[Federal Register Volume 81, Number 228 (Monday, November 28, 2016)]
[Notices]
[Pages 85573-85579]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-28442]



[[Page 85573]]

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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.

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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. A supplemental report containing additional information and 
analyses on the status of PMRs and PMCs is available on FDA's Web 
site.\1\
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    \1\ http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Post-marketingPhaseIVCommitments/ucm064436.htm.

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. 
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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\2\ or postapproval, if 
warranted.
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    \2\ 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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    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)).
     Under the Pediatric Research Equity Act (PREA), 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 U.S.C. 
356(c)(2)(A)) (Sec. Sec.  314.510 and 601.41 (21 CFR 314.510 and 
601.41)).
     For a drug that was approved on the basis of animal 
efficacy data because human efficacy trials are not ethical or feasible 
(Sec. Sec.  314.610(b)(1) and 601.91(b)(1)). PMRs for drug products 
approved under the animal efficacy rule\3\ 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.
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    \3\ 21 CFR 314.600 for drugs; 21 CFR 601.90 for biological 
products.
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B. Reporting Requirements

    Under the regulations (Sec. Sec.  314.81(b)(2)(vii) and 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\4\ 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.
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    \4\ An applicant must submit an annual status report on the 
progress of each open PMR/PMC within 60 days of the anniversary date 
of U.S. 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

    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.\5\ 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.\6\
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    \5\ 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.'' 
We update guidances periodically. To make sure you have the most 
recent version of a guidance, check the FDA Drugs guidance Web page 
at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
    \6\ 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.''

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[[Page 85574]]

     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).\7\
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    \7\ 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.
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     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.\8\
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    \8\ In some instances, an applicant may have justifiable reasons 
for delay of its PMR/PMC (see section I.D).
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     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 closed or open. Open PMRs/PMCs comprise those that are 
pending, ongoing, delayed, submitted, or terminated; whereas closed \9\ 
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.
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    \9\ Previous FDA reports on the status of PMRs/PMCs used the 
term ``completed'' to refer to PMRs/PMCs that are closed.
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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.\10\ On its own initiative or upon request, FDA may grant an 
extension of a pediatric assessment deferral, provided that certain 
applicable PREA criteria for deferral are still met and the applicant 
submits certain materials in support of the extension.\11\ 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).
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    \10\ This provision does not apply to PMRs required under other 
provisions, or to PMCs.
    \11\ See section 505B(a)(3)(B) of the FD&C Act.
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    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, 2015) are not included 
on the public Web site. The FDA Web site is updated quarterly.\12\ 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.
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    \12\ http://www.accessdata.fda.gov/scripts/cder/pmc/index.cfm.
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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) 2015 (FY2015) (i.e., as of September 30, 2015). 
Specifically, the report summarizes the status of all open

[[Page 85575]]

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.\13\
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    \13\ Although the data included in this report do not include a 
summary of reports that applicants have failed to file by their due 
date, the Agency notes that it may take appropriate regulatory 
action in the event reports are not filed on a timely basis.
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    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; \14\ (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. Sec.  
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 
\15\ (FY2009 to FY2015) for PMRs and PMCs open at the end of FY2015, or 
those closed within FY2015. 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. 
A more detailed summary of this information and additional information 
about PMRs/PMCs is provided on FDA's Web site at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Post-marketingPhaseIVCommitments/default.htm. In the supplemental report on 
FDA's Web site, information is presented separately for CDER and CBER.
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    \14\ At the end of FY2015, 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.
    \15\ 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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    Numbers published in this report and in the supplemental report on 
FDA's Web site 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, 
2015 (i.e., for FY2015). 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 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, 2015, there were 269 unique applicants with 
open PMRs/PMCs under 856 unique NDAs and BLAs. There were 194 unique 
NDA applicants (and 716 associated applications) and 75 unique BLA 
applicants (and 140 associated applications) with open PMRs/PMCs.

