[Federal Register Volume 62, Number 200 (Thursday, October 16, 1997)]
[Notices]
[Pages 53908-53910]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-27312]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Recombinant DNA Research: Proposed Actions Under the Guidelines

AGENCY: National Institutes of Health (NIH), PHS, DHHS.

ACTION: Notice of proposed actions under the NIH Guidelines for 
Research Involving Recombinant DNA Molecules (NIH Guidelines).

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SUMMARY: This notice sets forth proposed actions to be taken under the 
NIH Guidelines for Research Involving Recombinant DNA Molecules (59 FR 
34496, amended 59 FR 40170, 60 FR 20726, 61 FR 1482, 61 FR 10004, 62 FR 
4782). Interested parties are invited to submit comments concerning 
these proposals. These proposals will be considered by the Recombinant 
DNA Advisory Committee (RAC) at its meeting on December 15-16, 1997. 
After consideration of these proposals and comments by the RAC, the NIH 
Director will issue decisions in accordance with the NIH Guidelines.

DATES: Interested parties are invited to submit comments concerning the 
proposed actions. Comments received by December 8, 1997, will be 
reproduced and distributed to the RAC for consideration at its December 
15-16, 1997, meeting. After consideration of this proposal and comments 
by the RAC, the NIH Director will issue decisions in accordance with 
the NIH Guidelines.

ADDRESSES: Written comments and recommendations should be submitted to 
Debra Knorr, Office of Recombinant DNA Activities, National Institutes 
of Health, MSC 7010, 6000 Executive Boulevard, Suite 302, Bethesda, 
Maryland 20892-7010, Phone 301-496-9838, FAX 301-496-9839.
    All comments received in response to this notice will be considered 
and will be available for public inspection in the above office on 
weekdays between the hours of 8:30 a.m. and 5 p.m.

FOR FURTHER INFORMATION CONTACT:
Background documentation and additional information can be obtained 
from the Office of Recombinant DNA Activities, National Institutes of 
Health, MSC 7010, 6000 Executive Boulevard, Suite 302, Bethesda, 
Maryland 20892-7010, Phone 301-496-9838, FAX 301-496-9839. The Office 
of Recombinant DNA Activities web site is located at <a href="http://
www.nih.gov/od/orda">http://
www.nih.gov/od/orda</a> for further information about the office.

I. Supplementary Information

    The NIH will consider the following actions under the NIH 
Guidelines for Research Involving Recombinant DNA Molecules (NIH 
Guidelines):

I-A. Amendment to Appendix M-I, Submission Requirements--Human Gene 
Transfer Experiments, Under the NIH Guidelines

    During the June 12-13, 1997, RAC meeting, the following motions 
were approved by the Committee:
    (1) A motion was made that Appendix M-I, Submission Requirements--
Human Gene Transfer Experiments, should be amended to require 
investigators to submit documentation verifying that a human gene 
transfer protocol has been submitted to an appropriate Institutional 
Biosafety Committee (IBC). Evidence of IBC notification shall be 
provided at the time the protocol is submitted to ORDA. The motion 
passed by a vote of 8 in favor, 1 opposed, and no abstentions.
    (2) A motion was made to delete the requirement for submission of 
IBC and Institutional Review Board (IRB) approvals at the time of ORDA 
submission from Appendix M-I, Submission Requirements--Human Gene 
Transfer Experiments, of the NIH Guidelines. The motion passed by a 
vote of 7 in favor, 0 opposed, and 1 abstention.
    On September 10, 1997, a letter was received from the American 
Biological Safety Association requesting that the public comment period 
for the proposed actions under the NIH Guidelines published in the 
Federal Register on August 20, 1997 (62 FR 44387) be extended for an 
additional 60 days.
    During the September 12, 1997, RAC meeting, the RAC was scheduled 
to vote on the proposed actions to delete prior IBC and IRB approvals 
from the submission requirements, and to require investigators or 
sponsors to provide evidence of protocol submission to IBC.

[[Page 53909]]

Considering the request by the American Biological Safety Association 
to extend the public comment period, the RAC decided to modify the 
language of the proposed actions and to publish the revised version in 
the Federal Register for an additional 60 days.
    A motion was made by the RAC to amend the proposed actions 
published in the Federal Register on August 20, 1997, regarding the 
submission requirements as follows:
    ``The RAC recommends that final approvals from IBC and IRB should 
be withheld until after NIH/ORDA provides the IBC and IRB with RAC 
concerns (if any), and (1) NIH/ORDA notification that the protocol is 
exempt from full RAC review, or (2) NIH/ORDA notification that the 
protocol has triggered full RAC review. Human gene transfer protocols 
shall not be initiated prior to submission of final IBC and IRB 
approvals to NIH/ORDA.''
    The motion passed by a vote of 10 in favor, 0 opposed, and 2 
abstentions.

