27140 Federal Register / Vol. 72, No. 92 / Monday, May 14, 2007 / Notices 

Table 1 of this document provides a 

breakdown of the total estimated annual 

recordkeeping burden. FDA bases this 

hour burden estimate on its experience 

with the application of HACCP 

principles in food processing. 

The burden estimates in table 1 of this 

document are based on an estimate of 

the total number of juice manufacturing 

plants (i.e., 2,300) affected by the 

regulations. Included in this total are 

850 plants currently identified in FDA’s 

official establishment inventory plus 

1,220 very small apple juice 

manufacturers and 230 very small 

orange juice manufacturers. The total 

burden hours are derived by estimating 

the number of plants affected by each 

portion of this final rule and 

multiplying the corresponding number 

by the number of records required 

annually and the hours needed to 

complete the record. These numbers 

were obtained from the agency’s final 

regulatory impact analysis prepared for 

these regulations. 

Moreover, these estimates assume that 

every processor will prepare sanitary 

standard operating procedures and a 

HACCP plan and maintain the 

associated monitoring records and that 

every importer will require product 

safety specifications. In fact, there are 

likely to be some small number of juice 

processors that, based upon their hazard 

analysis, determine that they are not 

required to have a HACCP plan under 

these regulations. 

Dated: April 27, 2007. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. E7–9220 Filed 5–11–07; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2007N–0182] 

Agency Information Collection 

Activities; Proposed Collection; 

Comment Request; Information 

Program on Clinical Trials for Serious 

or Life-Threatening Diseases: 

Maintaining a Data Bank 

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 collection of information contained 

in the guidance entitled ‘‘Information 

Program on Clinical Trials for Serious or 

Life-Threatening Diseases and 

Conditions’’ dated March 18, 2002. 

DATES: Submit written or electronic 

comments on the collection of 

information by July 13, 2007. 

ADDRESSES: Submit electronic 

comments on the collection of 

information to: http://www.fda.gov/ 

dockets/ecomments. 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: 

Jonna Capezzuto, Office of the Chief 

Information Officer (HFA–250), Food 

and Drug Administration, 5600 Fishers 

Lane, Rockville, MD 20857, 301–827–

4659. 

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. 

Information Program on Clinical Trials 

for Serious or Life-Threatening 

Diseases: Maintaining a Data Bank 

(OMB Control Number 0910–0459)—

Extension 

In the Federal Register of March 18, 

2002 (65 FR 12022), FDA issued a 

guidance to industry on 

recommendations for investigational 

new drug application (IND) sponsors on 

submitting information about clinical 

trials for serious or life- threatening 

diseases to a Clinical Trials Data Bank 

developed by the National Library of 

Medicine (NLM), National Institutes of 

Health (NIH). This information is 

especially important for patients and 

their families seeking opportunities to 

participate in clinical trials of new drug 

treatments for serious or life-threatening 

diseases. The guidance describes three 

collections of information: Mandatory 

submissions, voluntary submissions, 

and certifications. 

Mandatory Submissions 

Section 113 of the Food and Drug 

Administration Modernization Act 

(FDAMA) of 1997 (the Modernization 

Act) (Public Law 105–115) requires that 

sponsors shall submit information to the 

Clinical Trials Data Bank when the 

clinical trial: (1) Involves a treatment for 

a serious or life-threatening disease and 

(2) is intended to assess the 

effectiveness of the treatment. The 

guidance discusses how sponsors can 

fulfill the requirements of section 113 of 

the Modernization Act. Specifically, 

sponsors should provide: (1) 

Information about clinical trials, both 

federally and privately funded, of 

experimental treatments (drugs, 

including biological products) for 

patients with serious or life-threatening 

diseases; (2) a description of the 

purpose of the experimental drug; (3) 

patient eligibility criteria; (4) the 

location of clinical trial sites; and (5) a 

point of contact for patients wanting to 

enroll in the trial. 

Senate 1789, ‘‘Best Pharmaceuticals 

for Children Act’’ (Public Law 107–109) 

(BPCA), established a new requirement 

for the Clinical Trials Data Bank 

mandated by section 113 of FDAMA. 

