[Printable PDF]
[Federal Register: December 1, 1999 (Volume 64, Number 230)]
[Proposed Rules]
[Page 67207-67216]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr01de99-24]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 314 and 601
[Docket No. 99N-1852]
RIN 0910-AB83
Postmarketing Studies for Human Drugs and Licensed Biological
Products; Status Reports
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to revise
the status reports section of the postmarketing annual reporting
requirements for drug and biological products, and to require
applicants to submit annual status reports for certain postmarketing
studies of licensed biological products. This proposed rule would
describe the types of postmarketing studies covered by these status
reports, the information to be included in the reports, and the type of
information that FDA would consider appropriate for public disclosure.
The agency is taking this action to implement section 130 of the Food
and Drug Administration Modernization Act of 1997 (FDAMA).
DATES: Submit written comments on the proposed rule by February 14,
2000. Submit written comments on the information collection provisions
by January 3, 2000.
ADDRESSES: Submit written comments to the Dockets Management Branch
[[Page 67208]]
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. Submit written comments on the information
collection provisions to the Office of Information and Regulatory
Affairs, Office of Management and Budget (OMB), New Executive Office
Bldg., 725 17th St. NW., Washington, DC 20503, Attn: Wendy Taylor, Desk
Officer for FDA.
FOR FURTHER INFORMATION CONTACT:
Paula S. McKeever, Center for Biologics Evaluation and Research
(HFM-17), Food and Drug Administration, 1401 Rockville Pike, suite
200N, Rockville, MD 20852-1448, 301-827-6344; or
Audrey A. Thomas, Center for Drug Evaluation and Research (HFD-7),
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857,
301-594-5625.
SUPPLEMENTARY INFORMATION:
I. Introduction
On November 21, 1997, the President signed the FDAMA into law
(Public Law 105-115). Section 130(a) of the FDAMA amended the Federal
Food, Drug, and Cosmetic Act (the act) by adding a new provision on
reports of postmarketing studies) (section 506B of the act (21 U.S.C.
356b)). Section 506B of the act provides FDA with additional authority
for monitoring the progress of postmarketing studies that companies
have made a commitment to conduct and also requires the agency to make
information that pertains to the status of these studies publicly
available.
Under section 506B(a) of the act, applicants that have committed to
conduct a postmarketing study for a drug or biological product that is
approved for marketing must submit to FDA a report on the progress of
the study or the reasons for the failure of the applicant to conduct
the study. This provision directs FDA to issue regulations that
prescribe the content of these reports.
Section 506B(a) of the act also states that these reports must be
submitted to FDA within 1 year after the approval of the product and
annually thereafter until the study is completed or terminated. This
provision applies to commitments for postmarketing studies that were
made on or after enactment of FDAMA, as well as those made prior to
enactment of FDAMA. For commitments made prior to enactment of FDAMA,
the act requires that an initial report be submitted to FDA within 6
months after the date of issuance of the final rule implementing
section 506B of the act. Section 506B(b) of the act specifies which
information in a status report may be considered public information.
Under section 506B(b) of the act, FDA may publicly disclose any
information pertaining to a status report under section 506B(a) to the
extent that the information is necessary to identify the applicant, or
to establish the status of a study and the reasons, if any, for failure
to conduct, complete, and report the study.
Section 506B(c) of the act directs FDA to develop and publish
annually in the Federal Register a report concerning this activity.
This report must provide information on the status of postmarketing
studies that applicants have committed to conduct under this provision
and for which reports have been submitted.
FDAMA also directs FDA, under section 130(b), to submit a specific
report to Congress by October 1, 2001. This report must contain a
summary of the status reports submitted under section 506B of the act,
an evaluation of the performance of applicants in fulfilling their
commitments to conduct postmarketing studies under this provision and
of FDA's timeliness in reviewing these postmarketing studies, and any
legislative recommendations regarding postmarketing studies.
Under the agency's existing postmarketing reporting regulations for
human drug products, at Sec. 314.81(b)(2) (21 CFR 314.81(b)(2)), each
applicant holding an approved new drug application (NDA) or abbreviated
new drug application (ANDA) must submit an annual report to FDA for the
drug product. This annual report is required to contain, among other
information, a section on status reports that includes a statement on
the current status of any postmarketing studies of the drug product
performed by, or on behalf of, the applicant (Sec. 314.81(b)(2)(vii)).
This section also permits applicants to include a list of any open
regulatory business with FDA concerning the drug product. In the
Federal Register of December 2, 1998 (63 FR 66632), FDA issued a final
rule amending these postmarketing reporting regulations to require that
annual reports contain, among other information, specific information
about the status of postmarketing clinical studies in pediatric
populations. In this proposed rule, FDA is proposing to amend these
regulations, including the new provisions issued in the final rule of
December 2, 1998, to implement the requirements of section 506B of the
act for human drug products. In a separate rulemaking, FDA plans to
propose additional amendments to the annual report requirements
pertaining to the nonclinical laboratory studies and clinical data
sections of the annual report. However, these amendments are beyond the
scope of this proposed rule.
Each applicant holding a biologics license application (BLA) must
submit an annual report to FDA describing any minor changes that may
relate to the safety or effectiveness of the product (Sec. 601.12(d)
(21 CFR 601.12(d)) and must also submit a separate annual report, in
accordance with the final rule of December 2, 1998 (63 FR 66632),
regarding postmarketing pediatric studies (Sec. 601.37 (21 CFR
601.37)). In this proposed rule, FDA is proposing to amend the
biologics regulations at part 601 (21 CFR part 601) by revising the
postmarketing annual reporting requirement at Sec. 601.37 and by adding
a new postmarketing annual reporting requirement, Sec. 601.70, to
implement the requirements of section 506B of the act for licensed
biological products. Proposed Sec. 601.70 would only apply to licensed
biological products that meet the definition of ``drug'' under the act;
it would not apply to biological products that also meet the definition
of ``medical device'' under the act, since section 506B does not cover
medical devices.
This proposed rule would only apply to human drug and biological
products; it would not apply to animal drug products. FDA intends to
amend its regulations to implement section 506B of the act for animal
drug products in a separate rulemaking.
