[Federal Register Volume 76, Number 186 (Monday, September 26, 2011)]
[Notices]
[Pages 59401-59404]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-24581]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-N-0275]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; Comment Request; Certification to 
Accompany Drug, Biological Product, and Device Applications or 
Submissions (Form FDA 3674)

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that a 
proposed collection of information has been submitted to the Office of 
Management and Budget (OMB) for review and clearance under the 
Paperwork Reduction Act of 1995.

DATES: Fax written comments on the collection of information by October 
26, 2011.

ADDRESSES: To ensure that comments on the information collection are 
received, OMB recommends that written comments be faxed to the Office 
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, 
FAX: 202-395-7285, or e-mailed to [email protected]. All 
comments should be identified with the OMB control number 0910-0616. 
Also include the FDA docket number found in brackets in the heading of 
this document.

FOR FURTHER INFORMATION CONTACT: Jonna Capezzuto, Office of Information 
Management, Food and Drug Administration, 1350 Piccard Dr., PI50-400B, 
Rockville, MD 20850, 301-796-3794, [email protected].

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance. Certification to Accompany Drug, Biological 
Product, and Device Applications or Submissions

(Form FDA 3674)--(OMB Control Number 0910-0616)--Extension

    The information required under section 402(j)(5)(B) of the Public 
Health Service Act (PHS Act) (42 U.S.C. 282(j)(5)(B)) is submitted in 
the form of a certification, Form FDA 3674, which accompanies 
applications and submissions currently submitted to FDA and is already 
approved by OMB. The OMB control numbers and expiration dates for 
submitting Form FDA 3674 under the following parts are: 21 CFR parts 
312 and 314 (human drugs) are 0910-0014, expiring August 31, 2011, and 
0910-0001, expiring May 31, 2011; 21 CFR parts 312 and 601 (biological 
products) are 0910-0014 and 0910-0338, expiring December 31, 2011; 21 
CFR parts 807 and 814 (devices) are 0910-0120, expiring December 31, 
2013, and 0910-0231, expiring December 31, 2013.
    Title VIII of the Food and Drug Administration Amendments Act of 
2007 (FDAAA) (Pub. L. 110-85) amended the PHS Act by adding section 
402(j) (42 U.S.C. 282(j)). The provisions require additional 
information to be submitted to the clinical trials data bank (http://ClinicalTrials.gov) \1\ previously established by the National 
Institutes of Health (NIH)/National Library of Medicine, including 
expanded information on clinical trials and information on the results 
of clinical trials. The provisions include responsibilities for FDA as 
well as several amendments to the Federal Food, Drug, and Cosmetic Act 
(the FD&C Act).
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    \1\ FDA has verified the Web site addresses throughout this 
document, but FDA is not responsible for any subsequent changes to 
the Web sites after this document publishes in the Federal Register.
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    One provision, section 402(j)(5)(B) of the PHS Act, requires that a 
certification accompany human drug, biological, and device product 
submissions made to FDA. Specifically, at the time of submission of an 
application under sections 505, 515, or 520(m) of the FD&C Act (21 
U.S.C. 355, 360e, or 360j(m)), or under section 351 of the PHS Act (42 
U.S.C. 262), or submission of a report under section 510(k) of the FD&C 
Act (21 U.S.C. 360(k)), such application or submission must be 
accompanied by a certification, Form FDA 3674, that all applicable 
requirements of section 402(j) of the PHS Act have been met. Where 
available, such certification must include the appropriate National 
Clinical Trial (NCT) numbers.
    The proposed extension of the collection of information is 
necessary to satisfy the previously mentioned statutory requirement.
    The importance of obtaining these data relates to adherence to the 
legal requirements for submissions to the clinical trials registry and 
results data bank and ensuring that individuals and organizations 
submitting applications or reports to FDA under the listed

[[Page 59402]]

provisions of the FD&C Act or the PHS Act adhere to the appropriate 
legal and regulatory requirements for certifying to having complied 
with those requirements. The failure to submit the certification 
required by section 402(j)(5)(B) of the PHS Act, and the knowing 
submission of a false certification are both prohibited acts under 
section 301 of the FD&C Act (21 U.S.C. 331). Violations are subject to 
civil money penalties.
    In January 2009, FDA issued ``Guidance for Sponsors, Industry, 
Researchers, Investigators, and Food and Drug Administration Staff 
Certifications To Accompany Drug, Biological Product, and Device 
Applications/Submissions: Compliance with Section 402(j) of The Public 
Health Service Act, Added By Title VIII of The Food and Drug 
Administration Amendments Act of 2007'' available at http://www.fda.gov/RegulatoryInformation/Guidances/ucm125335.htm. This 
guidance identified the applications and submissions that FDA 
considered should be accompanied by the certification form, Form FDA 
3674. The applications and submissions noted in the guidance are 
reflected in the burden analysis.

