Federal Register / Vol. 63, No. 12 / Tuesday, January 20, 1998 / Notices 2985

1The term unrelated allogeneic use means the

implantation, infusion, or transfer of a human

cellular or tissue-based product from one person to

another who is not a parent, sibling, or a child of

the donor.

2The term minimally manipulated means

processing of cells and nonstructural tissues that

does not alter the biological characteristics and

thus, potentially, the function or integrity of the

cells or tissues.

the Personal Responsibility and Work

Opportunity Reconciliation Act of 1996.

It consists of disaggregated and

aggregated demographic and program

information that will be used to

determine participation rates and other

statutorily required indicators for the

Temporary Assistance for Needy

Families (TANF) program. OMB

previously approved this data collection

under emergency procedures through

January 31, 1998. We are now

requesting an extension through

September 30, 1998, in order to

maintain the continuity of data

collection pending OMB approval of the

data collection instruments published in

the NPRM dated November 20, 1997.

Respondents: States and Territories.

ANNUAL BURDEN ESTIMATES

Instrument Number of respondents

Number of responses per

respondent

Average burden hours per

response

Total burden

hours

Emergency TANF Data Report ........................................................................ 54 4 451 97,416

Estimated Total Annual Burden

Hours: 97,416.

Additional Information

Copies of the proposed collection may

be obtained by writing to The

Administration for Children and

Families, Office of Information Services,

Division of Information Resource

Management Services, 370 L’Enfant

Promenade, S.W., Washington, D.C.

20447, Attn: ACF Reports Clearance

Officer.

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, 725 17th Street,

N.W., Washington, D.C. 20503, Attn:

Ms. Laura Oliven.

Dated: January 7, 1998.

Bob Sargis,

Acting Reports Clearance Officer.

[FR Doc. 98–1251 Filed 1–16–98; 8:45 am]

BILLING CODE 4184–01–M

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 97N–0497]

Request for Proposed Standards for

Unrelated Allogeneic Peripheral and

Placental/Umbilical Cord Blood

Hematopoietic Stem/Progenitor Cell

Products; Request for Comments

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice; request for comments.

SUMMARY: The Food and Drug

Administration (FDA) is requesting

submission of comments proposing

product standards intended to ensure

the safety and effectiveness of

minimally manipulated hematopoietic

stem/progenitor cells derived from

peripheral and cord blood for unrelated

allogeneic use.1 The comments should

include supporting clinical and

nonclinical laboratory data and other

relevant information. This information

will aid FDA in developing product

standards for hematopoietic stem/

progenitor cell products intended for

allogeneic use in recipients unrelated to

the donor (hereinafter referred to as

unrelated allogeneic), including

manufacturing controls and product

specifications. FDA is also announcing

its intention to phase-in implementation

of investigational new drug application

(IND) and license application

requirements for minimally

manipulated2 unrelated allogeneic

hematopoietic stem/progenitor cell

products 3 years after the date of

issuance of this notice to permit the

development of licensing standards for

those products where possible. This

action is taken in response to the

agency’s ‘‘Proposed Approach to

Regulation of Cellular and Tissue-based

Products,’’ which fullfills the objectives

of the administration’s ‘‘Reinventing the

Regulation of Human Tissue’’ initiated

to streamline regulatory requirements to

ease the burden on regulated industry,

while providing adequate protection to

the public health.

DATES: Submit requested standards and

supporting clinical and nonclinical

laboratory data by January 20, 2000.

ADDRESSES: Submit proposed product

standards and supporting data to the

Dockets Management Branch (HFA–

305), Food and Drug Administration,

12420 Parklawn Dr., rm. 1–23,

Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

Paula S. McKeever, Center for Biologics

Evaluation and Research (HFM–17),

Food and Drug Administration, 1401

Rockville Pike, Rockville, MD 20852–

1448, 301–827–6210.