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 
U.S. approval of the original application or an alternate reporting 
date that was granted by FDA (Sec. Sec.  314.81 and 21 CFR 601.70).\16\ 
Table 2 shows that there were 575 NDAs and BLAs with an ASR due in 
FY2015 (451 NDAs and 124 BLAs).\17\ Of the 451 NDA ASRs due in that 
fiscal year, 67 percent (304/451) were received on time, 14 percent 
(62/451) were not received on time, and 19 percent (85/451) were not 
received during FY2015. Of the 124 BLA ASRs due, 78 percent (97/124) 
were received on time, 13 percent (16/124) were not received on time, 
and 9 percent (11/124) were not received during FY2015.
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    \16\ An applicant must submit an ASR on the progress of each 
open PMR/PMC within 60 days of the anniversary date of U.S. 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.
    \17\ 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 FY2015. 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.
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C. Overview of On- and Off-Schedule Open PMRs/PMCs

    Table 3 shows that as of September 30, 2015, most open PMRs (88 
percent for NDAs and 91 percent for BLAs) and most open PMCs (69 
percent for NDAs and 78 percent for BLAs) were progressing on schedule.

D. Open and On-Schedule PMRs

    Table 4 shows that as of September 30, 2015, the majority of PMRs 
were pending (53 percent (535/1,010) of open NDA PMRs and 45 percent 
(100/223) of open BLA PMRs). PREA PMRs and FDAAA PMRs comprised 53 
percent (336/635) and 43 percent (270/635) of pending PMRs, 
respectively. The next largest category of open and on-schedule PMRs 
comprised those that were ongoing (29 percent (288/1,010) of NDA PMRs 
and 36 percent (80/223) of BLA PMRs).

E. Open and Off-Schedule PMRs

    Table 5 provides additional information on the status of open and 
off-schedule (i.e., delayed and terminated) PMRs. At the end of 
September 30, 2015, 12 percent (123/1,010) of the open NDA PMRs and 9 
percent (20/223) of the open BLA PMRs were off-schedule. Of the off-
schedule NDA PMRs, 97 percent (119/123) were off-schedule because they 
were delayed and the remaining 3 percent (4/123) were terminated. 
Similarly, 90 percent of the off-schedule BLA PMRs were delayed (18/
20).
    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 need for additional time to analyze results).

[[Page 85576]]

In this report, study or clinical trial status reflects the status in 
relation to the original\18\ study or clinical trial schedule 
regardless of whether FDA has acknowledged that additional time was 
required to complete the study or clinical trial.
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    \18\ With the exception of PREA PMRs for which a deferral 
extension of the final report submission date has been granted.
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F. Open On-Schedule and Off-Schedule PMCs

    Table 6 provides the status of open on-schedule and off-schedule 
PMCs and shows that as of September 30, 2015, the largest category of 
all open NDA PMCs were those that were pending (36 percent; 71/197). 
Most of the open BLA PMCs were ongoing at the end of FY2015 (39 
percent; 80/204). Off-schedule PMCs accounted for 31 percent (62/197) 
of open NDA PMCs and 22 percent (45/204) of open BLA PMCs. The majority 
of off-schedule NDA and BLA PMCs were delayed according to the original 
schedule milestones.

G. Closed PMRs and PMCs

    Table 7 provides details about PMRs and PMCs that were closed 
(released or fulfilled) within FY2015. The majority of closed PMRs were 
fulfilled (69 percent of NDA PMRs and 90 percent of BLA PMRs at the end 
of FY2015). Similarly, the majority of closed PMCs within FY2015 were 
fulfilled.