I. Investigational New Drug Applications

    FDA's Center for Drug Evaluation and Research (CDER) received 1,752 
investigational new drug applications (INDs) and 11,769 clinical 
protocol IND amendments in fiscal year (FY) 2010. CDER anticipates that 
IND and clinical protocol amendment submission rates will remain at or 
near this level in the near future.
    FDA's Center for Biologics Evaluation and Research (CBER) received 
281 new INDs and 1,471 clinical protocol IND amendments in FY 2010. 
CBER anticipates that IND and clinical protocol amendment submission 
rates will remain at or near this level in the near future.
    The estimated total number of submissions (new INDs and new 
protocol submissions) subject to mandatory certification requirements 
under section 402(j)(5)(B) of the PHS Act, is 13,521 for CDER plus 
1,752 for CBER, or 15,273 submissions per year. The minutes per 
response is the estimated number of minutes that a respondent would 
spend preparing the information to be submitted to FDA under section 
402(j)(5)(B) of the PHS Act, including the time it takes to enter the 
necessary information on the form.
    Based on its experience with current submissions, FDA estimates 
that approximately 15.0 minutes on average would be needed per response 
for certifications which accompany IND applications and clinical 
protocol amendment submissions. It is assumed that most submissions to 
investigational applications will reference only a few protocols for 
which the sponsor/applicant/submitter has obtained a NCT number from 
http://ClinicalTrials.gov prior to making the submission to FDA. It is 
also assumed that the sponsor/applicant/submitter has electronic 
capabilities allowing them to retrieve the information necessary to 
complete the form in an efficient manner.

II. Marketing Applications/Submissions

    In 2010, CDER and CBER received 165 new drug applications (NDA)/
biologics license applications (BLA)/resubmissions and 1,483 NDA/BLA 
amendments for which certifications are needed. CDER and CBER received 
191 efficacy supplements/resubmissions to previously approved NDAs/BLAs 
in FY 2010. CDER and CBER anticipate that new drug/biologic 
applications/resubmissions and efficacy supplement submission rates 
will remain at or near this level in the near future.
    FDA's Center for Devices and Radiological Health (CDRH) received a 
total of 892 new applications for premarket approvals (PMA), 510(k) 
submissions containing clinical information, PMA supplements, 
applications for humanitarian device exemptions (HDE) and amendments, 
for a total of 424 new applications/submissions in FY 2010. CDRH 
anticipates that application, amendment, supplement, and annual report 
submission rates will remain at or near this level in the near future.
    FDA's Office of Generic Drugs (OGD) received 854 abbreviated new 
drug applications (ANDAs) in FY 2010. OGD received 495 bioequivalence 
amendments/supplements FY 2010. OGD anticipates that application, 
amendment, and supplement submission rates will remain at or near this 
level in the near future.
    Based on its experience reviewing NDAs, BLAs, PMAs, HDEs, 510(k)s, 
and ANDAs and experience with current submissions of Form FDA 3674, FDA 
estimates that approximately 45.0 minutes on average would be needed 
per response for certifications which accompany NDA, BLA, PMA, HDE, 
510(k), and ANDA marketing applications and submissions. It is assumed 
that the sponsor/applicant/submitter has electronic capabilities 
allowing them to retrieve the information necessary to complete the 
form in an efficient manner.
    In the Federal Register of May 6, 2011 (76 FR 26305), FDA published 
a 60-day notice requesting public comment on the proposed collection of 
information. There were four comments submitted in response to the 60-
day Federal Register notice. Only two comments were directly related to 
the information collection. One comment was unrelated to the 
information collection. The remaining comment requested that FDA define 
a term contained in section 402(j)(1)(A)(ii) of the PHS Act (42 U.S.C. 
282(j)(1)(A)(ii)). The implementation of this provision, including 
defining any statutory terms, is the responsibility of NIH. NIH has 
indicated in the Unified Agenda that proposed rulemaking is anticipated 
in 2011. In addition, NIH has provided an elaboration of the definition 
of that term on its Web site at http://prsinfo.clinicaltrials.gov/ElaborationsOnDefinitions.pdf.
    One of the comments that directly addressed the information 
collection commented on the utility of the information collected 
through Form FDA 3674 and requested that FDA consider a means to 
associate the NCT number with the study numbers. Since the enactment of 
FDAAA, FDA has been involved in a technological effort designed to 
accomplish what has been suggested by the comment. FDA is currently 
involved in designing a software/computer system that can link the 
information provided on the Form FDA 3674 with actions taken in 
relation to that study, a future marketing application, and future 
actions taken in relation to the approved medical product. Part of this 
effort is designed to provide NIH information which will be displayed 
on its Web site for each clinical trial for which specific information 
is provided. An additional aspect for the effort is designed to link 
this information internally for various purposes including compliance 
efforts. This commenter also proposed changes to the timing of the 
certification submissions accompanying INDs based upon the requirements 
for submission of clinical trial information to http://ClinicalTrials.gov. FDA appreciates the comment but has implemented the 
statutory requirements in the most efficient manner possible. The 
statute requires FDA to obtain the certification upon submission of an 
IND despite the fact that submission of clinical trial information to 
http://ClinicalTrials.gov generally is not required at the time an IND 
is required to be submitted. In order to collect information on trials 
that are not applicable clinical trials, as suggested by the comment, 
either a