SUPPLEMENTARY INFORMATION:

I. Background

A. Use of Peripheral and Cord Blood

Stem/Progenitor Cells for Hematopoietic

Reconstitution

The field of hematologic

transplantation has changed

substantially during the last two

decades. Improved understanding of the

diverse aspects of human hematologic

precursors has facilitated their

experimental manipulation. Our

knowledge of their localization in

humans during both fetal and postnatal

development, growth regulation,

differentiation, homing, and of

phenotypic and functional

characteristics has facilitated the

development of new methods of

transplantation. Traditional bone

marrow transplantation, involving the

extraction of bone marrow by aspiration

from bone cavities with further

processing by density centrifugation, is

increasingly being supplanted by novel

approaches that include use of

hematopoietic stem/progenitor cells and

biotechnologic procedures to purify and

expand hematopoietic stem/progenitor

cells. Human cord blood, which is

enriched with pluripotent

hematopoietic stem/progenitor cells,

and peripheral blood, which can be

enriched in hematopoietic stem/

progenitor cells by a variety of
2986 Federal Register / Vol. 63, No. 12 / Tuesday, January 20, 1998 / Notices

3The term human cellular and tissue-based

product means a product containing human cells or

tissues or any cell or tissue-based component of

such a product.

4The term homologous use means the use of a

cellular or tissue-based product for a normal

function that is analogous to that of the cells or

tissues being replaced or supplemented.

5The term autologous use means the

implantation, transplantation, infusion, or transfer

of a human cellular or tissue-based product back

into the individual from whom the cells or tissue

comprising such product were removed.

6The term family-related allogeneic use means

the implantation, transplantation, infusion, or

transfer of a human cellular or tissue-based product

into a first-degree blood relative of the individual

from whom cells or tissue comprising such product

were removed.

interventions, have emerged as sources

of hematopoietic cells alternative to

bone marrow aspirates for bone marrow

reconstitution.

B. Stem/Progenitor Cell Workshops

FDA held a public workshop to

discuss procedures for preparation and

storage of cord blood stem/progenitor

cells on December 13, 1995 (60 FR

58088, November 24, 1995). The

workshop was jointly sponsored by FDA

and the National Heart, Lung, and Blood

Institute (NHLBI), National Institutes of

Health. The purpose of the workshop

was to identify and discuss steps for

collection, processing, and storage of

cord blood stem/progenitor cells for

transplantation and to identify what

additional post transplantation

scientific data are needed in this area.

A draft document, discussing an

appropriate regulatory approach for

placental/umbilical cord blood stem/

progenitor cell products for

transplantation, was made available at

the workshop, and a notice of

availability for comment was published

in the Federal Register of February 26,

1996 (61 FR 7087). In response to

requests to extend the comment period,

a notice extending the comment period

by 90 days was published in the Federal

Register of May 28, 1996 (61 FR 26473).

In the Federal Register of February 8,

1996 (61 FR 4786), FDA announced a

public workshop, jointly sponsored by

FDA and NHLBI to be held on February

22 and 23, 1996, to discuss procedures

for the preparation, processing, and

characterization of human peripheral

blood stem/progenitor cells. The

purpose of the workshop was to identify

and discuss the methods for the

collection, processing, and storage of

peripheral blood stem/progenitor cells

for transplantation and to identify areas

in need of further research. A draft

document was made available at the

workshop describing FDA’s proposed

regulatory approach for human

peripheral blood stem/progenitor cell

products for transplantation.

Based, in part, on information

presented at these meetings, FDA

recognized a need to reconsider whether

the concepts and procedures used to

regulate traditional biological products

were appropriate for regulation of

peripheral and cord blood

hematopoietic stem/progenitor cells and

other cellular and tissue-based products

which are a result of new technologies.

After consultation with representatives

of the involved public, FDA proposed a

new regulatory framework for cellular

and tissue-based products, including

hematopoietic stem/progenitor cells, in

February 1997, entitled ‘‘Reinventing

the Regulation of Human Tissue,’’ and

‘‘Proposed Approach to Regulation of

Cellular and Tissue-based Products.’’

On March 4, 1997, the agency

announced a public meeting, to be held

on March 17, 1997, to solicit

information and views from the

interested public on the agency’s

proposed regulatory approach for such

products, and the agency requested that

written comments be submitted to the

docket (62 FR 9721).

C. New Regulatory Approach for Human

Cellular and Tissue-Based Products

The proposed framework provides a

tiered approach to human cellular and

tissue-based product3 regulation. The

regulation focuses on three general

areas: (1) Preventing use of

contaminated tissues with the potential

for transmitting infectious diseases; (2)

preventing improper handling or

processing that might contaminate or

damage tissues, or produce cellular or

tissue-based products of inadequate

quality; and (3) ensuring that clinical

safety and effectiveness are

demonstrated for most tissues that are

highly processed, are used for other

than their homologous use,4 are

combined with nontissue components,

or have a systemic effect.