Information submitted to the data bank 

must now include ‘‘a description of 


pwalker on PROD1PC71 with NOTICES
Federal Register / Vol. 72, No. 92 / Monday, May 14, 2007 / Notices 27141 

1Estimate obtained from a review of 2,062 

protocols submitted to CDER between January 1, 

2002, and September 30, 2002. 

whether, and through what procedure, 

the manufacturer or sponsor of the 

investigation of a new drug will respond 

to requests for protocol exception, with 

appropriate safeguards, for singlepatient and expanded protocol use of 

the new drug, particularly in children.’’

The guidance was updated on January 

27, 2004, to include a discussion of how 

sponsors can fulfill the BPCA 

requirements. 

As part of the resubmission process 

for OMB approval, this information 

collection request (ICR) has been revised 

to include the burden associated with 

new requirements imposed by the 

Centers for Medicare and Medicaid 

Services (CMS). On September 19, 2000, 

the Health Care Financing 

Administration (now CMS) 

implemented a Clinical Trial Policy 

through the National Coverage 

Determination process. The Clinical 

Trial Policy was developed in response 

to a June 7, 2000, executive 

memorandum, issued by President 

Clinton, requiring Medicare to pay for 

routine patient costs in clinical trials. 

The original policy suggested that a 

registry be established into which 

studies meeting the criteria for coverage 

under the policy would be enrolled for 

administrative purposes. This registry 

was never established. 

On July 10, 2006, CMS opened a 

reconsideration of its national coverage 

determination on clinical trials. The 

purpose of the reconsideration is to 

further refine the policy to rename it the 

Clinical Research Policy (CRP) to 

address several ambiguities, including 

the link between the CRP and the 

Coverage with Evidence Development 

concept, and the authority to allow the 

agency to pay for the costs of limited 

investigational items. One requirement 

to qualify for coverage of clinical costs 

under the proposed policy is that the 

study must be enrolled in the NLM 

Clinical Trials Data Bank. 

Voluntary Submissions 

Section 113 of the Modernization Act 

also specifies that sponsors may 

voluntarily submit information 

pertaining to results of clinical trials, 

including information on potential 

toxicities or adverse effects associated 

with the use or administration of the 

investigational treatment. Sponsors may 

also voluntarily submit studies that are 

not trials to test effectiveness, or not for 

serious or life-threatening diseases, to 

the Clinical Trials Data Bank. 

Certifications 

Section 113 of the Modernization Act 

specifies that the data bank will not 

include information relating to a trial if 

the sponsor certifies to the Secretary of 

Health and Human Services (the 

Secretary) that disclosure of the 

information would substantially 

interfere with the timely enrollment of 

subjects in the investigation, unless the 

Secretary makes a determination to the 

contrary. 

Description of Respondents: A 

sponsor of a drug or biologic product 

regulated by the agency under the 

Federal Food, Drug, and Cosmetic Act 

or section 351 of the Public Health 

Service Act (42 U.S.C. 262) who submits 

a clinical trial to test effectiveness of a 

drug or biologic product for a serious or 

life-threatening disease. 

For the purposes of CMS, the 

respondents will be providers that are 

conducting or sponsoring clinical trials 

that are seeking to have the clinical 

costs of their studies reimbursed by 

Medicare. 

Burden Estimate: The information 

required under section 113(a) of the 

Modernization Act is currently 

submitted to FDA under 21 CFR part 

312, and this collection of information 

is approved under OMB Control 

Number 0910–0014 until May 31, 2009, 

and, therefore, does not represent a new 

information collection requirement. 

Instead, preparation of submissions 

under section 113 of the Modernization 

Act involves extracting and reformatting 

information already submitted to FDA. 

Procedures (where and how) for the 

actual submission of this information to 

the Clinical Trials Data Bank are 

addressed in the guidance. 

