Report on the Performance of Drug and Biologics Firms in Conducting Postmarketing Requirements and Commitments; Availability, 57996-58003 [2017-26470]
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Federal Register / Vol. 82, No. 235 / Friday, December 8, 2017 / Notices
Sciences Authority), and the United
States (U.S. FDA). The World Health
Organization and the Asia-Pacific
Economic Cooperation Life Sciences
Innovation Forum Regulatory
Harmonization Steering Committee are
IMDRF Official Observers. The Asian
Harmonization Working Party and the
Pan American Health Organization are
IMDRF Affiliate Organizations.
The IMDRF Management Committee
(IMDRF MC) chartered the SaMD
Working Group (WG) to develop a
regulatory framework for SaMD and to
develop converged principles for global
regulators to adopt in their respective
jurisdictions. The SaMD WG includes
representatives from the IMDRF
members, industry, academia, and other
key stakeholders as well as regional
harmonization initiatives from around
the world.
The IMDRF SaMD WG considered
comments received on the draft
guidance that was announced in the
Federal Register of October 14, 2016 (81
FR 71105). The SaMD WG also
considered public comments received
by other regulators and from other
global stakeholders. The final IMDRF/
SaMD WG/N41 document, ‘‘Software as
a Medical Device (SaMD): Clinical
Evaluation,’’ submitted to IMDRF MC
was revised appropriately in response to
all of the comments. The IMDRF MC in
Ottawa, Canada, at the 12th meeting
held from September 19 to 21, 2017,
unanimously approved the document
entitled ‘‘Software as a Medical Device
(SaMD): Clinical Evaluation.’’ This final
IMDRF/SaMD WG/N41 document is
available for regulatory implementation
according to the regulatory process in
each jurisdiction.
This guidance adopts the
internationally converged principles
agreed upon by the IMDRF. FDA
adoption of these principles provides
FDA with an initial framework when
further developing the Agency’s specific
regulatory approaches and expectations
for regulatory oversight. This guidance
does not provide recommendations for
FDA Staff and Industry to apply to
specific regulatory situations, nor does
it modify current regulatory
expectations, including those for
regulatory submissions, at this time.
FDA intends to consider the principles
of this guidance in the development of
regulatory approaches for SaMD and
digital health technologies. In
developing regulatory approaches based
on the principles of this guidance, the
Agency intends to follow a public
process, including providing
opportunities for public input. For more
information on FDA adoption of IMDRF
documents as an FDA guidance
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document, please see https://
www.fda.gov/MedicalDevices/
InternationalPrograms/IMDRF/
default.htm.
II. Significance of Guidance
This guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
The guidance represents the current
thinking of FDA on ‘‘Software as a
Medical Device (SaMD): Clinical
Evaluation.’’ It does not establish any
rights for any person and is not binding
on FDA or the public. You can use an
alternative approach if it satisfies the
requirements of the applicable statutes
and regulations. This guidance is not
subject to Executive Order 12866.
III. Electronic Access
Persons interested in obtaining a copy
of the guidance may do so by
downloading an electronic copy from
the Internet. A search capability for all
Center for Devices and Radiological
Health guidance documents is available
at https://www.fda.gov/MedicalDevices/
DeviceRegulationandGuidance/
GuidanceDocuments/default.htm. This
guidance document is also available at
https://www.regulations.gov. Persons
unable to download an electronic copy
of ‘‘Software as a Medical Device
(SaMD): Clinical Evaluation’’ may send
an email request to CDRH-Guidance@
fda.hhs.gov to receive an electronic
copy of the document. Please use the
document number 16039 to identify the
guidance you are requesting.
Dated: December 4, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017–26441 Filed 12–7–17; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2016–N–3083]
Report on the Performance of Drug
and Biologics Firms in Conducting
Postmarketing Requirements and
Commitments; Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of availability.
Under the Federal Food,
Drug, and Cosmetic Act (the FD&C Act),
the Food and Drug Administration (FDA
or Agency) is required to report
annually in the Federal Register on the
status of postmarketing requirements
(PMRs) and postmarketing
commitments (PMCs) required of, or
agreed upon by, holders of approved
drug and biological products. This
notice is the Agency’s report on the
status of the studies and clinical trials
that applicants have agreed to, or are
required to, conduct.
FOR FURTHER INFORMATION CONTACT:
Cathryn C. Lee, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 6484,
Silver Spring, MD 20993–0002, 301–
796–0700; or Stephen Ripley, Center for
Biologics Evaluation and Research,
Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 71, Rm.
7301, Silver Spring, MD 20993–0002,
240–402–7911.
SUPPLEMENTARY INFORMATION:
I. Background
A. Postmarketing Requirements and
Commitments
A PMR is a study or clinical trial that
an applicant is required by statute or
regulation to conduct postapproval. A
PMC is a study or clinical trial that an
applicant agrees in writing to conduct
postapproval, but that is not required by
statute or regulation. PMRs and PMCs
can be issued upon approval of a drug 1
or postapproval, if warranted.
FDA can require application holders
to conduct postmarketing studies and
clinical trials:
• To assess a known serious risk,
assess signals of serious risk, or identify
an unexpected serious risk related to the
use of a drug product (section 505(o)(3)
of the FD&C Act (21 U.S.C. 355(o)(3)), as
added by the Food and Drug
Administration Amendments Act of
2007 (FDAAA) (Pub. L. 110–85)).
• Under the Pediatric Research Equity
Act (PREA) (Pub. L. 108–155), to study
certain new drugs for pediatric
populations, when these drugs are not
adequately labeled for children. Under
section 505B(a)(3) of the FD&C Act (21
U.S.C. 355c), the initiation of these
studies may be deferred until required
safety information from other studies in
adults has first been submitted and
reviewed.
• To verify and describe the predicted
effect or other clinical benefit for drugs
approved in accordance with the
accelerated approval provisions in
section 506(c)(2)(A) of the FD&C Act (21
SUMMARY:
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1 For the purposes of this notice, references to
‘‘drugs’’ or ‘‘drug products’’ include drugs approved
under the FD&C Act and biological products
licensed under the Public Health Service Act other
than biological products that also meet the
definition of a device in section 201(h) of the FD&C
Act (21 U.S.C. 321(h)).
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description of the PMR/PMC, a schedule
for completing the PMR/PMC, and a
characterization of the current status of
the PMR/PMC. The report must also
provide an explanation of the PMR/PMC
status by describing briefly the progress
of the PMR/PMC. A PMR/PMC schedule
is expected to include the actual or
projected dates for the following: (1)
Submission of the final protocol to FDA;
(2) completion of the study or clinical
trial; and (3) submission of the final
report to FDA.
B. Reporting Requirements
Under the regulations (21 CFR
314.81(b)(2)(vii) and 21 CFR 601.70),
applicants of approved drugs are
required to submit annually a report on
the status of each clinical safety, clinical
efficacy, clinical pharmacology, and
nonclinical toxicology study or clinical
trial either required by FDA or that they
have committed to conduct, either at the
time of approval or after approval of
their new drug application (NDA),
abbreviated new drug application
(ANDA), or biologics license application
(BLA). Applicants are required to report
to FDA on these requirements and
commitments made for NDAs and
ANDAs under § 314.81(b)(2)(viii). The
status of PMCs concerning chemistry,
manufacturing, and production controls
and the status of other studies or
clinical trials conducted on an
applicant’s own initiative are not
required to be reported under
§§ 314.81(b)(2)(vii) and 601.70 and are
not addressed in this report.
Furthermore, section 505(o)(3)(E) of the
FD&C Act requires that applicants
report periodically on the status of each
required study or clinical trial and each
study or clinical trial ‘‘otherwise
undertaken . . . to investigate a safety
issue. . . .’’
An applicant must report on the
progress of the PMR/PMC on the
anniversary of the drug product’s
approval 3 until the PMR/PMC is
completed or terminated and FDA
determines that the PMR/PMC has been
fulfilled or that the PMR/PMC is either
no longer feasible or would no longer
provide useful information. The annual
status report (ASR) must include a
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U.S.C. 356(c)(2)(A)) (21 CFR 314.510
and 21 CFR 601.41).
• For a drug that was approved on the
basis of animal efficacy data because
human efficacy trials are not ethical or
feasible (21 CFR 314.610(b)(1) and 21
CFR 601.91(b)(1)). PMRs for drug
products approved under the animal
efficacy rule 2 can be conducted only
when the drug product is used for its
indication and when an exigency (or
event or need) arises. In the absence of
a public health emergency, these studies
or clinical trials will remain pending
indefinitely.
The status of the PMR/PMC must be
described in the ASR according to the
terms and definitions provided in
§§ 314.81 and 601.70. For its own
reporting purposes, FDA has also
established terms to describe when the
conditions of the PMR/PMC have been
met, and when it has been determined
that a PMR/PMC is no longer
necessary.4 The PMR/PMC status
categories are summarized in the
following list. As reflected in the
definitions, the status of a PMR/PMC is
generally determined based on the
original schedule.5
• Pending: The study or clinical trial
has not been initiated (i.e., no subjects
have been enrolled or animals dosed),
but does not meet the criteria for
delayed (i.e., the original projected date
for initiation of subject accrual or
initiation of animal dosing has not
passed).6
• Ongoing: The study or clinical trial
is proceeding according to or ahead of
the original schedule.
• Delayed: The study or clinical trial
is behind the original schedule.7
• Terminated: The study or clinical
trial was ended before completion, but
a final report has not been submitted to
FDA.
2 21 CFR 314.600 for drugs; 21 CFR 601.90 for
biological products.
3 An applicant must submit an annual status
report on the progress of each open PMR/PMC
within 60 days of the anniversary date of United
States approval of the original application or on an
alternate reporting date that was granted by FDA in
writing. Some applicants have requested and been
granted by FDA alternate annual reporting dates to
facilitate harmonized reporting across multiple
applications.
