0014 IND Regs SSA 2019 Ext

UNITED STATES FOOD & DRUG ADMINISTRATION
Investigational New Drug (IND) Regulations
21 CFR Part 312
OMB Control No. 0910-0014
SUPPORTING STATEMENT Part A: Justification
1. Circumstances Making the Collection of Information Necessary
This information collection supports Food and Drug Administration (FDA, us or we)
regulations. Section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act (21
U.S.C. 355(a)) provides that a new drug may not be introduced or delivered for introduction
into interstate commerce in the United States unless we have previously approved a new drug
application (NDA). We approve an NDA only if the sponsor of the application first
demonstrates that the drug is safe and effective for the conditions prescribed, recommended,
or suggested in the product’s labeling. Proof must consist, in part, of adequate and wellcontrolled studies, including studies in humans, that are conducted by qualified experts. We
are also charged, under section 505(i) of the FD&C Act (21 U.S.C. 355(i)), with promulgating
regulations governing the investigational use of drugs by qualified experts, including
regulations to ensure that clinical investigation of the safety and effectiveness of unapproved
new drugs and biological products can be conducted.
Accordingly, we have issued regulations in 21 CFR part 312 (Investigational New Drug
Application) that establish “procedures and requirements governing the use of investigational
new drugs, including procedures and requirements for the submission to, and review by,
[FDA] of investigational new drug applications (IND's).” The regulations set forth
information collection requirements covering the content and format of an initial application
submission, as well as amendments to that application; the reporting on significant revisions
of clinical investigation plans, as well as progress and safety reporting; and recordkeeping
requirements pertaining to the disposition of drugs, individual case histories, and certain other
documentation verifying the fulfillment of responsibilities by clinical investigators.
To assist respondents to the information collection, we have developed the following
collection instruments:



Form FDA 1571 entitled, “Investigational New Drug Application (IND)”; and
Form FDA 1572, “Statement of Investigator.”

Instructions for completing the forms are available on our website at www.fda.gov. We have
also issued procedural draft guidance for industry entitled, “Investigational New Drug
Applications Prepared and Submitted by Sponsor-Investigators,” also available from our
website at https://www.fda.gov/downloads/Drugs/Guidances/UCM446695.pdf. The
guidance document provides details of the informational content of an IND as well as
information needed to complete required forms.

Anyone intending to conduct a clinical investigation must submit Form FDA 1571 as
instructed. The reporting elements include: (1) a cover sheet containing background
information on the sponsor and investigator; (2) a table of contents; (3) an introductory
statement and general investigational plan; (4) an investigator’s brochure describing the drug
substance; (5) a protocol for each planned study; (6) chemistry, manufacturing, and control
information for each investigation; (7) pharmacology and toxicology information for each
investigation; and (8) previous human experience with the investigational drug.
Form FDA 1572 is completed, signed, and submitted by the IND sponsor before an
investigator may participate in an investigation. It includes background information on the
investigator as well as the investigation, and a general outline of the planned investigation and
study protocol.
We therefore request OMB approval of the information collection provisions found in 21 CFR
part 312, as well as Forms FDA 1571 and 1572 and associated instructions found on our
website and in agency guidance.
2. Purpose and Use of the Information Collection
The IND applications (and any supplements thereto) are reviewed by FDA medical officers
and other agency staff responsible for overseeing a specific study. The details and complexity
of the review requirements are dictated by the scientific procedures and human subject
safeguards that must be followed when conducting clinical tests of investigational new drugs.
The IND application enables us to monitor clinical investigations of unapproved new drugs
and biological products with regard to: (1) the safety of ongoing clinical investigations; (2)
whether clinical testing of a drug should be authorized; (3) the likelihood of reliable data on
the metabolism and pharmacological action of the drug in humans; (4) the timeliness of
reporting information on adverse reactions to the drug; (5) obtaining information on side
effects associated with increasing doses; (6) obtaining information on the drug’s
effectiveness; (7) ensuring the design of well-controlled, scientifically valid studies; and (8)
obtaining any other information pertinent to determining whether clinical testing should be
continued, and information related to the protection of human subjects.
Without the requisite information, we cannot authorize or monitor clinical investigations that
must be conducted before authorizing the sale and general use of new drugs. The reporting
and recordkeeping requirements set forth in the regulations enable us to monitor a study’s
progress, ensure the safety of subjects, ensure that a study will be conducted ethically, and
increase the likelihood that sponsors will conduct studies that will be useful in determining
whether a drug should be marketed and available for use in medical practice.
Upon receipt of the IND by FDA, an IND number will be assigned, and the application will
be forwarded to the appropriate reviewing division. The reviewing division will send a letter
to the Sponsor-Investigator providing notification of the IND number assigned, date of receipt
of the original application, address where future submissions to the IND should be sent, and
the name and telephone number of the FDA person to whom questions about the application
2