The Center for Drug Evaluation and 

Research (CDER) received 4,858 new 

protocols in 2005. CDER anticipates that 

protocol submission rates will remain at 

or near this level in the near future. Of 

these new protocols, an estimated twothirds1 are for serious or life-threatening 

diseases and would be subject to either 

voluntary or mandatory reporting 

requirements under section 113 of the 

Modernization Act. Two-thirds of 4,858 

protocols per year is 3,239 new 

protocols per year. An estimated 50 

percent1 of the new protocols for serious 

or life-threatening diseases submitted to 

CDER are for clinical trials involving 

assessment for effectiveness, and are 

subject to the mandatory reporting 

requirements under section 113 of the 

Modernization Act. Fifty percent of 

3,239 protocols per year is 1,620 new 

protocols per year subject to mandatory 

reporting. The remaining 3,238 new 

protocols per year are subject to 

voluntary reporting. 

The Center for Biologics Evaluation 

and Research (CBER) received 474 new 

protocols in 2005. CBER anticipates that 

protocol submission rates will remain at 

or near this level in the near future. An 

estimated two-thirds1 of the new 

protocols submitted to CBER are for 

clinical trials involving a serious or lifethreatening disease, and would be 

subject to either voluntary or mandatory 

reporting requirements under section 

113 of the Modernization Act. Twothirds of 474 new protocols per year is 

316 new protocols per year. An 

estimated 50 percent1 of the new 

protocols for serious or life-threatening 

diseases submitted to CBER are for 

clinical trials involving assessments for 

effectiveness. Fifty percent of 316 

protocols per year is an estimated 158 

new protocols per year subject to the 

mandatory reporting requirements 

under section 113 of the Modernization 

Act. The remaining 316 new protocols 

per year are subject to voluntary 

reporting. 

The estimated total number of new 

protocols for serious or life-threatening 

diseases subject to mandatory reporting 

requirements under section 113 of the 

Modernization Act is 1,620 for CDER 

plus 158 for CBER, or 1,778 new 

protocols per year. The remainder of 

protocols submitted to CDER or CBER 

will be subject to voluntary reporting, 

including clinical trials not involving a 

serious or life-threatening disease as 

well as trials in a serious or lifethreatening disease but not involving 

assessment of effectiveness. Therefore, 

the total number of protocols (5,332) 

minus the protocols subject to 

mandatory reporting requirements 

(1,778) will be subject to voluntary 

reporting, or 3,554 protocols. 

Our total burden estimate includes 

multi-center studies and accounts for 

the quality control review of the data 

before it is submitted to the data bank. 

The number of IND amendments 

submitted in 2005 for protocol changes 

(e.g., changes in eligibility criteria) was 

7,597 for CDER and 855 for CBER. The 

number of IND amendments submitted 

in 2005 for new investigators was 

11,287 for CDER and 532 for CBER. The 

number of protocol changes and new 

investigators was apportioned 

proportionally between mandatory and 

voluntary submissions. We recognize 

that single submissions may include 

information about multiple sites. 

Generally, there is no submission to 

FDA when an individual study site is no 

longer recruiting study subjects. For this 

analysis, we assumed that the number of 

study sites closed each year is similar to 


pwalker on PROD1PC71 with NOTICES
27142 Federal Register / Vol. 72, No. 92 / Monday, May 14, 2007 / Notices 

the number of new investigator 

amendments received by FDA (11,287 

CDER and 532 CBER). 

Generally, there is no submission to 

FDA when the study is closed to 

enrollment. We estimate the number of 

protocols closed to enrollment each year 

is similar to the number of new 

protocols submitted (4,858 CDER and 

474 CBER). 

The hours per response is the 

estimated number of hours that a 

respondent would spend preparing the 

information to be submitted under 

section 113(a) of the Modernization Act, 

including the time it takes to extract and 

reformat the information. FDA has been 

advised that some sponsors lack 

information system capabilities enabling 

efficient collection of company-wide 

information on clinical trials subject to 

reporting requirements under section 

113(a) of the Modernization Act. The 

estimation of burden under section 

113(a) reflects the relative inefficiency 

of this process for these firms. 

