8968 Federal Register / Vol. 75, No. 38 / Friday, February 26, 2010 / Notices 

Justification for the Exception to 

Competition 

The reason for this exception is to 

allow sufficient time for the HRSA’s 

Maternal and Child Health Bureau 

(MCHB) to align its fiscal resources and 

programmatic goals: 

• With the developing Maternal and 

Child Health Strategic Plan and with 

HRSA and Departmental plans; and, 

• With the Early Learning and 

Development Initiative of the 

Department of Health and Human 

Services and the Department of 

Education; and, to maintain during this 

transition period MCH programmatic 

support to the State and community 

MCH constituencies which currently are 

receiving technical assistance services 

from these MCHB grantees. 

The activities listed in the previous 

paragraph will not be completed in time 

for the FY 2010 grant competition. The 

MCHB proposes, therefore, to extend 

into FY 2011 the project periods of 

those grants scheduled to conclude in 

FY 2010 in order to have a larger and 

more current grant competition in FY 

2011 reflective of any and all 

programmatic changes resulting from 

the above referenced activities and 

actions. Delaying the competition into 

FY 2011 also allows the MCHB 

additional time to consult with and 

provide information to constituency 

groups about changes in program 

direction. Providing an extension with 

funds to these grantees through January 

31, 2011, will ensure the provision of 

technical assistance to the affected MCH 

constituencies continues without 

disruption. 

Dated: February 9, 2010. 

Mary K. Wakefield, 

Administrator. 

[FR Doc. 2010–3886 Filed 2–25–10; 8:45 am] 

BILLING CODE 4165–15–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2010–D–0090] 

Draft Guidance for Industry on 

Adaptive Design Clinical Trials for 

Drugs and Biologics; Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a draft guidance entitled 

‘‘Adaptive Design Clinical Trials for 

Drugs and Biologics.’’ The draft 

guidance provides sponsors and the 

review staff in FDA’s Center for Drug 

Evaluation and Research (CDER) and 

Center for Biologics Evaluation and 

Research (CBER) with information 

regarding adaptive design clinical trials 

when used in drug development 

programs. The draft guidance gives 

advice on various topics, such as what 

aspects of adaptive design clinical trials 

(i.e., clinical, statistical, regulatory) call 

for special consideration, when to 

interact with FDA while planning and 

conducting adaptive design studies, 

what information to include in the 

adaptive design for FDA review, and 

issues to consider in the evaluation of 

a completed adaptive design study. The 

draft guidance is intended to assist 

sponsors in planning and conducting 

adaptive design clinical studies, and to 

facilitate an efficient FDA review. 

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 June 1, 2010. 

ADDRESSES: Submit written requests for 

single copies of the draft guidance to the 

Division of Drug Information, Center for 

Drug Evaluation and Research, Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, rm. 2201, 

Silver Spring, MD 20993–0002, or to the 

Office of Communication, Outreach and 

Development, 1401 Rockville Pike, suite 

200N, Rockville, MD 20852–1448. Send 

one self-addressed adhesive label to 

assist that office in processing your 

requests. The draft guidance may also be 

obtained by mail by calling CBER at 1– 

800–835–4709 or 301–827–1800. 

Submit written comments on the draft 

guidance to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. Submit 

electronic comments to http:// 

www.regulations.gov. See the 

SUPPLEMENTARY INFORMATION section for 

electronic access to the draft guidance 

document. 

FOR FURTHER INFORMATION CONTACT: 

Robert T. O’Neill, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 21, rm. 3554, 

Silver Spring, MD 20993–0002, 301– 

796–1700; or 

Sue-Jane Wang, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 21, rm. 3554, 

Silver Spring, MD 20993–0002, 301– 

796–1700; or 

Marc Walton, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Bldg. 21, rm. 4524, 

Silver Spring, MD 20993–0002, 301– 

796–2600; or 

Stephen Ripley, Center for Biologics 

Evaluation and Research, Food and 

Drug Administration, 1401 Rockville 

Pike, suite 200N, Rockville, MD 20852– 

1448, 301–827–6210. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a draft guidance for industry entitled 

‘‘Adaptive Design Clinical Trials for 

Drugs and Biologics.’’ This guidance 

provides information regarding adaptive 

design trials when used in drug 

development programs. 