H. Distribution of the Status of PMRs and PMCs

    Tables 8 and 9 show the distribution of the statuses of PMRs/PMCs 
as of September 30, 2015, presented by the year that the PMR/PMC was 
established\19\ (FY2009 to FY2015).20 21 Note that the data 
shown for closed (fulfilled or released) PMRs/PMCs are for all PMRs/
PMCs that were closed as of FY2015. Therefore, data for PMRs/PMCs that 
were closed in prior fiscal years are included. Based on the data shown 
in table 8, an average of 254 PMRs were established each year since 
FY2009.\22\ Most PMRs that were established in the earlier years were 
either fulfilled or released. For example, as of September 30, 2015, 44 
percent (109/248) of the PMRs that were established in FY2009 were 
fulfilled, and 22 percent (55/248) 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, 2015, 89 percent (250/280) of the PMRs 
established in FY2015 were pending, and 6 percent (16/280) were 
ongoing. Overall, of the PMRs that were pending as of September 30, 
2015, 86 percent (527/616) were created within the past 3 years 
(FY2013, FY2014, and FY2015). Finally, table 8 shows that, on average, 
6 percent of the PMRs established since FY2009 were delayed as of 
September 30, 2015. Table 9 provides an overview of PMCs in a similar 
manner as table 8 does for PMRs and shows similar results for PMCs as 
those for PMRs as described above and in table 8.
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    \19\ 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.
    \20\ Tables 8 and 9 include data for only the past 7 fiscal 
years. Data on the distribution of statuses for PMRs/PMCs 
established in FY2008 and as of FY2014 are presented in the FY2014 
status of postmarketing requirements and commitments report (81 FR 
75411) (https://www.gpo.gov/fdsys/pkg/FR-2016-10-31/html/2016-26247.htm).
    \21\ The total number of PMRs/PMCs established in FY2009 through 
FY2014 reflects the data in FDA's databases as of September 30, 
2015. As a result of data corrections, as well as improvements in 
ascertainment of 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 (FY 2014) Federal 
Register report.
    \22\ 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) have 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 1--Applicants and Applications (NDA/BLA) With Open Postmarketing Requirements and Commitments
                                       [Numbers as of September 30, 2015]
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                                                                                                    Total (NDA
                                                                      NDA \1\         BLA \2\        and BLA)
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Number of unique applicants with open PMRs/PMCs.................             194              75             269
Number of applications with open PMRs/PMCs......................             716             140             856
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\1\ Includes two NDAs with associated PMRs/PMCs managed by CBER.
\2\ Includes BLAs managed by both CDER and CBER.


                                     Table 2--Annual Status Reports Received
                                     [Numbers as of September 30, 2015] \1\
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                                                                                  Received,  not   Expected  but
                                                                   Received,  on    on time \4\    not  received
                                                   Expected \2\    time \3\  (%        (% of           (% of
                                                                   of  expected)     expected)       expected)
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NDA.............................................             451       304 (67%)        62 (14%)        85 (19%)
BLA.............................................             124        97 (78%)        16 (13%)         11 (9%)
                                                 ---------------------------------------------------------------
    Total.......................................             575       401 (70%)        78 (14%)        96 (17%)
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\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.


[[Page 85577]]


               Table 3--Summary of On- and Off-Schedule Postmarketing Requirements and Commitments
                                     [Numbers as of September 30, 2015] \1\
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                                                       Open PMRs  N = 1,233             Open PMCs  N = 401
                                                 ---------------------------------------------------------------
                                                    NDA  (% of      BLA  (% of      NDA  (% of      BLA  (% of
                                                  Open NDA PMRs)  Open BLA PMRs)  Open NDA PMCs)  Open BLA PMCs)
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On-schedule.....................................       887 (88%)       203 (91%)       135 (69%)       159 (78%)
Off-schedule....................................       123 (12%)         20 (9%)        62 (31%)        45 (22%)
                                                 ---------------------------------------------------------------
    Total.......................................           1,010             223             197             204
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\1\ Percentages may not total 100 due to rounding.


