[Federal Register Volume 59, Number 90 (Wednesday, May 11, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-11466]
[[Page Unknown]]
[Federal Register: May 11, 1994]
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Part IX
Department of Health and Human Services
_______________________________________________________________________
National Institutes of Health
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Recombinant DNA Research: Proposed Actions Under the Guidelines; Notice
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Recombinant DNA Research: Proposed Actions Under the Guidelines
AGENCY: National Institutes of Health, PHS, HHS.
ACTION: Notice of proposed actions under the NIH guidelines for
research involving recombinant DNA molecules (51 FR 16958).
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SUMMARY: This notice sets forth proposed actions to be taken under the
National Institutes of Health (NIH) Guidelines for Research Involving
Recombinant DNA Molecules (51 FR 16958). Interested parties are invited
to submit comments concerning these proposals. These proposals will be
considered by the Recombinant DNA Advisory Committee at its meeting on
June 9-10, 1994. After consideration of these proposals and comments by
the Recombinant DNA Advisory Committee, the Director of the National
Institutes of Health will issue decisions in accordance with the NIH
Guidelines.
DATES: Comments received by May 26, 1994, will be reproduced and
distributed to the Recombinant DNA Advisory Committee for consideration
at its June 9-10, 1994, meeting.
ADDRESSES: Written comments and recommendations should be submitted to
Dr. Nelson A. Wivel, Director, Office of Recombinant DNA Activities
(ORDA), building 31, room 4B11, National Institutes of Health,
Bethesda, Maryland 20892, or sent by FAX to 301-496-9839.
All comments received in timely 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, building 31, room 4B11,
National Institutes of Health, Bethesda, Maryland 20892, (301) 496-
9838.
SUPPLEMENTARY INFORMATION: The NIH will consider the following actions
under the NIH Guidelines for Research Involving Recombinant DNA
Molecules:
I. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Drs. Sobol and Royston
In a letter dated October 6, 1993, Drs. Robert Sobol and Ivor
Royston of the San Diego Regional Cancer Center, San Diego, California,
submitted the human gene transfer protocol entitled: Injection of
Glioblastoma Patients with Tumor Cells Genetically Modified to Secrete
Interleukin-2 (IL-2): A Phase I Study to the Recombinant DNA Advisory
Committee for formal review and approval. At the December 2-3, 1993,
meeting, the Recombinant DNA Advisory Committee disapproved the
original protocol. The majority of the Recombinant DNA Advisory
Committee members concluded that the preclinical data derived from a
previous single patient protocol was inadequate to justify the
experiment. The motion to disapprove the protocol passed by a vote of
10 in favor, 5 opposed, and 1 abstention.
In a letter dated April 8, 1994, Drs. Sobol and Royston submitted a
revised protocol to the Recombinant DNA Advisory Committee for formal
review and approval.
II. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Dr. Curiel
In a letter dated April 13, 1994, Dr. David Curiel of the
University of Alabama, Birmingham, Alabama, submitted the human gene
transfer protocol entitled: Phase I Trial of a Polynucleotide Vaccine
to Human Carcinoembryonic Antigen in Patients with Metastatic
Colorectal Cancer to the Recombinant DNA Advisory Committee for formal
review and approval.
III. Addition to Appendix D of the NIH Guidelines Regarding a Human
Gene Transfer Protocol/Drs. Evans and Robbins
In a letter dated April 13, 1994, Drs. C. H. Evans and Paul Robbins
of the University of Pittsburgh, Pittsburgh, Pennsylvania, submitted
the human gene transfer protocol entitled: Clinical Trial to Assess the
Safety, Feasibility, and Efficacy of Transferring a Potentially Anti-
arthritic Cytokine Gene to Human Joints with Rheumatoid Arthritis to
the Recombinant DNA Advisory Committee for formal review and approval.
IV. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Drs. Heslop, Brenner, and Krance
In a letter dated April 6, 1994, Drs. Helen Heslop, Malcolm
Brenner, and Robert Krance of the St. Jude Children's Research
Hospital, Memphis, Tennessee, submitted the human gene transfer
protocol entitled: Use of Double Marking with Retroviral Vectors to
Determine Rate of Reconstitution of Untreated and Cytokine Expanded
CD34(+) Selected Marrow Cells in Patients Undergoing Autologous Bone
Marrow Transplantation to the Recombinant DNA Advisory Committee for
formal review and approval.
V. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Dr. Lyerly
In a letter dated April 12, 1994, Dr. H. Kim Lyerly of Duke
University Medical Center, Durham, North Carolina, submitted the human
gene transfer protocol entitled: A Pilot Study of Autologous Human
Interleukin-2 Gene Modified Tumor Cells in Patients with Refractory or
Recurrent Metastatic Breast Cancer to the Recombinant DNA Advisory
Committee for formal review and approval.
VI. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Drs. Economou, Glaspy, and McBride
In a letter dated April 11, 1994, Drs. James Economou, John Glaspy,
and William McBride of the University of California, Los Angeles,
California, submitted a human gene transfer protocol entitled: A Phase
I Testing of Genetically Engineered Interleukin-7 Melanoma Vaccines to
the Recombinant DNA Advisory Committee for formal review and approval.
VII. Addition to Appendix D of the NIH Guidelines Regarding a Human
Gene Transfer Protocol/Dr. Freedman
In a letter dated March 22, 1993, Dr. Ralph Freedman of M.D.
Anderson Cancer Center, Houston, Texas, submitted the human gene
transfer protocol entitled: Use of a Retroviral Vector to Study the
Trafficking Patterns of Purified Ovarian Tumor Infiltrating Lymphocyte
(TIL) Populations Used in Intraperitoneal Adoptive Immunotherapy of
Ovarian Cancer Patients: A Pilot Study to the Recombinant DNA Advisory
Committee for formal review and approval. At its June 7-8, 1993,
meeting the Recombinant DNA Advisory Committee deferred the protocol
until the investigators return to the full Recombinant DNA Advisory
Committee with the following:
(1) Data demonstrating efficient transduction of TIL,
(2) Sufficient information regarding demonstration of selectivity,
i.e., specific trafficking of TIL to tumor,
(3) Complete statistical analysis,
(4) Revised Informed Consent document in simplified language, and
(5) Address concerns about patient responsibility for research-
related costs. The motion to defer the protocol pending full
Recombinant DNA Advisory Committee review of additional information
passed by a vote of 18 in favor, 0 opposed, and no abstentions.
In a letter dated January 5, 1994, Dr. Freedman submitted a revised
protocol to the Recombinant DNA Advisory Committee for formal review
and approval. At its March 3-4, 1994, meeting, the Recombinant DNA
Advisory Committee deferred the protocol until the investigator returns
to the full Recombinant DNA Advisory Committee with:
(1) A modified protocol, which includes a revised treatment schema
that will provide statistically significant information, and
(2) A revised Informed Consent document that adequately describes
the procedures that will be performed in language understandable to lay
persons. The motion to defer the protocol pending full Recombinant DNA
Advisory Committee review of the additional information passed by a
vote of 12 in favor, 1 opposed, and no abstentions.
In a letter dated April 13, 1994, Dr. Freedman submitted a revised
protocol to the Recombinant DNA Advisory Committee for formal review
and approval.
VIII. Addition to Appendix D of the NIH Guidelines Regarding a Human
Gene Transfer Protocol/Drs. Deisseroth, Hortobagyi, and Champlin
In a letter dated April 12, 1994, Drs. Albert Deisseroth, Gabriel
Hortobagyi, and Richard Champlin of the M.D. Anderson Cancer Center,
Houston, Texas, submitted the human gene transfer protocol entitled:
Use of Safety-Modified Retroviruses to Introduce Chemotherapy
Resistance Sequences into Normal Hematopoietic Cells for
Chemoprotection During the Therapy of Breast Cancer: A Pilot Trial to
the Recombinant DNA Advisory Committee for formal review and approval.
IX. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Dr. Roth
In a letter dated April 12, 1994, Dr. Jack Roth of M.D. Anderson
Cancer Center, Houston, Texas, submitted the human gene transfer
protocol entitled: Clinical Protocol for Modification of Tumor
Suppressor Gene Expression and Induction of Apoptosis in Non-Small Cell
Lung Cancer (NSCLC) with an Adenovirus Vector Expressing Wildtype p53
and Cisplatin to the Recombinant DNA Advisory Committee for formal
review and approval.
X. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Dr. Lotze
In a letter dated April 13, 1994, Dr. Michael Lotze of the
University of Pittsburgh, Pittsburgh, Pennsylvania submitted the human
gene transfer protocol entitled: IL-12 Gene Therapy Using Direct
Injection of Tumor with Genetically Engineered Autologous Fibroblasts
to the Recombinant DNA Advisory Committee for formal review and
approval.
