33260 Federal Register / Vol. 74, No. 131 / Friday, July 10, 2009 / Notices 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2009–N–0291] 

Agency Information Collection 

Activities; Proposed Collection; 

Comment Request; Infectious Disease 

Issues in Xenotransplantation 

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 this 

notice. This notice solicits comments on 

the collection of information contained 

in the Public Health Service (PHS) 

guideline entitled ‘‘PHS Guideline on 

Infectious Disease Issues in 

Xenotransplantation’’ dated January 19, 

2001. 

DATES: Submit written or electronic 

comments on the collection of 

information by September 8, 2009. 

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: 

Jonna Capezzuto, Office of Information 

Management (HFA–710), Food and Drug 

Administration, 5600 Fishers Lane, 

Rockville, MD 20857, 301–796–3794. 

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. 

Infectious Disease Issues in 

Xenotransplantation (OMB Control 

Number 0910–0456)—Extension 

The statutory authority to collect this 

information is provided under sections 

351 and 361 of the PHS Act (42 U.S.C. 

262 and 264) and the provisions of the 

Federal Food, Drug, and Cosmetic Act 

that apply to drugs (21 U.S.C. 301 et 

seq.). The PHS guideline recommends 

procedures to diminish the risk of 

transmission of infectious agents to the 

xenotransplantation product recipient 

and to the general public. The PHS 

guideline is intended to address public 

health issues raised by 

xenotransplantation, through 

identification of general principles of 

prevention and control of infectious 

diseases associated with 

xenotransplantation that may pose a 

hazard to the public health. The 

collection of information described in 

this guideline is intended to provide to 

sponsors general guidance on the 

following topics: (1) The development 

of xenotransplantation clinical 

protocols; (2) the preparation of 

submissions to FDA; and (3) the 

conduct of xenotransplantation clinical 

trials. Also, the collection of 

information will help ensure that the 

sponsor maintains important 

information in a cross-referenced system 

that links the relevant records of the 

xenotransplantation product recipient, 

xenotransplantation product, source 

animal(s), animal procurement center, 

and significant nosocomial exposures. 

The PHS guideline describes an 

occupational health service program for 

the protection of health care workers 

involved in xenotransplantation 

procedures, caring for 

xenotransplantation product recipients, 

and performing associated laboratory 

testing. The guideline also describes a 

public health need for a national 

xenotransplantation database, which is 

currently under development by the 

PHS. The PHS guideline is intended to 

protect the public health and to help 

ensure the safety of using 

xenotransplantation products in 

humans by preventing the introduction, 

transmission, and spread of infectious 

diseases associated with 

xenotransplantation. 

The PHS guideline also recommends 

that certain specimens and records be 

maintained for 50 years beyond the date 

of the xenotransplantation. These 

include: (1) Records linking each 

xenotransplantation product recipient 

with relevant health records of the 

source animal, herd or colony, and the 

specific organ, tissue, or cell type 

included in or used in the manufacture 

of the product (3.2.7.1); (2) aliquots of 

serum samples from randomly selected 

animal and specific disease 

investigations (3.4.3.1); (3) source 

animal biological specimens designated 

for PHS use (3.7.1); animal health 

records (3.7.2), including necropsy 

results (3.6.4); and (4) recipients’ 

biological specimens (4.1.2). The 

retention period is intended to assist 

health care practitioners and officials in 

surveillance and in tracking the source 

of an infection, disease, or illness that 

might emerge in the recipient, the 

source animal, or the animal herd or 

colony after a xenotransplantation. 

The recommendation for maintaining 

records for 50 years is based on clinical 

experience with several human viruses 

that have presented problems in human 

to human transplantation and are 

therefore thought to share certain 

characteristics with viruses that may 

pose potential risks in 

xenotransplantation. These 

characteristics include long latency 

periods and the ability to establish 

persistent infections. Several also share 

the possibility of transmission among 

individuals through intimate contact 

with human body fluids. Human 

immunodeficiency virus (HIV) and 

Human T-lymphotropic virus are 

human retroviruses. Retroviruses 

contain ribonucleic acid that is reversetranscribed into deoxyribonucleic acid 

(DNA) using an enzyme provided by the 

virus and the human cell machinery. 


sroberts on DSKD5P82C1PROD with NOTICES
Federal Register / Vol. 74, No. 131 / Friday, July 10, 2009 / Notices 33261 

That viral DNA can then be integrated 

into the human cellular DNA. Both 

viruses establish persistent infections 

and have long latency periods before the 

onset of disease, 10 years and 40 to 60 

years, respectively. The human hepatitis 

viruses are not retroviruses, but several 

share with HIV the characteristic that 

they can be transmitted through body 

fluids, can establish persistent 

infections, and have long latency 

periods, e.g., approximately 30 years for 

Hepatitis C. 

