[Federal Register Volume 69, Number 159 (Friday, October 8, 2004)]
[Notices]
[Pages 60402-60405]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-22815]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2004N-0441]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; Application for FDA Approval to Market a New Drug

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing an 
opportunity for public comment on the proposed collection of certain 
information by the agency. Under the Paperwork Reduction Act of 1995 
(PRA), Federal agencies are required to publish notice in the Federal 
Register concerning each proposed collection of information, including 
each proposed extension of an existing collection of information, and 
to allow 60 days for public comment in response to the notice. This 
notice solicits comments on requirements governing applications for FDA 
approval to market a new drug.

DATES: Submit written or electronic comments on the collection of 
information by December 7, 2004.

ADDRESSES: Submit electronic comments on the collection of information 
to: http://www.fda.gov/dockets/ecomments. Submit written comments on 
the collection of information to the Division of Dockets Management 
(HFA 305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. All comments should be identified with the docket 
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Karen L. Nelson, Office of Management 
Programs (HFA 250), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301 827 1482.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal 
agencies must obtain approval from the Office of Management and Budget 
(OMB) for each collection of information they conduct or sponsor. 
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 
1320.3(c) and includes agency requests or requirements that members of 
the public submit reports, keep records, or provide information to a 
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) 
requires Federal agencies to provide a 60-day notice in the Federal 
Register concerning each proposed collection of information, including 
each proposed extension of an existing collection of information, 
before submitting the collection to OMB for approval. To comply with 
this requirement, FDA is publishing notice of the proposed collection 
of information listed below.
    With respect to the following 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.

Applications for FDA Approval to Market a New Drug-- 21 CFR Part 314--
(OMB Control Number 0910 0001)--Extension

    Under Section 505(a) of the Federal Food, Drug, and Cosmetic Act 
(the Act) (21 U.S.C. 355(a)), a new drug may not be commercially 
marketed in the United States, imported, or exported from the United 
States, unless an approval of an application filed with FDA under 
section 505(b) or 505(j) of the act is effective with respect to such 
drug. Section 505(b) and 505(j) of the act requires a sponsor to submit 
to FDA a new drug application (NDA) containing, among other things, 
full reports of investigations that show whether or not the drug is 
safe and effective for use, a full list of articles used as components 
in the drug, a full description of manufacturing methods, samples of 
the drugs required, specimens of the labeling proposed to be used, and 
certain patent information as applicable. Under the act, it is the 
sponsor's responsibility to provide the information needed by FDA to 
make a scientific and technical determination that the product is safe 
and effective.
    This information collection approval request is for all information 
requirements imposed on sponsors by the regulations under part 314 (21 
CFR 314), who apply for approval of a new drug application in order to 
market or to continue to market a drug.
    Section 314.50(a) requires that an application form (Form FDA 356h) 
be submitted that includes introductory information about the drug as 
well as a checklist of enclosures.
    Section 314.50(b) requires that an index be submitted with the 
archival copy of the application and that it reference certain sections 
of the application.
    Section 314.50(c) requires that a summary of the application be 
submitted that presents a good general synopsis of all the technical 
sections and other information in the application.
    Section 314.50(d) requires that the NDA contain the following 
technical sections about the new drug: Chemistry, manufacturing, and 
controls; nonclinical pharmacology and toxicology; human 
pharmacokinetics and bioavailability; microbiology; clinical data; and 
statistical section.
    Section 314.50(e) requires the applicant to submit samples of the 
drug if requested by FDA. In addition, the archival copy of the 
application must include copies of the label and all labeling for the 
drug.
    Section 314.50(f) requires that case report forms and tabulations 
be submitted with the archival copy.
    Section 314.50(h) requires that patent information, as described 
under Sec.  314.53, be submitted with the application.
    Section 314.50(i) requires that patent certification information be 
submitted in 505(b)(2) applications for patents claiming the drug, drug 
product, method of use, or method of manufacturing.
    Section 314.50(j) requires that applicants that request a period of 
marketing exclusivity submit certain information with the application.
    Section 314.50(k) requires that an archival, review, and field copy 
of the application be submitted.
    Section 314.52 requires that notice of certification of invalidity 
or noninfringement of a patent to patent holders and NDA holders be 
sent by 505(b)(2) applicants.
    Section 314.54 sets forth the content requirements for applications 
filed under section 505(b)(2) of the act.
    Section 314.60 sets forth reporting requirements for sponsors who 
amend an unapproved application.
    Section 314.65 states that the sponsor must notify FDA when 
withdrawing an unapproved application.
    Sections 314.70 and 314.71 require that supplements be submitted to 
FDA