XI. Addition to Appendix D of the NIH Guidelines Regarding a Human Gene
Transfer Protocol/Drs. Liu and Young
In a letter dated October 7, 1993, Drs. Johnson M. Liu and Neal S.
Young of the National Institutes of Health, Bethesda, Maryland,
submitted the human gene transfer protocol entitled: Retroviral
Mediated Gene Transfer of the Fanconi Anemia Complementation Group C
Gene to Hematopoietic Progenitors of Group C Patients to the
Recombinant DNA Advisory Committee for formal review and approval. At
the December 2-3, 1993, meeting, the Recombinant DNA Advisory Committee
deferred the protocol until the investigators return to the full
Recombinant DNA Advisory Committee with the following:
(1) Murine data demonstrating in vivo expression of the FACC gene
and safety data accumulated over a period of 4 months
demonstrating that the FACC-transduced cells do not produce any
untoward effects, i.e., malignant transformation:
(2) Data (cited in Dr. Cynthia Dunbar's December 1993 data
management report, Protocol #9206-025) regarding the possibility that
``stem cell factor could favor the growth of leukemic versus normal
progenitors during ex vivo culture periods;'' and
(3) Revised eligibility criteria sections for both the protocol and
Informed Consent document that describe the necessity for bone marrow
examination following each infusion.
The consensus of the Recombinant DNA Advisory Committee was that
the investigators were not required to submit this additional data
until 4 weeks prior to the Recombinant DNA Advisory Committee meeting
at which the information is reviewed. Submission of previously reviewed
information is not required. The motion to defer the protocol pending
full Recombinant DNA Advisory Committee review of additional
information passed by a vote of 14 in favor, 0 opposed, and 3
abstentions.
On May 2, 1994, Drs. Liu and Young submitted additional materials
relating to the human gene transfer protocol to the Recombinant DNA
Advisory Committee for formal review and approval.
XII. Amendment to Part I-D of the Points to Consider in the Design and
Submission of Protocols for the Transfer of Recombinant DNA Into the
Genome of Human Subjects, NIH Guidelines, Regarding Informed Consent/
Dr. Zallen
During the December 2-3, 1993, Recombinant DNA Advisory Committee
meeting, Dr. Gary Ellis, Director of the Office for Protection from
Research Risks (OPRR), NIH, Bethesda, Maryland, responded to the
written comments submitted by Dr. Zallen, Chair of the Working Group on
Informed Consent Issues. Dr. Ellis noted the Recombinant DNA Advisory
Committee's concern regarding specific issues that should be addressed
in human gene transfer protocol Informed Consent documents, i.e.,
request for autopsy, recommendations for male/female contraception,
separate Informed Consent documents when gene therapy is separate from
a clinical protocol, commitment to long-term patient follow-up, and
financial responsibility of the institution for all research-related
costs. During his presentation, Dr. Ellis provided the Recombinant DNA
Advisory Committee with background information regarding the roles of
both OPRR and local Institutional Review Boards (IRB) in the review of
research proposals involving human subjects. Dr. Ellis recommended that
the Recombinant DNA Advisory Committee draft a letter outlining its
specific recommendations to OPRR for distribution and consideration by
the local IRBs.
In a memorandum dated December 23, 1993, Dr. Ellis further
clarified the avenues that should be pursued by the Recombinant DNA
Advisory Committee with regard to the ``quality and content of informed
consent documents into constructive changes in the informed consent
process,'' specifically in relation to human gene transfer. Dr. Ellis
recommended that the Points to Consider should be amended to introduce
consistency in the Informed Consent document language.
During the March 3-4, 1994, Recombinant DNA Advisory Committee
meeting, Dr. Doris Zallen, Chair of the Working Group on Informed
Consent, provided a summary of the proposed amendments to Part I-D,
Informed Consent of the Points to Consider. Two versions of revised
Part I-D were presented:
(1) The version drafted by the working group, and
(2) A modified version incorporating the modifications suggested by
Mr. Alex Capron. The Recombinant DNA Advisory Committee recommended
that the working group should develop a consolidated version of part I-
D which includes language from both proposed documents. The Recombinant
DNA Advisory Committee suggested that questions should be prefaced with
an explanation as to the necessity for the requested information.
On April 27, 1994, Dr. Zallen submitted revised amendments to part
I-D, Informed Consent, of the Points to Consider in response to the
specific comments posed by the Recombinant DNA Advisory Committee at
its March 3-4, 1994, meeting. The proposed amendments read:
Part I-D Informed Consent
``In accordance with the requirements of DHHS regulations for the
protection of human subjects (45 CFR part 46), investigators shall
indicate how subjects will be informed about the proposed study, the
manner in which their consent will be solicited, and that the informed
consent form makes clear the special requirements of gene transfer
research.