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C. PMR/PMC Status Categories
4 See the guidance for industry entitled ‘‘Reports
on the Status of Postmarketing Study
Commitments—Implementation of Section 130 of
the Food and Drug Administration Modernization
Act of 1997’’ available at https://www.fda.gov/
downloads/Drugs/
GuidanceComplianceRegulatoryInformation/
Guidances/UCM080569.pdf.
5 The definitions for the terms ‘‘pending,’’
‘‘ongoing,’’ ‘‘delayed,’’ ‘‘terminated,’’ and
‘‘submitted’’ are adapted from §§ 314.81 and 601.70;
the definitions for the terms ‘‘fulfilled’’ and
‘‘released’’ are described in the guidance for
industry entitled ‘‘Reports on the Status of
Postmarketing Study Commitments—
Implementation of Section 130 of the Food and
Drug Administration Modernization Act of 1997.’’
6 It is important to note that PMRs/PMCs that are
in pending status are not yet delayed; that is, per
the milestones, the studies or clinical trials are
indeed on schedule and are not expected to be
underway yet.
7 In some instances, an applicant may have
justifiable reasons for delay of its PMR/PMC (see
section I.D).
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• Submitted: The study or clinical
trial has been completed or terminated,
and a final report has been submitted to
FDA.
• Fulfilled: The final report for the
study or clinical trial was submitted to
FDA and FDA notified the applicant
that the requirement or commitment
was fulfilled through written
correspondence.
• Released: FDA has informed the
applicant in writing that it is released
from its obligation to conduct the study
or clinical trial because the study or
clinical trial is no longer feasible, would
no longer provide useful information, or
the underlying application has been
formally withdrawn.
In addition to the above statuses,
PMRs/PMCs may also be characterized
as open or closed. Open PMRs/PMCs
comprise those that are pending,
ongoing, delayed, submitted, or
terminated; whereas closed 8 PMRs/
PMCs are either fulfilled or released.
Open PMRs are also described by
whether they are on- or off-schedule.
On-schedule PMRs/PMCs are those that
are pending, ongoing, or submitted. Offschedule PMRs/PMCs are those that
have missed one of the milestone dates
in the original schedule and are
categorized as either delayed or
terminated.
D. Additional Requirements
If an applicant fails to comply with
the original schedule for completion of
postmarketing studies or clinical trials
required under section 505(o)(3) of the
FD&C Act (i.e., under the FDAAA
authorities), or fails to submit periodic
reports on the status of the studies or
clinical trials, the applicant is
considered to be in violation of section
505(o)(3), unless it has demonstrated
good cause for its noncompliance or
other violation. Failure to meet an
original milestone and, as a result,
falling behind the original schedule is
one type of noncompliance with a PMR
issued under FDAAA. In these
circumstances, the FDAAA PMR is
considered delayed, with or without
good cause.
Section 505B(a)(3)(B) of the FD&C
Act, as amended by the Food and Drug
Administration Safety and Innovation
Act, authorizes FDA to grant an
extension of the deferred pediatric
assessments that are required under
PREA.9 On its own initiative or upon
request, FDA may grant an extension of
a pediatric assessment deferral,
8 Previous FDA reports on the status of PMRs/
PMCs used the term ‘‘completed’’ to refer to PMRs/
PMCs that are closed.
9 This provision does not apply to PMRs required
under other provisions, or to PMCs.
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provided that certain applicable PREA
criteria for deferral are still met and the
applicant submits certain materials in
support of the extension.10 Applicants
must submit requests for deferral
extensions to FDA not less than 90 days
before the date the deferral would
otherwise expire. If FDA grants the
extension of a pediatric study deferral,
this new deferral date is considered the
original due date of the PMR.
Consequently, the status of PREA PMRs
would be determined based on the new
deferral date (and not the original PREA
PMR schedule).
FDA may take enforcement action
against applicants who are
noncompliant with or otherwise fail to
conduct studies and clinical trials
required under FDA statutes and
regulations (see, for example, sections
505(o)(1), 502(z), and 303(f)(4) of the
FD&C Act (21 U.S.C. 355(o)(1), 352(z),
and 333(f)(4))).
II. Understanding FDA’s Data on
Postmarketing Studies and Clinical
Trials
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A. FDA’s Internal PMR/PMC Databases
Databases containing information on
PMRs/PMCs are maintained at the
Center for Drug Evaluation and Research
(CDER) and the Center for Biologics
Evaluation and Research (CBER). The
information in these databases is
periodically updated as new PMRs/
PMCs are issued, upon FDA review of
PMR/PMC ASRs or other PMR/PMC
correspondence, upon receipt of final
reports from completed studies and
clinical trials, and after the final reports
are reviewed and FDA determines that
the PMR/PMC has been fulfilled, or
when FDA determines that the PMR/
PMC is either no longer feasible or
would no longer provide useful
information. Because applicants
typically report on the status of their
PMRs/PMCs annually, and because
updating the status of PMRs/PMCs in
FDA’s databases involves FDA review of
received information, there is an
inherent lag in updating the data (that
is, the data are not real time). FDA
strives to maintain as accurate
information as possible on the status of
PMRs/PMCs.
Both CDER and CBER have
established policies and procedures to
help ensure that FDA’s data on PMRs/
PMCs are current and accurate. When
identified, data discrepancies are
addressed as expeditiously as possible
and/or are corrected in later reports.
10 See
section 505B(a)(3)(B) of the FD&C Act.
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B. Publicly Available PMR/PMC Data
FDA also maintains an online
searchable and downloadable database
that contains information about PMRs/
PMCs that is publicly reportable (i.e., for
which applicants must report on the
status of the study or clinical trial, as
required under section 506B of the
FD&C Act (21 U.S.C. 356b)). The data
are a subset of all PMRs/PMCs and
reflect only those postmarketing studies
and clinical trials that, at the time of
data retrieval, either had an open status
or were closed within the past year.
Information on PMRs/PMCs closed
more than a year before the date the data
are extracted (i.e., September 30, 2016)
is not included on the public Web site.
The FDA Web site is updated
quarterly.11 The FDA Web site does not
include information about PMCs
concerning chemistry, manufacturing,
and controls. It is FDA policy not to
post information on the Web site until
it has been verified and reviewed for
suitability for public disclosure.
III. About This Report
This report is published to fulfill the
annual reporting requirement under
section 506B(c) of the FD&C Act.
Information in this report covers any
PMR/PMC that was made, in writing, at
the time of approval or after approval of
an application or a supplement to an
application (see section I.A), and
summarizes the status of PMRs/PMCs in
fiscal year (FY) 2016 (i.e., as of
September 30, 2016). Specifically, the
report summarizes the status of all open
PMRs/PMCs through the end of the
fiscal year, and the status of only those
PMRs/PMCs that were closed in the
fiscal year. If a requirement or
commitment did not have a schedule, or
an ASR was not received in the previous
12 months, the PMR/PMC is categorized
according to the most recent
information available to the Agency.12
This report reflects combined data
from CDER and CBER. Information
summarized in the report includes the
following: (1) The number of applicants
with open PMRs/PMCs; 13 (2) the
number of open PMRs/PMCs; (3) the
number of applications for which an
ASR was expected but was not
11 https://www.accessdata.fda.gov/scripts/cder/
pmc/index.cfm.
12 Although the data included in this report do
not include a summary of reports that applicants
have failed to file by their due dates, the Agency
notes that it may take appropriate regulatory action
in the event reports are not filed on a timely basis.
13 At the end of FY2016, there were no PMRs/
PMCs for ANDAs that met the reporting
requirements under the Food and Drug
Administration Modernization Act of 1997.
Therefore, this report reflects information for NDAs
and BLAs only.
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submitted within 60 days of the
anniversary date of U.S. approval or an
alternate reporting date that was granted
by FDA; (4) FDA-verified status of open
PMRs/PMCs reported in
§ 314.81(b)(2)(vii) or § 601.70 ASRs; (5)
the status of closed PMRs/PMCs; and (6)
the distribution of the status by fiscal
year of establishment 14 (FY2010 to
FY2016) for PMRs and PMCs open at
the end of FY2016, or those closed
within FY2016. The tables in this report
distinguish between PMRs and PMCs,
PMRs/PMCs for NDAs and BLAs, and
on-schedule and off-schedule PMRs/
PMCs, according to the original
schedule milestones. Additional
information about PMRs/PMCs is
provided on FDA’s Web site at https://
www.fda.gov/Drugs/Guidance
ComplianceRegulatoryInformation/PostmarketingPhaseIVCommitments/
default.htm.
Numbers published in this report
cannot be compared with the numbers
resulting from searches of the publicly
accessible and downloadable database.
This is because this report incorporates
data for all PMRs/PMCs in FDA
databases as of the end of the fiscal year,
including PMRs/PMCs undergoing
review for accuracy. The publicly
accessible and downloadable database
includes a subset of PMRs/PMCs,
specifically those that, at the time of
data retrieval, either had an open status
or were closed within the past 12
months. In addition, the status
information in this report is updated
annually while the downloadable
database is updated quarterly (i.e., in
January, April, July, and October).
IV. Summary of Information on PMR/
PMC Status
This report provides information on
PMRs/PMCs as of September 30, 2016
(i.e., for FY2016). It is important to note
that a comparison of the number of open
and on-schedule or off-schedule PMRs/
PMCs over time can be misleading
because it does not take into account
that the cohort of open PMRs/PMCs is
not static from year to year. New PMRs/
PMCs are continually being established
for studies and clinical trials with
varying start dates and durations; and
other PMRs/PMCs are closed because
they are either fulfilled or released.
Also, ongoing PMRs/PMCs are carried
forward into the subsequent fiscal year.
