73104 Federal Register / Vol. 75, No. 228 / Monday, November 29, 2010 / Notices 

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. 

Animal Drug User Fee Cover Sheet; 

FDA Form 3546 (OMB Control Number 

0910–0539)—Extension 

Under section 740 of the Federal 

Food, Drug, and Cosmetic Act (the 

FD&C Act) (21 U.S.C. 379j–12), as 

amended by ADUFA, FDA has the 

authority to assess and collect for 

certain animal drug user fees. Because 

the submission of user fees concurrently 

with applications and supplements is 

required, review of an application 

cannot begin until the fee is submitted. 

The types of fees that require a cover 

sheet are certain animal drug 

application fees and certain 

supplemental animal drug application 

fees. The cover sheet (FDA Form 3546) 

is designed to provide the minimum 

necessary information to determine 

whether a fee is required for the review 

of an application or supplement, to 

determine the amount of the fee 

required, and to assure that each animal 

drug user fee payment and each animal 

drug application for which payment is 

made is appropriately linked to the 

payment that is made. The form, when 

completed electronically, will result in 

the generation of a unique payment 

identification number used in tracking 

the payment. FDA will use the 

information collected to initiate 

administrative screening of new animal 

drug applications and supplements to 

determine if payment has been received. 

FDA estimates the burden of this 

collection of information as follows: 

TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1

Section of the FD&C Act as amended by ADUFA Number of respondents 

Annual 

frequency per 

response 

Total annual 

responses 

Hours per 

response Total hours 

740(a)(1), FDA Form 3546 (Cover Sheet) .......................... 76 1 76 1 76 

Total .............................................................................. ........................ ........................ ........................ ........................ 76 

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

Respondents to this collection of 

information are new animal drug 

applicants or manufacturers. Based on 

FDA’s database system, there are an 

estimated 140 manufacturers of 

products or sponsors of new animal 

drugs potentially subject to ADUFA. 

However, not all manufacturers or 

sponsors will have any submissions in 

a given year and some may have 

multiple submissions. The total number 

of annual responses is based on the 

number of submissions received by FDA 

in fiscal year 2008. The estimated hours 

per response are based on past FDA 

experience with the various 

submissions. The hours per response are 

based on the average of these estimates. 

Dated: November 22, 2010. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2010–29820 Filed 11–26–10; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2010–N–0547] 

Clinical Development Programs for 

Sedation Products; Request for 

Assistance 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is seeking 

information on a variety of issues 

related to the clinical development and 

use of sedation products in adult and 

pediatric age groups. FDA is inviting 

any interested party, or parties, to 

facilitate an evaluation of critical 

fundamentals of the science related to 

sedation products by conducting and 

managing a coordination of activities 

that will bring together experts in the 

field, including from academia, patient 

organizations, and industry. The first 

step in this process would be for the 

party or parties to plan and hold one or 

more public meetings to discuss these 

issues. FDA intends to take into account 

the information provided from these 

activities as we develop FDA guidance 

on clinical development programs for 

sedation products. We intend to submit 

to the docket all the information 

received in response to this notice so 

that interested parties may be fully 

informed. 

DATES: Submit electronic or written 

comments on this notice by January 28, 

2011. 

ADDRESSES: Submit electronic 

comments on this notice to http:// 

www.regulations.gov. Submit written 

comments to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. 

FOR FURTHER INFORMATION CONTACT: Sara 

E. Stradley, Center for Drug Evaluation 

and Research, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 22, rm. 3162, Silver Spring, 

MD 20993–0002, 301–796–1298, 

FAX:301–796–9713, e-mail: 

sara.stradley@fda.hhs.gov. 

mstockstill on DSKH9S0YB1PROD with NOTICES

Federal Register / Vol. 75, No. 228 / Monday, November 29, 2010 / Notices 73105 

SUPPLEMENTARY INFORMATION: 

I. Background 

Because of the need for more 

information on the development of 

products intended to be used in humans 

for sedation in hospital and outpatient 

settings, FDA is requesting assistance 

from the public in conducting scientific 

analyses for the purpose of further 

understanding the physiology of 

sedation and clinical trial design issues 

related to the development of sedation 

products. 

