses/records. We attribute this
adjustment to an increase in the number
of affected applications and the number
of investigators. No program changes
were made.
DATES:
Dated: February 26, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
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’’).
[FR Doc. 2019–03828 Filed 3–1–19; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2018–D–1067]
Evaluation of Bulk Drug Substances
Nominated for Use in Compounding
Under Section 503B of the Federal
Food, Drug, and Cosmetic Act;
Guidance for Industry; Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of availability.
The Food and Drug
Administration (FDA or the Agency) is
announcing the availability of a final
guidance for industry entitled
‘‘Evaluation of Bulk Drug Substances
Nominated for Use in Compounding
Under Section 503B of the Federal
Food, Drug, and Cosmetic Act.’’ This
guidance describes policies that FDA
intends to use in evaluating bulk drug
substances nominated for use in
compounding under section 503B of the
Federal Food, Drug, and Cosmetic Act
(FD&C Act) for inclusion on the list of
bulk drug substances that can be used
in compounding under section 503B.
SUMMARY:
VerDate Sep<11>2014
17:33 Mar 01, 2019
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The announcement of the
guidance is published in the Federal
Register on March 4, 2019.
ADDRESSES: You may submit either
electronic or written comments on
Agency guidances at any time as
follows:
Electronic Submissions
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.
PO 00000
Frm 00065
Fmt 4703
Sfmt 4703
• 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–
2018–D–1067 for ‘‘Evaluation of Bulk
Drug Substances Nominated for Use in
Compounding Under Section 503B of
the Federal Food, Drug, and Cosmetic
Act.’’ Received comments will be placed
in the docket and, except for those
submitted as ‘‘Confidential
Submissions,’’ publicly viewable at
https://www.regulations.gov or at the
Dockets Management Staff between 9
a.m. and 4 p.m., Monday through
Friday.
• 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
E:\FR\FM\04MRN1.SGM
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]]>Agencies
[Federal Register Volume 84, Number 42 (Monday, March 4, 2019)]
[Notices]
[Pages 7388-7390]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-03828]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2012-N-0280]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Financial Disclosure
by Clinical Investigators
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency) 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: Fax written comments on the collection of information by April
3, 2019.
ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be faxed to the Office
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer,
Fax: 202-395-7285, or emailed to oira_submission@omb.eop.gov. All
comments should be identified with the OMB control number 0910-0396.
Also include the FDA docket number found in brackets in the heading of
this document.
FOR FURTHER INFORMATION CONTACT: Amber Sanford, Office of Operations,
Food and Drug Administration, Three White Flint North, 10A-12M, 11601
Landsdown St., North Bethesda, MD 20852, 301-796-8867,
PRAStaff@fda.hhs.gov.
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.
Financial Disclosure by Clinical Investigators
OMB Control Number 0910-0396--Extension
Respondents to this collection are sponsors of marketing
applications that contain clinical data from studies covered by the
regulations. These sponsors represent pharmaceutical, biologic, and
medical device firms. Respondents are also clinical investigators who
provide financial information to the sponsors of marketing
applications.
Table 1 of this document shows information that is the basis of the
estimated number of respondents in tables 2 through 4.
Table 1--Estimated Number of Applications, Clinical Trials, and Investigators Subject to the Regulation by Type
of Application \1\
----------------------------------------------------------------------------------------------------------------
Total number Number of
Application type of applications Number of trials Number of
applications affected investigators
----------------------------------------------------------------------------------------------------------------
Drugs:
[[Page 7389]]
New drug application (NDA), 35 26 3 to 10............... 3 to 100.
new molecular entity (NME).
NDA nonNME:
NDA efficacy supplement. 173 86 1 to 3................ 10 to 30.
Abbreviated new drug 1,152 250 1.1................... 2.
application (ANDA).
ANDA supplement......... 6,774 383 1..................... 2.
Biologics:
Biologics license 22 19 3 to 10............... 3 to 100.
application (BLA).
BLA efficacy supplement..... 16 14 1 to 3................ 10 to 30.
Medical Devices:
Premarket approval (PMA).... 48 48 1 to 3................ 10 to 20.
PMA supplement.............. 23 23 1 to 3................ 3 to 10.
Reclassification devices.... 3 1 1..................... 3 to 10.
510(k)...................... 4,000 200 1..................... 3 to 10.