Therefore, the number of on- and offschedule PMRs/PMCs can vary from
year to year, and a year-to-year
14 The establishment date is the date of the formal
FDA communication to the applicant that included
the final FDA-required (PMR) or requested (PMC)
postmarketing study or clinical trial.
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comparison of on- or off-schedule PMRs
(e.g., to assess for a potential trend) is
not appropriate. Finally, due to
rounding, the percentages in the tables
may not add up to 100 percent.
A. Applicants With Open PMRs/PMCs
there were 285 unique applicants with
open PMRs/PMCs under 890 unique
NDAs and BLAs. There were 207 unique
NDA applicants (and 734 associated
applications) and 78 unique BLA
applicants (and 156 associated
applications) with open PMRs/PMCs.
An applicant may have multiple
approved drug products, and an
approved drug product may have
multiple PMRs and/or PMCs. Table 1
shows that as of September 30, 2016,
TABLE 1—APPLICANTS AND APPLICATIONS (NDA/BLA) WITH OPEN POSTMARKETING REQUIREMENTS AND COMMITMENTS
[Numbers as of September 30, 2016]
NDA 1
Number of unique applicants with open PMRs/PMCs ............................................................
Number of applications with open PMRs/PMCs .....................................................................
1 As
Total
(NDA and BLA)
BLA 2
207
734
78
156
285
890
of September 30, 2016, there were only NDAs with associated PMRs/PMCs managed by CDER.
BLAs managed by both CDER and CBER.
2 Includes
B. Annual Status Reports Received
As previously mentioned, applicants
must submit an ASR on the progress of
each open PMR/PMC within 60 days of
the anniversary date of United States
approval of the original application or
an alternate reporting date that was
granted by FDA (§§ 314.81 and
601.70).15 Table 2 shows that there were
764 NDAs and BLAs with an ASR due
in FY2016 (622 NDAs and 142 BLAs).16
Of the 622 NDA ASRs due in that fiscal
year, 66 percent (411/622) were received
on time, 11 percent (66/622) were not
received on time, and 23 percent (145/
622) were not received during FY2016.
Of the 142 BLA ASRs due, 72 percent
(102/142) were received on time, 17
percent (24/142) were not received on
time, and 11 percent (16/142) were not
received during FY2016.
TABLE 2—ANNUAL STATUS REPORTS RECEIVED
[Numbers as of September 30, 2016] 1
Received,
on time 3
(% of expected)
2 Expected
Received,
not on time 4
(% of expected)
Expected but
not received
(% of expected)
NDA ...............
BLA ................
5 622
142
411 (66%)
102 (72%)
66 (11%)
24 (17%)
145 (23%)
16 (11%)
Total ........
764
513 (67%)
90 (12%)
161 (21%)
1 Percentages
may not total 100 due to rounding.
expected during fiscal year (within 60 days (before or after) of the anniversary of original approval date or alternate agreed-upon date).
3 ASR was received within 60 days (before or after) of the anniversary of the original approval date or alternate agreed-upon date.
4 ASR was received, but not within 60 days (before or after) of the anniversary of the original approval date or alternate agreed-upon date.
5 The total number of NDA ASRs expected in FY2016 (622) increased compared to the number of ASRs expected in FY2015 (451). The increase is primarily due to the establishment of several FDAAA safety PMRs for which a serious safety issue applied to a class of drug products.
In those cases, each applicant with a drug product (i.e., application) in the class was required to conduct the same postmarketing safety study or
trial, and each applicant was required to submit an ASR for that PMR. As a consequence, multiple ASRs were expected during FY2016 for the
same FDAAA safety PMR.
2 ASR
C. Overview of On- and Off-Schedule
Open PMRs/PMCs
Table 3 shows that as of September
30, 2016, most open PMRs (84 percent
for NDAs and 91 percent for BLAs) and
most open PMCs (71 percent for NDAs
and 83 percent for BLAs) were
progressing on schedule.
TABLE 3—SUMMARY OF ON- AND OFF-SCHEDULE POSTMARKETING REQUIREMENTS AND COMMITMENTS
[Numbers as of September 30, 2016] 1
Open PMRs
N = 1,323
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NDA
(% of open NDA PMRs)
On-schedule .....................................
Off-schedule .....................................
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BLA
(% of open BLA PMRs)
882 (84%)
169 (16%)
15 Some applicants have requested and been
granted by FDA alternate annual reporting dates to
facilitate harmonized reporting across multiple
applications.
16 The number of ASRs that were expected is
different from the total number of unique
Open PMCs
N = 365
NDA
(% of open NDA PMCs)
247 (91%)
25 (9%)
applications with open PMRs/PMCs because not all
applications had an ASR due during FY2016.
Applicants with PMRs/PMCs associated with
multiple applications may have submitted the ASR
to only one of the applications. In addition, if all
of the PMRs/PMCs for an application were
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123 (71%)
51 (29%)
BLA
(% of open BLA PMCs)
159 (83%)
32 (17%)
established in the preceding fiscal year, or if all
PMRs/PMCs for an application were closed before
the ASR due date, submission of an ASR would not
have been expected.
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TABLE 3—SUMMARY OF ON- AND OFF-SCHEDULE POSTMARKETING REQUIREMENTS AND COMMITMENTS—Continued
[Numbers as of September 30, 2016] 1
Open PMRs
N = 1,323
NDA
(% of open NDA PMRs)
Total ..........................................
1 Percentages
Open PMCs
N = 365
BLA
(% of open BLA PMRs)
1,051
NDA
(% of open NDA PMCs)
272
BLA
(% of open BLA PMCs)
174
191
may not total 100 due to rounding.
D. Open and On-Schedule PMRs
percent (517/1,051) and 45 percent
(123/272), respectively). PREA PMRs
and FDAAA PMRs comprised 55
percent (349/640) and 39 percent (249/
640) of pending PMRs, respectively. The
Table 4 shows that as of September
30, 2016, nearly half of the open NDA
and BLA PMRs were pending (49
next largest category of open and onschedule PMRs comprised those that
were ongoing (29 percent (306/1,051) of
NDA PMRs and 37 percent (100/272) of
BLA PMRs).
TABLE 4—SUMMARY OF OPEN AND ON-SCHEDULE POSTMARKETING REQUIREMENTS
[Numbers as of September 30, 2016] 1
NDA
N = 1,051
(% of open NDA PMRs)
Reporting authority/PMR status
Pending
Ongoing
BLA
N = 272
(% of open BLA PMRs)
Submitted
Pending
Ongoing
Submitted
Accelerated approval ...............................
PREA 2 .....................................................
Animal efficacy 3 .......................................
FDAAA safety ..........................................
16 (2%)
300 (28%)
4 (<1%)
197 (19%)
19 (2%)
124 (12%)
0
163 (16%)
3 (<1%)
14 (1%)
1 (<1%)
41 (4%)
13 (5%)
49 (18%)
9 (3%)
52 (19%)
10 (4%)
29 (11%)
0
61 (22%)
4 (1%)
8 (3%)
0
12 (4%)
Total ..................................................
517 (49%)
306 (29%)
59 (6%)
123 (45%)
100 (37%)
24 (9%)
1 Percentages
may not total 100 due to rounding.
2 Many PREA studies have a pending status. PREA studies are usually deferred because the drug product is ready for approval in adults. Initiation of these studies may be deferred until additional safety information from other studies has first been submitted and reviewed before beginning the studies in pediatric populations.
3 PMRs for drug products approved under the animal efficacy rule (21 CFR 314.600 for drugs; 21 CFR 601.90 for biological products) can be
conducted only when the drug product is used for its indication and when an exigency (or event or need) arises. In the absence of a public
health emergency, these studies or clinical trials will remain pending indefinitely.
E. Open and Off-Schedule PMRs
Table 5 provides additional
information on the status of open and
off-schedule PMRs (i.e., delayed and
terminated). At the end of September
30, 2016, 16 percent (169/1,051) of the
open NDA PMRs and 9 percent (25/272)
of the open BLA PMRs were off
schedule. Of the off-schedule NDA
PMRs, 97 percent (164/169) were off
schedule because they were delayed and
the remaining 3 percent (5/169) were
terminated. Similarly, 88 percent of the
off-schedule BLA PMRs were delayed
(22/25).
In certain situations, the original PMR
schedules were adjusted for
unanticipated delays in the progress of
the study or clinical trial (e.g.,
difficulties with subject enrollment in a
clinical trial for a marketed drug or the
need for additional time to analyze
results). In this report, study or clinical
trial status reflects the status in relation
to the original 17 study or clinical trial
schedule regardless of whether FDA has
acknowledged that additional time was
required to complete the study or
clinical trial.
TABLE 5—SUMMARY OF OPEN AND OFF-SCHEDULE POSTMARKETING REQUIREMENTS
[Numbers as of September 30, 2016] 1
NDA
N = 1,051
(% of open NDA PMRs)
Reporting authority/PMR status
sradovich on DSK3GMQ082PROD with NOTICES
Delayed
Accelerated approval .......................................................................................
PREA ...............................................................................................................
Animal efficacy .................................................................................................
FDAAA safety ..................................................................................................
9 (1%)
84 (8%)
0
71 (7%)
Terminated
1 (<1%)
2 (<1%)
0
2 (<1%)
17 With the exception of PREA PMRs for which
a deferral extension of the final report submission
date has been granted.
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BLA
N = 272
(% of open BLA PMRs)
Delayed
1 (<1%)
6 (2%)
0
15 (6%)
Terminated
0
2 (1%)
0
1 (<1%)
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Federal Register / Vol. 82, No. 235 / Friday, December 8, 2017 / Notices
TABLE 5—SUMMARY OF OPEN AND OFF-SCHEDULE POSTMARKETING REQUIREMENTS—Continued
[Numbers as of September 30, 2016] 1
NDA
N = 1,051
(% of open NDA PMRs)
Reporting authority/PMR status
Delayed
Total ..........................................................................................................
