35774 Federal Register / Vol. 61, No. 131 / Monday, July 8, 1996 / Notices

of which would constitute a clearly

unwarranted invasion of personal privacy.

(Catalog of Federal Domestic Assistance

Program Nos. 93.306, 93.333, 93.337, 93.393–

93.396, 93.837–93.844, 93.846–93.878,

93.892, 93.893, National Institutes of Health,

HHS)

Dated: July 1, 1996.

Susan K. Feldman,

Committee Management Officer, NIH.

[FR Doc. 96–17213 Filed 7–5–96; 8:45 am]

BILLING CODE 4140–01–M

Recombinant DNA Research: Notice of

Intent To Propose Amendments to the

NIH Guidelines for Research Involving

Recombinant DNA Molecules (NIH

Guidelines) Regarding Enhanced

Mechanisms for NIH Oversight of

Recombinant DNA Activities

AGENCY: National Institutes of Health

(NIH), HHS.

ACTION: Notice of Intent to Propose

Amendments.

SUMMARY: The NIH Director intends to

propose amendments to the NIH

Guidelines (59 FR 34496, amended 59

FR 40170, amended 60 FR 20726,

amended 61 FR 1482, amended 61 FR

10004) to enhance NIH mechanisms for

scientific and ethical oversight of

recombinant DNA activities. To

accomplish this objective, the NIH

Recombinant DNA Advisory Committee

(RAC) will be discontinued and all

approval responsibilities for

recombinant DNA experiments

involving human gene transfer will be

relinquished to the Food and Drug

Administration (FDA) which retains

statutory authority for such approval.

Enhancement of NIH oversight of

human gene therapy will be

accomplished through three distinct

mechanisms: (1) Establishment of the

Office of Recombinant DNA Activities

(ORDA) Advisory Committee (OAC) to

ensure public accountability for

recombinant DNA research and relevant

data, (2) implementation of Gene

Therapy Policy Conferences (GTPC) to

augment the quality and efficiency of

public discussion of the scientific merit

and the ethical issues relevant to gene

therapy clinical trials, and (3)

continuation of the publicly available,

comprehensive NIH database of human

gene transfer clinical trials, including

adverse event reporting.

Specifically, the NIH Director

proposes to realign and extend the

current roles and responsibilities of NIH

oversight of human gene transfer by

establishing OAC. This chartered

committee will be comprised of a

standing membership of 6 to 10

individuals representing the scientific,

legal, ethical, and public advocacy

communities. The OAC will meet

regularly to: (1) advise ORDA regarding

relevant gene therapy issues, (2) identify

and prioritize proposed conference

topics and participants, and (3)

periodically review and analyze data

submitted to the NIH gene therapy

database. Through ORDA, the OAC will

administer, propose modifications, and

promulgate amendments to the NIH

Guidelines. These NIH Guidelines,

which set forth accepted principles,

practices, and procedures under which

investigators and institutions may safely

conduct recombinant DNA research

under a variety of settings, will continue

to be the responsibility of the NIH

Director. Investigator compliance with

the relevant physical and biological

containment standards in the NIH

Guidelines ensures acceptable

protection for human health and the

environment.

The NIH Director proposes to convene

the Gene Therapy Policy Conferences at

regular intervals (3–4 times per year).

These conferences will offer the unique

advantage of assembling numerous

participants who possess significant

scientific, ethical, and legal expertise

and/or interest that is directly

applicable to a specific recombinant

DNA research issue. In order to enhance

the depth and value of scientific and

ethical/social discussion, each GTPC

will be devoted to a single issue relevant

to scientific merit and/or safety as it

relates to human gene therapy clinical

trials. These may include topics such as

basic research on the use of novel gene

delivery vehicles and applications to

human gene therapy, novel applications

of gene transfer, or relevant ethical/

societal implications of a particular

application of gene transfer technology.

Although NIH will no longer be

responsible for the approval of gene

therapy protocols, these modifications

do not preclude the use of a novel

protocol as a focus for a conference

discussion, i.e., a novel protocol

captured by the NIH database could be

added by OAC, in consultation with

ORDA, to a list of potential policy

conference topics.