                                           Table 4--Summary of Open and On-Schedule Postmarketing Requirements
                                                         [Numbers as of September 30, 2015] \1\
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                                                               NDA  N = 1,010  (% of Open NDA PMRs)             BLA  N = 223  (% of Open BLA PMRs)
             Reporting authority/PMR status              -----------------------------------------------------------------------------------------------
                                                              Pending         Ongoing        Submitted        Pending         Ongoing        Submitted
--------------------------------------------------------------------------------------------------------------------------------------------------------
Accelerated approval....................................         12 (1%)         25 (3%)         3 (<1%)          7 (3%)          7 (2%)         1 (<1%)
PREA \2\................................................       290 (29%)       121 (12%)         18 (2%)        46 (20%)         18 (8%)          9 (4%)
Animal efficacy \3\.....................................         4 (<1%)               0         1 (<1%)          6 (3%)               0               0
FDAAA safety \4\........................................   229 \3\ (23%)       142 (14%)         42 (4%)        41 (18%)        55 (25%)         13 (6%)
(since March 25, 2008)..................................
                                                         -----------------------------------------------------------------------------------------------
    Total...............................................       535 (53%)       288 (29%)         64 (6%)       100 (45%)        80 (36%)        23 (10%)
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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 (Sec.   314.600 for drugs; Sec.   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.
\4\ Includes one NDA PMR FDAAA safety study from CBER in pending status.


                      Table 5--Summary of Open and Off-Schedule Postmarketing Requirements
                                     [Numbers as of September 30, 2015] \1\
----------------------------------------------------------------------------------------------------------------
                                                   NDA N = 1,010 (% of Open NDA     BLA N = 223 (% of Open BLA
                                                               PMRs)                           PMRs)
         Reporting authority/PMR status          ---------------------------------------------------------------
                                                      Delayed       Terminated        Delayed       Terminated
----------------------------------------------------------------------------------------------------------------
Accelerated approval............................         3 (<1%)         2 (<1%)         1 (<1%)               0
PREA............................................         64 (6%)         2 (<1%)          5 (2%)         2 (<1%)
Animal efficacy.................................               0               0               0               0
FDAAA safety....................................         52 (5%)               0         12 (5%)               0
(since March 25, 2008)..........................
                                                 ---------------------------------------------------------------
    Total.......................................       119 (12%)         4 (<1%)         18 (8%)         2 (<1%)
----------------------------------------------------------------------------------------------------------------
\1\ Percentages may not total 100 due to rounding.


           Table 6--Summary of Open Postmarketing Commitments
                 [Numbers as of September 30, 2015] \1\
------------------------------------------------------------------------
                                          NDA N = 197 (%  BLA N = 204 (%
                                            Open PMCs)      Open PMCs)
------------------------------------------------------------------------
On-Schedule.............................  ..............  ..............
Pending.................................        71 (36%)        54 (26%)
Ongoing.................................        40 (20%)        80 (39%)
Submitted...............................        24 (12%)        25 (12%)
Total...................................       135 (68%)       159 (77%)
Off-Schedule............................  ..............  ..............
Delayed.................................        59 (30%)        43 (21%)

[[Page 85578]]

 
Terminated..............................          3 (2%)          2 (1%)
                                         -------------------------------
    Total...............................        62 (31%)        45 (22%)
------------------------------------------------------------------------
\1\ Percentages may not total 100 due to rounding.


      Table 7--Summary of Closed \1\ Postmarketing Requirements and
                               Commitments
                 [Numbers as of September 30, 2015] \2\
------------------------------------------------------------------------
       Postmarketing requirements           NDA N = 195     BLA N = 40
------------------------------------------------------------------------
Closed PMRs (% of Total Closed PMRs)      ..............  ..............
Requirement met (fulfilled).............       134 (69%)        36 (90%)
Requirement not met (released and new           31 (16%)          1 (2%)
 revised requirement issued)............
Requirement no longer feasible or drug          30 (15%)          3 (8%)
 product withdrawn (released)...........
------------------------------------------------------------------------
Postmarketing Commitments                            NDA             BLA
                                                  N = 56          N = 32
------------------------------------------------------------------------
Closed PMCs (% of Total Closed PMCs)....  ..............  ..............
Requirement met (fulfilled).............        46 (82%)        27 (84%)
Requirement not met (released and new             1 (2%)          2 (6%)
 revised requirement issued)............
Requirement no longer feasible or drug           9 (16%)          3 (9%)
 product withdrawn (released)...........
------------------------------------------------------------------------
\1\ The table shows data for those PMRs/PMCs that were closed (fulfilled
  or released) within FY2015. Therefore, data for PMRs/PMCs that were
  closed in prior fiscal years are not included.
\2\ Percentages may not total 100 due to rounding.


