Agency Information Collection Activities: Proposed Collection; Comment Request

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,

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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.)

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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.)

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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 Burden1

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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