56708 Federal Register / Vol. 70, No. 187 / Wednesday, September 28, 2005 / Notices 

In the Federal Register of June 10, 

2005 (70 FR 33907), FDA published a 

60-day notice soliciting comments on 

this collection of information. In 

response to this notice, no comments 

were received. 

The respondents for VFD drugs are 

Veterinarians, distributors of animal 

feeds containing VFD drugs, and clients 

utilizing medicated feeds containing 

VFD drugs. 

FDA estimates the burden for this 

collection of information as follows: 

TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1

21 CFR Section No. of Respondents Annual Frequency per 

Response Total Annual Responses Hours per Response Total Hours 

558.6(a)(3) through 

558.6(a)(5) 15,000 25 375,000 0.25 93,750 

558.6(d)(1)(i) 

through 

558.6(d)(1)(iii) 1,500 1 500 0.25 125 

558.6(d)(1)(iv) 20 1 20 0.25 5 

558.6(d)(2) 1,000 5 5,000 0.25 1,250 

514.1(b)(9) 1 1 1 3.00 3 

Total Hours 95,133 

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

TABLE 2.—ESTIMATED ANNUAL RECORDKEEPING BURDEN1

21 CFR No. of Recordkeepers Annual Frequency per 

Recordkeeper Total Annual Records Hours per Record Total Hours 

558.6(c)(1) through 

558.6(c)(4) 112,500 10 1,125,000 .0167 18,788 

558.6(e)(1) through 

558.6(e)(3) 5,000 75 375,000 .0167 6,263 

Total Hours 25,051 

1There are no capitals cost or operating and maintenance cost associated with this collection of information. 

The estimate of the times required for 

record preparation and maintenance is 

based on agency communication with 

industry. Other information needed to 

calculate the total burden hours are 

derived from agency records and 

experience. 

Dated: September 22, 2005. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. 05–19393 Filed 9–27–05; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2005N–0208] 

Agency Information Collection 

Activities; Submission for Office of 

Management and Budget Review; 

Comment Request; Dissemination of 

Information on Unapproved/New Uses 

for Marketed Drugs, Biologics, and 

Devices 

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 October 28, 

2005. 

ADDRESSES: OMB is still experiencing 

significant delays in the regular mail, 

including first class and express mail, 

and messenger deliveries are not being 

accepted. 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: Fumie Yokota, Desk Officer 

for FDA, FAX: 202–395–6974. 

FOR FURTHER INFORMATION CONTACT: 

Karen L. Nelson, Office of Management 

Programs (HFA–250), Food and Drug 

Administration, 5600 Fishers Lane, 

Rockville, MD 20857, 301–827–1482. 

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. 

Dissemination of Information on 

Unapproved/New Uses for Marketed 

Drugs, Biologics, and Devices (OMB 

Control Number 0910–0390)—Extension 

In the Federal Register of November 

20, 1998 (63 FR 64556), FDA published 

a final rule that added a new part 99 (21 

CFR part 99) entitled ‘‘Dissemination of 

Information on Unapproved/New Uses 

for Marketed Drugs, Biologics, and 

Devices.’’

The final rule implemented section 

401 of the Food and Drug 

Administration Modernization Act of 

1997 (FDAMA) (Public Law 105–115). 

In brief, section 401 of FDAMA 

amended the Federal Food, Drug, and 

Cosmetic Act (the act) (21 U.S.C. 360aaa 

through 360aaa-6) to permit drug, 

biologic, and device manufacturers to 

disseminate certain written information 

concerning the safety, effectiveness, or 

benefits of a use that is not described in 

the product’s approved labeling to 

health care practitioners, pharmacy 

benefit managers, health insurance 

issuers, group health plans, and Federal 

and State Government agencies, 

provided that the manufacturer 

complies with certain statutory 

requirements. For example, the 

information that is to be disseminated 

must be about a drug or device that is 

being marketed legally; it must be in the 

form of an unabridged reprint or copy 

of a peer-reviewed journal article or 

reference publication; and it must not be 

derived from another manufacturer’s 

clinical research, unless that other 

manufacturer has given its permission 

for the dissemination. The information 

Federal Register / Vol. 70, No. 187 / Wednesday, September 28, 2005 / Notices 56709 

must be accompanied by certain 

information, including a prominently 

displayed statement that the 

information discusses a use (or uses) 

that has not been approved or cleared by 

FDA. Additionally, 60 days before 

dissemination, the manufacturer must 

submit to FDA a copy of the information 

to be disseminated, any other clinical 

trial information that the manufacturer 

has relating to the safety or effectiveness 

of the new use, any reports of clinical 

experience that pertain to the safety of 

the new use, and a summary of such 

information. 