II. Request for Assistance 

FDA is inviting any interested group 

or consortium of interested groups from 

academia, industry, practitioners, as 

well as patients and their 

representatives to conduct and manage 

the coordination of a critical evaluation 

of certain fundamentals of the science 

related to sedation products. Initially, 

the party or parties would organize and 

hold one or more public meetings or 

workshops to discuss relevant questions 

associated with the spectrum of 

sedation, particularly as it relates to 

procedural and intensive care unit (ICU) 

sedation, as well as associated clinical 

trial design issues. FDA believes that a 

public meeting would help solicit 

feedback from all parties leading to 

conceptual advances and a discussion of 

such advances in a concept paper. This 

discussion would take into account 

challenges involved in assessment of 

sedation and emphasize the rationale for 

various approaches to key clinical trial 

design issues involving sedation 

products. The effort would ultimately 

lead to developing a draft guidance that 

would be issued by FDA for broad 

public comment before finalization, 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

III. Suggestions 

FDA welcomes other suggestions of 

activities that could be undertaken as 

part of this guidance development 

effort. 

IV. Possible Questions/Issues o Be 

Considered 

To provide a starting point for 

discussion, FDA has developed a list of 

some key concepts that the interested 

parties may want to consider for 

discussion at the meeting as follows: 

1. Currently, sedation is studied 

primarily in the procedural and ICU 

settings. Procedural sedation may 

involve an outpatient setting, and may 

require the institution of Monitored 

Anesthesia Care (MAC). There is great 

interest among health care providers 

with varied medical backgrounds in 

sedation for surgical and diagnostic 

procedures in the outpatient setting. 

What generally constitutes MAC, and 

what qualifies a product for MAC? How 

should the need for MAC be assessed in 

clinical trials involving sedation 

products? 

2. Assessment of procedural sedation 

involves conducting clinical trials in a 

wide range of diagnostic and surgical 

procedures. What surgical and 

diagnostic procedures are of particular 

value in assessing the procedural 

sedation indication? Are there certain 

procedures that should be evaluated for 

every product that seeks the procedural 

sedation indication, or can the range of 

trials be governed by the pharmacologic 

profile of the product? Should the scope 

of the sedation guidance apply to 

settings other than procedural or ICU 

sedation? 

3. There are patient subgroups in 

which the use of sedation products 

should be particularly evaluated. For 

example, pediatric and geriatric age 

groups often require dose adjustment 

because of varying metabolic needs and 

other clinical parameters. In addition, 

dose adjustment may be required in 

patients with renal and hepatic 

impairment. Are there other patient 

subgroups that require specific 

evaluation in clinical trials involving 

sedation products? 

4. Sedation products usually are used 

as infusions that are titrated to achieve 

the desired sedation effect. What are 

optimal trial designs for sedation 

products? Should clinical trials 

involving sedation products be placebocontrolled or active-controlled? 

Currently, Midazolam, Propofol, 

Ketamine, and Dexmedetomidine are 

commonly used sedation products. Of 

these, Midazolam is the most commonly 

used active comparator in sedation 

product trial designs. Is it possible to 

accurately predict the actual size of the 

treatment effect based on use of 

Midazolam or other commonly used 

sedation products? Although trial 

designs involving these products are 

believed to be predictive, it may not be 

possible to generalize from them. If 

active- and placebo-controlled product 

trial designs are not optimal, what 

alternative designs can be used to 

support sedation claims? Would doseescalation comparative trial designs be 

useful in studying sedation products? 