should be directed. Studies shall not be initiated until 30 days after the date of receipt of the
IND by FDA unless you receive earlier notification by FDA that studies may begin.
3. Use of Improved Information Technology and Burden Reduction
Even though we are moving toward electronic IND submissions, paper submissions are
acceptable but must be submitted in triplicate (the original and two photocopies are
acceptable). We estimate 76% of all INDs will be submitted electronically. We are unaware
of any legal or technological obstacles to reducing burden.
4. Efforts to Identify Duplication and Use of Similar Information
Regulations under 21 CFR part 312; subpart I provide for expanded access to investigational
drugs for treatment use, including emergency use by individual patients in certain instances.
We have established a separate information collection to support these requirements, which is
currently approved under OMB Control No. 0910-0814. We are currently reviewing the latter
collection and will consolidate the information collections, if appropriate. We are otherwise
unaware of duplicative or similar information collection.
5. Impact on Small Businesses or Other Small Entities
The IND regulations provide for certain waivers and exemptions but are otherwise intended to
enable FDA to fulfill its mandate to ensure the safe study and use of investigational drugs. At
the same time, we assist small businesses in complying with our regulations through our
Regional Small Business Representatives and through the scientific and administrative staffs
within the agency. We also provide a Small Business Guide on our website at
http://www.fda.gov/
6. Consequences of Collecting the Information Less Frequently
The timing of an IND application is determined by the respondent. Subsequently, however,
information collection schedules are consistent with those prescribed in the applicable
regulations. To effectively monitor the progress of ongoing studies and ensure the safety of
study participants, we must obtain timely information regarding adherence to regulatory
responsibilities, as well as any serious adverse effects or other safety issues. Less frequent
reporting or fewer recordkeeping requirements might compromise or unnecessarily risk the
safety of investigation participants as well as the public health.
7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5
The information collection requirements under 21 CFR § 312.32 (IND safety reporting)
provide for more-than-quarterly reporting with regard to the submission of safety information
(i.e., information on adverse drug reactions as well as other information on new studies or
modifications of existing studies). However, we believe this is necessary for ensuring the
safety of clinical investigations. The regulations also prescribe a specific format for the IND
3

application and follow-up amendments that may not be the same format as that employed by
sponsors for their own purposes. These formatting requirements are intended to expedite
FDA review and to save Agency resources that can be invested in assisting sponsors in
developing approvable marketing applications.
8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the
Agency
In accordance with 5 CFR 1320.8(d), we published a 60-day notice for public comment in the
Federal Register of October 4, 2018 . No comments were received that pertaining to the
information collection.
9. Explanation of Any Payment or Gift to Respondents
No remuneration is provided to respondents to the information collection.
10. Assurance of Confidentiality Provided to Respondents
In developing this proposed collection, staff from FDA’s Center for Drug Evaluation and
Research (CDER) consulted the FDA Privacy Officer to identify potential risks to the privacy
of individuals whose information may be handled by or on behalf of FDA in association with
the Individual Patient Expanded Access Applications: Form FDA 3926, if finalized as
proposed. In this case, the subject information collection employing proposed Form FDA
3926 does solicit personally identifiable information (PII) that will be collected and
maintained by FDA/CDER.
Although PII is collected, this collection is not subject to the Privacy Act and the particular
notice and other requirements of the Act do not apply. Specifically, we do not use name or
any other personal identifier to routinely retrieve records from the greater collection of Form
FDA 3926 submissions.
The PII to be collected has been minimized to protect the privacy of the individuals. To
ensure against the solicitation or submission of unnecessary PII, the form has been designed
to provide fields only information required to meet the intended purpose behind the form.
Within text fields, we provide example or lists of relevant information and this will inform
submissions to include relevant information and not irrelevant information including
unnecessary PII. We have also developed instruction that accompany Form FDA 3926 with
direction that further supports privacy. For example, it specifies that full patient name should
never be submitted. And, FDA has prepared guidance for physicians completing the form to
further support the privacy and confidentiality of individuals and the accuracy, integrity, and
relevancy of the information collected.
We also note that information submitted to FDA is protected from inappropriate disclosure
under FDA disclosure regulations at 21 CFR part 20.