There is great interest in the 

possibility that clinical trials can be 

designed with ‘‘adaptive’’ features (i.e., 

changes in design or analyses guided by 

examination of the accumulated data at 

an interim point in the trial) that can 

make the studies more efficient (e.g., 

shorter duration, fewer patients), more 

likely to demonstrate an effect of the 

drug if one exists, or more informative 

(e.g., by providing broader doseresponse information). The draft 

guidance discusses clinical, statistical, 

and regulatory aspects of a wide range 

of adaptive design clinical studies that 

can be proposed as part of a drug 

development program, including both 

familiar and less familiar approaches. 

As more experience is obtained with the 

less familiar designs, sponsors can 

improve their understanding of 

circumstances where these designs are 

most useful or may pose risks to study 

integrity and interpretation. The draft 

guidance describes aspects of adaptive 

design trials that deserve special 

consideration and provides advice on 

the information that should be provided 

to FDA and how best to interact with 

FDA to facilitate an efficient review. 

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 adaptive design clinical trials for 

drugs and biologics. 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 statutes 

and regulations. 

II. Paperwork Reduction Act of 1995 

Under the Paperwork Reduction Act 

of 1995 (the PRA) (44 U.S.C. 3501– 

3520), Federal agencies must obtain 


sroberts on DSKD5P82C1PROD with NOTICES
Federal Register / Vol. 75, No. 38 / Friday, February 26, 2010 / Notices 8969 

approval from the Office of Management 

and Budget (OMB) for each collection of 

information that 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 for each proposed 

collection of information before 

submitting the collection to OMB for 

approval. To comply with this 

requirement, FDA is publishing this 

notice of the proposed collection of 

information set forth in this document. 

With respect to the collection of 

information associated with this draft 

guidance, FDA invites comments on the 

following topics: (1) Whether the 

proposed information collected is 

necessary for the proper performance of 

FDA’s functions, including whether the 

information will have practical utility; 

(2) the accuracy of FDA’s estimated 

burden of the proposed information 

collected, including the validity of the 

methodology and assumptions used; (3) 

ways to enhance the quality, utility, and 

clarity of the information collected; and 

(4) ways to minimize the burden of 

information collected on the 

respondents, including through the use 

of automated collection techniques, 

when appropriate, and other forms of 

information technology. 

A. Develop Written Standard Operating 

Procedures (SOPs) (Reporting and 

Recordkeeping Burdens) 

In the drug development process, it is 

particularly important to protect study 

blinding of an adaptive design study, 

where the design is modified after 

examination of unblinded interim data, 

to avoid the introduction of bias in the 

study conduct and to maintain 

confidence in the validity of the study’s 

result. The draft guidance recommends 

that sponsors include in the adaptive 

design protocol comprehensive and 

prospective written SOPs that define 

who will implement the interim 

analysis and adaptation plan, and all 

monitoring and related procedures for 

accomplishing the implementation, 

providing for the strict control of access 

to unblinded data. The draft guidance 

discusses the information that should be 

included in the SOPs and other issues 

that should be addressed: (1) 

Identification of the personnel who will 

perform the interim analyses and who 

will have access to the interim results; 

(2) how that access will be controlled 

and how the interim analyses will be 

performed, including how any potential 

irregularities in the data (e.g., 

withdrawals, missing values) will be 

managed; (3) how adaptation decisions 

will be made; (4) whether there are any 

foreseeable impediments to complying 

with the SOPs; (5) how compliance with 

the SOPs will be documented and 

monitored; and (6) what information, 

under what circumstances, is permitted 

to be passed from the Data Monitoring 

Committee (DMC) to the sponsor or 

investigators. The draft guidance 

recommends extensively documenting 

the rules of operation of the DMC (or 

other involved groups) and including a 

description of the responsibilities of 

each entity involved in the process. 

