[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]


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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.

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.
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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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    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.
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    \2\ 21 CFR 314.600 for drugs; 21 CFR 601.90 for biological 
products.
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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.
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    \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

    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\
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    \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.''
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     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\
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    \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.
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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.\7\
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    \7\ 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 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.
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    \8\ 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.\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).
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    \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.
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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, 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.
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    \11\ https://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) 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\
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    \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.
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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; \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.
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    \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.
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    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]
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                                                                                                 Total (NDA and
                                                                    NDA \1\         BLA \2\           BLA)
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Number of unique applicants with open PMRs/PMCs...............             207              78               285
Number of applications with open PMRs/PMCs....................             734             156               890
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\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.
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    \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\
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                                                         Received, on time   Received, not on   Expected but not
                                          \2\ Expected       \3\ (% of        time \4\ (% of     received (% of
                                                             expected)          expected)          expected)
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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%)
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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.
\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\
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                                                                     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)
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On-schedule.........................................                882 (84%)                247 (91%)                123 (71%)                159 (83%)
Off-schedule........................................                169 (16%)                  25 (9%)                 51 (29%)                 32 (17%)
                                                     ---------------------------------------------------------------------------------------------------

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    Total...........................................                    1,051                      272                      174                      191
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\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\
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                                                                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%)
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\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.
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    \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\
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                                                   NDA N = 1,051 (% of open NDA     BLA N = 272 (% of open BLA
                                                               PMRs)                           PMRs)
         Reporting authority/PMR status          ---------------------------------------------------------------
                                                      Delayed       Terminated        Delayed       Terminated
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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%)
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\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\
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                                    NDA N = 174 (%      BLA N = 191 (%
                                      open PMCs)          open PMCs)
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On-Schedule:
    Pending.....................            62 (36%)            52 (27%)
    Ongoing.....................            40 (23%)            83 (43%)
    Submitted...................            21 (12%)            24 (13%)
                                 ---------------------------------------
        Total...................           123 (71%)           159 (83%)
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Off-Schedule:
    Delayed.....................            50 (29%)            30 (16%)
    Terminated..................              1 (1%)              2 (1%)
                                 ---------------------------------------
        Total...................            51 (29%)            32 (17%)
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\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
--------------------------------------------------------------------------------------------------------------------------------------------------------
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%)
                                                              ------------------------------------------------------------------------------------------
    Total \4\................................................           94           80           41           46           56           63           60
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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


