[Federal Register Volume 73, Number 80 (Thursday, April 24, 2008)]
[Pages 22157-22159]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-9007]



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 applicants of approved drug and 
biological products. This is the agency's report on the status of the 
studies applicants have agreed to or are required to conduct.

Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, rm. 6464, 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 
commitment. 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.
    On September 27, 2007, the President signed Public Law 110-85, the 
Food and Drug Administration Amendments Act of 2007 (FDAAA). Section 
901, in Title IX of FDAAA, creates a new section 505(o) of the act 
authorizing FDA to require certain studies and clinical trials for 
prescription drugs and biological products approved under section 505 
of the act or section 351 of the Public Health Service Act. This new 
authority became effective on March 25, 2008. FDA is considering how 
this new authority will be integrated with postmarketing commitments. 
FDA expects that next year's report will reflect this integration.
    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

[[Page 22158]]

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 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 subject 
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 (i.e., no 
subjects have been enrolled or animals dosed), but does not meet the 
criterion for delayed (i.e., the original projected date for initiation 
of subject accrual or initiation of animal dosing has not passed);
     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;
     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 applicants 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 applicants to CDER and CBER is provided on FDA's Web site at http://www.fda.gov/cder/pmc. 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, 2007. 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 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, 2007)
                                                                            NDAs/ANDAs  (% of    BLAs\1\  (% of
                                                                                  Total)             Total)
Applicants with open postmarketing commitments                                            136                 54
Number of open postmarketing commitments                                                1,281                401
Status of open postmarketing commitments
     Pending                                                                911 (71%)          133 (33%)
          Postmarketing commitment created within the last year (FY07)              165 (18%)           41 (31%)
          Postmarketing commitment created within the past 2 years (FY06            361 (40%)           99 (74%)
           and FY07)
          Postmarketing commitment created within the past 3 years (FY05,           489 (54%)          111 (83%)
           FY06, and FY07)
     Ongoing                                                                173 (14%)           98 (24%)
     Delayed                                                                  39 (3%)           86 (22%)

[[Page 22159]]

     Terminated                                                              1 (0.1%)             3 (1%)
     Submitted                                                              157 (12%)           81 (20%)
Concluded studies                                                                         133                 26
(October 1, 2006--September 30, 2007)
     Commitment met                                                         101 (76%)           21 (81%)
     Commitment not met                                                       1 (<1%)                  0
     Study no longer needed or feasible                                      31 (23%)            5 (19%)
Applications with open postmarketing commitments with annual reports due,        115 (37%)\2\           41 (51%)
 but not submitted within 60 days of the anniversary date of U.S. approval
\1\ On October 1, 2003, FDA completed a consolidation of certain products formerly regulated by CBER into 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 statistics for CDER BLA postmarketing study commitments will continue to be counted
  under BLA totals in this table.
\2\ 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 FY06 for 115/115 (100 percent) of NDAs/ANDAs
  and 20/41 (49 percent) of BLAs.

    Dated: April 15, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-9007 Filed 4-23-08; 8:45 am]