34196 Federal Register / Vol. 65, No. 103 / Friday, May 26, 2000 / Notices

communities in the vicinity of DOE facilities,

workers at DOE facilities, and other persons

potentially exposed to radiation or to

potential hazards from non-nuclear energy

production use. HHS has delegated program

responsibility to CDC.

In addition, a memo was signed in October

1990 and renewed in November 1992

between ATSDR and DOE. The MOU

delineates the responsibilities and

procedures for ATSDR’s public health

activities at DOE sites required under

sections 104, 105, 107, and 120 of the

Comprehensive Environmental Response,

Compensation, and Liability Act (CERCLA or

‘‘Superfund’’). These activities include health

consultations and public health assessments

at DOE sites listed on, or proposed for, the

Superfund National Priorities List and at

sites that are the subject of petitions from the

public; and other health-related activities

such as epidemiologic studies, health

surveillance, exposure and disease registries,

health education, substance-specific applied

research, emergency response, and

preparation of toxicological profiles.

Purpose: This subcommittee is charged

with providing advice and recommendations

to the Director, CDC, and the Administrator,

ATSDR, regarding community, American

Indian Tribes, and labor concerns pertaining

to CDC’s and ATSDR’s public health

activities and research at this DOE site. The

purpose of this meeting is to provide a forum

for community, American Indian Tribal, and

labor interaction, and serve as a vehicle for

community concerns to be expressed as

advice and recommendations to CDC and

ATSDR.

Matters To Be Discussed: Agenda items

include an update on Pit 9 work; an update

from the Risk Assessment Corporation (RAC);

a report on the January 2000 National Cancer

Institute workshop held in Rockville,

Maryland on the health effects of I–131

related to Nevada Test Site fallout; and an

update on the Evaluation Work Group

project.

Agenda items are subject to change as

priorities dictate.

Contact Person for More Information:

Arthur J. Robinson, Jr., Executive Secretary,

INEELHES, Radiation Studies Branch,

Division of Environmental Hazards and

Health Effects, NCEH, CDC, 4770 Buford

Highway, NE, M/S F–35, Atlanta, Georgia

30341–3724, telephone 770/488–7040, fax

770/488–7044.

The Director, Management Analysis and

Services Office, has been delegated the

authority to sign Federal Register notices

pertaining to announcements of meetings and

other committee management activities, for

both CDC and ATSDR.

Dated: May 19, 2000.

Julia M. Fuller,

Acting Director, Management Analysis and

Services Office, Centers for Disease Control

and Prevention (CDC).

[FR Doc. 00–13130 Filed 5–25–00; 8:45 am]

BILLING CODE 4163–18–P

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 96M–0311]

Agency Information Collection

Activities; Proposed Collection;

Comment Request

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, 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 Public Health Service (PHS)

guideline entitled ‘‘PHS Guideline on

Infectious Disease Issues in

Xenotransplantation.’’

DATES: Submit written comments on the

collection of information by July 25,

2002.

ADDRESSES: Submit written requests for

single copies of the guideline entitled

‘‘PHS Guideline on Infectious Disease

Issues in Xenotransplantation’’ to the

Office of Communication, Training, and

Manufacturers Assistance (HFM–40),

Center for Biologics Evaluation and

Research (CBER), Food and Drug

Administration, 1401 Rockville Pike,

Rockville, MD 20852–1448. Send one

self-addressed adhesive label to assist

that office in processing your requests.

The document may also be obtained by

mail by calling the CBER Voice

Information System at 1–800–835–4709

or 301–827–1800, or by fax by calling

the FAX Information System at 1–888–

CBER–FAX or 301–827–3844.

Submit written comments on the

collection of information to the Dockets

Management Branch (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:

Karen L. Nelson, Office of Information

Resources Management (HFA–250),

Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857,

301–827–1482.

SUPPLEMENTARY INFORMATION:

I. Background

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 request

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,

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: (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.