In addition, the PHS guideline 

recommends that a record system be 

developed that allows easy, accurate, 

and rapid linkage of information among 

the specimen archive, the recipient’s 

medical records, and the records of the 

source animal for 50 years. The 

development of such a record system is 

a one-time burden. Such a system is 

intended to cross-reference and locate 

relevant records of recipients, products, 

source animals, animal procurement 

centers, and nosocomial exposures. 

Respondents to this collection of 

information are the sponsors of clinical 

studies of investigational 

xenotransplantation products under 

investigational new drug applications 

(INDs) and xenotransplantation product 

procurement centers, referred to as 

source animal facilities. There are an 

estimated 12 respondents who are 

sponsors of INDs that include protocols 

for xenotransplantation in humans. 

Other respondents for this collection of 

information are an estimated 18 source 

animal facilities which provide source 

xenotransplantation product material to 

sponsors for use in human 

xenotransplantation procedures. These 

18 source animal facilities keep medical 

records of the herds/colonies as well as 

the medical records of the individual 

source animal(s). The total annual 

reporting and recordkeeping burden is 

estimated to be approximately 156 

hours. The burden estimates are based 

on FDA’s records of 

xenotransplantation-related INDs and 

estimates of time required to complete 

the various reporting and recordkeeping 

tasks described in the guideline. FDA 

does not expect the level of clinical 

studies using xenotransplantation to 

increase significantly in the next few 

years. 

FDA is requesting an extension of 

OMB approval for the following 

reporting and recordkeeping 

recommendations in the PHS guideline: 

TABLE 1.—REPORTING RECOMMENDATIONS

PHS Guideline Section Description 

3.2.7.2 Notify sponsor or FDA of new archive site when the source animal facility or sponsor ceases operations. 

3.4 Standard operating procedures (SOPs) of source animal facility should be available to review bodies. 

3.5.1 Include increased infectious risk in informed consent if source animal quarantine period of 3 weeks is shortened. 

3.5.4 Sponsor to make linked records described in section 3.2.7 available for review. 

3.5.5 Source animal facility to notify clinical center when infectious agent is identified in source animal or herd after 

xenotransplantation product procurement. 

TABLE 2.—RECORDKEEPING RECOMMENDATIONS

PHS Guideline Section Description 

3.2.7 Establish records linking each xenotransplantation product recipient with relevant records. 

4.3 Sponsor to maintain cross-referenced system that links all relevant records (recipient, product, source animal, animal 

procurement center, and nosocomial exposures). 

3.4.2 Document results of monitoring program used to detect introduction of infectious agents which may not be apparent 

clinically. 

3.4.3.2 Document full necropsy investigations including evaluation for infectious etiologies. 

3.5.1 Justify shortening a source animal’s quarantine period of 3 weeks prior to xenotransplantation product procurement. 

3.5.2 Document absence of infectious agent in xenotransplantation product if its presence elsewhere in source animal does 

not preclude using it. 

3.5.4 Add summary of individual source animal record to permanent medical record of the xenotransplantation product recipient. 

3.6.4 Document complete necropsy results on source animals (50-year record retention). 

3.7 Link xenotransplantation product recipients to individual source animal records and archived biologic specimens. 

4.2.3.2 Record base-line sera of xenotransplantation health care workers and specific nosocomial exposure. 

4.2.3.3 and 4.3.2 Keep a log of health care workers’ significant nosocomial exposure(s). 