1 Percentages
BLA
N = 272
(% of open BLA PMRs)
Terminated
164 (16%)
Delayed
5 (<1%)
Terminated
22 (8%)
3 (1%)
may not total 100 due to rounding.
F. Open On-Schedule and Off-Schedule
PMCs
Table 6 provides the status of open
on-schedule and off-schedule PMCs. As
of September 30, 2016, most open, on-
schedule NDA PMCs were pending (36
percent; 62/174) and most open, onschedule BLA PMCs were ongoing (43
percent; 83/191). Fewer open NDA and
BLA PMCs were considered off
schedule (29 percent (51/174) and 17
percent (32/191), respectively). The
majority of off-schedule NDA and BLA
PMCs were delayed according to the
original schedule milestones.
TABLE 6—SUMMARY OF OPEN POSTMARKETING COMMITMENTS
[Numbers as of September 30, 2016] 1
NDA
N = 174
(% open PMCs)
BLA
N = 191
(% open PMCs)
On-Schedule:
Pending .............................................................................................................................................
Ongoing ............................................................................................................................................
Submitted ..........................................................................................................................................
62 (36%)
40 (23%)
21 (12%)
52 (27%)
83 (43%)
24 (13%)
Total ...........................................................................................................................................
123 (71%)
159 (83%)
Off-Schedule:
Delayed .............................................................................................................................................
Terminated ........................................................................................................................................
50 (29%)
1 (1%)
30 (16%)
2 (1%)
Total ...........................................................................................................................................
51 (29%)
32 (17%)
1 Percentages
may not total 100 due to rounding.
G. Closed PMRs and PMCs
Table 7 provides details about PMRs
and PMCs that were closed (fulfilled or
released) within FY2016. The majority
of closed PMRs were fulfilled (72
percent of NDA PMRs and 82 percent of
BLA PMRs) at the end of FY2016.
Similarly, the majority of closed PMCs
were fulfilled at the end of FY2016.
TABLE 7—SUMMARY OF CLOSED 1 POSTMARKETING REQUIREMENTS AND COMMITMENTS
[Numbers as of September 30, 2016] 2
NDA
Postmarketing Requirements
Closed PMRs (% of Total Closed PMRs) ...............................................................................................................
Requirement met (fulfilled) ...............................................................................................................................
Requirement not met (released and new revised requirement issued) ...........................................................
Requirement no longer feasible or drug product withdrawn (released) ..........................................................
Postmarketing Commitments
Closed PMCs (% of Total Closed PMCs) ...............................................................................................................
Requirement met (fulfilled) ...............................................................................................................................
Requirement not met (released and new revised requirement issued) ...........................................................
Requirement no longer feasible or drug product withdrawn (released) ..........................................................
BLA
N = 174
126 (72%)
19 (11%)
29 (17%)
N = 33
27 (82%)
4 (12%)
2 (6%)
N= 54
44 (82%)
1 (2%)
9 (17%)
N=28
23 (82%)
1 (4%)
4 (14%)
sradovich on DSK3GMQ082PROD with NOTICES
1 The table shows data for those PMRs/PMCs that were closed (fulfilled or released) within FY2016. Therefore, data for PMRs/PMCs that were
closed in prior fiscal years are not included.
2 Percentages may not total 100 due to rounding.
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Federal Register / Vol. 82, No. 235 / Friday, December 8, 2017 / Notices
Based on the data shown in table 8,
an average of 261 PMRs were
established each year since FY2010.21
Most PMRs that were established in the
earlier years were either fulfilled or
released. For example, as of September
30, 2016, 54 percent (122/224) of the
PMRs that were established in FY2010
were fulfilled, and 12 percent (27/224)
were released. The majority of PMRs
that were established in more recent
years were either pending (i.e., not yet
underway) or ongoing (i.e., still in
H. Distribution of the Statuses of PMRs
and PMCs
Tables 8 and 9 show the distribution
of the statuses of PMRs/PMCs as of
September 30, 2016, presented by the
years that the PMRs/PMCs were
established 18 (FY2010 to FY2016).19 20
Note that the data shown for closed
(fulfilled or released) PMRs/PMCs are
for all PMRs/PMCs that were closed as
of FY2016. Therefore, data for PMRs/
PMCs that were closed in prior fiscal
years are included.
progress and on schedule). For example,
as of September 30, 2016, 86 percent
(232/269) of the PMRs established in
FY2016 were pending, and 8 percent
(22/269) were ongoing. Overall, of the
PMRs that were pending as of
September 30, 2016, 83 percent (510/
614) were created within the past 3
years (FY2014, FY2015, and FY2016).
Finally, table 8 shows that, on average,
7 percent (137/1,829) of the PMRs
established since FY2010 were delayed
as of September 30, 2016.
TABLE 8—SUMMARY OF STATUS OF POSTMARKETING REQUIREMENTS ESTABLISHED 1 BETWEEN FY2010 AND FY2016 2
[Numbers as of September 30, 2016] 3
Fiscal year of PMR establishment
PMR status as of FY2016 (% of total
PMRs in each establishment year)
2010
2011
2012
2013
2014
2015
2016
Pending ....................................................
Ongoing ....................................................
Submitted .................................................
Delayed ....................................................
Terminated ...............................................
Released ..................................................
Fulfilled .....................................................
8 (4%)
26 (12%)
15 (7%)
26 (12%)
0
27 (12%)
122 (54%)
16 (6%)
49 (19%)
7 (3%)
18 (7%)
2 (<1%)
59 (23%)
110 (42%)
24 (11%)
52 (24%)
9 (4%)
25 (11%)
1 (<1%)
30 (14%)
79 (36%)
56 (20%)
69 (25%)
8 (3%)
30 (11%)
0
33 (12%)
82 (29%)
114 (39%)
80 (27%)
12 (4%)
25 (9%)
0
14 (5%)
48 (16%)
164 (58%)
52 (18%)
16 (6%)
13 (4%)
1 (<1%)
5 (2%)
33 (12%)
232 (86%)
22 (8%)
2 (1%)
0
0
4 (2%)
9 (3%)
Total 4 ................................................
224
261
220
278
293
284
269
1 The
establishment date is the date of the formal FDA communication to the applicant that included the final FDA-required (PMR) or -requested (PMC) postmarketing study or clinical trial.
2 The table shows data for PMRs that were closed (fulfilled or released) as of FY2016. Therefore, data for PMRs that were closed in prior fiscal
years are included.
3 Percentages may not total 100 due to rounding.
4 The total number of PMRs/PMCs established in FY2010 through FY2016 reflects the data in FDA’s databases as of September 30, 2016.
Because of data corrections and improvements in ascertaining the PMR/PMC establishment date, some of the total numbers of PMRs/PMCs established in each fiscal year are different from those reported in the prior fiscal year’s (FY2015) Federal Register report.
Table 9 provides an overview of PMCs
in a similar format as table 8 for PMRs.
The results for PMCs are similar to those
for PMRs as described above and in
table 8.
TABLE 9—SUMMARY OF STATUS OF POSTMARKETING COMMITMENTS ESTABLISHED 1 BETWEEN FY2010 AND FY2016 2
[Numbers as of September 30, 2016] 3
Fiscal year of PMC establishment
PMR status as of FY2016 (% of total
PMCs in each establishment year)
2010
2011
2012
2013
2014
2015
2016
Pending ....................................................
Ongoing ....................................................
Submitted .................................................
Delayed ....................................................
Terminated ...............................................
Released ..................................................
Fulfilled .....................................................
1 (1%)
11 (12%)
8 (9%)
13 (14%)
0
10 (11%)
51 (54%)
3 (4%)
17 (21%)
1 (1%)
5 (6%)
0
12 (15%)
42 (53%)
0
11 (27%)
2 (5%)
4 (10%)
0
1 (2%)
23 (56%)
3 (7%)
16 (35%)
3 (7%)
3 (7%)
0
1 (2%)
20 (43%)
8 (14%)
19 (34%)
7 (13%)
0
0
0
22 (39%)
25 (40%)
18 (28%)
1 (2%)
5 (8%)
0
1 (2%)
13 (21%)
48 (80%)
4 (7%)
2 (3%)
0
0
0
6 (10%)
Total 4 ................................................
94
80
41
46
56
63
60
sradovich on DSK3GMQ082PROD with NOTICES
1 The establishment date is the date of the formal FDA communication to the applicant that included the final FDA-required (PMR) or requested
(PMC) postmarketing study or clinical trial.
18 The establishment date is the date of the formal
FDA communication to the applicant that included
the final FDA-required (PMR) or requested (PMC)
postmarketing study or clinical trial.
19 Tables 8 and 9 include data for only the past
7 fiscal years. Data on the distribution of statuses
for PMRs/PMCs established in FY2009 and as of
FY2015 are presented in the FY2015 status of
postmarketing requirements and commitments
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report (81 FR 85573) (https://
www.federalregister.gov/d/2016-28442).
20 The total number of PMRs/PMCs established in
FY2010 through FY2016 reflects the data in FDA’s
databases as of September 30, 2016. Because of data
corrections and improvements in ascertaining the
PMR/PMC establishment date, some of the total
numbers of PMRs/PMCs established in each fiscal
year are different from those reported in the prior
fiscal year’s (FY2015) Federal Register report.
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21 The number of PMRs issued at any particular
period is determined by a variety of factors
including but not necessarily limited to: (1) The
number of NDAs approved in that period; (2)
whether additional efficacy or clinical benefit
issues were evaluated; (3) if any drug-associated
serious risk(s) had been identified; and (4) whether
or not FDA determines that a postmarketing study
or clinical trial is necessary to further assess risk(s)
or efficacy issues.
