Federal Register / Vol. 86, No. 162 / Wednesday, August 25, 2021 / Notices 47505 

FOR FURTHER INFORMATION CONTACT: 

Jonathan Resnick, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 32, Rm. 3160, 

Silver Spring, MD 20993–0002, 301– 

796–7997, 

Jonathan.Resnick@fda.hhs.gov: or 

Stephen Ripley, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration, Bldg. 71, Rm. 

7301, Silver Spring, MD 20993–0002, 

240–402–7911. 

SUPPLEMENTARY INFORMATION: FDA is 

issuing this Federal Register notice to 

announce that eCTD validations 1306 

and 1323, described in ‘‘Specifications 

for eCTD Validation Criteria,’’ have been 

raised to high validation errors. 

Beginning March 1, 2022, FDA will 

reject submissions that fail either of 

these validations. 

According to the guidance for 

industry entitled ‘‘Providing Regulatory 

Submissions in Electronic Format— 

Certain Human Pharmaceutical Product 

Applications and Related Submissions 

Using the eCTD Specifications,’’ 

submissions subject to section 745A(a) 

of the Federal Food, Drug, and Cosmetic 

Act must be submitted in eCTD format 

using the version of eCTD currently 

supported by FDA (unless such 

submission is exempt from the 

electronic submission requirements or if 

FDA has granted a waiver). The version 

of eCTD currently supported by FDA is 

specified in the Data Standards Catalog. 

eCTD submissions must follow FDA 

eCTD technical specification entitled 

‘‘The Comprehensive Table of Contents 

Headings and Hierarchy.’’ Documents 

which are not properly referenced in the 

eCTD backbone as described in the ‘‘M2 

eCTD: Electronic Common Technical 

Document Specification’’ and ‘‘The 

eCTD Backbone Files Specification for 

Module 1,’’ result in content that is not 

accessible within FDA eCTD technical 

specification ‘‘The Comprehensive 

Table of Contents Headings and 

Hierarchy.’’ eCTD validations 1306 (‘‘No 

leaf element for file’’) and 1323 (‘‘No file 

for leaf element’’), within the 

‘‘Specifications for eCTD Validation 

Criteria,’’ describe parts of the eCTD 

specifications which were not followed 

correctly. Rejection for failing to pass 

either eCTD validations 1306 or 1323 

will begin on March 1, 2022. 

Dated: August 18, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–18303 Filed 8–24–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2021–N–0356] 

Agency Information Collection 

Activities; Submission for Office of 

Management and Budget Review; 

Comment Request; Establishment and 

Operation of Clinical Trial Data 

Monitoring Committees 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA, Agency, or we) is 

announcing that a proposed collection 

of information has been submitted to the 

Office of Management and Budget 

(OMB) for review and clearance under 

the Paperwork Reduction Act of 1995. 

DATES: Submit written comments 

(including recommendations) on the 

collection of information by September 

24, 2021. 

ADDRESSES: To ensure that comments on 

the information collection are received, 

OMB recommends that written 

comments be submitted to https://

www.reginfo.gov/public/do/PRAMain. 

Find this particular information 

collection by selecting ‘‘Currently under 

Review—Open for Public Comments’’ or 

by using the search function. The OMB 

control number for this information 

collection is 0910–0581. Also include 

the FDA docket number found in 

brackets in the heading of this 

document. 

FOR FURTHER INFORMATION CONTACT: 

Domini Bean, Office of Operations, 

Food and Drug Administration, Three 

White Flint North, 10A–12M, 11601 

Landsdown St., North Bethesda, MD 

20852, 301–796–5733, PRAStaff@

fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: In 

compliance with 44 U.S.C. 3507, FDA 

has submitted the following proposed 

collection of information to OMB for 

review and clearance. 

Establishment and Operation of 

Clinical Trial Data Monitoring 

Committees 

OMB Control Number 0910–0581— 

Extension 

This collection of information 

supports Agency regulations and 

associated Agency guidance. Sponsors 

are required to monitor studies 

evaluating new drugs, biologics, and 

devices (21 CFR 312.50 and 312.56 for 

drugs and biologics, and 21 CFR 812.40 

and 812.46 for devices). Various 

individuals and groups play different 

roles in clinical trial monitoring. One 

such group is a data monitoring 

committee (DMC), appointed by a 

sponsor to evaluate the accumulating 

outcome data in some trials. A clinical 

trial DMC is a group of individuals with 

pertinent expertise that reviews on a 

regular basis accumulating data from 

one or more ongoing clinical trials. The 

DMC advises the sponsor regarding the 

continuing safety of current trial 

subjects and those yet to be recruited to 

the trial, as well as the continuing 

validity and scientific merit of the trial. 

