23730 Federal Register / Vol. 77, No. 77 / Friday, April 20, 2012 / Notices 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2011–N–0908] 

Agency Information Collection 

Activities; Submission for Office of 

Management and Budget Review; 

Comment Request; Guidance for 

Clinical Trial Sponsors: Establishment 

and Operation of Clinical Trial Data 

Monitoring Committees 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) 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: Fax written comments on the 

collection of information by May 21, 

2012. 

ADDRESSES: To ensure that comments on 

the information collection are received, 

OMB recommends that written 

comments be faxed to the Office of 

Information and Regulatory Affairs, 

OMB, Attn: FDA Desk Officer, FAX: 

202–395–7285, or emailed to 

oira_submission@omb.eop.gov. All 

comments should be identified with the 

OMB control number 0910–0581. Also 

include the FDA docket number found 

in brackets in the heading of this 

document. 

FOR FURTHER INFORMATION CONTACT: Ila 

S. Mizrachi, Office of Information 

Management, Food and Drug 

Administration, 1350 Piccard Dr., PI50– 

400B, Rockville, MD 20850, 301–796– 

7726, Ila.Mizrachi@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. 

Guidance for Clinical Trial Sponsors: 

Establishment and Operation of 

Clinical Trial Data Monitoring 

Committees—(OMB Control Number 

0910–0581)—Extension 

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 referenced in 

this document 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. The guidance addresses 

the roles, responsibilities, and operating 

procedures of DMCs, 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; 

• 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 

(§ 314.50(d)(5)(ii) (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 

(§ 812.150(b)(1) (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 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 


tkelley on DSK3SPTVN1PROD with NOTICES
Federal Register / Vol. 77, No. 77 / Friday, April 20, 2012 / Notices 23731 

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 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 in the next few 

years. 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; § 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 December 

22, 2011 (76 FR 79689), FDA published 

a 60-day notice requesting public 

comment on the proposed collection of 

information. No comments were 

received. 

FDA estimates the burden of this 

collection of information 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. 

TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1

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/reporting activity Number of 

respondents 

Number of 

responses per 

respondent 

Total annual 

responses 

Average 

burden per 

response 

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. 


tkelley on DSK3SPTVN1PROD with NOTICES
23732 Federal Register / Vol. 77, No. 77 / Friday, April 20, 2012 / Notices 

Dated: April 16, 2012. 

Leslie Kux, 

Assistant Commissioner for Policy. 

[FR Doc. 2012–9533 Filed 4–19–12; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2011–N–0511] 

Agency Information Collection 

Activities; Announcement of Office of 

Management and Budget Approval; 

Current Good Manufacturing Practices 

and Related Regulations for Blood and 

Blood Components; and Requirements 

for Donor Testing, Donor Notification, 

and ‘‘Lookback’’ 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing 

that a collection of information entitled 

‘‘Current Good Manufacturing Practices 

and Related Regulations for Blood and 

Blood Components; and Requirements 

for Donor Testing, Donor Notification, 

and ‘ Lookback’ ’’ has been approved by 

the Office of Management and Budget 

(OMB) under the Paperwork Reduction 

Act of 1995. 

FOR FURTHER INFORMATION CONTACT: Ila 

S. Mizrachi, Office of Information 

Management, Food and Drug 

Administration, 1350 Piccard Dr., PI50– 

400B, Rockville, MD 20850, 301–796– 

7726, ila.mizrachi@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: On 

January 3, 2012, the Agency submitted 

a proposed collection of information 

entitled ‘‘Current Good Manufacturing 

Practices and Related Regulations for 

Blood and Blood Components; and 

Requirements for Donor Testing, Donor 

Notification, and ‘Lookback’ ’’ to OMB 

for review and clearance under 44 

U.S.C. 3507. An Agency may not 

conduct or sponsor, and a person is not 

required to respond to, a collection of 

information unless it displays a 

currently valid OMB control number. 

OMB has now approved the information 

collection and has assigned OMB 

control number 0910–0116. The 

approval expires on April 30, 2015. A 

copy of the supporting statement for this 

information collection is available on 

the Internet at http://www.reginfo.gov/ 

public/do/PRAMain. 

Dated: April 16, 2012. 

Leslie Kux, 

Assistant Commissioner for Policy. 

[FR Doc. 2012–9531 Filed 4–19–12; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2012–N–0369] 

Agency Information Collection 

Activities; Proposed Collection; 

Comment Request; Regulations Under 

the Federal Import Milk Act 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

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 

extension of an existing collection of 

information, and to allow 60 days for 

public comment in response to the 

notice. This notice solicits comments on 

the reporting and recordkeeping 

requirements of FDA’s regulations 

implementing the Federal Import Milk 

Act (FIMA). 

DATES: Submit either electronic or 

written comments on the collection of 

information by June 19, 2012. 

ADDRESSES: Submit electronic 

comments on the collection of 

information to http:// 

www.regulations.gov. Submit written 

comments on the collection of 

information to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, Rm. 

1061, Rockville, MD 20852. All 

comments should be identified with the 

docket number found in brackets in the 

heading of this document. 

FOR FURTHER INFORMATION CONTACT: 

Domini Bean, Office of Information 

Management, Food and Drug 

Administration, 1350 Piccard Dr., PI50– 

400T, Rockville, MD 20850, 301–796– 

5733, domini.bean@fda.hhs.gov. 

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 extension 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 these topics: (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. 

Regulations Under the Federal Import 

Milk Act—21 CFR Part 1210 (OMB 

Control Number 0910–0212)—Extension 

Under FIMA (21 U.S.C. 141–149), 

milk or cream may be imported into the 

United States only by the holder of a 

valid import milk permit (21 U.S.C. 

141). Before such permit is issued: (1) 

All cows from which import milk or 

cream is produced must be physically 

examined and found healthy; (2) if the 

milk or cream is imported raw, all such 

cows must pass a tuberculin test; (3) the 

dairy farm and each plant in which the 

milk or cream is processed or handled 

must be inspected and found to meet 

certain sanitary requirements; (4) 

bacterial counts of the milk at the time 

of importation must not exceed 

specified limits; and (5) the temperature 

of the milk or cream at time of 

importation must not exceed 50° F (21 

U.S.C. 142). 

FDA’s regulations in part 1210 (21 

CFR part 1210) implement the 

provisions of FIMA. Sections 1210.11 

and 1210.14 require reports on the 

sanitary conditions of, respectively, 

dairy farms and plants producing milk 

and/or cream to be shipped to the 

United States. Section 1210.12 requires 


tkelley on DSK3SPTVN1PROD with NOTICES