4.3.1 Document each xenotransplant procedure. 

5.2 Document location and nature of archived PHS specimens in health care records of xenotransplantation product recipient and source animal. 


sroberts on DSKD5P82C1PROD with NOTICES
33262 Federal Register / Vol. 74, No. 131 / Friday, July 10, 2009 / Notices 

FDA estimates the burden of this 

collection of information as follows: 

TABLE 3.—ESTIMATED ANNUAL REPORTING BURDEN1

PHS Guideline 

Section 

No. of 

Respondents 

Annual Frequency 

per Response 

Total Annual 

Responses 

Hours per 

Response Total Hours 

3.2.7.22 1 1 1 0 .5 0 .5 

3.43 12 0 .17 2 0 .08 0 .16 

3.5.14 12 0 .08 (0–1) 1 0 .25 0 .25 

3.5.45 12 1 12 0 .5 6 .0 

3.5.54 18 0 .06 (0–1) 1 0 .2 0 .2 

Total 7 .11 

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

2 No animal facility or sponsor has ceased operations in the last 3 years, however, we are using 1 for estimation purposes. 

3FDA’s records indicate that an average of two INDs are expected to be submitted per year. 

4To our knowledge, has not occurred in the past 3 years and is expected to continue to be a rare occurrence. 

5Based on an estimate of 36 patients treated over a 3-year period, the average number of xenotransplantation product recipients per year is 

estimated to be 12. 

TABLE 4.—ESTIMATED ANNUAL RECORDKEEPING BURDEN1

PHS Guideline 

Section 

No. of 

Recordkeepers 

Annual Frequency 

per Recordkeeping 

Total Annual 

Records 

Hours per 

Record Total Hours 

3.2.72 1 1 1 16 16 .0 

4.33 12 1 12 0 .83 9 .96 

3.4.24 12 11 132 0 .25 33 .0 

3.4.3.25 18 4 72 0 .3 21 .6 

3.5.16 12 0 .08 (0–1) 1 0 .5 0 .5 

3.5.26 12 0 .08 (0–1) 1 0 .25 0 .25 

3.5.4 12 1 12 0 .17 2 .04 

3.6.47 12 2 24 0 .25 6 .0 

3.77 18 1 .33 24 0 .08 1 .92 

4.2.3.28 12 25 300 0 .17 51 .0 

4.2.3.26 12 0 .08 (0–1) 1 0 .17 0 .17 

4.2.3.3 and 4.3.26 12 0 .08 (0–1) 1 0 .17 0 .17 

4.3.1 12 1 12 0 .25 3 .0 

5.29 12 3 36 0 .08 2 .88 

Total 148 .49 

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

2A one-time burden for new respondents to set up a recordkeeping system linking all relevant records. FDA estimates one new sponsor annually. 3FDA estimates there is minimal recordkeeping burden associated with maintaining the record system. 

3FDA estimates there is minimal recordkeeping burden associated with maintaining the record system. 

4 Monitoring for sentinel animals (subset representative of herd) plus all source animals. There are approximately 6 sentinel animals per herd x 

1 herd per facility x 18 facilities = 108 sentinel animals. There are approximately 24 source animals per year (see footnote 7 of this table); 108 + 

24 = 132 monitoring records to document. 5 Necropsy for animal deaths of unknown cause estimated to be approximately 4 per herd per year x 1 herd per facility x 18 facilities = 72. 6 Has not occurred in the past 3 years and is expected to continue to be a rare occurrence. 

7On average two source animals are used for preparing xenotransplantation product material for one recipient. The average number of source 

animals is 2 source animals per recipient x 12 recipients annually = 24 source animals per year. (See footnote 5 of table 3 of this document.) 8FDA estimates there are approximately 12 clinical centers doing xenotransplantation procedures x approximately 25 health care workers involved per center = 300 health care workers. 9Twenty-four source animal records + 12 recipient records = 36 total records. 


sroberts on DSKD5P82C1PROD with NOTICES
Federal Register / Vol. 74, No. 131 / Friday, July 10, 2009 / Notices 33263 

Because of the potential risk for crossspecies transmission of pathogenic 

persistent virus, the guideline 

recommends that health records be 

retained for 50 years. Because these 

records are medical records, the 

retention of such records for up to 50 

years is not information subject to the 

PRA (5 CFR 1320.3(h)(5)). Also, because 

of the limited number of clinical studies 

with small patient populations, the 

number of records is expected to be 

insignificant at this time. 