Based on FDA’s data on the number of 

sponsors that would be covered by the 

draft guidance, we estimate that 

approximately 180 SOPs related to 

adequate design will be sent to FDA 

each year, and that each SOP will take 

approximately 6 hours to develop, 

maintain, and update. 

The draft guidance recommends that 

sponsors document and maintain 

records of the SOPs. Documenting and 

maintaining records is considered 

recordkeeping under the PRA. We 

estimate that 180 SOPs related to 

adaptive design will be documented and 

maintained each year, and that each 

SOP will take approximately 30 minutes 

to document and maintain. 

B. Perform Simulations and Analyze 

Data (Reporting Burden) 

The draft guidance discusses study 

simulations that may be useful in 

evaluating different designs. Because 

patient safety is a concern in adaptive 

design dose escalation studies, the draft 

guidance recommends that sponsors use 

simulations to explore the features of 

different study designs with regard to 

the balance of efficiency (study size) 

and subject safety. The draft guidance 

recommends that sponsors include 

these simulations and their respective 

analyses with the selected design. We 

estimate that 90 simulations and their 

respective analyses will be sent to FDA 

each year, and that each simulation and 

its analysis will take approximately 40 

hours to prepare and submit. 

This draft guidance also refers to 

previously approved collections of 

information found in FDA regulations. 

Sections VII, VIII, IX, XI, and XII of the 

guidance request that certain 

information be submitted to FDA and 

certain recordkeeping be performed by 

the sponsor. We may request this 

information under 21 CFR 312.23, 

312.30, 314.50, 314.126, and 601.2. The 

collections of information in 21 CFR 

parts 312, 314, and 601 have been 

approved under OMB control numbers 

0910–0014, 0910–0001, and 0910–0338, 

respectively. 

FDA estimates the burden of this 

collection of information as follows: 

TABLE 1.—ESTIMATED REPORTING BURDEN1

Number of 

Respondents 

Number of Responses 

per Respondent Total Responses Hours per Response Total Hours 

Develop written SOPs 30 6 180 6 1,080 

Perform simulations and analyze 

data 30 3 90 40 3,600 

Total 4,680 

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

TABLE 2.—ESTIMATED RECORDKEEPING BURDEN1

Number of 

Recordkeepers 

Number of Records 

per Recordkeeping Total Records Hours per Record Total Hours 

Develop written SOPs 30 6 180 0.5 90 


sroberts on DSKD5P82C1PROD with NOTICES
8970 Federal Register / Vol. 75, No. 38 / Friday, February 26, 2010 / Notices 

TABLE 2.—ESTIMATED RECORDKEEPING BURDEN1—Continued 

Number of 

Recordkeepers 

Number of Records 

per Recordkeeping Total Records Hours per Record Total Hours 

Total 90 

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

III. Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) written or electronic 

comments regarding this document. 

Submit a single copy of electronic 

comments or two paper copies of any 

mailed comments, except that 

individuals may submit one paper copy. 

Comments are to be identified 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. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the document at http:// 

www.fda.gov/Drugs/Guidance

ComplianceRegulatoryInformation/ 

Guidances/default.htm, http:// 

www.fda.gov/BiologicsBloodVaccines/ 

GuidanceComplianceRegulatory

Information/default.htm, or http:// 

www.regulations.gov. 

Dated: February 22, 2010. 

Leslie Kux, 

Acting Assistant Commissioner for Policy. 

[FR Doc. 2010–3980 Filed 2–25–10; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2008–D–0391] 

Guidance for Industry on Submission 

of Documentation in Applications for 

Parametric Release of Human and 

Veterinary Drug Products Terminally 

Sterilized by Moist Heat Processes; 

Availability 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing the 

availability of a guidance for industry 

entitled ‘‘Submission of Documentation 

in Applications for Parametric Release 

of Human and Veterinary Drug Products 

Terminally Sterilized by Moist Heat 

Processes.’’ This guidance provides 

recommendations to applicants on 

information to include in support of 

parametric release for sterile products 

terminally sterilized by moist heat when 

submitting a new drug application 

(NDA), abbreviated new drug 

application (ANDA), new animal drug 

application (NADA), abbreviated new 

animal drug application (ANADA), or 

biologics license application (BLA). 