In May 1996, the Office of Inspector General of the Department of
Health and Human Services issued a report regarding FDA's oversight of
postmarketing study commitments for prescription drugs (Ref. 1). This
study found that the number of postmarketing study commitments was
increasing and that the agency did not have formal standards or
procedures for monitoring postmarketing studies or for establishing
whether a postmarketing study commitment had been met. At the same
time, FDA was developing formal procedures for tracking the progress of
postmarketing study commitments, an effort that began in February 1995
when the agency recognized the need for such procedures. These
procedures were implemented in October 1996. The proposed revisions to
the human drug and biologics regulations in this rule will facilitate
FDA's current system for tracking postmarketing study commitments.
In addition to the regulatory changes proposed in this rule, FDA
will issue guidance regarding section 506B of the act. This guidance
will describe in greater detail the type of information
[[Page 67209]]
that applicants should submit to the agency in a status report for a
postmarketing study of an approved drug or licensed biological product,
the implementation schedule for submission of these status reports to
the agency, how FDA will track information obtained for postmarketing
studies, and the schedule for FDA review of status reports and final
study reports for postmarketing studies. In accordance with the
agency's Good Guidance Practices (62 FR 8961, February 27, 1997), FDA
will make the guidance available in draft form for public comment
before issuing a final guidance. FDA is also in the process of
reviewing and revising, as necessary, its internal operating procedures
related to tracking commitments made for the conduct of postmarketing
studies under this provision for approved drug and licensed biological
products.
II. Description of the Proposed Rule
A. Introduction
The proposed rule would amend the postmarketing annual reporting
requirements for human drug products under Sec. 314.81(b)(2) by
reorganizing the status reports section, at Sec. 314.81(b)(2)(vii), to
require that the information contained in this section be provided to
FDA in a different format. FDA is proposing that this information be
included in the annual report in three different sections. One section
would contain, as described below (see section II.B of this document),
status reports for those postmarketing studies of the drug product
(i.e., clinical safety, clinical efficacy, clinical pharmacology and
nonclinical toxicology) that are required by FDA (e.g., pediatric
studies) or that an applicant has committed, in writing, to conduct
either at the time of approval of an application or a supplement to an
application, or after approval of an application or a supplement
consistent with section 506B of the act (proposed
Sec. 314.81(b)(2)(vii)). This section would also include, for pediatric
studies, a statement that indicates whether postmarketing clinical
studies in pediatric populations were required by FDA under Sec. 201.23
(21 CFR 201.23). Another section would contain status reports for any
other postmarketing studies of the drug product (proposed
Sec. 314.81(b)(2)(viii)) (e.g., chemistry, manufacturing, and controls,
stability of the product), and the third section would contain, at the
applicant's discretion, a list of any open regulatory business with FDA
concerning the drug product (proposed Sec. 314.81(b)(2)(ix)). FDA would
use the information provided under proposed Sec. 314.81(b)(2)(vii) to
meet its reporting obligations under section 506B of the act (annual
report in the Federal Register) and section 130(b) of FDAMA (report to
congressional committees by October 1, 2001). FDA does not intend to
use information provided under proposed Sec. 314.81(b)(2)(viii) for
this purpose. This proposed change in the structure of the annual
report would facilitate FDA's preparation of its annual reports and its
report to Congress without imposing a new reporting burden on
applicants with approved NDA's and ANDA's because these applicants are
currently required to report such information to FDA.
The proposed rule would also create a new subpart G under part 601
entitled ``Postmarketing Studies'' and a new Sec. 601.70 under subpart
G. Proposed Sec. 601.70 would require, as described in section II.B of
this document, annual reports of the status of postmarketing studies
for licensed biological products (i.e., clinical safety, clinical
efficacy, clinical pharmacology, and nonclinical toxicology) that are
required by FDA (e.g., pediatric studies) or that an applicant has
committed, in writing, to conduct either at the time of approval of an
application or a supplement to an application, or after approval of an
application or a supplement. Proposed Sec. 601.37(c) would require that
the status of postmarketing pediatric studies that are covered under
proposed Sec. 601.70 be reported to FDA under proposed Sec. 601.70
rather than under Sec. 601.37. FDA notes that biological products
previously approved under the product license application and
establishment license application process are included wherever BLA,
the new form of application for biological products, is used in this
preamble.
B. Scope of Proposed Rule
Postmarketing studies for marketed human drug and licensed
biological products are conducted for a variety of purposes (e.g., new
indication, safety, medication errors, pharmacokinetics, pharmacology,
chemistry, marketing, stability, use in special populations such as
children). Some of these postmarketing studies are conducted by an
applicant on its own initiative. Other postmarketing studies are
required by FDA to be conducted by applicants such as assessing the
safety and effectiveness of new drugs and biologics in pediatric
patients (Sec. 314.55 (21 CFR 314.55) and Sec. 601.27. Others result
from an applicant's commitment, in writing, to the agency to conduct
the study at the time of approval of an application (e.g, an NDA, ANDA,
BLA, or supplement), after approval of an application (e.g., as a
result of suspected adverse drug reaction reports), as a condition of
accelerated approval of new drugs and biological products for serious
or life-threatening illnesses (subpart H of part 314 (21 CFR part 314),
and subpart E of part 601 respectively), or as a deferred submission of
pediatric studies (Secs. 314.55(b) and 601.27(b)). Studies that
applicants commit to conduct at the time of approval of an application
are usually intended to address concerns about the risks, benefits, or
optimal use of a drug or biological product that do not warrant
delaying approval of the application.
This proposed rule would define postmarketing studies for which
status reports must be submitted under section 506B of the act as those
that concern clinical safety, clinical efficacy, clinical pharmacology
or nonclinical toxicology studies and that are required by FDA (e.g.,
pediatric studies) or that are committed to, in writing, either at the
time of approval of an application or a supplement or after approval of
an application or supplement. FDA is proposing to include clinical
studies such as safety, efficacy, and pharmacology studies within the
scope of this rule because these types of studies provide the most
relevant and useful additional information about the risks, benefits,
and optimal use to patients and consumers of an approved drug or
licensed biological product. In addition, FDA is proposing to include
nonclinical toxicology studies within the scope of this rule, although
such studies typically cannot be performed on human subjects, because
they are very useful to further evaluate the safety of a marketed drug
or biological product.
For the purpose of this rule, clinical safety and clinical efficacy
studies would include human epidemiological studies. Examples of
clinical pharmacology studies are pharmacokinetic and pharmacodynamic
studies. For all of the postmarketing studies described previously,
Secs. 314.81(b)(2)(vii) and 601.70 would require applicants to provide
status reports to FDA regarding the progress of such studies.