The final rule sets forth the criteria 

and procedures for making such 

submissions to FDA. Under the final 

rule, submissions include certification 

that the manufacturer has completed 

clinical studies necessary to submit a 

supplemental application to FDA for the 

new use, and will submit the 

supplemental application within 6 

months after its initial dissemination of 

information. If the manufacturer has 

planned, but not completed, such 

studies, the submission includes 

proposed protocols and a schedule for 

conducting the studies, as well as 

certification that the manufacturer will 

complete the clinical studies and submit 

a supplemental application no later than 

36 months after its initial dissemination 

of information. The final rule also 

permits manufacturers to request 

extensions of the time period for 

completing a study and submitting a 

supplemental application, and to 

request an exemption from the 

requirement to submit a supplemental 

application. The final rule prescribes 

the timeframe within which the 

manufacturer shall maintain records 

that would enable it to take corrective 

action. The final rule requires the 

manufacturer to submit lists pertaining 

to the disseminated articles and 

reference publications, the categories of 

persons (or individuals) receiving the 

information, and a notice and summary 

of any additional research or data (and 

a copy of the data) relating to the 

product’s safety or effectiveness for the 

new use. The final rule requires the 

manufacturer to maintain a copy of the 

information, lists, records, and reports 

for 3 years after it has ceased 

dissemination of the information and to 

make the documents available to FDA 

for inspection and copying. 

FDA based its estimates of the number 

of submissions it will receive, and the 

number of manufacturers who would be 

subject to part 99, on the average of the 

total number of required submissions 

received during 2002, 2003, and 2004. 

The estimated burden hours for these 

provisions are based on the following 

calculations: 

Section 99.201(a)(1) requires the 

manufacturer to provide an identical 

copy of the information to be 

disseminated, including any 

information required under § 99.103. 

Because the manufacturer must compile 

this information in order to prepare its 

submission to FDA, FDA estimates that 

40 hours will be required per 

submission. Because 10 annual 

responses are expected under 

§ 99.201(a)(1), the estimated total 

burden for this provision is 400 hours 

(10 annual responses x 40 hours per 

response). 

Section 99.201(a)(2) requires the 

manufacturer to submit clinical trial 

information pertaining to the safety and 

effectiveness of the new use, clinical 

experience reports on the safety of the 

new use, and a summary of the 

information. FDA estimates 24 burden 

hours per response for this provision for 

assembling, reviewing, and submitting 

the information and assumes that the 

manufacturer will have already acquired 

some of this information in order to 

decide whether to disseminate 

information on an unapproved use 

under part 99. The estimated total 

burden for this provision is 240 hours 

(10 annual responses x 24 hours per 

response). 

Section 99.201(a)(3) requires the 

manufacturer to explain its search 

strategy when assembling its 

bibliography. FDA estimates that only 1 

hour will be required for the 

explanation because the manufacturer 

would have developed and used its 

search strategy before preparing the 

bibliography. Because 10 annual 

responses are expected under 

§ 99.201(a)(3), the estimated total 

burden for this provision is 10 hours (10 

annual responses x 1 hour per 

response). 

Section 99.201(b) simply requires the 

manufacturer’s attorney, agent, or other 

authorized official to sign its 

submissions, certifications, and requests 

for an exemption. FDA estimates that 

only 30 minutes are necessary for such 

signatures. Because 10 annual responses 

are expected under § 99.201(b), the 

estimated total burden for this provision 

is 5 hours (10 annual responses x 0.5 

hours per response). 

Section 99.201(c) requires the 

manufacturer to provide two copies 

with its original submission. Copying 

the submission should not be timeconsuming, so FDA estimates the 

burden to be 30 minutes. Because 10 

annual responses are expected under 

§ 99.201(c), the estimated total burden 

for this provision is 5 hours (10 annual 

responses x 0.5 hours per response). 