PHS Guideline on Infectious Disease

Issues in Xenotransplantation

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.). This PHS guideline is revised

based on public comment to a previous

document entitled ‘‘Draft Public Health

Service (PHS) Guideline on Infectious

Disease Issues in Xenotransplantation

(August 1996),’’ which published in the

Federal Register of September 23, 1996

(61 FR 49919). The PHS guideline

recommends procedures to diminish the

risk of transmission of infectious agents

to the xenotransplantation product

recipient and 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

Federal Register / Vol. 65, No. 103 / Friday, May 26, 2000 / Notices 34197

xenotransplantation that may pose a

hazard to the public health. The

collection of information described in

this guideline is intended to provide

general guidance to sponsors in: (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

public health needs for: (1) A pilot

national xenotransplant data base,

which is currently under development

by the PHS; (2) a central PHS biologic

specimen archive; and (3) the

Secretary’s Advisory Committee on

Xenotransplantation (SACX), which is

being developed and implemented by

the Department of Health and Human

Services (DHHS). These public health

programs and this PHS guideline are

intended to protect the public health

and help ensure the safety of using

xenotransplantation products in

humans by preventing the introduction,

transmission, and spread of infectious

diseases associated with

xenotransplantation.

Respondents to this collection of

information are the sponsors of clinical

studies of investigational

xenotransplantation products under

investigational new drug applications

(IND’s) and xenotransplantation product

procurement centers, referred to as

source animal facilities. Currently, there

are 11 respondents who are sponsors of

IND’s, which include protocols for

xenotransplantation in humans. Other

respondents for this collection of

information are 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 PHS guideline proposes 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. Although the draft

guideline discussed holding specimens

and records indefinitely, comments

described this recommendation as

impractical and unfeasible.

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. They contain

ribonucleic acid that is reversetranscribed into deoxyribonucleic acid

(DNA) using an enzyme provided by the

virus and the cell machinery. That DNA

can then be integrated into the 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. If record

systems are maintained in a computer

data base, electronic backups should be

kept in a secure office facility and

backup on hard copy should be

routinely performed (4.1.2.2). The

development of such a record system

would be a one-time burden. Such a

system is intended to cross-reference

and locate relevant records or

recipients, source animals and facilities,

and specimens of both the recipient and

the source animal. Based on agency

experience in establishing new, small

volume, recordkeeping and tracking

systems, we estimate approximately 16

hours would be necessary for each

sponsor to set up the records system.

The total annual reporting and

recordkeeping burden is estimated to be

approximately 327 hours. The burden

estimates are based on FDA’s records of

xenotransplantation-related IND’s and

estimates of time required to create an

appropriate record system and to

complete the various reporting and

recordkeeping tasks described in the

guideline. A total of 22 IND’s have been

submitted since 1994 resulting in an

average of 4 IND submissions per year.

A total of 87 patients have been treated

over a 3-year period indicating there are

on average 29 xenotransplantation

product recipients per year. FDA does

not expect the level of clinical studies

using xenotransplantation to increase

significantly in the next few years;

therefore, the agency is using these

historical figures in projecting burdens

for the next 3 years.

FDA is requesting 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 source animal facility or sponsor ceases operations.

3.4 Standard operating procedures (SOP’s) 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.

34198 Federal Register / Vol. 65, No. 103 / Friday, May 26, 2000 / Notices

TABLE1.—REPORTING RECOMMENDATIONS—Continued

PHS Guideline Section Description

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 and 4.3 Establish records linking each xenotransplantation product recipient with relevant records. Sponsor to maintain crossreferenced 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.

FDA estimates the burden for 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 18 0 0 0.5 0

3.2.7.22 11 0 0 0.5 0

3.43 11 0.4 4 0.08 0.3

3.5.14 11 0.09 1 0.25 0.25

3.5.45 11 2.6 29 0.5 14.5

3.5.54 18 0.06 1 0.2 0.2

Total 15.25

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 to date and none are expected to cease operation in the next several years.

3FDA’s records indicate that an average of four IND’s have been and are expected to be submitted per year.

4 Has not occurred in the past 5 years and is expected to continue to be a rare occurrence.

5Based on 87 patients treated over the last 3 years, the average number of xenotransplantation product recipients per year is estimated to be

29.