Postmarketing studies designed to evaluate other types of issues
such as manufacturing and control issues (e.g., stability of the
product, development of new tests or specifications) and medication
errors (e.g., attributable to the labels, labeling and/or packaging of
the product) would be reported for drug products, as described below,
under proposed Sec. 314.81(b)(2)(viii) rather than under proposed
Sec. 314.81(b)(2)(vii), and
[[Page 67210]]
would not be required to be reported under Sec. 601.70 for licensed
biological products.
This proposed rule would require, as stated previously, status
reports, under proposed Secs. 314.81(b)(2)(vii) and 601.70, for
postmarketing studies that either are required by FDA (e.g., pediatric
studies) or that applicants commit, in writing, to conduct either at
the time of approval of an application or a supplement to an
application, or after approval of an application or a supplement.
Under proposed Sec. 314.81(b)(2)(viii), applicants with approved
NDA's and ANDA's would be required to provide status reports for any
postmarketing study not reported under proposed Sec. 314.81(b)(2)(vii)
(e.g., chemistry, manufacturing, and controls, stability of the
product, medication errors). These would include postmarketing studies
performed by, or on behalf of, the applicant, whether or not the
studies are required or subject to commitments. Proposed
Sec. 314.81(b)(2)(viii) does not represent a new reporting burden for
applicants with approved NDA's or ANDA's because these applicants are
currently required to provide status reports for these studies in their
postmarketing annual reports. FDA is not proposing a similar reporting
requirement for postmarketing studies of licensed biological products
in this proposed rule. Applicants with licensed biological products may
voluntarily submit status reports to FDA for postmarketing studies that
are not required to be reported under proposed Sec. 601.70.
The agency is committed to harmonizing its reporting requirements
for drugs and biologics as much as possible. Section 123(f) of FDAMA
requires FDA to take measures to minimize differences in the review and
approval of products required to have approved BLA's under section 351
of the Public Health Service Act (42 U.S.C. 262) and products required
to have approved NDA's under section 505(b)(1) of the act (21 U.S.C.
355(b)(1)). At the present time, FDA is considering whether to amend
its biologics regulations in a separate rulemaking to require the
submission of information in postmarketing annual reports currently
submitted to the agency by applicants with approved NDA's and ANDA's
under Sec. 314.81(b)(2)(i) through (b)(2)(vi). FDA requests comment on
whether the postmarketing annual report for licensed biological
products under Sec. 601.12(d), (changes to an approved application),
Sec. 601.37 (annual reports of postmarketing pediatric studies), and
proposed Sec. 601.70 should be combined into a single annual report and
whether such a report should include additional information as required
in Sec. 314.81(b)(2)(i) through (b)(2)(vi). However, FDA has determined
that requiring such additional information is beyond the scope of this
proposed rulemaking and that it is appropriate, at this time, to
harmonize only the drugs and biologics postmarketing annual reporting
requirements as they relate to section 506B of the act.
C. Content of Status Reports
Current regulations (Sec. 314.81(b)(2)(vii)) do not prescribe the
content of status reports of postmarketing studies. In this proposed
rule, FDA is proposing to set forth the format and content of these
reports, as described in section 506B of the act, which requires
sufficient information to identify the applicant of the postmarketing
study, the specific study being conducted, the status of the study, and
the reasons, if any, for the applicant's failure to complete the study.
Under proposed Sec. 314.81(b)(2)(vii) and (b)(2)(viii) and
Sec. 601.70(b), a status report for a postmarketing study would be
required to contain the following information:
1. Applicant's name.
2. Product name. This would include the approved product's
established/proper name and proprietary name, if applicable.
3. NDA number, ANDA number, BLA/reference number, or supplement
number of the approved product.
4. Date of product's U.S. approval.
5. Date of postmarketing study commitment. This date would be the
same as the date of the product's U.S. approval for commitments made,
in writing, at the time of U.S. approval of an application; would be
the date of U.S. approval of the supplement for commitments made, in
writing, at the time of U.S. approval of a supplement; and would be the
date of written commitment for commitments made after U.S. approval of
an application or supplement.
6. Description of postmarketing study commitment. For clinical
studies, this section would include the purpose of the postmarketing
study, the patient population addressed by the study, the number of
patients and/or subjects to be included in the study, and the
indication and dosage(s) that are to be studied. For nonclinical
studies, this section would include the type and purpose of the study
(e.g., carcinogenicity study to determine effects of chronic dosing).
7. Schedule for conduct, completion, and reporting of the
postmarketing study commitment. This section would include projected
dates for initiation of the different phases of the study, for
completion of the study, and for submission of the final study report
to FDA. This schedule should reflect a reasonable, but aggressive
timetable for completing the postmarketing study commitment. Although
some delays in a study may be unanticipated, it is expected that
studies would progress as originally scheduled. If the original
schedule is revised under section 9 of this status report, the revised
schedule would also be reported in this section (i.e., section 7) in
the next report with a note indicating that the schedule has been
revised as reported in the previous status report.
8. Current status of the postmarketing study commitment. Applicants
would categorize the status of each postmarketing study using one of
the following terms that describe the study's status on the U.S.
anniversary date of approval of the application or other agreed upon
date:
a. Pending. The study has not been initiated (i.e., first patient
has not been enrolled).
b. Ongoing. The study is proceeding according to or ahead of the
original schedule described in section 7 of the status report. If a
study has been completed but the final study report has not been
submitted to FDA, the date the study was completed would be provided.
c. Delayed. The study is proceeding but is behind the original
schedule described in section 7 of the status report. The original
schedule would serve as the basis for defining a study as ``delayed,''
even if a revised schedule is provided.
d. Terminated. The study was ended before completion.
e. Submitted. The study has been completed (i.e., last patient
finished the protocol) or terminated and a final study report has been
submitted to FDA. This category would include the date the final study
report was submitted to FDA.
9. Explanation of the study's status. This section would include a
brief description of the status of the study, including the number of
patients and/or subjects enrolled to date and an explanation of the
study's status identified under section 8 of the status report (e.g.,
delayed due to difficulty in patient accrual, terminated because study
would no longer provide useful information, terminated because study is
no longer feasible, terminated because of adverse events or other
safety issues associated with the use of the product). This section
would also include a
[[Page 67211]]
revised schedule, as well as the reason(s) for the revision, if the
schedule under section 7 of the status report has changed since the
last annual report. This revised schedule would be included, as noted
previously, under section 7 of the next report.
