Federal Register / Vol. 65, No. 202 / Wednesday, October 18, 2000 / Notices 62359

Program (NV), $92,216, September 1,

2000 to August 31, 2001; University of

Colorado Health Science Center (CO),

$327,364, September 29, 2000 to

September 28, 2003; University of North

Dakota (ND), $327,365, September 1,

2000 to August 31, 2003; Metropolitan

Family Services (IL), $250,000,

September 30, 2000 to September 29,

2001; Santa Clara Indian Pueblo (NM),

$461,000, September 1, 2000 to August

31, 2001; City of Norwalk (CA), $36,886,

September 30, 2000 to September 29,

2001; Elderly Services Inc. (VT),

$783,836, September 30, 2000 to March

30, 2002; VNA Home Health, Inc. (WI),

$89,575, September 1, 2000 to August

31, 2001; City of Norwalk (CA), $36,886,

September 30, 2000 to September 29,

2001; Pension Rights Center (DC),

$187,500, April 1, 2000 to March 30,

2003; Legal Services for the Elderly

(NY), $75,000, March 1, 2000 to

February 28, 2003; California Advocates

for Nursing Home Reform (CA), $75,000,

March 1, 2000 to February 28, 2003;

Older Womens League, Inc. (DC),

$74,919, May 1, 2000 to April 30, 2003;

Pima Council on Aging (AZ), $75,000,

May 1, 2000 to April 30, 2003; Chicago

Department on Aging (IL), $74,353,

September 30, 2000 to September 29,

2003; University of Alabama (AL),

$74,928, September 30, 2000 to

September 29, 2003; Oregon Health

Sciences University (OR), $922,160,

August 1, 2000 to January 31, 2002; and

Texas Tech University Health Sciences

Center School of Medicine (TX),

$1,857,786, August 1, 2000 to July 31,

2001.

All awards were made consistent with

the terms of Senate Report 106–166 and

House Report 106–370 which

accompany the Consolidated

Appropriations Act for FY 2000 (Pub. L.

106–113).

FOR FURTHER INFORMATION CONTACT:

Edwin L. Walker, 202–619–1828.

Dated: October 10, 2000.

Jeanette C. Takamura,

Assistant Secretary for Aging.

[FR Doc. 00–26734 Filed 10–17–00; 8:45 am]

BILLING CODE 4154–01–U

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 96M–0311]

Agency Information Collection

Activities; Submission for OMB

Review; Comment Request; Public

Health Service (PHS) Guideline on

Infectious Disease Issues in

Xenotransplantation

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing

that the proposed collection of

information listed below has been

submitted to the Office of Management

and Budget (OMB) for review and

clearance under the Paperwork

Reduction Act of 1995 (the PRA).

DATES: Submit written comments on the

collection of information by November

17, 2000.

ADDRESSES: Submit written comments

on the collection of information to the

Office of Information and Regulatory

Affairs, OMB, New Executive Office

Bldg., 725 17th St. NW., rm. 10235,

Washington, DC 20503, Attn: Wendy

Taylor, Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT:

JonnaLynn P. Capezzuto, Office of

Information Resources Management

(HFA–250), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–827–4659.

SUPPLEMENTARY INFORMATION: In

compliance with 44 U.S.C. 3507, FDA

has submitted the following proposed

collection of information to OMB for

review and clearance.

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

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 PHS guideline also

describes public health needs for: (1) A

pilot national xenotransplant data base,

which is currently under development

by PHS; (2) a central PHS biologic

specimen archive; and (3) the

Secretary’s Advisory Committee on

Xenotransplantation, which is being

developed and implemented by the

Department of Health and Human

Services. 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

62360 Federal Register / Vol. 65, No. 202 / Wednesday, October 18, 2000 / Notices

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

PHS 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 humanto-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 (HTLV)

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 343 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

PHS 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

number 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.

In the Federal Register of May 26,

2000 (65 FR 34196), FDA, on behalf of

PHS, published a 60-day notice for

public comment on the proposed

collection of information provisions in

the PHS guideline on infectious disease

issues in xenotransplantation. FDA

received four letters of comment in

response to the notice. One of the letters

did not provide any comments on the

information collection provisions. PHS

is responding below to those comments

which address information collection

issues. Other comments, not related to

the proposed information collection

provisions, will be considered by PHS

in future revisions of the guideline.