----------------------------------------------------------------------------------------------------------------
\1\ Source: Agency estimates.
In the Federal Register of September 27, 2018 (83 FR 48819), FDA
published a 60-day notice requesting public comment on the proposed
collection of information. FDA received one comment, however, it was
not responsive to the four collection of information topics solicited
and therefore this comment will not be discussed in this document.
FDA estimates the burden of this collection of information as
follows:
Reporting Burden
Under Sec. 54.4(a) (21 CFR 54.4(a)), applicants submitting an
application that relies on clinical studies must submit a complete list
of clinical investigators who participated in a covered clinical study,
and must either certify to the absence of certain financial
arrangements with clinical investigators (Form FDA 3454) or, under
Sec. 54.4(a)(3), disclose to FDA the nature of those arrangements and
the steps taken by the applicant or sponsor to minimize the potential
for bias (Form FDA 3455).
FDA estimates that almost all applicants submit a certification
statement under Sec. 54.4(a)(1) and (a)(2). Preparation of the
statement using Form FDA 3454 should require no more than 1 hour per
study. The number of respondents is based on the estimated number of
affected applications.
When certification is not possible and disclosure is made using
Form FDA 3455, the applicant must describe, under Sec. 54.4(a)(3), the
financial arrangements or interests and the steps that were taken to
minimize the potential for bias in the affected study. As the applicant
would be fully aware of those arrangements and the steps taken to
address them, describing them will be straightforward. The Agency
estimates that it will take about 5 hours to prepare this narrative.
Based on our experience with this collection, FDA estimates that
approximately 10 percent of the respondents with affected applications
will submit disclosure statements.
Table 2--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of
21 CFR section Number of responses per Total annual Average burden Total hours
respondents respondent responses per response
----------------------------------------------------------------------------------------------------------------
Certification--54.4(a)(1) and 1,050 1 1,050 1 1,050
(a)(2)--Form FDA 3454..........
Disclosure--54.4(a)(3)--Form FDA 105 1 105 5 525
3455...........................
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 1,575
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Recordkeeping Burden
Under Sec. 54.6, the sponsors of covered studies must maintain
complete records of compensation agreements with any compensation paid
to nonemployee clinical investigators, including information showing
any financial interests held by the clinical investigator, for 2 years
after the date of approval of the applications. Sponsors of covered
studies maintain many records regarding clinical investigators,
including protocol agreements and investigator resumes or curriculum
vitae. FDA estimates that an average of 15 minutes will be required for
each recordkeeper to add this record to the clinical investigator's
file.
Table 3--Estimated Annual Recordkeeping Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Average burden
21 CFR section Number of records per Total annual per Total hours \2\
recordkeepers recordkeeper records recordkeeping
--------------------------------------------------------------------------------------------------------------------------------------------------------
Recordkeeping--54.6................................................ 1,050 1 1,050 0.25 263
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Numbers have been rounded.
[[Page 7390]]
Third-Party Disclosure Burden
Under Sec. 54.4(b), clinical investigators supply to the sponsor
of a covered study financial information sufficient to allow the
sponsor to submit complete and accurate certification or disclosure
statements. Clinical investigators are accustomed to supplying such
information when applying for research grants. Also, most people know
the financial holdings of their immediate family and records of such
interests are generally accessible because they are needed for
preparing tax records. For these reasons, FDA estimates that the time
required for this task may range from 5 to 15 minutes; we used the
mean, 10 minutes, for the average burden per disclosure. The number of
respondents is the sum of the number of affected applications
multiplied by the mean of the estimated number of investigators for
each application type (rounded) (see table 1 of this document).
Table 4--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of
21 CFR section Number of disclosures per Total annual Average burden Total hours \2\
respondents respondent disclosures per disclosure
--------------------------------------------------------------------------------------------------------------------------------------------------------
54.4(b)--Clinical Investigators.................................... 7,894 1 7,894 0.17 1,342
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Numbers have been rounded.
Our estimated burden for the information collection reflects an
overall increase of 222 hours and a corresponding increase of 893
responses/records. We attribute this adjustment to an increase in the
number of affected applications and the number of investigators. No
program changes were made.
Dated: February 26, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
[FR Doc. 2019-03828 Filed 3-1-19; 8:45 am]
BILLING CODE 4164-01-P