FDA believes that the information proposed to be required in status
reports would provide the agency with sufficient data for review of the
progress of ongoing postmarketing studies under this section. These
reports would also provide FDA with sufficient information to meet the
agency's reporting obligations under section 130 of FDAMA (i.e., annual
report in the Federal Register on the status of postmarketing studies,
report to congressional committees by October 1, 2001).
D. Log of Outstanding Regulatory Business
Current regulations (Sec. 314.81(b)(2)(vii)), as noted previously
(see section I of this document), permit applicants with approved NDA's
and ANDA's to include in the status reports section of annual reports a
list of any open regulatory business with FDA concerning the drug
product that is the subject of the annual report. FDA would continue to
permit applicants to submit such information in annual reports under
proposed Sec. 314.81(b)(2)(ix). For clarification, FDA is proposing to
provide examples of the types of open regulatory business that would be
reported under proposed Sec. 314.81(b)(2)(ix). These would include a
list of the applicant's unanswered correspondence with the agency and a
list of the agency's unanswered correspondence with the applicant.
Proposed Sec. 601.70 does not contain a similar provision for
outstanding regulatory business. However, as noted previously (see
section II.B of this document), FDA is considering a separate
rulemaking that would require the same postmarketing annual reporting
requirements for drugs and biologics.
E. Report Submission Requirements
Current regulations at Sec. 314.81(b), require applicants with
approved drug products to submit two copies of an annual report to FDA.
Under Sec. 314.81(b)(2), these annual reports are required to be
submitted within 60 days of the anniversary date of U.S. approval of
the application to the FDA division responsible for reviewing the
application and these reports. Each annual report is required to be
accompanied by a completed transmittal Form FDA-2252 (Transmittal of
Periodic Reports for Drugs for Human Use) that includes all the
information required under Sec. 314.81(b)(2) that the applicant
received or otherwise obtained during the annual reporting interval,
which ends on the U.S. anniversary date. FDA is proposing to amend
these regulations by replacing the phrase ``Periodic Reports'' with the
phrase ``Annual Reports'' to correct an error and by making other minor
changes to provide clarity.
Currently, applicants with licensed biological products must submit
reports, under Sec. 601.12(d), describing certain minor changes to an
approved BLA, and under Sec. 601.37, providing information on
postmarketing pediatric studies, each year within 60 days of the
anniversary date of approval of the application. Proposed
Sec. 601.70(c) and (d) would require applicants with licensed
biological products to submit a separate annual report to FDA
describing the status of certain postmarketing studies using submission
requirements similar to those required for drugs under
Sec. 314.81(b)(2) and for licensed biologics under Secs. 601.12(d) and
601.37. Applicants with licensed biological products would submit two
copies of an annual progress report to FDA within 60 days of the
anniversary date of the U.S. approval of the application for the
product. Each annual progress report would be accompanied by a
completed transmittal Form FDA-2252 that includes all the information
required under proposed Sec. 601.70 that the applicant received or
otherwise obtained during the annual reporting interval, which ends on
the U.S. anniversary date. These annual progress reports would be
submitted for all postmarketing studies of a licensed biological
product covered under the scope of this proposed rule including those
that are required by FDA (e.g., pediatric studies) and those that an
applicant committed, in writing, to conduct on or after the effective
date of any final rule that may issue based on this proposed rule and
prior to the effective date.
For drugs and biologics with approved NDA's, ANDA's, and BLA's, FDA
intends, as noted previously (see section II.A of this document), to
fulfill its annual reporting requirement mandated by section 506B(c) of
the act by publishing in the Federal Register, the status of
postmarketing study commitments reported under proposed
Secs. 314.81(b)(2)(vii) and 601.70. Furthermore, FDA will post
additional information on the agency's web page (see section G.2 of
this document). This additional information will include an applicant's
failure to submit a status report under proposed
Secs. 314.81(b)(2)(vii) and 601.70 for any postmarketing study
commitment that the agency has formally tracked (i.e., commitments
included in agency databases which were made, in writing, at the time
of approval or after approval of an application or a supplement to an
application, and commitments made as a condition of accelerated
approval, or required studies for assessing the safety and
effectiveness of drugs and biologics in pediatric patients).
A status report under proposed Secs. 314.81(b)(2)(vii) and 601.70
would be submitted to FDA until the agency notifies the applicant, in
writing, that the study commitment has been fulfilled or acknowledges
that the study is either no longer feasible or would no longer provide
useful information. Applicants may indicate in their status report that
a study has been terminated because it is either no longer feasible or
would no longer provide useful information. However, these applicants
would be required to submit a final study report to FDA and continue to
submit status reports for the study until the agency evaluates the
final study report and concurs, in writing, with the applicant's
determination. To expedite the process, FDA encourages applicants to
submit a final study report to the agency as soon as they have
determined that a postmarketing study commitment is to be terminated.
F. Public Disclosure of Information
Section 506B(b) of the act requires FDA to publicly disclose any
information pertaining to a status report described in section 506B(a)
of the act to the extent that such information is necessary to: (1)
Identify the sponsor or (2) establish the status of the postmarketing
study and the reasons, if any, for any failure to carry out the study.
Therefore, FDA is proposing to state in the rule its authority to
disclose any information contained within or relating to postmarketing
studies under proposed Sec. 314.81(b)(2)(vii) or proposed Sec. 601.70,
if the information is necessary to establish the identity of the
applicant or the status of the study, including the reasons, if any,
for the applicant's failure to conduct, complete, and report the study.
However, FDA would not disclose trade secrets as defined in 21 CFR
20.61(a) or information described in 21 CFR 20.63, the disclosure of
which would constitute an unwarranted invasion of personal privacy.
Information necessary to establish the status of a postmarketing study
would include the study protocol, patient accrual rates, reports of
unexpected (i.e., unlabeled) suspected adverse drug
[[Page 67212]]
reactions, and study results. Some of these types of information such
as study protocols for certain postmarketing studies and adverse event
reports for certain postmarketing studies are currently publicly
available. Section 130(b) of FDAMA provides FDA with statutory
authority to disclose data and information, including certain
information that may be considered to constitute confidential
commercial information. Section 130(b) of FDAMA constitutes
authorization by law for the purposes of 18 U.S.C. 1905 to disclose
certain information that could otherwise be considered nondisclosable
confidential commercial information.