I-B. Amendments to Institutional Biosafety Committee (IBC) Approvals of 
Experiments Involving Transgenic Rodents Under Section III of the NIH 
Guidelines

    Section III-C-4, Experiments Involving Whole Animals, of the NIH 
Guidelines stipulates that all transgenic animal experiments are 
subject to IBC approval before initiation. In a correspondence dated 
April 22, 1997, Dr. George Gutman, an IBC representative of the 
University of California, Irvine, California, inquired whether 
experiments involving production or use of transgenic mice under 
Biosafty Level 1 containment could be initiated simultaneous with IBC 
notification. Current requirements under the NIH Guidelines require 
that IBC approval be obtained prior to initiation of such experiments.
    The RAC discussed this issue during its June 1997 meeting, 
recommending that this requirement be changed to initiation 
simultaneous with IBC notification. The RAC agreed that the requirement 
for IBC approval prior to initiation is unnecessary and recommended 
that the NIH Guidelines should be amended such that: (1) The generation 
of transgenic rodents at the Biosafety Level 1 containment (not all 
animals ) can be initiated simultaneous with IBC notification, and (2) 
the purchase and use of transgenic rodents should be exempt from the 
NIH Guidelines. A motion was made that these proposed changes to the 
NIH Guidelines should be published it the Federal Register for 
consideration at the September 12, 1997, RAC meeting. The proposed 
action would allow: (1) The generation of transgenic rodents that 
require Biosafety Level 1 containment to be included under Section III-
D, Experiments that Require IBC Notice Simultaneous with Initiation; 
and (2) the purchase and use of transgenic rodents should be exempt 
from the NIH Guidelines. The motion passed by a vote of 9 in favor, 0 
opposed, and no abstentions.
    On September 10, 1997, a letter was received from the American 
Biological Safety Association requesting that the public comment period 
for the proposed actions under the NIH Guidelines published in the 
Federal Register on August 20, 1997 (62 FR 44387) be extended for an 
additional 60 days.
    During the September 12, 1997, RAC meeting, the RAC was scheduled 
to vote on the issues surrounding the amendments to IBC approvals of 
experiments involving transgenic rodents. Considering the request by 
the American Biological Safety Association to extend the public comment 
period, the RAC decided to modify the language of the proposed actions 
and to publish the revised version in the Federal Register for 
additional public comment as requested by the American Biological 
Safety Association. The RAC accepted the proposed actions with the 
deletion of two words ``and use'' from the language, ``the purchase and 
use of transgenic rodent * * *'' A motion was made by the RAC to accept 
the amendments to the NIH Guidelines with regard to: (1) The generation 
of transgenic rodents at the Biosafety Level 1 containment (not all 
animals) can be initiated simultaneously with IBC notification, and (2) 
the purchase of transgenic rodents should be exempt from the NIH 
Guidelines. The motion passed by a vote of 11 in favor, 0 opposed, and 
no abstentions.

II. Proposed Actions Regarding Amendments to the NIH Guidelines

    The NIH will consider the following proposed actions under the NIH 
Guidelines:

II-A. Proposed Amendments to Section III-C-4, Experiments Involving 
Whole Animals

[Section III-C are experiments that require Institutional Biosafety 
Committee approval before initiation.]
    Section III-C-4-c is proposed to be amended to read:
    ``Section III-C-4-c. Exceptions under Section III-C-4.
    ``Section III-C-4-c-(1). Experiments involving the generation of 
transgenic rodents that require BL1 containment are described under 
Section III-D-3, Experiments Involving Transgenic Rodents.
    ``Section III-C-4-c-(2). The purchase of transgenic rodents is 
exempt from the NIH Guidelines under Section III-E, Exempt Experiments 
(see Appendix C-VI, The Purchase of Transgenic Rodents).''

