0672 Supporting Statement A 2016

Investigational New Drug (IND) Safety Reporting Requirements
for Human Drug and Biological Products and Safety Reporting
Requirements for Bioavailability and Bioequivalence Studies in Humans
OMB Control No. 0910-0672
SUPPORTING STATEMENT
A. Justification
1. Circumstances Making the Collection of Information Necessary
In the Federal Register of September 29, 2010 (75 FR 59960), FDA published a final rule
entitled “Investigational New Drug Safety Reporting Requirements for Human Drug and
Biological Products and Safety Reporting Requirements for Bioavailability and Bioequivalence
Studies in Humans.” The rule clarified the agency's expectations for timely review, evaluation,
and submission of relevant and useful safety information and implemented internationally
harmonized definitions and reporting standards for Investigational New Drug (IND) safety
reports. The rule also required safety reporting for bioavailability and bioequivalence studies.
The rule was intended to improve the utility of IND safety reports, expedite FDA's review of
critical safety information, better protect human subjects enrolled in clinical trials, and
harmonize safety reporting requirements internationally.
As a result of the rulemaking FDA regulations were revised to include additional reporting
requirements. These revisions are reflected in 21 CFR parts 312 and 320. Because these
provisions may be incorporated into the currently approved information collection provisions
found in OMB Control Nos. 0910-0014 Investigational New Drug Regulations and 0910-0291
MedWatch: FDA Medical Products Reporting Program, respectively, the agency will revise
those collections accordingly. In the interim, FDA is requesting OMB approval of the instant
information collection provisions found in the following regulations:
21 CFR 312.32(c)(1)(ii) and (c)(1)(iii); section 312.32(c)(1)(ii) requires reporting to FDA, in an
IND safety report, of potential serious risks from clinical trials within 15 calendar days for
findings from epidemiological studies, pooled analyses of multiple studies, or other clinical
studies that suggest a significant risk in humans exposed to the drug. Section 312.32(c)(1)(iii)
specifies the requirements for reporting to FDA in an IND safety report potential serious risks
from clinical trials within 15 calendar days for findings from in vitro testing that suggest a
significant risk to humans.
21 CFR 312.32(c)(1)(iv) requires reporting to FDA in an IND safety report within 15 calendar
days of any clinically important increase in the rate of occurrence of serious suspected adverse
reactions over that listed in the protocol or investigator brochure.
21 CFR 320.31(d) requires mandatory safety reporting for bioavailability and bioequivalence
studies on Form FDA 3500A (approved under OMB Control No. 0910-0291) or other electronic
format FDA can process.

2. Purpose and Use of the Information Collection
The information collection is intended to improve the utility of IND safety reports, expedite
FDA's review of critical safety information, better protect human subjects enrolled in clinical
trials, and harmonize safety reporting requirements internationally.
3. Use of Improved Information Technology and Burden Reduction
Information collection is conducted electronically through agency-supported technology.
4. Efforts to Identify Duplication and Use of Similar Information
The information collection reflects burden that would otherwise be captured under OMB Control
Nos. 0910-0014, Investigational New Drug Regulations and 0910-0291, MedWatch: FDA’s
Medical Products Reporting Program. FDA will incorporate the burden under the instant
collection into these collections accordingly.
5. Impact on Small Businesses or Other Small Entities
While the information collection provisions apply to small and large businesses alike, FDA aids
small businesses in complying with its requirements through the agency’s Regional Small
Business Representatives and through the scientific and administrative staffs within the agency.
FDA has provided a Small Business Guide on the agency’s website at
http://www.fda.gov/oc/industry/.
6. Consequences of Collecting the Information Less Frequently
The reporting frequency is prescribed in accordance with the Federal Food, Drug, and Cosmetic
Act regarding the safety of human subjects in clinical studies. FDA must have information about
studies before they begin. Also, in monitoring the progress of ongoing studies, FDA needs
timely information on serious adverse effects and significant new information derived from
animal studies, from foreign marketing experience, and other study data. Less frequent reporting
increases the potential risk to human health and exposure to unsafe drugs.
7. Special Circumstances Relating to the Guidelines in 5 CFR 1320.5
The agency’s IND regulations require more than a quarterly reporting schedule (21 CFR 312.32)
to ensure expedited FDA review of product applications. At the same time, FDA feels these
reporting requirements impose the minimum burden necessary while allowing us to make
informed determinations of safety and effectiveness.