4

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
Below, we estimate the burden of the information collection as reported by FDA’s Center for
Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research
(CBER) as follows:
Table 1.--Estimated Annual Reporting Burden for Human Drugs (CDER)1
21 CFR Section
No. of
No. of
Total
Average
Respondents
Responses
Annual
Burden per
per
Responses
Response
Respondent
§ 312.2(e); Requests for FDA advice on
400
1
400
24
the applicability of part 312 to a planned
clinical investigation.
§ 312.8; Requests to charge for an
74
1.23
91
48
investigational drug.
§ 312.10; Requests to waive a requirement
86
1.84
158
24
in part 312.
§ 312.23(a) through (f); IND content and
2,187
1.7
3,718
1,600
format (including Form
FDA 1571)
§ 312.30(a) through (e); Protocol
4,418
5.52
24,387
284
amendments.
§ 312.31(b); Information amendments.
6,691
3.32
22,214
100
§ 312.32(c) and (d); IND safety reports.
867
15.78
13,681
32
§ 312.33(a) through (f); IND annual
3,376
2.86
9,655
360
reports.
§ 312.38(b) and (c); Notifications of
930
1.61
1,497
28
withdrawal of an IND.
§ 312.42; Sponsor requests that a clinical
198
1.38
273
284
hold be removed, including sponsor
submission of a complete response to the
issues identified in the clinical hold order.
§ 312.44(c) and (d); Sponsor responses to
12
1.16
14
16
FDA when IND is terminated.
§ 312.45(a) and (b); Sponsor requests for
231
1.84
425
12
or responses to an inactive status
determination of an IND by FDA.
§ 312.47; Meetings, including “End-of122
1.51
184
160
Phase 2” meetings and “Pre-NDA”
meetings.
§ 312.54(a); Sponsor submissions to FDA
15
2.4
36
48
concerning investigations involving an

5

Total Hours

9,600
4,368
3,792
5,948,800
6,925,908
2,221,400
437,792
3,475,800
41,916
77,532

224
5,100
29,440
1,728

Table 1.--Estimated Annual Reporting Burden for Human Drugs (CDER)1
21 CFR Section
No. of
No. of
Total
Average
Respondents
Responses
Annual
Burden per
per
Responses
Response
Respondent
exception from informed consent under §
50.24.
§ 312.54(b); Sponsor notifications to FDA
2
1
2
48
and others concerning an IRB
determination that it cannot approve
research because it does not meet the
criteria in the exception from informed
consent in § 50.24(a).
6,100
7
42,700
80
§ 312.56(b), (c), and (d); Sponsor
notifications to FDA and others resulting
from: (1) the sponsor’s monitoring of all
clinical investigations and determining that
an investigator is not in compliance with
the investigation agreements; (2) the
sponsor’s review and evaluation of the
evidence relating to the safety and
effectiveness of the investigational drug;
and (3) the sponsor’s determination that
the investigational drug presents an
unreasonable and significant risk to
subjects.
§ 312.58(a); Sponsor’s submissions of
73
1
73
8
clinical investigation records to FDA on
request during FDA inspections.
§ 312.70; During the disqualification
4
1
4
40
process of a clinical investigator by FDA,
the number of investigator responses or
requests to FDA following FDA’s
notification to an investigator of its failure
to comply with investigation requirements.
§ 312.110(b)(4) and (b)(5); Written
11
26.28
289
75
certifications and written statements
submitted to FDA relating to the export of
an investigational drug.
§ 312.120(b); Submissions to FDA of
1,414
8.62
12,189
32
“supporting information” related to the use
of foreign clinical studies not conducted
under an IND.
§ 312.120(c); Waiver requests submitted to
35
2.34
82
24
FDA related to the use of foreign clinical
studies not conducted under an IND.
§ 312.130; Requests for disclosable
3
1
3
8
information in an IND and for
investigations involving an exception from
informed consent under § 50.24.
§§ 312.310(b) and 312.305(b);
935
2.77
2,590
8
Submissions related to expanded access
and treatment of an individual patient.

6

Total Hours

96

3,416,000

584
160

21,675

390,048

1,968
24

20,720

Table 1.--Estimated Annual Reporting Burden for Human Drugs (CDER)1
21 CFR Section
No. of
No. of
Total
Average
Respondents
Responses
Annual
Burden per
per
Responses
Response
Respondent
§ 312.310(d); Submissions related to
480
2.15
1,032
16
emergency use of an investigational new
drug.
§§ 312.315(c) and 312.305(b);
118
2.52
297
120
Submissions related to expanded access
and treatment of an intermediate-size
patient population.
§ 312.320(b); Submissions related to a
10
12.9
129
300
treatment IND or treatment protocol.
Total

