[Federal Register Volume 63, Number 182 (Monday, September 21, 1998)]
[Notices]
[Pages 50241-50244]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-25142]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

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


Agency Information Collection Activities; Submission for OMB 
Review; 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 that the 
proposed collection of information listed below has been submitted to 
the Office of Management and Budget (OMB) for review and clearance 
under the Paperwork Reduction Act of 1995 (the PRA).

DATES: Submit written comments on the collection of information by 
October 21, 1998.

ADDRESSES: Submit written comments on the collection of information to 
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.

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: In compliance with section 3507 of the PRA 
(44 U.S.C. 3507), FDA has submitted the following proposed collection 
of information to OMB for review and clearance.

Application 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) 
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 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.

[[Page 50242]]

    Section 314.50(h) requires that patent information as described 
under Sec. 314.53 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 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(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 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 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 and that certain content and notification 
procedures be followed. (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 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)(i) and (c)(1)(iii) establish recordkeeping 
requirements for reports of postmarketing adverse drug experiences. 
(Sections 314.80(c)(1)(i) and (c)(1)(iii) 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 314.81(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).
    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)(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 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 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's 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 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)(3) states 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 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 
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

[[Page 50243]]

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 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 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) provides 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. (Section 314.110(b) is included under 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 an applicant request within 10 
days after receipt of a not approvable letter, 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. 314.120, and is not included in the hour burden estimates in Table 
1 of this document.)
    Section 314.120(a)(5) requires that an applicant notify FDA within 
10 days after receipt of a not approvable letter, 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.)
    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) set 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 regulation, 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) set forth the requirements for 
submitting a 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 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 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. 
(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 regulation, 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 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 submit all promotional 
materials to FDA for consideration during the preapproval review 
period. (The burden hours required for

[[Page 50244]]

Sec. Sec. 314.550 are reported and approved under OMB control number 
0910-0376, which published in the Federal Register at 62 FR 55408 and 
is 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 or 
antibiotic drug, and any person who owns an approved application or 
abbreviated application.
    In the Federal Register of May 28, 1998 (63 FR 29229), the agency 
requested comments on the proposed collection of information. No 
comments were received.
    Elsewhere in this issue of the Federal Register, the agency has 
published a Notice of Availability of a Draft Guidance for Industry on 
Submission of Abbreviated Reports and Synopses in Support of Marketing 
Applications in accordance with section 118 of the FDA Modernization 
Act. The goal of the draft guidance is to reduce the submission burden 
of applicants where appropriate. The estimated PRA reporting burden for 
Sec. 314.50 reflects an anticipated reduction of 300 hours in burden.
    Based on the information provided by the pharmaceutical industry 
for the number of hours per response, on FDA's estimate of the 
reduction in reporting resulting from the draft guidance for submitting 
abbreviated reports and synopses for marketing applications, and on 
FDA's prior experience with respondents, the number of responses per 
respondent, and the number of total annual responses, FDA estimates the 
burden of this collection as follows:

                                  Table 1.--Estimated Annual Reporting Burden1                                  
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                                                  No. of                                                        
21 CFR Section [Form Number]      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           1,300           161,200         
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) [3331]               140               5             700              48            33,600         
314.81(b)(2) [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         
314.98(c) [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                                                                                         2,121,270         
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of            
  information.                                                                                                  


    Dated: September 9, 1998.
 William K. Hubbard,
 Associate Commissioner for Policy Coordination.
[FR Doc. 98-25142 Filed 9-18-98; 8:45 am]
BILLING CODE 4160-01-F