5. How is sedation defined and what 

are appropriate outcome measures to 

assess sedation? At present, there is 

diverse opinion among health care 

providers regarding the definition of 

sedation. For example, is the assessment 

of anxiolysis and agitation a separate 

entity or is it contained within the 

spectrum of sedation itself? Should this 

depend upon the known pharmacologic 

profile of the product? Currently, the 

primary efficacy endpoint in sedation 

clinical trials is usually assessed using 

sedation scales. Commonly used 

sedation scales include the Ramsey 

Sedation Scale, Richmond Agitation and 

Sedation Scale, and Mean Observer’s 

Assessment of Agitation/Sedation Scale. 

How appropriate is the use of such 

sedation scales in clinical trials 

involving sedation products? Should all 

sedation scales be standardized and 

validated? 

6. Sedation scales are used for 

assessing the primary efficacy endpoint 

for sedation products. What are 

meaningful secondary efficacy 

endpoints in such trials? Are subjective 

and objective assessments of memory, 

recall, anxiety, agitation, delirium, 

among others, appropriate as efficacy 

endpoints? Which of these efficacy 

endpoints should be considered 

clinically significant? If so, what 

outcome measures and trial designs 

should be used? Specifically, how 

should anxiolysis and agitation be 

assessed within the realm of products 

primarily indicated for sedation 

purposes and not to treat an anxiety 

disorder or agitation? Should there be 

different scales for assessing each 

component, or can the assessment be 

contained within the spectrum of 

sedation using an appropriate scale? 

Further, is an accurate assessment of 

anxiolysis feasible given the multiple 

variables that can affect anxiety in a 

procedural sedation setting that would 

have to be standardized (e.g., physician 

and practice setting profile, preprocedure anticipatory patient 

prepping, individual thresholds for 

anxiety)? 

7. ICU sedation products are often 

used for periods longer than 24 hours. 

Should an ICU sedation indication 

include a short-term (less than 24 hours) 

and long-term (more than 24 hours) use 

assessment for purposes of efficacy and 

safety? Long-term use may be associated 

with tolerance/tachyphylaxis and a 

dose-related increase in adverse effects. 

What should the size and duration of 

exposure of the safety database be for 

sedation products? 

V. Comments 

Interested persons should submit 

comments and expressions of interest in 

conducting and managing a critical 

evaluation to the Division of Dockets 

Management (see ADDRESSES). It is only 

necessary to send one set of comments. 

It is no longer necessary to send two 

copies of mailed comments. Identify 

comments with the docket number 

mstockstill on DSKH9S0YB1PROD with NOTICES

73106 Federal Register / Vol. 75, No. 228 / Monday, November 29, 2010 / Notices 

found in brackets in the heading of this 

document. Received comments may be 

seen in the Division of Dockets 

Management between 9 a.m. and 4 p.m., 

Monday through Friday. 

Dated: November 17, 2010. 

Leslie Kux, 

Acting Assisitant Commissioner for Policy. 

[FR Doc. 2010–29927 Filed 11–26–10; 8:45 am] 

BILLING CODE 4160–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2010–D–0565] 

Draft Guidance for Industry and Food 

and Drug Administration Staff; 

Establishing the Performance 

Characteristics of In Vitro Diagnostic 

Devices for the Detection of 

Clostridium difficile; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of the draft guidance 

document entitled ‘‘Establishing the 

Performance Characteristics of In Vitro 

Diagnostic Devices for the Detection of 

Clostridium difficile.’’ This draft 

guidance document describes FDA’s 

recommendations concerning 510(k) 

submissions for various types of in vitro 

diagnostic devices (IVDs) intended to be 

used for detecting Clostridium difficile 

(C. difficile). This draft guidance is not 

final nor is it in effect at this time. 

DATES: Although you can comment on 

any guidance at any time (see 21 CFR 

10.115(g)(5)), to ensure that the Agency 

considers your comment on this draft 

guidance before it begins work on the 

final version of the guidance, submit 

written or electronic comments on the 

draft guidance by February 28, 2011. 