Table 2.--Estimated Annual Reporting Burden for Biologics (CBER)1
21 CFR Section
No. of
No. of
Total
Average
Respondents
Responses
Annual
Burden per
per
Responses
Response
Respondent
312.2(e)
217
1.18
256
24
Requests for FDA advice on the
applicability of part 312 to a planned
clinical investigation.
312.8
20
1.50
30
48
Requests to charge for an investigational
drug.
312.10
2
1
2
24
Requests to waive a requirement in part
312.
312.23(a) through (f)
335
1.35
452
1,600
IND content and format.
312.30(a) through (e)
694
5.84
4,053
284
Protocol amendments.
312.31 (b)
77
2.43
187
100
Information amendments.
312.32(c) and (d)
161
8.83
1,422
32
IND Safety reports.
312.33(a) through (f)
745
2.14
1,594
360
IND Annual reports.
312.38(b) and (c)
134
1.69
226
28
Notifications of withdrawal of an IND.
312.42
67
1.30
87
284
Sponsor requests that a clinical hold be
removed, including sponsor submission of a
complete response to the issues identified in
the clinical hold order.
312.44(c) and (d)
Sponsor responses to FDA when IND is
terminated.
312.45(a) and (b)

Total Hours

16,512
35,640

38,700
23,125,527

Total Hours

6,144

1,440
48
723,200
1,151,052
18,700
45,504
573,840
6,328
24,708

34

1.15

39

16

624

55

1.38

76

12

912

7

21 CFR Section

Sponsor requests for or responses to an
inactive status determination of an IND by
FDA.
312.47
Meetings, including "End-of-Phase 2"
meetings and "Pre-NDA" meetings.
312.53(c)
Investigator reports submitted to the
sponsor, including Form FDA-1572,
curriculum vitae, clinical protocol, and
financial disclosure.
312.54(a)
Sponsor submissions to FDA concerning
investigations involving an exception from
informed consent under 21 CFR 50.24.
312.54(b)
Sponsor notifications to FDA and others
concerning an IRB determination that it
cannot approve research because it does not
meet the criteria in the exception from
informed consent in 50.24(a).
312.55(a)
Number of investigator brochures submitted
by the sponsor to each investigator.
312.55(b)
Number of sponsor reports to investigators
on new observations, especially adverse
reactions and safe use.
312.56(b), (c), and (d)
Sponsor notifications to FDA and others
resulting from: (1) The sponsor’s
monitoring of all clinical investigations and
determining that an investigator is not in
compliance with the investigation
agreements; (2) the sponsor’s review and
evaluation of the evidence relating to the
safety and effectiveness of the
investigational drug; and (3) the sponsor’s
determination that the investigational drug
presents an unreasonable and significant
risk to subjects.
312.58(a)
Number of sponsor’s submissions of
clinical investigation records to FDA on
request during FDA inspections.

No. of
Respondents

No. of
Responses
per
Respondent

Total
Annual
Responses

Average
Burden per
Response

Total Hours

88

1.75

154

160

24,640

453

6.33

2,867

80

229,360

1

1

1

48

48

1

1

1

48

48

239

1.91

456

48

21,888

243

4.95

1,203

48

57,744

108

2.21

239

80

19,120

7

1

7

8

56

8

21 CFR Section

312.64
Number of investigator reports to the
sponsor, including progress reports, safety
reports, final reports, and financial
disclosure reports.
312.70
During the disqualification process of a
clinical investigator by FDA, the number of
investigator responses or requests to FDA
following FDA’s notification to an
investigator of its failure to comply with
investigation requirements.
312.110(b)(4) and (b)(5)
Number of written certifications and written
statements submitted to FDA relating to the
export of an investigational drug.
312.120(b)
Number of submissions to FDA of
“supporting information” related to the use
of foreign clinical studies not conducted
under an IND.
312.120(c)
Number of waiver requests submitted to
FDA related to the use of foreign clinical
studies not conducted under an IND.
312.130
Number of requests for disclosable
information in an IND and for
investigations involving an exception from
informed consent under § 50.24.
312.310(b) and 312.305(b)
Number of submissions related to expanded
access and treatment of an individual
patient.
312.310(d)
Number of submissions related to
emergency use of an investigational new
drug.
312.315(c) and 312.305(b)
Number of submissions related to expanded
access and treatment of an intermediate-size
patient population.
312.320(b)
Number of submissions related to a
treatment IND or treatment protocol.
Total