[[Page 59403]]

statutory change or, possibly, rulemaking would be required.
    The remaining comment contended that the estimates FDA used in its 
burden estimates should be adjusted significantly upward. We do not 
agree with the comment's conclusions. FDA has based the burden hours on 
the totality of the time needed for the information collection and not 
(as claimed by the commenter) on the completion of the form itself. As 
noted in our previous information collection and this one, we 
anticipated that entities submitting Form FDA 3674 would implement 
systems that would simplify collection of the information. We have 
received feedback based on submitters' experience over the past 3\1/2\ 
years that suggests these types of systems have been implemented. 
Furthermore, given the responsibilities required for registering and 
updating trials on http://ClinicalTrials.gov and current FDA 
requirements, unrelated to Form FDA 3674, for submission of trial 
information for marketing applications, the information required for 
completion of this form should be easy to compile. FDA's experience in 
responding to calls on the form and questions presented at meetings and 
conferences does not accord with the practices noted in this comment 
and does not support the burden estimates proposed by the comment. In 
fact, the only other comment submitted directly related to the 
information collection indicated that the ``estimate of the burden of 
the proposed collection of information, including the validity of the 
methodology and assumption used, seems reasonable.''
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
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                                                             No. of           No. of
                                                           respondents      respondents       No. of       Total annual   Average burden
                  FDA Center activity                   (investigational    (marketing     responses per     responses     per response     Total hours
                                                          applications)    applications)    respondent
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                                                                          CDER
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New Applications (IND)................................            1,752   ..............               1           1,752            0.25             438
                                                                                                                               (15 min.)
Clinical Protocol Amendments (IND)....................           11,769   ..............               1          11,769            0.25           2,943
                                                                                                                               (15 min.)
New Marketing Applications/Resubmissions (NDA/BLA)....  ................             157               1             157            0.75             118
                                                                                                                               (45 min.)
Clinical Amendments to Marketing Applications.........  ................           1,466               1           1,466            0.75           1,100
                                                                                                                               (45 min.)
Efficacy Supplements/Resubmissions....................  ................             166               1             166            0.75             125
                                                                                                                               (45 min.)
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                                                                          CBER
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New Applications (IND)................................              281   ..............               1             281            0.25              70
                                                                                                                               (15 min.)
Clinical Protocol Amendments (IND)....................            1,471   ..............               1           1,471            0.25             368
                                                                                                                               (15 min.)
New Marketing Applications/Resubmissions..............  ................               8               1               8            0.75               6
                                                                                                                               (45 min.)
Clinical Amendments to Marketing Applications.........  ................              17               1              17            0.75              13
                                                                                                                               (45 min.)
Efficacy Supplements/Resubmissions (BLA only).........  ................              25               1              25            0.75              19
                                                                                                                               (45 min.)
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                                                                          CDRH
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New Marketing Applications (includes PMAs, HDEs,        ................             892               1             892            0.75             669
 Supplements and 510(k)s expected to contain clinical                                                                          (45 min.)
 data)................................................
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                                                                          OGD
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Original Applications.................................  ................             854               1             854            0.75             641
                                                                                                                               (45 min.)
BE Supplements/Amendments.............................  ................             495  ..............  ..............            0.75             372
                                                                                                                               (45 min.)
    Total.............................................  ................  ..............  ..............  ..............  ..............          6,882
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.



[[Page 59404]]

    Dated: September 20, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-24581 Filed 9-23-11; 8:45 am]
BILLING CODE 4160-01-P