While the act requires manufacturers 

to provide a submission to FDA before 

they disseminate information on 

unapproved/new uses, it also permits 

the following actions for manufacturers: 

(1) To have completed studies and 

promise to submit a supplemental 

application for the new use within 6 

months after the date of initial 

dissemination; (2) to provide protocols, 

a schedule for completing studies, and 

submit a supplemental application for 

the new use within 36 months after the 

date of initial dissemination; (3) to have 

completed studies and have submitted a 

supplemental application for the new 

use; or (4) to request an exemption from 

the requirement to submit a 

supplemental application. These 

possible scenarios are addressed in 

§§ 99.201(a)(4)(i)(A), (a)(4)(ii)(A), (a)(5), 

and 99.205(b). Based on the average of 

the total number of required 

submissions received during 2002, 

2003, and 2004, FDA has made the 

following burden estimates: 

Section 99.201(a)(4)(i)(A) requires the 

manufacturer, if the manufacturer has 

completed studies needed for the 

submission of a supplemental 

application for the new use, to submit 

the protocol(s) for the completed 

studies, or, if the protocol(s) was 

submitted to an investigational new 

drug application (IND) or investigational 

device exemption (IDE), to submit the 

IND or IDE number(s), the date of 

submission of the protocol(s), the 

protocol number(s), and the date of any 

amendments to the protocol(s). FDA 

estimates that 30 hours will be required 

for this response because this is 

information that each manufacturer 

already maintains for its drugs or 

devices. The estimated total burden for 

this provision is 210 hours (7 annual 

responses x 30 hours per response). 

For manufacturers who submit the 

protocol(s) and a schedule for 

conducting studies, § 99.201(a)(4)(ii)(A) 

requires the manufacturer to include, in 

its schedule, the projected dates on 

which the manufacturer expects the 

principal study events to occur. FDA 

estimates a manufacturer will need 

approximately 60 hours to include the 

projected dates because it would have to 

contact the studies’ principal 

investigator(s) and other company 

officials. The estimated total burden for 

this provision is 420 hours (7 annual 

responses x 60 hours per response). 

If the manufacturer has submitted a 

supplemental application for the new 

use, § 99.201(a)(5) requires a crossreference to that supplemental 

application. FDA estimates that only 1 

56710 Federal Register / Vol. 70, No. 187 / Wednesday, September 28, 2005 / Notices 

hour will be needed because 

manufacturers already maintain this 

information. The estimated total burden 

for this provision is 2 hours (2 annual 

responses x 1 hour per response). 

FDA has not received any requests for 

an exemption under § 99.205(b). 

However, for purposes of this request 

for OMB approval, FDA estimates that 

annually one manufacturer may submit 

one exemption request under 

§ 99.205(b). FDA estimates that the 

reporting burden for each exemption 

request will be 82 hours. Therefore, the 

estimated total burden for this provision 

is 82 hours (1 annual response x 82 

hours per response). 

Under § 99.203, a manufacturer that 

has certified that it will complete 

studies necessary to submit a 

supplemental application within 36 

months after its submission to FDA, but 

later finds that it will be unable to 

complete such studies or submit a 

supplemental application within that 

time period, may request an extension 

of time from FDA. Such requests for 

extension should be limited, occurring 

less than 1 percent of the time, because 

manufacturers and FDA, when 

developing or reviewing study 

protocols, should be able to identify 

when a study will require more than 36 

months to complete. Section 99.203 

contemplates extension requests under 

two different scenarios. Under 

§ 99.203(a), a manufacturer may make 

an extension request before it makes a 

submission to FDA regarding the 

dissemination of information under part 

99. The agency expects such requests to 

be limited, occurring less than 1 percent 

of the time (or one annual response), 

and that such requests will result in a 

reporting burden of 10 hours per 

request. The estimated total burden for 

this provision, therefore, is 10 hours (1 

annual response x 10 hours per 

response). Section 99.203(b) specifies 

the contents of a request to extend the 

time for completing planned studies 

after the manufacturer has provided its 

submission to FDA. The required 

information includes a description of 

the studies, the current status of the 

studies, reasons why the studies cannot 

be completed on time, and an estimate 

of the additional time needed. FDA 

estimates that 10 hours will be needed 

for reporting the required information 

under § 99.203(b) because it would 

require consultation between the 

manufacturer and key individuals (such 

as the studies’ principal investigator(s)). 

As in the case of § 99.203(a), the 

expected number of responses is very 

small (one annual response), and the 

estimated total burden for this provision 

is 10 hours (1 annual response x 10 

hours per response). 

Section 99.203(c) requires two copies 

of an extension request (in addition to 

the request required under section 

554(c)(3) of the act (21 U.S.C. 360aaa3(c)(3))). FDA estimates that these 

copies will result in a minimal reporting 

burden of 30 minutes. However, this 

requirement would apply to extension 

requests under § 99.203(a) and (b), so 

the estimated total number of annual 

responses is two, resulting in an 

estimated total burden for this provision 

of 1 hour (2 annual responses x 0.5 

hours per response). 