Information collections in this 

guideline not included in tables 1 

through 4 of this document can be 

found under existing regulations and 

approved under the OMB control 

numbers as follows: (1) ‘‘Current Good 

Manufacturing Practice for Finished 

Pharmaceuticals,’’ 21 CFR 211.1 through 

211.208, approved under OMB control 

number 0910–0139; (2) ‘‘Investigational 

New Drug Application,’’ 21 CFR 312.1 

through 312.160, approved under OMB 

control number 0910–0014; and (3) 

information included in a license 

application, 21 CFR 601.2, approved 

under OMB control number 0910–0338. 

(Although it is possible that a 

xenotransplantation product may not be 

regulated as a biological product (e.g., it 

may be regulated as a medical device), 

FDA believes, based on its knowledge 

and experience with 

xenotransplantation, that any 

xenotransplantation product subject to 

FDA regulation within the next 3 years 

will most likely be regulated as a 

biological product.) However, FDA 

recognized that some of the information 

collections go beyond approved 

collections; assessments for these 

burdens are included in tables 1 through 

4. 

In table 5 of this document, FDA 

identifies those collection of 

information activities that are already 

encompassed by existing regulations or 

are consistent with voluntary standards 

which reflect industry’s usual and 

customary business practice. 

TABLE 5.—COLLECTION OF INFORMATION REQUIRED BY CURRENT REGULATIONS AND STANDARDS

PHS Guideline Section Description of Collection of Information Activity 21 CFR Section (unless otherwise stated) 

2.2.1 Document off-site collaborations 312.52 

2.5 Sponsor ensures counseling patient + family + contacts 312.62(c) 

3.1.1 and 3.1.6 Document well-characterized health history and lineage of source animals 312.23(a)(7)(a) and 211.84 

3.1.8 Registration with and import permit from the Centers for Disease Control and 

Prevention 

42 CFR 71.53 

3.2.2 Document collaboration with accredited microbiology labs 312.52 

3.2.3 Procedures to ensure the humane care of animals 9 CFR parts 1, 2, and 3 and 

PHS Policy1

3.2.4 Procedures consistent for accreditation by the Association for Assessment and 

Accreditation of Laboratory Animal Care International (AAALAC International) 

and consistent with the National Research Council’s (NRC) Guide 

AAALAC International Rules of 

Accreditation2 and NRC 

Guide3

3.2.5, 3.4, and 3.4.1 Herd health maintenance and surveillance to be documented, available, and in 

accordance with documented procedures; record standard veterinary care 

211.100 and 211.122 

3.2.6 Animal facility SOPs PHS Policy1

3.3.3 Validate assay methods 211.160(a) 

3.6.1 Procurement and processing of xenografts using documented aseptic conditions 211.100 and 211.122 

3.6.2 Develop, implement, and enforce SOP’s for procurement and screening processes 211.84(d) and 211.122(c) 

3.6.4 Communicate to FDA animal necropsy findings pertinent to health of recipient 312.32(c) 

3.7.1 PHS specimens to be linked to health records; provide to FDA justification for 

types of tissues, cells, and plasma, and quantities of plasma and leukocytes 

collected 

312.23(a)(6) 

4.1.1 Surveillance of xenotransplant recipient; sponsor ensures documentation of surveillance program life-long (justify >2 yrs.); investigator case histories (2 yrs. 

After investigation is discontinued) 

312.23(a)(6)(iii)(f) and 

(a)(6)(iii)(g), and 312.62(b) 

and (c) 

4.1.2 Sponsor to justify amount and type of reserve samples 211.122 

4.1.2.2 System for prompt retrieval of PHS specimens and linkage to medical records 

(recipient and source animal) 

312.57(a) 

4.1.2.3 Notify FDA of a clinical episode potentially representing a xenogeneic infection 312.32 

4.2.2.1 Document collaborations (transfer of obligation) 312.52 


sroberts on DSKD5P82C1PROD with NOTICES
33264 Federal Register / Vol. 74, No. 131 / Friday, July 10, 2009 / Notices 

TABLE 5.—COLLECTION OF INFORMATION REQUIRED BY CURRENT REGULATIONS AND STANDARDS—Continued 

PHS Guideline Section Description of Collection of Information Activity 21 CFR Section (unless otherwise stated) 

4.2.3.1 Develop educational materials (sponsor provides investigators with information 

needed to conduct investigation properly) 

