[Federal Register: May 21, 2003 (Volume 68, Number 98)]
[Page 27822-27823]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]



Food and Drug Administration

[Docket No. 03N-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 first report on the status of 
the study commitments that sponsors have agreed to conduct and for 
which an annual status report on the study has been received by FDA.

FOR FURTHER INFORMATION CONTACT: Kim Colangelo, Center for Drug 
Evaluation and Research (HFD-20), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-3937; or Robert Yetter, 
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 (section 506B of the act (21 U.S.C. 356b)) requiring 
reports of postmarketing studies for human drugs and biological 
products. Section 506B 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 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 establishing 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 26, 2001. The regulations apply only to human 
drugs, including biological drugs. They do not apply to animal drugs or 
to licensed 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 drugs 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, BLA, or supplement. 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.  
    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: (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:
    [sbull] Pending: The study has not been initiated, but does not 
meet the criterion for delayed;
    [sbull] Ongoing: The study is proceeding according to or ahead of 
the original schedule;
    [sbull] Delayed: The study is behind the original schedule;
    [sbull] Terminated: The study was ended before completion, but a 
final study report has not been submitted to FDA; or
    [sbull] 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

[[Page 27823]]

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://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 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 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, 2002. If a commitment did not have a schedule and 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 To CBER and CDER
                                       (Numbers as of September 30, 2002)
                                                         NDAs/ANDAs (% of total)          BLAs (% of total)
Applicants with open postmarketing commitments                                 126                            44
Number of open postmarketing commitments                                     1,339                           223
Status of open postmarketing commitments              ............................  ............................
  [sbull] Pending                                                        820 (61%)                      67 (30%)
  [sbull] Ongoing                                                        285 (21%)                     102 (46%)
  [sbull] Delayed                                                          25 (2%)                       17 (8%)
  [sbull] Terminated                                                        8 (1%)                        2 (1%)
  [sbull] Submitted                                                      201 (15%)                      35 (16%)
Concluded studies                                                              349                            52
  [sbull] Commitment met                                                 240 (69%)                      47 (90%)
  [sbull] Commitment not met                                                0 (0%)                        1 (2%)
  [sbull] Study no longer needed or feasible                             109 (31%)                        4 (8%)
Open postmarketing commitments with annual report                        289 (22%)                      77 (35%)
 due but not received

    Dated: May 12, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-12720 Filed 5-20-03; 8:45 am]