No. of
Respondents

Total
Annual
Responses

Average
Burden per
Response

Total Hours

2,728

No. of
Responses
per
Respondent
3.82

10,421

24

250,104

5

1

5

40

200

18

1

18

75

1,350

280

9.82

2,750

32

88,000

7

2.29

16

24

384

350

1.34

469

8

3,752

78

1.08

84

8

672

76

2.76

210

16

3,360

9

1

9

120

1,080

1

1

1

300

300
3,254,606

9

Table 3.--Estimated Annual Recordkeeping Burden for Human Drugs (CDER)1
21 CFR Section
No. of
No. of Records
Total
Average
Recordkeepers
per
Annual
Burden per
Recordkeeper
Records
Recordkeeping
§ 312.52(a); Sponsor records for the
1,300
1
1,300
2
transfer of obligations to a contract
research organization.
§ 312.57; Sponsor recordkeeping
13,000
1
13,000
100
showing the receipt, shipment, or other
disposition of the investigational drug
and any financial interests.
§ 312.62(a); Investigator recordkeeping
13,000
1
13,000
40
of the disposition of drugs.
§ 312.62(b); Investigator recordkeeping
13,000
1
13,000
40
of case histories of individuals.
§ 312.160(a)(3); Records pertaining to
547
1.43
782
0.50
the shipment of drugs for
(30 minutes)
investigational use in laboratory
research animals or in vitro tests.
§ 312.160(c); Shipper records of
547
1.43
782
0.50
alternative disposition of unused drugs.
(30 minutes)
§ 312.53(c); Investigator reports
1,732
7.94
13,752
80
submitted to the sponsor, including
Form FDA 1572, curriculum vitae,
clinical protocol, and financial
disclosure.
§ 312.55(a); Investigator brochures
995
4
3,980
48
submitted by the sponsor to each
investigator.
§ 312.55(b); Sponsor reports to
995
4
3,980
48
investigators on new observations,
especially adverse reactions and safe
use.
§ 312.64; Investigator reports to the
13,000
1
13,000
24
sponsor, including progress reports,
safety reports, final reports, and
financial disclosure reports.
58,116
76,576
1
There are no capital costs or operating and maintenance costs associated with this collection of information.

10

Total
Hours
2,600
1,300,000

520,000
520,000
391

391
1,100,160

191,040
191,040

312,000

4,137,622

Table 4.--Estimated Annual Recordkeeping Burden for Biologics (CBER)1
No. of
No. of
Total
Average
Total
21 CFR Section
Recordkeepers
Records per
Annual
Burden per
Hours
Recordkeeper Records Recordkeeping
312.52(a)
75
1.40
105
2
210
Sponsor records for the transfer of
obligations to a contract research
organization.
312.57
335
2.70
904
100
90,400
Sponsor recordkeeping showing the
receipt, shipment, or other disposition
of the investigational drug, and any
financial interests.
312.62(a)
453
1
453
40
18,120
Investigator recordkeeping of the
disposition of drugs.
312.62(b)
453
1
453
40
18,120
Investigator recordkeeping of case
histories of individuals.
312.160(a)(3)
111
1.40
155
0.5
78
Records pertaining to the shipment of
(30 minutes)
drugs for investigational use in
laboratory research animals or in vitro
tests.
312.160(c)
111
1.40
155
0.5
78
Shipper records of alternative
(30 minutes)
disposition of unused drugs.
Total
127,006
1
There are no capital costs or operating and maintenance costs associated with this collection of information.

12b. Annualized Cost Burden Estimate
We estimate an average pharmaceutical industry wage rate of $75.00 per hour for
preparing and submitting the information collection requirements under 21 CFR part 314.
Multiplied times the total hour burden estimated above, the total labor cost burden to
respondents is $2,299,857,075.
13. Estimates of Other Total Annual Costs to Respondents and/or Recordkeepers/Capital
Costs
There are no capital, start-up, operating or maintenance costs associated with this information
collection
14. Annualized Cost to the Federal Government
We allocate approximately 835 FTEs to the reviewing the submissions under 21 CFR part
312. Assuming each FTE costs approximately $175,000 for these review activities, the total
cost burden to the Federal Government is approximately $146,125,000.
11

15. Explanation for Program Changes or Adjustments
Because we have received an increased number of IND submissions since last OMB approval
of the information collection, we have increased our estimate of the associated burden
accordingly. The information collection, therefore, reflects a cumulative increase in burden
by 81,332 annual responses and 7,843,950 burden hours attributable to a growing number of
investigational new drug applications and associated research.
16. Plans for Tabulation and Publication and Project Time Schedule
There are no publications or other schedules.
17. Reason(s) Display of OMB Expiration Date is Inappropriate
FDA will display the OMB expiration date as required by 5 CFR 1320.5
18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification statement.

12