Under the tiered approach, FDA

intends to impose Federal requirements

only to the extent necessary to protect

the public health, with minimal

regulation for some products and with

increasing degrees of oversight as the

potential risk increases. For example,

tissues transplanted from one person to

another for their normal structural or

reproductive functions and without

undergoing extensive processing will be

subject to requirements for infectious

disease screening and testing, and to

requirements for good processing and

handling procedures, but will not need

FDA marketing approval before

distribution and use. Thus, FDA expects

that most processors of reproductive

tissue, tissue products currently

regulated under 21 CFR part 1270, and

other minimally manipulated products

will not be required to seek FDA

premarket approval of their products

nor to submit detailed clinical

information about their products to

FDA. The agency intends to regulate as

biological drugs or devices those tissues

that are processed extensively,

combined with nontissue components,

promoted or labeled for use other than

homologous use, or (with limited

exceptions) that have systemic effect on

the body. Minimally manipulated

hematopoietic stem/progenitor cells

derived from peripheral and cord blood,

for unrelated allogeneic use, would

therefore be regulated as biological

drugs under the Public Health Service

Act and the Federal Food, Drug, and

Cosmetic Act. FDA does not intend to

request clinical data to demonstrate

safety and effectiveness for cellular and

tissue-based products with systemic

effect that are for autologous use5 or

family-related allogeneic use6 or for

reproductive tissues for reproductive

use providing such products are

minimally manipulated, for homologous

use, and not combined with a nontissue

component. FDA intends to require that

establishments manufacturing such

minimally manipulated hematopoietic

stem/progenitor cell products for

hematopoietic reconstitution register

and list their products with FDA,

comply with good tissue practice

regulations, and ensure that all labeling

and promotional materials are clear,

accurate, balanced, and nonmisleading.

D. Application of the Proposed

Regulatory Approach to Hematopoietic

Stem/Progenitor Cell Products

For unrelated allogeneic

hematopoietic stem/progenitor cells

intended for hematopoietic

reconstitution, provided they are not

more than minimally manipulated (i.e.,

processing does not alter the biological

characteristics of the cells), the agency

believes that it may be possible to

develop product standards and

establishment and processing controls

based on existing clinical trial data or

data developed in the near future

demonstrating the safety and efficacy of

the cells. If adequate information can be

developed, the agency intends to issue

guidance for establishment controls,

processing controls, and product

standards in accordance with the

agency’s ‘‘Good Guidance Practices,’’

issued in the Federal Register of

February 27, 1997 (62 FR 8961). FDA

intends to propose that, in lieu of

individual applications containing

clinical data, licensure may be granted
Federal Register / Vol. 63, No. 12 / Tuesday, January 20, 1998 / Notices 2987

for products certified as meeting issued

standards. To allow sufficient time for

data and standards to be developed, the

agency will phase-in IND and license

application requirements for minimally

manipulated unrelated allogeneic

hematopoietic stem/progenitor cell

products for hematopoietic

reconstitution 3 years following the date

of issuance of this Federal Register

notice. FDA is inviting product

providers, professional groups, and

other interested persons to submit to the

agency proposed standards and

supporting data designed to ensure the

safety and effectiveness of minimally

manipulated hematopoietic stem/

progenitor cell products for

hematopoietic reconstitution. Proposed

standards should be supported by

adequate data and other relevant

information. In order to permit

development of useful standards within

the phase-in period for enforcement of

premarket application requirements,

FDA suggests that interested parties

work together to achieve consensus on

uniform standards before submission to

FDA. FDA will evaluate the information

submitted. If the agency determines that

the submissions support the

development of standards, FDA intends

to issue such standards through the

agency’s guidance documents

procedures. If FDA determines that

adequate establishment and processing

controls and product standards are not

available, the agency intends to enforce

IND and license application

requirements at the close of the 3 year

period. FDA reminds affected parties

that cells that have been more than

minimally manipulated (e.g., expanded,

activated, genetically modified or

otherwise have their biological

characteristics altered) or combined

with nontissue components continue to

require IND’s and licensing approval,

and are not subject to a phase-in period

for enforcement of these requirements.