G. Proposed Implementation Scheme
1. Effective Dates
FDA proposes that any final rule that may issue based on this
proposed rule become effective 90 days after its date of publication in
the Federal Register. Applicants with approved applications for human
drug and licensed biological products (that are not medical devices)
would be subject to the annual reporting requirements in this proposed
rule. In addition, applicants that have entered into a commitment prior
to November 21, 1997, to conduct a postmarketing study described under
proposed Sec. 314.81(b)(2)(vii) or proposed Sec. 601.70 would be
required, as mandated by FDAMA, to submit an initial report to FDA
within 6 months after the effective date of any final rule that may
issue based on this proposed rule. Thus, in some cases, an applicant
would be required to submit two reports to FDA in the first year after
the effective date of the final rule (i.e., an initial report
containing only information required under proposed
Sec. 314.80(b)(2)(vii) or proposed Sec. 601.70 due within 6 months
after the effective date and a complete annual report based on the
product's anniversary date of U.S. approval due in the 7th to 12th
month after the effective date). After the first year, applicants would
only be required to submit one annual report to FDA each year.
This proposed rule does not affect the existing reporting
requirements issued in the final rule of December 2, 1998 (63 FR
66632). Any changes to the provisions in the final rule of December 2,
1998, that are proposed in this rule would be in effect on the
effective date of any final rule that may issue based on this proposed
rule.
2. Annual Federal Register Report
Consistent with section 506B(c) of the act, FDA will publish
annually a report in the Federal Register. This report will provide a
brief summary of the status of postmarketing study commitments for
approved drugs and licensed biological products that applicants have
submitted to FDA under proposed Secs. 314.81(b)(2)(vii) and 601.70. The
report will include the number of pending, ongoing, delayed, and
terminated postmarketing study commitments, as well as the number of
final study reports that have been submitted to FDA, the number of
study commitments that FDA has deemed fulfilled, and the number of
applicants that failed to submit a status report to the agency for
unfulfilled postmarketing study commitments. Detailed information
regarding the status of these postmarketing studies will be posted on
FDA's web page at ``http://www.fda.gov''. The web site will contain, at
a minimum, the following information for each postmarketing study
commitment: Name of the applicant, application number, product name,
dosage form, product use category, type of study, commitment
description, commitment date, projected study completion date, current
status of commitment, applicant summary of status, annual report due
date, and date annual report received.
III. Request for Comments
Interested persons may, on or before February 14, 2000, submit to
the Dockets Management Branch (address above) written comments
regarding this proposal. Two copies of any comments are to be
submitted; except that individuals may submit one copy. Comments are to
be identified with the docket number found in brackets in the heading
of this document. Received comments may be seen in the office above
between 9 a.m. and 4 p.m., Monday through Friday.
IV. Environmental Impact
The agency has determined under 21 CFR 25.30(h) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
V. Analysis of Impacts
FDA has examined the impact of this proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612).
Executive Order 12866 directs agencies to assess all costs and benefits
of available regulatory alternatives and, when regulation is necessary,
to select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). Under the Regulatory
Flexibility Act, if a rule would have a significant economic impact on
a substantial number of small entities, the agency must analyze
regulatory options that would minimize any significant impact of the
rule on small entities. Title II of the Unfunded Mandates Reform Act (2
U.S.C. 1501 et seq.) requires that agencies prepare a written statement
and economic analysis before proposing any rule that may result in an
expenditure by State, local, and tribal governments, in the aggregate,
or by the private sector of $100 million (adjusted annually for
inflation) in any 1 year.
The agency believes that this rule is consistent with the
principles set out in the Executive Order and in these two statutes.
OMB has determined that the proposed rule is a significant regulatory
action as defined by the Executive Order and so is subject to review.
The rule would require applicants that have committed, in writing, to
conduct a postmarketing study for an approved drug or biologic product
to submit annual reports on the progress of the study or on the reasons
for the failure of the applicant to conduct, complete, and report the
study. The rule would permit FDA to publicly disclose information
concerning these postmarketing studies, thereby providing patients,
consumers, and the medical community with access to important and
useful information.
A. Nature of Impact
Currently, applicants holding approved NDA's or ANDA's are required
to submit annual reports to the agency that include information on the
current status of any postmarketing studies of the drug product
performed by, or on the behalf of the applicant. Although the proposed
rule prescribes the format for the required information, this
requirement would add no new economic burden for the majority of NDA
and ANDA applicants. About half of the applicants holding approved
NDA's or ANDA's with outstanding postmarketing study commitments made
prior to the enactment of FDAMA may incur a small cost the first year,
if their annual report is due within the last 6 months after the
effective date of issuance of the final rule and they must submit one
initial report within the first 6 months after the effective date. FDA
estimates that there will be approximately 116 such reports submitted,
which will require about 16 hours per report to complete. Assuming an
average wage rate of $35 per hour,
[[Page 67213]]
the estimated, one-time cost of this provision is $64,960.
Applicants with licensed biological products are currently required
to submit information on postmarketing studies in pediatric populations
in annual reports to the agency. These applicants will incur additional
costs to comply with the proposed requirements in this proposed rule.
The agency estimates that about 33 applicants will submit approximately
43 postmarketing status reports annually for approved licensed
biological products. As the reporting requirements are not extensive
and the information is readily accessible to the applicant, FDA
estimates that establishments will require about 16 hours to complete
the required information. Assuming an average wage rate of $35 per
hour, the estimated incremental cost of the annual reporting
requirement will be $560 per report, for an industry total of $24,080
per year. As with applicants holding NDA's or ANDA's, a few applicants
with licensed biological products with outstanding postmarketing study
commitments may also incur an additional, one-time cost because they
must submit their initial report within the first 6 months after the
effective date of the final rule and an annual report within the last 6
months of the year. FDA estimates there will be approximately seven
such reports, for a total one-time cost of about $4,000.
B. Small Business Impacts
The requirements in this proposed rule will not have a significant
economic impact on a substantial number of small entities. Although it
is possible that some firms may feel added pressure to honor the agreed
upon commitments, the agency does not expect the proposed rule to
result in an increased number of completed postmarketing studies. Nor
does it believe that applicants will incur significantly increased
costs from completing studies earlier than intended, as a result of the
reporting, tracking, and disclosure activities implemented by the
agency. Because affected applicants holding NDA's and ANDA's must
currently submit annual reports to the agency, they already have
procedures in place to monitor their postmarketing studies. The
additional reporting requirement for applicants holding approved BLA's
and the reformatting of the annual reports for applicants holding NDA's
and ANDA's would be minimal. To simplify the reporting requirement
further, however, the agency will publish a guidance for industry to
aid applicants in preparing reports in the proper format.