Part 1-D-1. Communication of the Study to Potential Participants
Part I-D-1-a. Which members of the research group and/or
institution will be responsible for contacting potential participants
and for describing the study to them? What procedures will be used to
avoid potential conflicts of interest if the investigator is also
providing medical care to potential subjects?
Part I-D-1-b. Where will discussions or other means of informing
individuals about the proposed study take place?
Part I-D-1-c. How will the major points covered in Parts I-A
through I-C of the Points to Consider be disclosed to potential
participants and/or their parents or guardians in language that is
understandable to them?
Part I-D-1-d. What is the length of time that the potential
participants will have to make a decision about their participation in
the study?
Part I-D-1-e. If the study involves pediatric or mentally
handicapped subjects, how will the assent of each person be obtained?
Part I-D-2. Informed Consent Document
``Investigators submitting human gene transfer proposals for
Recombinant DNA Advisory Committee review must include the Informed
Consent document as approved by the local Institutional Review Board. A
separate consent document should be used for the gene transfer portion
of a research project when gene transfer is used as an adjunct in the
study of another technique, such as when the gene is used as a `marker'
or when it is used to enhance the power of immunotherapy for cancer.
``Because of the relative novelty of the procedures that are used,
the potentially irreversible consequences of the procedures performed,
and the possibility that many of the potential risks remain undefined,
the Informed Consent document shall include the following specific
information in addition to any requirements of the DHHS regulations for
the protection of human subjects (45 CFR part 46). Indicate if each of
the specified items appears in the consent form or, if not in the
consent form, how those items will be presented to potential subjects.
Include an explanation if any of the following items is omitted from
the consent process or document.
Part I-D-2-a. General Requirements of Human Subjects Research
Part I-D-2-a-(1). Description/purpose of study. ``The subjects
should be provided a detailed explanation in non-technical language of
the purpose of the study and the procedures associated with the conduct
of the proposed study, including a description of the gene-transfer
component.
Part I-D-2-a-(2). Alternatives. ``The consent form should indicate
the availability of other therapies, including the possibility of other
investigational therapies and approaches.
Part I-D-2-a-(3). Voluntary participation. ``The subjects should be
informed that participation in the study is voluntary and that failure
to participate in the study, or withdrawal of consent, will not result
in any penalty or loss of benefits to which the subjects are otherwise
entitled.
Part I-D-2-a-(4). Benefits. ``The subjects should be provided with
an accurate description of the possible benefits, if any, of
participating in the proposed study. For experiments which are not
reasonably expected to provide a therapeutic benefit to subjects, the
consent form shall clearly state that no direct clinical benefit to
subjects is expected to occur as a result of participation in the
study, although knowledge may be gained that may benefit others.
Part I-D-2-a-(5). Possible risks, discomforts, and side effects.
``There should be a clear itemization in the consent form of types of
adverse experiences, the relative severities, and the expected
frequencies. For consistency of definition, side effects that are
listed as mild should be ones which do not require a therapeutic
intervention. Moderate side effects require an intervention. Severe
side effects are potentially fatal or life-threatening, disabling, or
require prolonged hospitalization. Rare side effects occur in less than
one in one thousand subjects, uncommon side effects in less than 1% of
subjects, common side effects in one to 10% of subjects, and frequent
side effects are those which occur in more than 10% of subjects.
``The consent form should provide information regarding the
approximate number of people who have received the genetic material
under study. It is also necessary to warn potential subjects that for
genetic materials previously used in relatively few or no humans,
unforeseen risks are possible, including ones that could be severe.
``Any possible adverse medical consequences that may occur if the
subjects withdraw from the study once the experiment has started should
be indicated.
``Part I-D-2-a-(6). Costs. ``The subjects should be provided with
information about any financial costs associated with their
participation in the experiment and in the long-term follow-up to the
experiment that are not covered by the investigators or the
institutions involved. Comparable financial information for other
available alternatives, including other investigational therapies,
should also be provided.
``In the consent form, subjects should be informed about the extent
to which they will be responsible for any costs for medical treatment
required as a direct result of research-related injury.