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8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the
Agency
In accordance with 5 CFR 1320.8(d), FDA published a 60 day notice for public comment in the
Federal Register of March 18, 2016 (81 FR 14860). No comments were received in response to
the notice.
9. Explanation of Any Payment or Gift to Respondents
No payment or gift is made to respondents to the information collection.
10. Assurance of Confidentiality Provided to Respondents
The release of information submitted to FDA under an IND is governed by the provisions of 21
CFR 312.5 and 314.430. In general, these provisions do not permit public disclosure of
information in IND files unless that information has previously been publicly disclosed. The
unauthorized use or disclosure of trade secrets required in applications is specifically prohibited
under Section 310(j) of the act.
11. Justification for Sensitive Questions
The information collection contains no questions of a sensitive nature.
12. Estimates of Annualized Hour Burden and Costs
Description of Respondents: Respondents to the collection are businesses or other “for-profit”
organizations sponsoring IND applications, or anyone otherwise subject to 21 CFR parts 312 and
320.
We estimate the burden of the information collection as follows:
12a. Annualized Hour Burden Estimate
Table 1 – CDER Estimated Annual Reporting Burden1
21 CFR Section

320.31(d) Bioavailability and
Bioequivalence Safety Reports
312.32(c)(1)(ii) and (c)(1)(iii)
IND Safety Reports
312.32(c)(1)(iv) IND Safety
Reports

TOTAL
1

No. of
Respondents

Total
Annual
Responses
195

Avg.
Burden per
Response
14

Total
Hours

13

No. of
Responses per
Respondent
15

100

6

600

12

7,200

10

1

10

12

120

123

805

2,730

10,050

There are no capital costs or operating and maintenance costs associated with this collection of information.

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Table 2 – CBER Estimated Annual Reporting Burden1
21 CFR Section

320.31(d) Bioavailability and
Bioequivalence Safety Reports
312.32(c)(1)(ii) and (c)(1)(iii)
IND Safety Reports
312.32(c)(1)(iv) IND Safety
Reports

TOTAL
1

No. of
Respondents

Total
Annual
Responses
1

Avg.
Burden per
Response
14

Total
Hours

1

No. of
Responses per
Respondent
1

137

4

548

12

6,576

5

1.4

7

12

84

143

556

14

6,674

There are no capital costs or operating and maintenance costs associated with this collection of information.

12b. Annualized Cost Burden Estimate
Costs to respondents are reflected in currently approved collections 0910-0014 and 0910-0291.
FDA will consolidate the annual hourly burden associated with the instant collection
accordingly.
13. Estimates of Other Total Annual Cost Burden 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
Cost of the information collection is absorbed under currently allocated resources.
15. Explanation for Program Changes or Adjustments
The burden reflects an increase FDA attributes to an increase in the number of respondents and
submissions as a result of the reporting requirements in the the rulemaking for the underlying
regulations. Specifically we have included 551 additional responses and 6,604 additional hours.
We have also eliminated the estimated costs previously included as we believe these were
realized upon implementation of the rule which became effective March 28, 2011. Before
expiration of the instant collection, burden associated with provisions under 21 CFR part 312
will be consolidated into OMB Control No. 0910-0014, Investigational New Drug Regulations;
and burden associated with provisions under 21 part 320 will be consolidated into OMB Control
No. 0910-0291, MedWatch: FDA’s Medical Products Reporting Program. The agency plans to
revise these collections accordingly.
16. Plans for Tabulation and Publication and Project Time Schedule
The agency has no plans for any publication regarding the information collection.

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17. Reason(s) Display of OMB Expiration Date is Inappropriate
Display is appropriate.
18. Exceptions to Certification for Paperwork Reduction Act Submissions
There are no exceptions to the certification.

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