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Federal Register / Vol. 82, No. 235 / Friday, December 8, 2017 / Notices
58003
2 The table shows data for PMCs that were closed (fulfilled or released) as of FY2016. Therefore, data for PMCs that were closed in prior fiscal
years are included.
3 Percentages may not total 100 due to rounding.
4 The total number of PMRs/PMCs established in FY2010 through FY2016 reflects the data in FDA’s databases as of September 30, 2016.
Because of data corrections, as well as improvements in ascertaining the PMR/PMC establishment date, some of the total numbers of PMRs/
PMCs established in each fiscal year are different from those reported in the prior fiscal year’s (FY2015) Federal Register report.
Dated: December 4, 2017.
Leslie Kux,
Associate Commissioner for Policy.
on or before April 16, 2018. The https://
www.regulations.gov electronic filing
system will accept comments until
midnight Eastern Time at the end of
April 16, 2018. 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.
[FR Doc. 2017–26470 Filed 12–7–17; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
Electronic Submissions
[Docket No. FDA–2017–N–6607]
Oncology Center of Excellence
Listening Session; Public Meeting;
Request for Comments
AGENCY:
Food and Drug Administration,
HHS.
Notice of public meeting;
request for comments.
ACTION:
The Food and Drug
Administration (FDA, the Agency, or
we) is announcing the following public
meeting entitled ‘‘Oncology Center of
Excellence (OCE): Listening Session.’’
The purpose of the public meeting and
the docket for comments is for
stakeholders to provide
recommendations to the Agency
regarding FDA’s OCE. Specifically, the
Agency solicits comments regarding
what stakeholders desire of the OCE in
terms of structure, function, regulatory
purview, and activity.
DATES: The public meeting will be held
on Thursday, March 15, 2018, from 9
a.m. to 12 noon. Submit either
electronic on written comments on this
public meeting by April 16, 2018. See
the SUPPLEMENTARY INFORMATION section
for registration date and information.
ADDRESSES: The public meeting will be
held at the FDA White Oak Campus,
10903 New Hampshire Ave., Bldg. 31
Conference Center, the Great Room (Rm.
1503), Silver Spring, MD 20993–0002.
Entrance for the public meeting
participants (non-FDA employees) is
through Building 1 where routine
security check procedures will be
performed. For parking and security
information, please refer to https://
www.fda.gov/AboutFDA/
WorkingatFDA/BuildingsandFacilities/
WhiteOakCampusInformation/
ucm241740.htm.
You may submit comments as
follows. Please note that late, untimely
filed comments will not be considered.
Electronic comments must be submitted
sradovich on DSK3GMQ082PROD with NOTICES
SUMMARY:
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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–
2017–N–6607 for ‘‘Oncology Center of
Excellence (OCE): Listening Session.’’
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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/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:
Tamy Kim, Oncology Center of
Excellence, Office of the Commissioner,
Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 22, Rm.
2206, Silver Spring, MD 20993–0002,
E:\FR\FM\08DEN1.SGM
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]]>Agencies
[Federal Register Volume 82, Number 235 (Friday, December 8, 2017)]
[Notices]
[Pages 57996-58003]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-26470]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2016-N-3083]
Report on the Performance of Drug and Biologics Firms in
Conducting Postmarketing Requirements and Commitments; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
-----------------------------------------------------------------------
SUMMARY: Under the Federal Food, Drug, and Cosmetic Act (the FD&C Act),
the Food and Drug Administration (FDA or Agency) is required to report
annually in the Federal Register on the status of postmarketing
requirements (PMRs) and postmarketing commitments (PMCs) required of,
or agreed upon by, holders of approved drug and biological products.
This notice is the Agency's report on the status of the studies and
clinical trials that applicants have agreed to, or are required to,
conduct.
FOR FURTHER INFORMATION CONTACT: Cathryn C. Lee, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 6484, Silver Spring, MD 20993-0002, 301-
796-0700; or Stephen Ripley, Center for Biologics Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
71, Rm. 7301, Silver Spring, MD 20993-0002, 240-402-7911.
SUPPLEMENTARY INFORMATION:
I. Background
A. Postmarketing Requirements and Commitments
A PMR is a study or clinical trial that an applicant is required by
statute or regulation to conduct postapproval. A PMC is a study or
clinical trial that an applicant agrees in writing to conduct
postapproval, but that is not required by statute or regulation. PMRs
and PMCs can be issued upon approval of a drug \1\ or postapproval, if
warranted.
---------------------------------------------------------------------------
\1\ For the purposes of this notice, references to ``drugs'' or
``drug products'' include drugs approved under the FD&C Act and
biological products licensed under the Public Health Service Act
other than biological products that also meet the definition of a
device in section 201(h) of the FD&C Act (21 U.S.C. 321(h)).
---------------------------------------------------------------------------
FDA can require application holders to conduct postmarketing
studies and clinical trials:
To assess a known serious risk, assess signals of serious
risk, or identify an unexpected serious risk related to the use of a
drug product (section 505(o)(3) of the FD&C Act (21 U.S.C. 355(o)(3)),
as added by the Food and Drug Administration Amendments Act of 2007
(FDAAA) (Pub. L. 110-85)).
Under the Pediatric Research Equity Act (PREA) (Pub. L.
108-155), to study certain new drugs for pediatric populations, when
these drugs are not adequately labeled for children. Under section
505B(a)(3) of the FD&C Act (21 U.S.C. 355c), the initiation of these
studies may be deferred until required safety information from other
studies in adults has first been submitted and reviewed.
To verify and describe the predicted effect or other
clinical benefit for drugs approved in accordance with the accelerated
approval provisions in section 506(c)(2)(A) of the FD&C Act (21
[[Page 57997]]
U.S.C. 356(c)(2)(A)) (21 CFR 314.510 and 21 CFR 601.41).
For a drug that was approved on the basis of animal
efficacy data because human efficacy trials are not ethical or feasible
(21 CFR 314.610(b)(1) and 21 CFR 601.91(b)(1)). PMRs for drug products
approved under the animal efficacy rule \2\ can be conducted only when
the drug product is used for its indication and when an exigency (or
event or need) arises. In the absence of a public health emergency,
these studies or clinical trials will remain pending indefinitely.
---------------------------------------------------------------------------
\2\ 21 CFR 314.600 for drugs; 21 CFR 601.90 for biological
products.
---------------------------------------------------------------------------
B. Reporting Requirements
Under the regulations (21 CFR 314.81(b)(2)(vii) and 21 CFR 601.70),
applicants of approved drugs are required to submit annually a report
on the status of each clinical safety, clinical efficacy, clinical
pharmacology, and nonclinical toxicology study or clinical trial either
required by FDA or that they have committed to conduct, either at the
time of approval or after approval of their new drug application (NDA),
abbreviated new drug application (ANDA), or biologics license
application (BLA). Applicants are required to report to FDA on these
requirements and commitments made for NDAs and ANDAs under Sec.
314.81(b)(2)(viii). The status of PMCs concerning chemistry,
manufacturing, and production controls and the status of other studies
or clinical trials conducted on an applicant's own initiative are not
required to be reported under Sec. Sec. 314.81(b)(2)(vii) and 601.70
and are not addressed in this report. Furthermore, section 505(o)(3)(E)
of the FD&C Act requires that applicants report periodically on the
status of each required study or clinical trial and each study or
clinical trial ``otherwise undertaken . . . to investigate a safety
issue. . . .''
An applicant must report on the progress of the PMR/PMC on the
anniversary of the drug product's approval \3\ until the PMR/PMC is
completed or terminated and FDA determines that the PMR/PMC has been
fulfilled or that the PMR/PMC is either no longer feasible or would no
longer provide useful information. The annual status report (ASR) must
include a description of the PMR/PMC, a schedule for completing the
PMR/PMC, and a characterization of the current status of the PMR/PMC.
The report must also provide an explanation of the PMR/PMC status by
describing briefly the progress of the PMR/PMC. A PMR/PMC schedule is
expected to include the actual or projected dates for the following:
(1) Submission of the final protocol to FDA; (2) completion of the
study or clinical trial; and (3) submission of the final report to FDA.
---------------------------------------------------------------------------
\3\ An applicant must submit an annual status report on the
progress of each open PMR/PMC within 60 days of the anniversary date
of United States approval of the original application or on an
alternate reporting date that was granted by FDA in writing. Some
applicants have requested and been granted by FDA alternate annual
reporting dates to facilitate harmonized reporting across multiple
applications.
---------------------------------------------------------------------------
C. PMR/PMC Status Categories
The status of the PMR/PMC must be described in the ASR according to
the terms and definitions provided in Sec. Sec. 314.81 and 601.70. For
its own reporting purposes, FDA has also established terms to describe
when the conditions of the PMR/PMC have been met, and when it has been
determined that a PMR/PMC is no longer necessary.\4\ The PMR/PMC status
categories are summarized in the following list. As reflected in the
definitions, the status of a PMR/PMC is generally determined based on
the original schedule.\5\
---------------------------------------------------------------------------
\4\ See the guidance for industry entitled ``Reports on the
Status of Postmarketing Study Commitments--Implementation of Section
130 of the Food and Drug Administration Modernization Act of 1997''
available at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM080569.pdf.
\5\ The definitions for the terms ``pending,'' ``ongoing,''
``delayed,'' ``terminated,'' and ``submitted'' are adapted from
Sec. Sec. 314.81 and 601.70; the definitions for the terms
``fulfilled'' and ``released'' are described in the guidance for
industry entitled ``Reports on the Status of Postmarketing Study
Commitments--Implementation of Section 130 of the Food and Drug
Administration Modernization Act of 1997.''