[[Page 60403]]

for certain changes to an approved application.
    Section 314.72 requires sponsors to report to FDA any transfer of 
ownership of an application.
    Section 314.80(c)(1) and (c)(2) sets forth requirements for 
expedited adverse drug experience postmarketing reports and followup 
reports, as well as for periodic adverse drug experience postmarketing 
reports (Form FDA 3500A). (The burden hours for Sec.  314.80(c)(1) and 
(c)(2) are already approved by OMB under 0910-0230 and 0910-0291 and 
are not included in the hour burden estimates in table 1 of this 
document).
    Section 314.80(i) establishes recordkeeping requirements for 
reports of postmarketing adverse drug experiences. (The burden hours 
for Sec.  314.80(i) are already approved by OMB under 0910-0230 and 
0910-0291 and are not included in the hour burden estimates in table 1 
of this document).
    Section 314.81(b)(1) requires that field alert reports be submitted 
to FDA (Form FDA 3331).
    Section 314.81(b)(2) requires that annual reports be submitted to 
FDA (Form FDA 2252). This form has been revised as a result of the 
requirements in the final rule ``Postmarketing Studies for Approved 
Human Drug and Licensed Biological Products; Status Reports,'' 
published in the Federal Register of October 30, 2000 (65 FR 64607). 
The rule describes the types of postmarketing studies covered by the 
status reports, the information to be included in the reports, and the 
type of information that FDA would consider appropriate for public 
disclosure. The rule implemented section 130(a) of the Food and Drug 
Administration Modernization Act of 1997 (FDAMA). The changes to the 
form include adding new spaces for the new status reports, reporting 
for biological products, and editorial changes. A copy of the revised 
form is available at http://www.fda.gov/dockets/ecomments, using the 
docket number of this proposed collection of information.
    Section 314.81(b)(3)(i) requires that drug advertisements and 
promotional labeling be submitted to FDA (Form FDA 2253).
    Section 314.81(b)(3)(iii) sets forth reporting requirements for 
sponsors who withdraw an approved drug product from sale. (The burden 
hours for Sec.  314.81(b)(3)(iii) are already approved by OMB under 
0910-0045 and are not included in the hour burden estimates in table 1 
of this document).
    Section 314.90 sets forth requirements for sponsors who request 
waivers from FDA for compliance with Sec. Sec.  314.50 through 314.81. 
(The information collection hour burden estimate for NDA waiver 
requests is included in table 1 of this document under estimates for 
Sec. Sec.  314.50, 314.60, 314.70 and 314.71).
    Section 314.93 sets forth requirements for submitting a suitability 
petition in accordance with 21 CFR 10.20 and 10.30. (The burden hours 
for Sec.  314.93 are already approved by OMB under 0910-0183 and are 
not included in the hour burden estimates in table 1 of this document).
    Section 314.94(a) and (d) requires that an abbreviated new drug 
application (ANDA) contain the following information: Application form; 
table of contents; basis for ANDA submission; conditions of use; active 
ingredients; route of administration, dosage form, and strength; 
bioequivalence; labeling; chemistry, manufacturing, and controls; 
samples; patent certification.
    Section 314.95 requires that notice of certification of invalidity 
or noninfringement of a patent to patent holders and NDA holders be 
sent by ANDA applicants.
    Section 314.96 sets forth requirements for amendments to an 
unapproved ANDA.
    Section 314.97 sets forth requirements for submitting supplements 
to an approved ANDA for changes that require FDA approval.
    Section 314.98(a) sets forth postmarketing adverse drug experience 
reporting and recordkeeping requirements for ANDAs. (The burden hours 
for Sec.  314.98(a) are already approved by OMB under 0910-0230 and 
0910-0291 and are not included in the hour burden estimates in table 1 
of this document).
    Section 314.98(c) requires other postmarketing reports for ANDAs: 
Field alert reports (Form FDA 3331), annual reports (Form FDA 2252), 
and advertisements and promotional labeling (Form FDA 2253). (The 
information collection hour burden estimate for field alert reports is 
included in table 1 of this document under Sec.  314.81(b)(1); the 
estimate for annual reports is included under Sec.  314.81(b)(2); the 
estimate for advertisements and promotional labeling is included under 
Sec.  314.81(b)(3)(i)).
    Section 314.99(a) requires that sponsors comply with certain 
reporting requirements for withdrawing an unapproved ANDA and for a 
change in ownership of an ANDA.
    Section 314.99(b) sets forth requirements for sponsors who request 
waivers from FDA for compliance with Sec. Sec.  314.92 through 314.99. 
(The information collection hour burden estimate for ANDA waiver 
requests is included in table 1 of this document under estimates for 
Sec. Sec.  314.94(a) and (d), 314.96, and 314.97).
    Section 314.101(a) states that if FDA refuses to file an 
application, the applicant may request an informal conference with FDA 
and request that the application befiled over protest.
    Section 314.107(c)(4) requires notice to FDA by ANDA or 505(b)(2) 
application holders of any legal action concerning patent infringement.
    Section 314.107(e)(2)(iv) requires that an applicant submit a copy 
of the entry of the order or judgment to FDA within 10 working days of 
a final judgment.
    Section 314.107(f) requires that ANDA or 505(b)(2) applicants 
notify FDA of the filing of any legal action filed within 45 days of 
receipt of the notice of certification. A patent owner may also notify 
FDA of the filing of any legal action for patent infringement. The 
patent owner or approved application holder who is an exclusive patent 
licensee must submit to FDA a waiver that waives the opportunity to 
file a legal action for patent infringement.
    Section 314.110(a)(3) and (a)(4) states that, after receipt of an 
FDA approvable letter, an applicant may request an opportunity for a 
hearing on the question of whether there are grounds for denying 
approval of the application. (The burden hours for Sec.  314.110(a)(3) 
and (a)(4) are included under the parts 10 through 16 (21 CFR parts 10 
through 16) hearing regulations, in accordance with Sec.  314.201, and 
are not included in the hour burden estimates in table 1 of this 
document).
    Section 314.110(a)(5) states that, after receipt of an approvable 
letter, an applicant may notify FDA that it agrees to an extension of 
the review period so that it can determine whether to respond further.
    Section 314.110(b) states that, after receipt of an approvable 
letter, an ANDA applicant may request an opportunity for a hearing on 
the question of whether there are grounds for denying approval of the 
application. (The burden hours for Sec.  314.110(b) are included under 
the parts 10 through 16 hearing regulations, in accordance with Sec.  
314.201, and are not included in the hour burden estimates in table 1 
of this document).
    Section 314.120(a)(3) states that, after receipt of a not 
approvable letter, an applicant may request an opportunity for a 
hearing on the question of whether there are grounds for denying 
approval of the application. (The burden hours for Sec.  314.120(a)(3) 
are included under the parts 10 through 16 hearing

