[Federal Register Volume 63, Number 102 (Thursday, May 28, 1998)]
[Notices]
[Pages 29229-29233]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-14050]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration
[Docket No. 98N-0304]


Agency Information Collection Activities: Proposed Collection; 
Comment Request

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 
(the PRA), Federal agencies are required to publish notice in the 
Federal Register concerning each proposed collection of information, 
including each proposed reinstatement 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 comments on the collection of information by July 
27, 1998.

ADDRESSES: Submit written comments on the collection of information to 
the Dockets Management Branch (HFA-305), Food and Drug Administration,

[[Page 29230]]

12420 Parklawn Dr., rm. 1-23, Rockville, MD 20857. 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 Information 
Resources Management (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 reinstatement 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 set forth in this document.
    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)--Reinstatement

    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 (j) of the act is effective with respect to such 
drug. Section 505(b) and (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 part 314) , who apply for approval of a NDA in order to market or 
to continue to market a drug.
    The following sections in part 314 set forth the specific format 
and content requirements for NDA's.
    Section 314.50(a) requires that an application form (Form FDA 356h) 
must be submitted that includes basic introductory information about 
the drug as well as a checklist of enclosures. (Section 314.50(a) is 
already approved by OMB under 0910-0338 and is not included in the hour 
burden estimates in Table 1 of this document.)
    Section 314.50(b) requires that an index must be submitted with the 
archival copy of the application and that it must reference certain 
sections of the application.
    Section 314.50(c) requires that a summary of the application must 
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 that the applicant must 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 
must be submitted with the archival copy.
    Section 314.50(h) requires that patent information as described 
under Sec. 314.53 must be submitted with the application. (Section 
314.50(h) is already approved by OMB under 0910-0305 and is not 
included in the hour burden estimates in Table 1 of this document.)
    Section 314.50(i) requires that a patent certification information 
must be submitted in 505(b)(2) applications for patents claiming the 
drug, drug product, method of use, or method of manufacturing. (Section 
314.50(i) is already approved by OMB under 0910-0305 and is not 
included in the hour burden estimates in Table 1 of this document.)
    Section 314.50(j) requires that applicants that request a period of 
marketing exclusivity must submit certain information with the 
application. (Section 314.50(j) is already approved by OMB under 0910-
0305 and is not included in the hour burden estimates in Table 1 of 
this document.)
    Section 314.50(k) requires that an archival, review, and field copy 
of the application must be submitted.
    Section 314.52 requires that notice of certification of invalidity 
or noninfringement of a patent to patent holders and NDA holders must 
be sent by 505(b)(2) applicants and must follow certain content and 
notification procedures. (Section 314.52 is already approved by OMB 
under 0910-0305 and is not included in the hour burden estimates in 
Table 1 of this document.)
    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 must be 
submitted to FDA 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). (Section 314.80(c)(1) and (c)(2) is already 
approved by OMB under 0910-0230 and 0910-0291 and is not included in 
the hour burden estimates in Table 1 of this document.)
    Section 314.80(c)(1)(iii) and (i) establishes recordkeeping 
requirements for reports of postmarketing adverse drug experiences. 
(Section 314.80(c)(1)(iii) and (i) is already approved by OMB under 
0910-0230 and 0910-0291 and is not included in the hour burden 
estimates in Table 1 of this document.)

[[Page 29231]]

    Section 314.81(b)(1) requires that field alert reports must be 
submitted to FDA (Form FDA 3331).
    Section 314.81(b)(2) requires that annual reports must be submitted 
to FDA (Form FDA 2252).
    Section 314.81(b)(3)(i) requires that drug advertisements and 
promotional labeling must be submitted to FDA (Form FDA 2253). (Section 
314.81(b)(3)(i) is already approved by OMB in ``Transmittal of 
Advertisements and Promotional Labeling for Drugs and Biologics for 
Human Use,'' which published in the Federal Register of October 24, 
1997 (62 FR 55408), and is not included in the hour burden estimates in 
Table 1 of this document.)
    Section 314.81(b)(3)(iii) sets forth reporting requirements for 
sponsors who withdraw an approved drug product from sale. (Section 
314.81(b)(3)(iii) is already approved by OMB under 0910-0045 and is 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 Secs. 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 Secs. 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. (Section 314.93 is 
already approved by OMB under 0910-0183 and is not included in the hour 
burden estimates in Table 1 of this document.)
    The following sections in part 314 set forth requirements when 
submitting an abbreviated new drug application (ANDA).
    Section 314.94(a) and (d) requires that an ANDA must contain the 
following and 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; and patent 
certification.
    Section 314.95 requires that notice of certification of invalidity 
or noninfringement of a patent to patent holders and NDA holders must 
be sent by ANDA applicants. (Section 314.95 is already approved by OMB 
under 0910-0305 and is not included in the hour burden estimates in 
Table 1 of this document.)
    Section 314.96 sets forth requirements for amendments to an 
unapproved application.
    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. (Section 314.98(a) is already 
approved by OMB under 0910-0230 and 0910-0291 and is not included in 
the hour burden estimates in Table 1 of this document.)
    Section 314.98(c) requires other postmarketing reports: 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 advertisements and promotional labeling is included under 
Sec. 314.81(b)(3)(i).)
    Section 314.99(a) requires that sponsors must 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 Secs. 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 
Secs. 314.94(a) and (d), 314.96, and 314.97.)
    Section 314.101(a) requires that, if FDA refuses to file an 
application, the applicant may request an informal conference with FDA 
and request that the application be filed 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(c)(4) is already approved by OMB under 0910-0305 and 
is not included in the hour burden estimates in Table 1 of this 
document.)
    Section 314.107(e)(2)(iv) requires that an applicant must submit a 
copy of the entry of the order or judgement to FDA within 10 working 
days of a final judgement. (Section 314.107(e)(2)(iv) is already 
approved by OMB under 0910-0305 and is not included in the hour burden 
estimates in Table 1 of this document.)
    Section 314.107(f) requires that an ANDA or 505(b)(2) applicants 
must 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 314.107(f) is 
already approved by OMB under 0910-0305 and is not included in the hour 
burden estimates in Table 1 of this document.)
    Section 314.110(a)(3) and (a)(4) requires 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. (Section 314.110(a)(3) and (a)(4) is 
included under the parts 10 through 16 (21 CFR part 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 314.110(a)(5) requires 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) requires 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. (Section 314.110(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 314.120(a)(3) requires 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. (Section 314.120(a)(3) 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 314.120(a)(5) requires 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) states 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. (Section 
314.122(a) is already approved by OMB under 0910-0183 and is not 
included in the hour burden estimates in Table 1 of this document.)