---------------------------------------------------------------------------
Pending: The study or clinical trial has not been
initiated (i.e., no subjects have been enrolled or animals dosed), but
does not meet the criteria for delayed (i.e., the original projected
date for initiation of subject accrual or initiation of animal dosing
has not passed).\6\
---------------------------------------------------------------------------
\6\ It is important to note that PMRs/PMCs that are in pending
status are not yet delayed; that is, per the milestones, the studies
or clinical trials are indeed on schedule and are not expected to be
underway yet.
---------------------------------------------------------------------------
Ongoing: The study or clinical trial is proceeding
according to or ahead of the original schedule.
Delayed: The study or clinical trial is behind the
original schedule.\7\
---------------------------------------------------------------------------
\7\ In some instances, an applicant may have justifiable reasons
for delay of its PMR/PMC (see section I.D).
---------------------------------------------------------------------------
Terminated: The study or clinical trial was ended before
completion, but a final report has not been submitted to FDA.
Submitted: The study or clinical trial has been completed
or terminated, and a final report has been submitted to FDA.
Fulfilled: The final report for the study or clinical
trial was submitted to FDA and FDA notified the applicant that the
requirement or commitment was fulfilled through written correspondence.
Released: FDA has informed the applicant in writing that
it is released from its obligation to conduct the study or clinical
trial because the study or clinical trial is no longer feasible, would
no longer provide useful information, or the underlying application has
been formally withdrawn.
In addition to the above statuses, PMRs/PMCs may also be
characterized as open or closed. Open PMRs/PMCs comprise those that are
pending, ongoing, delayed, submitted, or terminated; whereas closed \8\
PMRs/PMCs are either fulfilled or released. Open PMRs are also
described by whether they are on- or off-schedule. On-schedule PMRs/
PMCs are those that are pending, ongoing, or submitted. Off-schedule
PMRs/PMCs are those that have missed one of the milestone dates in the
original schedule and are categorized as either delayed or terminated.
---------------------------------------------------------------------------
\8\ Previous FDA reports on the status of PMRs/PMCs used the
term ``completed'' to refer to PMRs/PMCs that are closed.
---------------------------------------------------------------------------
D. Additional Requirements
If an applicant fails to comply with the original schedule for
completion of postmarketing studies or clinical trials required under
section 505(o)(3) of the FD&C Act (i.e., under the FDAAA authorities),
or fails to submit periodic reports on the status of the studies or
clinical trials, the applicant is considered to be in violation of
section 505(o)(3), unless it has demonstrated good cause for its
noncompliance or other violation. Failure to meet an original milestone
and, as a result, falling behind the original schedule is one type of
noncompliance with a PMR issued under FDAAA. In these circumstances,
the FDAAA PMR is considered delayed, with or without good cause.
Section 505B(a)(3)(B) of the FD&C Act, as amended by the Food and
Drug Administration Safety and Innovation Act, authorizes FDA to grant
an extension of the deferred pediatric assessments that are required
under PREA.\9\ On its own initiative or upon request, FDA may grant an
extension of a pediatric assessment deferral,
[[Page 57998]]
provided that certain applicable PREA criteria for deferral are still
met and the applicant submits certain materials in support of the
extension.\10\ Applicants must submit requests for deferral extensions
to FDA not less than 90 days before the date the deferral would
otherwise expire. If FDA grants the extension of a pediatric study
deferral, this new deferral date is considered the original due date of
the PMR. Consequently, the status of PREA PMRs would be determined
based on the new deferral date (and not the original PREA PMR
schedule).
---------------------------------------------------------------------------
\9\ This provision does not apply to PMRs required under other
provisions, or to PMCs.
\10\ See section 505B(a)(3)(B) of the FD&C Act.
---------------------------------------------------------------------------
FDA may take enforcement action against applicants who are
noncompliant with or otherwise fail to conduct studies and clinical
trials required under FDA statutes and regulations (see, for example,
sections 505(o)(1), 502(z), and 303(f)(4) of the FD&C Act (21 U.S.C.
355(o)(1), 352(z), and 333(f)(4))).
II. Understanding FDA's Data on Postmarketing Studies and Clinical
Trials
A. FDA's Internal PMR/PMC Databases
Databases containing information on PMRs/PMCs are maintained at the
Center for Drug Evaluation and Research (CDER) and the Center for
Biologics Evaluation and Research (CBER). The information in these
databases is periodically updated as new PMRs/PMCs are issued, upon FDA
review of PMR/PMC ASRs or other PMR/PMC correspondence, upon receipt of
final reports from completed studies and clinical trials, and after the
final reports are reviewed and FDA determines that the PMR/PMC has been
fulfilled, or when FDA determines that the PMR/PMC is either no longer
feasible or would no longer provide useful information. Because
applicants typically report on the status of their PMRs/PMCs annually,
and because updating the status of PMRs/PMCs in FDA's databases
involves FDA review of received information, there is an inherent lag
in updating the data (that is, the data are not real time). FDA strives
to maintain as accurate information as possible on the status of PMRs/
PMCs.
Both CDER and CBER have established policies and procedures to help
ensure that FDA's data on PMRs/PMCs are current and accurate. When
identified, data discrepancies are addressed as expeditiously as
possible and/or are corrected in later reports.
B. Publicly Available PMR/PMC Data
FDA also maintains an online searchable and downloadable database
that contains information about PMRs/PMCs that is publicly reportable
(i.e., for which applicants must report on the status of the study or
clinical trial, as required under section 506B of the FD&C Act (21
U.S.C. 356b)). The data are a subset of all PMRs/PMCs and reflect only
those postmarketing studies and clinical trials that, at the time of
data retrieval, either had an open status or were closed within the
past year. Information on PMRs/PMCs closed more than a year before the
date the data are extracted (i.e., September 30, 2016) is not included
on the public Web site. The FDA Web site is updated quarterly.\11\ The
FDA Web site does not include information about PMCs concerning
chemistry, manufacturing, and controls. It is FDA policy not to post
information on the Web site until it has been verified and reviewed for
suitability for public disclosure.
---------------------------------------------------------------------------
\11\ https://www.accessdata.fda.gov/scripts/cder/pmc/index.cfm.
---------------------------------------------------------------------------
III. About This Report
This report is published to fulfill the annual reporting
requirement under section 506B(c) of the FD&C Act. Information in this
report covers any PMR/PMC that was made, in writing, at the time of
approval or after approval of an application or a supplement to an
application (see section I.A), and summarizes the status of PMRs/PMCs
in fiscal year (FY) 2016 (i.e., as of September 30, 2016).
Specifically, the report summarizes the status of all open PMRs/PMCs
through the end of the fiscal year, and the status of only those PMRs/
PMCs that were closed in the fiscal year. If a requirement or
commitment did not have a schedule, or an ASR was not received in the
previous 12 months, the PMR/PMC is categorized according to the most
recent information available to the Agency.\12\
---------------------------------------------------------------------------
\12\ Although the data included in this report do not include a
summary of reports that applicants have failed to file by their due
dates, the Agency notes that it may take appropriate regulatory
action in the event reports are not filed on a timely basis.
---------------------------------------------------------------------------
This report reflects combined data from CDER and CBER. Information
summarized in the report includes the following: (1) The number of
applicants with open PMRs/PMCs; \13\ (2) the number of open PMRs/PMCs;
(3) the number of applications for which an ASR was expected but was
not submitted within 60 days of the anniversary date of U.S. approval
or an alternate reporting date that was granted by FDA; (4) FDA-
verified status of open PMRs/PMCs reported in Sec. 314.81(b)(2)(vii)
or Sec. 601.70 ASRs; (5) the status of closed PMRs/PMCs; and (6) the
distribution of the status by fiscal year of establishment \14\ (FY2010
to FY2016) for PMRs and PMCs open at the end of FY2016, or those closed
within FY2016. The tables in this report distinguish between PMRs and
PMCs, PMRs/PMCs for NDAs and BLAs, and on-schedule and off-schedule
PMRs/PMCs, according to the original schedule milestones. Additional
information about PMRs/PMCs is provided on FDA's Web site at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Post-marketingPhaseIVCommitments/default.htm.
---------------------------------------------------------------------------
\13\ At the end of FY2016, there were no PMRs/PMCs for ANDAs
that met the reporting requirements under the Food and Drug
Administration Modernization Act of 1997. Therefore, this report
reflects information for NDAs and BLAs only.
\14\ The establishment date is the date of the formal FDA
communication to the applicant that included the final FDA-required
(PMR) or requested (PMC) postmarketing study or clinical trial.
---------------------------------------------------------------------------
Numbers published in this report cannot be compared with the
numbers resulting from searches of the publicly accessible and
downloadable database. This is because this report incorporates data
for all PMRs/PMCs in FDA databases as of the end of the fiscal year,
including PMRs/PMCs undergoing review for accuracy. The publicly
accessible and downloadable database includes a subset of PMRs/PMCs,
specifically those that, at the time of data retrieval, either had an
open status or were closed within the past 12 months. In addition, the
status information in this report is updated annually while the
downloadable database is updated quarterly (i.e., in January, April,
July, and October).
IV. Summary of Information on PMR/PMC Status
This report provides information on PMRs/PMCs as of September 30,
2016 (i.e., for FY2016). It is important to note that a comparison of
the number of open and on-schedule or off-schedule PMRs/PMCs over time
can be misleading because it does not take into account that the cohort
of open PMRs/PMCs is not static from year to year. New PMRs/PMCs are
continually being established for studies and clinical trials with
varying start dates and durations; and other PMRs/PMCs are closed
because they are either fulfilled or released. Also, ongoing PMRs/PMCs
are carried forward into the subsequent fiscal year. Therefore, the
number of on- and off-schedule PMRs/PMCs can vary from year to year,
and a year-to-year
[[Page 57999]]
comparison of on- or off-schedule PMRs (e.g., to assess for a potential
trend) is not appropriate. Finally, due to rounding, the percentages in
the tables may not add up to 100 percent.