The remaining reporting and 

recordkeeping burdens are as shown in 

the following estimates: 

Section 99.501(a)(1) requires the 

manufacturer to maintain records that 

identify recipients by category or 

individually. Under § 99.301(a)(3), FDA 

will notify the manufacturer if it needs 

to maintain records identifying 

individual recipients because of special 

safety considerations associated with 

the new use. This means that, in most 

cases, the manufacturer will only have 

to maintain records identifying 

recipients by category. In either event, 

the manufacturer will know if it must 

maintain records that identify 

individual recipients before it begins 

disseminating information. The time 

required to identify recipients 

individually should be minimal, and the 

time required to identify recipients by 

category should be even less. Therefore, 

FDA estimates the burden for this 

provision to be 10 hours, and, because 

8 annual records are expected under 

§ 99.501(a)(1), the estimated total 

burden for this provision is 80 hours (8 

annual records x 10 hours per record). 

Section 99.501(a)(2) requires the 

manufacturer to maintain a copy of the 

information it disseminates. This task is 

not expected to be time-consuming, so 

FDA estimates the burden to be 1 hour. 

Because eight annual records are 

expected under § 99.501(a)(2), the 

estimated total burden for this provision 

is 8 hours (8 annual records x 1 hour per 

record). 

Section 99.501(b)(1) requires the 

manufacturer to submit to FDA 

semiannually a list containing the 

articles and reference publications that 

were disseminated in the preceding 6- 

month period. FDA estimates a burden 

of 8 hours for this provision. The 

burden may be less if the manufacturer 

develops and updates the list while it 

disseminates articles and reference 

publications during the 6-month period 

(as opposed to generating a completely 

new list at the end of each 6-month 

period), and if the volume of 

disseminated materials is small. The 

estimated total burden for this provision 

is 160 hours (10 responses submitted 

semiannually x 8 hours per response). 

Section 99.501(b)(2) requires 

manufacturers that disseminate 

information to submit to FDA 

semiannually a list that identifies the 

categories of providers who received the 

articles and reference publications. 

Section 99.501(b)(2) also requires the 

list to identify which category of 

recipients received each particular 

article or reference publication. If each 

of the 10 submissions under part 99 

results in disseminated information, 

§ 99.501(b)(2) would result in 20 lists 

(10 submissions x 2 submissions 

semiannually) identifying which 

category of recipients received each 

particular article or reference 

publication. The agency estimates the 

burden to be only 1 hour per response 

because this type of information is 

maintained as a usual and customary 

business practice, and the estimated 

total burden for this provision is 20 

hours (20 responses submitted 

semiannually x 1 hour per response). 

In relation to § 99.201(a)(2), 

§ 99.501(b)(3) requires the manufacturer 

to provide, on a semiannual basis, a 

notice and summary of any additional 

clinical research or other data relating to 

the safety and effectiveness of the new 

use and, if it possesses such research or 

data, to provide a copy to FDA. This 

burden should not be as extensive as 

that in § 99.201(a)(2), so FDA estimates 

the burden to be 20 hours per response, 

for an estimated total burden of 400 

hours for this provision (10 responses 

submitted semiannually x 20 hours per 

response). 

If a manufacturer discontinues or 

terminates a study before completing it, 

§ 99.501(b)(4) requires the manufacturer 

to state the reasons for discontinuing or 

terminating the study in its next 

progress report. FDA estimates that 

annually this will affect only 1 percent 

of all applications (8 x 0.01 = 0.08, 

rounded up to 1) and only one 

manufacturer. FDA estimates 2 hours of 

reporting time for this requirement 

because the manufacturer should know 

the reasons for discontinuing or 

terminating the study and would only 

need to provide those reasons in its 

progress report. The estimated total 

burden for this provision is 2 hours (1 

annual response x 2 hours per 

response). 

Section 99.501(b)(5) requires the 

manufacturer to submit any new or 

additional information that relates to 

whether the manufacturer continues to 

meet the requirements for the 

exemption after an exemption has been 

Federal Register / Vol. 70, No. 187 / Wednesday, September 28, 2005 / Notices 56711 

granted. FDA estimates that 10 percent 

of all submissions will contain an 

exemption request (8 annual 

submissions x 0.10 = 0.8, rounded up to 

1), and has assumed that all exemption 

requests will be granted, for an 

estimated total of 1 annual response. 

