0001 NDAs SSA 2017 Ext

U.S. Food & Drug Administration
Applications for FDA Approval to Market a New Drug
OMB Control No. 0910 0001
SUPPORTING STATEMENT Part A: Justification
1. Circumstances Making the Collection of Information Necessary
This information collection supports Food and Drug Administration (FDA) regulations.
Specifically, under section 505(a) of the Federal Food, Drug, and Cosmetic Act (FFDCA or 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. Under the
act, it is the sponsor's responsibility to provide the information needed by FDA to make a
scientific and technical determination as to whether the product is safe and effective for use.
Regulations regarding the approval of new drug applications are codified under 21 CFR Part
314, and include information collection provisions. To assist respondents in this regard, FDA
has created the following:





Form FDA 0356h1 (and instructions): Application to Market a New or Abbreviated New
Drug or Biologic for Human Use;
Form FDA 2252 (and instructions): Transmittal of Annual Reports for Drugs and
Biologics For Human Use (21 CFR 314.81);
Form FDA 2253 (and instructions): Transmittal of Advertisements and Promotional
Labeling For Drugs and Biologics For Human Use; and
Forms FDA 3331/3331a: Field Alert Report and Instruction

Therefore, unless otherwise noted, this information collection requests approval for the
provisions found in the associated regulations, accompanying forms, and discussed in this
supporting statement.
2. Purpose and Use of the Information Collection
Section 505 of the FFDCA requires that a new drug may not be marketed unless the
manufacturer provides FDA with scientific evidence that the drug is both safe and effective. The
regulations at 21 CFR part 314 state: [t]he purpose of this part is to establish an efficient and
thorough drug review process in order to: (a) Facilitate the approval of drugs shown to be safe
and effective; and (b) ensure the disapproval of drugs not shown to be safe and effective. These
regulations are also intended to establish an effective system for FDA's surveillance of marketed
drugs. Therefore, without the information provided by respondents regarding the drug products
they seek to market, we would not be able to adequately protect the public health by assuring
1

Burden associated with Form FDA 0356h is approved under OMB Control No. 0910-0338: General
Licensing Provisions: Biologics License Application, Changes to an Approved Application, Labeling,
Revocation and Suspension (21 CFR Part 601).

their safety and efficacy.
3. Use of Improved Information Technology and Burden Reduction
We encourage the electronic submission of information required under part 314, and have issued
several guidance documents describing the process for submitting information in electronic
format. These guidance documents and others are available at FDA's web site
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
4. Efforts to Identify Duplication and Use of Similar Information
We are unaware of duplicative information collection. In some cases, regulations may warrant
the establishment of an independent information collection request. For example, some, but not
all, applications may be associated with patent information; and some, but not all, applications
may require labeling for specific populations. In such cases and where relevant in this
supporting statement, we have cross -referenced the applicable OMB Control No.
5. Impact on Small Businesses or Other Small Entities
The regulations at 21 CFR Part 314 do not provide exemptions for small businesses. However,
FDA has established various agency components to assist small businesses in complying with
our regulations. Contact information may be found on our website at https://www.fda.gov.
Additionally, and as mentioned above, FDA’s Center for Drug Evaluation and Research (CDER)
has issued guidance on a variety of topics associated with new and abbreviated drug applications.
These documents are developed to assist respondents with the regulatory requirements and are
available online.
6. Consequences of Collecting the Information Less Frequently
Information collection schedule is consistent with statutory requirements under the FFDCA.
7. Special Circumstances Relating to the Guidelines in 5 CFR 1320.5(d)(2)
There are the following special circumstances relating to the information collection: (1) sections
of 21 CFR 314 require reporting in less than 30 days – these are postmarketing reports and
expedited notification to FDA and are necessary to determine as soon as possible whether a
threat to the public health exists that warrants immediate regulatory action; (2) more than an
original and 2 copies of a submission is required (e.g., four copies of draft labeling or 12 copies
of final printed labeling) in order to permit concurrent (and, consequently, quicker) review of the
application; (3) although applicants are required to submit proprietary, trade secret, and other
confidential information, this information is protected under FDA regulations and the FFDCA
(see number 10 below); and (4) the specific format and content requirements for application
submissions is necessary to ensure complete submissions (and reduce the need for timeconsuming resubmissions) and to assist FDA in efficient reviews.
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8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the
Agency
In the Federal Register of May , 26, 2017 (82 FR 24351) FDA published a notice soliciting
public comment on the information collection. One comment was received suggesting that
human drug and biologic applicants be required to include a preliminary Structured Benefit Risk
(SBR) table upon submission of applications for marketing approval. As discussed in our 30day notice of December 12, 2017, (82 FR 58403), while we appreciate and are considering this
suggestion, because the regulations currently impose no such requirement, we have made no
adjustments to the information collection. In addition to seeking public input through notice and
comment in the Federal Register, we regularly obtain informal feedback through our
participation in conferences and workshops sponsored by trade organizations such as The Food
and Drug Law Institute, The Drug Information Association, The Pharmaceutical Research and
Manufacturers of America, and The International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for Human Use.
9. Explanation of Any Payment or Gift to Respondents
No payment or gift is provided to respondents.
10. Assurance of Confidentiality Provided to Respondents
Confidentiality of the information submitted under these reporting requirements is protected
under 21 CFR 314.430 and under 21 CFR part 20. The unauthorized use or disclosure of trade
secrets required in applications is specifically prohibited under section 310(j) of the FFDCA.
11. Justification for Sensitive Questions
There are no questions of a sensitive nature.
12. Estimates of Annualized Burden Hours and Costs
12a. Annualized Hour Burden Estimate
Table 1 – Estimated Annual Reporting Burden
21 CFR Part 314