[[Page 60404]]

regulations, in accordance with Sec.  314.201, and are not included in 
the hour burden estimates in table 1 of this document).
    Section 314.120(a)(5) states that, after receipt of a not 
approvable letter, an applicant may notify FDA that it agrees to an 
extension of the review period so that it can determine whether to 
respond further.
    Section 314.122(a) requires that an ANDA or a suitability petition 
that relies on a listed drug that has been voluntarily withdrawn from 
sale must be accompanied by a petition seeking a determination whether 
the drug was withdrawn for safety or effectiveness reasons. (The burden 
hours for Sec.  314.122(a) are already approved by OMB under 0910-0183 
and are not included in the hour burden estimates in table 1 of this 
document).
    Section 314.122(d) sets forth requirements for relisting petitions 
for unlisted discontinued products. (The burden hours for Sec.  
314.122(d) are already approved by OMB under 0910-0183 and are not 
included in the hour burden estimates in table 1 of this document).
    Section 314.126(c) sets forth requirements for a petition to waive 
criteria for adequate and well-controlled studies. (The burden hours 
for Sec.  314.126(c) are already approved by OMB under 0910-0183 and 
are not included in the hour burden estimates in table 1 of this 
document).
    Section 314.151(a) and (b) set forth requirements for the 
withdrawal of approval of an ANDA and the applicant's opportunity for a 
hearing and submission of comments. (The burden hours for Sec.  
314.151(a) and (b) are included under the parts 10 through 16 hearing 
regulations, in accordance with Sec.  314.201, and are not included in 
the hour burden estimates in table 1 of this document).
    Section 314.151(c) sets forth the requirements for withdrawal of 
approval of an ANDA and the applicant's opportunity to submit written 
objections and participate in a limited oral hearing. (The burden hours 
for Sec.  314.151(c) are included under the parts 10 through 16 hearing 
regulations, in accordance with Sec.  314.201, and are not included in 
the hour burden estimates in table 1 of this document).
    Section 314.152(b) sets forth the requirements for suspension of an 
ANDA when the listed drug is voluntarily withdrawn for safety and 
effectiveness reasons, and the applicant's opportunity to present 
comments and participate in a limited oral hearing. (The burden hours 
for Sec.  314.152(b) is included under the parts 10 through 16 hearing 
regulations, in accordance with Sec.  314.201, and is not included in 
the hour burden estimates in table 1 of this document).
    Section 314.161(b) and (e) sets forth the requirements for 
submitting a petition to determine whether a listed drug was 
voluntarily withdrawn from sale for safety or effectiveness reasons. 
(The burden hours for Sec.  314.161(b) and (e) are already approved by 
OMB under 0910-0183 and are not included in the hour burden estimates 
in table 1 of this document).
    Section 314.200(c), (d), and (e) requires that applicants or others 
subject to a notice of opportunity for a hearing who wish to 
participate in a hearing file a written notice of participation and 
request for a hearing as well as the studies, data, and so forth, 
relied on. Other interested persons may also submit comments on the 
notice. This section also sets forth the content and format 
requirements for the applicants' submission in response to notice of 
opportunity for hearing. (The burden hours for Sec.  314.200(c), (d), 
and (e) are included under the parts 10 through 16 hearing regulations, 
in accordance with Sec.  314.201, and are not included in the hour 
burden estimates in table 1 of this document).
    Section 314.200(f) states that participants in a hearing may make a 
motion to the presiding officer for the inclusion of certain issues in 
the hearing. (The burden hours for Sec.  314.200(f) are included under 
the parts 10 through 16 hearing regulations, in accordance with Sec.  
314.201, and are not included in the hour burden estimates in table 1 
of this document).
    Section 314.200(g) states that a person who responds to a proposed 
order from FDA denying a request for a hearing provide sufficient data, 
information, and analysis to demonstrate that there is a genuine and 
substantial issue of fact which justifies a hearing. (The burden hours 
for Sec.  314.200(g) are included under the parts 10 through 16 hearing 
regulations, in accordance with Sec.  314.201, and is not included in 
the hour burden estimates in table 1 of this document.)
    Section 314.420 states that an applicant may submit to FDA a drug 
master file in support of an application, in accordance with certain 
content and format requirements.
    Section 21 CFR 314.430 states that data and information in an 
application are disclosable under certain conditions, unless the 
applicant shows that extraordinary circumstances exist. (The burden 
hours for Sec.  314.430 is included under the parts 10 through 16 
hearing regulations, in accordance with Sec.  314.201, and is not 
included in the hour burden estimates in table 1 of this document).
    Section 314.530(c) and (e) states that, if FDA withdraws approval 