DATES: Submit written or electronic 

comments on agency guidances at any 

time. 

ADDRESSES: Submit written requests for 

single copies of the guidance to the 

Division of Drug Information, Center for 

Drug Evaluation and Research, Food 

and Drug Administration, 10903 New 

Hampshire Ave., Bldg. 51, rm. 2201, 

Silver Spring, MD 20993–0002; the 

Communications Staff (HFV–12), Center 

for Veterinary Medicine, 7519 Standish 

Pl., Rockville, MD 20855; the Office of 

Communication, Outreach and 

Development (HFM–40), Center for 

Biologics Evaluation and Research 

(CBER), 1401 Rockville Pike, Rockville, 

MD 20852–1448. Send one selfaddressed adhesive label to assist that 

office in processing your requests. The 

guidance may also be obtained by mail 

by calling CBER at 1–800–835–4709 or 

301–827–1800. Submit written 

comments on the guidance to the 

Division of Dockets Management (HFA– 

305), Food and Drug Administration, 

5630 Fishers Lane, rm. 1061, Rockville, 

MD 20852. Submit electronic comments 

to http://www.regulations.gov. See the 

SUPPLEMENTARY INFORMATION section for 

electronic access to the guidance 

document. 

FOR FURTHER INFORMATION CONTACT: 

Marla Stevens-Riley, Center for Drug 

Evaluation and Research (HFD– 

600), Food and Drug 

Administration, 7500 Standish Pl., 

Rockville, MD 20855, 240–276– 

9310, or 

Stephen Ripley, Center for Biologics 

Evaluation and Research (HFM–17), 

Food and Drug Administration, 

1401 Rockville Pike, suite 200N, 

Rockville, MD 20852, 301–827– 

6210; or 

Mai Huynh, Center for Veterinary 

Medicine (HFV–142), Food and 

Drug Administration, 7500 Standish 

Pl., Rockville, MD 20855, 240–276– 

8273. 

SUPPLEMENTARY INFORMATION: 

I. Background 

FDA is announcing the availability of 

a guidance for industry entitled 

‘‘Submission of Documentation in 

Applications for Parametric Release of 

Human and Veterinary Drug Products 

Terminally Sterilized by Moist Heat 

Processes.’’ The guidance addresses the 

information that should be submitted in 

an NDA, ANDA, NADA, ANADA, or 

BLA in support of parametric release for 

sterile products terminally sterilized by 

moist heat. 

‘‘Parametric release’’ is defined as a 

sterility assurance release program 

where demonstrated control of the 

sterilization process enables a firm to 

use defined critical process controls, in 

lieu of the sterility test, to fulfill the 

intent of 21 CFR 211.167(a). Under this 

strategy, market release of terminally 

sterilized products can be based upon 

meeting the defined sterilization 

parameters and not on performing an 

approved sterility test. Meeting the 

requirements of the parametric release 

process can provide greater assurance 

that a batch meets the sterility 

requirement than can be achieved with 

a sterility test of finished units drawn 

from the batch. 

Parametric release allows 

manufacturers to replace sterility testing 

of samples drawn from the finished 

product as a release criterion with 

acceptance criteria for the control of 

identified process parameters. 

Parametric release of the batch is then 

based on documented evidence of the 

control of critical parameters, removing 

the need for testing of samples drawn 

from the finished product. 

An application to FDA is required to 

obtain approval for parametric release. 

The approval of parametric release is 

based on an assessment of the 

applicant’s proposed critical process 

parameters and how they are controlled. 

Demonstrated reliability of the 

production terminal sterilization cycle, 

microbiological control and monitoring, 

and control of production cycle 

parameters within established validated 

limits is part of this assessment. FDA 

conducts scientific evaluation of the 

parametric release program as part of a 

cooperative effort between FDA product 

reviewers and the compliance program. 


sroberts on DSKD5P82C1PROD with NOTICES