The guidance document entitled 

‘‘Guidance for Clinical Trial Sponsors: 

Establishment and Operation of Clinical 

Trial Data Monitoring Committees’’ 

(March 2006) is intended to assist 

sponsors of clinical trials in determining 

when a DMC is needed for monitoring 

a study and how such committees 

should operate and is available from our 

website at: https://www.fda.gov/media/ 

75398/download. The guidance 

addresses the roles, responsibilities, and 

operating procedures of DMCs and 

describes certain reporting and 

recordkeeping responsibilities, 

including the following: (1) Sponsor 

reporting to FDA on DMC 

recommendations related to safety; (2) 

standard operating procedures (SOPs) 

for DMCs; (3) DMC meeting records; (4) 

sponsor notification to the DMC 

regarding waivers; and (5) DMC reports 

based on meeting minutes to the 

sponsor. 

1. Sponsor Reporting to FDA on DMC 

Recommendations Related to Safety 

The requirement of the sponsor to 

report DMC recommendations related to 

serious adverse events in an expedited 

manner in clinical trials of new drugs 

(§ 312.32(c)) (21 CFR 312.32(c)) would 

not apply when the DMC 

recommendation is related to an excess 

of events not classifiable as serious. 

Nevertheless, the Agency recommends 

in the guidance that sponsors inform 

FDA about all recommendations related 

to the safety of the investigational 

product whether or not the adverse 

event in question meets the definition of 

‘‘serious.’’ 

2. SOPs for DMCs 

In the guidance, FDA recommends 

that sponsors establish procedures to do 

the following things: 

• Assess potential conflicts of interest 

of proposed DMC members; 

• ensure that those with serious 

conflicts of interest are not included in 

the DMC; 


khammond on DSKJM1Z7X2PROD with NOTICES
47506 Federal Register / Vol. 86, No. 162 / Wednesday, August 25, 2021 / Notices 

• provide disclosure to all DMC 

members of any potential conflicts that 

are not thought to impede objectivity 

and, thus, would not preclude service 

on the DMC; 

• identify and disclose any 

concurrent service of any DMC member 

on other DMCs of the same, related, or 

competing products; 

• ensure separation, and designate a 

different statistician to advise on the 

management of the trial, if the primary 

trial statistician takes on the 

responsibility for interim analysis and 

reporting to the DMC; and 

• minimize the risks of bias that are 

associated with an arrangement under 

which the primary trial statistician takes 

on the responsibility for interim 

analysis and reporting to the DMC, if it 

appears infeasible or highly impractical 

for any other statistician to take over 

responsibilities related to trial 

management. 

3. DMC Meeting Records 

The Agency recommends in the 

guidance that the DMC or the group 

preparing the interim reports to the 

DMC maintain all meeting records. This 

information should be submitted to FDA 

with the clinical study report (21 CFR 

314.50(d)(5)(ii)). 

4. Sponsor Notification to the DMC 

Regarding Waivers 

The sponsor must report to FDA 

certain serious and unexpected adverse 

events in drugs and biologics trials 

(§ 312.32) and unanticipated adverse 

device effects in the case of device trials 

(21 CFR 812.150(b)(1)). The Agency 

recommends in the guidance that 

sponsors notify DMCs about any 

waivers granted by FDA for expedited 

reporting of certain serious events. 

5. DMC Reports of Meeting Minutes to 

the Sponsor 

The Agency recommends in the 

guidance that DMCs should issue a 

written report to the sponsor based on 

the DMC meeting minutes. Reports to 

the sponsor should include only those 

data generally available to the sponsor. 

The sponsor may convey the relevant 

information in this report to other 

interested parties, such as study 

investigators. Meeting minutes or other 

information that include discussion of 

confidential data would not be provided 

to the sponsor. 

Description of the Respondents: The 

submission and data collection 

recommendations described in this 

document affect sponsors of clinical 

trials and DMCs. 