A. Applicants With Open PMRs/PMCs
An applicant may have multiple approved drug products, and an
approved drug product may have multiple PMRs and/or PMCs. Table 1 shows
that as of September 30, 2016, there were 285 unique applicants with
open PMRs/PMCs under 890 unique NDAs and BLAs. There were 207 unique
NDA applicants (and 734 associated applications) and 78 unique BLA
applicants (and 156 associated applications) with open PMRs/PMCs.
Table 1--Applicants and Applications (NDA/BLA) With Open Postmarketing Requirements and Commitments
[Numbers as of September 30, 2016]
----------------------------------------------------------------------------------------------------------------
Total (NDA and
NDA \1\ BLA \2\ BLA)
----------------------------------------------------------------------------------------------------------------
Number of unique applicants with open PMRs/PMCs............... 207 78 285
Number of applications with open PMRs/PMCs.................... 734 156 890
----------------------------------------------------------------------------------------------------------------
\1\ As of September 30, 2016, there were only NDAs with associated PMRs/PMCs managed by CDER.
\2\ Includes BLAs managed by both CDER and CBER.
B. Annual Status Reports Received
As previously mentioned, applicants must submit an ASR on the
progress of each open PMR/PMC within 60 days of the anniversary date of
United States approval of the original application or an alternate
reporting date that was granted by FDA (Sec. Sec. 314.81 and
601.70).\15\ Table 2 shows that there were 764 NDAs and BLAs with an
ASR due in FY2016 (622 NDAs and 142 BLAs).\16\ Of the 622 NDA ASRs due
in that fiscal year, 66 percent (411/622) were received on time, 11
percent (66/622) were not received on time, and 23 percent (145/622)
were not received during FY2016. Of the 142 BLA ASRs due, 72 percent
(102/142) were received on time, 17 percent (24/142) were not received
on time, and 11 percent (16/142) were not received during FY2016.
---------------------------------------------------------------------------
\15\ Some applicants have requested and been granted by FDA
alternate annual reporting dates to facilitate harmonized reporting
across multiple applications.
\16\ The number of ASRs that were expected is different from the
total number of unique applications with open PMRs/PMCs because not
all applications had an ASR due during FY2016. Applicants with PMRs/
PMCs associated with multiple applications may have submitted the
ASR to only one of the applications. In addition, if all of the
PMRs/PMCs for an application were established in the preceding
fiscal year, or if all PMRs/PMCs for an application were closed
before the ASR due date, submission of an ASR would not have been
expected.
Table 2--Annual Status Reports Received
[Numbers as of September 30, 2016] \1\
----------------------------------------------------------------------------------------------------------------
Received, on time Received, not on Expected but not
\2\ Expected \3\ (% of time \4\ (% of received (% of
expected) expected) expected)
----------------------------------------------------------------------------------------------------------------
NDA.................................... \5\ 622 411 (66%) 66 (11%) 145 (23%)
BLA.................................... 142 102 (72%) 24 (17%) 16 (11%)
------------------------------------------------------------------------
Total.............................. 764 513 (67%) 90 (12%) 161 (21%)
----------------------------------------------------------------------------------------------------------------
\1\ Percentages may not total 100 due to rounding.
\2\ ASR expected during fiscal year (within 60 days (before or after) of the anniversary of original approval
date or alternate agreed-upon date).
\3\ ASR was received within 60 days (before or after) of the anniversary of the original approval date or
alternate agreed-upon date.
\4\ ASR was received, but not within 60 days (before or after) of the anniversary of the original approval date
or alternate agreed-upon date.
\5\ The total number of NDA ASRs expected in FY2016 (622) increased compared to the number of ASRs expected in
FY2015 (451). The increase is primarily due to the establishment of several FDAAA safety PMRs for which a
serious safety issue applied to a class of drug products. In those cases, each applicant with a drug product
(i.e., application) in the class was required to conduct the same postmarketing safety study or trial, and
each applicant was required to submit an ASR for that PMR. As a consequence, multiple ASRs were expected
during FY2016 for the same FDAAA safety PMR.
C. Overview of On- and Off-Schedule Open PMRs/PMCs
Table 3 shows that as of September 30, 2016, most open PMRs (84
percent for NDAs and 91 percent for BLAs) and most open PMCs (71
percent for NDAs and 83 percent for BLAs) were progressing on schedule.
Table 3--Summary of On- and Off-Schedule Postmarketing Requirements and Commitments
[Numbers as of September 30, 2016] \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Open PMRs N = 1,323 Open PMCs N = 365
---------------------------------------------------------------------------------------------------
NDA (% of open NDA BLA (% of open BLA NDA (% of open NDA BLA (% of open BLA
PMRs) PMRs) PMCs) PMCs)
--------------------------------------------------------------------------------------------------------------------------------------------------------
On-schedule......................................... 882 (84%) 247 (91%) 123 (71%) 159 (83%)
Off-schedule........................................ 169 (16%) 25 (9%) 51 (29%) 32 (17%)
---------------------------------------------------------------------------------------------------
[[Page 58000]]
Total........................................... 1,051 272 174 191
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Percentages may not total 100 due to rounding.
D. Open and On-Schedule PMRs
Table 4 shows that as of September 30, 2016, nearly half of the
open NDA and BLA PMRs were pending (49 percent (517/1,051) and 45
percent (123/272), respectively). PREA PMRs and FDAAA PMRs comprised 55
percent (349/640) and 39 percent (249/640) of pending PMRs,
respectively. The next largest category of open and on-schedule PMRs
comprised those that were ongoing (29 percent (306/1,051) of NDA PMRs
and 37 percent (100/272) of BLA PMRs).
Table 4--Summary of Open and On-Schedule Postmarketing Requirements
[Numbers as of September 30, 2016] \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
NDA N = 1,051 (% of open NDA PMRs) BLA N = 272 (% of open BLA PMRs)
Reporting authority/PMR status -----------------------------------------------------------------------------------------------
Pending Ongoing Submitted Pending Ongoing Submitted
--------------------------------------------------------------------------------------------------------------------------------------------------------
Accelerated approval.................................... 16 (2%) 19 (2%) 3 (<1%) 13 (5%) 10 (4%) 4 (1%)
PREA \2\................................................ 300 (28%) 124 (12%) 14 (1%) 49 (18%) 29 (11%) 8 (3%)
Animal efficacy \3\..................................... 4 (<1%) 0 1 (<1%) 9 (3%) 0 0
FDAAA safety............................................ 197 (19%) 163 (16%) 41 (4%) 52 (19%) 61 (22%) 12 (4%)
-----------------------------------------------------------------------------------------------
Total............................................... 517 (49%) 306 (29%) 59 (6%) 123 (45%) 100 (37%) 24 (9%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Percentages may not total 100 due to rounding.
\2\ Many PREA studies have a pending status. PREA studies are usually deferred because the drug product is ready for approval in adults. Initiation of
these studies may be deferred until additional safety information from other studies has first been submitted and reviewed before beginning the
studies in pediatric populations.
\3\ PMRs for drug products approved under the animal efficacy rule (21 CFR 314.600 for drugs; 21 CFR 601.90 for biological products) can be conducted
only when the drug product is used for its indication and when an exigency (or event or need) arises. In the absence of a public health emergency,
these studies or clinical trials will remain pending indefinitely.
E. Open and Off-Schedule PMRs
Table 5 provides additional information on the status of open and
off-schedule PMRs (i.e., delayed and terminated). At the end of
September 30, 2016, 16 percent (169/1,051) of the open NDA PMRs and 9
percent (25/272) of the open BLA PMRs were off schedule. Of the off-
schedule NDA PMRs, 97 percent (164/169) were off schedule because they
were delayed and the remaining 3 percent (5/169) were terminated.
Similarly, 88 percent of the off-schedule BLA PMRs were delayed (22/
25).
In certain situations, the original PMR schedules were adjusted for
unanticipated delays in the progress of the study or clinical trial
(e.g., difficulties with subject enrollment in a clinical trial for a
marketed drug or the need for additional time to analyze results). In
this report, study or clinical trial status reflects the status in
relation to the original \17\ study or clinical trial schedule
regardless of whether FDA has acknowledged that additional time was
required to complete the study or clinical trial.
---------------------------------------------------------------------------
\17\ With the exception of PREA PMRs for which a deferral
extension of the final report submission date has been granted.
Table 5--Summary of Open and Off-Schedule Postmarketing Requirements
[Numbers as of September 30, 2016] \1\
----------------------------------------------------------------------------------------------------------------
NDA N = 1,051 (% of open NDA BLA N = 272 (% of open BLA
PMRs) PMRs)
Reporting authority/PMR status ---------------------------------------------------------------
Delayed Terminated Delayed Terminated
----------------------------------------------------------------------------------------------------------------
Accelerated approval............................ 9 (1%) 1 (<1%) 1 (<1%) 0
PREA............................................ 84 (8%) 2 (<1%) 6 (2%) 2 (1%)
Animal efficacy................................. 0 0 0 0
FDAAA safety.................................... 71 (7%) 2 (<1%) 15 (6%) 1 (<1%)
---------------------------------------------------------------
[[Page 58001]]
Total....................................... 164 (16%) 5 (<1%) 22 (8%) 3 (1%)
----------------------------------------------------------------------------------------------------------------
\1\ Percentages may not total 100 due to rounding.
F. Open On-Schedule and Off-Schedule PMCs
Table 6 provides the status of open on-schedule and off-schedule
PMCs. As of September 30, 2016, most open, on-schedule NDA PMCs were
pending (36 percent; 62/174) and most open, on-schedule BLA PMCs were
ongoing (43 percent; 83/191). Fewer open NDA and BLA PMCs were
considered off schedule (29 percent (51/174) and 17 percent (32/191),
respectively). The majority of off-schedule NDA and BLA PMCs were
delayed according to the original schedule milestones.