Two comments addressed the PHS

guideline recommendation that records

be retained for 50 years.

(Comment 1) One comment stated

that although the need for record

retention is very important, the

retention of records for 50 years would

be an undue burden on a sponsor.

(Comment 2) The other comment

stated that, in view of rapidly changing

technology that would require

conversion of data whenever newer

computer systems are acquired, the

retention period would constitute an

undue burden because of the difficulty

of maintaining linked, computerized

data throughout this period of time.

The 50-year retention period is

intended to assist health care

practitioners and public health officials

in infectious disease surveillance and in

tracking the source of an infection,

disease, or illness that might emerge in

the xenotransplantation product

recipient, the source animal, or the

animal herd or colony following

xenotransplantation. The

recommendation for maintaining

records for 50 years is based on clinical

experience with several human viruses

that have presented problems in humanto-human transplantation and are

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 of these

human viruses can also be transmitted

among individuals through intimate

contact with human body fluids. For

example, HIV and HTLV are human

retroviruses that 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).

As new computer data systems are

developed, both software and hardware

manufacturers typically provide for the

transfer or conversion of existing data

into a new system. With today’s rapidly

developing information technology,

such transfers and conversions are usual

and customary practice. It is the

responsibility of the sponsor to ensure

that all data are appropriately

transferred to, and retrievable from,

their new/updated computer systems.

Because of the need for the long-term

monitoring of the health of

xenotransplantation product recipients

and source animals, a sponsor should

ensure that these data remain

compatible with the computerized data

systems that will be used during the 50-

year retention period.

Federal Register / Vol. 65, No. 202 / Wednesday, October 18, 2000 / Notices 62361

Two comments addressed the

submission of information to a national

xenotransplantation data base.

(Comment 3) One comment stated

that it would be redundant to maintain

records for 50 years and submit the

same information to the National

Xenotransplantation Database (NXD).

(Comment 4) The other comment

stated that it would constitute an

additional burden to submit information

to the NXD for companies that already

submit these data to FDA.

The NXD is not operational, but rather

is in a pilot phase at this time. In

developing this data base, PHS will

make an effort, whenever possible, to

avoid the imposition of any redundant

or excess paperwork requirements. The

public will be offered an opportunity to

comment on any information collection

burdens associated with the NXD prior

to implementation. Sponsors should,

however, recognize that they should

maintain information that goes beyond

what may be proposed for submission to

the NXD. Such information includes, for

example, personal identifiers that would

enable PHS to contact specific

individuals in case of a public health

emergency, information on recipient

contacts and health care workers,

detailed information on the

xenotransplantation procedure, and

detailed information on husbandry of

the source animal. Finally, because

sponsors will need to monitor patient

health over time, retention of records

that are more complete than data

submitted to the NXD will be necessary.

(Comment 5) One comment stated

that under sections 3.4.1 and 3.4.3.2, all

incidents that affect herd or colony

health that are recorded by a source

animal facility should also be reported

to FDA.

PHS agrees that in some cases

incidents affecting animal herd or

colony health should be reported to

FDA. For example, under

§ 312.32(c)(1)(i)(B) (21 CFR

312.32(c)(1)(i)(B)), a sponsor must notify

FDA and all participating investigators

of ‘‘[a]ny finding from laboratory

animals that suggests a significant risk

for human subjects * * *’’ Thus, if a

health event in the source herd or

colony suggests that recipients of

xenotransplantation products from the

source animals in that herd/colony may

be at significant risk, the health event

must be reported to FDA. However, as

with any herd of animals, many health

events may occur, such as injuries and

minor illnesses. These events should be

assessed, as appropriate, to determine

whether there are any health

implications for the xenotransplantation

product recipients. Primary

responsibility for designing and

monitoring the conduct of

xenotransplantation clinical trial rests

with the sponsor (e.g., 21 CFR

312.23(a)(6)(iii)(d) and 312.50). As part

of the sponsor’s responsibility when

filing an IND, procedures should be

developed to identify incidents that

negatively affect the health of the herd

or colony. This information is relevant

to the safety review of every

xenotransplantation product

application. Such information, as well

as the procedures to collect the

information, should be reported to FDA.