The information sought under 

§ 99.501(b)(5) pertains solely to new or 

additional information and is not 

expected to be as extensive as the 

information required to obtain an 

exemption. Thus, FDA estimates the 

burden for § 99.501(b)(5) to be 41 hours 

per response (or half the burden 

associated with an exemption request), 

for an estimated total burden of 41 

hours for this provision (1 annual 

response x 41 hours per response). 

Section 99.501(c) requires the 

manufacturer to maintain records for 3 

years after it has ceased dissemination 

of the information. FDA estimates the 

burden for this provision to be 1 hour. 

Because eight annual records are 

expected under § 99.501(c), the 

estimated total burden for this provision 

is 8 hours (8 annual records x 1 hour per 

record). 

The estimates for §§ 99.201(a)(1), 

(a)(2), (a)(3), (b), (c), 99.501(b)(1), (b)(2), 

and (b)(3) have been increased by two 

responses each to account for 

manufacturer resubmissions. In 

addition, the estimate for 

§ 99.201(a)(4)(i)(A) and (a)(4)(ii)(A) has 

been increased by one response each to 

account for manufacturer 

resubmissions. 

Respondents are all manufacturers 

(persons and businesses, including 

small businesses) of drugs, biologics, 

and device products. 

In the Federal Register of June 16, 

2005 (70 FR 35099), FDA published a 

60-day notice requesting public 

comment on the information collection 

provisions. No comments were received. 

FDA estimates the burden of this 

collection of information as follows: 

TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1

21 CFR Section No. of 

Respondents 

Annual Responses 

per Respondent 

Total Annual 

Responses 

Hours per 

Response Total Hours 

99.201(a)(1) 5 1 10 40 400 

99.201(a)(2) 5 1 10 24 240 

99.201(a)(3) 5 1 10 1 10 

99.201(a)(4)(i)(A) 6 1 7 30 210 

99.201(a)(4)(ii)(A) 6 1 7 60 420 

99.201(a)(5) 1 1 2 1 2 

99.201(b) 5 1 10 0 .5 5 

99.201(c) 5 1 10 0 .5 5 

99.203(a) 1 1 1 10 10 

99.203(b) 1 1 1 10 10 

99.203(c) 1 1 2 0 .5 1 

99.205(b) 1 1 1 82 82 

99.501(b)(1) 5 3 20 8 160 

99.501(b)(2) 5 1 20 1 20 

99.501(b)(3) 5 1 20 20 400 

99.501(b)(4) 1 1 1 2 2 

99.501(b)(5) 1 1 1 41 41 

Total Hours 2,018 

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

TABLE 2.—ESTIMATED ANNUAL RECORDKEEPING BURDEN1

21 CFR Section No. of 

Recordkeepers 

Annual Frequency 

per Recordkeeping 

Total Annual 

Records 

Hours per 

Record Total Hours 

99.501(a)(1) 5 1 8 10 80 

99.501(a)(2) 5 1 8 1 8 

99.501(c) 5 1 8 1 8 

Total Hours 96 

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

56712 Federal Register / Vol. 70, No. 187 / Wednesday, September 28, 2005 / Notices 

The estimated burden associated with 

the information collection requirements 

for these provisions is 2,114 hours. 

Dated: September 22, 2005. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. 05–19394 Filed 9–27–05; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[FDA 225–04–4007] 

Memorandum of Understanding 

between the Food and Drug 

Administration, Forensic Chemistry 

Center and the Federal Bureau of 

Investigation 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is providing 

notice of a memorandum of 

understanding (MOU) between the Food 

and Drug Administration and the 

Federal Bureau of Investigation (FBI). 

The purpose of this MOU is to establish 

the general policies and procedures that 

will govern administrative, logistical, 

and operational support to FBI missions 

including cost reimbursable activities. 

DATES: The agreement became effective 

December 22, 2004. 

FOR FURTHER INFORMATION CONTACT:

For the FDA: Fred Fricke, Food and 

Drug Administration, Forensic 

Chemistry Center, 6751 Steger Dr., 

Cincinnati, OH 45237, 513–679–

2700. 

For the FBI: David L. Wilson, Federal 

Bureau of Investigation Laboratory, 

Chemical Biological Sciences Unit, 

Quantico, VA 22135, 703–632–

7766. 

SUPPLEMENTARY INFORMATION: In 

accordance with 21 CFR 20.108(c), 

which states that all written agreements 

and MOUs between FDA and others 

shall be published in the Federal 

Register, the agency is publishing notice 

of this MOU. 

Dated: September 20, 2005. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

BILLING CODE 4160–01–S