ADDRESSES: Submit written requests for 

single copies of the draft guidance 

document entitled ‘‘Establishing the 

Performance Characteristics of In Vitro 

Diagnostic Devices for the Detection of 

Clostridium difficile’’ to the Division of 

Small Manufacturers, International, and 

Consumer Assistance, Center for 

Devices and Radiological Health, Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 66, Rm. 4613, 

Silver Spring, MD 20993–0002. Send 

one self-addressed adhesive label to 

assist that office in processing your 

request, or fax your request to 301–847– 

8149. See the SUPPLEMENTARY

INFORMATION section for information on 

electronic access to the guidance. 

Submit electronic comments on the 

draft guidance to http:// 

www.regulations.gov. Submit written 

comments to the Division of Dockets 

Management, Food and Drug 

Administration, 5630 Fishers Lane, Rm. 

1061, Rockville, MD 20852. Identify 

comments with the docket number 

found in brackets in the heading of this 

document. 

FOR FURTHER INFORMATION CONTACT: 

Stephen Lovell, Center for Devices and 

Radiological Health, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 66, Rm. 4435, Silver Spring, 

MD 20993–0002, 301–796–6968. 

SUPPLEMENTARY INFORMATION: 

I. Background 

This draft guidance includes 

recommendations concerning 510(k) 

submissions for various types of (IVDs) 

intended to be used for detecting C. 

difficile. The document is a revision of 

‘‘Review Criteria for Assessment of 

Laboratory Tests Directed at Assisting in 

the Diagnosis of C. difficile Associated 

Disease’’ issued on May 31, 1990. It is 

updated to include new issues and 

technologies identified since the 1990 

guidance. Such methods include 

detection of C. difficile nucleic acids 

(e.g., C. difficile toxin B gene by nucleic 

acid amplification methods such as the 

Real-Time Polymerase Chain Reaction 

technique). 

II. Significance of Guidance 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized will 

represent the Agency’s current thinking 

on establishing the performance 

characteristics of in vitro diagnostic 

devices for the detection of C. difficile. 

It does not create or confer any rights for 

or on any person and does not operate 

to bind FDA or the public. An 

alternative approach may be used if 

such approach satisfies the 

requirements of the applicable statute 

and regulations. 

III. Electronic Access 

Persons interested in obtaining a copy 

of the draft guidance may do so by using 

the Internet. A search capability for all 

CDRH guidance documents is available 

at http://www.fda.gov/MedicalDevices/ 

DeviceRegulationandGuidance/ 

GuidanceDocuments/default.htm. 

Guidance documents are also available 

at http://www.regulations.gov. To 

receive ‘‘Establishing the Performance 

Characteristics of In Vitro Diagnostic 

Devices for the Detection of Clostridium 

difficile,’’ you may either send an e-mail 

request to dsmica@fda.hhs.gov to 

receive an electronic copy of the 

document or send a fax request to 301– 

847–8149 to receive a hard copy. Please 

use the document number 1715 to 

identify the guidance you are 

requesting. 

IV. Paperwork Reduction Act of 1995 

This draft guidance refers to 

previously approved collections of 

information found in FDA regulations 

and guidance documents. These 

collections of information are subject to 

review by the Office of Management and 

Budget (OMB) under the Paperwork 

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

3520). The collections of information in 

21 CFR part 807 subpart E have been 

approved under OMB control number 

0910–0120; the collections of 

information in 21 CFR part 812 have 

been approved under OMB control 

number 0910–0078; the collections of 

information in 42 CFR section 493.15 

have been approved under OMB control 

number 0910–0598; the collections of 

information in 21 CFR section 50.23 

have been approved under OMB control 

number 0910–0586; and the collections 

of information in 21 CFR section 56.115 

have been approved under OMB control 

number 0910–0130. 

V. Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) either electronic or written 

comments regarding this document. It is 

only necessary to send one set of 

comments. It is no longer necessary to 

send two copies of mailed comments. 

Identify comments with the docket 

number found in brackets in the 

heading of this document. Received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday. 

Dated: November 22, 2010. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2010–29794 Filed 11–26–10; 8:45 am] 

BILLING CODE 4160–01–P 

mstockstill on DSKH9S0YB1PROD with NOTICES