The findings and recommendations of

the GTPC will be submitted to the NIH

Director and will be made available to

multiple Department of Health and

Human Services (DHHS) components,

including the FDA and the Office for

Protection from Research Risks (OPRR).

The NIH Director anticipates that this

expanded public policy forum will

serve as a model for interagency

communication and collaboration,

concentrated expert discussion of novel

scientific issues and their potential

societal implications, and enhanced

opportunity for public discussion of

specific issues and the potential impact

of such applications on human health

and the environment.

Finally, the NIH Director proposes to

maintain the administration of gene

therapy clinical trial data management

functions through ORDA and in

consultation with the OAC. Using

current definitions, NIH will continue to

capture incoming protocol information,

ongoing data (including adverse and

significant clinical events), and longterm follow-up data. In compliance with

the NIH Guidelines, investigators will

continue to be required to register

human gene transfer experiments with

ORDA to ensure continued public

access to the comprehensive human

gene transfer clinical trial database.

DATES: Written comments must be

received by August 7, 1996.

ADDRESSES: Written comments should

be submitted to the Office of

Recombinant DNA Activities, Office of

Science Policy, National Institutes of

Health, 6000 Executive Boulevard, Suite

302, Bethesda, Maryland, 20892–7010.

Fax transmissions may be sent to (301)

496–9839.

FOR FURTHER INFORMATION CONTACT:

Debra Knorr, Office of Recombinant

DNA Activities, 6000 Executive

Boulevard, Suite 302, Bethesda,

Maryland, 20892–7010, (301) 496–9838.

SUPPLEMENTARY INFORMATION:

I. Background

In 1974, the National Academy of

Sciences (NAS) established a Committee

on Recombinant DNA Molecules which

was charged with examining the risks

associated with recombinant DNA

research and recommending specific

actions or guidelines. The NAS

Committee report requested: (1) that

certain experiments be voluntarily

deferred; (2) that plans to construct

recombinants with animal DNA should

be carefully weighed; (3) that the NIH

Director establish a committee to

oversee a program to evaluate

hypothetical risks, to develop

procedures to minimize the spread of

recombinant DNA molecules, and to

recommend guidelines to be followed

by investigators; and (4) that an

international meeting be convened to

review progress and discuss ways to

deal with potential hazards.

In that same year, the Department of

Health, Education, and Welfare

(currently the Department of Health and

Human Services (DHHS)) chartered a

committee (later identified as the RAC)

in response to the NAS report. In 1975,
Federal Register / Vol. 61, No. 131 / Monday, July 8, 1996 / Notices 35775

RAC held its first meeting to establish

appropriate biological and physical

containment practices and procedures

that were later developed into a set of

guidelines for the safe conduct of

recombinant DNA research (the NIH

Guidelines). Subsequently, the NIH

created ORDA to provide administrative

support to the RAC.

In 1982, an in-depth examination of

the broad ethical implications of human

gene therapy research, The Social and

Ethical Issues of Genetic Engineering

with Human Beings (Splicing Life), was

published by the President—s

Commission for the Study of Ethical

Problems in Medicine and Biomedical

and Behavioral Research. Splicing Life

proposed that, ‘‘. . . since laboratory

biohazards related to recombinant DNA

research were no longer regarded as

urgent matters, the NIH should extend

its purview over recombinant DNA

research beyond environmental issues

to human gene therapy.’’

They recommended that the

membership of the RAC should be

broadened to include a combination of

Federal and non-Federal scientists, lay

public participants, and ethicists. In

response to Splicing Life, the NIH

established the RAC Human Gene

Therapy Subcommittee which was

subsequently merged with the parent

committee to become the current RAC.

II. Rationale for Change

In recognition of the committee’s

critical role in maintaining public

accountability for recombinant DNA

research, the NIH Director weighed a

variety of factors prior to announcing

NIH’s intent to change and enhance its

current oversight responsibilities for

recombinant DNA research. In order to

clarify the rationale for the proposed

changes described herein, a series of

questions and answers are provided

below.

1. On what basis does the NIH conclude

that this is the optimal time to eliminate

the RAC and realign NIH’s

responsibilities to public discussion and

data management of human gene

therapy clinical trials?