Part I-D-2-b. Specific Requirements of Gene Transfer Research
Part I-D-2-b-(1). Use of barrier contraception. ``To avoid the
possibility that any of the reagents employed in gene transfer research
could cause harm to a developing fetus, female subjects should be
informed that they should not be pregnant during the course of their
participation in the study. Both male and female subjects should be
informed when barrier contraception is required during the active phase
of their participation in the study.
Part I-D-2-b-(2). Long-term follow-up. ``To permit evaluation of
long-term safety and efficacy of gene transfer, the prospective
subjects should be informed that they are expected to cooperate in
long-term follow-up that extends beyond the active phase of the study.
A list should be provided in the consent form of persons who can be
contacted in the event that questions arise during the follow-up
period. The principal investigator should request that subjects always
keep the laboratory informed of a current address and telephone number.
``The subjects should also be informed that any significant
findings resulting from the study will be made known to them and/or
their parent or guardian including new information about the
experimental procedure, the physical reactions experienced by other
individuals involved in the study, and any long-term effects that have
been noted.
``Part I-D-2-b-(3). Request for autopsy. ``To obtain vital
information about the safety and efficacy of gene transfer, subjects
should be informed that at the time of death, whenever that may occur,
an autopsy will be requested and that they should advise their families
of this request and of its scientific and medical importance.
Part I-D-2-b-(4). Interest of media and others in the research. To
alert the subjects that others may have an interest in the innovative
character of the experiment and the status of treated subjects:
``The subjects should be informed that the institution and
investigators will make every effort to provide protection from the
media in an effort to protect participants' privacy;
``The subjects should be informed that representatives of
applicable Federal agencies (e.g., NIH, Food and Drug Administration),
representatives of collaborating institutions, vector suppliers, etc.,
will have access to medical records of the participants.''
XIII. Deletion of Appendix L of the NIH Guidelines Regarding Release
Into the Environment/Dr. Wivel
On April 29, 1994, Dr. Nelson Wivel of the Office of Recombinant
DNA Activities, National Institutes of Health, Bethesda, Maryland,
requested that Appendix L, Release into the Environment of Certain
Plants, be deleted from the NIH Guidelines.
The Office of Recombinant DNA Activities (ORDA) requests that
Appendix L, Release into the Environment of Certain Plants, be deleted
from the NIH Guidelines based on the following:
(1) Section I of the NIH Guidelines allows experiments to proceed
that are reviewed and approved by another Federal agency that has
jurisdiction for review and approval without the necessity for NIH
review or approval (52 FR 31849);
(2) The Recombinant DNA Advisory Committee has not reviewed any
deliberate release experiment involving recombinant DNA since 1984;
(3) At its May 30-31, 1991, meeting, the Recombinant DNA Advisory
Committee recommended that Section III-A-2 be deleted from the NIH
Guidelines; and
(4) Experiments involving deliberate release into the environment
are currently reviewed within the framework of existing Federal
regulations, i.e., the Environmental Protection Agency (EPA) and the
United States Department of Agriculture (USDA).
Section I of the NIH Guidelines was amended on August 24, 1987,
such that any recombinant DNA experiment (other than human gene
transfer) may proceed without Recombinant DNA Advisory Committee and
NIH approval if it has been reviewed and approved by another Federal
agency that has jurisdiction over such a proposal. The amended version
(52 FR 31849) of Section I reads as follows:
Section I-A. Purpose
``* * * Any recombinant DNA experiment, which according to the NIH
Guidelines requires approval by the NIH, must be submitted to the NIH
or to another Federal agency that has jurisdiction for review and
approval. Once approval, or other applicable clearances, has been
obtained from a Federal agency other than the NIH (whether the
experiment is referred to that agency by the NIH or sent directly there
by the submitter), the experiment may proceed without the necessity for
NIH review or approval * * *.''
On December 6, 1990, the Recombinant DNA Advisory Committee
Planning Subcommittee recommended that the requirement for Recombinant
DNA Advisory Committee review of experiments involving deliberate
environmental release of organisms containing recombinant DNA be
eliminated from the NIH Guidelines. This recommendation reflected the
fact that the Federal regulatory agencies, the USDA and EPA, are
responsible for the review and approval of environmental release
experiments. The Recombinant DNA Advisory Committee reviewed the
request and recommended that the following sections be deleted from the
NIH Guidelines:
Section III-A-2
Deliberate release into the environment of any organism containing
recombinant DNA except those listed below. The term ``deliberate
release'' is defined as a planned introduction of recombinant DNA-
containing microorganisms, plants, or animals into the environment.