C. Conclusion
The previous cost estimates demonstrate that this rule is not
economically significant under Executive Order 12866. The Unfunded
Mandates Reform Act does not require a cost-benefit analysis of this
rule, because the rule will not result in an expenditure by State,
local, or tribal governments, in the aggregate, or by the private
sector of $100 million in any 1 year. Finally, the agency certifies
that the proposed rule will not have a significant economic impact on a
substantial number of small entities.
VI. The Paperwork Reduction Act of 1995
This proposed rule contains information collection provisions that
are subject to review by OMB under the Paperwork Reduction Act of 1995
(44 U.S.C. 3501-3520). A description of these provisions is shown below
with an estimate of the annual reporting burden. Included in the
estimate is the time for reviewing the instructions, searching existing
data sources, gathering and maintaining the data needed, and completing
and reviewing each collection of information.
FDA invites comments on: (1) Whether the proposed collection of
information is necessary for the proper performance of FDA's functions,
including whether the information will have practical utility; (2) the
accuracy of FDA's estimate of the burden of the proposed collection of
information, including the validity of the methodology and assumptions
used; (3) ways to enhance the quality, utility, and clarity of the
information to be collected; and (4) ways to minimize the burden of the
collection of information on respondents, including through the use of
automated collection techniques, when appropriate, and other forms of
information technology.
Title: Reporting the Status of Postmarketing Studies for Human
Drugs and Licensed Biological Products.
Description: Section 506B of the act provides FDA with additional
authority for monitoring the progress of postmarketing studies that
companies have made a commitment to conduct and also requires the
agency to make the status of these studies publicly available.
Under section 506B(a) of the act, applicants that have committed to
conduct a postmarketing study for an approved human drug or biological
product must submit to FDA a report of the progress of the study or the
reasons for the failure of the applicant to conduct the study. This
report must be submitted within 1 year after the U.S. approval of the
product and annually thereafter until the study is completed or
terminated. Under Secs. 314.81(b)(2)(vii) and (b)(2)(viii), and
601.70(b), information submitted in a status report would be limited to
that which is needed to sufficiently identify each applicant that has
committed to conduct a postmarketing study, the status of the study
that is being reported, and the reasons, if any, for the applicant's
failure to conduct, complete, and report the study.
Currently under Sec. 314.81(b)(2), applicants holding an NDA or an
ANDA must submit status reports on postmarketing studies for the
approved human drug product as part of an annual report to FDA. The
agency is proposing to amend Sec. 314.81(b)(2)(vii) to specify
information that must be included in status reports submitted under
section 506B of the act (studies of clinical safety, clinical efficacy,
clinical pharmacology, and nonclinical toxicology that are required by
FDA or that an applicant commits, in writing, to conduct either at the
time of approval of an application or a supplement to an application or
after approval of an application or supplement). Proposed
Sec. 314.81(b)(2) also adds paragraph (b)(2)(viii) which would require
status information on any postmarketing study commitments not reported
under paragraph (b)(2)(vii) that are being performed by, or on behalf
of, the applicant; and paragraph (b)(2)(ix) which would allow the
applicant to list any open regulatory business with FDA concerning the
drug product subject to the application. For licensed biological
products, FDA proposes to create Sec. 601.70 to require postmarketing
status reports for studies of clinical safety, clinical efficacy,
clinical pharmacology, and nonclinical toxicology that are required by
FDA or that an applicant of a BLA commits to conduct, in writing, at
the time of approval of an application or a supplement to an
application or after approval of an application or a supplement. FDA is
also proposing to revise Sec. 601.37(c) to require that the status of
postmarketing pediatric studies described in proposed Sec. 601.70 be
reported under proposed Sec. 601.70 rather than Sec. 601.37.
This proposed rule is intended to provide FDA with specific
procedures for monitoring the progress of postmarketing studies that
companies have made a commitment, in writing, to conduct and also to
permit the agency to make the status of these studies publicly
available.
Description of Respondents: Applicants holding approved
[[Page 67214]]
applications for human drugs and biological products that have
committed to conduct postmarketing studies.
Under current Sec. 314.81(b)(2), applicants with approved NDA's and
ANDA's for human drugs are required to submit to the agency two copies
of the annual reports that must include information on the current
status of any postmarketing study (OMB No. 0910-0001).
Proposed Sec. 314.81(b)(2)(vii), (b)(2)(viii), and (b)(2)(ix) would
expressly require status information to be provided in a specific
format as part of the status reports of postmarketing study commitments
(clinical safety, clinical efficacy, clinical pharmacology, and
nonclinical toxicology), a subpart of the annual report. Based on past
experience, the agency estimates that each applicant holding an
approved NDA or ANDA would expend an additional 8 hours, to reformat
the annual report. This is a one-time burden required under proposed
Sec. 314.81(b)(2)(vii). Based on the number of drug applicants in past
years who have committed to conduct postmarketing studies, the agency
estimates that this provision would apply to approximately 183
applicants and approximately 462 postmarketing studies.
Based upon information obtained from the Center for Biologics
Evaluation and Research's computerized application and license tracking
database, the agency estimates that approximately 33 applicants with 43
approved BLA's have committed to conduct approximately 86 postmarketing
studies (clinical safety, clinical efficacy, clinical pharmacology, and
nonclinical toxicology) and would be required to submit an annual
progress report on those postmarketing studies under proposed
Sec. 601.70. Proposed Sec. 601.70 requires postmarketing studies status
reports for the first time for biological products. Based on past
experience with reporting under Sec. 314.81(b)(2), the agency estimates
that approximately 8 hours annually is required for an applicant to
gather, complete, and submit the appropriate information for each
report (approximately two studies per report). Included in these 8
hours is the time necessary to initially format the status report.
Applicants holding NDA's, ANDA's, and BLA's whose anniversary date
of U.S. approval of the application falls within the latter half of the
year after the effective date of any final rule that may issue based on
this proposed rule are required under section 506B of the act to submit
an initial report to FDA for postmarketing studies committed to be
conducted prior to November 21, 1997, within 6 months after the
effective date of any final rule in addition to the reports required by
the final rule. This information collection is a statutory requirement
for which the proposed regulations add no additional burden other than
prescribing the format. The burden of setting up the format is
calculated under Secs. 314.81(b)(2)(vii) and 601.70(b).