Since its inception, the NIH has

continuously relinquished oversight of

various elements in the field of

recombinant DNA research, as such

elements reached maturity. From l979–

l983, several major revisions were made

to the NIH Guidelines when putative

risks to the public did not materialize

and the initial restrictions were deemed

unnecessary. In 1991, the NIH’s

oversight of environmental release of

genetically modified organisms was

relinquished and these responsibilities

were ceded to the U.S. Department of

Agriculture and the Environmental

Protection Agency. These changes were,

in part, motivated by the recognition

that NIH did not have the statutory

authority or the ‘‘tools’’ to function as a

regulatory agency.

In 1995, a similar devolution of NIH

oversight of human gene therapy

occurred. By this time, the RAC had

reviewed and approved 113 gene

therapy protocols and over 1,000

patients had been enrolled in worldwide trials. The RAC, the scientific

community, and the public had a

substantial base of information

regarding the use and safety of many of

the vectors employed in, and target

diseases addressed by, human gene

therapy. Subsequent analyses revealed

that the human health and

environmental safety concerns

expressed at the inception of gene

therapy clinical trials had not

materialized. Absent evidence for

substantial safety concerns for gene

therapy protocols which have been

previously tested, on March 6, 1995, the

RAC voted to recommend approval of

amendments to the NIH Guidelines that

would eliminate RAC review and

approval of human gene therapy

experiments not considered to be novel.

Under this mechanism, all protocols

determined not to represent a novel

gene therapy delivery strategy or target

disease that could adversely affect

human health were considered exempt

from RAC review and approval and

were forwarded directly to the FDA.

This streamlined process, which became

known as the NIH and FDA

‘‘Consolidated Review,’’ eliminated

unnecessary and time consuming

duplication of effort by the NIH and the

FDA. On April 17, 1995, the NIH

Director approved these amendments to

the NIH Guidelines. Once again, the NIH

relinquished a portion of its oversight of

recombinant DNA research to the

agency (FDA) with statutory

responsibility to approve such

protocols.

Since the implementation of

consolidated review in July 1995, only

six of the 36 protocols submitted to

ORDA required RAC review and

approval; and five of those six protocols

were already in the system before

consolidated review. The consolidated

review process proved to be so

successful in eliminating the need for

RAC review and approval, that NIH

canceled both the March and June 1996

RAC meetings due to the lack of novel

protocols requiring RAC attention.

The NIH Director has concluded that

the current proposal to enhance NIH

oversight of recombinant DNA activities

is timely and appropriate based on the

current base of knowledge, the need for

substantial discussion of gene therapy

techniques which are not yet being

tested in humans, and the duplication of

review and approval by the NIH while

the FDA holds the statutory authority.

Thus, the NIH Director proposes the

termination of the RAC, relinquishing of

all protocol approval to the FDA and the

creation of two new entities to enhance

the depth and breadth of public

discussion of gene therapy issues.

2. Why does the NIH propose to replace

the RAC?

The proposed actions regarding the

RAC should not be viewed narrowly as

‘‘eliminating’’ the RAC. Rather, these

actions were developed in a timely and

appropriate response to a series of

publicly debated discussions over a

period of several years. The NIH

Director maintains that the

establishment of the OAC and the

convening of the GTPC are effective and

innovative responses to this rapidly

changing area of biomedical research

based on the foundation of scientific

knowledge that has been gained over the

last six years and overlapping

responsibilities of other Federal

agencies. This proposal optimizes

current Federal resources, maintains

public access to information, and

facilitates public discussion of novel

issues relevant to human gene therapy

research. NIH concludes that it is not

the RAC per se that is critical for public

accountability, but the system by which

NIH continues to provide public

discussion of the scientific, safety, and

ethical/legal issues related to human

gene therapy.

As proposed, the OAC will provide a

smaller, but fully representational,

standing committee with a range of

advisory and administrative oversight

responsibilities similar, but not

identical to, the RAC. In contrast,

participation in the proposed GTPC will

be subject to recommendations by the

OAC and ORDA and, as such, will

provide the necessary flexibility to

engender in-depth, expert discussion of

scientific issues and societal

implications that cannot be achieved

under current mechanisms. The GTPC

will continue to maintain favorable RAC

attributes such as continued public

access to conference discussions and

recommendations, publication of

scheduled meeting dates and proposed

agendas in the Federal Register, and

publication of official conference

minutes. Eliminating RAC protocol

approval reduces duplication of effort

with the FDA while enhancing the time

and effort devoted to both ongoing and
35776 Federal Register / Vol. 61, No. 131 / Monday, July 8, 1996 / Notices

anticipated gene therapy policy issues

deserving of substantial public

discussion.