312.50 

4.3 Sponsor to keep records of receipt, shipment, and disposition of investigative 

drug; investigator to keep records of case histories 

312.57 and 312.62(b) 

1The ‘‘Public Health Service Policy on Humane Care and Use of Laboratory Animals’’ (http://www.grants.nih.gov/grants/olaw/references/ 

phspol.htm). (FDA has verified the Web site address, but is not responsible for subsequent changes to the Web site address after this document 

publishes in the Federal Register.) 2AAALAC International Rules of Accreditation (http://www.aaalac.org/accreditation/rules.cfm). (FDA has verified the Web site address, but is 

not responsible for subsequent changes to the Web site address after this document publishes in the Federal Register.) 3The NRC’s ‘‘Guide for the Care and Use of Laboratory Animals’’ (1996). 

Dated: July 2, 2009. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E9–16334 Filed 7–9–09; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Administration for Children and 

Families 

Submission for OMB Review; 

Comment Request 

Title: Tribal TANF Data Report, TANF 

Annual Report, and Reasonable Cause/ 

Corrective Action Documentation 

Process—Final. 

OMB No.: 0970–0215. 

Description: 42 U.S.C. 612 (section 

412 of the Social Security Act as 

amended by Public Law 104–193, the 

Personal Responsibility and Work 

Opportunity Reconciliation Act of 1996 

(PRWORA), mandates that federally 

recognized Indian Tribes with an 

approved Tribal TANF program collect 

and submit to the Secretary of the 

Department of Health and Human 

Services data on the recipients served 

by the Tribes programs. This 

information includes both aggregated 

and disaggregated data on case 

characteristics and individual 

characteristics. In addition, Tribes that 

are subject to a penalty are allowed to 

provide reasonable cause justifications 

as to why a penalty should not be 

imposed or may develop and implement 

corrective compliance procedures to 

eliminate the source of the penalty. 

Finally, there is an annual report, which 

requires the Tribes to describe program 

characteristics. All of the above 

requirements are currently approved by 

OMB and the Administration for 

Children and Families is simply 

proposing to extend them without any 

changes. 

Respondents: Indian Tribes. 

ANNUAL BURDEN ESTIMATES

Instrument Number of 

respondents 

Number of 

responses per 

respondent 

Average 

burden hours 

per response 

Total burden 

hours 

Final Tribal TANF Data Report ........................................................................ 62 4 451 111,848 

Tribal TANF Annual Report ............................................................................. 62 1 40 2,480 

Tribal TANF Reasonable Cause/Corrective .................................................... 62 1 60 3,720 

Estimated Total Annual Burden 

Hours: 118,048. 

Additional Information: Copies of the 

proposed collection may be obtained by 

writing to the Administration for 

Children and Families, Office of 

Administration, Office of Information 

Services, 370 L’Enfant Promenade, SW., 

Washington, DC 20447, Attn: ACF 

Reports Clearance Officer. All requests 

should be identified by the title of the 

information collection. E-mail address: 

infocollection@acf.hhs.gov. 

OMB Comment: OMB is required to 

make a decision concerning the 

collection of information between 30 

and 60 days after publication of this 

document in the Federal Register. 

Therefore, a comment is best assured of 

having its full effect if OMB receives it 

within 30 days of publication. Written 

comments and recommendations for the 

proposed information collection should 

be sent directly to the following: 

Office of Management and Budget, 

Paperwork Reduction Project, Fax: 

202–395–7245. Attn: Desk Officer for 

the Administration for Children and 

Families. 

Dated: July 7, 2009. 

Janean Chambers, 

Reports Clearance Officer. 

[FR Doc. E9–16320 Filed 7–9–09; 8:45 am] 

BILLING CODE 4184–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Administration for Children and 

Families 

Submission for OMB Review; 

Comment Request 

Title: Developmental Disabilities 

Protection & Advocacy Program 

Statement of Goals and Priorities. 

OMB No.: 0980–0270. 

Description: Federal statute and 

regulation require each State Protection 

and Advocacy (P&A) System to prepare 

and submit to public comment a 

Statement of Goals and Priorities (SGP) 

for the P&A for Developmental 

Disabilities (PADD) program for each 

coming fiscal year. While the P&A is 

mandated to protect and advocate under 

a range of different Federally authorized 


sroberts on DSKD5P82C1PROD with NOTICES