[Federal Register: March 3, 2006 (Volume 71, Number 42)]
[Page 10978-10979]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]



Food and Drug Administration

Report on the Performance of Drug and Biologics Firms in 
Conducting Postmarketing Commitment Studies; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.


SUMMARY: The Food and Drug Administration (FDA) is required, under the 
Food and Drug Administration Modernization Act of 1997 (Modernization 
Act), to report annually in the Federal Register on the status of 
postmarketing study commitments made by sponsors of approved drug and 
biological products. This is the agency's report on the status of the 
studies sponsors have agreed to or are required to conduct.

FOR FURTHER INFORMATION CONTACT: Beth Duvall-Miller, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, rm. 6466, Silver Spring, MD 20993-0002, 301-
796-0700; or Robert Yetter, Center for Biologics Evaluation and 
Research (HFM-25), Food and Drug Administration, 1400 Rockville Pike, 
Rockville, MD 20852, 301-827-0373.


I. Background

    Section 130(a) of the Modernization Act (Public Law 105-115) 
amended the Federal Food, Drug, and Cosmetic Act (the act) by adding a 
new provision requiring reports of certain postmarketing studies 
(section 506B of the act (21 U.S.C. 356b)) for human drug and 
biological products. Section 506B of the act provides FDA with 
additional authority to monitor the progress of a postmarketing study 
commitment that an applicant has been required or has agreed to conduct 
by requiring the applicant to submit a report annually providing 
information on the status of the postmarketing study commitment. This 
report must also include reasons, if any, for failure to complete the 
    On December 1, 1999 (64 FR 67207), FDA published a proposed rule 
providing a framework for the content and format of the annual progress 
report. The proposed rule also clarified the scope of the reporting 
requirement and the timing for submission of the annual progress 
reports. The final rule, published on October 30, 2000 (65 FR 64607), 
modified annual report requirements for new drug applications (NDAs) 
and abbreviated new drug applications (ANDAs) by revising Sec.  
314.81(b)(2)(vii) (21 CFR 314.81(b)(2)(vii)). The rule also created a 
new annual reporting requirement for biologics license applications 
(BLAs) by establishing Sec.  601.70 (21 CFR 601.70). These regulations 
became effective on April 30, 2001. The regulations apply only to human 
drug and biological products. They do not apply to animal drug or to 
biological products that also meet the definition of a medical device.
    Sections 314.81(b)(2)(vii) and 601.70 apply to postmarketing 
commitments made on or before enactment of the Modernization Act 
(November 21, 1997) as well as those made after that date. Sections 
314.81(b)(2)(vii) and 601.70 require applicants of approved drug and 
biological products to submit annually a report on the status of each 
clinical safety, clinical efficacy, clinical pharmacology, and 
nonclinical toxicology study that is required by FDA (e.g., accelerated 
approval clinical benefit studies) or that they have committed to 
conduct either at the time of approval or after approval of their NDA, 
ANDA, or BLA. The status of other types of postmarketing commitments 
(e.g., those concerning chemistry, manufacturing, production controls, 
and studies 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. It should be noted, however, that 
applicants are required to report to FDA on these commitments made for 
NDAs and ANDAs under Sec.  314.81(b)(2)(viii).
    According to the regulations, once a postmarketing study commitment 
has been made, an applicant must report on the progress of the 
commitment on the anniversary of the product's approval until the 
postmarketing study commitment is completed or terminated, and FDA 
determines that the postmarketing study commitment has been fulfilled 
or that the postmarketing study commitment is

[[Page 10979]]