3. Why not continue RAC review and

approval of gene therapy protocols?

In 1990, when the RAC first turned its

attention to human gene therapy, the

NIH was the sole source of the

substantial expertise necessary to

review the relatively new field of

human gene therapy. Since that time,

the FDA has created a new Division of

Cellular and Gene Therapies and has

committed substantial resources to the

development of review capabilities in

this arena. At its inception, it was

critical for the RAC to conduct a caseby-case review of human gene transfer

protocols, since each new protocol

invariably set a new precedent. Six

years later, the RAC has relinquished

most of its review and approval

activities under the ‘‘consolidated’’

review plan which forwards all but

novel protocols directly to the FDA for

consideration.

During the six years of RAC review

and approval, there has been

considerable discussion of the

juxtaposition of the NIH mandate to

oversee the most meritorious medical

research and the RAC mission to

approve or disapprove individual

protocols based predominantly on

issues of safety. By adopting a new

model of public discussion that does not

require approval, the NIH can, through

the proposed policy conferences, engage

in substantive critique of the scientific

merit of a line of research without

having to give an NIH stamp of approval

on the basis of limited threat to human

health or safety.

4. Did NIH accept the recommendations

of the RAC Ad Hoc Advisory Committee

(Verma Committee)?

The decision to retire the RAC does

not foreclose on the recommendations

of the Verma Committee. The NIH

Director accepted most of the

recommendations of the RAC Ad Hoc

Review Committee. However, rather

than implement the recommendations

through the RAC, the Director proposes

a new structure for NIH oversight of

human gene therapy.

Specifically: (1) The first

recommendation calls for continuation

of consolidated review by the RAC.

Under the proposal contained herein,

the RAC is eliminated and consolidated

review will not be maintained. (2) A

second recommendation calls for an

open public forum for discussion of

protocols which contain a new

technology or novel departures in

human gene transfer research. The

proposed Gene Therapy Policy

Conferences will not only preserve such

a forum, but will provide for more indepth discussion of both the science

and the ethical issues related to a

specific gene therapy issue. In this

manner, it will enhance the type of

public access that has been

characteristic of the RAC. Although this

proposal does not provide for review

and approval of individual protocols, it

does not preclude the use of a novel

protocol as a focus for a conference

discussion; a novel protocol captured by

the NIH database could be raised by the

OAC, in consultation with ORDA, to the

list of policy conference topics. (3) The

recommendation that RAC should

develop criteria for consolidated review

would not be applicable to the proposed

new structure, since this proposal cedes

review and approval to the FDA.

However, as stated above, the OAC will

have the authority to recommend a

novel protocol captured by the NIH

database for public discussion at a

policy conference. (4) The fourth

recommendation that the RAC should

provide advice on policy matters

revolving around gene therapy and

other recombinant DNA issues would be

fully met by the proposed Gene Therapy

Policy Conferences. Because each of

these conferences will focus on a single

issue, it is the Director’s contention that

policy advice will be substantially

augmented under this new mechanism.

The NIH cannot, however, give the RAC,

or any other NIH standing or ad hoc

body, the authority to give policy advice

or make recommendations to the FDA.

The NIH has had and will continue to

have open and frequent dialogue with

the FDA about gene therapy policy

matters related to safety, scientific and

ethical issues and fully expects the FDA

to recommend policy conference topics

to OAC and ORDA. (5) The proposed

maintenance of the NIH gene therapy

database fully responds to the

recommendation regarding the

continued need for data monitoring and

adverse event reporting. The Office of

Recombinant DNA Activities (ORDA)

has retained the services of a contractor

to assist in the development of a

computer software package that will

have sufficient capacity to monitor and

evaluate gene transfer protocols.

5. Will there be a mechanism for

continuing to review gene therapy

informed consent documents?