No. of
Respondents

SUBPART B – APPLICATIONS
314.50(a)-(g)2, (i)-(l)--Content
and format of a 505(b)(1) or
505(b)(2) application
2

No. of
Responses
per
Respondent

Total
Annual
Responses

Avg.
Burden
per
Response

1.33

503

1,921

378

Total Hours

966,263

21 CFR 314.50(h) requires patent information and burden is approved under OMB Control No. 0910-

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21 CFR Part 314

No. of
Respondents

No. of
Responses
per
Respondent
7
3

Total
Annual
Responses
21

Avg.
Burden
per
Response
16

3

627

16

10,032

9.96
71.63

5,618
1,934

80
2

449,440
3,868

7.04

5,897

150

884,550

2.04
-

289
-

2
-

578
-

19.98

6,834

8

54,672

5.07
81.66

4,632
43,198

40
2

185,280
86,396

-

-

-

-

-

-

-

-

3.75

676.5

480

324,720

26.66

13,647

80

1,091,760

314.52--Non-infringement of
patents (NDAs)
314.95--Non-infringement of
209
patents (ANDAs)
314.60--Amendments
564
314.65--Withdrawal of
27
unapproved applications
314.70 and 314.71-838
Supplements and submissions
314.72--Change of ownership
142
314.80-Postmarketing reporting
of adverse drug experiences3
314.81--Other postmarketing
342
reports and 314.81(b)(1) field
alert reports
314.81(b)(2)--Annual reports
913
314.81(b)(3)(i) --Promotional
529
labeling
314.81(b)(3)(iii)-withdrawal
from sale4
SUBPART C – ABBREVIATED APPLICATIONS
314.93-Petition to request a
change from a listed drug5
314.94(a) and (d)--ANDA
180.5
content
314.96(a)(1)--Amendments to
514
unapproved ANDAs

Total Hours

336

0513: Applications for FDA Approval to Market a New Drug: Patent Submission and Listing
Requirements and Application of 30-month Stays on Approval of Abbreviated New Drug Applications
Certifying That a Patent Claiming a Drug Is Invalid or Will Not Be Infringed.
3

Burden approved under OMB Control Nos. 0910-0230 (Postmarketing Adverse Drug Experience
Reporting) and 0910-0291 (FDA’s MEDWATCH Program – Paper Reporting).

4

Burden approved under OMB Control No. 0910-0045: Registration of Producers of Drugs and Listing
of Drugs in Commercial Distribution.

5

Burden approved under OMB Control No. 0910-0191: Administrative Practices and Procedures;
Formal Evidentiary Public Hearing.