II-B. Proposed Amendments to Section III-D, Experiments That Require 
Institutional Biosafety Committee Notice Simultaneous With Initiation

    Section III-D-3 is proposed to be amended to read:
    ``Section III-D-3. Experiments Involving Transgenic Rodents
    ``This section covers experiments involving the generation of 
rodents in which the animal's genome has been altered by stable 
introduction of recombinant DNA, or DNA derived therefrom, into the 
germ-line (trangenic rodents). Only experiments that require BL1 
containment are covered under this section; experiments that require 
BL2, BL3, or BL4 containment are covered under Section III-C-4, 
Experiments Involving Whole Animals.''

II-C. Proposed Amendments to Appendix C, Exemptions Under Section III-
E-6

    A new section, Appendix C-VI, is proposed to read:

``Appendix C-VI. The Purchase of Transgenic Rodents

    ``The purchase of transgenic rodents for experiments that require 
BL1 containment are exempt from the NIH Guidelines.''

[The old Appendix C-VI, Footnotes and References of Appendix C, will be 
renumbered to Appendix C-VII through Appendix C-VII-E.]

II-D. Proposed Amendments to Appendix M, The Points To Consider in the 
Design and Submission of Protocols for the Transfer of Recombinant DNA 
Molecules Into the Genome of One or More Human Subjects (Points To 
Consider)

    Appendix M-I is proposed to be amended to read:

``Appendix M-I. Submission Requirements--Human Gene Transfer 
Experiments

    ``Investigators must submit the following material to the Office of 
Recombinant DNA Activities, National Institutes of Health/MSC 7010, 
6000 Executive Boulevard, Suite 302, Bethesda, Maryland 20892-7010, 
301-496-9838 (see exemption in Appendix M-IX-A, Footnotes of Appendix 
M). Proposals will be submitted in the

[[Page 53910]]

following order: (1) Scientific abstract; (2) non-technical abstract; 
(3) Responses to Appendix M-II through Appendix M-V, Description of the 
Proposal, Informed Consent, Privacy and Confidentiality, and Special 
Issues (the pertinent responses can be provided in the clinical 
protocol or as an appendix to the clinical protocol); (4) clinical 
protocol (as submitted to the local IBC and IRB); (5) Informed Consent 
document prepared for IRB submission (see Appendix M-III, Informed 
Consent); (6) a letter stating that submission has been made to the 
IBC; (7) appendices (including tables, figures, and manuscripts); and 
(8) curricula vitae for each key professional person in biographical 
sketch format.

    Note: The final approvals from IBC and IRB should be withheld 
until after NIH/ORDA provides IBC and IRB with RAC concerns (if 
any), and (1) NIH/ORDA notification that the protocol is exempt from 
full RAC review, or (2) NIH/ORDA notification that the protocol has 
triggered full RAC review. Human gene transfer protocols shall not 
be initiated prior to submission of final IBC and IRB approvals to 
NIH/ORDA.

III. Addition to Appendix D of the NIH Guidelines Regarding a Human 
Gene Transfer Protocol/Dr. Crystal

    In a letter dated August 25, 1997, Dr. Ronald Crystal of New York 
Hospital-Cornell Medical Center, New York, New York, submitted a human 
gene transfer protocol entitled: Systemic and Respiratory Immune 
Response to Administration of an Adenovirus Type 5 Gene Transfer Vector 
(Ad<INF>GV</INF>CD.10) (NIH Protocol 9708-209) to NIH/ORDA in 
accordance with Appendix M-I, Submission Requirements--Human Gene 
Transfer Experiments, of the NIH Guidelines. Dr. Crystal requested 
permission to present a brief overview of relevant data during the 
September 12, 1997, RAC meeting, prior to the RAC's final 
recommendation on the necessity for full RAC review. The RAC agreed to 
allow Dr. Crystal to give a brief presentation on the relevant data. 
Following the September 12, 1997, RAC meeting, the RAC noted that there 
were a significant number of issues remaining; therefore, the protocol 
should be discussed by the full RAC at its next scheduled meeting.

IV. Discussion on Novel Gene Transfer Technologies

    The RAC will have a discussion on novel gene transfer technologies. 
Presentations may include herpesvirus vectors and human artificial 
chromosomes.
    OMB's ``Mandatory Information Requirements for Federal Assistance 
Program Announcements'' (45 FR 39592) 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 to be not 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 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: October 8, 1997.
Lana R. Skirboll,
Associate Director for Science Policy, National Institutes of Health.
[FR Doc. 97-27312 Filed 10-11-97; 8:45 am]
BILLING CODE 4140-01-M