Table 1.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
No. of Annual Frequency Total Annual Hours per
21 CFR Section Respondents per Response Responses Response Total Hours
----------------------------------------------------------------------------------------------------------------
314.81(b)(2)(vii), 183 2.5 462 8 3,696
(b)(2)(viii),
(b)(2)(ix)\2\
601.70(b) and (d) 33 2.6 86 8 688
Total 4,384
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs with this collection of information.
\2\ One-time burden for reformatting annual report.
In compliance with section 3507(d) of the Paperwork Reduction Act
of 1995 (44 U.S.C. 3507(d)), the agency has submitted the information
collection provisions of this proposed rule to OMB for review.
Interested persons are requested to send comments regarding this
information collection by January 3, 2000, to the Office of Information
and Regulatory Affairs, OMB, New Executive Office Bldg., 725 17th St.
NW., rm. 10235, Washington, DC 20503, Attn: Desk Officer for FDA.
VII. Reference
The following reference has been placed on display in the Dockets
Management Branch (address above) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday.
1. ``Postmarketing Studies of Prescription Drugs,'' Department
of Health and Human Services, Office of the Inspector General Final
Report, May 1996.
List of Subjects
21 CFR Part 314
Administrative practice and procedure, Confidential business
information, Drugs, Reporting and recordkeeping requirements.
21 CFR Part 601
Administrative practice and procedure, Biologics, Confidential
business information.
Therefore, under the Federal Food, Drug, and Cosmetic Act, the
Public Health Service Act, and under authority delegated to the
Commissioner of Food and Drugs, it is proposed that 21 CFR parts 314
and 601 be amended as follows:
PART 314--APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG
1. The authority citation for 21 CFR part 314 is revised to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 356b, 371,
374, 379e.
2. Section 314.81 is amended by revising the introductory text of
paragraph (b)(2), by revising paragraph (b)(2)(vii), and by adding
paragraphs (b)(2)(viii) and (b)(2)(ix) to read as follows:
Sec. 314.81 Other postmarketing reports.
* * * * *
(b) * * *
(2) Annual report. The applicant shall submit the following
information each year within 60 days of the anniversary date of U.S.
approval of the application. The applicant shall submit two copies of
the report to the FDA division responsible for reviewing the
application. Each annual report is required to be accompanied by a
completed transmittal Form FDA-2252 (Transmittal of Annual Reports for
Drugs for Human Use), which may be obtained from the PHS Forms and
Publications Distribution Center, 12100 Parklawn Dr., Rockville, MD
20857, and is required to include all the information required under
this section that the applicant received or otherwise obtained during
the annual reporting interval, which ends on the U.S. anniversary date.
The report is required to contain in the order listed:
* * * * *
(vii) Status reports of postmarketing study commitments. A status
report of each postmarketing study of the drug product concerning
clinical safety, clinical efficacy, clinical pharmacology,
[[Page 67215]]
and nonclinical toxicology that is required by FDA (e.g., pediatric
studies) or that the applicant has committed, in writing, to conduct
either at the time of approval of an application for the drug product
or a supplement to an application, or after approval of an application
or a supplement. For pediatric studies, the status report shall include
a statement indicating whether postmarketing clinical studies in
pediatric populations were required by FDA under Sec. 201.23 of this
chapter. The status of these postmarketing studies shall be reported
annually until FDA notifies the applicant, in writing, that the agency
concurs with the applicant's determination that the study commitment
has been fulfilled or that the study is either no longer feasible or
would no longer provide useful information.
(a) Content of status report. The following information shall be
provided for each postmarketing study reported under this paragraph:
(1) Applicant's name.
(2) Product name. Include the approved drug product's established
name and proprietary name, if applicable.
(3) NDA, ANDA (abbreviated new drug application), or supplement
number.
(4) Date of product's U.S. approval.
(5) Date of postmarketing study commitment.
(6) Description of postmarketing study commitment. For clinical
studies, include the purpose of the postmarketing study, the patient
population addressed by the study, the number of patients and/or
subjects to be included in the study, and the indication and dosage(s)
that are to be studied. For nonclinical studies, include the type and
purpose of the study.
(7) Schedule for conduct, completion, and reporting of the
postmarketing study commitment. Include projected dates for initiation
of the different phases of the study, for completion of the study, and
for submission of the final study report to FDA. Provide a revised
schedule, in addition to the original schedule, if the original
schedule was revised in the previous report.
(8) Current status of the postmarketing study commitment.
Categorize the status of each postmarketing study using one of the
following terms that describes the study's status on the anniversary
date of U.S. approval of the application or other agreed upon date:
(i) Pending. The study has not been initiated.
(ii) Ongoing. The study is proceeding according to or ahead of the
original schedule described under paragraph (b)(2)(vii)(a)(7) of this
section. Include the date the study was completed, if a study has been
completed but the final study report has not been submitted to FDA.
(iii) Delayed. The study is proceeding but is behind the original
schedule described under paragraph (b)(2)(vii)(a)(7) of this section.
(iv) Terminated. The study was ended before completion.
(v) Submitted. The study has been completed or terminated and a
final study report has been submitted to FDA. Include the date the
final study report was submitted to FDA.
(9) Explanation of the study's status. Provide a brief description
of the status of the study, including the number of patients and/or
subjects enrolled to date and an explanation of the study's status
identified under paragraph (b)(2)(vii)(a)(8) of this section. Provide a
revised schedule, as well as the reason(s) for the revision, if the
schedule under paragraph (b)(2)(vii)(a)(7) of this section has changed
since the last report.
(b) Public disclosure of information. Except for the information
described in this paragraph, FDA may publicly disclose any information
concerning a postmarketing study, within the meaning of paragraph
(b)(2)(vii) of this section, if the agency determines that the
information is necessary to identify the applicant or to establish the
status of the study including the reasons, if any, for failure to
conduct, complete, and report the study. Information necessary to
establish the status of a postmarketing study includes the study
protocol, patient accrual rates, reports of unexpected suspected
adverse drug reactions, and study results. Under this section, FDA will
not publicly disclose trade secrets, as defined in Sec. 20.61 of this
chapter, or information, described in Sec. 20.63 of this chapter, the
disclosure of which would constitute an unwarranted invasion of
personal privacy.