TABLE 4.—ESTIMATED ANNUAL RECORDKEEPING BURDEN1

PHS Guideline Section No. of

Recordkeepers

Annual

Frequency per

Recordkeeping

Total Annual

Records

Hours per

Recordkeeper Total Hours

3.2.7 and 4.32 11 1 N/A 16 172

3.4.23 11 15.1 166 3.77 41.5

3.4.3.24 18 4.0 72 1.32 23.8

3.5.15 11 0.09 (0–1)1 0.045 0.5

3.5.25 11 0.09 (0–1)1 0.023 0.25

3.5.4 11 2.6 29 0.45 4.9

3.6.46 11 5.3 58 1.32 14.5

3.76 18 3.2 58 0.26 4.6

4.2.3.27 11 27.3 300 4.64 51

4.2.3.25 11 0.09 (0–1)1 0.015 0.17

4.2.3.3 and 4.3.25 11 0.09 (0–1)1 0.015 0.17

4.3.1 11 2.6 29 0.66 7.25

5.28 11 7.9 87 0.63 6.96

Total 327.6

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

Federal Register / Vol. 65, No. 103 / Friday, May 26, 2000 / Notices 34199

2A one-time burden for setting up a recordkeeping system which rapidly links information regarding the specimen archive, the recipient’s medical records, and source animals. 3 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 58 source animals per year (see footnote 6 of this table); 108 +

58 = 166 monitoring records to document. 4 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. 5 Has not occurred in the past 5 years and is expected to continue to be a rare occurrence.

6On average 2 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 29 recipients annually = 58 source animals per year. (See footnote 5 of table 3 of this document.) 7FDA estimates there are approximately 12 clinical centers doing xenotransplantation procedures x approximately 25 health care workers involved per center = 300 health care workers. 8Fifty-eight source animal records + 29 recipient records = 87 total records.

Because xenotransplantation is a

relatively new area of medical science,

potential problems and adverse effects

are not well known. Because of the

potential risk for cross-species

transmission of infectious agents from

source animals to patients, their close

contacts, and the general public and the

latency period of known human

pathogenic persistent virus, the

guideline recommends that health

records be retained for 50 years. Since

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 small and,

therefore, the capital and operating costs

are expected to be insignificant at this

time.

Many of the information collections

described in this guideline are not new

and can be found under existing

regulations and, therefore, are not

included in the hour burden estimates

in tables 1 through 4 of this document.

These information collections are

included under the 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 601.1 through

601.3, approved under OMB control

number 0910–0124. (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 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 otherwisestated)

2.2.1 Document off-site collaborations 312.52

2.5 Sponsor ensure 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 Prevention42 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 SOP’s 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 (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

4.2.3.1 Develop educational materials (sponsor provides investigators with information needed to conduct investigation properly)312.50

34200 Federal Register / Vol. 65, No. 103 / Friday, May 26, 2000 / 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 otherwisestated)

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). 2AAALAC International Rules of Accreditation (http://www.aaalac.org/html/rules.html).

3The NRC’s ‘‘Guide for the Care and Use of Laboratory Animals’’ (1996).

II. Electronic Access

Persons with access to the Internet

may obtain the guideline at http://

www.fda.gov/cber/guidelines.htm.

Dated: May 23, 2000.

William K. Hubbard,

Senior Associate Commissioner for Policy,

Planning, and Legislation.

[FR Doc. 00–13340 Filed 5–25–00; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[FDA 225–99–7000]

Memorandum of Understanding

Between the Food and Drug

Administration, the Centers for

Disease Control and Prevention, the

U.S. Department of Agriculture, the

U.S. Department of Defense, and the

Environmental Protection Agency

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 FDA, the

Centers for Disease Control and

Prevention, the U.S. Department of

Agriculture, the U.S. Department of

Defense, and the Environmental

Protection Agency. The purpose of the

MOU is to establish an interagency

coordinating committee on animal

production and food health with the

goal of improving animal and public

health.

DATES: The agreement became effective

November 17, 1999.

FOR FURTHER INFORMATION CONTACT:

Robert C. Livingston, Center for

Veterinary Medicine (HFV–1), Food and

Drug Administration, 7500 Standish Pl.,

Rockville, MD 20855, 301–594–5903.

SUPPLEMENTARY INFORMATION: In

accordance with 21 CFR 20.108(c),

which states that all written agreements

and MOU’s between FDA and others

shall be published in the Federal

Register, the agency is publishing notice

of this MOU.

Dated: May 19, 2000.

William K. Hubbard,

Senior Associate Commissioner for Policy,

Planning, and Legislation.

The MOU is set forth in its entirety as

follows:

BILLING CODE 4160–01–F