4

21 CFR Part 314

No. of
Respondents

No. of
Responses
per
Respondent
343
17.57

Total
Annual
Responses

Avg.
Burden
per
Response
80

Total Hours

314.97--Supplements to
6027
482,160
ANDAs
314.98-Postmarketing reports6
314.99(a)--Responsibilities of
265
7.04
1867
2
3,734
ANDA Applicants
SUBPART D – FDA ACTION ON APPLICATIONS AND ABBREVIATED APPLICATIONS
314.101(a)—ANDA filing
1
1
1
.5
.5
(30 min.)
314.103-Dispute resolution
75
2
150
5
750
SUBPART G – MISCELLANEOUS PROVISIONS
314.420--Drug Master Files
500
2.06
1,028
61
62,708
SUBPART H – ACCELERATED APPROVAL OF NEW DRUGS FOR SERIOUS OR LIFETHREATENING ILLNESSES
314.550--Promotional material
29
7.76
225
120
27,000
and subpart H applications
TOTAL
4,634,247.5

The estimates above are based on our experience with the information collection. Other
relevant regulations are discussed as follows:
Section 314.95 requires that any notice of certification of invalidity or non-infringement of a
patent to each patent owner and the NDA holder be sent by ANDA applicants. Burden hours for
§ 314.95 are approved under OMB Control No. 0910-0786: Abbreviated New Drug Applications
and 505(b)(2) Applications.
Section 314.96 sets forth requirements for amendments to an unapproved ANDA and section
314.97 sets forth requirements for submitting supplements to an approved ANDA for certain
changes to the application (burden hours for § 314.96 and 314.97 are approved under OMB
Control No. 0910-0786 are therefore not included in table 1 above);
Section 314.107 – Abbreviated New Drug Applications and 505(b)(2) Applications provisions,
unless otherwise specified, are approved under OMB Control No. 0910-0786 – id.;
section 314.110(b)(3) states that, after receipt of an FDA complete response letter, an applicant
must either 1) resubmit the application addressing all the deficiencies identified in the complete
response letter, 2) withdraw the application, or 3) request an opportunity for a hearing on the
question of whether there are grounds for denying approval of the application. The burden hours
for § 314.110(b)(3) are included under parts 10 through 16 (21 CFR parts 10 through 16)
6

Burden approved under OMB Control Nos. 0910-0230 (Postmarketing Adverse Drug Experience
Reporting) and 0910-0291 (FDA’s MEDWATCH Program – Paper Reporting).

5

hearing regulations, in accordance with § 314.201 and are OMB approved in 0910-0191.
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 § 314.122(a) are approved under OMB Control No. 0910-0191.
Section 314.122(d) sets forth requirements for relisting petitions for unlisted discontinued
products. The burden hours for § 314.122(d) are approved under OMB Control No. 0910-0191.
Sections 314.125 and 314.127 state that FDA may refuse to approve an NDA or an ANDA and
will provide the applicant written notice of an opportunity for a hearing under section 314.200
along with the reason for refusal to approve the application, including lack of a patent
certification or statement with respect to each listed patent for an approved drug product that is
pharmaceutically equivalent to the drug product for which the original 505(b)(2) application is
submitted and was approved before the original 505(b)(2) was submitted. The burden hours for
section 314.125 and 314.127 (refuse to approve an ANDA) are approved by OMB and are
included under parts 10 through 16 (21 CFR parts 10 and 16) hearing regulations, in accordance
with § 314.201. The burden hours for these collections are approved under OMB Control No.
0910-0191.
Section 314.126(c) sets forth requirements for a petition to waive criteria for adequate and wellcontrolled studies. The burden hours for § 314.126(c) are approved by OMB under 0910-0191
Sections 314.150(a) and (b) and 314.151(a) and (b) set forth requirements for the withdrawal of
approval of an NDA or ANDA and the applicant's opportunity for a hearing and submission of
comments. The burden hours for § 314.151(a) and (b) are included under parts 10 through 16
hearing regulations, in accordance with § 314.201. This information collection burden is
approved by OMB in 0910-0191.
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 § 314.151(c) are included under parts 10 through 16 hearing regulations,
in accordance with § 314.201, approved by OMB under OMB control number 0910-0191.
Section 314.153(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 has an
opportunity to present comments and participate in a limited oral hearing. The burden hours for
§ 314.152(b) are included under parts 10 through 16 hearing regulations, in accordance with §
314.201, and are approved under OMB Control No. 0910-0191.
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 § 314.161(b) and (e) are approved under OMB Control No. 0910-0191.
Section 314.200(c), (d), and (e) requires that applicants or others subject to a notice of
6