Table 6--Summary of Open Postmarketing Commitments
[Numbers as of September 30, 2016] \1\
------------------------------------------------------------------------
NDA N = 174 (% BLA N = 191 (%
open PMCs) open PMCs)
------------------------------------------------------------------------
On-Schedule:
Pending..................... 62 (36%) 52 (27%)
Ongoing..................... 40 (23%) 83 (43%)
Submitted................... 21 (12%) 24 (13%)
---------------------------------------
Total................... 123 (71%) 159 (83%)
------------------------------------------------------------------------
Off-Schedule:
Delayed..................... 50 (29%) 30 (16%)
Terminated.................. 1 (1%) 2 (1%)
---------------------------------------
Total................... 51 (29%) 32 (17%)
------------------------------------------------------------------------
\1\ Percentages may not total 100 due to rounding.
G. Closed PMRs and PMCs
Table 7 provides details about PMRs and PMCs that were closed
(fulfilled or released) within FY2016. The majority of closed PMRs were
fulfilled (72 percent of NDA PMRs and 82 percent of BLA PMRs) at the
end of FY2016. Similarly, the majority of closed PMCs were fulfilled at
the end of FY2016.
Table 7--Summary of Closed \1\ Postmarketing Requirements and
Commitments
[Numbers as of September 30, 2016] \2\
------------------------------------------------------------------------
NDA BLA
------------------------------------------------------------------------
Postmarketing Requirements
Closed PMRs (% of Total Closed PMRs).... N = 174 N = 33
Requirement met (fulfilled)......... 126 (72%) 27 (82%)
Requirement not met (released and 19 (11%) 4 (12%)
new revised requirement issued)....
Requirement no longer feasible or 29 (17%) 2 (6%)
drug product withdrawn (released)..
Postmarketing Commitments
Closed PMCs (% of Total Closed PMCs).... N= 54 N=28
Requirement met (fulfilled)......... 44 (82%) 23 (82%)
Requirement not met (released and 1 (2%) 1 (4%)
new revised requirement issued)....
Requirement no longer feasible or 9 (17%) 4 (14%)
drug product withdrawn (released)..
------------------------------------------------------------------------
\1\ The table shows data for those PMRs/PMCs that were closed (fulfilled
or released) within FY2016. Therefore, data for PMRs/PMCs that were
closed in prior fiscal years are not included.
\2\ Percentages may not total 100 due to rounding.
[[Page 58002]]
H. Distribution of the Statuses of PMRs and PMCs
Tables 8 and 9 show the distribution of the statuses of PMRs/PMCs
as of September 30, 2016, presented by the years that the PMRs/PMCs
were established \18\ (FY2010 to FY2016).\19\ \20\ Note that the data
shown for closed (fulfilled or released) PMRs/PMCs are for all PMRs/
PMCs that were closed as of FY2016. Therefore, data for PMRs/PMCs that
were closed in prior fiscal years are included.
---------------------------------------------------------------------------
\18\ The establishment date is the date of the formal FDA
communication to the applicant that included the final FDA-required
(PMR) or requested (PMC) postmarketing study or clinical trial.
\19\ Tables 8 and 9 include data for only the past 7 fiscal
years. Data on the distribution of statuses for PMRs/PMCs
established in FY2009 and as of FY2015 are presented in the FY2015
status of postmarketing requirements and commitments report (81 FR
85573) (https://www.federalregister.gov/d/2016-28442).
\20\ The total number of PMRs/PMCs established in FY2010 through
FY2016 reflects the data in FDA's databases as of September 30,
2016. Because of data corrections and improvements in ascertaining
the PMR/PMC establishment date, some of the total numbers of PMRs/
PMCs established in each fiscal year are different from those
reported in the prior fiscal year's (FY2015) Federal Register
report.
---------------------------------------------------------------------------
Based on the data shown in table 8, an average of 261 PMRs were
established each year since FY2010.\21\ Most PMRs that were established
in the earlier years were either fulfilled or released. For example, as
of September 30, 2016, 54 percent (122/224) of the PMRs that were
established in FY2010 were fulfilled, and 12 percent (27/224) were
released. The majority of PMRs that were established in more recent
years were either pending (i.e., not yet underway) or ongoing (i.e.,
still in progress and on schedule). For example, as of September 30,
2016, 86 percent (232/269) of the PMRs established in FY2016 were
pending, and 8 percent (22/269) were ongoing. Overall, of the PMRs that
were pending as of September 30, 2016, 83 percent (510/614) were
created within the past 3 years (FY2014, FY2015, and FY2016). Finally,
table 8 shows that, on average, 7 percent (137/1,829) of the PMRs
established since FY2010 were delayed as of September 30, 2016.
---------------------------------------------------------------------------
\21\ The number of PMRs issued at any particular period is
determined by a variety of factors including but not necessarily
limited to: (1) The number of NDAs approved in that period; (2)
whether additional efficacy or clinical benefit issues were
evaluated; (3) if any drug-associated serious risk(s) had been
identified; and (4) whether or not FDA determines that a
postmarketing study or clinical trial is necessary to further assess
risk(s) or efficacy issues.
Table 8--Summary of Status of Postmarketing Requirements Established \1\ Between FY2010 and FY2016 \2\
[Numbers as of September 30, 2016] \3\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Fiscal year of PMR establishment
PMR status as of FY2016 (% of total PMRs in each ------------------------------------------------------------------------------------------
establishment year) 2010 2011 2012 2013 2014 2015 2016
--------------------------------------------------------------------------------------------------------------------------------------------------------
Pending...................................................... 8 (4%) 16 (6%) 24 (11%) 56 (20%) 114 (39%) 164 (58%) 232 (86%)
Ongoing...................................................... 26 (12%) 49 (19%) 52 (24%) 69 (25%) 80 (27%) 52 (18%) 22 (8%)
Submitted.................................................... 15 (7%) 7 (3%) 9 (4%) 8 (3%) 12 (4%) 16 (6%) 2 (1%)
Delayed...................................................... 26 (12%) 18 (7%) 25 (11%) 30 (11%) 25 (9%) 13 (4%) 0
Terminated................................................... 0 2 (<1%) 1 (<1%) 0 0 1 (<1%) 0
Released..................................................... 27 (12%) 59 (23%) 30 (14%) 33 (12%) 14 (5%) 5 (2%) 4 (2%)
Fulfilled.................................................... 122 (54%) 110 (42%) 79 (36%) 82 (29%) 48 (16%) 33 (12%) 9 (3%)
------------------------------------------------------------------------------------------
Total \4\................................................ 224 261 220 278 293 284 269
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ The establishment date is the date of the formal FDA communication to the applicant that included the final FDA-required (PMR) or -requested (PMC)
postmarketing study or clinical trial.
\2\ The table shows data for PMRs that were closed (fulfilled or released) as of FY2016. Therefore, data for PMRs that were closed in prior fiscal years
are included.
\3\ Percentages may not total 100 due to rounding.
\4\ The total number of PMRs/PMCs established in FY2010 through FY2016 reflects the data in FDA's databases as of September 30, 2016. Because of data
corrections and improvements in ascertaining the PMR/PMC establishment date, some of the total numbers of PMRs/PMCs established in each fiscal year
are different from those reported in the prior fiscal year's (FY2015) Federal Register report.
Table 9 provides an overview of PMCs in a similar format as table 8
for PMRs. The results for PMCs are similar to those for PMRs as
described above and in table 8.
Table 9--Summary of Status of Postmarketing Commitments Established \1\ Between FY2010 and FY2016 \2\
[Numbers as of September 30, 2016] \3\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Fiscal year of PMC establishment
PMR status as of FY2016 (% of total PMCs in each ------------------------------------------------------------------------------------------
establishment year) 2010 2011 2012 2013 2014 2015 2016
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Pending...................................................... 1 (1%) 3 (4%) 0 3 (7%) 8 (14%) 25 (40%) 48 (80%)
Ongoing...................................................... 11 (12%) 17 (21%) 11 (27%) 16 (35%) 19 (34%) 18 (28%) 4 (7%)
Submitted.................................................... 8 (9%) 1 (1%) 2 (5%) 3 (7%) 7 (13%) 1 (2%) 2 (3%)
Delayed...................................................... 13 (14%) 5 (6%) 4 (10%) 3 (7%) 0 5 (8%) 0
Terminated................................................... 0 0 0 0 0 0 0
Released..................................................... 10 (11%) 12 (15%) 1 (2%) 1 (2%) 0 1 (2%) 0
Fulfilled.................................................... 51 (54%) 42 (53%) 23 (56%) 20 (43%) 22 (39%) 13 (21%) 6 (10%)
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Total \4\................................................ 94 80 41 46 56 63 60
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\1\ The establishment date is the date of the formal FDA communication to the applicant that included the final FDA-required (PMR) or requested (PMC)
postmarketing study or clinical trial.
[[Page 58003]]
\2\ The table shows data for PMCs that were closed (fulfilled or released) as of FY2016. Therefore, data for PMCs that were closed in prior fiscal years
are included.
\3\ Percentages may not total 100 due to rounding.
\4\ The total number of PMRs/PMCs established in FY2010 through FY2016 reflects the data in FDA's databases as of September 30, 2016. Because of data
corrections, as well as improvements in ascertaining the PMR/PMC establishment date, some of the total numbers of PMRs/PMCs established in each fiscal
year are different from those reported in the prior fiscal year's (FY2015) Federal Register report.
Dated: December 4, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-26470 Filed 12-7-17; 8:45 am]
BILLING CODE 4164-01-P