                         Table 8--Summary of Status of Postmarketing Requirements Established \1\ Between FY2009 and FY2015 \2\
                                                         [Numbers as of September 30, 2015] \3\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                 Fiscal year of PMR establishment
PMR Status as of FY2015 (% of total PMRs ---------------------------------------------------------------------------------------------------------------
       in each establishment year)             2009            2010            2011            2012            2013            2014            2015
--------------------------------------------------------------------------------------------------------------------------------------------------------
Pending.................................         14 (6%)         11 (5%)        27 (10%)        37 (17%)        91 (33%)       186 (68%)       250 (89%)
Ongoing.................................        38 (15%)        40 (18%)        54 (21%)        59 (27%)        79 (28%)        46 (17%)         16 (6%)
Submitted...............................         10 (4%)         16 (7%)         11 (4%)         14 (7%)         11 (4%)          9 (3%)         10 (4%)
Delayed.................................         21 (8%)         18 (8%)         16 (6%)         19 (9%)         22 (8%)          7 (3%)               0
Terminated..............................         1 (<1%)               0               0               0               0               0               0
Released................................        55 (22%)        27 (12%)        56 (22%)        28 (13%)         16 (6%)          7 (3%)          2 (1%)
Fulfilled...............................       109 (44%)       112 (50%)        95 (37%)        58 (27%)        59 (21%)         19 (7%)          2 (1%)
                                         ---------------------------------------------------------------------------------------------------------------
    Total \4\...........................             248             224             259             215             278             274             280
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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 FY2015. 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 FY2009 through FY2014 reflects the data in FDA's databases as of September 30, 2015. As a result of
  data corrections, as well as improvements in ascertainment of 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 (FY2014) Federal Register report.


                          Table 9--Summary of Status of Postmarketing Commitments Established \1\ Between FY2009 and FY2015 \2\
                                                         [Numbers as of September 30, 2015] \3\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                 Fiscal year of PMC establishment
PMC Status as of FY2015 (% of total PMCs ---------------------------------------------------------------------------------------------------------------
       in each establishment year)             2009            2010            2011            2012            2013            2014            2015
--------------------------------------------------------------------------------------------------------------------------------------------------------
Pending.................................          3 (6%)          2 (2%)          3 (4%)          1 (2%)         8 (17%)        35 (57%)        49 (90%)
Ongoing.................................          3 (6%)        18 (19%)        23 (28%)        14 (30%)        15 (33%)        14 (23%)          1 (2%)
Submitted...............................          1 (2%)        11 (12%)          3 (4%)          2 (4%)           4(9%)          2 (3%)          2 (4%)

[[Page 85579]]

 
Delayed.................................         6 (13%)        12 (13%)         8 (10%)         6 (13%)          4 (9%)               0               0
Terminated..............................          1 (2%)               0               0               0               0               0               0
Released................................          4 (8%)          7 (7%)        10 (12%)          1 (2%)          1 (2%)               0          1 (2%)
Fulfilled...............................        30 (63%)        44 (47%)        35 (43%)        22 (48%)        14 (30%)        10 (16%)          1 (2%)
                                         ---------------------------------------------------------------------------------------------------------------
    Total \4\...........................              48              94              82              46              46              61              54
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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 PMCs that were closed (fulfilled or released) as of FY2015. 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 FY2009 through FY2014 reflects the data in FDA's databases as of September 30, 2015. As a result of
  data corrections, as well as improvements in ascertainment of 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 (FY2014) Federal Register report.


    Dated: November 21, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-28442 Filed 11-25-16; 8:45 am]
 BILLING CODE 4164-01-P