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 § 314.200(c), (d), and (e) are included under
parts 10 through 16 hearing regulations, in accordance with § 314.201, and are approved under
OMB Control No. 0910-0191.
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
§ 314.200(f) are included under parts 10 through 16 hearing regulations, in accordance with
§ 314.201, and are approved under OMB Control No. 0910-0191.
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
§ 314.200(g) are included under parts 10 through 16 hearing regulations, in accordance with
§ 314.201, and are approved under OMB Control No. 0910-0191.
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. (The burden hours
for § 314.430 are included under parts 10 through 16 hearing regulations, in accordance with
§ 314.201, and are approved in OMB 0910-0191.
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 § 314.530(c) and (e) are included under parts
10 through 16 hearing regulations, in accordance with § 314.201, and are approved in OMB
0910-0191.
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
§ 314.530(f) are already approved in OMB 0910-0194.
Section 314.550 requires an applicant with a new drug product being considered for accelerated
approval to submit copies of all promotional materials to the FDA during the preapproval and
post-approval periods.
Section 314.610(b)(1) requires that applicants include a plan or approach to postmarketing study
commitments in applications for approval of new drugs when human efficacy studies are not
ethical or feasible, and provide status reports of postmarketing study commitments. (The
information collection burden estimate for § 314.610(b)(1) is included in table 1 under the
7

estimates for §§ 314.50 (a), (b), (c), (d), (e), (f), (k) and (l) and 314.81(b)(2)).
Section 314.610(b)(3) requires that applicants propose labeling to be provided to patient
recipients in applications for approval of new drugs when human efficacy studies are not ethical
or feasible. (The information collection burden estimate for § 314.610(b)(3) is included in table
1 under the estimates for § 314.50(e)).
Section 314.630 requires that applicants provide postmarketing safety reporting for applications
for approval of new drugs when human efficacy studies are not ethical or feasible. The burden
hours for § 314.630 are already approved by OMB under OMB 0910-0230 and 0910-0291.
Section 314.640 requires that applicants provide promotional materials for applications for
approval of new drugs when human efficacy studies are not ethical or feasible. (The information
collection burden estimate for § 314.640 is included in table 1 above under the estimates for
§ 314.81(b)(3)(i)).
12b. Annualized Cost Burden Estimate
FDA estimates an average pharmaceutical industry wage rate of $75.00 per hour for
preparing and submitting the information collection requirements under 21 CFR 314. When
multiplied by the burden hours above, the cost to respondents is estimated at $347,512,312.
13. Estimates of Other Total Annual Costs to Respondents and/or Recordkeepers/Capital Costs
There are no capital costs or operating and maintenance costs associated with this collection of
information.
14. Annualized Cost to the Federal Government
FDA has allocated 835 FTEs to reviewing submissions under 21 CFR 314. Where the cost of
each FTE is approximately $175,000 (fully-loaded), the total cost burden to the Federal
Government is estimated at $146,125,000.
15. Explanation for Program Changes or Adjustments
The estimated burden for the information collection reflects an increase of 1,212,941 annual
hours and 7,429 annual responses. We have made this adjustment based on updated data on the
number of drug applications we have received. Also, we have revised the IC list
appearing at www.reginfo.gov by consolidating the 17 previously itemized regulatory
provisions into 4 elements. We believe this will assist the reader by more easily identifying the
summary of cumulative fluctuations for the collection. At the same time, readers may still view
estimated burden associated with individual provisions by referring to our 60-day and 30-day
notices and in the burden table found at Q.12: Estimates of Annualized Burden Hours
and Costs of this supporting statement.
8

16. Plans for Tabulation and Publication and Project Time Schedule
FDA does not intend to publish tabulated results of these information collection requirements.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
Display of the OMB Expiration date is appropriate.
18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.

9