Burden Estimate: Table 1 of this 

document provides the burden estimate 

of the annual reporting burden for the 

information to be submitted in 

accordance with the guidance. Table 2 

of this document provides the burden 

estimate of the annual recordkeeping 

burden for the information to be 

maintained in accordance with the 

guidance. Table 3 of this document 

provides the burden estimate of the 

annual third-party disclosure burden for 

the information to be submitted in 

accordance with the guidance. 

Reporting, Recordkeeping, and ThirdParty Disclosure Burdens: Based on 

information from FDA review divisions, 

FDA estimates that there are 

approximately 740 clinical trials with 

DMCs regulated by the Center for 

Biologics Evaluation and Research, the 

Center for Drugs Evaluation and 

Research, and the Center for Devices 

and Radiological Health. FDA estimates 

that the average length of a clinical trial 

is 2 years, resulting in an annual 

estimate of 370 clinical trials. Because 

FDA has no information on which to 

project a change in the use of DMCs, 

FDA estimates that the number of 

clinical trials with DMCs will not 

change significantly. For purposes of 

this information collection, FDA 

estimates that each sponsor is 

responsible for approximately 10 trials, 

resulting in an estimated 37 sponsors 

that are affected by the guidance 

annually. 

Based on information provided to 

FDA by sponsors that have typically 

used DMCs for the kinds of studies for 

which this guidance recommends them, 

FDA estimates that the majority of 

sponsors have already prepared SOPs 

for DMCs, and only a minimum amount 

of time is necessary to revise or update 

them for use for other clinical studies. 

FDA receives very few requests for 

waivers regarding expedited reporting of 

certain serious events; therefore, FDA 

has estimated one respondent per year 

to account for the rare instance a request 

may be made. Based on FDA’s 

experience with clinical trials using 

DMCs, FDA estimates that the sponsor 

on average would issue two interim 

reports per clinical trial to the DMC. 

FDA estimates that the DMCs would 

hold two meetings per year per clinical 

trial resulting in the issuance of two 

DMC reports of meeting minutes to the 

sponsor. One set of both of the meeting 

records should be maintained per 

clinical trial. 

The ‘‘Average Burden per Response’’ 

and ‘‘Average Burden per 

Recordkeeping’’ are based on FDA’s 

experience with comparable 

recordkeeping and reporting provisions 

applicable to FDA regulated industry. 

The ‘‘Average Burden per Response’’ 

includes the time the respondent would 

spend reviewing, gathering, and 

preparing the information to be 

submitted to the DMC, FDA, or the 

sponsor. The ‘‘Average Burden per 

Recordkeeping’’ includes the time to 

record, gather, and maintain the 

information. 

The information collection provisions 

in the guidance for 21 CFR 312.30, 

312.32, 312.38, 312.55, and 312.56 have 

been approved under OMB control 

number 0910–0014; 21 CFR 314.50 has 

been approved under OMB control 

number 0910–0001; and 21 CFR 812.35 

and 812.150 have been approved under 

OMB control number 0910–0078. 

In the Federal Register of April 29, 

2021 (86 FR 22690), we published a 60- 

day notice requesting public comment 

on the proposed collection of 

information. No comments were 

received. 

We estimate the burden of the 

information collection as follows: 

TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1

Section of guidance/reporting activity Number of 

respondents 

Number of 

responses per 

respondent 

Total annual 

responses 

Average burden 

per response Total hours 

5.—Sponsor reporting to FDA on DMC recommendations related to safety.37 1 37 0.50 (30 minutes) ... 18.5 

Total ...................................................................... ........................ ........................ ........................ ................................ 18.5 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 


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Federal Register / Vol. 86, No. 162 / Wednesday, August 25, 2021 / Notices 47507 

1See also 49 U.S.C. 44939. 

TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1

Section of guidance/recordkeeping activity Number of 

recordkeepers 

Number of 

records per 

recordkeeper 

Total annual 

records 

Average 

burden per 

recordkeeping 

Total hours 

4.1. and 6.4—SOPs for DMCs ............................................ 37 1 37 8 296 

4.4.3.2.—DMC meeting records .......................................... 370 1 370 2 740 

Total .............................................................................. ........................ ........................ ........................ ........................ 1,036 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

TABLE 3—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1

Section of guidance/disclosure activity Number of 

respondents 

Number of 

disclosures per 

respondent 

Total annual 

disclosures 

Average burden 

per disclosure Total hours 

4.4.1.2.—Sponsor notification to the DMC regarding 

waivers.