II. Request for Product Standards with

Supporting Clinical and Nonclinical

Data

A. Purpose

FDA is inviting product providers,

professional groups, and other

interested persons to submit to the

agency proposed product standards

with supporting clinical and nonclinical

laboratory data, and other relevant

information, designed to ensure the

safety and effectiveness of minimally

manipulated hematopoietic stem/

progenitor cells derived from peripheral

and placental/umbilical cord blood for

unrelated allogeneic hematopoietic

reconstitution. Submitted data may be

specific for a patient subset, e.g.,

pediatric patients, and should identify

the patient subset, if applicable.

FDA is requesting that proposed

establishment controls include

standards for personnel, facilities,

quality management, standard operating

procedures, staff training and

competence, and process validation.

Establishment controls should also

include standards for recordkeeping

regarding donors, processing,

quarantine, storage, labeling,

distribution, tracking, handling of errors

and accidents, deviations from standard

operating procedures, suspected adverse

reactions, and quality control processes.

FDA is requesting that proposed

processing controls include standards

for donor selection, informed consent,

donor testing and screening,

histocompatibility testing, collection

procedures, product testing, volume

reduction methods, cryopreservation,

storage conditions in liquid and frozen

state, storage monitoring, transportation

within and between facilities,

temperature limits, packaging, and

thawing procedures. The processing

controls should include standards for

testing for product contamination,

product viability, composition, and

functionality, and include when and

how such testing is to be performed.

FDA is requesting that proposed

product standards include the criteria

for acceptance of a unit of

hematopoietic stem/progenitor cells

derived from peripheral or placental/

umbilical cord blood. Criteria should

include volume of the product, viable

cell number (specified as nucleated or

mononuclear cells), storage temperature

limits, microbial or other contamination

limits, and any other appropriate

characteristics of the product, e.g., CD34

positive cell enumeration. For

peripheral blood hematopoietic stem/

progenitor cell products, information

regarding the treatment regimens of the

donors with mobilizing agents should

also be provided including the type of

mobilizing agent, duration of

mobilization, and the number of

apheresis collections.

The agency is suggesting that

evidence of hematopoietic stem/

progenitor cell engraftment for these

products be consistently expressed as

the time, expressed as number of days

from the day of hematopoietic stem/

progenitor cell infusion to the day that

a neutrophil count of equal to or greater

than 500 cells/μL is obtained, and the

time, expressed as number of days from

the day of hematopoietic stem/

progenitor cell infusion to the first of 3

consecutive days in which the

transfusion-independent platelet count

of equal to or greater than 20,000

platelets/μL is demonstrated in the

recipient. Information relevant to

sustained platelet engraftment, such as

the number of days from the day of

hematopoietic stem/progenitor cell

infusion to the day in which a

transfusion-independent platelet count

of equal to or greater than 50,000

platelets/μL is observed, should also be

provided. Data provided should include

the extent of HLA (human leukocyte

antigen) disparity, the nucleated cell

dose/kg body weight of the recipient,

the weight, age, and underlying disease

of the recipient, the extent and severity

of Graft-Versus-Host Disease, the criteria

utilized for evidence for allogeneic cell

engraftment, and any other important

information regarding the safety and

efficacy of the infused product, e.g.,

incidence of infection. In addition, a

description of the methods used for data

evaluation, including statistical

techniques, should be included.

B. Review and Consolidation of

Submitted Information by FDA

FDA will review and assess the

information submitted, and evaluate it

as to its application in issuing

hematopoietic stem/progenitor cell

product standards. FDA may find it

necessary to present any or all of the

aspects of the standards and/or data for

public discussion. Any public meeting

held by FDA will be announced to the

public prior to the date of the meeting.

Subsequent to receiving sufficient

standards with supporting data, FDA

intends to adopt appropriate standards

as guidance and announce their

availability in the Federal Register.

III. Submissions

Interested persons may, on or before

January 20, 2000 submit to the Dockets

Management Branch (address above)

written proposed standards and

supporting clinical and nonclinical

laboratory data. Two copies of standards

and data should be submitted, except

that individuals may submit one copy.

Standards and data should be identified

with the docket number found in

brackets in the heading of this

document. All information submitted

will be placed on public display and

will be subject to public disclosure. Any

information that is not intended to be

made public must be deleted before

submission to the Dockets Management

Branch. Trade secrets and confidential

commercial information, as well as

information that could be used to

identify individual patients or others

whose privacy should be maintained,

should be deleted before being

submitted. All comments proposing
2988 Federal Register / Vol. 63, No. 12 / Tuesday, January 20, 1998 / Notices

standards with supporting data will be

available for public examination in the

Dockets Management Branch (address

above) between 9 a.m. and 4 p..m.,

Monday through Friday.