PHS has revised the guideline in section

3 to note the requirements for

developing such procedures and for

submitting the procedures to FDA.

(Comment 6) One comment stated

that under section 2.5.7, clinical

investigators should report to FDA any

serious or unexplained illnesses of

xenotransplantation product recipients

that are reported to them.

PHS agrees that serious or

unexplained illnesses should be

reported but they should be reported by

the sponsor rather than by the clinical

investigator. For example, under

§ 312.32(c)(1)(i)(A), a sponsor must

notify FDA and all participating

investigators of any adverse experience

associated with the use of an

investigational product that is both

serious and unexpected. The sponsor is

in the best position to evaluate such

events and determine the implications

of the event for the safety of the

xenotransplantation product and any

potential impact such product may have

on the clinical study.

FDA is requesting OMB approval for

the following reporting and

recordkeeping recommendations in the

PHS guideline, except as noted:

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.

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.—REPORTING RECOMMENDATIONS

PHS Guideline Section Description

3.2.31 Procedures to ensure the humane care of animals.

3.2.42 Incorporate procedures consistent with accreditation by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International) and consistent with the National Research Council’s

(NRC’s) Guide.

3.2.63 Animal facility SOP’s should be described.

3.2.7 and 4.3 Establish records linking each xenotransplantation product recipient with relevant records, including SOP’s of animal procurement, facility herd health surveillance, and lifelong health history of source animal. Maintain crossreferenced system that links all relevant records (recipient, product, source animal, animal procurement center,

and significant 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 Document justification for 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.

62362 Federal Register / Vol. 65, No. 202 / Wednesday, October 18, 2000 / Notices

TABLE 2.—REPORTING RECOMMENDATIONS—Continued

PHS Guideline Section Description

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 baseline 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.

1These procedures are set forth in 9 CFR parts 1, 2, and 3 and the ‘‘Public Health Service Policy on Humane Care and Use of Laboratory

Animals’’ (http://www.grants.nih.gov/grants/olaw/references/phspol.htm) and are considered usual and customary practice. 2These procedures are set forth in the AAALAC International Rules of Accreditation (http://www.aaalac.org) and the NRC’s ‘‘Guide for the

Care and Use of Laboratory Animals’’ (1996) and are considered usual and customary practice. 3These procedures are set forth in the ‘‘Public Health Service Policy on Humane Care and Use of Laboratory Animals’’ (http://www.grants.nih.gov/grants/olaw/references/phspol.htm) and are considered usual and customary practice.

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.

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.)

Federal Register / Vol. 65, No. 202 / Wednesday, October 18, 2000 / Notices 62363

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, they

are not considered ‘‘information’’ as that

term is defined under 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 601.2, approved

under OMB control number 0910–0427.

(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 expects, 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.)

TABLE 5.—COLLECTIONS OF INFORMATION UNDER CURRENT REGULATIONS

PHS Guideline

Section Description of Collection of Information Activity 21 CFR Section (unless otherwisestated)

2.2.1 Document offsite 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)(iv)(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

3.2.5, 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

3.3.3 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

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)

Dated: October 10, 2000.

Margaret M. Dotzel,

Associate Commissioner for Policy.

[FR Doc. 00–26671 Filed 10–17–00; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

Ophthalmic Devices Panel of the

Medical Devices Advisory Committee;

Notice of Meeting

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

This notice announces a forthcoming

meeting of a public advisory committee

of the Food and Drug Administration

(FDA). The meeting will be open to the

public.

Name of Committee: Ophthalmic

Devices Panel of the Medical Devices

Advisory Committee.

General Function of the Committee:

To provide advice and

recommendations to the agency on

FDA’s regulatory issues.

Date and Time: The meeting will be

held on November 8, 2000, 8:30 a.m. to

5 p.m.

Location: Holiday Inn, Walker/

Whetstone Rooms, Two Montgomery

Village Ave., Gaithersburg, MD.