1 1 1 0.25 (15 minutes) ... 0.25 

4.4.3.2.—DMC reports of meeting minutes to the 

sponsor.

370 2 740 1 ............................. 740 

Total .................................................................... ........................ .......................... ........................ ................................ 740.25 

1There are no capital costs or operating and maintenance costs associated with this collection of information. 

Based on a review of the information 

collection since our last request for 

OMB approval, we have made no 

adjustments to our burden estimate. 

Dated: August 5, 2021. 

Lauren K. Roth, 

Acting Principal Associate Commissioner for 

Policy. 

[FR Doc. 2021–18235 Filed 8–24–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HOMELAND 

SECURITY 

Transportation Security Administration 

[Docket No. TSA–2004–19147] 

Intent To Request Revision From OMB 

of One Current Public Collection of 

Information: Flight Training Security 

AGENCY: Transportation Security 

Administration, DHS. 

ACTION: 60-Day notice. 

SUMMARY: The Transportation Security 

Administration (TSA) invites public 

comment on one currently approved 

Information Collection Request (ICR), 

Office of Management and Budget 

(OMB) control number 1652–0021, that 

we will submit to OMB for a revision, 

in compliance with the Paperwork 

Reduction Act (PRA). The ICR describes 

the nature of the information collection 

and its expected burden. The collection 

involves information necessary to 

conduct security threat assessments for 

all non-U.S. citizens, non-U.S. 

nationals, and other designated 

individuals seeking flight instruction 

(‘‘candidates’’) from Federal Aviation 

Administration (FAA)-certified flight 

training providers. Pursuant to statute, 

TSA will use the information collected 

to determine whether a candidate poses 

or is suspected of posing a threat to 

aviation or national security, and is thus 

prohibited from receiving flight training. 

Additionally, flight training providers 

are required to conduct a security 

awareness training program for their 

employees and to maintain records 

associated with this training. 

DATES: Send your comments by October 

25, 2021. 

ADDRESSES: Comments may be emailed 

to TSAPRA@dhs.gov or delivered to the 

TSA PRA Officer, Information 

Technology (IT), TSA–11, 

Transportation Security Administration, 

6595 Springfield Center Drive, 

Springfield, VA 20598–6011. 

FOR FURTHER INFORMATION CONTACT: 

Christina A. Walsh at the above address, 

or by telephone (571) 227–2062. 

SUPPLEMENTARY INFORMATION: 

Comments Invited 

In accordance with the Paperwork 

Reduction Act of 1995 (44 U.S.C. 3501 

et seq.), an agency may not conduct or 

sponsor, and a person is not required to 

respond to, a collection of information 

unless it displays a valid OMB control 

number. The ICR documentation will be 

available at http://www.reginfo.gov 

upon its submission to OMB. Therefore, 

in preparation for OMB review and 

approval of the following information 

collection, TSA is soliciting comments 

to— 

(1) Evaluate whether the proposed 

information requirement is necessary for 

the proper performance of the functions 

of the agency, including whether the 

information will have practical utility; 

(2) Evaluate the accuracy of the 

agency’s estimate of the burden; 

(3) Enhance the quality, utility, and 

clarity of the information to be 

collected; and 

(4) Minimize the burden of the 

collection of information on those who 

are to respond, including using 

appropriate automated, electronic, 

mechanical, or other technological 

collection techniques or other forms of 

information technology. 

Information Collection Requirement 

OMB Control Number 1652–0021, 

Flight Training Security. Under 49 CFR 

part 1552, TSA conducts security threat 

assessments for all non-U.S. citizens, 

non-U.S. nationals, and other 

designated individuals seeking flight 

instruction with Federal Aviation 

Administration (FAA)-certified flight 

training providers.1 The purpose of this 

requirement is to ensure flight training 

candidates do not pose a threat to 

aviation or national security and thus 

can be permitted to receive flight 

training. The collection of information 

required under 49 CFR part 1552 

includes candidates’ biographic 

information and fingerprints, which 

TSA uses to perform the security threat 

assessment. 

Additionally, flight training providers 

are required to maintain records of 

security awareness training provided to 

their employees. See subpart B of 49 

CFR part 1552. This training, which is 


khammond on DSKJM1Z7X2PROD with NOTICES