of a drug approved under the accelerated approval procedures, the 
applicant has the opportunity to request a hearing and submit data and 
information. (The burden hours for Sec.  314.530(c) and (e) are 
included under the parts 10 through 16 hearing regulations, in 
accordance with Sec.  314.201, and are not included in the hour burden 
estimates in table 1 of this document).
    Section 314.530(f) requires that an applicant first submit a 
petition for stay of action before requesting an order from a court for 
a stay of action pending review. (The burden hours for Sec.  314.530(f) 
are already approved by OMB under 0910-0194 and are not included in the 
hour burden estimates in table 1 of this document).
    Respondents to this collection of information are all persons who 
submit an application or abbreviated application or an amendment or 
supplement to FDA under part 314 to obtain approval of a new drug, and 
any person who owns an approved application or abbreviated application.

                                 Table 1.--Estimated Annual Reporting Burden\1\
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   21 CFR Section; [Form          No. of        No. of Responses   Total Annual      Hours Per
          Number]              Respondents       per Respondent      Responses       Response       Total Hours
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314.50 (a), (b), (c), (d),          72                  1.44          104           1,642             170,768
 (e), (f), (h), and (k)
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314.50(i) and                      194                  2.34          454               2                 908
 314.94(a)(12)
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314.50(j)                           70                  3.71          260               2                 520
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[[Page 60405]]

 
314.52 and 314.95                   24                  2.25           54              16                 864
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314.54                              16                  1              16             300               4,800
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314.60                             275                 19.06        5,242              80             419,320
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314.65                              10                  1              10               2                  20
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314.70 and 314.71                  234                 10.99        2,572             150             385,800
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314.72                              61                  4.52          276               2                 552
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314.81(b)(1) [3331]                115                  3.88          447               8               3,576
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314.81(b)(2) [2252]                612                 12.47        7,632              40             305,280
----------------------------------------------------------------------------------------------------------------
314.81(b)(3)(i) [2253]             332                 44.09       14,638               2              29,276
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314.94(a) and (d)                  100                  4.59          459             480             220,320
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314.96                             275                 23.63        6,500              80             520,000
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314.97                             200                 16.75        3,350              80             268,000
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314.99(a)                           44                  2.02           89               2                 178
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314.101(a)                           2                  1               2                .50                1
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314.107(c)(4),                       3                  2               6               1                   6
 314.107(e)(2)(iv), and
 314.107(f)
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314.110(a)(5)                       41                  1.26           52                .50               26
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314.120(a)(5)                       12                  1.16           14                .50                7
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314.420                            403                  1.72          694              61              42,334
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Total                                                                                               2,372,556
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.


    Dated: October 5, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-22815 Filed 10-6-04; 11:56 am]
BILLING CODE 4160-01-S