Based on its experience reviewing 

INDs, consideration of the information 

in the previous paragraphs, and further 

consultation with sponsors who submit 

protocol information to the Clinical 

Trials Data Bank, FDA estimated that 

approximately 4.6 hours on average 

would be needed per response. The 

estimate incorporates 2.6 hours for data 

extraction and 2.0 hours for reformatting 

based on data collected from 

organizations currently submitting 

protocols to the Clinical Trials Data 

Bank. We considered quality control 

issues when developing the current 

burden estimates of 2.6 hours for data 

extraction and the 2.0 hours estimated 

for reformatting. Additionally, the 

Internet-based data entry system 

developed by NIH incorporates features 

that further decrease the sponsor’s time 

requirements for quality control 

procedures. The Clinical Trials Data 

Bank was set up to receive protocol 

information transmitted electronically 

by sponsors. Approximately 10 percent 

of sponsors electronically transmit 

information to the Clinical Trials Data 

Bank. If the sponsor chooses to 

manually enter the protocol 

information, the data entry system 

allows it to be entered in a uniform and 

efficient manner primarily through pulldown menus. As sponsors’ familiarity 

with the data entry system increases, the 

hourly burden will continue to 

decrease. 

A sponsor of a study subject to the 

requirements of section 113 of the 

Modernization Act will have the option 

of submitting data under that section or 

certifying to the Secretary that 

disclosure of information for a specific 

protocol would substantially interfere 

with the timely enrollment of subjects 

in the clinical investigation. FDA has no 

means to accurately predict the 

proportion of protocols subject to the 

requirements of section 113 of the 

Modernization Act that will be subject 

to a certification submission. To date, 

no certifications have been received. It 

is anticipated that the burden associated 

with such certification will be 

comparable to that associated with 

submission of data regarding a protocol. 

Therefore, the overall burden is 

anticipated to be the same, regardless of 

whether the sponsor chooses data 

submission or certification for 

nonsubmission. Table 1 of this 

document reflects the estimate of this 

total burden. 

FDA estimates the burden of this 

collection of information as follows: 

TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1

New Protocols Recruitment 

Complete 

Protocol 

Changes 

New 

Investigators Site Closed Total Responses 

Hours per 

Response Total Hours 

CDER (mandatory) 1,620 1,620 2,507 3,725 13,197 4.6 60,706 

CBER (mandatory) 158 158 282 176 950 4.6 4,370 

CDER (voluntary) 3,238 3,238 5,090 7,562 26,690 4.6 122,774 

CDER (voluntary) 316 316 573 356 1,917 4.6 8,818 

Total 196,668 

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

CMS Burden Estimate: 

The burden associated with CMS’

requirements is the time and effort 

necessary for the provider to extract the 

data elements from the study protocol 

and reformatting and entering the 

information into the data bank. We 

estimate that approximately 745 clinical 

research studies will register on the 

NLM data bank. The number was 

derived from a search of the database on 

September 1, 2006 restricting the search 

by age (e.g., > 65 years of age); sponsor 

(e.g., NIH, industry, other federal 

agency, university/organization); Phase 

II, III or IV; and by type of study (e.g., 

cancers and other neoplasms, diagnosis, 

and devices). The age, sponsor, and 

study phase was applied to each of the 

three separate searches by type of study. 

The following number of studies by 

study type, including trials no longer 

recruiting was 562 for diagnosis, 164 for 

cancers and other neoplasms, and 19 for 

devices. In determining the total 

number of hours requested, the CMS 

estimate uses the same assumptions 

used by the FDA to estimate its total 

number of burden hours. Therefore, the 

total annual burden associated with this 

requirement is 27,480 hours (5,974 

responses x 4.6 hours per response). 

We believe the combined estimate of 

burden attributable to FDA and CMS 

requirements, 224,148 burden hours 

(196,668 burden hours + 27,480 burden 

hours) accurately reflects the total 

burden associated with this information 

collection request. We recognize that 

companies who are less familiar with 

the data entry system and the Clinical 

Trials Data Bank will require greater 

than 4.6 hours per response. However, 

as sponsor familiarity with the system 

increases, the hourly estimate will 

decrease. 

Dated: May 8, 2007. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. E7–9221 Filed 5–11–07; 8:45 am] 

BILLING CODE 4160–01–S 


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