As needs dictate, both OAC and the

GTPC will provide a forum for the

oversight of human gene therapy

informed consent. It is expected that an

entire conference may be devoted to

such informed consent issues in the

context of gene therapy. The NIH

Director will continue, when

appropriate, to make amendments to

sections of the NIH Guidelines, Points to

Consider relevant to informed consent

procedures during gene therapy clinical

trials. Investigators and IRBs engaged in,

or reviewing, human gene therapy trials

are expected to employ the NIH

Guidelines, Points to Consider for this

purpose. However, under the proposal

contained herein, neither the OAC nor

the GTPC will engage in protocol-byprotocol review of informed consent

documents.

The sixteen Federal agencies that

engage in human subjects research

reference the Common Rule and, thus,

abide by the principle of giving full

authority of individual approval of

informed consent documents to locally

constituted Institutional Review Boards

(IRBs). These responsibilities remain

solely within the regulatory framework

of OPRR through the local IRBs. OPRR

oversees implementation of 45 CFR Part

46 in all domestic and foreign

institutions or sites receiving DHHS

funds. OPRR requires each institution

that conducts or supports research

involving human subjects to set forth

the procedures it will use to protect

human subjects in a policy statement

called an Assurance of Compliance.

Finally, there is no other disease,

disability, or methodology that, at

present, requires a Federal review of

individual informed consent

documents. It is the proposal of the NIH

Director that human gene therapy

informed consent documents be subject

to the same procedures as all other

forms of human subject research.

OMB’s ‘‘Mandatory Information

Requirements for Federal Assistance

Program Announcements’’ (45 FR

39592, June 11, 1980) requires a

statement concerning the official

government programs contained in the

Catalog of Federal Domestic Assistance.

Normally, NIH lists in its

announcements the number and title of

affected individual programs for the

guidance of the public. Because the

guidance in this notice covers not only

virtually every NIH program but also

essentially every Federal research

program in which DNA recombinant

molecule techniques could be used, it

has been determined not to be cost

effective or in the public interest to

attempt to list these programs. Such a

list would likely require several

additional pages. In addition, NIH could

not be certain that every Federal

program would be included as many

Federal agencies, as well as private

organizations, both national and

international, have elected to follow the
Federal Register / Vol. 61, No. 131 / Monday, July 8, 1996 / Notices 35777

NIH Guidelines. In lieu of the individual

program listing, NIH invites readers to

direct questions to the information

address above about whether individual

programs listed in the Catalog of

Federal Domestic Assistance are

affected.

Dated: June 28, 1996.

Harold Varmus,

Director, National Institutes of Health.

[FR Doc. 96–17349 Filed 7–5–96; 8:45 am]

BILLING CODE 4140–01–P

DEPARTMENT OF HOUSING AND

URBAN DEVELOPMENT

Office of the Assistant Secretary for

Housing—Federal Housing

Commissioner

[Docket No. FR–4032–N–02]

Notice of Proposed Information

Collection: Comment Request

AGENCY: Office of the Assistant

Secretary for Housing, HUD.

ACTION: Notice.

SUMMARY: The proposed information

collection requirement described below

will be submitted to the Office of

Management and Budget (OMB) for

review, as required by the Paperwork

Reduction Act. The Department is

soliciting public comments on the

subject proposal.

DATES: Comments due: September 6,

1996.

ADDRESSES: Interested persons are

invited to submit comments regarding

this proposal. Comments should refer to

the proposal by name and/or OMB

Control Number and should be sent to:

Oliver Walker, Reports Liaison Officer,

Office of Housing, Department of

Housing & Urban Development, 451 7th

Street, SW, Room 9116, Washington, DC

20410.

FOR FURTHER INFORMATION CONTACT:

Oliver Walker, Room 9116, Department

of Housing and Urban Development,

451 7th Street, SW, Washington, DC

20410, (202) 708–1694, or, TTY for

hearing and speech impaired, (202)

708–4594 (these are not toll-free

numbers) for copies of the proposed

collection of information.

SUPPLEMENTARY INFORMATION: The

Department will submit the proposed

information collection to OMB for

review, as required by the information

collection to OMB for review, as

required by the Paperwork Reduction

Act of 1995 (44 U.S.C. chapter 35, as

amended).