(viii) Status of other postmarketing studies. A status report of
any postmarketing study not included under paragraph (b)(2)(vii) of
this section that is being performed by, or on behalf of, the
applicant. The applicant shall provide information as prescribed under
paragraphs (b)(2)(vii)(a)(1) through (b)(2)(vii)(a)(9) of this section
for each of the postmarketing studies required to be reported under
this paragraph.
(ix) Log of outstanding regulatory business. To facilitate
communications between FDA and the applicant, the report may, at the
applicant's discretion, also contain a list of any open regulatory
business with FDA concerning the drug product subject to the
application (e.g., a list of the applicant's unanswered correspondence
with the agency, a list of the agency's unanswered correspondence with
the applicant).
PART 601--LICENSING
3. The authority citation for 21 CFR part 601 is revised to read as
follows:
Authority: 15 U.S.C. 1451-1561; 21 U.S.C. 321, 351, 352, 353,
355, 356b, 360, 360c-360f, 360h-360j, 371, 374, 379e, 381; 42 U.S.C.
216, 241, 262, 263, 264; sec. 122, Pub. L. 105-115, 111 Stat. 2322
(21 U.S.C. 355 note).
4. Section 601.37 is amended by revising the second sentence in
paragraph (c) to read as follows:
Sec. 601.37 Annual reports of postmarketing pediatric studies.
* * * * *
(c) * * * The statement shall include whether postmarketing
clinical studies in pediatric populations were required or agreed to,
and, if so, the status of these studies shall be reported to FDA in
annual progress reports of postmarketing studies under Sec. 601.70
rather than under this section.
5. Subpart G, consisting of Sec. 601.70, is added to part 601 to
read as follows:
Subpart G--Postmarketing Studies
Sec. 601.70 Annual progress reports of postmarketing studies
(a) General requirements. This section applies to all required
postmarketing studies (e.g., pediatric studies) and postmarketing
studies that an applicant has committed, in writing, to conduct either
at the time of approval of an application or a supplement to an
application, or after approval of an application or a supplement.
Postmarketing studies within the meaning of this section are those that
concern:
(1) Clinical safety;
(2) Clinical efficacy;
(3) Clinical pharmacology; and
(4) Nonclinical toxicology.
(b) What to report. Each applicant of a licensed biological product
shall submit a report to FDA on the status of postmarketing studies for
each approved product application. The report shall include the status
of each study which is required by FDA (e.g., pediatric studies) or
which the applicant has committed, in writing, to conduct, including
any reasons for the applicant's failure to conduct or to progress with
the study. The status of these postmarketing studies shall be
[[Page 67216]]
reported annually until FDA notifies the applicant, in writing, that
the agency concurs with the applicant's determination that the study
commitment has been fulfilled, or that the study is either no longer
feasible or would no longer provide useful information. Each annual
progress report shall be accompanied by a completed transmittal Form
FDA-2252, which may be obtained from the PHS Forms and Publications
Distribution Center, 12100 Parklawn Dr., Rockville, MD 20857, and shall
include all the information required under this section that the
applicant received or otherwise obtained during the annual reporting
interval, which ends on the U.S. anniversary date. The report shall
provide the following information for each postmarketing study:
(1) Applicant's name.
(2) Product name. Include the approved product's proper name and
the proprietary name, if applicable.
(3) Biologics license application (BLA)/reference or supplement
number. The biologics license application number, reference number, or
supplement number of the approved product.
(4) Date of product's U.S. approval.
(5) Date of postmarketing study commitment.
(6) Description of postmarketing study commitment. For clinical
studies, include the purpose of the postmarketing study, the patient
population addressed by the postmarketing study, the number of patients
and/or subjects to be included in the study, and the indication and
dosage(s) that are to be studied. For nonclinical studies, include the
type and purpose of the study.
(7) Schedule for conduct, completion, and reporting of the
postmarketing study commitment. Include projected dates for initiation
of the different phases of the study, for completion of the study, and
for submission of the final study report to FDA. Provide a revised
schedule, in addition to the original schedule, if the original
schedule was revised in the previous report.
(8) Current status of the postmarketing study commitment.
Categorize the status of each postmarketing study using one of the
following terms that describes the study's status on the anniversary
date of the U.S. approval of the application or other agreed date:
(i) Pending. The study has not been initiated.
(ii) Ongoing. The study is proceeding according to or ahead of the
original schedule described under paragraph (b)(7) of this section.
Include the date the study was completed, if a study has been completed
but the final study report has not been submitted to FDA.
(iii) Delayed. The study is proceeding but is behind the original
schedule described under paragraph (b)(7) of this section.
(iv) Terminated. The study was ended before completion.
(v) Submitted. The study has been completed or terminated, and a
final study report has been submitted to FDA. Include the date the
final study report was submitted to FDA.
(9) Explanation of the study's status. Provide a brief description
of the status of the study, including the number of patients and/or
subjects enrolled to date and an explanation of the study's status
identified under paragraph (b)(8) of this section. Provide a revised
schedule, as well as the reason(s) for the revision, if the schedule
under paragraph (b)(7) of this section has changed since the previous
report.
(c) When to report. Annual progress reports for postmarketing study
commitments entered into by applicants shall be reported to FDA within
60 days of the anniversary date of the U.S. approval of the application
for the product.
(d) Where to report. Submit two copies of the annual progress
report of postmarketing studies to the Food and Drug Administration,
Center for Biologics Evaluations and Research, Document Control Center
(HFM-99), suite 200N, 1401 Rockville Pike, Rockville, MD 20852-1448.
(e) Public disclosure of information. Except for the information
described in this paragraph, FDA may publicly disclose any information
concerning a postmarketing study, within the meaning of this section,
if the agency determines that the information is necessary to identify
an applicant or to establish the status of the study including the
reasons, if any, for failure to conduct, complete, and report the
study. Information necessary to establish the status of a postmarketing
study includes the study protocol, patient accrual rates, reports of
unexpected suspected adverse drug experiences, and study results. Under
this section, FDA will not publicly disclose trade secrets, as defined
in Sec. 20.61 of this chapter, or information described in Sec. 20.63
of this chapter, the disclosure of which would constitute an
unwarranted invasion of personal privacy.
Dated: August 9, 1999.
Margaret M. Dotzel,
Acting Associate Commissioner for Policy.
[FR Doc. 99-31123 Filed 11-30-99; 8:45 am]
BILLING CODE 4160-01-F