[[Page 29232]]

    Section 314.122(d) sets forth requirements for relisting petitions 
for unlisted discontinued products. (Section 314.122(d) is already 
approved by OMB under 0910-0183 and is 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. (Section 314.126(c) 
is already approved by OMB under 0910-0183 and is not included in the 
hour burden estimates in Table 1 of this document.)
    Section 314.151(a) and (b) sets forth requirements for the 
withdrawal of and approval of an ANDA and the applicant's opportunity 
for a hearing and submission of comments. (Section 314.151(a) and (b) 
is included under the parts 10 through 16 hearing regulations, in 
accordance with Sec. 314.201, and it is 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. (Section 
314.151(c) 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 314.152(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. (Section 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 and petition to determine whether a listed drug was 
voluntarily withdrawn from sale for safety or effectiveness reasons. 
(Section 314.161(b) and (e) is already approved by OMB under 0910-0183 
and is 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 must 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. (Section 314.200(c), (d), and (e) 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 314.200(f) requires that participants in a hearing may make 
a motion to the presiding officer for the inclusion of certain issues 
in the hearing. (Section 314.200(f) 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 314.200(g) requires that a person may respond to a proposed 
order from FDA denying a request for a hearing by providing sufficient 
data, information, and analysis to demonstrate that there is a genuine 
and substantial issue of fact which justifies a hearing. (Section 
314.200(g) 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 314.420 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 314.430 states that data and information in an application 
are disclosable under certain conditions, unless the applicant shows 
that extraordinary circumstances exist. (Section 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) requires 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. (Section 314.530(c) and (e) 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(f) requires that an applicant must first submit a 
petition for stay of action before requesting an order from a court for 
a stay of action pending review. (Section 314.530(f) is already 
approved by OMB under 0910-0194 and is not included in the hour burden 
estimates in Table 1 of this document.)
    Section 314.550 requires that applicants must submit all 
promotional materials to FDA for consideration during the preapproval 
review period. (Section 314.550 is already approved by OMB in 
``Transmittal of Advertisements and Promotional Labeling for Drugs and 
Biologics for Human Use,'' which published in the Federal Register (62 
FR 55408), and is not included in the hour burden estimates in Table 1 
of this document.)
    Based on information provided by the pharmaceutical industry for 
the number of ``hours per response,'' and based on submissions 
collected and data tabulated by FDA for the ``number of respondents,'' 
the ``number of responses per respondent,'' and the number of ``total 
annual responses,'' FDA estimates the burden of this collection of 
information as follows:

                                  Table 1.--Estimated Annual Reporting Burden<SUP>1                                  
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                                                  No. of                                                        
     21 CFR Section/Form          No. of       Responses per   Total Annual      Hours per        Total Hours   
                                Respondents     Respondents      Responses       Response                       
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314.50(b), (c), (d), (e),                                                                                       
 (f), and (k)                      83               1.49          124           1,600             198,400       
314.54                              4               1.25            5             300               1,500       
314.60                            144              16.89        2,432              80             194,560       
314.65                             18               1.28           23               2                  46       
314.70 and 314.71                 418               5.33        2,229             300             668,700       
314.72                             59               2.17          128               2                 256       
314.81(b)(1) (FDA 3331)           140               5             700              48              33,600       
314.81(b)(2) (FDA 2252)           269               9.06        2,438              40              97,520       
314.94(a) and (d)                 117               3.96          464             480             222,720       
314.96                            315              12.43        3,915              80             313,200       
314.97                            152              19.74        3,000              80             240,000       

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314.98(c) (FDA 2252)              265              17.17        4,551              40             182,040       
314.99(a)                          46              13.04          600               2               1,200       
314.110(a)(5)                      55               1.13           62               8                 496       
314.120(a)(5)                      26               1.12           29               8                 232       
314.420                           450               1.11          500               8               4,000       
Total Burden Hours                                                                              2,158,470       
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\1\There are no capital costs or operating and maintenance costs associated with this collection of information.


    Dated: May 20, 1998.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 98-14050 Filed 5-27-98; 8:45 am]
BILLING CODE 4160-01-F