either no longer feasible or would no longer provide useful 
information. The annual progress report must include a description of 
the postmarketing study commitment, a schedule for completing the study 
commitment, and a characterization of the current status of the study 
commitment. The report must also provide an explanation of the 
postmarketing study commitment's status by describing briefly the 
postmarketing study commitment's progress. A postmarketing study 
commitment schedule is expected to include the actual or projected 
dates for the following: (1) Submission of the study protocol to FDA, 
(2) completion of patient accrual or initiation of an animal study, (3) 
completion of the study, and (4) submission of the final study report 
to FDA. The postmarketing study commitment status must be described in 
the annual report according to the following definitions:
     Pending: The study has not been initiated, but does not 
meet the criterion for delayed;
     Ongoing: The study is proceeding according to or ahead of 
the original schedule;
     Delayed: The study is behind the original schedule;
     Terminated: The study was ended before completion, but a 
final study report has not been submitted to FDA; or
     Submitted: The study has been completed or terminated, and 
a final study report has been submitted to FDA.
    Databases containing information on postmarketing study commitments 
are maintained at the Center for Drug Evaluation and Research (CDER) 
and the Center for Biologics Evaluation and Research (CBER). 
Information in this report covers any postmarketing study commitment 
that was made, in writing, at the time of approval or after approval of 
an application or a supplement to an application, including those 
required (e.g., to demonstrate clinical benefit of a product following 
accelerated approval) and those agreed to with the applicant. 
Information summarized in this report includes: (1) The number of 
applicants with open (uncompleted) postmarketing commitments, (2) the 
number of open postmarketing commitments, (3) the status of open 
postmarketing commitments as reported in Sec.  314.81(b)(2)(vii) or 
Sec.  601.70 annual reports, (4) the status of concluded postmarketing 
studies as determined by FDA, and (5) the number of applications with 
open postmarketing commitments for which sponsors did not submit an 
annual report within 60 days of the anniversary date of U.S. approval.
    Additional information about postmarketing study commitments made 
by sponsors to CDER and CBER are provided on FDA's Web site at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder.
 Like this notice, the site does not list 

postmarketing study commitments containing proprietary information. It 
is FDA policy not to post information on the Web site until it has been 
reviewed for accuracy. The numbers published in this notice cannot be 
compared with the numbers resulting from searches of the Web site. This 
notice incorporates totals for all postmarketing study commitments in 
FDA databases, including those undergoing review for accuracy. The 
report in this notice will be updated annually while the Web site is 
updated quarterly (in January, April, July, and October).

II. Summary of Information From Postmarketing Study Progress Reports

    This report summarizes the status of postmarketing commitments as 
of September 30, 2005. If a commitment did not have a schedule or a 
postmarketing progress report was not received, the commitment is 
categorized according to the most recent information available to the 
    Data in table 1 of this document are numerical summaries generated 
from FDA databases. The data are broken out according to application 
type (NDAs/ANDAs or BLAs).

   Table 1.--Summary of Postmarketing Study Commitments (Numbers as of
                           September 30, 2005)
                                   NDAs/ANDAs (% of      BLAs\1\ (% of
                                        Total)              Total)
Applicants With Open              154                 44
 Postmarketing Commitments
Number of Open Postmarketing      1,231               321
Status of Open Postmarketing      ..................  ..................
 Pending                  797 (65%)           118 (37%)
 Ongoing                  231 (19%)           94 (29%)
 Delayed                  28 (2%)             53 (17%)
 Terminated               3 (<1%)             0
 Submitted                172 (14%)           56 (17%)
Concluded Studies (October 1,     156                 56
 2004 Through September 30,
 Commitment Met           136 (87%)           41 (73%)
 Commitment Not Met       5 (3%)              0
 Study No Longer Needed   15 (10%)            15 (27%)
 or Feasible
Applications With Open            170 (47%)\2\        37 (50%)
 Postmarketing Commitments With
 Annual Reports Due, but Not
 Submitted Within 60 Days of the
 Anniversary Date of U.S.
\1\ On October 1, 2003, FDA completed a consolidation of certain
  products formerly regulated by the CBER into the CDER. The previous
  association of BLA reviews only with CBER is no longer valid; BLAs are
  now received by both CBER and CDER. Fiscal year (FY) statistics for
  CDER BLA postmarketing study commitments will continue to be counted
  under BLA totals in this table.
\2\ The search strategy was improved for the FY 2005 report and may
  explain, in part, the increased number of applications categorized as
  having overdue annual reports. Note that this statistic counts all
  annual reports submitted more than 60 days after the anniversary date
  of U.S. approval as overdue, including reports that may have been
  submitted on a modified reporting schedule in accordance with prior
  FDA agreement. Of the applications categorized as having overdue
  annual reports using this definition, annual reports were subsequently
  submitted in FY 2005 for 170/170 (100 percent) of NDAs/ANDAs and 19/37
  (51 percent) of BLAs.

    Dated: February 23, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-3019 Filed 3-2-06; 8:45 am]