The Notice is soliciting comments

from members of the public and

affecting agencies concerning the

proposed collection of information to:

(1) Evaluate whether the proposed

collection of information is necessary

for the proper performance of the

functions of the agency, including

whether the information will have

practical utility; (2) Evaluate the

accuracy of the agency’s estimate of the

burden of the proposed collection of

information; (3) Enhance the quality,

utility, and clarity of the information to

be collected; and (4) Minimize the

burden of the collection of information

on those who are to respond; including

through the use of appropriate

automated collection techniques or

other forms of information technology,

e.g., permitting electronic submission of

responses.

This Notice also lists the following

information:

Title of Proposal: Single Family

Mortgage Insurance—Loss Mitigation

Procedures

OMB Control Number, if applicable:

[N/A—none yet assigned]

Description of the need for the

information and proposed use: New

section 24 CFR 203.605, ‘‘Loss

Mitigation Evaluation,’’ requires

mortgagees to perform an evaluation of

each defaulting mortgagor’s

circumstances to determine which if

any of the available loss mitigation

techniques are appropriate in order to

assist the mortgagor to:

(a) Reinstate the mortgage and retain

ownership of the affected property, or

(b) Avoid foreclosure, and mitigate

the losses to the Department by

encouraging the mortgagor to sell the

property or, if the mortgagor has no

equity in the property, to pursue a buyer

under the pre-foreclosure (’’short’’) sale

procedure or to voluntarily convey the

deed in lieu of what would otherwise be

the imminent foreclosure of the

mortgage.

This evaluation must be performed no

later than when three monthly mortgage

installments are due and unpaid, and

must be performed monthly thereafter

while the account is in default and such

foreclosure avoidance and loss

mitigation options remain under

consideration.

This information is needed to

ascertain whether adequate and prudent

loan servicing was performed by the

mortgagee. If a mortgagee submits a

claim for FHA insurance benefits, this

information will be subject to post-claim

review under the Department’s lender

monitoring activities.

Agency form numbers, if applicable:

Documentation simply added to

lender’s servicing files on HUD–27011

insurance claim form.

Members of affected public:

Mortgagees, loan servicing entities.

Estimation of the total numbers of

hours needed to prepare the information

collection, including:

(a) Number of respondents: Each FHA

approved lender will be required to

respond as part of standard procedures

for servicing defaulted loans.

(b) Frequency of response: 625,000

(based on 250,000 90-day defaults; 50%

self-cure; 125,000 90+ day defaults

averaging 3-additional months).

(c) Hours of response: 625,000 @ 0.25

hrs = 156,250 hours.

Status of the proposed information

collection: Pending approval.

Authority: Section 3506 of the Paperwork

Reduction Act of 1995, 44 U.S.C. chapter 35,

as amended.

Dated: June 27, 1996.

Nicolas P. Retsinas,

Assistant Secretary for Housing—Federal

Housing Commissioner.

[FR Doc. 96–17176 Filed 7–5–96; 8:45 am]

BILLING CODE 4210–27–M

[Docket Nos. FR–3903–N–04 and FR–3904–

N–05]

Announcement of Funding Awards for

Supportive Housing for the Elderly and

Persons With Disabilities, FY 1995

AGENCY: Office of the Assistant

Secretary for Housing—Federal Housing

Commissioner, HUD.

ACTION: Announcement of funding

awards.

SUMMARY: In accordance with section

102(a)(4)(C) of the Department of

Housing and Urban Development

Reform Act of 1989, this announcement

notifies the public of funding award

decisions made by the Department as a

result of competitions for funding under

the following two notices of funding

availability: Supportive Housing for the

Elderly and Supportive Housing for

Persons with Disabilities. This

announcement contains the names and

addresses of the awardees and the

amount of the award.

FOR FURTHER INFORMATION CONTACT:

Jane Luton, Division Director, New

Product Division, Office of Multifamily

Housing Division, Department of

Housing and Urban Development, Room

6142, 451 Seventh Street SW.,

Washington, DC 20410–0500; telephone

(202) 708–2866. (This is not a toll-free

number.) A telecommunications device

for hearing- and speech-impaired

individuals (TTY) is available at 1–800–

877–8339 (Federal Information Relay

Service).