Dated: January 8, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–1171 Filed 1–16–98; 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

regulatory issues. Date and Time: The meeting will be

held on February 12 and 13, 1998, 8

a.m. to 5 p.m.

Location: Parklawn Bldg., conference

rooms D and E, 5600 Fishers Lane,

Rockville, MD.

Contact Person: Sara M. Thornton,

Center for Devices and Radiological

Health (HFZ–460), Food and Drug

Administration, 9200 Corporate Blvd.,

Rockville, MD 20850, 301–594–2053, or

FDA Advisory Committee Information

Line, 1–800–741–8138 (301–443–0572

in the Washington, DC area), code

12396, or the world wide web at http:/

/www.fda.gov. Please call the

Information Line for up-to-date

information on this meeting.

Agenda: On February 12, 1998, the

committee will discuss specific

questions related to the development of

contact lens extended wear clinical

testing guidance for 7-day extended

wear, prolonged extended wear beyond

7 days, and overnight use of contact

lenses for orthokeratology. On February

13, 1998, the committee will discuss,

make recommendations, and vote on a

premarket approval application (PMA)

for a broad beam excimer laser for the

correction of myopia with astigmatism

using laser in-situ keratomileusis. The

committee will also discuss, make

recommendations, and vote on a PMA

for a scanning excimer laser for the

correction of myopia with astigmatism

using photorefractive keratectomy. Procedure: Interested persons may

present data, information, or views,

orally or in writing, on issues pending

before the committee. Written

submissions may be made to the contact

person by February 6, 1998. Oral

presentations from the public will be

scheduled between approximately 8:30

a.m. and 9:30 a.m. on February 12 and

13, 1998. Time allotted for each

presentation may be limited. Those

desiring to make formal oral

presentations should notify the contact

person before February 2, 1998, and

submit a brief statement of the general

nature of the evidence or arguments

they wish to present, the names and

addresses of proposed participants, and

an indication of the approximate time

requested to make their presentation.

Notice of this meeting is given under

the Federal Advisory Committee Act (5

U.S.C. app. 2).

Dated: January 12, 1998.

Michael A. Friedman,

Deputy Commissioner for Operations.

[FR Doc. 98–1170 Filed 1–16–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 93N–0195]

Agency Information Collection

Activities; Announcement of OMB

Approval

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing

that a collection of information entitled

‘‘Procedures for the Safe Processing and

Importing of Fish and Fishery Products’’

has been approved by the Office of

Management and Budget (OMB) under

the Paperwork Reduction Act of 1995

(the PRA).

FOR FURTHER INFORMATION CONTACT:

Margaret R. Schlosburg, Office of

Information Resources Management

(HFA–250), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–827–1223.

SUPPLEMENTARY INFORMATION: In the

Federal Register of October 31, 1997 (62

FR 58973), the agency announced that

the proposed information collection had

been submitted to OMB for review and

clearance under section 3507 of the PRA

(44 U.S.C. 3507). An agency may not

conduct or sponsor, and a person is not

required to respond to, a collection of

information unless it displays a

currently valid OMB control number.

OMB has now approved the information

collection and has assigned OMB

control number 0910–0354. The

approval expires on December 31, 2000.

Dated: January 8, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–1167 Filed 1–16–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 97N–0040]

Agency Information Collection

Activities; Announcement of OMB

Approval

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing

that a collection of information entitled

‘‘Survey of Food Safety Practices of

Food Processing Firms’’ has been

approved by the Office of Management

and Budget (OMB) under the Paperwork

Reduction Act of 1995 (the PRA).

FOR FURTHER INFORMATION CONTACT:

Margaret R. Schlosburg, Office of

Information Resources Management

(HFA–250), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–827–1223.

SUPPLEMENTARY INFORMATION: In the

Federal Register of August 7, 1997 (62

FR 42559), the agency announced that

the proposed information collection had

been submitted to OMB for review and

clearance under section 3507 of the PRA

(44 U.S.C. 3507). An agency may not

conduct or sponsor, and a person is not

required to respond to, a collection of

information unless it displays a

currently valid OMB control number.

OMB has now approved the information

collection and has assigned OMB

control number 0910–0355. The

approval expires on November 30, 2000.

Dated: January 9, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–1168 Filed 1–16–98; 8:45 am]

BILLING CODE 4160–01–F