Section III-A-2-a. Introductions conducted under conditions
considered to be accepted scientific practices in which there is
adequate evidence of biological and/or physical control of the
recombinant DNA-containing organisms. The nature of such evidence is
described in appendix L.
Section III-A-2-b. Deletion derivatives and single base changes not
otherwise covered by the NIH Guidelines.
Section III-A-2-c. For extrachromosomal elements and microorganisms
(including viruses), rearrangements and amplifications within a single
genome. Rearrangements involving the introduction of DNA from different
strains of the same species would not be covered by this exemption.
Based on these amendments to the NIH Guidelines, that have
previously been recommended by the Recombinant DNA Advisory Committee,
and the fact that the principals of planned introduction are now in
place which provide a risk-assessment method by other Federal
regulatory agencies, the Office of Recombinant DNA Activities requests
that Appendix L be deleted from the NIH Guidelines.
Appendix L will be deleted as follows:
Appendix L. Release Into the Environment of Certain Plants
Appendix L-I. General Information
``Appendix L specifies conditions under which certain plants as
specified below, may be approved for release into the environment.
Experiments in this category cannot be initiated without submission
of relevant information on the proposed experiment to NIH, review by
the RAC Plant Working Group, and specific approval by the NIH
Director. Such experiments also require the approval of the IBC
before initiation. Information on specific experiments which have
been approved will be available in ORDA and will be listed in
appendix L-III when the Guidelines are republished.
``Experiments which do not meet the specifications of appendix
L-II fall under section III-A and require RAC review and NIH and IBC
approval before initiation.
Appendix L-II. Criteria Allowing Review by the RAC Plant Working
Group Without the Requirement for Full RAC Review
``Approval may be granted by ORDA in consultation with the Plant
Working Group without the requirement for full RAC review (IBC
review is also necessary) for growing plants containing recombinant
DNA in the field under the following conditions:
Appendix L-II-A. The plant species is a cultivated crop of a
genus that has no species known to be a noxious weed.
Appendix L-II-B. The introduced DNA consists of well/
characterized genes containing no sequences harmful to humans,
animals, or plants.
Appendix L-II-C. The vector consists of DNA:
(i) From exempt host-vector systems (see Appendix C);
(ii) From plants of the same or closely related species;
(iii) From nonpathogenic prokaryotes or nonpathogenic lower
eukaryotic plants;
(iv) From plant pathogens only if sequences resulting in
production of disease symptoms have been deleted; or
(v) Chimeric vectors constructed from sequences defined in (i)
or (iv) above. The DNA may be introduced by any suitable method. If
sequences resulting in production of disease symptoms are retained
for purposes of introducing the DNA into the plant, greenhouse-grown
plants must be shown to be free of such sequences before such
plants, their derivatives, or seed can be used in field tests.
Appendix L-II-D. Plants are grown in controlled access fields
under specified conditions appropriate for the plant under study and
the geographical location. Such conditions should include provisions
for using good cultural and pest control practices, for physical
isolation from plants of the same species outside of the
experimental plot in accordance with pollination characteristics of
the species, and the prevention of plants containing recombinant DNA
from becoming established in the environment. Review by the IBC
should include an appraisal by scientists knowledgeable of the crop,
its production practices, and the local geographical conditions.
Procedures for assessing alterations in and the spread of organisms
containing recombinant DNA must be developed. The results of the
outlined tests must be submitted for review by the IBC. Copies must
also be submitted to the Plant Working Group of the RAC.
XIV. Amendment to Part VI of the Points To Consider, NIH Guidelines,
Regarding Expedite Review/Dr. Wivel
On April 29, 1994, Dr. Nelson Wivel of the Office of Recombinant
DNA Activities, National Institutes of Health, Bethesda, Maryland,
requested that part VI, Procedures to be Followed for Expedited Review,
of the Points to Consider be amended to clarify submission requirements
for Expedited Review.
The Procedures to be Followed for Expedited Review currently reads:
``4. Regardless of the method of review, the Points to Consider
must be the standard review for all gene transfer protocols.''
The proposed amendment reads:
``4. Regardless of the method of review, the Points to Consider
must be the standard review for all gene transfer protocols; therefore,
submission of the Points to Consider is required.''
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 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: May 4, 1994.
Suzanne Medgyesi-Mitschang,
Acting Deputy Director for Science Policy and Technology Transfer.
[FR Doc. 94-11466 Filed 5-10-94; 8:45 am]
BILLING CODE 4140-01-P