[Federal Register: March 15, 2004 (Volume 69, Number 50)]
[Page 12162-12164]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]



Food and Drug Administration

[Docket No. 2003N-0170]

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.

    Beth Duvall-Miller, Food and Drug Administration, Center for Drug 
Evaluation and Research (HFD-20), 5600 Fishers Lane, Rockville, MD 
20857, 301-594-3937; or
    Robert Yetter, Food and Drug Administration, Center for Biologics 
Evaluation and Research (HFM-25), 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 (NDA) and 
abbreviated new drug applications (ANDA) 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 
(BLA) 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).

[[Page 12163]]

    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 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 
     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 open postmarketing 
commitments for which FDA did not receive an annual report.
    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 information currently available on the Web 
site includes only postmarketing study commitments made since January 
1, 1991. 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 the FDA 
databases, including those made prior to 1991 as well as those 
undergoing review for accuracy. The report in this notice will be 
updated annually while the Web site will be updated quarterly (in 
April, July, October, and January).

II. Summary of Information From Postmarketing Study Progress Reports

    This report summarizes the status of postmarketing commitments as 
of September 30, 2003. 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, 2003)
                         NDAs/ANDAs (% of Total)     BLAs (% of Total)
Applicants with open     122                      48
Number of open           1,338                    278
Status of open           .......................  ......................
       864 (65%)                69 (25%)
       268 (20%)                108 (39%)
       21 (2%)                  32 (12%)
       5 (0.4%)                 5 (2%)
       180 (13%)                64 (23%)
Concluded studies        79                       69
 (October 1, 2002,
 through September 30,
       74 (94%)                 62 (90%)
 Commitment met
       0 (0%)                   1 (1%)
 Commitment not met
       5 (6%)                   6 (9%)
 Study no longer needed
 or feasible
Open postmarketing       22 (6%)                  35 (17%)
 commitments with
 annual report due but
 not received

[[Page 12164]]

    Dated: March 3, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-5757 Filed 3-12-04; 8:45 am]